Ju Wang

© 2016 American Chemical Society.A tetravalent cerium macrocyclic complex was prepared with an octadentate terephthalamide ligand comprised of hard catecholate donors and characterized in the solution state by spectrophotometric titrations and electrochemistry and in the crystal by X-ray diffraction. The solution-state studies showed that L exhibits a remarkably high affinity toward Ce4+, with log β110 = 61 and ΔG = -348 kJ/mol, compared with log β110 = 32.02 for the analogous Pr3+ complex. In addition, L exhibits an unusual preference for forming CeL4- relative to formation of the analogous actinide complex, ThL4-, which has β110 = 53.7. The extreme stabilization of tetravalent cerium relative to its trivalent state is also evidenced by the shift of 1.91 V in the redox potential of the Ce3+/Ce4+ couple of the complex. The unprecedented behavior prompted an electronic structure analysis using L3- and M5,4-edge X-ray absorption near-edge structure spectroscopies and configuration interaction calculations, which showed that 4f-orbital bonding in CeLK4 has partial covalent character due to ligand-to-metal charge transfer in the ground state. The experimental results are presented in the context of earlier measurements on tetravalent cerium compounds, indicating that the amount of LMCT for CeLK4 is similar to that observed for [Et4N]2[CeCl6] and CeO2 and significantly less than that for the organometallic sandwich compound cerocene, 2Ce. A simple model to rationalize changes in 4f orbital bonding for tri- and tetravalent lanthanide and actinide compounds is also provided.

© 2016 The Royal Society of Chemistry.The electronic structure in the complete series of stable lanthanide sesquioxides, Ln2O3, has been evaluated using oxygen K-edge X-ray absorption spectroscopy with a scanning transmission X-ray microscope. The experimental results agree with recent synthetic, spectroscopic and theoretical investigations that provided evidence for 5d orbital involvement in lanthanide bonding, while confirming the traditional viewpoint that there is little Ln 4f and O 2p orbital mixing. However, the results also showed that changes in the energy and occupancy of the 4f orbitals can impact Ln 5d and O 2p mixing, leading to several different bonding modes for seemingly identical Ln2O3 structures. On moving from left to right in the periodic table, abrupt changes were observed for the energy and intensity of transitions associated with Ln 5d and O 2p antibonding states. These changes in peak intensity, which were directly related to the amounts of O 2p and Ln 5d mixing, were closely correlated to the well-established trends in the chemical accessibility of the 4f orbitals towards oxidation or reduction. The unique insight provided by the O K-edge XAS is discussed in the context of several recent theoretical and physical studies on trivalent lanthanide compounds.

We report coregistration of near-infrared diffuse optical spectroscopy and magnetic resonance imaging for the study of animal model tumors. A combined broadband steady-state and frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue. Tissue hemoglobin oxygen saturation also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 ± 5%, whereas StO2 determined for necrotic tissue was 43 ± 6%. © 2003 Optical Society of America.

We present a combined near-infrared diffuse optical spectroscopy and Magnetic Resonance Imaging system for the study of animal model tumors. A combined broad-band steady-state and frequency domain optical spectroscopy apparatus was integrated with the MRI. The physiological properties of tissue rendered by MRI, including vascular volume fraction and water, were compared with chromophore concentrations as determined from the parameters obtained by optical measurements. DOS measurements provided oxyhemoglobin, deoxy-hemoglobin, and water concentration locally in tumors. A method for coregistration of the information obtained by both modalities was developed. Using Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, illustrating which tissue structure was probed optically. Finally, two optical contrast agents, indocyanine green and methylene blue, were employed and their kinetics were measured by DOS system from different locations on the tumor and compared with Gd-DTPA enhancement maps obtained from MRI.

We present a study of the dynamics of optical contrast agents indocyanine green and methylene blue in an adenocarcinoma rat tumor model. Measurements are conducted with a combined frequency-domain and steady-state optical technique that facilitates rapid measurement of tissue absorption in the 650–1000-nm spectral region. Tumors were also imaged by use of contrast-enhanced magnetic resonance imaging and coregistered with the location of the optical probe. The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin, and water are measured simultaneously each second for approximately 10 min. The differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise from differences in their effective molecular weights. ICG, because of its binding to plasma proteins, behaves as a macromolecular contrast agent with a low vascular permeability. A compartmental model describing ICG dynamics is used to quantify physiologic parameters related to capillary permeability. In contrast, MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the vasculature into the extravascular, extracellular space, and is sensitive to blood flow and the arterial input function. © 2003 Optical Society of America.

