Substituted <i>N</i> -(Biphenyl-4′-yl)methyl ( <i>R</i> )-2-Acetamido-3-methoxypropionamides: Potent Anticonvulsants That Affect Frequency (Use) Dependence and Slow Inactivation of Sodium Channels

Lee, Hyosung,Park, Ki Duk,Torregrosa, Robert,Yang, Xiao-Fang,Dustrude, Erik T.,Wang, Yuying,Wilson, Sarah M.,Barbosa, Cindy,Xiao, Yucheng,Cummins, Theodore R.,Khanna, Rajesh,Kohn, Harold American Chemical Society 2014 Journal of medicinal chemistry Vol.57 No.14

<P/><P>We prepared 13 derivatives of <I>N</I>-(biphenyl-4′-yl)methyl (<I>R</I>)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound’s whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI = TD<SUB>50</SUB>/ED<SUB>50</SUB>) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na<SUP>+</SUP> channel slow inactivation and displayed frequency (use) inhibition of Na<SUP>+</SUP> currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.</P>

The Additivity of True or Apparent Phosphorus Digestibility Values in Some Feed Ingredients for Growing Pigs

Fang, R.J.,Li, T.J.,Yin, F.G.,Yin, Y.L.,Kong, X.F.,Wang, K.N.,Yuan, Z.,Wu, G.Y.,He, J.H.,Deng, Z.Y.,Fan, M.Z. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.7

Two experiments were conducted to determine the additivity of apparent or true digestibility of phosphorus (P) in soybean meal (SBM), peas, faba beans, corn, oats, broken rice meal, rough rice meal, buckwheat, and sorghum for growing pigs. Chromic oxide (0.3%) was used as a digestion marker in both experiments. Each experiment lasted for 12 d, which consisted of a 7-d dietary adaptation period followed by a 5-d fecal collection period. Experiment 1 involved 6 diets: the SBM-based control diet; 4 diets with corn, oats, rough rice meal and broken rice meal substituted for SBM; and an additional diet with a representative mixture of the 5 ingredients. In Experiment 2, 6 diets were prepared similarly, except that the tested ingredients besides SBM were faba beans, peas, buckwheat, and sorghum. In each experiment, six barrows with an initial average individual BW of 20.5 kg were fed one of the six diets according to a $6{\times}6$ Latin square design. The apparent and true P digestibility values for the nine tested ingredients were determined by the substitution method. There were no differences (p>0.05) between the determined and the predicted true P digestibility values for the mixture of ingredients in Experiments 1 and 2. However, the determined and the predicted apparent P digestibility values for the mixture of ingredients differed (p = 0.059) in Experiment 1, but not in Experiment 2. These results indicate that true P digestibility values are additive in ingredients containing low levels of phytate phosphorus and anti-nutritional factors, whereas the apparent P digestibility values are not always additive in single feed ingredients for growing pigs.

Observation of multiple thresholds in the many-atom cavity QED microlaser

Fang-Yen, C.,Yu, C. C.,Ha, S.,Choi, W.,An, K.,Dasari, R. R.,Feld, M. S. American Physical Society 2006 Physical review. A. Atomic, molecular, and optical Vol.73 No.4

Sulfur hexafluoride (SF6) emissions in East Asia determined by inverse modeling

Fang, X.,Thompson, R. L.,Saito, T.,Yokouchi, Y.,Kim, J.,Li, S.,Kim, K. R.,Park, S.,Graziosi, F.,Stohl, A. Copernicus GmbH 2014 Atmospheric chemistry and physics Vol.14 No.9

