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Find video protocols related to scientific articles indexed in Pubmed.
Electron small polarons and their transport in bismuth vanadate: a first principles study.
Phys Chem Chem Phys
PUBLISHED: 11-13-2014
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Relatively low electron mobility has been thought to be a key factor that limits the overall photocatalytic performance of BiVO4, but the behavior of electrons has not been fully elucidated. We examine electron localization and transport in BiVO4 using hybrid density functional theory calculations. An excess electron is found to remain largely localized on one V atom. The predicted hopping barrier for the small polaron is 0.35 eV (with inclusion of 15% Hartree-Fock exchange), and tends to increase almost linearly with lattice constant associated with pressure and/or temperature changes. We also examine the interaction between polarons, and discuss the possible concentration-dependence of electron mobility in BiVO4.
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Atypical Carcinoid Tumor of the Lung: a Surveillance, Epidemiology, and End Results Database Analysis.
J Thorac Oncol
PUBLISHED: 11-06-2014
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Atypical carcinoid (AC) of the lung is a rare form of thoracic malignancy. The limited knowledge of its biology and outcome stems largely from small, single institution experiences. We analyzed the Surveillance, Epidemiology, and End Results database (SEER) to better understand the clinical characteristics of this disease.
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Equilibrium Chemical Vapor Deposition Growth of Bernal-Stacked Bilayer Graphene.
ACS Nano
PUBLISHED: 11-04-2014
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Using ethanol as the carbon source, self-limiting growth of AB-stacked bilayer graphene (BLG) has been achieved on Cu via an equilibrium chemical vapor deposition (CVD) process. We found that during this alcohol catalytic CVD (ACCVD) a source-gas pressure range exists to break the self-limitation of monolayer graphene on Cu, and at a certain equilibrium state it prefers to form uniform BLG with a high surface coverage of ?94% and AB-stacking ratio of nearly 100%. More importantly, once the BLG is completed, this growth shows a self-limiting manner, and an extended ethanol flow time does not result in additional layers. We investigate the mechanism of this equilibrium BLG growth using isotopically labeled (13)C-ethanol and selective surface aryl functionalization, and results reveal that during the equilibrium ACCVD process a continuous substitution of graphene flakes occurs to the as-formed graphene and the BLG growth follows a layer-by-layer epitaxy mechanism. These phenomena are significantly in contrast to those observed for previously reported BLG growth using methane as precursor.
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Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone.
J. Neurooncol.
PUBLISHED: 09-05-2014
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The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan-Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.
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Fast synthesis of high-quality reduced graphene oxide at room temperature under light exposure.
Nanoscale
PUBLISHED: 08-21-2014
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An approach of presenting new reducing reagents, sodium-benzophenone (Na-B) or Na-B in the presence of the hydrazine (Na-B-H) system under light exposure could produce rGOs with/without N-doping at room temperature in both the solution phase and on a solid substrate. Benzophenone activated those solutions acting as a photosensitizer under light. It was assumed that the newly generated radical anions with electrons from Na-B under light can reduce GO to rGO sheets (rGONa-B1). In addition, the Na-B-H system can allow a higher degree of reduction with the doping of nitrogen atoms by the introduction of hydrazine to produce radical anions and electrons with a sodium hydrazide complex, which helps decrease the sheet resistance of the as-made rGONa-B-H2. The excellent properties (very low oxygen content (C/O ?16.2), and low sheet resistance (?130 ? square(-1))) of the rGOs were confirmed by XPS, XRD, IR, Raman spectroscopy, TGA, wettability, and sheet resistance measurements. High-quality rGO films on flexible substrates could be prepared by directly immersing the GO films in these solutions for several minutes.
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Predictors of survival outcomes in phase 1 relapsed or refractory multiple myeloma patients.
Cancer
PUBLISHED: 08-19-2014
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The categories of the International Myeloma Working Group (IMWG) response criteria for multiple myeloma are based on the magnitude of the change in paraprotein and the normalization of the free light chain ratio (rFLC). However, the relationship between the response by these biomarkers and clinical outcomes has not been validated with novel compounds in the phase 1 setting. Early response predictors may have prognostic value and speed development plans for new agents.
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Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer.
Cancer Med
PUBLISHED: 08-13-2014
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Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (?50% reduction in IC50 ) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a 5-gene expression profile.
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Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck.
Cancer
PUBLISHED: 08-07-2014
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Platinum-based therapy combined with cetuximab is standard first-line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN.
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Triple-negative breast carcinoma in African American and Caucasian women: clinicopathology, immunomarkers, and outcome.
Appl. Immunohistochem. Mol. Morphol.
PUBLISHED: 07-26-2014
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Breast cancers are often classified on the presence/absence of hormone receptors, and growth factor oncogenes (estrogen receptor, progesterone receptor, HER2). Triple-negative breast cancers, negative for these markers, do not benefit from targeted therapy. We compared clinicopathologic parameters and immunohistochemical markers of prognostic and/or predictive significance, and outcome between African American and Caucasian triple-negative breast cancer patients.
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Polarization characteristics of semipolar (112?2) InGaN/GaN quantum well structures grown on relaxed InGaN buffer layers and comparison with experiment.
Opt Express
PUBLISHED: 07-01-2014
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Partial strain relaxation effects on polarization ratio of semipolar (112?2) InxGa1?xN/GaN quantum well (QW) structures grown on relaxed InGaN buffers were investigated using the multiband effective-mass theory. The absolute value of the polarization ratio gradually decreases with increasing In composition in InGaN buffer layer when the strain relaxation ratio (?0y?y???y?y?)/?0y?y? along y?-axis is assumed to be linearly proportional to the difference of lattice constants between the well and the buffer layer. Also, it changes its sign for the QW structure grown on InGaN buffer layer with a relatively larger In composition (x > 0.07). These results are in good agreement with the experiment. This can be explained by the fact that, with increasing In composition in the InGaN subsrate, the spontaneous emission rate for the y?-polarization gradually increases while that for x?-polarization decreases due to the decrease in a matrix element at the band-edge (k? = 0).