© 2015 Elsevier B.V.This article demonstrates an instrumented mouthguard capable of non-invasively monitoring salivary uric acid levels. The enzyme -modified screen printed electrode system has been integrated onto a mouthguard platform along with anatomically-miniaturized instrumentation electronics featuring a potentiostat, microcontroller, and a Bluetooth Low Energy transceiver. Unlike RFID-based biosensing systems, which require large proximal power sources, the developed platform enables real-time wireless transmission of the sensed information to standard smartphones, laptops, and other consumer electronics for on-demand processing, diagnostics, or storage. The mouthguard biosensor system offers high sensitivity, selectivity, and stability towards uric acid detection in human saliva, covering the concentration ranges for both healthy people and hyperuricemia patients. The new wireless mouthguard biosensor system is able to monitor SUA level in real-time and continuous fashion, and can be readily expanded to an array of sensors for different analytes to enable an attractive wearable monitoring system for diverse health and fitness applications.

© Hsiao et al.; licensee BioMed Central.Background: Identifying cellular signaling pathways that become corrupted in the presence of androgens that increase the metastatic potential of organ-confined tumor cells is critical to devising strategies capable of attenuating the metastatic progression of hormone-naïve, organ-confined tumors. In localized prostate cancers, gene fusions that place ETS-family transcription factors under the control of androgens drive gene expression programs that increase the invasiveness of organ-confined tumor cells. C-X-C chemokine receptor type 4 is a downstream target of ERG, whose upregulation in prostate-tumor cells contributes to their migration from the prostate gland. Recent evidence suggests that CXCR4-mediated proliferation and metastasis of tumor cells is regulated by CXCR7 through its scavenging of chemokine CXCL12. However, the role of androgens in regulating CXCR4-mediated motility with respect to CXCR7 function in prostate-cancer cells remains unclear. Methods: Immunocytochemistry, western blot, and affinity-purification analyses were used to study how androgens influenced the expression, subcellular localization, and function of CXCR7, CXCR4, and androgen receptor in LNCaP prostate-tumor cells. Moreover, luciferase assays and quantitative polymerase chain reaction were used to study how chemokines CXCL11 and CXCL12 regulate androgen-regulated genes in LNCaP prostate-tumor cells. Lastly, cell motility assays were carried out to determine how androgens influenced CXCR4-dependent motility through CXCL12. Results: Here we show that, in the LNCaP prostate-tumor cell line, androgens coordinate the expression of CXCR4 and CXCR7, thereby promoting CXCL12/CXCR4-mediated cell motility. RNA interference experiments revealed functional interactions between AR and CXCR7 in these cells. Co-localization and affinity-purification experiments support a physical interaction between AR and CXCR7 in LNCaP cells. Unexpectedly, CXCR7 resided in the nuclear compartment and modulated AR-mediated transcription. Moreover, androgen-mediated cell motility correlated positively with the co-localization of CXCR4 and CXCR7 receptors, suggesting that cell migration may be linked to functional CXCR4/CXCR7 heterodimers. Lastly, CXCL12-mediated cell motility was CXCR7-dependent, with CXCR7 expression required for optimal expression of CXCR4 protein. Conclusions: Overall, our results suggest that inhibition of CXCR7 function might decrease the metastatic potential of organ-confined prostate cancers.

© 2014 American Chemical Society.Attempts to apply artificial nano/micromotors for diverse biomedical applications have inspired a variety of strategies for designing motors with diverse propulsion mechanisms and functions. However, existing artificial motors are made exclusively of synthetic materials, which are subject to serious immune attack and clearance upon entering the bloodstream. Herein we report an elegant approach that turns natural red blood cells into functional micromotors with the aid of ultrasound propulsion and magnetic guidance. Iron oxide nanoparticles are loaded into the RBCs, where their asymmetric distribution within the cells results in a net magnetization, thus enabling magnetic alignment and guidance under acoustic propulsion. The RBC motors display efficient guided and prolonged propulsion in various biological fluids, including undiluted whole blood. The stability and functionality of the RBC motors, as well as the tolerability of regular RBCs to the ultrasound operation, are carefully examined. Since the RBC motors preserve the biological and structural features of regular RBCs, these motors possess a wide range of antigenic, transport, and mechanical properties that common synthetic motors cannot achieve and thus hold considerable promise for a number of practical biomedical uses.

IMPORTANCE: Most evaluations of pay-for-performance incentives have focused on large-group practices. Thus, the effect of P4P in small practices, where many US residents receive care, is largely unknown. Furthermore, whether electronic health records with chronic disease management capabilities support small-practice response to P4P has not been studied. OBJECTIVE: To assess the effect of P4P incentives on quality in EHR-enabled small practices in the context of an established quality improvement initiative. DESIGN, SETTING, AND PARTICIPANTS: A cluster-randomized trial of small primary care clinics in New York City from April 2009 through March 2010. A city program provided all participating clinics with the same EHR software with decision support and patient registry functionalities and quality improvement specialists offering technical assistance. INTERVENTIONS: Incentivized clinicswere paid for each patient whose care met the performance criteria, but they received higher payments for patients with comorbidities, who had Medicaid insurance, or who were uninsured. Quality reports were given quarterly to both the intervention and control groups. MAIN OUTCOMES AND MEASURES: Comparison of differences in performance improvement, from the beginning to the end of the study, between control and intervention clinics for aspirin or antithrombotic prescription, blood pressure control, cholesterol control, and smoking cessation interventions. Mixed-effects logistic regression was used to account for clustering of patients within clinics, with a treatment by time interaction term assessing the statistical significance of the effect of the intervention. RESULTS: Participating clinics had similar baseline characteristics, with a mean of 4592 patients at the intervention group clinics and 3042 at the control group clinics. Intervention clinics had greater adjusted absolute improvement in rates of appropriate antithrombotic prescription, blood pressure control, and in smoking cessation interventions. Intervention clinics performed better on all measures for Medicaid and uninsured patients except cholesterol control, but no differences were statistically significant. CONCLUSIONS AND RELEVANCE: Among small EHR-enabled clinics, a P4P incentive program compared with usual care resulted in modest improvements in cardiovascular care processes and outcomes. Because most proposed P4P programs are intended to remain in place more than a year, further research is needed to determine whether this effect increases or decreases over time. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00884013.

