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Bioaerosol concentrations in residential buildings located in the Northeastern US have not been widely studied. Here, in 2011-2015, we studied the presence and seasonal variability of culturable fungi and bacteria in three multi-family apartment buildings and correlated the bioaerosol concentrations with building ventilation system types and environmental parameters. A total of 409 indoor and 86 outdoor samples were taken. Eighty-five percent of investigated apartments had indoor-outdoor (I/O) ratios of culturable fungi below 1, suggesting minimal indoor sources of fungi. In contrast, 56% of the apartments had I/O ratios for culturable bacteria above 1, indicating the prominence of indoor sources of bacteria. Culturable fungi I/O ratios in apartments serviced by central heating, ventilation, and air-conditioning (HVAC) system were lower than those in apartments with window AC. The type of ventilation system did not have a significant effect on the presence of indoor culturable bacteria. A significant positive association was determined between indoor dew point (DP) levels and indoor culturable fungi (P

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations in the PKD1 (~85%) or PKD2 (~15%) gene which, respectively, encode polycystin-1 (PC1) and polycystin-2 (PC2). How PC1 regulates cell proliferation and apoptosis has been studied for decades but the underlying mechanisms remain controversial. Protein kinase RNA-activated (PKR) is activated by interferons or double-stranded RNAs, inhibits protein translation, and induces cell apoptosis. In a previous study, we found that PC1 reduces apoptosis through suppressing the PKR/eIF2α signaling. Whether and how PKR is involved in PC1-inhibited proliferation and protein synthesis remains unknown. Here we found that knockdown of PKR abolishes PC1-inhibited proliferation and translation. Because suppressed PKR-eIF2α signaling/activity by PC1 would stimulate, rather than inhibit, the proliferation and translation, we examined the effect of dominant negative PKR mutant K296R that has no kinase activity and found that it enhances the inhibition of proliferation and translation by PC1. Thus, our study showed that inhibition of cell proliferation and protein synthesis by PC1 is mediated by the total expression but not the kinase activity of PKR, possibly through physical association.

In this work, a new process is developed to improve the functional stability of Ni-rich NiTi alloys. Repetitive temperature- and stress-induced phase transformation is first conducted to generate dislocation networks in the grain interior. Dislocations serve as nucleation sites for Ni₄Ti₃ nanoprecipitates, which are formed after subsequent low-temperature (523 K) aging. With the presence of dislocations, a homogeneous distribution of nanoprecipitates in the grains is expected, enhancing the strength of the NiTi matrix and resisting plastic deformation during the martensitic transformation. As a result, an improved functional stability of NiTi alloys is achieved. ispartof: Scripta Materialia vol:163 pages:57-61 status: published

X-ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry were combined to characterize the surface oxides (native oxides and passive films) formed on Ni-based alloys containing chromium and molybdenum. Two alloys were studied, Ni-20Cr and Ni-20Cr-10Mo (in wt.%). For Ni-20Cr, both native oxide and passive films formed in acidic medium present a duplex structure comprising a Ni and Cr outer hydroxide layer and a Cr inner oxide layer. The Ni-20Cr-10Mo alloy presents a similar bilayer structure, but with Mo oxide located at the outer layer/inner layer interface. Cr enrichment is observed after passivation for both alloys. The corrosion resistance in acidic solution containing chlorides is enhanced by Mo, and by electrochemical pre-passivation in Cl free solution.

V-4Cr-4Ti alloy, one of the promising candidate structural materials for fusion first wall/blanket applications, was annealed in different temperatures (800 °C and 1000 °C) followed by hydrogen and subsequent helium ions irradiation. It is designed for ion irradiations by forming different size of precipitates, intending to investigate the effect of interfacial coherency characteristic on the irradiation damage behavior at an atomic scale. The microstructure was studied by transmission electron microscopy and the effect of irradiation hardening was evaluated by nanoindentation technique. The results show that TiC precipitate with different size and density was formed during the heat treatment. The lattice matching and the resulting strain state at the interface between the precipitate and the matrix were also investigated quantitatively. The samples with large precipitate exhibited a relatively lower irradiation hardening rate than the one with smaller precipitate, which attributes to the distinct aggregation of He atoms at the interface between the larger precipitate and vanadium alloy matrix. It suggests that the strain state at the interface between the precipitate and the matrix plays a key role in determining the distribution state of irradiation defects thus affect the irradiation damage behavior significantly.

To enhance the anti-friction and anti-wear properties of the WC/TiC/Co carbide, micro-EDM was selected to fabricate textured micro-holes on the carbide surface, and graphite was embedded into the micro-holes to form self-lubricating tools. Dry machining tests on AISI 1045 hardened steel were carried out with the self-lubricating tool and conventional ones. The cutting temperature and tool wear were investigated and compared. The results showed that the self-lubricating tool embedded with graphite exhibited excellent efficiency and stability in reducing cutting temperature, and then the tool wear was reduced compared to that of the conventional one. Through the analysis of test results and cutting temperature distribution theory, the mechanisms responsible are put forward: the first one is the formation of a graphite film on the tool rake face, which is conducive to reducing the temperature of chip and tool caused by tool-chip friction and chip deformation; the other one is attributed to the reduced actual contact length at the tool-chip interface due to the micro-holes, which is propitious to lower the temperature of chip and tool caused by tool-chip friction, supply more graphite, and store chip debris.

