Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

Auclair, Sarah,Liu, Fengliang,Niu, Qingli,Hou, Wei,Churchyard, Gavin,Morgan, Cecilia,Frahm, Nicole,Nitayaphan, Sorachai,Pitisuthithum, Punnee,Rerks-Ngarm, Supachai,Kimata, Jason T.,Soong, Lynn,Franchi Public Library of Science 2018 PLoS pathogens Vol.14 No.2

<▼1><P>The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV <I>in vitro</I>. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.</P></▼1><▼2><P><B>Author summary</B></P><P>Development of a safe and efficacious HIV vaccine is a critical global health priority. Recombinant viral vectors are an important platform for HIV vaccine delivery. Recent clinical trials testing candidate HIV vaccines based on Ad5 vectors failed and reported excess HIV infections in some vaccine recipients, underscoring the necessity to investigate HIV susceptibility of viral vector-specific CD4 T cells in HIV vaccination. By using PBMC samples from clinical trials that examined two important HIV vaccine vectors (canarypox viral vector ALVAC and human Ad5 vector), we here report that compared to Ad5 vector, the ALVAC-specific CD4 T cells are more resistant to HIV infection, providing evidence for distinct HIV susceptibility of CD4 T-cell populations induced by different HIV vaccine vectors. Our findings present new insights into our understanding of HIV vaccine-induced immunity and help improve the design and immune assessment of viral vectors for the development of HIV vaccines.</P></▼2>

Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

Pan, Youdong,Tian, Tian,Park, Chang Ook,Lofftus, Serena Y.,Mei, Shenglin,Liu, Xing,Luo, Chi,O’Malley, John T.,Gehad, Ahmed,Teague, Jessica E.,Divito, Sherrie J.,Fuhlbrigge, Robert,Puigserver, Pere,Kru Macmillan Publishers Limited, part of Springer Nat 2017 Nature Vol.543 No.7644

Tissue-resident memory T (T<SUB>RM</SUB>) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of T<SUB>RM</SUB> cells are obscure. Here we show that mouse CD8<SUP>+</SUP> T<SUB>RM</SUB> cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8<SUP>+</SUP> T<SUB>RM</SUB> cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (T<SUB>CM</SUB>) cells in lymph nodes. In vitro, CD8<SUP>+</SUP> T<SUB>RM</SUB> cells, but not CD8<SUP>+</SUP> T<SUB>CM</SUB> cells, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8<SUP>+</SUP> T<SUB>RM</SUB> cells. The persistence of CD8<SUP>+</SUP> T<SUB>RM</SUB> cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8<SUP>+</SUP> T<SUB>RM</SUB> cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8<SUP>+</SUP> T<SUB>RM</SUB> cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8<SUP>+</SUP> T<SUB>RM</SUB> cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8<SUP>+</SUP> T<SUB>RM</SUB> cells, and suggest that CD8<SUP>+</SUP> T<SUB>RM</SUB> cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity.

