A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Chen, Han,Li, Chunyan,Peng, Xinxin,Zhou, Zhicheng,Weinstein, John N.,Caesar-Johnson, Samantha J.,Demchok, John A.,Felau, Ina,Kasapi, Melpomeni,Ferguson, Martin L.,Hutter, Carolyn M.,Sofia, Heidi J.,Ta Elsevier 2018 Cell Vol.173 No.2

<P><B>Summary</B></P> <P>The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on “chromatin-state” to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Systematic analysis of enhancer expression across ∼9,000 samples of 33 cancer types </LI> <LI> Global enhancer activation positively correlates with aneuploidy but not mutations </LI> <LI> A computational method that infers causal enhancer-target-gene relationships </LI> <LI> Enhancers as key regulators of therapeutic targets, including PD-L1 </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Effect of dietary lactulose supplementation on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers

Zhao, P.Y.,Li, H.L.,Mohammadi, M.,Kim, I.H. Elsevier 2016 Poultry science Vol.95 No.1

<P>A 35 d trial was conducted to evaluate the effects of dietary lactulose on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. A total of 816 1-day-old male Ross broilers (40.2 +/- 0.4 g) were allotted to 4 dietary treatments using 12 cages with 17 chicks per cage. Treatments were: 1) CON, basal diet; 2) L05, CON + 0.05% lactulose; 3) L10, CON + 0.10% lactulose; and 4) L15, CON + 0.15% lactulose. Higher (P < 0.05) body weight gain (BWG) and lower (P < 0.05) feed conversion ratio (FCR) were observed in broilers fed the L15 diet compared with those fed the CON diet during d 22 to 35. During d 0 to 35, BWG was higher (P < 0.05) and FCR was lower (P < 0.05) in broilers fed lactulose diets than those fed the CON diet. Additionally, broilers fed L15 diets had the highest BWG (P < 0.05) and lowest FCR (P < 0.05). The apparent total tract digestibility (ATTD) of DM and nitrogen (N) was increased (P < 0.05) in broilers fed the L15 diet compared with those fed the CON diet. Drip loss was decreased (P < 0.05) in L10 and L15 treatments compared with CON treatment on d 1, d 3, and d 5. On d 3, lowest (P < 0.05) drip loss was observed in the L15 treatment. Excreta E. coli counts in the L15 treatment were decreased (P < 0.05) on d 14, but Lactobacillus counts in the L15 treatment were increased (P < 0.05) on d 14 and d 35 compared with the CON diet. A linear effect (P < 0.05) was observed on BWG (d 22 to 35), FCR (d 0 to 35), the ATTD of DM and N, drip loss, E. coli (d 14), and Lactobacillus (d 14 and d 35) counts. In conclusion, dietary supplementation of 0.15% lactulose can improve growth performance and nutrient digestibility; as well as increase the proliferation of Lactobacillus and decrease E. coli counts in excreta.</P>

Fungal diversity notes 253–366: taxonomic and phylogenetic contributions to fungal taxa

Li, G. J.,Hyde, K. D.,Zhao, R. L.,Hongsanan, S.,Abdel-Aziz, F. A.,Abdel-Wahab, M. A.,Alvarado, P.,Alves-Silva, G.,Ammirati, J. F.,Ariyawansa, H. A. Springer Science and Business Media 2016 FUNGAL DIVERSITY Vol.78 No.1