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Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily IV busulfan fludarabine etoposide regimen in pediatric and infant ALL patients.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-30-2014
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Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance anti-leukemic effect. But toxicities have been reported in some studies using busulfan, cyclophosphamide and etoposide (BuCyVP) regimen. Recently, a reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted dose of busulfan has been recommended to improve the outcome of hematopoietic stem cell transplantation (HSCT). In this study, we evaluated the outcome of HSCT using a targeted once-daily intravenous (IV) busulfan fludarabine etoposide (BuFluVP) regimen in pediatric and infant ALL. Busulfan (? 1 year-120 mg/m(2) and < 1 year-80 mg/m(2)) was administered once daily as the first dose on day -8, and targeted dose of busulfan was used according to the TDM results on day -7 ? -5. A total of 44 patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 7 (15.9%) patients, but all of them were successfully treated. Cumulative incidence of treatment-related mortality and relapse were 9.1% and 9.9%. One-year overall survival (OS) and event free survival (EFS) of all patients were 86.2% and 83.8%, respectively. Twelve patients (27.3%) were infants at diagnosis, and 1-year OS of these patients was 83.3%. Our study demonstrated that HSCT using a targeted once-daily IV BuFluVP regimen showed favorable outcome and could be one option for HSCT in pediatric and infant ALL.
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Preoperative quantification of perceptions of surgical frailty.
J. Surg. Res.
PUBLISHED: 06-23-2014
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Frailty has gained recognition as an objective measure of a patient's physiologic reserve that ideally can replace the subjective biases of surgeons. In this study, we sought to examine the concordance between patient and attending surgeon perceptions of the patient's "fitness" before surgery. We then correlated these ratings with the patient's objective frailty scores.
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Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer.
ACS Nano
PUBLISHED: 06-14-2014
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Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin ?1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.
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Influence of V-pits on the efficiency droop in InGaN/GaN quantum wells.
Opt Express
PUBLISHED: 06-13-2014
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We discuss the influence of V-pits and their energy barrier, originating from its facets of (101¯1) planes, on the luminescence efficiency of InGaN LEDs. Experimental analysis using cathodoluminescence (CL) exhibits that thin facets of V-pits of InGaN quantum wells (QWs) appear to be effective in improving the emission intensity, preventing the injected carriers from recombining non-radiatively with threading dislocations (TDs). Our theoretical calculation based on the self-consistent approach with adopting k?p method reveals that higher V-pit energy barrier heights in InGaN QWs more efficiently suppress the non-radiative recombination at TDs, thus enhancing the internal quantum efficiency (IQE).
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Human papillomavirus 16 oncoprotein regulates the translocation of ?-catenin via the activation of epidermal growth factor receptor.
Cancer
PUBLISHED: 06-09-2014
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To understand the mechanism of frequent and early lymph node metastasis in high-risk human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), this study investigated whether ?-catenin is regulated by the HPV oncoprotein and contributes to OPSCC metastasis.
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Mass production of graphene quantum dots by one-pot synthesis directly from graphite in high yield.
Small
PUBLISHED: 04-19-2014
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One of the most efficient and straightforward methods for production of graphene quantum dots (GQDs) could be their direct preparation from graphite powder by one-pot synthesis using high-powered microwave irradiation. It is believed that in this way, graphite can be multiply broken by repeated redox reactions, which leads to a high yield and mass production.
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A long lasting ?1 adrenergic receptor stimulation of cAMP/protein kinase A (PKA) signal in cardiac myocytes.
J. Biol. Chem.
PUBLISHED: 04-08-2014
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Small-molecule, ligand-activated G protein-coupled receptors are generally thought to be rapidly desensitized within a period of minutes through receptor phosphorylation and internalization after repeated or prolonged stimulation. This transient G protein-coupled receptor activation remains at odds with many observed long-lasting cellular and physiological responses. Here, using live cell imaging of cAMP with a FRET-based biosensor and myocyte contraction assay, we show that the catecholamine-activated ?1 adrenergic receptor (?1AR) continuously stimulates second messenger cAMP synthesis in primary cardiac myocytes and neurons, which lasts for more than 8 h (a decay t½ of 3.9 h) in cardiac myocytes. However, the ?1AR-induced cAMP signal is counterbalanced and masked by the receptor-bound phosphodiesterase (PDE) 4D8-dependent cAMP hydrolysis. Inhibition of PDE4 activity recovers the receptor-induced cAMP signal and promotes contractile response in mouse hearts during extended periods of agonist stimulation. ?1AR associates with PDE4D8 through the receptor C-terminal PDZ motif-dependent binding to synaptic-associated protein 97 (SAP97). Knockdown of SAP97 or mutation of the ?1AR PDZ motif disrupts the complex and promotes sustained agonist-induced cAMP activity, PKA phosphorylation, and cardiac myocyte contraction response. Together, these findings unveil a long lasting adrenergic signal in neurons and myocytes under prolonged stimulation and an underappreciated role of PDE that is essential in classic receptor signaling desensitization and in maintaining a long lasting cAMP equilibrium for ligand-induced physiological response.
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NILCO biomarkers in breast cancer from Chinese patients.
BMC Cancer
PUBLISHED: 04-02-2014
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Notch, IL-1 and leptin are known pro-angiogenic factors linked to breast cancer development, tumor aggressiveness and poor prognosis. A complex crosstalk between these molecules (NILCO) has been reported in breast cancer cell lines. However, whether NILCO biomarkers are differentially expressed in estrogen responsive (ER+), unresponsive (ER-) and triple negative (TNBC) breast cancer tissues is unknown.
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A sodium manganese oxide cathode by facile reduction for sodium batteries.