<P>Abstract. Sulfur hexafluoride (SF6) has a global warming potential of around 22 800 over a 100-year time horizon and is one of the greenhouse gases regulated under the Kyoto Protocol. Around the year 2000 there was a reversal in the global SF6 emission trend, from a decreasing to an increasing trend, which was likely caused by increasing emissions in countries that are not obligated to report their annual emissions to the United Nations Framework Convention on Climate Change. In this study, SF6 emissions during the period 2006-2012 for all East Asian countries - including Mongolia, China, Taiwan, North Korea, South Korea and Japan - were determined by using inverse modeling and in situ atmospheric measurements. We found that the most important sources of uncertainty associated with these inversions are related to the choice of a priori emissions and their assumed uncertainty, the station network as well as the meteorological input data. Much lower uncertainties are due to seasonal variability in the emissions, inversion geometry and resolution, and the measurement calibration scale. Based on the results of these sensitivity tests, we estimate that the total SF6 emission in East Asia increased rapidly from 2404 ± 325 Mg yr−1 in 2006 to 3787 ± 512 Mg yr−1 in 2009 and stabilized thereafter. China contributed 60-72% to the total East Asian emission for the different years, followed by South Korea (8-16%), Japan (5-16%) and Taiwan (4-7%), while the contributions from North Korea and Mongolia together were less than 3% of the total. The per capita SF6 emissions are highest in South Korea and Taiwan, while the per capita emissions for China, North Korea and Japan are close to global average. During the period 2006-2012, emissions from China and from South Korea increased, while emissions from Taiwan and Japan decreased overall. </P>

INFLUENCE OF INJECTION PARAMETERS ON THE TRANSITION FROM PCCI COMBUSTION TO DIFFUSION COMBUSTION IN A SMALL-BORE HSDI DIESEL ENGINE

T. FANG,R. E. COVERDILL,C.-F. F. LEE,R. A. WHITE 한국자동차공학회 2009 International journal of automotive technology Vol.10 No.3

In this paper, the influence of injection parameters on the transition from Premixed Charge Combustion Ignition (PCCI) combustion to conventional diesel combustion was investigated in an optically accessible High-Speed Direct-Injection (HSDI) diesel engine using multiple injection strategies. The heat release characteristics were analyzed using incylinder pressure for different operating conditions. The whole cycle combustion process was visualized with a high-speed video camera by simultaneously capturing the natural flame luminosity from both the bottom of the optical piston and the side window, showing the three dimensional combustion structure within the combustion chamber. Eight operating conditions were selected to address the influences of injection pressure, injection timing, and fuel quantity of the first injection on the development of second injection combustion. For some cases with early first injection timing and a small fuel quantity, no liquid fuel is found when luminous flame points appear, which shows that premixed combustion occurs for these cases. However, with the increase of first injection fuel quantity and retardation of the first injection timing, the combustion mode transitions from PCCI combustion to diffusion flame combustion, with liquid fuel being injected into the hot flame. The observed combustion phenomena are mainly determined by the ambient temperature and pressure at the start of the second injection event. The start-of-injection ambient conditions are greatly influenced by the first injection timing, fuel quantity, and injection pressure. Small fuel quantity and early injection timing of the first injection event and high injection pressure are preferable for low sooting combustion. In this paper, the influence of injection parameters on the transition from Premixed Charge Combustion Ignition (PCCI) combustion to conventional diesel combustion was investigated in an optically accessible High-Speed Direct-Injection (HSDI) diesel engine using multiple injection strategies. The heat release characteristics were analyzed using incylinder pressure for different operating conditions. The whole cycle combustion process was visualized with a high-speed video camera by simultaneously capturing the natural flame luminosity from both the bottom of the optical piston and the side window, showing the three dimensional combustion structure within the combustion chamber. Eight operating conditions were selected to address the influences of injection pressure, injection timing, and fuel quantity of the first injection on the development of second injection combustion. For some cases with early first injection timing and a small fuel quantity, no liquid fuel is found when luminous flame points appear, which shows that premixed combustion occurs for these cases. However, with the increase of first injection fuel quantity and retardation of the first injection timing, the combustion mode transitions from PCCI combustion to diffusion flame combustion, with liquid fuel being injected into the hot flame. The observed combustion phenomena are mainly determined by the ambient temperature and pressure at the start of the second injection event. The start-of-injection ambient conditions are greatly influenced by the first injection timing, fuel quantity, and injection pressure. Small fuel quantity and early injection timing of the first injection event and high injection pressure are preferable for low sooting combustion.

