ABSTRACT
Solar photovoltaic (PV) energy generation is highly dependent on weather conditions and only applicable when the sun is shining during the daytime, leading to a mismatch between demand and supply. Merging PVs with battery storage is the straightforward route to counteract the intermittent nature of solar generation. Capacity (or energy density), overall efficiency, and stability at elevated temperatures are among key battery performance metrics for an integrated PV-battery system. The performance of high-capacity silicon (Si)/graphite (Gr) anode and LiNi0.6Mn0.2Co0.2O2 (NMC622) cathode cells at room temperature, 45, and 60 °C working temperatures for PV modules are explored. The electrochemical performance of both half and full cells are tested using a specially formulated electrolyte, 1 M LiPF6 in ethylene carbonate: diethyl carbonate, with 5 wt % fluoroethylene carbonate, 2 wt % vinylene carbonate, and 1 wt % (2-cyanoethyl)triethoxysilane. To demonstrate solar charging, perovskite solar cells (PSCs) are coupled to the developed batteries, following the evaluation of each device. An overall efficiency of 8.74% under standard PV test conditions is obtained for the PSC charged lithium-ion battery via the direct-current-direct-current converter, showing the promising applicability of silicon/graphite-based anodes in the PV-battery integrated system.
ABSTRACT
PURPOSE: The Hedgehog pathway plays an important role in stem-cell biology and malignant transformation. Therefore, we investigated the expression and prognostic impact of Hedgehog pathway members in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: Pretreatment samples from 104 newly diagnosed AML patients (AMLSG 07-04 trial) were analyzed by qPCR, and expression of Hedgehog family members was correlated with clinical outcome. Inhibition of GLI by GANT61 or shRNA was investigated in AML cells in vitro and in vivo. RESULTS: Expression of receptors Smoothened and Patched-1 and their downstream mediators, GLI1, GLI2, and GLI3, was found in AML patients in contrast to Hedgehog ligands. GLI2 expression had a significant negative influence on event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS; P = 0.037, 0.026, and 0.013, respectively) and was correlated with FLT3 mutational status (P < 0.001). Analysis of a second, independent patient cohort confirmed the negative impact of GLI2 on EFS and OS (P = 0.007 and 0.003, respectively; n = 290). Within this cohort, GLI1 had a negative prognostic impact (P < 0.001 for both EFS and OS). Although AML cells did not express Hedgehog ligands by qPCR, AML patients had significantly increased Desert Hedgehog (DHH) plasma levels compared with healthy subjects (P = 0.002), in whom DHH was presumably provided by bone marrow niche cells. Moreover, the GLI inhibitor GANT61 or knockdown of GLI1/2 by shRNA caused antileukemic effects, including induction of apoptosis, reduced proliferation, and colony formation in AML cells, and a survival benefit in mice. CONCLUSIONS: GLI expression is a negative prognostic factor and might represent a novel druggable target in AML.
Subject(s)
Biomarkers, Tumor/metabolism , Leukemia, Myeloid, Acute/metabolism , Transcription Factors/metabolism , Adolescent , Adult , Animals , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Line, Tumor , DNA Mutational Analysis , Disease-Free Survival , Female , Hedgehog Proteins/metabolism , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Mice, Inbred NOD , Mice, SCID , Middle Aged , Neoplasm Transplantation , Prognosis , Proportional Hazards Models , Pyridines/pharmacology , Pyrimidines/pharmacology , Receptors, G-Protein-Coupled/genetics , Signal Transduction , Smoothened Receptor , Transcription Factors/genetics , Treatment Outcome , Young Adult , Zinc Finger Protein GLI1ABSTRACT
BACKGROUND: Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. OBJECTIVE: We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. METHODS: Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. RESULTS: IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. CONCLUSION: Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.