Chem Asian J
PUBLISHED: 04-01-2014
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A nonstoichiometric sodium manganese oxide (Na(x)MnO(2+?)) cathode useful for sodium batteries was synthesized by an ambient-temperature strategy that involved facile reduction of aqueous sodium permanganate in sodium iodide and subsequent heat treatment at 600?°C. Combined powder X-ray diffraction and synchrotron X-ray diffraction analyses confirmed the annealed sample to belong to a Na(x)MnO2 phase with a P2-hexagonal structure. The ICP-AES results confirmed the stoichiometry of the sample to be Na0.53MnO(2+?) . Electron microscopy studies revealed the particle size of the electrode to be in the range of a few hundred nanometers. The Na0.53MnO(2+?) cathode delivered an average discharge capacity of 170?mA?h?g(-1) with a stable plateau at 2.1?V for the initial 25?cycles versus sodium. Ex?situ XANES studies confirmed the reversible intercalation of sodium into Na0.53MnO(2+?) and suggested the accommodation of over-stoichiometric Mn(4+) ions to contribute towards the performance of the electrode.
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Vertical alignments of graphene sheets spatially and densely piled for fast ion diffusion in compact supercapacitors.
ACS Nano
PUBLISHED: 04-01-2014
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Supercapacitors with porous carbon structures have high energy storage capacity. However, the porous nature of the carbon electrode, composed mainly of carbon nanotubes (CNTs) and graphene oxide (GO) derivatives, negatively impacts the volumetric electrochemical characteristics of the supercapacitors because of poor packing density (<0.5 g cm(-3)). Herein, we report a simple method to fabricate highly dense and vertically aligned reduced graphene oxide (VArGO) electrodes involving simple hand-rolling and cutting processes. Because of their vertically aligned and opened-edge graphene structure, VArGO electrodes displayed high packing density and highly efficient volumetric and areal electrochemical characteristics, very fast electrolyte ion diffusion with rectangular CV curves even at a high scan rate (20 V/s), and the highest volumetric capacitance among known rGO electrodes. Surprisingly, even when the film thickness of the VArGO electrode was increased, its volumetric and areal capacitances were maintained.
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Clinicopathologic Features and Outcome of Young Adults With Stage IV Colorectal Cancer.
Am. J. Clin. Oncol.
PUBLISHED: 03-26-2014
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Colorectal cancer has a distinct clinicopathologic presentation in younger patients. The aim of this paper was to evaluate the outcome of younger (age below 50 y) and older patients with stage IV (advanced) colorectal cancer in the modern era of combination chemotherapy.
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Concurrent therapy with taxane versus non-taxane containing regimens in locally advanced squamous cell carcinomas of the head and neck (SCCHN): a systematic review.
Oral Oncol.
PUBLISHED: 03-18-2014
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Platinum compounds remain the most widely utilized systemic agents in combination with radiation for treating SCCHN in the concurrent setting. Despite recent interest in using taxanes in this setting, there is a lack of randomized clinical trials to support this approach. We conducted a systematic review of published clinical trials of taxane-containing versus standard non-taxane-based regimens used in definitive treatment of SCCHN.
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A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes.
Cancer
PUBLISHED: 03-17-2014
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The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes ("unknown primaries").
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Diagnostic accuracy of ultrasonic histogram features to evaluate radiation toxicity of the parotid glands: a clinical study of xerostomia following head-and-neck cancer radiotherapy.
Acad Radiol
PUBLISHED: 03-06-2014
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To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT).
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HPV-associated lung cancers: an international pooled analysis.
Carcinogenesis
PUBLISHED: 02-12-2014
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Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.
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Pyro-synthesis of a high rate nano-Li3V2(PO4)3/C cathode with mixed morphology for advanced Li-ion batteries.
Sci Rep
PUBLISHED: 01-27-2014
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A monoclinic Li3V2(PO4)3/C (LVP/C) cathode for lithium battery applications was synthesized by a polyol-assisted pyro-synthesis. The polyol in the present synthesis acts not only as a solvent, reducing agent and a carbon source but also as a low-cost fuel that facilitates a combustion process combined with the release of ultrahigh exothermic energy useful for nucleation process. Subsequent annealing of the amorphous particles at 800°C for 5?h is sufficient to produce highly crystalline LVP/C nanoparticles. A combined analysis of X-ray diffraction (XRD) and neutron powder diffraction (NPD) patterns was used to determine the unit cell parameters of the prepared LVP/C. Electron microscopic studies revealed rod-type particles of length ranging from nanometer to micrometers dispersed among spherical particles with average particle-sizes in the range of 20-30?nm. When tested for Li-insertion properties in the potential windows of 3-4.3 and 3-4.8?V, the LVP/C cathode demonstrated initial discharge capacities of 131 and 196?mAh/g (~100% theoretical capacities) at 0.15 and 0.1?C current densities respectively with impressive capacity retentions for 50 cycles. Interestingly, the LVP/C cathode delivered average specific capacities of 125 and 90?mAh/g at current densities of 9.6?C and 15?C respectively within the lower potential window.
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Ferroelectric coupling effect on the energy-band structure of hybrid heterojunctions with self-organized P(VDF-TrFE) nanomatrices.
Adv. Mater. Weinheim
PUBLISHED: 01-25-2014
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Ferroelectric coupling effects on the energy-band structure of hybrid heterojunctions are investigated using hybrid photovoltaic devices with poly(3-hexylthiophene-2,5-diyl) (P3HT)/ZnO and poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)). The self-organized P(VDF-TrFE):P3HT photoactive layer forms a novel architecture consisting of P3HT domains in a P(VDF-TrFE) matrix. The energy-band structure at the interface of the p-n heterojunction is tuned by artificial control of the ferroelectric polarization of the P(VDF-TrFE) material, consequently modulating the photovoltaic performance of the hybrid photovoltaic devices.
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Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma.
Pancreas
PUBLISHED: 10-25-2013
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FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX.
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Clinical efficacy of targeted biologic agents as second-line therapy of advanced thyroid cancer.
