Targeting Intra-Pulmonary P53-Dependent Long Non-Coding RNA Expression as a Therapeutic Intervention for Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage

Diffuse alveolar hemorrhage (DAH) in systemic lupus erythematosus (SLE) is associated with significant mortality, requiring a thorough understanding of its complex mechanisms to develop novel therapeutics for disease control. Activated p53-dependent apoptosis with dysregulated long non-coding RNA (lncRNA) expression is involved in the SLE pathogenesis and correlated with clinical activity. We examined the expression of apoptosis-related p53-dependent lncRNA, including H19, HOTAIR and lincRNA-p21 in SLE-associated DAH patients. Increased lincRNA-p21 levels were detected in circulating mononuclear cells, mainly in CD4+ and CD14+ cells. Higher expression of p53, lincRNA-p21 and cell apoptosis was identified in lung tissues. Lentivirus-based short hairpin RNA (shRNA)-transduced stable transfectants were created for examining the targeting efficacy in lncRNA. Under pristane stimulation, alveolar epithelial cells had increased p53, lincRNA-p21 and downstream Bax levels with elevated apoptotic ratios. After pristane injection, C57/BL6 mice developed DAH with increased pulmonary expression of p53, lincRNA-p21 and cell apoptosis. Intra-pulmonary delivery of shRNA targeting lincRNA-p21 reduced hemorrhage frequencies and improved anemia status through decreasing Bax expression and cell apoptosis. Our findings demonstrate increased p53-dependent lncRNA expression with accelerated cell apoptosis in the lungs of SLE-associated DAH patients, and show the therapeutic potential of targeting intra-pulmonary lncRNA expression in a pristane-induced model of DAH.     

A new strategy for Phase I analysis in SPC

The Phase I analysis in statistical process control usually includes a task of filtering out out‐of‐control data in the historical data set via control charting. The conventional procedure for this is an iterative procedure that first uses all the samples to set up initial trial control limits and discards all the ‘out‐of‐control’ samples accordingly, and then iteratively repeats the screening step on the remaining samples until no more ‘out‐of‐control’ samples are detected. For simplicity, the ‘out‐of‐control’ samples here refer to the samples with their monitoring statistics exceeding the trial control limits. It is found in this study that this procedure throws away too many useful in‐control samples. To overcome this drawback, we propose and study a new iterative procedure that discards only one ‘out‐of‐control’ sample (i.e. the most extreme one) at each iteration. Our simulation study, using the Shewhart X Chart for illustration, demonstrates that the new one‐at‐a‐time procedure reduces dramatically the occurrences of false alarms. For cost‐saving, we further suggest a new strategy on when to stop and inspect the process to look for assignable causes for samples signaling out‐of‐control alarms. To determine the control limits, both the traditional method that controls the individual false‐alarm‐rate and the Bonferroni method that controls the overall false‐alarm‐rate are considered. The performances of the proposed schemes are evaluated and compared in terms of the false‐alarm rate and the detecting power via simulation studies. Copyright © 2009 John Wiley & Sons, Ltd.     

Statistical process monitoring using an empirical Bayes multivariate process control chart

In this paper, we describe the theory underlying an empirical Bayesian approach to monitoring two or more process characteristics simultaneously. If the data is continuous and multivariate in nature, often the multivariate normal distribution can be used to model the process. Then, using Bayesian theory, we develop techniques to implement empirical Bayes process monitoring of the multivariable process. Lastly, an example is given to illustrate the use of our techniques. Copyright © 2001 John Wiley & Sons, Ltd.     

Impact of battery weight and charging patterns on the economic and environmental benefits of plug-in hybrid vehicles

Plug-in hybrid electric vehicle (PHEV) technology is receiving attention as an approach to reducing US dependency on foreign oil and greenhouse gas (GHG) emissions from the transportation sector. PHEVs require large batteries for energy storage, which affect vehicle cost, weight, and performance. We construct PHEV simulation models to account for the effects of additional batteries on fuel consumption, cost, and GHG emissions over a range of charging frequencies (distance traveled between charges). We find that when charged frequently, every 20 miles or less, using average US electricity, small-capacity PHEVs are less expensive and release fewer GHGs than hybrid electric vehicles (HEVs) or conventional vehicles. For moderate charging intervals of 20–100 miles, PHEVs release fewer GHGs, but HEVs have lower lifetime costs. High fuel prices, low-cost batteries, or high carbon taxes combined with low-carbon electricity generation would make small-capacity PHEVs cost competitive for a wide range of drivers. In contrast, increased battery specific energy or carbon taxes without decarbonization of the electricity grid would have limited impact. Large-capacity PHEVs sized for 40 or more miles of electric-only travel do not offer the lowest lifetime cost in any scenario, although they could minimize GHG emissions for some drivers and provide potential to shift air pollutant emissions away from population centers. The tradeoffs identified in this analysis can provide a space for vehicle manufacturers, policymakers, and the public to identify optimal decisions for PHEV design, policy and use. Given the alignment of economic, environmental, and national security objectives, policies aimed at putting PHEVs on the road will likely be most effective if they focus on adoption of small-capacity PHEVs by urban drivers who can charge frequently.     

