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Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitroand in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

A model based on the perfectly stirred reactor (PSR) concept is used to correlate the minimum extinguishing concentration (MEC) of gaseous KOH, which was established in the cup-burner experiment. Both physical and chemical mechanisms of fire suppression are considered in PSR modeling. The combustion process of the CH4/air and gaseous KOH mixture contains a complex chain branch reaction. A high gaseous KOH concentration of type K agent in the methane flame results in strong flame inhibition. The influence of gaseous KOH on the combustion process involves capturing OH free radicals in the flames and reaching the inhibition effect by controlling key elementary reactions containing OH radicals in the combustion process. By calculation of the intermediate product production rate of the fire-extinguishing agent at a high temperature through the PSR model, the main paths of gaseous KOH inhibiting the methane combustion reaction can be obtained. An increased KOH concentration will not change the reaction mechanism.

Clay mineral plays a crucial role in determining permeability and affecting mechanical properties of caprock formations in geologic carbon sequestration (GCS) and enhanced oil recovery (EOR) engineering. In the corresponding environment, CO2–H2O intercalation not only causes swelling or shrinkage of clay mineral but also results in affecting mechanical properties of mineral. However, influence of quantitative CO2/H2O adsorption on mechanical properties of clay still remains unknown. This work investigated evolutions of elastic properties of Ca-MMT with variable CO2–H2O component using molecular dynamic method. Elastic coefficients Cij, bulk modulus K, shear modulus G, Young’s modulus Eii, and Poisson’s ratio Eijwere correlated to qualified adsorption of CO2–H2O mixture. We obtained the following conclusions: (1) in-plane elastic constants, bulk modulus, shear modulus, and Young’s modulus E33had distinct correlation with the profile of d001spacing as a function of H2O content at fixed CO2content; (2) no distinct evolution profile was found in Poisson’s ratio as a function of CO2or H2O content; (3) we revealed that the mixture of CO2/H2O caused decrease in strength of clay mineral; and (4) varying ranges of all elastic constant were summarized for clay-CO2–H2O considered in this work.

The MnO2/carbon nanotubes (CNTs) composites were prepared through a modified one-pot reaction process, in which CNTs were coated by cross-linked MnO2flakes uniformly. The composition, morphology, and microstructure of the products were characterized using TG, XRD, XPS, Raman, FESEM, TEM, and STEM. It reveals that the MnO2layer stands on the sidewalls of the inner nanotubes uniformly about 50 nm thick, and the loading of MnO2on the CNTs reaches 84%. Furthermore, the supercapacitive performances were investigated by cyclic voltammogram (CV), galvanostatic charge–discharge, and electrochemical impedance spectroscopy (EIS). The experimental results indicate that the composite exhibits not only high specific capacitance of 201 F g–1and rate capability (the specific capacitance at 20 A g–1is 70% of that at 1 A g–1), but also excellent cycle stability (no obvious capacitance decay after 10 000 cycles at 1 A g–1). An asymmetric electrochemical capacitor was assembled by using the obtained MnO2/CNTs composite as positive electrode and activated carbon (AC) as negative electrode. The as-assembled AC//MnO2/CNTs capacitor can cycle reversibly in a voltage of 0–1.5 V and give a high energy density of 13.3 Wh kg–1at a power density of 600 W kg–1.

The degradation kinetics of cloxacillin sodium (CS) under real production conditions was determined using high‐performance liquid chromatography (HPLC). Degradation in methanol (MeOH) follows zero‐order kinetics. The introduction of water kept the degradation order but decreased the rate constant, while butyl acetate (BA) accelerated the degradation and shifted the kinetics to first order. In the MeOH/BA system, the pH‐dependent degradation rate generally increased when increasing the pH, except for a distinct drop at about pH 6.5. In aqueous solution, the effect of temperature was determined and the apparent activation energy of degradation was found to be 80.34 ± 5.88 kJ mol–1. The degradation products were analyzed using HPLC, mass spectrometry, and infrared spectroscopy, and a pathway toward cloxalloic acid via cloxacilloic acid as intermediate is proposed.