OPTIMIZATION RESEARCH FOR A HIGH PRESSURE COMMON RAIL DIESEL ENGINE BASED ON SIMULATION

Y. LIU,Y.-T. ZHANG,T. QIU,X. DING,Q. XIONG 한국자동차공학회 2010 International journal of automotive technology Vol.11 No.5

ABSTRACT−A TP (Temperature Phase) model is presented to carry out optimization calculation for a high-pressure common rail diesel engine. Temperature is the most important parameter in the TP model. For the lower branch (when temperature T < 850 K) of the S-shaped curve (auto-ignition phase), a 6-step ad-hoc model with adjusted rate constants of nheptane is used, referred to steady state assumption. Steady state assumption is based on the observation that, due to very fast chemical processes in combustion problems, many chemical species and reactions are in a quasi-steady state or partial equilibrium. When a species is assumed to be in the steady state, the corresponding differential equation can be replaced by an algebraic relation, which reduces the computational costs. For the middle branch (850 K ≤ T < 1100 K) of the S-shaped curve, a 4-step model is used to calculate the unstable phase. For the upper branch (T≥1100 K) of the S-shaped curve, onestep model is used because the one-step model has widely been used in descriptions of flame stability where it essentially serves as a model that produces a thin flame with strong temperature sensitivity. When zone temperature T<1500 K, only the soot precursors –PAHs (Polycyclic aromatic hydrocarbons) is created and there is no soot emission. When zone temperature T≥1500 K, PAHs and soot source terms (particle inception, surface growth, oxidation, coagulation) are calculated. The TP model is then applied in multidimensional simulations to carry out optimizing, which reduces experiment cost. The results of cylinder pressures, the corresponding heat release rates, NOx and soot with variation of injection time at constant rail pressure, variation of EGR-rate at constant rail pressure and variation of rail pressure at constant EGR-rate between simulation and experimental data are analyzed. The results indicate that the TP model can carry out optimization and CFD (computational fluid dynamics) and can be a tool to calculate for a high-pressure common rail diesel engine.

The enhanced phosphorescence from Alq₃ fluorescent materials by phosphor sensitization

Tsuboi, T.,Kwon, J.H.,Liu, X.,Huang, W. Elsevier Sequoia 2014 Journal of photochemistry and photobiology Chemist Vol.291 No.-

The green emission accompanied with intense red phosphorescence is observed from the tris(8-hydroxyquinoline) aluminum (Alq<SUB>3</SUB>) in the heavily doped tris(2-phenylpyridine) iridium [Ir(ppy)<SUB>3</SUB>] films. This photoluminescence (PL) emission mechanism is studied by the PL excitation (PLE) spectra for the red and green emissions. From the PLE spectrum for the red emission, the energy transfer from Ir(ppy)<SUB>3</SUB> to Alq<SUB>3</SUB> is confirmed. The increase of the green emission with increasing temperature from 12K is explained by the endothermic back Forster energy transfer from the triplet T<SUB>1</SUB> state of Ir(ppy)<SUB>3</SUB> to the singlet S<SUB>1</SUB> state of Alq<SUB>3</SUB>. It is suggested that this back transfer is partially responsible for the decrease of the red emission intensity corresponding to the increase of the green emission. Unlike the Forster energy transfer, the Dexter energy transfer from the T<SUB>1</SUB> state of Ir(ppy)<SUB>3</SUB> to the T<SUB>1</SUB> state of Alq<SUB>3</SUB> is highly efficient. The explanation for this process is presented here. The green emission is not attributed to Ir(ppy)<SUB>3</SUB> but to Alq<SUB>3</SUB>, because not only the green emission profile but also the red emission profile is quite similar to the δ-phase polycrystalline Alq<SUB>3</SUB>. From these results, it is concluded that the Alq<SUB>3</SUB> forms a δ-phase polycrystalline state to accept the phosphor sensitization. The unusual enhancement of the red phosphorescence from the Alq<SUB>3</SUB> is explained by the mixing of the T<SUB>1</SUB> state of Ir(ppy)<SUB>3</SUB> with the T<SUB>1</SUB> state of Alq<SUB>3</SUB> under the Dexter energy transfer of short range process, by taking into account that the T<SUB>1</SUB> state of Ir(ppy)<SUB>3</SUB> contains the singlet state by the strong spin-orbit coupling.

The Probiotic and Adherence Properties of Lactobacillus reuteri Pg4 Expressing the Rumen Microbial β-Glucanase

Yu, B.,Liu, J.R.,Hsiao, F.S.,Lee, T.T.,Chiou, P.W.S. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.9

This study was conducted to evaluate the potential of the transformed Lactobacillus reuteri Pg4 (T-Pg4) harboring the ${\beta}$-glucanase gene as a poultry probiotic. The probiotic properties of the T-Pg4 strain were evaluated in vitro by their adherence capability and acid and bile salt tolerance, and were evaluated in vivo by their survival and adhesion in the gastrointestinal tract (GIT) of specific-pathogen-free (SPF) chickens. The results showed that the T-Pg4 strain exhibited resistance to acidic conditions and contact with bile salt, and adhered efficiently to the crop and intestinal epithelial cells of chickens in vitro. The T-Pg4 strain also could survive and colonize the gastrointestinal epithelium of the experimental SPF chickens in vivo. In addition, radial enzyme diffusion was used to demonstrate that the Lactobacillus spp. randomly isolated from the GIT of the SPF chickens fed T-Pg4 possessed ${\beta}$-glucanase secretion capability. These findings have demonstrated that the transformed L. reuteri Pg4 survives transit through the stomach and intestine, and may secrete ${\beta}$-glucanase in the chicken GIT. Therefore, it is suggested that this organism could be used as a multifunctional poultry probiotic.

