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Biomedical subjects

G Yu

Publications and source records attributed to G Yu.

At least 19 recordsLinked to original sources

Spin correlations in the electron-doped high-transition-temperature superconductor Nd2-xCexCuO4+/-delta.

High-transition-temperature (high-T(c)) superconductivity develops near antiferromagnetic phases, and it is possible that magnetic excitations contribute to the superconducting pairing mechanism. To assess the role of antiferromagnetism, it is essential to understand the doping and temperature dependence of the two-dimensional antiferromagnetic spin correlations. The phase diagram is asymmetric with respect to electron and hole doping, and for the comparatively less-studied electron-doped materials, the antiferromagnetic phase extends much further with doping and appears to overlap with the superconducting phase. The archetypal electron-doped compound Nd2-xCexCuO4+/-delta (NCCO) shows bulk superconductivity above x approximately 0.13 (refs 3, 4), while evidence for antiferromagnetic order has been found up to x approximately 0.17 (refs 2, 5, 6). Here we report inelastic magnetic neutron-scattering measurements that point to the distinct possibility that genuine long-range antiferromagnetism and superconductivity do not coexist. The data reveal a magnetic quantum critical point where superconductivity first appears, consistent with an exotic quantum phase transition between the two phases. We also demonstrate that the pseudogap phenomenon in the electron-doped materials, which is associated with pronounced charge anomalies, arises from a build-up of spin correlations, in agreement with recent theoretical proposals.

Journal Article↗

PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies.

Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory molecules, plays an important role in the regulations of the cellular and humoral immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies named 10E10 and 2H11 were successfully generated and further characterized. Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T lymphocytes, B lymphocytes and dendritic cells. Then, by using immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD-L1 was found in human gastric carcinoma specimens but not in normal or gastric adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1. Taken together, these results showed that the two functional mouse anti-human PD-L1 monoclonal antibodies we generated might be of great value for further exploration of the costimulatory molecule regulating network and immunointervention for tumor immunotherapy.

Animals↗

The expression analysis of ICOS-L on activated T cells and immature dendritic cells as well as malignant B cells and Grave's-disease-derived thyroid tissues by two novel mAbs against human ICOS-L.

ICOS-L, a newly identified member of B7 superfamily, plays an important role in immune responses. In this article, we report on two novel mouse anti-human ICOS-L monoclonal antibodies (mAbs) named as 11C4 and 12B11, whose specificities were verified by methods of flow cytometry, western blotting, and epitope competition assay. The two mAbs bound to distinct ICOS-L epitopes on B cells. Interestingly, mAb 11C4 could well recognize ICOS-L molecule on activated T cells and Jurkat cell lines, which is different from commercial anti-ICOS-L mAb (clone number MIH12) and the other mAb 12B11. In addition, we found that the expression of ICOS-L molecule was only detected on the surface of immature monocyte-derived dendritic cells (Mo-DCs) and was sharply decreased after induction of mature Mo-DCs activated by tumor necrosis factor-alpha or CD40. Furthermore, we showed that 11C4 could effectively suppress the maturation of Mo-DCs in vitro as evidenced by the low expression of CD80, CD86, CD83, and human leukocyte antigen-DR, which suggested that ICOS-L may be involved in the maturation of Mo-DCs. Using immunohistochemistry staining with mAb 11C4, the expression of ICOS-L was found in B lymphoma tissues and thyroid tissues from the Grave's disease but not in thyroid adenoma and normal thyroid tissues.

Animals↗

Carbon sinks and sources in China's forests during 1901-2001.