Local temporal shot-to-shot variation of a high-energy laser system is measured in order to model the maximum fluence that any location on the optic will be exposed to after N shots (Max-of-N). We constructed a model to derive an equivalent-Max-of-N fluence distribution from a series of shots of differing energy and contrast in order to calculate damage initiation and optics lifetime. This model allows prediction for Max-of-N effects when direct measurements of the fluence distribution are not available. Comparison to different laser systems will be presented in order to gain insight as to the physical origins of the Max-of-N effect.

Historically, the rate at which laser-induced damage sites grow on the exit surface of SiO_2 optics under subsequent illumination with nanosecond-laser pulses of any wavelength was believed to depend solely on laser fluence. We demonstrate here that much of the scatter in previous growth observations was due to additional parameters that were not previously known to affect growth rate, namely the temporal pulse shape and the size of a site. Furthermore, the remaining variability observed in the rate at which sites grow is well described in terms of Weibull statistics. The effects of site size and laser fluence may both be expressed orthogonally in terms of Weibull coefficients. In addition, we employ a clustering algorithm to explore the multiparameter growth space and expose average growth trends. Conversely, this analysis approach also identifies sites likely to exhibit growth rates outside the norm. The ability to identify which sites are likely to grow abnormally fast in advance of the manifestation of such behavior will significantly enhance the accuracy of predictive models over those based on average growth behaviors.

We have found the local temporal shot-to-shot variation of the NIF high-energy laser system to be relatively constant (~3.4% to 4.2% of the mean fluence). We have developed a statistical model that predicts the maximum fluence distribution any particular location will be exposed to after N independent shots (the so-called max-of-N fluence distribution) using the measured shot-to-shot variance; this method allows for an estimate of maximum optics fluence exposure.

Impact damage caused by ground vehicles and equipment colliding with the structural components of aircraft is a significant source of damage to commercial aircraft that may go unreported. Most common are blunt impacts from ground maintenance and service vehicles and equipment with attached elastomeric bumpers that protect the aircraft to some degree but may not leave externally visible evidence of an impact. This research examines the types of impact threats to a composite airplane fuselage, impact testing of composite specimens that simulate airplane fuselage specimens, and the visible detectability of the damage. The test program has two distinct aspects: (a) prediction through analysis and (b) small- and large-scale quasistatic indentation testing.

Degradation of the Ni/yttria‐stabilised zirconia (YSZ) anode of the solid oxide fuel cell has been evaluated in the coal syngas containing different PH3concentrations in the temperature range from 750 to 900 °C. Thermodynamic equilibrium calculations show that PH3in the coal syngas gas is converted mostly to P2O3at 750–900 °C. The phosphorous impurity reacts with the Ni‐YSZ anode to form phosphates. The P‐impurity poisoning leads to the deactivation of the Ni catalyst and to the reduction in the electronic conductivity of the anode. The impurity poisoning effect on the anode is exacerbated by increase in the temperature and/or the PH3concentration.

Abstract: Darwin’s contributions to evolutionary biology are well known, but his contributions to genetics are much less known. His main contribution was the collection of a tremendous amount of genetic data, and an attempt to provide a theoretical framework for its interpretation. Darwin clearly described almost all genetic phenomena of fundamental importance, such as prepotency (Mendelian inheritance), bud variation (mutation), heterosis, reversion (atavism), graft hybridization (Michurinian inheritance), sex-limited inheritance, the direct action of the male element on the female (xenia and telegony), the effect of use and disuse, the inheritance of acquired characters (Lamarckian inheritance), and many other observations pertaining to variation, heredity and development. To explain all these observations, Darwin formulated a developmental theory of heredity — Pangenesis — which not only greatly influenced many subsequent theories, but also is supported by recent evidence.