To improve the tribological properties of the cemented carbide, Ti–MoS2/Zr composite coatings were deposited on the substrate surface by medium-frequency magnetron sputtering coupled with multi-arc ion plating. The morphology and fundamental properties of the coatings were examined. Dry machining test on AISI 1045 hardened steel was carried out with the coated tool and uncoated tool. The variation of cutting temperature was tested by a TH5104 thermo tracer. The results showed that cutting speed had a profound effect on the cutting temperature. In low-speed cutting of less than 120 m/min, the cutting temperature was decreased by 18–22% and flank wear resistance was improved by 25–30% in comparison with that of uncoated tool, while in high-speed cutting, there was not much difference in cutting performance owing to the high temperature caused by the elevated cutting speed. Through the analysis of cutting heat distribution theory, two responsible mechanisms are found: as lubricating additive between the tool and chip sliding couple, the Ti–MoS2/Zr composite coatings contribute to the decrease of average shear stress on the rake face and the thermal barrier effect in heat conduction. These may result in the decrease of the cutting temperature of tool and chip, and hence the improvement of tool wear resistance.

International audience; An approach preventing contact to ambient air during transfer from liquid environment for electrochemical treatment to UHV environment for surface analysis by X-Ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry was applied to study the mechanisms of Cr and Mo enrichments in the passive oxide film formed on 316L austenitic stainless steel. Starting from the air-formed native oxide-covered surface, exposures were conducted in aqueous sulfuric acid solution first at open circuit potential and then under anodic polarization in the passive range. At open circuit potential the thickness of the bi-layered oxide film was observed to decrease and the enrichments of both Cr(III) and Mo, mostly Mo(VI), to markedly increase as well as the film hydroxylation. This is due to preferential dissolution of the Fe(III) oxide/hydroxide, not compensated by oxide growth in the absence of an electric field established by anodic polarization. Anodic polarization in the passive domain causes the bi-layered structure of the oxide film to re-grow by oxidation of iron, chromium and molybdenum, without impacting the Cr enrichment and only slightly mitigating the Mo enrichment. De-hydroxylation of the inner layer is also promoted upon anodic polarization. These results show that the treatment of the surface oxide film in acid solution at open circuit potential enhances Cr and Mo enrichments and promotes hydroxylation. Passivation by anodic polarization allows dehydroxylation, yielding more Cr oxide, without markedly affecting the Mo enrichment, also beneficial for the corrosion resistance.

In order to meet the requirements of miniaturization and low cost of rolling missiles, the roll-isolated strapdown inertial navigation systems began to be applied to such weapon systems. This paper proposes an adaptive control approach based on LuGre friction torque model to eliminate the influence of the nonlinear characteristics of the friction torque of the roll-isolated platform at low speed. Two nonlinear state observers are used to estimate the unknown state variables in LuGre model, and the parameters of the model are adaptively estimated. The global asymptotic stability of the system is proved by Lyapunov method. The simulation results show that compared with the traditional control approaches, this approach improves the control precision and low-speed performance of the roll-isolated platform, and can meet the performance requirements of the roll-isolated strapdown inertial navigation system.

In this work, we proposed a process to improve the functional stability of Ni-rich NiTi alloys, which combines surface nano-crystallization by means of ultrasonic shot peening and subsequent low-temperature (523 K) aging treatment. The as-annealed coarse-grained NiTi plates were fist subjected to ultrasonic shot peening, which generates nano-grains at the surface region, and introduces dislocation networks in the interior of the NiTi sample. Both the grain boundaries and the dislocations could serve as the heterogenous nucleation sites for Ni4Ti3 nanoprecipitates during subsequent low-temperature aging treatment. Therefore, with the presence of nano-grains and dislocation networks, a homogeneous distribution of Ni4Ti3 nanoprecipitates in the sample is expected, which will strengthen largely the NiTi matrix and resist the plastic activities during the repetitive martensitic transformation. As a result, the improved stability during cyclic superelastic loading is achieved.

Sequential dual-ion irradiation is a useful technique for experimental exploration on the synergistic effects of ion accumulation and cascade damage. In this research, the helium-ion accumulation concomitant with displacement damage induced by helium and iron ions irradiation in China low active martensitic (CLAM) steel was studied by ion-irradiation, transmission electron microscopy and nano-indentation technique. The helium bubbles formed under continuous implantation of helium ions at room temperature and the helium dose forming observed bubbles resolved by TEM clearly in CLAM steel is around 0.7 × 10 17 –1.0 × 10 17 He + /cm 2 under single 100 keV He + irradiation. Significant irradiation hardening was observed in the samples with various ion- and dose-irradiations. Positive correlation between the hardening increment and the helium-ion dose has been established in single helium-ion irradiated samples. On the other hand, the subsequent Fe-ion irradiation greatly promoted the formation and growth of helium bubbles as well as dislocation loops in sequential dual-ion irradiated samples. No significant contribution of the subsequent Fe-ion irradiation on the hardness increment was found for the sequential dual-ion irradiated samples. It is suggested that the defects recombination, the combination effects of size and density of defects contribute to the degree of irradiation hardening. The calculated hardness increment based on dispersion strengthening model and the experimental microstructure analysis followed the same trend as the experimental nano-indentation data.

Accurate characterization of particulate matter (PM) exposure in young children is difficult, because personal samplers are often too heavy, bulky or impractical to be used. The Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler was developed to help address this problem. In this study, we measured inhalable PM exposures in 2-year-olds via a lightweight personal sampler worn in a small backpack and evaluated the use of a robotic sampler with an identical sampling train for estimating PM exposure in this age group. PM mass concentrations measured by the personal sampler ranged from 100 to almost 1,200 μg/m3, with a median value of 331 μg/m3. PM concentrations measured by PIPER were considerably lower, ranging from 14 to 513 μg/m3 with a median value of 56 μg/m3. Floor cleaning habits and activity patterns of the 2-year-olds varied widely by home; vigorous play and recent floor cleaning were most associated with higher personal exposure. Our findings highlight the need for additional characterization of children’s activity patterns and their effect on personal exposures.