Association between PCR-RFLP Polymorphisms of Five Gene Loci and Milk Traits in Chinese Holstein

Zhang, R.F.,Chen, H.,Lei, C.Z.,Fang, X.T.,Zhang, Y.D.,Hu, S.R.,Su, L.H. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.2

The objective of this study was to assess the association of polymorphisms in ${\kappa}$-cn, ${\beta}$-lg, ${\beta}$-lg 5′ flanking region, CSN1S2, and IGFBP-3 genes with milk production traits and mastitis-related traits in Chinese Holstein. Traits analyzed were 305 day standard milk yield, protein percentage, fat percentage, the ratio of fat percentage and protein percentage, pre-somatic cell count, somatic cell count, and somatic cell score, respectively. CSN1S2 locus was uninformative because only one genotype BB was found in Chinese Holstein. Allele frequencies of A and B in IGFBP-3 gene were 0.5738 and 0.4262 in Chinese Holstein population, which was different from reported Qinchuan cattle population. The genotypes of animals at IGFBP-3 locus significantly affected 305 day standard milk yield, protein percentage, and somatic cell score. The ${\beta}$-lg genotypes had a significant effect on protein percentage and the ratio of fat percentage and protein percentage. Polymorphism in ${\beta}$-lg 5′ flanking region was associated with 305 day standard milk yield, protein percentage, fat percentage, pre-somatic cell count, and somatic cell count. No significant associations of the polymorphism in ${\kappa}$-cn gene were observed for any trait.

Low Temperature Premixed Combustion within a Small Bore High Speed Direct Injection (HSDI) Optically Accessible Diesel Engine Using a Retarded Single Injection

Tiegang Fang,R. E. COVERDILL,C.-F. F. LEE,R. A. WHITE 한국자동차공학회 2008 International journal of automotive technology Vol.9 No.5

An optically accessible single-cylinder high speed direct-injection (HSDI) Diesel engine equipped with a Bosch common rail injection system was used to study low temperature Modulated Kinetics (MK) combustion with a retarded single main injection. High-speed liquid fuel Mie-scattering was employed to investigate the liquid distribution and evolution. By carefully setting up the optics, three-dimensional images of fuel spray were obtained from both the bottom of the piston and the side window. The NOx emissions were measured in the exhaust pipe. The influence of injection pressure and injection timing on liquid fuel evolution and combustion characteristics was studied under similar fuel quantities. Interesting spray development was seen from the side window images. Liquid impingement was found for all of the cases due to the small diameter of the piston bowl. The liquid fuel tip hits the bowl wall obliquely and spreads as a wall jet in the radial direction of the spray. Due to the bowl geometry, the fuel film moves back into the central part of the bowl, which enhances the airfuel mixing process and prepares a more homogeneous air-fuel mixture. Stronger impingement was seen for high injection pressures. Injection timing had little effect on fuel impingement. No liquid fuel was seen before ignition, indicating premixed combustion for all the cases. High-speed combustion video was taken using the same frame rate. Ignition was seen to occur on or near the bowl wall in the vicinity of the spray tip, with the ignition delay being noticeably longer for lower injection pressure and later injection timing. The majority of the flame was confined to the bowl region throughout the combustion event. A more homogeneous and weaker flame was observed for higher injection pressures and later injection timing. The combustion structure also proves the mixing enhancement effect of the liquid fuel impingement. The results show that ultralow sooting combustion is feasible in an HSDI diesel engine with a higher injection pressure, a higher EGR rate, or later injection timing, with little penalty on power output. It was also found that injection timing has more influence on HCCI-like combustion using a single main injection than the other two factors studied. Compared with the base cases, simultaneous reductions of soot and NOx were obtained by increasing EGR rate and retarding injection timing. By increasing injection pressure, NOx emissions were increased due to leaner and faster combustion with better air-fuel mixing. However, smoke emissions were significantly reduced with increased injection pressure. An optically accessible single-cylinder high speed direct-injection (HSDI) Diesel engine equipped with a Bosch common rail injection system was used to study low temperature Modulated Kinetics (MK) combustion with a retarded single main injection. High-speed liquid fuel Mie-scattering was employed to investigate the liquid distribution and evolution. By carefully setting up the optics, three-dimensional images of fuel spray were obtained from both the bottom of the piston and the side window. The NOx emissions were measured in the exhaust pipe. The influence of injection pressure and injection timing on liquid fuel evolution and combustion characteristics was studied under similar fuel quantities. Interesting spray development was seen from the side window images. Liquid impingement was found for all of the cases due to the small diameter of the piston bowl. The liquid fuel tip hits the bowl wall obliquely and spreads as a wall jet in the radial direction of the spray. Due to the bowl geometry, the fuel film moves back into the central part of the bowl, which enhances the airfuel mixing process and prepares a more homogeneous air-fuel mixture. Stronger impingement was seen for high injection pressures. Injection timing had little effect on fuel impingement. No liquid fuel was seen before ignition, indicating premixed combustion for all the cases. High-speed combustion video was taken using the same frame rate. Ignition was seen to occur on or near the bowl wall in the vicinity of the spray tip, with the ignition delay being noticeably longer for lower injection pressure and later injection timing. The majority of the flame was confined to the bowl region throughout the combustion event. A more homogeneous and weaker flame was observed for higher injection pressures and later injection timing. The combustion structure also proves the mixing enhancement effect of the liquid fuel impingement. The results show that ultralow sooting combustion is feasible in an HSDI diesel engine with a higher injection pressure, a higher EGR rate, or later injection timing, with little penalty on power output. It was also found that injection timing has more influence on HCCI-like combustion using a single main injection than the other two factors studied. Compared with the base cases, simultaneous reductions of soot and NOx were obtained by increasing EGR rate and retarding injection timing. By increasing injection pressure, NOx emissions were increased due to leaner and faster combustion with better air-fuel mixing. However, smoke emissions were significantly reduced with increased injection pressure.