Abstract.ObjectiveTo investigate the effects of recombinant human growth hormone (rhGH) on rat acute lung injury (ALI).MethodsALI was mimicked by intraperitoneal (i. p.) injection ofE. coli. Female Sprague-Dawley rats were randomized into three groups: control group, injected with physiologic saline (i. p.); ALI group, received a bolus injection ofE. coli(1  ?  1010cfu/l, 15 ml/kg, i. p.) followed by intramuscular physiologic saline injection; and ALI + GH group, received a bolus administration ofE. coli, and then treated with intramuscular rhGH injection (2.25 U/kg/d). ALI group and ALI + GH group were subdivided into day 1 and day 3 subgroups, respectively. Left lungs were lavaged and bronchial alveolar lavage fluid (BALF) was harvested. Lung injury score, lung wet-to-dry weight (W/D) ratio, percentage of neutrophils (PMNs) in BALF, lung permeability index (LPI), intercellular adhesion molecule-1(ICAM-1) expression and activation of nuclear factor-kappa B (NF-κB) in the lungs were determined.Results(1) On day 1 and day 3, the lung injury score, lung W/D ratio, LPI and protein content in BALF were significantly higher in the ALI group than in the control and ALI + GH groups. rhGH attenuated lung injuries significantly. (2) Compared with the control group, the percentage of PMNs in BALF was elevated significantly in the ALI and ALI + GH groups, especially in ALI group. (3) Nuclear positive rate of NF-κB and ICAM-1 expression at the levels of protein and mRNA in the lung in the ALI group on day 1 and day 3 were higher than in the control group. rhGH diminished activation of NF-κB and expression of ICAM-1 in the lung markedly.ConclusionsTreatment with rhGH can significantly attenuate lung injury in the endotoxemic rats, which may be attributed to the reduction of the expression of ICAM-1, the influence on the adhesion and activation of PMNs, the inhibition of the activation of NF-κB and the regulation of the transcription of certain proinflammatory cytokines.

A thermally induced spatial and temporal dephasing model of second-harmonic generation has been developed to describe the conversion efficiency and its degradation of periodically poled potassium titanium phosphate (PPKTP) in a cw, single-pass frequency conversion system. The model confirms the experimental data that show that second-harmonic power greater than 800 mW (15 kW/cm^2) causes two-photon nonlinear absorption, leading to time-dependent photochromic damage in PPKTP. This added absorption degrades the conversion efficiency from an initial value of 19% to an unrecoverable asymptotic value of ∼8% in 2 h at 145 kW/cm^2 of pump intensity through thermal detuning phase mismatch.

We use the variational method to find the optimum launch conditions that can sustain path-averaged solitons in a periodically amplified, constant-dispersion, optical communication system even when amplifier spacing is comparable to or larger than the dispersion length. We determine the amount of prechirping and the initial peak power required and show that both the pulse width and the chirp recover their initial values at each amplifier. The prechirped solitons are different from the standard solitons in constant dispersion since their width and chirp are allowed to vary over each amplifier section. This feature results in an interesting regime in which amplifier spacing can exceed the dispersion length. Numerical solutions of the nonlinear Schrödinger equation show that the use of prechirped solitons improves stability in comparison with guiding-center solitons in constant-dispersion fiber links.

The correlations of essential element Se between human hair and kidney-cortex, liver, and lung from the same subjects were investigated by instrumental neutron activation analysis, using the reaction76Se (n, γ)77mSe, for 24 Chinese autopsies. The concentration of Se is higher in kidney-cortex (2.04–5.36 mg/kg) than in liver (0.73–2.29), lung (0.50–1.85), and hair (0.37–1.43). It is important to know that there are significant relationships of Se concentration between hair and the other three internal organs. The correlation coefficient by linear regression analysis are 0.639, 0.570, and 0.635 for liver, lung, and kidney-cortex, respectively; and thePvalues are all less than 0.01 for the three tissues.

In order to study the relationships between trace element concentrations of hair and internal body burdens, a radiochemical NAA technique has been used for determination of the elements As, Cd, and Hg in autopsy samples of liver, kidney-cortex, lung, and hair from 24 male persons who died by accident. High significant positive correlations were observed between the As concentration in hair and in kidney-cortex, and between Cd and Zn concentrations in kidney-cortex. The contents of Cd, both for lung and kidney-cortex, were related to the smoking habits of the subjects.

