Effect of Charge on the Deposition of Electrostatically Charged Inhalable Aerosol in Lung Model

Inhalable drugs are widely used for treating lung diseases such as asthma, emphysema, and cystic fibrosis. The aerosol particles in these inhalable drugs may be charged electrostatically. The deposition of these inhaled therapeutic aerosol particles in the different regions of the lung depends on the particle aerodynamic diameter, electrostatic charge distribution, particulate number density, breathing rate, aerodynamics of the lung, ambient temperature, and relative humidity (RH). The primary mechanisms for lung deposition of inhaled particles are impaction, gravitational settling, diffusion, interception, and electrostatic attraction. To simulate lung deposition, electrostatically charged aerosol particles are introduced through a throat section into a glass bead lung model. The E-SPART analyzer was used to measure aerosol deposition as a function of the particle charge and size. Experiments were carried out to determine the increase in deposition efficiency as a function of the net charge-to-mass ratio (Q/M) of aerosol particles. Using a fairly monodisperse aerosol of 5.0 um count median aerodynamic diameter, it was found that the total deposition efficiency increased from 54% to 91% when Q/M increased from 0.5 to 9.67 |muC/g. The data show that enhanced delivery of the therapeutic aerosol in the lung can be achieved by controlling the electrostatic charge on the inhaled aerosol particles

Isolated Eigenvalues of the Ferromagnetic Spin-J XXZ Chain with Kink Boundary Conditions

We investigate the low-lying excited states of the spin J ferromagnetic XXZ chain with Ising anisotropy Delta and kink boundary conditions. Since the third component of the total magnetization, M, is conserved, it is meaningful to study the spectrum for each fixed value of M. We prove that for J>= 3/2 the lowest excited eigenvalues are separated by a gap from the rest of the spectrum, uniformly in the length of the chain. In the thermodynamic limit, this means that there are a positive number of excitations above the ground state and below the essential spectrum

Reduction of Dendrite Formations to Improve the Appearance of the Powder Cured Films for Automotive Industry

The appearance of powder-coated films is dependent upon powder chemistry and spraying parameters. One of the most important physical factors controlling the powder film appearance is the microdeposition of the powder particles on the grounded substrate. During the electrostatic deposition of powder, the formation of dendrites and agglomerates was observed; these formations have an adverse effect on the final film appearance and their elimination may result in smoother and glossier films. Dendrites are generated due to bipolar charging and inter-particulate electrostatic attractive forces. The corona charging technique is mostly used in industrial powder coating applications. At low corona voltages (- 40 to - 60 kV) a greater degree of bipolar charging was observed compared to that at higher voltages (- 80 to - 100 kV). At the higher voltages, the increase n number of ions produces a more unipolar charging and higher charge-to-mass ratios. As the film builds up, the powder transfer efficiency decreases as the repulsion forces between oncoming charged particles and the already deposited powder layer increase. By controlling the deposition patterns, the final film appearance can be improved. The smoothest films were obtained when the voltage was ramped from - 60 to - 100 kV. Another method to reduce dendrite formations was to deposit powder particles charged unipolarly by first separating them from the oppositely charged ones by using a charge separator

Electrostatic Microencapsulation of Composite Particulate Materials for Manufacturing and Environmental Applications

Electrostatic microencapsulation is a dry coating process where two powders, one containing the fines and the other relatively larger particles, are separately dispersed in air and pre-charged with opposite polarity, using corona charging for electrostatic coagulation. These oppositely charged core and guest particles experience attractive electrostatic forces and generate composite particles. Preliminary experiments of electrostatic microencapsulation were performed using Anionic Exchange Resin (AG 1-X8) as the host particle and Red Toner (Omega 4000) as the guest particles. An electrostatic microencapsulation tower has been designed for generation of composite particles using particles of different particle size distribution

Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes

OBJECTIVE: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years. RESULTS: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide. CONCLUSIONS: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide

Lieb-Robinson Bounds for Harmonic and Anharmonic Lattice Systems

We prove Lieb-Robinson bounds for the dynamics of systems with an infinite dimensional Hilbert space and generated by unbounded Hamiltonians. In particular, we consider quantum harmonic and certain anharmonic lattice systems

Considerations in the determination of orientational order parameters from X-ray scattering experiments

An assessment of the data processing and analysis methods used to obtain the second- and fourth-rank orientational order parameters of liquid crystals from X-ray scattering experiments has been carried out, using experimental data from four extensively studied alkyl-cyanobiphenyls and calculated data generated from two general types of theoretical orientational distribution function. The application of a background subtraction and two different baseline correction methods to the scattering profiles is assessed, along with three different methods to analyse the processed data. The choice of baseline correction method is shown to have a significant effect: an offset to zero overestimates the order parameters from the experimental and calculated data sets, particularly for lower order parameters arising from broad distributions, whereas an offset to a value estimated from regions of low scattering intensity provides experimental values close to those reported from other experimental techniques. By contrast, the three different analysis methods are shown generally to result in relatively small absolute differences between the order parameters. We outline a straightforward general approach to experimental X-ray scattering data processing and analysis for uniaxial phases that results in order parameters that match well with those reported using other experimental techniques

A chirped-pulse Fourier-transform microwave/pulsed uniform flow spectrometer. I. The low-temperature flow system

We report the development of a new instrument that combines chirped-pulse microwave spectroscopy with a pulsed uniform supersonic flow. This combination promises a nearly universal detection method that can deliver isomer and conformer specific, quantitative detection and spectroscopic characterization of unstable reaction products and intermediates, product vibrational distributions, and molecular excited states. This first paper in a series of two presents a new pulsed-flow design, at the heart of which is a fast, high-throughput pulsed valve driven by a piezoelectric stack actuator. Uniform flows at temperatures as low as 20 K were readily achieved with only modest pumping requirements, as demonstrated by impact pressure measurements and pure rotational spectroscopy. The proposed technique will be suitable for application in diverse fields including fundamental studies in spectroscopy, kinetics, and reaction dynamics.National Science Foundation (U.S.) (Award MRI-ID 1126380

Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus , and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV). MERS-CoV, like other coronaviruses, carries genes that encode accessory proteins that antagonize the host antiviral response, often the type I interferon response, and contribute to virulence. We found that MERS-CoV NS4b and homologs from related lineage C bat betacoronaviruses BtCoV-SC2013 (SC2013) and BtCoV-HKU5 (HKU5) are members of the 2H-phosphoesterase (2H-PE) enzyme family with phosphodiesterase (PDE) activity. Like murine coronavirus NS2, a previously characterized PDE, MERS NS4b, can antagonize activation of the OAS-RNase L pathway, an interferon-induced potent antiviral activity. Furthermore, MERS-CoV mutants with deletion of genes encoding accessory proteins NS3 to NS5 or NS4b alone or inactivation of the PDE can activate RNase L during infection of Calu-3 cells. Our report may offer a potential target for therapeutic intervention if NS4b proves to be critical to pathogenesis in in vivo models of MERS-CoV infection