Video-rate tomographic phase microscopy.

Fang-Yen, Christopher,Choi, Wonshik,Sung, Yongjin,Holbrow, Charles J,Dasari, Ramachandra R,Feld, Michael S SPIE--the International Society for Optical Engine 2011 JOURNAL OF BIOMEDICAL OPTICS Vol.16 No.1

<P>Tomographic phase microscopy measures the 3-D refractive index distribution of cells and tissues by combining the information from a series of angle-dependent interferometric phase images. In the original device, the frame rate was limited to 0.1 frames per second (fps) by the technique used to acquire phase images, preventing measurements of moving or rapidly changing samples. We describe an improved tomographic phase microscope in which phase images are acquired via a spatial fringe pattern demodulation method, enabling a full tomogram acquisition rate of 30 fps. In addition, in this system the refractive index is calculated by a diffraction tomography algorithm that accounts for the effects of diffraction in the 3-D reconstruction. We use the instrument to quantitatively monitor rapid changes in refractive index within defined subregions of cells due to exposure to acetic acid or changes in medium osmolarity.</P>

Cascade random-quasi-phase-matched harmonic generation in polycrystalline ZnSe

Kupfer, R.,Quevedo, H. J.,Smith, H. L.,Lisi, L. A.,Tiwari, G.,Richmond, C. G.,Bowers, B. B.,Fang, L.,Hegelich, B. M. American Institute of Physics 2018 JOURNAL OF APPLIED PHYSICS - Vol.124 No.24

Rescue of epithelial HCO₃⁻ secretion in murine intestine by apical membrane expression of the cystic fibrosis transmembrane conductance regulator mutant F508del

Xiao, Fang,Li, Junhua,Singh, Anurag Kumar,Riederer, Brigitte,Wang, Jiang,Sultan, Ayesha,Park, Henry,Lee, Min Goo,Lamprecht, Georg,Scholte, Bob J.,De Jonge, Hugo R.,Seidler, Ursula Blackwell Publishing Ltd 2012 The Journal of physiology Vol.590 No.21