Background: The p53 tumor suppressor and its related protein, p73, share a homologous DNA binding domain, and mouse genetics studies have suggested that they have overlapping as well as distinct biological functions. Both p53 and p73 are activated by genotoxic stress to regulate an array of cellular responses. Previous studies have suggested that p53 and p73 independently activate the cellular apoptotic program in response to cytotoxic drugs. The goal of this study was to compare the promoter-binding activity of p53 and p73 at steady state and after genotoxic stress induced by hydroxyurea. Results: We employed chromatin immunoprecipitation, the NimbleGen promoter arrays and a model-based algorithm for promoter arrays to identify promoter sequences enriched in anti-p53 or anti-p73 immunoprecipitates, either before or after treatment with hydroxyurea, which increased the expression of both p53 and p73 in the human colon cancer cell line HCT116-3. We calculated a model-based algorithm for promoter array score for each promoter and found a significant correlation between the promoter occupancy profiles of p53 and p73. We also found that after hydroxyurea treatment, the p53-bound promoters were still bound by p73, but p73 became associated with additional promoters that that did not bind p53. In particular, we showed that hydroxyurea induces the binding of p73 but not p53 to the promoter of MLH3, which encodes a mismatch repair protein, and causes an up-regulation of the MLH3 mRNA. Conclusion: These results suggest that hydroxyurea exerts differential effects on the promoter-binding functions of p53 and p73 and illustrate the power of model-based algorithm for promoter array in the analyses of promoter occupancy profiles of highly homologous transcription factors. © 2009 Huang et al; licensee BioMed Central Ltd.

Background: High throughput screens with RNA interference technology enable loss-of-function analyses of gene activities in mammalian cells. While the construction of genome-scale shRNA libraries has been successful, results of large-scale screening of those libraries can be difficult to analyze because of the relatively high noise levels and the fact that not all shRNAs in a library are equally effective in silencing gene expression. Results: We have screened a library consisting of 43,828 shRNAs directed against 8,500 human genes for functions that are necessary in cell detachment induced by a constitutively activated c-Abl tyrosine kinase. To deal with the issues of noise and uncertainty of knockdown efficiencies, we employed an analytical strategy that combines quantitative data analysis with biological knowledge, i.e. Gene Ontology and pathway information, to increase the power of the RNAi screening technique. Using this strategy we found 16 candidate genes to be involved in Abl-induced disruption of cell adhesion, and verified that the knockdown of IL6ST is associated with enhanced cell attachment. Conclusion: Our results suggest that the power of genome-wide quantitative shRNA screens can be significantly increased when analyzed using a systems biology-based approach to identify functional gene networks. © 2008 Huang et al; licensee BioMed Central Ltd.

In this paper, I attempt to show how Davidson’s anti-sceptical argument can respond to the closureRK-based radical scepticism. My approach will focus on the closureRK principle rather than the possibility that our beliefs could be massively wrong. I first review Davidson’s principle of charity and the triangulation argument, and then I extract his theory on content of a belief. According to this theory, content of a belief is determined by its typical cause and other relevant beliefs. With this constraint on content, I argue that doubt must be local. Furthermore, since one cannot rationally believe that one’s commitment to the cause of beliefs could be false, our commitment to the denial of a sceptical hypothesis is not a knowledge-apt belief. Therefore, the closureRK principle is not applicable to rational evaluations of this commitment. As a result, the closureRK-based sceptical argument fails while the closureRK principle remains.

In contemporary epistemology, sceptical arguments are motivated either by the closure principle or the underdetermination principle. Therefore, it is very important to figure out the structure of the sceptical argument before coming up with an anti-sceptic strategy. With a review of the debate on the relationship between the two principles from Anthony Brueckner to Kevin McCain, it is argued that while maintaining the weak closed justification , closure and underdetermination are not logically equivalent. As a result, two independent responses are needed to answer the sceptical problem satisfactorily. Also, in order to secure a philosophically significant notion of justification and evidence, reasons are given to hold WCJ*, as opposed to rejecting it. This understanding of the sceptical argument would help to focus the real challenge of scepticism