<P>Notes on 113 fungal taxa are compiled in this paper, including 11 new genera, 89 new species, one new subspecies, three new combinations and seven reference specimens. A wide geographic and taxonomic range of fungal taxa are detailed. In the Ascomycota the new genera Angustospora (Testudinaceae), Camporesia (Xylariaceae), Clematidis, Crassiparies (Pleosporales genera incertae sedis), Farasanispora, Longiostiolum (Pleosporales genera incertae sedis), Multilocularia (Parabambusicolaceae), Neophaeocryptopus (Dothideaceae), Parameliola (Pleosporales genera incertae sedis), and Towyspora (Lentitheciaceae) are introduced. Newly introduced species are Angustospora nilensis, Aniptodera aquibella, Annulohypoxylon albidiscum, Astrocystis thailandica, Camporesia sambuci, Clematidis italica, Colletotrichum menispermi, C. quinquefoliae, Comoclathris pimpinellae, Crassiparies quadrisporus, Cytospora salicicola, Diatrype thailandica, Dothiorella rhamni, Durotheca macrostroma, Farasanispora avicenniae, Halorosellinia rhizophorae, Humicola koreana, Hypoxylon lilloi, Kirschsteiniothelia tectonae, Lindgomyces okinawaensis, Longiostiolum tectonae, Lophiostoma pseudoarmatisporum, Moelleriella phukhiaoensis, M. pongdueatensis, Mucoharknessia anthoxanthi, Multilocularia bambusae, Multiseptospora thysanolaenae, Neophaeocryptopus cytisi, Ocellularia arachchigei, O. ratnapurensis, Ochronectria thailandica, Ophiocordyceps karstii, Parameliola acaciae, P. dimocarpi, Parastagonospora cumpignensis, Pseudodidymosphaeria phlei, Polyplosphaeria thailandica, Pseudolachnella brevifusiformis, Psiloglonium macrosporum, Rhabdodiscus albodenticulatus, Rosellinia chiangmaiensis, Saccothecium rubi, Seimatosporium pseudocornii, S. pseudorosae, Sigarispora ononidis and Towyspora aestuari. New combinations are provided for Eutiarosporella dactylidis (sexual morph described and illustrated) and Pseudocamarosporium pini. Descriptions, illustrations and/or reference specimens are designated for Aposphaeria corallinolutea, Cryptovalsa ampelina, Dothiorella vidmadera, Ophiocordyceps formosana, Petrakia echinata, Phragmoporthe conformis and Pseudocamarosporium pini. The new species of Basidiomycota are Agaricus coccyginus, A. luteofibrillosus, Amanita atrobrunnea, A. digitosa, A. gleocystidiosa, A. pyriformis, A. strobilipes, Bondarzewia tibetica, Cortinarius albosericeus, C. badioflavidus, C. dentigratus, C. duboisensis, C. fragrantissimus, C. roseobasilis, C. vinaceobrunneus, C. vinaceogrisescens, C. wahkiacus, Cyanoboletus hymenoglutinosus, Fomitiporia atlantica, F. subtilissima, Ganoderma wuzhishanensis, Inonotus shoreicola, Lactifluus armeniacus, L. ramipilosus, Leccinum indoaurantiacum, Musumecia alpina, M. sardoa, Russula amethystina subp. tengii and R. wangii are introduced. Descriptions, illustrations, notes and / or reference specimens are designated for Clarkeinda trachodes, Dentocorticium ussuricum, Galzinia longibasidia, Lentinus stuppeus and Leptocorticium tenellum. The other new genera, species new combinations are Anaeromyces robustus, Neocallimastix californiae and Piromyces finnis from Neocallimastigomycota, Phytophthora estuarina, P. rhizophorae, Salispina, S. intermedia, S. lobata and S. spinosa from Oomycota, and Absidia stercoraria, Gongronella orasabula, Mortierella calciphila, Mucor caatinguensis, M. koreanus, M. merdicola and Rhizopus koreanus in Zygomycota.</P>

Numerical studies on the effects of the lateral boundary on soil-structure interaction in homogeneous soil foundations

Li, Z.N.,Li, Q.S.,Lou, M.L. Techno-Press 2005 Structural Engineering and Mechanics, An Int'l Jou Vol.20 No.4

In this paper, the finite element method is applied to investigate the effect of the lateral boundary in homogenous soil on the seismic response of a superstructure. Some influencing factors are presented and discussed, and several parameters are identified to be important for conducting soil-structure interaction experiments on shaking tables. Numerical results show that the cross-section width L, thickness H, wave propagation velocity and lateral boundaries of soil layer have certain influences on the computational accuracy. The dimensionless parameter L/H is the most significant one among the influencing factors. In other words, a greater depth of soil layer near the foundation should be considered in shaking table tests as the thickness of the soil layer increases, which can be regarded as a linear relationship approximately. It is also found that the wave propagation velocity in soil layer affects the numerical accuracy and it is suggested to consider a greater depth of the soil layer as the wave propagation velocity increases. A numerical study on a soil-structure experimental model with a rubber ring surrounding the soil on a shaking table is also conducted. It is found the rubber ring has great effect on the soil-structure interaction experiments on shaking table. The experimental precision can be improved by reasonably choosing the elastic parameter and width of the rubber ring.