Autosomalplease go to the Account Update page (http://mts.hindawi.com/update/) in our Manuscript Tracking System and after you have logged in click on the ORCID link at the top of the page. This link will take you to the ORCID website where you will be able to create an account for yourself. Once you have done so, your new ORCID will be saved in our Manuscript Tracking System automatically."?> dominant polycystic kidney disease (ADPKD) is associated with a number of cellular defects such as hyperproliferation, apoptosis, and dedifferentiation. Mutations in polycystin-1 (PC1) account for ∼85% of ADPKD. Here, we showed that wild-type (WT) or mutant PC1 composed of the last five transmembrane (TM) domains and the C-terminus (termed PC1-5TMC) inhibits cell proliferation and protein translation, as well as the downstream effectors of mTOR, consistent with previous reports. Knockdown of B56α, a subunit of the protein phosphatase 2A (PP2A) complex, or application of PP2A inhibitor okadaic acid or calyculin A, abolished the inhibitory effect of PC1 and PC1-5TMC on proliferation, indicating that PP2A/B56α mediates the regulation of cell proliferation by PC1. In addition to the phosphorylated S6 and 4EBP1, B56α was also downregulated by PC1 and PC1-5TMC. Furthermore, the downregulation of B56α, which may be mediated by mTOR but not AKT, can account for the dependence of PC1-inhibited proliferation on PP2A.

Time of Flight Secondary Ion Mass Spectroscopy, X-Ray Photoelectron Spectroscopy, in situ Photo-Current Spectroscopy and electrochemical analysis were combined to characterize the physicochemical alterations induced by electrochemical passivation of the surface oxide film providing corrosion resistance to 316L stainless steel. The as-prepared surface is covered by a ~2 nm thick, mixed (Cr(III)-Fe(III)) and bi-layered hydroxylated oxide. The inner layer is highly enriched in Cr(III) and the outer layer less so. Molybdenum is concentrated, mostly as Mo(VI), in the outer layer. Nickel is only present at trace level. These inner and outer layers have band gap values of 3.0 and 2.6-2.7 eV, respectively, and the oxide film would behave as an insulator. Electrochemical passivation in sulfuric acid solution causes the preferential dissolution of Fe(III) resulting in the thickness decrease of the outer layer and its increased enrichment in Cr(III) and Mo(IV-VI). The further Cr(III) enrichment of the inner layer causes loss of photoactivity and improved corrosion protection with the anodic shift of the corrosion potential and the increase of the polarization resistance by a factor of ~4. Aging in the passive state promotes the Cr enrichment in the inner barrier layer of the passive film., Comment: 27 pages, 4 tables, 14 figures

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 which encodes polycystin-1 (PC1) and polycystin-2, respectively. PC1 was previously shown to slow cell proliferation and inhibit apoptosis but the underlying mechanisms remain elusive or controversial. Here we showed in cultured mammalian cells and Pkd1 knockout mouse kidney epithelial cells that PC1 and its truncation mutant comprising the last five transmembrane segments and the intracellular C-terminus (PC1-5TMC) down-regulate the phosphorylation of protein kinase R (PKR) and its substrate eukaryotic translation initiation factor 2 alpha (eIF2α). PKR is known to be activated by interferons and dsRNAs, inhibits protein synthesis and induces apoptosis. By co-immunoprecipitation experiments we found that PC1 truncation mutants associate with PKR, or with PKR and its activator PACT. Further experiments showed that PC1 and PC1-5TMC reduce phosphorylation of eIF2α through inhibiting PKR phosphorylation. Our TUNEL experiments using tunicamycin, an apoptosis inducer, and GADD34, an inhibitor of eIF2α phosphorylation, demonstrated that PC1-5TMC inhibits apoptosis of HEK293T cells in a PKR-eIF2α-dependent manner, with concurrent up- and down-regulation of Bcl-2 and Bax, respectively, revealed by Western blotting. Involvement of PC1-regulated eIF2α phosphorylation and a PKR-eIF2α pathway in cell apoptosis may be an important part of the mechanism underlying ADPKD pathogenesis.

With the in-depth study of the cloud, Paas platform, one of the three service of cloud computing models, is being more and more people know and attention. This paper studies the Docker lightweight containers engine technology, using the discovery, cadvisor, influxdb, sky DNS services provide basic business support of cloud computing platform, using the Core OS cluster, developed a cloud computing platform based on the Docker; Complete cloud computing platform for all services distributed configuration, deployment, monitoring; Achieved an open platform with a standard access interface specification, supports rapid installation and operation of all types of applications, provides standard application interfaces and development interface.

We computationally study the chiral transition process of the α-Ala molecule under confined different sizes of armchair SWBNNTs to explore the confinement effect. We find that the influence of a confinement environment (in armchair SWBNNTs) on the α-Ala molecule would lead to different reaction pathways. Meanwhile, the preferred reaction pathway is also different in various sizes of armchair SWBNNTs, and their energy barriers for the rate-limiting step decrease rapidly with the decreasing of the diameters of the nanotubes. It is obvious that significant decrease of the chiral transition energy barrier occurs compared with the isolated α-Ala molecule chirality conversion mechanism, by ∼15.6 kcal mol–1, highlighting the improvement in the activity the enantiomers of α-Ala molecule. We concluded that the confinement environment has a significant impact at the nanoscale on the enantiomer transformation process of the chiral molecule.