Highly stable strained layer leaky-mode diode laser arrays

A simple fabrication process for InGaAs strained quantum well leaky-mode laser arrays is demonstrated. The arrays are ten-element devices grown by two-step metal-organic chemical vapor deposition. The structure consists of a strained quantum well InGaAs graded index-separate confinement active region and a thin (0.12 μm), transparent GaAs waveguide region. The near-field pattern typical of leaky-mode phase-locked arrays was measured. Fundamental mode oscillation was observed up to 2 A (threshold was as low as 175 mA). The authors observed a 1 μs pulsed optical output power of 172 mW per facet and a far-field angle (full width at half maximum) of 1.6 times the diffraction limit at 1 A. This is the first reported operation of a strained quantum well leaky-mode laser utilizing a built-in index step     

Decomposition of singular large sparse matrix by adding dummy links and dummy degrees

Abstract

This paper proposes a simple scheme to decompose an n×n nonpositive definite matrix, A, associated with simultaneous equations, A X = B, into a triple‐factors (lower triangular, diagonal, and upper triangular matrices), i.e., Å = L D U, without interchanging rows or columns of A, but with A expanded with new rows and new columns to an m×m matrix Å. Whenever a near‐zero diagonal element, say ā_ii , is encountered and used as a pivoting element, an appropriate positive real number, say p, is added to this diagonal element, and a new term —px_k is also added to the i‐th equation, where x_k is a new variable called “dummy variable'’. If we also add a new equation —px_i + px_k = 0 to enforce the new added variable x_k equal to x_i then the modified i‐th equation has the same effect as the original equation. Therefore, the original solution X can be found directly from the expanded solution of the modified expanded equation. The method is very useful in solving the following problems: (1) nonlinear problems near the limit state, (2) postbuckling analysis, (3) system equations with constraint conditions, and (4) getting eigenvectors from eigenvalues.     

Effect of barbituric acid on the self-polymerization reaction of bismaleimides

Barbituric acid (BTA) was used as an initiator for the homopolymerization of bismaleimide (BMI). The reaction was controlled by the amount of barbituric acid and ended up with solvent-soluble oligomers. The effects of varying the amounts of BTA, as well as the reaction time, on BMI's self-polymerization reaction were investigated. The thus-formed oligomers were characterized by gel permeation chromatography (GPC), infrared spectra (IR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The degree of reaction increased proportionally to the concentration of BTA or the length of the reaction time. Thus, solvent-soluble BMI oligomer can be controlled and obtained.     

Transverse Shear Effect on Flutter of Composite Panels

The effect of transverse shear deformation on the supersonic flutter of composite panels has been investigated using the finite element method. First‐order shear‐deformation laminated‐plate theory and quasi‐steady aerodynamic theory are employed for the analysis. The total displacement of the plate is expressed as the sum of the displacement due to bending and the displacement due to shear deformation. Thus, the aerodynamic pressure induced by the plate motion is also the sum of the pressure induced by bending deformation and the pressure induced by shear deformation. Numerical results show that the transverse shear deformation may have a significant effect on the flutter boundary if aerodynamic damping were small or neglected in the determination of flutter boundary.     

Low-threshold, high-power, 1.3-μm wavelength, InGaAsP-InPetched-facet folded-cavity surface-emitting lasers

A 1.3-μm wavelength, InGaAsP-InP folded-cavity, surface-emitting laser with CH₄-H₂ reactive ion-etched vertical and 45° angled facets was demonstrated for the first time. Continuous-wave threshold currents of 32 mA have been achieved, with >15 mW CW power for the surface-emitted light. These surface-emitting lasers with two dry-etched facets are suitable for wafer-level testing and for monolithic integration with other InP-based photonic devices     

Poly(9,9-dihexylfluorene) derivatives containing electron-transporting aromatic triazole segments: Synthesis, optical and electrochemical properties

We prepared three new poly(9,9-dihexylfluorene) derivatives (P1–P3) containing kinked aromatic triazole (triphenyl-1,2,4-triazole derivative) via Suzuki coupling polymerization. These copolymers were soluble in common organic solvents and showed high decomposition temperatures (T_d = 416–454 °C). The optical and electrochemical properties of P1–P3 were compared with poly(9,9-dihexylfluorene) (PFO) and P4 and P5 in which the linkages of the aromatic triazole were different. After introducing the triazole units, absorption spectra showed blue shift (388 nm → 372 nm) due to reduced conjugation, but PL spectra remained almost unchanged (417–418 nm). The linkages of triazole with fluorene segments in P1–P5 were different: (1) fluorene segments linked with triazole through a kinked angle (P1 and P2), (2) triazole as a branch unit (P3) and as terminal groups (P4), (3) fluorene segments linked with triazole in a linear way (P5). As estimated from semi-empirical MNDO calculation, two twisted conformations (ca. 90° each) exist between triazole core and fluorene groups. These kinked conformation and twisted structure increased the PL efficiency (Φ_PL = 0.60–0.73, Φ_PL = 0.58 for PFO) and partially inhibited annealing-induced excimer formation. From cyclic voltammetric results, P1–P3 exhibited better electron affinity (LUMO: −2.75 to −2.82 eV) than PFO (LUMO: −2.52 eV).