Oncologist
PUBLISHED: 10-23-2013
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Targeted biologic agents showed clinically meaningful efficacy as front-line therapy for advanced radioiodine-refractory and medullary thyroid cancer. The clinical benefit of these agents beyond the front line has yet to be established. Methods. We assessed the clinical benefit of targeted agents in patients with advanced differentiated and medullary thyroid cancer treated at a single academic cancer center. We determined efficacy and compared front-line and second-line benefit using biochemical and anatomic response, time to treatment failure, and progression-free survival (PFS). Statistical differences were assessed by t test and chi-square test. Survival curves were generated by the Kaplan-Meier method. Differences in survival were assessed using the log-rank test, and a p value <.05 was considered significant. Results. We identified 39 patients with advanced differentiated and medullary thyroid cancer treated with targeted biologic agents. Median age was 56.3 years. Overall, 25 men and 14 women participated. Histology showed 23% medullary and 77% differentiated cancer. Nineteen patients progressed on front-line therapy and subsequently received second-line therapy. Targeted agents conferred clinically meaningful benefit in the second-line setting in terms of biochemical response (13.3%), clinical benefit (83.3%), median time to treatment failure (4.0 months; 95% confidence interval: 2.6-8.2), and median PFS (4.6 months; 95% confidence interval: 3.2-8.2). Second-line benefit (median PFS) was more modest in comparison to the front-line setting in both genders (women: 3 months vs. 12.2 months; men: 6 months vs. 19.7 months), in differentiated cancers (4.1 months vs. 15.7 months), and with vascular targeting agents (4.4 months vs. 20.1 months). Conclusion. Patients with advanced thyroid cancer derived meaningful clinical benefit from additional therapy with a biologic agent following disease progression on front-line targeted therapy.
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Natural killer cell development and maturation in aged mice.
Mech. Ageing Dev.
PUBLISHED: 06-25-2013
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The effect of aging on natural killer cell homeostasis is not well studied in humans or in animal models. We compared natural killer (NK) cells from young and aged mice to investigate age-related defects in NK cell distribution, and development. Our findings indicate aged mice have reduced NK cells in most peripheral tissues, but not in bone marrow. Reduction of NK cells in periphery was attributed to a reduction of the most mature CD11b(+) CD27(-) NK cells. Apoptosis was not found to explain this specific reduction of mature NK cells. Analysis of NK cell development in bone marrow revealed that aged NK cells progress normally through early stages of development, but a smaller percentage of aged NK cells achieved terminal maturation. Less mature NK cells in aged bone marrow correlated with reduced proliferation of immature NK cells. We propose advanced age impairs bone marrow maturation of NK cells, possibly affecting homeostasis of NK cells in peripheral tissues. These alterations in NK cell maturational status have critical consequences for NK cell function in advanced age: reduction of the mature circulating NK cells in peripheral tissues of aged mice affects their overall capacity to patrol and eliminate cancerous and viral infected cells.
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Treatment utilization and surgical outcome of ampullary and duodenal adenocarcinoma.
J Surg Oncol
PUBLISHED: 06-22-2013
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Ampullary (AMP-A) and duodenal adenocarcinomas (DA) are rare tumors. The literature regarding treatment and outcome is very limited. The objective of this project is to compare the outcomes of AMP-A and DA.
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Investigation of non-segregation graphene growth on Ni via isotope-labeled alcohol catalytic chemical vapor deposition.
Nanoscale
PUBLISHED: 06-12-2013
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Here we present CVD growth of graphene on Ni and investigate the growth mechanism using isotopically labeled (13)C-ethanol as the precursor. Results show that during low-pressure alcohol catalytic CVD (LP-ACCVD), a growth time of less than 30 s yields graphene films with high surface coverage (>80%). Moreover, when isotopically labeled ethanol precursors were sequentially introduced, Raman mapping revealed that both (12)C and (13)C graphene flakes exist. This shows that even at high temperature (?900 °C) the graphene flakes form independently, suggesting a different growth mechanism for ethanol-derived graphene on Ni from the segregation process for methane-derived graphene. We interpret this growth mechanism using a direct surface-adsorptive growth model in which small carbon fragments catalyzed from ethanol decomposition products first nucleate at metal step edges or grain boundaries to initiate graphene growth, and then expand over the entire metal surface.
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Acetylated Tubulin (AT) as a Prognostic Marker in Squamous Cell Carcinoma of the Head and Neck.
Head Neck Pathol
PUBLISHED: 05-23-2013
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Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens. We also examined AT expression on pre-therapy tissues of patients with SCCHN receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT expression was assessed on archival cases of SCCHN with (N = 63) and without (N = 82) locoregional lymph node metastases (LNM). The predominant tumor site was oral cavity (52 %). Immunohistochemistry staining was based on staining intensity and percentage of tumor cells stained to create a weighted index (WI). A total of nine patients who received TPF IC were evaluable for response by RECIST and also had pre-therapy tissues available. A significant independent correlation between AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend in improved OS for patients with an AT WI below the median compared to those above the median for patients with no LNM (p = 0.054). For patients treated with induction TPF, we observed an inverse correlation between AT expression and response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and primary site. There was an observed trend correlating AT with presence nodal metastases. The observed inverse correlation with response to taxane based chemotherapy needs validation in a larger sample size.
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Effect of prophylactic cranial irradiation on survival in elderly patients with limited-stage small cell lung cancer.
Cancer
PUBLISHED: 05-13-2013
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Prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiotherapy, yet to the best of the authors knowledge, data specific to the elderly population are lacking.
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Quantitative Dosimetry for Yttrium-90 Radionuclide Therapy: Tumor Dose Predicts Fluorodeoxyglucose Positron Emission Tomography Response in Hepatic Metastatic Melanoma.
J Vasc Interv Radiol
PUBLISHED: 05-08-2013
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To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases.
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Real-world effectiveness of systemic agents approved for advanced non-small cell lung cancer: a SEER-Medicare analysis.
Oncologist
PUBLISHED: 05-01-2013
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Disparity exists between patients with lung cancer enrolled in clinical trials and patients treated in the community setting. This study assessed the real-world effectiveness of cytotoxic agents that became available for the treatment of non-small cell lung cancer (NSCLC) in the last 2 decades.
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Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.
Prostate
PUBLISHED: 04-30-2013
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Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models.
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Direct physical exfoliation of few-layer graphene from graphite grown on a nickel foil using polydimethylsiloxane with tunable elasticity and adhesion.