International audience; Electrochemical polarization measurements were combined with surface analysis by Time of Flight Secondary Ion Mass Spectroscopy (ToF-SIMS), X-Ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscopy (AFM) to study the alterations of the passive film on 316L austenitic stainless steel induced by the presence of chlorides in sulfuric acid electrolyte. The work was performed at a stage of initiation of localized corrosion preceding metastable pitting at the micrometer scale as verified by current transient analysis and AFM. The results show that Cl-ions enter the bilayer structure of the surface oxide already formed in the native oxide-covered initial surface state at concentrations below the detection limit of XPS (< 0.5 at%), mostly in the hydroxide outer layer where Fe(III) and Mo(IV,VI) species are concentrated but barely in the oxide inner layer enriched in Cr(III). Their main effect is to produce a less resistive passive state by poisoning dehydroxylation and further Cr(III) and Mo(IV,VI) enrichments obtained in the absence of chlorides. This detrimental effect can be suppressed by pre-passivation in a Cl-free electrolyte, which blocks the entry of chlorides in the passive film, including in the outer exchange layer, and enables the beneficial aging-induced variations of the composition to take place despite the presence of chlorides in the environment.

Highlights • Heart failure is increasing in prevalence associated with a huge economic burden. • ACE2 is a negative regulator of the renin–angiotensin system. • Elevated ACE2 activity is a biomarker in heart failure. • Enhancing ACE2 action may have unique therapeutic effects in patients with heart failure., Angiotensin converting enzyme 2 (ACE2), is a monocarboxypeptidase which metabolizes several peptides including the degradation of Ang II, a peptide with vasoconstrictive/proliferative/effects, to generate Ang 1–7, which acting through its receptor Mas exerts vasodilatory/anti-proliferative actions. The classical pathway of the RAS involving the ACE-Ang II-AT1 receptor axis is antagonized by the second arm constituted by the ACE2-Ang 1–7/Mas receptor axis. Loss of ACE2 enhances the adverse pathological remodeling susceptibility to pressure-overload and myocardial infarction. Human recombinant ACE2 is also a negative regulator of Ang II-induced myocardial hypertrophy, fibrosis and diastolic dysfunction and suppresses pressure-overload induced heart failure. Due to its characteristics, the ACE2-Ang 1–7/Mas axis may represent new possibilities for developing novel therapeutic strategies for the treatment of heart failure. Human recombinant ACE2 has been safely administered to healthy human volunteers intravenously resulting in sustained lowering of plasma Ang II levels. In this review, we will summarize the beneficial effects of ACE2 in heart disease and the potential use of human recombinant ACE2 as a novel therapy for heart failure.

Rationale: The classic phagocyte nicotinamide adenine dinucleotide phosphate oxidase (gp91 phox or Nox2) is expressed in the heart. Nox2 activation requires membrane translocation of the p47 phox subunit and is linked to heart failure. We hypothesized that loss of p47 phox subunit will result in decreased reactive oxygen species production and resistance to heart failure. Objective: To define the role of p47 phox in pressure overload–induced biomechanical stress. Methods and Results: Eight-week-old male p47 phox null (p47 phox knockout [KO]), Nox2 null (Nox2KO), and wild-type mice were subjected to transverse aortic constriction–induced pressure overload. Contrary to our hypothesis, p47 phox KO mice showed markedly worsened systolic dysfunction in response to pressure overload at 5 and 9 weeks after transverse aortic constriction compared with wild-type–transverse aortic constriction mice. We found that biomechanical stress upregulated N-cadherin and β-catenin in p47 phox KO hearts but disrupted the actin filament cytoskeleton and reduced phosphorylation of focal adhesion kinase. p47 phox interacts with cytosolic cortactin by coimmunoprecipitation and double immunofluorescence staining in murine and human hearts and translocated to the membrane on biomechanical stress where cortactin interacted with N-cadherin, resulting in adaptive cytoskeletal remodeling. However, p47 phox KO hearts showed impaired interaction of cortactin with N-cadherin, resulting in loss of biomechanical stress–induced actin polymerization and cytoskeletal remodeling. In contrast, Nox2 does not interact with cortactin, and Nox2-deficient hearts were protected from pressure overload–induced adverse myocardial and intracellular cytoskeletal remodeling. Conclusions: We showed a novel role of p47 phox subunit beyond and independent of nicotinamide adenine dinucleotide phosphate oxidase activity as a regulator of cortactin and adaptive cytoskeletal remodeling, leading to a paradoxically enhanced susceptibility to biomechanical stress and heart failure.

With hot construction of smart city, problem such as resources are difficult to share due to information isolated islands, repeated construction, etc. has been exposed. Based on the cloud computing and large data technology, this paper realizes the issues of accessing, processing and storage of multi-source data in urban construction as well as deep analysis and employment of data by service bus platform; also it integrates various kinds of infrastructure services to achieve one procedure from accessing to processing of multi-source data, facilitating the unified application and management, which is the trend of future development of smart city platform construction.

This study used several real-time and filter-based aerosol instruments to measure PM2.5 levels in a high-rise residential green building in the Northeastern US and compared performance of those instruments. PM2.5 24-hr average concentrations were determined using a Personal Modular Impactor (PMI) with 2.5 µm cut (SKC Inc., Eighty Four, PA) and a direct reading pDR-1500 (Thermo Scientific, Franklin, MA) as well as its filter. 1-hr average PM2.5 concentrations were measured in the same apartments with an Aerotrak Optical Particle Counter (OPC) (model 8220, TSI, Inc., Shoreview, MN) and a DustTrak DRX mass monitor (model 8534, TSI, Inc., Shoreview, MN). OPC and DRX measurements were compared with concurrent 1-hr mass concentration from the pDR-1500. The pDR-1500 direct reading showed approximately 40% higher particle mass concentration compared to its own filter (n = 41), and 25% higher PM2.5 mass concentration compared to the PMI2.5 filter. The pDR-1500 direct reading and PMI2.5 in non-smoking homes...

Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase capable of metabolizing angiotensin II (Ang II) into angiotensin-(1-7) [Ang-(1-7)], has emerged as a potential therapeutic target. We hypothesized that ACE2 is a negative regulator of Ang II-mediated pathological effects in vivo. In Wistar-Kyoto (WKY) rats, Ang II infusion (0.1 μg min(-1) kg(-1)) induced a pressor response, activation of NADPH oxidase and generation of superoxide in the heart, kidney and blood vessels; these effects were significantly blunted by recombinant human ACE2 (rhACE2; 2 mg kg(-1)), in association with a lowering of plasma Ang II and elevation of Ang-(1-7) levels. In the spontaneously hypertensive rat (SHR) model, rhACE2 (2 mg kg(-1) day(-1)) delivered over a 14 day period partly corrected the hypertension, the NADPH oxidase activation and the increased superoxide generation in the heart, kidney and blood vessels. Treatment with rhACE2 inhibited Ang II-mediated phosphorylation of the myocardial extracellular signal-regulated kinase 1/2 pathway in WKY rats, with congruent results seen in SHR hearts. Hence, rhACE2 is an important negative regulator of the Ang II-induced pressor response and NADPH oxidase activation and suppresses pathological myocardial signalling, thereby providing a novel therapeutic agent with which to antagonize an activated renin-angiotesin system.

The motion of elongated, ellipsoidal fibers in low Reynolds number flows was studied using a computational modeling approach. The computer model resolved the coupled translational and rotational motion of fibers in laminar flows. The computational model was applied in a circular duct and the transport and deposition of ellipsoidal fibers with different sizes and aspect ratios were simulated. An experimental setup was also developed and deposition of glass fibers in a pipe flow in laminar flow regime was measured. A fiber classifier was used to generate fibers with different aspect ratios in controlled condition. The computational model predictions were compared with the experimental data and good agreement was observed. It was found that the flow shear rate, the fiber aspect ratio, and the particle-to-fluid density ratio significantly affect the transport and deposition of ellipsoidal fibers. It was also found that the computational model should account for the duct flow entrance region in order to provide physically realistic predictions. Attention was given to comparing the effectiveness of using equivalent spheres to approximate the elongated fibers. Several commonly used equivalent spheres were studied, and their suitability for characterizing motion of ellipsoidal fiber particles in the laminar flow was studied.

Indoor exposures to allergens, mold spores and endotoxin have been suggested as etiological agents of asthma; therefore, accurate determination of those exposures, especially in young children (6–36 months), is important for understanding the development of asthma. Since use of personal sampling equipment in this population is difficult, and in children < 1 year of age impossible, we developed a personal sampling surrogate: the Pretoddler Inhalable Particulate Environmental Robotic sampler (PIPER) to better estimate their exposures. During sampling, PIPER simulates the activity patterns, speed of motion and the height of the breathing zones of young children, and mechanically resuspends the deposited dust just as a young child does during running and crawling. The concentrations of allergens, mold spores and endotoxin measured by PIPER were compared to those measured using traditional stationary air sampling in 75 homes in central New Jersey, US. Endotoxin was detected in all homes with median concentrations of 1.0 and 0.55 EU/m3 for PIPER and stationary sampler, respectively. The difference in median concentrations obtained using the two methods was statistically significant for homes with carpeted floors (p= 0.0001) in the heating season. For such homes, the average ratio of endotoxin concentration measured by PIPER and the stationary sampler was 2.96 (95% CI 2.29–3.63). Fungal spores were detected in all homes, with median fungal concentrations of 316 and 380 spores/m3 for PIPER and stationary sampler, respectively. For fungi, the difference between the two sampling methods was not statistically significant. For both sampling methods, the total airborne mold levels were statistically significantly higher in the non-heating season than in the heating season. Allergens were detected in ~15% of investigated homes. The data indicate that the traditional stationary air sampling methods may substantially underestimate personal exposures to endotoxin, especially due to resuspension of dust from carpeted floor surfaces. A personal sampling surrogate, such as PIPER, is a feasible approach to estimate personal exposures in young children. PIPER should be seriously considered as the sampling platform for future exposure studies in young children.

Exposure and dose estimation are essential to understanding the etiology of environmentally linked childhood diseases. The behavior of resuspended particulate matter (PM) suggests that stationary measurements may underestimate household exposures in young children (ages 6-36 months). Because of the size and weight of the sampling equipment, use of personal samplers in this age group is either difficult or impossible. The Pretoddler Inhalable Particulate Environmental Robotic (PIPER Mk IV) sampler has been developed to provide a surrogate method to ascertain personal exposures to PM for this age group. As part of a study of childhood asthma, 55 homes in central New Jersey were tested. Simultaneous sampling for inhalable PM using stationary (110 cm height) and PIPER mobile sampler were carried out. In homes with bare floors (N=21), the absolute difference was 3.9 μg/m3 (SE=3.01; p=0.217) and relative difference (PIPER/Stationary) was 1.12 (linearized SE=0.11). On carpets (N=34), the absolute difference was 54.1 μg/m3 (SE=13.50; p=0.0003), and the relative difference was 2.30 (linearized SE=0.34). The results confirm the importance of understanding the personal dust cloud caused by children's activity in a room, particularly when rugs or carpets are present.