The Role of Tumor Microenvironment in Mycosis Fungoides and Sézary Syndrome

( Zhaorui Liu ),( Xuesong Wu ),( Sam T. Hwang ),( Jie Liu ) 대한피부과학회 2021 Annals of Dermatology Vol.33 No.6

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphomas (CTCLs). Most cases of MF display an indolent course during its early stage. However, in some patients, it can progress to the tumor stage with potential systematic involvement and a poor prognosis. SS is defined as an erythrodermic CTCL with leukemic involvements. The pathogenesis of MF and SS is still not fully understood, but recent data have found that the development of MF and SS is related to genetic alterations and possibly to environmental influences. In CTCL, many components interacting with tumor cells, such as tumor-associated macrophages, fibroblasts, dendritic cells, mast cells, and myeloid-derived suppressor cells, as well as with chemokines, cytokines and other key players, establish the tumor microenvironment (TME). In turn, the TME regulates tumor cell migration and proliferation directly and indirectly and may play a critical role in the progression of MF and SS. The TME of MF and SS appear to show features of a Th2 phenotype, thus dampening tumorrelated immune responses. Recently, several studies have been published on the immunological characteristics of MF and SS, but a full understanding of the CTCL-related TME remains to be determined. This review focuses on the role of the TME in MF and SS, aiming to further demonstrate the pathogenesis of the disease and to provide new ideas for potential treatments targeted at the microenvironment components of the tumor.

Experimental study on seismic performance of steel reinforced concrete T-shaped columns

Zuqiang Liu,Chaofeng Zhou,Jianyang Xue,Roberto T. Leon 국제구조공학회 2020 Steel and Composite Structures, An International J Vol.36 No.3

This study investigates the seismic performance of steel reinforced concrete (SRC) T-shaped columns under low cyclic loading tests. Based on test results of ten half-scale column specimens, failure patterns, hysteretic behavior, skeleton curves, ultimate strength, ductility, stiffness degradation and energy dissipation capacity were analyzed. The main variables included loading angles, axial compression ratios and steel ratios. The test results show that the average values of the ductility factor and the equivalent viscous damping coefficient with respect to the failure of the columns were 5.23 and 0.373, respectively, reflecting good seismic performance. The ductility decreased and the initial stiffness increased as the axial compression ratio of the columns increased. The strength increased with increasing steel ratio, as expected. The columns displaced along the web had higher strength and initial stiffness, while the columns displaced along the flange had better ductility and energy dissipation capacity. Based on the test and analysis results, a formula is proposed to calculate the effective stiffness of SRC T-shaped columns.

Influence of aromatic heterocycle of conjugated side chains on photovoltaic performance of benzodithiophene-based wide-bandgap polymers

Xue, X.,Fan, B.,Liu, T.,Sun, X.,Huo, L.,Ha, S.,Choi, H.,Kim, T.,Kim, J.,Wei, D. Royal Society of Chemistry 2016 Polymer chemistry Vol.7 No.24