This paper reports the annual carbon (C) balance of China's forests during 1901-2001 estimated using the Integrated Terrestrial Ecosystem C-budget model (InTEC). Annual carbon source and sink distributions are simulated for the same period using various spatial datasets including land cover and leaf area index (LAI) obtained from remote sensing, soil texture, climate, forest age, and nitrogen deposition. During 1901-1949, China's forests were a source of 21.0+/-7.8 Tg C yr(-1) due to disturbances (human activities). Its size increased to 122.3+/-25.3 Tg C yr(-1) during 1950-1987 due to intensified human activities in the late 1950s, early 1960s, 1970s and early 1980s. The forests became large sinks of 176.7+/-44.8 Tg C yr(-1) during 1988-2001, owing to large-scale plantation and forest regrowth in previously disturbed areas as well as growth stimulation by nondisturbance factors such as climatic warming, atmospheric CO(2) fertilization, and N deposition. From 1901 to 2001, China's forests were a small carbon source of 3.32 Pg C, about 32.9+/-22.3 Tg C yr(-1). The overall C balance in biomass from InTEC generally agrees with previous results derived from forest inventories of China's forests. InTEC results also include C stock variation in soils and are therefore more comprehensive than previous results. The uncertainty in InTEC results is still large, but it can be reduced if a detailed forest age map becomes available.

Agriculture↗

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Bioterrorism↗

Magnetic field effect on the superconducting magnetic gap of Nd1.85Ce0.15CuO4.

Inelastic neutron-scattering measurements on the archetypical electron-doped material Nd1.85Ce0.15CuO4 up to a high relative magnetic-field strength, H/H(c2) approximately 50%, reveal a simple linear magnetic-field effect on the superconducting magnetic gap and the absence of field-induced in-gap states. The extrapolated gap-closing field value is consistent with the upper critical field H(c2), and the high-field response resembles that of the paramagnetic normal state.

Journal Article↗

Neprilysin activity and expression are controlled by nicastrin.

We recently demonstrated that the presenilin-dependent gamma-secretase complex regulates the expression and activity of neprilysin, one of the main enzymes that degrade the amyloid beta-peptide (Abeta) which accumulates in Alzheimer's disease. Here, we examined the influence of endogenous nicastrin (NCT), a member of the gamma-secretase complex, on neprilysin physiology. We show that nicastrin deficiency drastically lowers neprilysin expression, membrane-bound activity and mRNA levels, but it did not modulate the expression of two other putative Abeta-cleaving enzymes, endothelin-converting enzyme and insulin-degrading enzyme. Furthermore, we show that nicastrin restores neprilysin activity and expression in nicastrin-deficient, but not presenilin-deficient fibroblasts, indicating that the control of neprilysin necessitates the complete gamma-secretase complex harbouring its four reported components. Finally, we show that NCT expression peaked 24 h after NCT cDNA transfection of wild-type and NCT-/- fibroblasts, while neprilysin expression drastically increased only after 36 h and was maximal at 48 h. This delayed effect on neprilysin expression correlates well with our demonstration of an indirect gamma-secretase-dependent modulation of neprilysin at its transcriptional level.

Alzheimer Disease↗

The effect of bi-level positive airway pressure mechanical ventilation on gas exchange during general anaesthesia.

BACKGROUND: Atelectasis may occur and ventilation-perfusion mismatch may increase during general anaesthesia with neuromuscular paralysis and mechanical ventilation, though preservation of some intermittent muscle contraction might mitigate this process. There is still no ideal manoeuvre to minimize such mismatch or atelectasis. Bi-level positive airway pressure (BiPAP) ventilation adjusts to extra breaths and improves gas exchange during recovery of diaphragm function after neuromuscular paralysis. We hypothesize that BiPAP ventilation may limit the development of pulmonary shunt and may improve ventilation-perfusion mismatch when compared with standard IPPV, with or without PEEP when neuromuscular paralysis has been used during surgery. METHODS: Twenty ventilated patients either on BiPAP or IPPV with or without PEEP were studied randomly using the multiple inert gas elimination technique (MIGET) at 60 and 120 min after rocuronium at induction and after 60 min. Non-invasive cardiac output (NICO) monitoring and plasma concentrations of rocuronium were measured. We compared the data of MIGET, gas exchange, haemodynamic variables and pulmonary mechanics measurements between the different ventilatory modes. RESULTS: Intrapulmonary shunt (blood flow to V(A)/Q < 0.005) did not increase at 60 min of anaesthesia in any of the different ventilation modes compared with the shunt value before anaesthesia. Log standard deviation of perfusion increased in IPPV, with and without PEEP groups, compared with the baseline (P< 0.05) but did not increase in the BiPAP group. BiPAP ventilation generated a higher level of Pa(O2)than IPPV with or without PEEP (P<0.05). CONCLUSION: BiPAP ventilation was beneficial in decreasing ventilation-perfusion mismatch and improving oxygenation when compared with conventional IPPV (with or without PEEP).