The nutritionally indispensable amino acids (IAA) alone do not maintain body nitrogen (N) balance; a source of “nonspecific” nitrogen from dispensable amino acids (DAA), such as from glycine and alanine or other N compounds, is required. However, the in vivo regulation of the metabolism of these amino acids in humans with varying nutritional states has received little study. Hence, the effects of N intake and the IAA:DAA ratio on kinetic aspects of whole-body alanine and glycine metabolism were examined in eight healthy young adult male subjects. They received an L-amino acid diet supplying N equivalent to about 1.5 g and 0.6 g protein (N × 6.25) per kilogram body weight per day. All were studies at each N level with the IAA:DAA ratio (wt/wt) of 1:1 and 1:0, each for a 7-d diet period. Constant primed, intravenous infusions of L-[l-13C]leucine together with either L-[15N]alanine (four subjects) or [15N]glycine (four subjects) were given to each subject at the end of the diet period, after an overnight fast, to determine rates of de novo whole-body alanine and glycine N synthesis. The rate of alanine synthesis was similar (P> 0.05) for all four diets. Glycine de novo N synthesis declined (P< 0.01) with removal of dietary DAA, especially at the lower intake, where the mean rates [micromoles/(kilogram·hour)] were 59 and 20 for 1:1 and 1:0 ratios, respectively. The possible significance of reduced rates of glycine N synthesis for maintenance of protein nutritional status in the healthy adult is discussed.

Experimental results from the generation of Raman sidebands using optical vortices are presented. By generating two sets of sidebands originating from different locations in a Raman-active crystal, one set containing optical orbital angular momentum and the other serving as a reference, Young’s double slit experiment was simultaneously realized for each sideband. The interference between the two sets of sidebands was used to determine the helicity and topological charge in each order. Topological charges in all orders were found to be discrete and follow selection rules predicted by a cascaded Raman process.

We demonstrate energy exchange between two filament-forming femtosecond laser beams in liquid methanol. Our results are consistent with those of previous works documenting coupling between filaments in air; in addition, we identify an unreported phenomenon in which the direction of energy exchange oscillates at increments in the relative pulse delay equal to an optical period (2.6 fs). Energy transfer from one filament to another may be used in remote sensing and spectroscopic applications utilizing femtosecond laser filaments in water and air.

We report pulse-shaper-assisted phase control of a broad spectrum, aiming to synthesize nonsinusoidal waveforms. We first generate multiple-order coherent Raman sidebands by focusing two laser beams into a piece of diamond. Then we combine five sidebands into a single beam by using a prism. Our setup allows for both coarse, manual phase adjustments and fine tuning of the spectral phases. A flat spectral phase across these five frequency-separated sub-bands is achieved, which implies generation of two to three optical-cycle pulses.

We present an empirical model that describes the experimentally observed laser-induced bulk damage and conditioning behavior in deuterated potassium dihydrogen phosphate (DKDP) crystals. The model expands on an existing nanoabsorber precursor model and the multistep absorption mechanism to include two populations of absorbing defects, one with linear absorption and another with nonlinear absorption. We show that this model connects previously uncorrelated small-beam damage initiation probability data to large-beam damage density measurements over a range of nanosecond pulse widths. In addition, this work predicts the damage behavior of laser-conditioned DKDP.

Optical parametric chirped-pulse amplification (OPCPA) in nonlinear crystals has the potential to produce extremes of peak and average power but is limited either in energy by crystal growth issues or in average power by crystal thermo-optic characteristics. Recently, large (7.5 cm diameter × 25 cm length) crystals of yttrium calcium oxyborate (YCOB) have been grown and utilized for high-average-power second-harmonic generation. Further, YCOB has the necessary thermo-optic properties required for scaling OPCPA systems to high peak and average power operation for wavelengths near 1 μm. We report what is believed to be the first use of YCOB for OPCPA. Scalability to higher peak and average power is addressed.

To investigate knockdown resistance (kdr)-like mutations associated with pyrethroid resistance in Anopheles sinensis (Wiedemann, 1828), from Guangxi province, southwest China, a segment of a sodium channel gene was sequenced and genotyped using three new genotyping assays. Direct sequencing revealed the presence of TTG-to-TCG and TTG-to-TTT mutations at allele position L1014, which led to L1014S and L1014F substitutions in a few individual and two novel substitutions of N1013S and L1014W in two DNA templates. A low frequency of the kdr allele mostly in the heterozygous state of L1014S and L1014F was observed in this mosquito population. In this study, the genotyping of An. sinensis using three polymerase chain reaction-based methods generated consistent results, which agreed with the results of DNA sequencing. In total, 52 mosquitoes were genotyped using a direct sequencing assay. The number of mosquitoes and their genotypes were as follows: L/L = 24, L/S = 19, L/F = 8, and F/W = 1. The allelic frequency of L1014, 1014S, and 1014F were 72, 18, and 9%, respectively.