Man-made vitreous fibers (MMVFs) have been used as a substitute for asbestos in industrial and residential applications. This shift has raised the concerns of the potential hazards associated with inhalation of these fibers. The human nose is an important protective organ that captures harmful particles and then clears them from human respiratory tract. However, studies have shown that some or even most of the inhalable fibrous particles can penetrate human nose and deposit into the deep lung. The understanding of fibrous particle deposition in the human nasal passage has important occupational health and possible drug delivery applications. To study the deposition pattern and influential factors, three realistic human nasal models were used and a dielectrophoretic classifier was applied to generate test aerosol of glass fibers with a narrow length distribution. These models were made by using stereolithography based on MRI data from two human subjects. Regional and total deposition efficiencies were measured for five different flow rates: 4, 8, 12, 15, and 18 Lpm and four different fiber length ranges: 10–19, 20–29, 30–39, and 40– 49 μ m . This study found that deposition of glass fibers (with about 1 μ m diameter) in human nasal passage is mainly due to inertial impaction and these fibers orientated themselves normal to the flow direction before deposition occurs. An effective aerodynamic diameter is defined such that the deposition efficiencies of glass fibers are comparable with those of spherical particles. Non-dimensional parameters were defined and an empirical model based on the experimental results is proposed to calculate fibrous particle deposition efficiency in human nose. Empirical expressions were also developed to estimate the pressure drop across the nasal model. Thus, empirical equations are now available for the prediction of total deposition in the human nasal tract for the fibrous particles under constant inspiring flow rates. In addition, this study suggested that these equations can also be used to predict the deposition of spherical particles.

A new organic salt nonlinear optical crystal, l -arginine trifluoroacetate (LATF), has been grown from aqueous solutions. Growth morphology was deduced by the Bravais–Friedel Donnay–Harker (BFDH) model and the influence of pH value on crystal growth using the micro-crystallization method was studied. The results show that the growth properties could be improved by adding appropriate amount of HCl. Etch patterns on the {1 0 1} facet of LATF crystals are also illustrated and described.

Development of asthma in young children may be associated with high exposure to particulate matter (PM). However, typical stationary samplers may not represent the personal exposure of children ages 3 and younger since they may not detect particles resuspended from the floor as children play, thus reducing our ability to correlate exposure and disease etiology. To address this, an autonomous robot, the Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler, was developed to simulate the movements of children as they play on the floor. PIPER and a stationary sampler took simultaneous measurements of particle number concentration in six size channels using an optical particle counter and inhalable PM on filters in 65 homes in New Jersey, USA. To study particle resuspension, for each sampler we calculated the ratio of particle concentration measured while PIPER was moving to the average concentration of particles measured during a reference period when PIPER remained still. For all investigated particle sizes, higher particle resuspension was observed by PIPER compared to the stationary sampler. In 71% of carpeted homes a more significant (at the α = 0.05 level) resuspension of particles larger than 2.5 μm was observed by PIPER compared to the stationary sampler. Typically, particles larger than 2.5 μm were resuspended more efficiently than smaller particles, over both carpeted and bare floors. Additionally, in carpeted homes estimations of PM

A 3D computational model was developed to study the flow and the transport and deposition of nano-size particle in a realistic human nasal passage. The nasal cavity was constructed from a series of MRI images of coronal sections of a nose of a live human subject. For several breathing rates associated with low or moderate activities, the steady state flows in the nasal passage were simulated numerically. The airflow simulation results were compared with the available experimental data for the nasal passage. Despite the anatomical differences of the human subjects used in the experiments and computer model, the simulation results were in qualitative agreement with the experimental data. Deposition and transport of ultrafine particles (1 to 100 nm) in the nasal cavity for different breathing rates were also simulated using an Eulerian-Lagrangian approach. The simulation results for the nasal capture efficiency were found to be in reasonable agreement with the available experimental data for a number of human subjects given typical anatomical differences. The computational results for the nasal capture efficiency for nano-particles and various breathing rates in the laminar regime were found to correlate well with the ratio of particle diffusivity to the breathing rate especially for the particles smaller than 20 nm. Based on the simulated results, a semi-empirical equation for the capture efficiency of the nasal passage for nano-size particles was fitted in terms of Peclet number.

The use of man-made vitreous fibers (MMVFs) as a substitute for asbestos in industrial and residential applications has raised the concerns of the potential hazards associated with inhalable aerosolized fibers. The complex movement of fiber makes it difficult to predict the pattern of fiber deposition in human airways from the behavior of spherical particles. Difficulties in producing monodisperse length fibers has been an obstacle to study fibrous particle deposition in the human respiratory system. To address this problem, a narrow length distribution of fibers was generated using dielectrophoretic classification. Dielectrophoresis is the motion of neutral matter in a nonuniform electric field due to an induced dipole moment. It is sensitive to the conductivity of the matter in the field. A fiber classifier has been used to study the influence of atmospheric humidity on the behavior of glass fibers. Glass fibers, as insulators, can not be classified by the dielectrophoretic classifier. However, our stud...

Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in ~15% of autosomal dominant polycystic kidney disease. Filamins are actin-binding proteins implicated in scaffolding and membrane stabilization. Here we studied the effects of filamin on PC2 stability using filamin-deficient human melanoma M2, filamin-A (FLNA)-replete A7, HEK293 and IMCD cells together with FLNA siRNA/shRNA knockdown (KD). We found that the presence of FLNA is associated with higher total and plasma membrane PC2 protein expression. Western blotting analysis in combination with FLNA KD showed that FLNA in A7 cells represses PC2 degradation, prolonging the half-life from 2.3 to 4.4 hours. By co-immunoprecipitation and Far Western blotting we found that the FLNA C-terminus (FLNAC) reduces the FLNA-PC2 binding and PC2 expression, presumably through competing with FLNA for binding PC2. We further found that FLNA mediates PC2 binding with actin through forming complex PC2-FLNA-actin. FLNAC acted as a blocking peptide and disrupted the link of PC2 with actin through disrupting the PC2-FLNA-actin complex. Finally, we demonstrated that the physical interaction of PC2-FLNA is Ca-dependent. Taken together, our current study indicates that FLNA anchors PC2 to the actin cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase stability, and possibly regulate PC2 function in a Ca-dependent manner.