Magnetic Study of Heavily Mn-doped CuO Thin Films

L. Li,B. Lv,J. Z. Cai,W. Q. Zou,X. S. Wu,F. M. Zhang 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.10

Cu0.7Mn0.3O films were deposited by Plasma Enhanced Chemical Vapor Deposition and annealed in different atmospheres. The XRD diffraction results indicate that samples annealed in air and N2 both show pure CuO phases, while the film annealed in O2 has a secondary phase CuMn2O4. The content of Mn was confirmed by Energy dispersive X-ray spectroscopy. The M-T and M-H curves show that the average magnetic moment of the films prepared in O2 is larger than those prepared in air and in N2 atmosphere. Ferromagnetic segments Mn-O-Cu-O-Mn can be used to understand the ferromagnetism of CuO under heavily Mn-doping. And the magnetic moment per Mn ions calculated on the base of this chain model is consistent with the experimental result.

The PPARα activator fenofibrate inhibits voltage-dependent K⁺ channels in rabbit coronary arterial smooth muscle cells

Li, H.,Shin, S.E.,Seo, M.S.,An, J.R.,Jung, W.K.,Ha, K.S.,Han, E.T.,Hong, S.H.,Bang, H.,Bae, Y.M.,Firth, A.L.,Choi, I.W.,Park, W.S. North-Holland 2017 European journal of pharmacology Vol.812 No.-

<P>We examined the effects of the PPAR alpha activator fenofibrate on voltage-dependent K+ (Kv) channels using a patch clamp technique in native rabbit coronary arterial smooth muscle cells. Kv current was inhibited by application of fenofibrate in a concentration-dependent manner, with an apparent IC50 value of 6.39 +/- 0.53 mu M and a slope value (Hill coefficient) of 1.63 +/- 0.10. Fenofibrate accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for fenofibrate were 0.81 +/- 0.05 mu M-1 s(-1) and 4.70 +/- 0.47 s(-1), respectively. Although fenofibrate did not affect the steady-state activation curves, fenofibrate shifted the inactivation curves toward a more negative potential. Application of train pulses (1 or 2 Hz) progressively increased the fenofibrate-induced inhibition of the Kv channel, and the recovery time constant from inactivation was increased in the presence of fenofibrate, which suggested that the inhibitory effect of fenofibrate is use-dependent. Another PPAR alpha activator, bezafibrate and PPARa inhibitor, GW 6471, did not affect the Kv current and also did not change the inhibitory effect of fenofibrate on the Kv current. From these results, we suggest that fenofibrate inhibited Kv current in a state-, time-, and use-dependent manner, completely independent of PPAR alpha activation.</P>

Characterization of the major dehydrogenase related to d-lactic acid synthesis in Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293

Li, L.,Eom, H.J.,Park, J.M.,Seo, E.,Ahn, J.E.,Kim, T.J.,Kim, J.H.,Han, N.S. IPC Science and Technology Press ; Elsevier Scienc 2012 Enzyme and microbial technology Vol.51 No.5

Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 is a lactic acid bacterium that converts pyruvate mainly to d-(-)-lactic acid by using d-(-)-lactate dehydrogenase (ldhD). The aim of this study was to identify the gene responsible for d-lactic acid formation in this organism and to characterize the enzyme to facilitate the production of optically pure d-lactic acid. A genomic analysis of L. mesenteroides ATCC 8293 revealed that 7 genes encode lactate-related dehydrogenase. According to transcriptomic, proteomic, and phylogenetic analyses, LEUM_1756 was the major gene responsible for the production of d-lactic acid. The LEUM_1756 gene, of 996bp and encoding 332 amino acids (36.5kDa), was cloned and overexpressed in Escherichia coli BL21(DE3) Star from an inducible pET-21a(+) vector. The enzyme was purified by Ni-NTA column chromatography and showed a specific activity of 4450U/mg, significantly higher than those of other previously reported ldhDs. The gel permeation chromatography analysis showed that the purified enzyme exists as tetramers in solution and this was the first report among lactic acid bacteria. The pH and temperature optima were pH 8.0 and 30<SUP>o</SUP>C, respectively, for the pyruvate reduction reaction, and pH 11.0 and 20<SUP>o</SUP>C, respectively, for the lactate oxidation reaction. The K<SUB>m</SUB> kinetic parameters for pyruvate and lactate were 0.58mM and 260mM, respectively. In addition, the k<SUB>cat</SUB> values for pyruvate and lactate were 2900s<SUP>-1</SUP> and 2280s<SUP>-1</SUP>, respectively. The enzyme was not inhibited by Ca<SUP>2+</SUP>, Co<SUP>2+</SUP>, Cu<SUP>2+</SUP>, Mg<SUP>2+</SUP>, Mn<SUP>2+</SUP>, Na<SUP>+</SUP>, or urea, but was inhibited by 1mM Zn<SUP>2+</SUP> and 1mM SDS.