Nanotechnology
PUBLISHED: 04-19-2013
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We firstly introduce a facile method for the site-specific direct physical exfoliation of few-layer graphene sheets from cheap and easily enlargeable graphite grown on a Ni foil using an optimized polydimethylsiloxane (PDMS) stamp. By decreasing the PDMS cross-linking time, the PDMS elasticity is reduced to ?52 kPa, similar to that of a typical gel. As a result of this process, the PDMS becomes more flexible yet remains in a handleable state as a stamp. Furthermore, the PDMS adhesion to a graphite/Ni surface, as measured by the peel strength, increases to ?5.1 N m?¹, which is approximately 17 times greater than that of typical PDMS. These optimized properties allow the PDMS stamp to have improved contact with the graphite/Ni surface, including the graphite wrinkles. This process is verified, and changes in surface morphology are observed using a 3D laser scanning microscope. Under conformal contact, the optimized PDMS stamp demonstrates the site-specific direct physical exfoliation of few-layer graphene sheets including mono- and bi-layer graphene sheets from the graphite/Ni substrate without the use of special equipment, conditions or chemicals. The number of layers of the exfoliated graphene and its high quality are revealed by the measured Raman spectroscopy. The exfoliation method using tunable elasticity and adhesion of the PDMS stamp can be used not only for cost-effective mass production of defect-less few-layer graphene from the graphite substrate for micro/nano device arrays but also for nano-contact printing of various structures, devices and cells.
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Cutting edge: antibody-dependent memory-like NK cells distinguished by FcR? deficiency.
J. Immunol.
PUBLISHED: 01-23-2013
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Because NK cells lack gene-recombination machinery and are thought to be relatively short-lived, it is unclear whether NK cells can mount long-term effective recall responses to reinfections by diverse pathogens. In this article, we report that FcR?-deficient NK cells, which we recently identified and termed g(-)NK cells, possess distinct memory features directed by FcR-mediated Ab-dependent target recognition. The presence of g(-)NK cells was associated with prior human CMV (HMCV) infection, yet g(-)NK cell responses were not restricted to HCMV-infected target cells. In the presence of virus-specific Abs, g(-)NK cells had greatly enhanced functional capabilities, superior to conventional NK cells, and were highly responsive to cells infected with either HCMV or HSV-1. Remarkably, the g(-)NK cell subset persisted long-term at nearly constant levels in healthy individuals. Therefore, FcR? deficiency distinguishes an Ab-dependent memory-like NK cell subset with enhanced potential for broad antiviral responses.
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Soluble FAS ligand as a biomarker of disease recurrence in differentiated thyroid cancer.
Cancer
PUBLISHED: 01-22-2013
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Reliable predictive biomarkers are required to address the challenge of disease recurrence after thyroid cancer surgery. For this study, the authors assessed the association of cellular-based and serum-based immunologic mediators with thyroid cancer recurrence.
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Oleic acid stimulates complete oxidation of fatty acids through protein kinase A-dependent activation of SIRT1-PGC1? complex.
J. Biol. Chem.
PUBLISHED: 01-17-2013
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Fatty acids are essential components of the dynamic lipid metabolism in cells. Fatty acids can also signal to intracellular pathways to trigger a broad range of cellular responses. Oleic acid is an abundant monounsaturated omega-9 fatty acid that impinges on different biological processes, but the mechanisms of action are not completely understood. Here, we report that oleic acid stimulates the cAMP/protein kinase A pathway and activates the SIRT1-PGC1? transcriptional complex to modulate rates of fatty acid oxidation. In skeletal muscle cells, oleic acid treatment increased intracellular levels of cyclic adenosine monophosphate (cAMP) that turned on protein kinase A activity. This resulted in SIRT1 phosphorylation at Ser-434 and elevation of its catalytic deacetylase activity. A direct SIRT1 substrate is the transcriptional coactivator peroxisome proliferator-activated receptor ? coactivator 1-? (PGC1?), which became deacetylated and hyperactive after oleic acid treatment. Importantly, oleic acid, but not other long chain fatty acids such as palmitate, increased the expression of genes linked to fatty acid oxidation pathway in a SIRT1-PGC1?-dependent mechanism. As a result, oleic acid potently accelerated rates of complete fatty acid oxidation in skeletal muscle cells. These results illustrate how a single long chain fatty acid specifically controls lipid oxidation through a signaling/transcriptional pathway. Pharmacological manipulation of this lipid signaling pathway might provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.
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Final results from phase II trial of neoadjuvant docetaxel and capecitabine given sequentially or concurrently for HER2-negative breast cancers.
Clin. Breast Cancer
PUBLISHED: 01-16-2013
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The combination of docetaxel and capecitabine has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer compared with docetaxel alone. We hypothesized that the combination of docetaxel and capecitabine, given concomitantly or sequentially, would present a nonanthracycline-based treatment option for patients with early stage and locally advanced breast cancer.
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Endoplasmic reticulum aminopeptidase-1 functions regulate key aspects of the innate immune response.
PLoS ONE
PUBLISHED: 01-01-2013
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Endoplasmic reticulum aminopeptidase-1 (ERAP1) is a multifunctional, ubiquitously expressed enzyme whose peptide-trimming role during antigen processing for presentation by MHC I molecules is well established, however, a role for ERAP1 in modulating global innate immune responses has not been described to date. Here we demonstrate that, relative to wild type mice, mice lacking ERAP1 exhibit exaggerated innate immune responses early during pathogen recognition, as characterized by increased activation of splenic and hepatic NK and NKT cells and enhanced production of pro-inflammatory cytokines such as IL12 and MCP1. Our data also revealed that ERAP1 is playing a critical role in NK cell development and function. We observed higher frequencies of terminally matured NK cells, as well as higher frequencies of licensed NK cells (expressing the Ly49C and Ly49I receptors) in ERAP1-KO mice, results that positively correlated with an enhanced NK activation and IFN? production by ERAP1-KO mice challenged with pro-inflammatory stimuli. Furthermore, during pathogen recognition, ERAP1 regulates IL12 production by CD11c(+) DCs specifically, with increases in IL12 production positively correlated with an increased phagocytic activity of splenic DCs and macrophages. Collectively, our results demonstrate a previously unrecognized, more central role for the ERAP1 protein in modulating several aspects of both the development of the innate immune system, and its responses during the initial stages of pathogen recognition. Such a role may explain why ERAP1 has been implicated by GWAS in the pathogenesis of autoimmune diseases that may be precipitated by aberrant responses to pathogen encounters.