Particulate matter (PM) and its constituents are recognized risk factors for the development of respiratory symptoms and illness in children. Most measurements of exposure have relied upon stationary indoor monitors (SIMs), overlooking the role of resuspended PM. To improve exposure characterization to resuspended aerosol PM, a recently developed methodology has been employed. The goal of this study was to characterize the resuspendable fraction of house dust and early childhood exposures to PM and its constituents in the child’s home and compare conventional SIM and the Pre-toddler Inhalable Particulate Environmental Robotic (PIPER), an innovative mobile sampler. The study seeks to demonstrate that PIPER provides a more relevant estimate of exposure from inhalable particulate matter through improved correlation with respiratory symptoms in young children. Seventy-five households with children between 3 and 59 months of age were recruited from clinics in central New Jersey. Demographic information, and responses to a health questionnaire based upon that used by the International Study of Allergies and Asthma in Childhood (ISAAC), and household data were collected. Household exposures to inhalable PM (PM100) and endotoxin were determined with simultaneous SIM and mobile (PIPER) sampling. Univariate and multivariate analyses were carried out. History of wheeze (“recent” (

X-ray diffraction and Mossbauer measurements indicate that melt spinning at different wheel velocities causes as-quenched Pr7Fe88B5 ribbons to have distinctive structures. Depending on their as-quenched structures, the phase transformations of the ribbons during annealing may take place in one of the following sequences: (1) amorphous phase (Am)+Pr2Fe14B+α-Fe→Pr2Fe14B+α-Fe; (2) Am+α-Fe→Am′+α-Fe→α-Fe+1:7 phase+Pr2Fe14B→Pr2Fe14B+α-Fe; and (3) Am→Am′+α-Fe→1:7 phase+α-Fe→ Pr2Fe14B+α-Fe. However, for all the ribbon samples, the microstructures after optimal annealing with respect to magnetic properties were found to only consist of two magnetic phases: Pr2Fe14B and α-Fe. The optimum magnetic properties of H c j and Jr, and the squareness of the demagnetization curves of the annealed ribbons deteriorate drastically with increasing quenching rate of unannealed precursors. Taking into account TEM results, the values of αex and Neff derived from the temperature dependence of the coercivity, these deteriorated effects can be attributed to the formation of a coarser and more irregular microstructure during annealing in the samples initially melt spun with higher wheel speeds.

Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion.Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to heart disease.

Background Coronary artery disease leading to myocardial ischemia is the most common cause of heart failure. Apelin ( APLN ), the endogenous peptide ligand of the APJ receptor, has emerged as a novel regulator of the cardiovascular system. Methods and Results Here we show a critical role of APLN in myocardial infarction ( MI ) and ischemia‐reperfusion ( IR ) injury in patients and animal models. Myocardial APLN levels were reduced in patients with ischemic heart failure. Loss of APLN increased MI ‐related mortality, infarct size, and inflammation with drastic reductions in prosurvival pathways resulting in greater systolic dysfunction and heart failure. APLN deficiency decreased vascular sprouting, impaired sprouting of human endothelial progenitor cells, and compromised in vivo myocardial angiogenesis. Lack of APLN enhanced susceptibility to ischemic injury and compromised functional recovery following ex vivo and in vivo IR injury. We designed and synthesized two novel APLN analogues resistant to angiotensin converting enzyme 2 cleavage and identified one analogue, which mimicked the function of APLN , to be markedly protective against ex vivo and in vivo myocardial IR injury linked to greater activation of survival pathways and promotion of angiogenesis. Conclusions APLN is a critical regulator of the myocardial response to infarction and ischemia and pharmacologically targeting this pathway is feasible and represents a new class of potential therapeutic agents.

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs). While TIMP2 and TIMP3 inhibit MMPs, TIMP3 also inhibits activation of pro-MMP2, whereas TIMP2 promotes it. Here we assessed the differential role of TIMP2 and TIMP3 in renal injury using the unilateral ureteral obstruction model. Gene microarray assay showed that post obstruction, the lack of TIMP3 had a greater impact on gene expression of intermediate, late injury- and repair-induced transcripts, kidney selective transcripts, and solute carriers. Renal injury in TIMP3 −/− , but not in TIMP2 −/− , mice increased the expression of collagen type I/III, connective tissue growth factor, transforming growth factor-β, and the downstream Smad2/3 pathway. Interestingly, ureteral obstruction markedly increased MMP2 activation in the kidneys of TIMP3 −/− mice, which was completely blocked in the kidneys of TIMP2 −/− mice. These changes are consistent with enhanced renal tubulointerstitial fibrosis in TIMP3 −/− and its reduction in TIMP2 −/− mice. The activities of tumor necrosis factor-α–converting enzyme, caspase-3, and mitogen-activated kinases were elevated in the kidneys of TIMP3 −/− mice but not TIMP2 −/− mice, suggesting enhanced activation of apoptotic and pathological signaling pathways only in the obstructed kidney of TIMP3 −/− mice. Thus, TIMP2 and TIMP3 play differential and contrasting roles in renal injury: TIMP3 protects from damage, whereas TIMP2 promotes injury through MMP2 activation.