<P>Extensive efforts have been focused on the study of wide-band gap (WBG) polymers due to their important applications in multiple junction and ternary blend organic solar cells. Herein, three WBG copolymers named PBDT(X)-T1 (X = O, S, Se) were synthesized based on the benzodithiophene (BDT) donor unit and 1,3-bis(5-bromothiophen-2-yl)-5,7-bis(2-ethylhexyl)-4H, 8H-benzo[1,2-c: 4,5-c']dithiophene-4,8-dione (T1) acceptor unit. Different aromatic heterocycle groups (furan, thiophene and selenophene) were introduced to modify the BDT unit to investigate the influence of conjugated side chains on the photovoltaic properties of conjugated polymers. Photophysical properties, electrochemistry, charge transport and crystalline properties of the polymers were studied to discuss the role of chalcogen atoms on the performance of conjugated polymers. Solar cells based on these three WBG copolymers were fabricated. Among them, the PBDT(Se)-T1-based solar cell shows the best photovoltaic performance with the highest power conversion efficiency (PCE) of 8.52%, an open-circuit voltage (V-oc) of 0.91 V, and a high fill factor (FF) of 72%. The high crystallinity and preferential face-on orientation in the blend film partially explain the superior photovoltaic performance achieved in PBDT(Se)-T1-based solar cells. The results indicate the important role of chalcogen atoms in conjugated side chains and that high photovoltaic performance can be realized through side chain engineering of BDT-based WBG conjugated polymers.</P>

Flow characteristics around a row of circular and wavy cylinders

K. Lam,T. Cai,Y. F. Lin,Y. Liu 대한기계학회 2007 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.21 No.11

The near-wake and flow interference around a row of five circular cylinders, staggered wavy cylinders and nonstaggered wavy cylinders are investigated experimentally by using PIV and LIF techniques. The effects and characteristics of employing wavy cylinders instead of circular cylinders are discussed. The cylinders were arranged at T/d=1.5 with Re ranging from 125 to 40000. Results showed the staggered wavy cylinders give rise to a more stable flow pattern with less fluctuation and longer wake vortex closure length.

Energy and Ileal Digestible Amino Acid Concentrations for Growing Pigs and Performance of Weanling Pigs Fed Fermented or Conventional Soybean Meal

Wang, Y.,Lu, W.Q.,Li, D.F.,Liu, X.T.,Wang, H.L.,Niu, S.,Piao, X.S. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.5

A new strategy of co-inoculating Bacillus subtilis MA139 with Streptococcus thermophilus and Saccharomyces cerevisiae was used to produce fermented soybean meal (FSBM). Three experiments were conducted to determine the concentration of digestible energy (DE) and metabolizable energy (ME) (Exp. 1), apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids (AA) (Exp. 2), and feeding value (Exp. 3) of FSBM produced by this new strategy (NFSB) compared with soybean meal (SBM) and conventionally available FSBM (Suprotein). In Exp. 1, twenty-four barrows (initial body weight [BW] of $32.2{\pm}1.7kg$) were randomly allotted to 1 of 4 diets with 6 replicates per diet. A corn basal diet and 3 diets based on a mixture of corn and 1 of 3 soybean products listed above were formulated and the DE and ME contents were determined by the difference method. The results showed that there were no differences in DE and ME between SBM and either FSBM product (p>0.05). In Exp. 2, eight barrows (initial BW of $26.8{\pm}1.5kg$) were fitted with ileal T-cannulaes and used in a replicated $4{\times}4$ Latin square design. Three corn-starch-based diets were formulated using each of the 3 soybean products as the sole source of AA. A nitrogen-free diet was also formulated to measure endogenous losses of AA. The results showed that the SID of all AA except arginine and histidine was similar for NFSB and SBM (p>0.05), but Suprotein had greater (p<0.05) SID of most AA except lysine, aspartate, glycine and proline than NFSB. In Exp. 3, a total of 144 piglets (initial BW of $8.8{\pm}1.2$ kg) were blocked by weight and fed 1 of 4 diets including a control diet with 24% SBM as well as diets containing 6% and 12% NFSB or 12% Suprotein added at the expense of SBM. During d 15 to 28, replacing SBM with 6% NFSB significantly improved average daily gain (ADG) and average daily feed intake (ADFI) (p<0.05) for nursery piglets. During the overall experiment, ADG of piglets fed diets containing 6% NFSB was significantly greater (p<0.05) than that of piglets fed SBM. In conclusion, fermentation with the new strategy did not affect the energy content or the AID and the SID of AA in SBM. However, inclusion of 6% NFSB in diets fed to nursery piglets improved performance after weaning likely as a result of better nutritional status and reduced immunological challenge.