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Scram1 is a modifier of spinal cord resistance for astrocytoma on mouse Chr 5.
Mamm. Genome
PUBLISHED: 08-25-2011
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Tumor location can profoundly affect morbidity and patient prognosis, even for the same tumor type. Very little is known about whether tumor location is determined stochastically or whether genetic risk factors can affect where tumors arise within an organ system. We have taken advantage of the Nf1-/+;Trp53-/+cis mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether astrocytomas are found in the spinal cord. We identify a locus on distal Chr 5, termed Scram1 for spinal cord resistance to astrocytoma modifier 1, with a LOD score of 5.0 and a genome-wide significance of P < 0.004. Mice heterozygous for C57BL/6J×129S4/SvJae at this locus show less astrocytoma in the spinal cord compared to 129S4/SvJae homozygous mice, although we have shown previously that 129S4/SvJae mice are more resistant to astrocytoma than C57BL/6J. Furthermore, the astrocytomas that are found in the spinal cord of Scram1 heterozygous mice arise in older mice. Because spinal cord astrocytomas are very rare and difficult to treat, a better understanding of the genetic factors that govern astrocytoma in the spine may lead to new targets of therapy or prevention.
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Noise reduction in genome-wide perturbation screens using linear mixed-effect models.
Bioinformatics
PUBLISHED: 06-17-2011
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High-throughput perturbation screens measure the phenotypes of thousands of biological samples under various conditions. The phenotypes measured in the screens are subject to substantial biological and technical variation. At the same time, in order to enable high throughput, it is often impossible to include a large number of replicates, and to randomize their order throughout the screens. Distinguishing true changes in the phenotype from stochastic variation in such experimental designs is extremely challenging, and requires adequate statistical methodology.
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Natural killer cell function is altered during the primary response of aged mice to influenza infection.
Mech. Ageing Dev.
PUBLISHED: 04-14-2011
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Influenza is a public health concern, especially for the elderly. While influenza vaccination is efficacious in the young, it offers only limited protection in the elderly. Thus, it becomes imperative to understand age-related changes in the primary response to influenza infection. This study identified potential age-related defects in natural killer (NK) cell function during influenza infection. We showed that NK cells from aged mice were reduced and had impaired function and altered phenotype in lungs during influenza infection. Aged NK cells demonstrated decreased IFN-? production, but not degranulation, after influenza infection. However, after ex vivo activation with YAC-1 cells, aged NK cells demonstrated both reduced IFN-? production and degranulation. IFN-? was also reduced in aged NK cells after activation with anti-NKp46 and soluble cytokines. IFN-?, and IL-12p40 mRNA expression was not significantly different from that observed in adult mice. Analysis of NK cell subsets indicated that aged mice had more immature and less terminally mature NK cells. These data suggest that aging affects the numbers, function and phenotype of NK cells. Thus, these defects in NK cell function could impair the ability of aged mice to induce a strong antiviral immune response during the early stages of the infection.
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Dopamine-induced mineralization of calcium carbonate vaterite microspheres.
Langmuir
PUBLISHED: 08-28-2010
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Two biogenic materials from mussels are attracting attention from scientists: calcium carbonate (CaCO(3)), the most widely studied biomineral that composes the shell, or nacre, of mussels, and dopamine, a small catechol-containing biomimetic molecule of adhesive foot proteins secreted by mussels. We have incorporated these two materials into the biomimetic mineralization process to produce stable vaterite microspheres, which are the most unstable crystalline phase of CaCO(3). Spherical vaterite crystals were readily formed within two minutes in the presence of dopamine undergoing polymerization and were preserved for over two months in aqueous solution. The microspheres consisted of nanoparticles smaller than 100 nm and exhibited porous and spherulitic cross sections. The prolonged maintenance of spherical structure is attributed to the affinitive interaction between calcium in the vaterite microspheres and catechols from dopamine retarding the dissolution of vaterite and the growth of calcite crystals. The mussel-inspired inducement of a stable vaterite phase suggests a facile route for the synthesis of complex organic-inorganic hybrid materials utilizing biogenic systems.
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The N-terminal extension domain of the C. elegans half-molecule ABC transporter, HMT-1, is required for protein-protein interactions and function.
PLoS ONE
PUBLISHED: 07-12-2010
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Members of the HMT-1 (heavy metal tolerance factor 1) subfamily of the ATP-binding cassette (ABC) transporter superfamily detoxify heavy metals and have unique topology: they are half-molecule ABC transporters that, in addition to a single transmembrane domain (TMD1) and a single nucleotide-binding domain (NBD1), possess a hydrophobic NH2-terminal extension (NTE). These structural features distinguish HMTs from other ABC transporters in different species including Drosophila and humans. Functional ABC transporters, however, are comprised of at least four-domains (two TMDs and two NDBs) formed from either a single polypeptide or by the association of two or four separate subunits. Whether HMTs act as oligomers and what role the NTE domain plays in their function have not been determined.
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Mussel-inspired transformation of CaCO3 to bone minerals.
Biomaterials
PUBLISHED: 04-26-2010
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We report a mussel-inspired route to create carbonated bone hydroxyapatite from CaCO(3) vaterite microspheres. When catechol-containing dopamine, a biomimetic small molecule of mussel adhesive proteins, was incorporated during the mineralization of CaCO(3), the oxidative polymerization of dopamine stabilized the formation of spherical vaterite, the most unstable phase among CaCO(3) crystalline structures. Thus-formed vaterite microspheres were readily transformed to carbonated hydroxyapatite crystals when incubated in a simulated body fluid at human body temperature. We found that dopamine not only stabilized the vaterite phase but also influenced the level of conversion to carbonated hydroxyapatites. Considering that carbonated hydroxyapatites are highly bioresorbable, similar to natural bone and dentin, the synthesis of a mussel-inspired hybrid material showing good in vitro bone bioactivity should present a new prospect for future applications in the treatment of bone defects and bone degenerative diseases.