Diabetic nephropathy is the most common cause of end-stage renal disease. Polymorphism in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene, and the ECM-bound inhibitor of matrix metalloproteinases (MMPs), has been linked to diabetic nephropathy in humans. To elucidate the mechanism, we generated double mutant mice in which the TIMP3 gene was deleted in the genetic diabetic Akita mouse background. The aggravation of diabetic injury occurred in the absence of worsening of hypertension or hyperglycemia. In fact, myocardial TIMP3 levels were not affected in Akita hearts, and cardiac diastolic and systolic function remained unchanged in the double mutant mice. However, TIMP3 levels increased in Akita kidneys and deletion of TIMP3 exacerbated the diabetic renal injury in the Akita mouse, characterized by increased albuminuria, mesangial matrix expansion, and kidney hypertrophy. The progression of diabetic renal injury was accompanied by the upregulation of fibrotic and inflammatory markers, increased production of reactive oxygen species and NADPH oxidase activity, and elevated activity of TNF-α-converting enzyme (TACE) in the TIMP3−/−/Akita kidneys. Moreover, while the elevated phospho-Akt (S473 and T308) and phospho-ERK1/2 in the Akita mice was not detected in the TIMP3−/−/Akita kidneys, PKCβ1 (but not PKCα) was markedly elevated in the double mutant kidneys. Our data provide definitive evidence for a critical and selective role of TIMP3 in diabetic renal injury consistent with gene expression findings from human diabetic kidneys.

Loss of angiotensin (Ang)-converting enzyme 2 (ACE2) and inability to metabolize Ang II to Ang 1-7 perpetuate the actions of Ang II after biomechanical stress and exacerbate early adverse myocardial remodeling. Ang receptor blockers are known to antagonize the effect of Ang II by blocking Ang II type 1 receptor (AT 1 R) and also by upregulating the ACE2 expression. We directly compare the benefits of AT 1 R blockade versus enhancing Ang 1-7 action in pressure-overload–induced heart failure in ACE2 knockout mice. AT 1 R blockade and Ang 1-7 both resulted in marked recovery of systolic dysfunction in pressure-overloaded ACE2-null mice. Similarly, both therapies attenuated the increase in NADPH oxidase activation by downregulating the expression of Nox2 and p47 phox subunits and also by limiting the p47 phox phosphorylation. Biomechanical stress-induced increase in protein kinase C-α expression and phosphorylation of extracellular signal–regulated kinase 1/2, signal transducer and activator of transcription 3, Akt, and glycogen synthase kinase 3β were normalized by irbesartan and Ang 1-7. Ang receptor blocker and Ang 1-7 effectively reduced matrix metalloproteinase 2 activation and matrix metalloproteinase 9 levels. Ang II–mediated cellular effects in cultured adult cardiomyocytes and cardiofibrolasts isolated from pressure-overloaded ACE2-null hearts were inhibited to similar degree by AT 1 R blockade and stimulation with Ang 1-7. Thus, treatment with the AT 1 R blocker irbesartan and Ang 1-7 prevented the cardiac hypertrophy and improved cardiac remodeling in pressure-overloaded ACE2-null mice by suppressing NADPH oxidase and normalizing pathological signaling pathways.

Rationale: Diabetic cardiovascular complications are reaching epidemic proportions. Angiotensin-converting enzyme-2 (ACE2) is a negative regulator of the renin-angiotensin system. We hypothesize that loss of ACE2 exacerbates cardiovascular complications induced by diabetes. Objective: To define the role of ACE2 in diabetic cardiovascular complications. Methods and Results: We used the well-validated Akita mice, a model of human diabetes, and generated double-mutant mice using the ACE2 knockout (KO) mice (Akita/ACE2 −/y ). Diabetic state was associated with increased ACE2 in Akita mice, whereas additional loss of ACE2 in these mice leads to increased plasma and tissue angiotensin II levels, resulting in systolic dysfunction on a background of impaired diastolic function. Downregulation of SERCA2 and lipotoxicity were equivalent in Akita and Akita/ACE2KO hearts and are likely mediators of the diastolic dysfunction. However, greater activation of protein kinase C and loss of Akt and endothelial nitric oxide synthase phosphorylation occurred in the Akita/ACE2KO hearts. Systolic dysfunction in Akita/ACE2KO mice was linked to enhanced activation of NADPH oxidase and metalloproteinases, resulting in greater oxidative stress and degradation of the extracellular matrix. Impaired flow-mediated dilation in vivo correlated with increased vascular oxidative stress in Akita/ACE2KO mice. Treatment with the AT1 receptor blocker, irbesartan rescued the systolic dysfunction, normalized altered signaling pathways, flow-mediated dilation, and the increased oxidative stress in the cardiovascular system. Conclusions: Loss of ACE2 disrupts the balance of the renin-angiotensin system in a diabetic state and leads to an angiotensin II/AT1 receptor-dependent systolic dysfunction and impaired vascular function. Our study demonstrates that ACE2 serves as a protective mechanism against diabetes-induced cardiovascular complications.

Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10-15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein. © 2012 Wang et al. Fil: Wang, Qian. University of Alberta; Canadá Fil: Dai, Xiao-Qing. University of Alberta; Canadá Fil: Li, Qiang. University of Alberta; Canadá Fil: Wang, Zuocheng. University of Alberta; Canadá Fil: Cantero, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Biofísica; Argentina Fil: Li, Shu. University of Alberta; Canadá Fil: Shen, Ji. Wuhan University; China Fil: Tu, Jian-Cheng. Wuhan University; China Fil: Cantiello, Horacio Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Biofísica; Argentina. Massachusetts General Hospital And Harvard Medical School; Estados Unidos Fil: Chen, Xing-Zhen. University of Alberta; Canadá