<P><B>Key points</B></P><P><P>Cystic fibrosis (CF) is a lethal disease characterized by low rates of epithelial Cl<SUP>−</SUP> and HCO<SUB>3</SUB><SUP>−</SUP> secretion and obstruction of the airways and gastrointestinal and reproductive organs by sticky mucus. HCO<SUB>3</SUB><SUP>−</SUP> secretion has recently been demonstrated to be necessary for mucus hydration.</P><P>The most frequent CF mutation is F508del. This mutant protein is usually degraded in the proteasome. New therapeutic strategies have been developed which deliver F508del to the plasma membrane.</P><P>Utilizing transgenic F508del mutant and cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice, apical membrane expression of F508del protein was found to be associated with enhanced stimulation of intestinal HCO<SUB>3</SUB><SUP>−</SUP> secretion.</P><P>The predominant molecular mechanism for enhanced F508del HCO<SUB>3</SUB><SUP>−</SUP> stimulation appeared to be the activation of a Cl<SUP>−</SUP> recycling pathway, with Cl<SUP>−</SUP> exit via membrane‐resident F508del protein and Cl<SUP>−</SUP> entry in exchange for HCO<SUB>3</SUB><SUP>−</SUP> by apical Cl<SUP>−</SUP>/HCO<SUB>3</SUB><SUP>−</SUP> exchange. In contrast, the predominant molecular mechanism for cAMP‐activated HCO<SUB>3</SUB><SUP>−</SUP> secretion in WT intestine appears to be HCO<SUB>3</SUB><SUP>−</SUP> exit via CFTR itself.</P></P><P><B>Abstract </B> This study investigated whether expression of the common cystic fibrosis transmembrane conductance regulator (CFTR) mutant F508del in the apical membrane of enterocytes confers increased bicarbonate secretory capacity on the intestinal epithelium of F508del mutant mice compared to that of CFTR knockout (KO) mice. CFTR KO mice, F508del mutant mice (F508del) and wild‐type (WT) littermates were bred on the FVB/N background. F508del isolated brush border membrane (BBM) contained approximately 5–10% fully glycosylated band C protein compared to WT BBM. Similarly, the forskolin (FSK)‐induced, CFTR‐dependent short‐circuit current (Δ<I>I</I><SUB>sc</SUB>) of F508del mucosa was approximately 5–10% of WT, whereas the HCO<SUB>3</SUB><SUP>−</SUP> secretory response (<IMG src='/wiley-blackwell_img/equation/TJP_5291_mu1.gif' alt ='inline image'/>) was almost half that of WT in both duodenum and mid‐colon studied <I>in vitro</I> and <I>in vivo.</I> While WT intestine retained full FSK‐induced <IMG src='/wiley-blackwell_img/equation/TJP_5291_mu2.gif' alt ='inline image'/> in the absence of luminal Cl<SUP>−</SUP>, the markedly higher <IMG src='/wiley-blackwell_img/equation/TJP_5291_mu3.gif' alt ='inline image'/> than Δ<I>I</I><SUB>sc</SUB> in F508del intestine was dependent on the presence of luminal Cl<SUP>−</SUP>, and was blocked by CFTR inhibitors. The Ste20‐related proline–alanine‐rich kinases (SPAK/OSR1), which are downstream of the with‐no‐lysine (K) protein kinases (WNK), were rapidly phosphorylated by FSK in WT and F508del, but significantly more slowly in CFTR KO intestine. In conclusion, the data demonstrate that low levels of F508del membrane expression in the intestine of F508del mice significantly increased FSK‐induced HCO<SUB>3</SUB><SUP>−</SUP> secretion mediated by Cl<SUP>−</SUP>/HCO<SUB>3</SUB><SUP>−</SUP> exchange. However, in WT mucosa FSK elicited strong SPAK/OSR1 phosphorylation and Cl<SUP>−</SUP>‐independent HCO<SUB>3</SUB><SUP>−</SUP> efflux. This suggests that therapeutic strategies which deliver F508del to the apical membrane have the potential to significantly enhance epithelial HCO<SUB>3</SUB><SUP>−</SUP> secretion.</P>