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Effects of MHC class I alleles on licensing of Ly49A+ NK cells.
J. Immunol.
PUBLISHED: 03-01-2010
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NK cells are innate immune lymphocytes that can react to cells lacking self-MHC class I. However, NK cells that cannot engage self-MHC through an inhibitory receptor are resistant to stimulation through their activation receptors. To become licensed (i.e., functionally competent to be triggered through its activation receptors), an NK cell must engage host MHC class I via a MHC class I-specific inhibitory receptor, such as a member of the murine Ly49 family. To explore potential determinants of NK cell licensing on a single Ly49 receptor, we have investigated the relative licensing impacts of the b, d, k, q, r, and s H2 haplotypes on Ly49A(+) NK cells. The results indicate that licensing is essentially analog but is saturated by moderate-binding MHC class I ligands. Interestingly, licensing exhibited a strong inverse correlation with a measure of cis engagement of Ly49A. Finally, licensing of Ly49A(+) NK cells was found to be less sensitive to MHC class I engagement than Ly49A-mediated effector inhibition, suggesting that licensing establishes a margin of safety against NK cell autoreactivity.
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A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.
PLoS ONE
PUBLISHED: 02-14-2010
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Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.
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Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock.
J. Exp. Med.
PUBLISHED: 11-23-2009
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The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications.
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One-pot synthesis of imines and secondary amines by Pd-catalyzed coupling of benzyl alcohols and primary amines.
J. Org. Chem.
PUBLISHED: 03-07-2009
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Imines and secondary amines were synthesized selectively by controlling reaction conditions for the Pd-catalyzed one-pot reactions of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.
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Light to moderate alcohol consumption and disability: variable benefits by health status.
Am. J. Epidemiol.
PUBLISHED: 01-24-2009
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In adults, light to moderate alcohol consumption is associated with lower risks for heart disease, diabetes, and mortality. This study examined whether light to moderate alcohol use is also associated with lower risk of incident physical disability over two 5-year periods in 4,276 noninstitutionalized adults in the United States, aged 50 years or older, by using data from 3 waves of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study surveys from 1982 to 1992. Light/moderate drinking (<15 drinks per week and <5 per drinking day or 4 per drinking day for women) was associated with reduced risk for incident disability or death over 5 years, compared with abstention (adjusted odds ratio = 0.77; P = 0.008). Among survivors, light/moderate drinking was associated with lower risk for incident disability, compared with abstention (adjusted odds ratio = 0.75; P = 0.009). In stratified analyses, disability risk decreased with light/moderate drinking in a dose-dependent fashion in men and women with good or better self-reported health but not in men or women with fair or worse self-reported health. Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor health.
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Activation mechanisms of natural killer cells during influenza virus infection.
PLoS ONE
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During early viral infection, activation of natural killer (NK) cells elicits the effector functions of target cell lysis and cytokine production. However, the cellular and molecular mechanisms leading to NK cell activation during viral infections are incompletely understood. In this study, using a model of acute viral infection, we investigated the mechanisms controlling cytotoxic activity and cytokine production in response to influenza (flu) virus. Analysis of cytokine receptor deficient mice demonstrated that type I interferons (IFNs), but not IL-12 or IL-18, were critical for the NK cell expression of both IFN-? and granzyme B in response to flu infection. Further, adoptive transfer experiments revealed that NK cell activation was mediated by type I IFNs acting directly on NK cells. Analysis of signal transduction molecules showed that during flu infection, STAT1 activation in NK cells was completely dependent on direct type I IFN signaling, whereas STAT4 activation was only partially dependent. In addition, granzyme B induction in NK cells was mediated by signaling primarily through STAT1, but not STAT4, while IFN-? production was mediated by signaling through STAT4, but not STAT1. Therefore, our findings demonstrate the importance of direct action of type I IFNs on NK cells to mount effective NK cell responses in the context of flu infection and delineate NK cell signaling pathways responsible for controlling cytotoxic activity and cytokine production.
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Radiation therapy target volume reduction in pediatric rhabdomyosarcoma: implications for patterns of disease recurrence and overall survival.
Cancer
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The use of radiation therapy (RT) "cone-down" boost to reduce high-dose treatment volumes according to tumor response to induction chemotherapy in patients with pediatric rhabdomyosarcoma (RMS) may reduce treatment morbidity, yet the impact on tumor control is unknown.
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High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome.
BMC Genomics
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To balance the demand for uptake of essential elements with their potential toxicity living cells have complex regulatory mechanisms. Here, we describe a genome-wide screen to identify genes that impact the elemental composition (ionome) of yeast Saccharomyces cerevisiae. Using inductively coupled plasma - mass spectrometry (ICP-MS) we quantify Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, P, S and Zn in 11890 mutant strains, including 4940 haploid and 1127 diploid deletion strains, and 5798 over expression strains.
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Identification of human NK cells that are deficient for signaling adaptor FcR? and specialized for antibody-dependent immune functions.
Int. Immunol.
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NK cells respond to tumor and virus-infected cells directly through several activation receptors, including natural cytotoxicity receptors, or indirectly through the activating Fc receptor CD16 for antibody-coated cells. Triggering of NK-cell effector functions through these receptors depends on physically associated transmembrane signaling adaptors, such as FcR? (also known as Fc?RI?) and CD3?, both of which have been traditionally believed to be expressed by all mature NK cells. However, we have identified a distinct subset of human NK cells that are deficient for FcR? expression but express normal levels of CD3?. FcR?-deficient NK cells were readily detectable in about one-third of the healthy individuals examined. The deficiency was confined to the CD56(dim) population and was due to low FcR? mRNA. FcR?-deficient NK cells displayed dramatically reduced expression of the natural cytotoxicity receptors NKp46 and NKp30 but still expressed substantial levels of CD16. Compared to FcR?-expressing NK cells, FcR?-deficient NK cells showed poor direct reactivity toward tumor targets as measured by cytokine production and degranulation. Unexpectedly, however, FcR?-deficient NK cells exhibited significantly more robust responsiveness upon stimulation through CD16, particularly for cytokine production, compared to FcR?-expressing NK cells. Thus, our study reveals FcR?-deficient NK cells as a novel subset of human NK cells that have remarkably potent responses toward antibody-coated targets. These findings also illustrate a differential contribution of FcR? and CD3? for the expression and functional activity of their associated receptors.