Aged↗

MCM7 amplification and overexpression are associated with prostate cancer progression.

The genomic DNA profiles of prostate cancers with aggressive features were compared to the profiles of matched normal DNA to identify genes that are selectively amplified in the cancer cells. One of the identified genes, MCM7, which is a component of the DNA replication licensing complex, has been studied extensively both at the DNA and protein levels in human prostate tissues. Approximately half of the prostate cancer specimens studied showed MCM7 gene amplification, and 60% of the aggressive prostate cancer specimens had increased MCM7 protein expression. Amplification or overexpression of MCM7 was significantly associated with relapse, local invasion and a worse tumor grade. Constitutive expression of MCM7 in a human prostate cancer cell line, DU145, resulted in markedly increased DNA synthesis and cell proliferation compared to vector-only controls, and an increased cell invasion in vitro. Indeed, MCM7 overexpression produced primary tumors 12 times larger than vector-only controls and resulted in a rapid demise of mice bearing those tumors. These studies implicate MCM7, and the DNA replication licensing gene family, in prostate cancer progression, growth and invasion.

Animals↗

Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer.

BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. RESULTS: We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.

Adenocarcinoma↗

Characterization and application of two novel monoclonal antibodies against human OX40: costimulation of T cells and expression on tumor as well as normal gland tissues.

OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response. Here, we newly generated two specific mouse antihuman OX40 monoclonal antibodies (mAbs) (2G2 and 1F7), whose specificities are quite different from the available OX40 mAb (ACT35) by competition assay. It was also found that both mAbs could enhance the proliferation, activation and differentiation of T lymphocytes primed by anti-CD3 mAb. These results evidenced that both were functional antihuman OX40 mAbs. Furthermore, stained by 2G2 and 1F7, FCM and immunohistochemistry detected the constitutive expression of OX40 on tumor cell lines from epithelium, breast cancer and glioma tissues. Meanwhile, the non-tumor tissues (thyroid gland, stomach gland) were also found OX40 expression. These results suggested that OX40 is not only expressed in activated T cells, but also in some tumors as well as normal gland tissues. Such expression pattern indicated that OX40 may be a valuable surface antigen in unveiling its expression and function outside the immune system. Briefly, these novel antibodies may contribute to the evaluation of the mechanism of tumor metastasis and eventually shed light on further study of tumor immunotherapy and autoimmune diseases.

Animals↗

Chromate sorption and reduction kinetics onto an aminated biosorbent.

A novel biosorbent was prepared by chemically grafting of polyethylenimine (PEI) onto the fungal biomass of Penicillium chrysogenum through a two-step reaction. The modified biosorbent is favorable for the removal of anionic Cr(VI) species from aqueous solution due to the protonation of amine groups on the biomass surface. The sorption capacity for Cr(VI) increased by 7.2-fold after surface modification. Sorption kinetics results show that the pseudo-second-order kinetic model described the experimental data well. During the sorption process, X-ray photoelectron spectroscopy (XPS) was used to analyze the chromium species on the biosorbent surface and the results indicate that part of the Cr(VI) ions were reduced to Cr(III) ions which can be chelated with the amine groups on the biomass surface. The reduced Cr(III) ions formed some aggregates on the surface at higher solution pHs.

Adsorption↗

Charge-transfer excitations in the model superconductor HgBa(2)CuO(4+delta).

We report a Cu -edge resonant inelastic x-ray scattering (RIXS) study of charge-transfer excitations in the 2-8 eV range in the structurally simple compound HgBa(2)CuO(4+delta) at optimal doping (T(c)=96.5 K). The spectra exhibit a significant dependence on the incident photon energy which we carefully utilize to resolve a multiplet of weakly dispersive (<0.5 eV) electron-hole excitations, including a mode at 2 eV. The observation of this 2 eV excitation suggests the existence of a remnant charge-transfer gap deep in the superconducting phase. Quite generally, our results, which include additional data for the Mott insulator La(2)CuO(4), demonstrate the importance of exploring the incident photon-energy dependence of the RIXS cross section.