Enhanced performance of LSCF cathode through surface modification

Liu, M.,Ding, D.,Blinn, K.,Li, X.,Nie, L.,Liu, M. Pergamon Press ; Elsevier Science Ltd 2012 International journal of hydrogen energy Vol.37 No.10

Mixed ionic-electronic conductors in the family of La<SUB>x</SUB>Sr<SUB>1-x</SUB>Co<SUB>y</SUB>Fe<SUB>1-y</SUB>O<SUB>3-δ</SUB> (LSCF) have been widely studied as cathode materials for solid oxide fuel cells (SOFCs). However, the long-term stability and the limited surface catalytic activity are still a concern. Here we report a new catalyst La<SUB>0.4875</SUB>Ca<SUB>0.0125</SUB>Ce<SUB>0.5</SUB>O<SUB>2-δ</SUB> (LCC), which can significantly enhance the performance and stability of LSCF cathodes when applied as a thin-film coating on LSCF surface. For example, with 5 μL 0.25 mol L<SUP>-1</SUP> LCC solution infiltrated into LSCF cathode, the cathodic polarization resistance was reduced by ∼60% (to ∼0.076 Ω cm<SUP>2</SUP>) at 750 <SUP>o</SUP>C, leading to a peak power density of ∼1.25 W/cm<SUP>2</SUP>, which is ∼18% higher than that for the unmodified LSCF cathode in an anode-supported cell. In addition, stable power output was observed for over 500 h operation at 750 <SUP>o</SUP>C under a constant voltage of 0.7 V.

A new constructive neural network method for noise processing and its application on stock market prediction

Xi, L.,Muzhou, H.,Lee, M.H.,Li, J.,Wei, D.,Hai, H.,Wu, Y. Elsevier Science, B.V 2014 Applied soft computing Vol.15 No.-

In this paper, in order to optimize neural network architecture and generalization, after analyzing the reasons of overfitting and poor generalization of the neural networks, we presented a class of constructive decay RBF neural networks to repair the singular value of a continuous function with finite number of jumping discontinuity points. We proved that a function with m jumping discontinuity points can be approximated by a simplest neural network and a decay RBF neural network in L<SUP>2</SUP>(@?) by each @? error, and a function with m jumping discontinuity point y=f(x),x@?E@?@?<SUP>d</SUP> can be constructively approximated by a decay RBF neural network in L<SUP>2</SUP>(@?<SUP>d</SUP>) by each ε>0 error. Then the whole networks will have less hidden neurons and well generalization in the same of the first part. A real world problem about stock closing price with jumping discontinuity have been presented and verified the correctness of the theory.

Prevalence and prediction of augmented renal clearance in the neurocritical care population

Cook Aaron M.,Li David,Nestor Melissa A.,Bastin Melissa L. Thompson 대한신경집중치료학회 2022 대한신경집중치료학회지 Vol.15 No.2

Background: Augmented renal clearance (ARC; creatinine clearance [CrCl] >130 mL/min/1.73 m2) is prevalent in patients with neurological injuries and may influence their exposure to important pharmacological therapies. Little is known about the relationship between estimated and measured CrCl in this population.Methods: This single-center, prospective, observational cohort study aimed to describe the association between ARC and estimated CrCl and neurological outcomes in a broad neurocritical care population. Prospective patient screening criteria included adults aged 18–85 years, with critical illness due to neurologic causes (such as ischemic stroke or subarachnoid hemorrhage) and lack of renal dysfunction on admission. Patients who had at least one urine CrCl measurement performed within the first 7 days of hospitalization were included. Two cohorts were evaluated: those with ARC and those without ARC. Results: Fifty-seven patients were included, of whom 49 (86%) exhibited ARC. Subjects with ARC were more likely to be male and had a significantly higher median measured CrCl (201.7 mL/min/1.73 m2) than those without ARC (109.8 mL/min/1.73 m2). The Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) score displayed the strongest association (vs. CrCl equations) with ARC development (area under the receiver operating characteristic curve, 0.648). Conclusion: The prevalence of ARC in the present study of a broad neurocritical care population appeared to be high (86%). The ARCTIC score had higher sensitivity and specificity for diagnosing ARC than the common serum creatinine-based estimation.