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Mapping quantitative trait loci onto a phylogenetic tree.
Genetics
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Despite advances in genetic mapping of quantitative traits and in phylogenetic comparative approaches, these two perspectives are rarely combined. The joint consideration of multiple crosses among related taxa (whether species or strains) not only allows more precise mapping of the genetic loci (called quantitative trait loci, QTL) that contribute to important quantitative traits, but also offers the opportunity to identify the origin of a QTL allele on the phylogenetic tree that relates the taxa. We describe a formal method for combining multiple crosses to infer the location of a QTL on a tree. We further discuss experimental design issues for such endeavors, such as how many crosses are required and which sets of crosses are best. Finally, we explore the methods performance in computer simulations, and we illustrate its use through application to a set of four mouse intercrosses among five inbred strains, with data on HDL cholesterol.
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Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts.
Proc. Natl. Acad. Sci. U.S.A.
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Inflammation is a significant player in the progression of heart failure and has detrimental effects on cardiac function. Prostaglandin (PG)E2, a major proinflammatory prostanoid in the cardiovascular system, is a potent stimulus in inducing intracellular cAMP but minimally affects cardiac contractile function. Here, we show that the PGE2 stimulation attenuates the adrenergic-induced cardiac contractile response in animal hearts. Stimulation with PGE2 leads to stimulatory G protein (Gs)-dependent production of cAMP. However, the induced cAMP is spatially restricted because of its degradation by phosphodiesterase (PDE)4 and cannot access the intracellular sarcoplasmic reticulum (SR) for increasing calcium signaling and myocyte contraction. Moreover, pretreatment with PGE2 significantly inhibits PKA activities at the SR induced by a ?-adrenergic agonist, isoproterenol, and subsequently blocks isoproterenol-induced PKA phosphorylation of phospholamban and contractile responses in myocytes. Further analysis reveals that the PGE2-induced cAMP/PKA is sufficient to phosphorylate and activate PDE4D isoforms, which, in turn, spatially inhibits the diffusion of adrenergic-induced cAMP from the plasma membrane to the SR. Inhibition of PDE4 rescues the adrenergic-induced increase in cAMP/PKA activities at the SR, PKA phosphorylation of phospholamban, and contractile responses in PGE2-pretreated myocytes. Thus, this offers an example that one Gs-coupled receptor is able to inhibit the intracellular signaling transduction initiated by another Gs-coupled receptor via controlling the diffusion of cAMP, presenting a paradigm for G protein-coupled receptor (GPCR) signal transduction. It also provides a mechanism for the integration of signaling initiated by different neurohormonal stimuli, as well as long-term effects of chronically circulating proinflammatory factors in myocardium.
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Surface ferromagnetic p-type ZnO nanowires through charge transfer doping.
ACS Appl Mater Interfaces
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We report first-principles theoretical investigation of p-type charge transfer doping of zinc oxide (ZnO) nanowires by molecular adsorption. We find that spontaneous dissociative adsorption of fluorine molecules introduces half-emptying of otherwise fully filled oxygen-derived surface states. The resulting surface Fermi level is so close to the valence band maximum of the ZnO nanowire that the nanowire undergoes significant p-type charge transfer doping. Those half-filled surface states are fully spin-polarized and lead to surface ferromagnetism that is stable at room temperature. We also analyze the kinetic control regime of the surface transfer doping and find that it may result in nonequilibrium steady states. The present results suggest that postgrowth engineering of surface states has high potential in manipulating ZnO nanostructures useful for both electronics and spintronics.
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Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12.
Neuro-oncology
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While many cancers show a sex bias, the genetic basis and molecular mechanisms underlying sex bias are not always clear. Astrocytoma and glioblastoma show male predominance in humans. We have shown previously that glial tumors forming in the Nf1-/+; Trp53-/+cis (NPcis) mouse model also show a sex bias in some genetic contexts. Using cross-species comparisons we have identified candidate male-specific modifiers of astrocytoma/glioblastoma. Linkage analysis of B6X(B6X129)-NPcis mice identifies a modifier of astrocytoma resistance specific to males, named Arlm1, on distal mouse Chr 12. Arlm1 is syntenic to human Chr 7p15, 7p21, 7q36, and 14q32 regions that are altered in human glioblastoma. A subset of these genes shows male-specific correlations to glioblastoma patient survival time and represents strong candidates for the Arlm1 modifier gene. Identification of male-specific modifier genes will lead to a better understanding of the molecular basis of male predominance in astrocytoma and glioblastoma.
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Low-temperature synthesis of LiFePO4 nanocrystals by solvothermal route.
Nanoscale Res Lett
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LiFePO4 nanocrystals were synthesized at a very low temperature of 170°C using carbon nanoparticles by a solvothermal process in a polyol medium, namely diethylene glycol without any heat treatment as a post procedure. The powder X-ray diffraction pattern of the LiFePO4 was indexed well to a pure orthorhombic system of olivine structure (space group: Pnma) with no undesirable impurities. The LiFePO4 nanocrystals synthesized at low temperature exhibited mono-dispersed and carbon-mixed plate-type LiFePO4 nanoparticles with average length, width, and thickness of approximately 100 to 300 nm, 100 to 200 nm, and 50 nm, respectively. It also appeared to reveal considerably enhanced electrochemical properties when compared to those of pristine LiFePO4. These observed results clearly indicate the effect of carbon in improving the reactivity and synthesis of LiFePO4 nanoparticles at a significantly lower temperature.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.