Journal Article↗

A pilot study of fatty acid metabolism in oral squamous cell carcinoma.

This study was undertaken to determine the characteristics of fatty acid synthesis in squamous carcinoma cells and to assess the possibility of exploiting this synthesis pathway in anticancer therapy. Incorporation of [(3)H]acetate into total lipids of the TCA-83 squamous carcinoma cell line and normal gingival fibroblasts was measured. The effects of cerulenin, a specific, potent, noncompetitive inhibitor of fatty acid synthase (FAS), on growth of TCA-83 cells and normal gingival fibroblasts was determined by the MTT method, and the effect of cerulenin on apoptosis was determined by electrophoresis of cellular DNA. Incorporation of [(3)H]acetate into total lipids was significantly higher in TCA-83 cells (68 +/- 12.7 cpm per 2 x 10(5) cells) than in normal gingival fibroblasts (13 +/- 4.2 cpm per 2 x 10(5) cells; P = 0.011). Cerulenin inhibited TCA-83 cell growth in a dose-dependent manner, even at 2.5 microg/ml, a concentration at which normal gingival fibroblasts were not inhibited. After exposure to cerulenin, TCA-83 cells showed typical apoptotic DNA ladders. These results indicate that cerulenin exerts selective cytotoxic effects on squamous carcinoma cells and can induce their apoptosis. These findings suggest that targeting of fatty acid synthesis may be useful in the treatment of squamous cell carcinomas.

Apoptosis↗

A universal scaling relation in high-temperature superconductors.

Since the discovery of superconductivity at elevated temperatures in the copper oxide materials there has been a considerable effort to find universal trends and correlations amongst physical quantities, as a clue to the origin of the superconductivity. One of the earliest patterns that emerged was the linear scaling of the superfluid density (rho(s)) with the superconducting transition temperature (T(c)), which marks the onset of phase coherence. This is referred to as the Uemura relation, and it works reasonably well for the underdoped materials. It does not, however, describe optimally doped (where T(c) is a maximum) or overdoped materials. Similarly, an attempt to scale the superfluid density with the d.c. conductivity (sigma(dc)) was only partially successful. Here we report a simple scaling relation (rho(s) proportional, variant sigma(dc)T(c), with sigma(dc) measured at approximately T(c)) that holds for all tested high-T(c) materials. It holds regardless of doping level, nature of dopant (electrons versus holes), crystal structure and type of disorder, and direction (parallel or perpendicular to the copper-oxygen planes).

Journal Article↗

Phase association of polycyclic aromatic hydrocarbons in the Minjiang River Estuary, China.

Persistent organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) are of great concern due to their persistence, bioaccumulation and toxic effects. In this work the levels of 16 priority PAHs were determined in water, pore water, sediment, soil and vegetable samples from Minjiang River Estuary, China. Total PAH concentrations varied from 9.9 to 474 microg/l in water, 82.1 to 239 microg/l in pore water, 112 to 877 ng/g dry wt. in surficial sediments, 128 to 465 ng/g dry wt. in soil and 8600 to 111,000 ng/g dry wt. in Chinese vegetables. Overall, the mean concentrations of PAHs were present in higher levels in pore water than that in surface water, due possibly to higher concentrations of dissolved organic carbon or colloids with which the hydrophobic pollutants were strongly associated. Such a concentration gradient implies a potential flux of pollutants from sediment pore water to overlying water. Contamination was dominated by high molecular mass PAH compounds in all samples, indicating combustion-derived sources (for example, pyrolysis at high temperature). The levels of PAHs in water and vegetable were relatively high in comparison to other studies, although PAHs in sediment and soil were comparable to those found in many other similar environments. The ratios of selected PAHs indicated again that PAHs in Minjiang River Estuary were mainly derived from incomplete combustion of fossil fuel.

China↗