Suppressing Nickel Oxide/Perovskite Interface Redox Reaction and Defects for Highly Performed and Stable Inverted Perovskite Solar Cells.

The inorganic hole transport layer of nickel oxide (NiOx ) has shown highly efficient, low-cost, and scalable in perovskite photovoltaics. However, redox reactions at the interface between NiOx and perovskites limit their commercialization. In this study, ABABr (4-(2-Aminoethyl) benzoic acid bromide) between the NiOx and different perovskite layers to address the issues has been introduced. How the ABABr interacts with NiOx and perovskites is experimentally and theoretically investigated. These results show that the ABABr molecule chemically reacts with the NiOx via electrostatic attraction on one side, whereas on the other side, it forms a strong hydrogen bond via the NH3 + group with perovskites layers, thus directly diminishing the redox reaction between the NiOx and perovskites layers and passivating the layer surfaces. Additionally, the ABABr interface modification leads to significant improvements in perovskite film morphology, crystallization, and band alignment. The perovskites solar cells (PSCs) based on an ABABr interface modification show power conversion efficiency (PCE) improvement by over 13% and maintain over 90% of its PCE after continuous operation at maximum power point for over 500 h. The work not only contributes to the development of novel interlayers for stable PSCs but also to the understanding of how to prevent interface redox reactions.

Comparison of DNA methylation patterns across tissue types in infants with tetralogy of Fallot.

BACKGROUND: Environmental factors may influence the development of tetralogy of Fallot (TOF), and DNA methylation patterns may reveal specific chemical signatures of perturbations during cardiac development. We investigated whether blood and buccal cells could be viable surrogates for myocardium. METHODS: We measured epigenome-wide DNA methylation at 866,895 5'-cytosine-phosphate-guanine-3' (CpG) sites in blood (n=3), buccal cells (n=3), and right ventricular myocardium (n=4) collected from infants with TOF and compared the percent of differentially methylated CpG sites across tissue types. Gene-specific DNA methylation profiles were also analyzed for ten representative genes associated with heart development. Welch's ANOVAs compared general methylation between tissue types. RESULTS: Comparison of DNA methylation profiles across blood, buccal, and myocardium suggested myocardium and buccal samples were most similar, differing in DNA methylation at only 1.3% (11,386) of CpG sites whereas myocardium and blood were most dissimilar, having 146,857 statistically dissimilar methylated CpG sites (~17% dissimilarity; adjusted p < 0.01 for each site). Buccal swabs were significantly more variable (p < .001) than either blood or myocardial samples. In gene-specific analyses, SCO2, GATA4, NOTCH4, WNT7A, and DKK2 showed conserved DNA methylation profiles across tissue types, while HAND1, JAG1, NKX2-5, TBX5 and TBX20 showed more distinctive tissue-specific patterns of DNA methylation. CONCLUSIONS: Compared with blood, buccal tissue more closely mirrors the myocardial methylome, with >10-fold similarity. Nevertheless, both buccal and blood tissue capture highly conserved DNA methylation patterns at specific genetic loci related to cardiac development. Buccal cheek swabs may be a useful surrogate tissue type for future investigations of TOF-specific epigenetic profiles.

Flexibility of Room-Temperature-Synthesized Amorphous CdO-In2O3 Alloy Films and Their Application as Transparent Conductors in Solar Cells.

Due to their low-temperature deposition, high mobility (>10 cm2/V·s), and electrical conductivity, amorphous ionic oxide semiconductors (AIOSs) have received much attention for their applications in flexible and/or organic electro-optical devices. Here, we report on a study of the flexibility of CdO-In2O3 alloy thin films, deposited on a polyethylene terephthalate (PET) substrate by radio frequency magnetron sputtering at room temperature. Cd1-xInxO1+δ alloys with the composition of x > 0.6 are amorphous, exhibiting a high electron mobility of 40-50 cm2/V·s, a low resistivity of ∼3 × 10-4 Ω·cm, and high transmittance over a wide spectral window of 350 to >1600 nm. The flexibility of both crystalline and amorphous Cd1-xInxO1+δ films on the PET substrate was investigated by measuring their electrical resistivity after both compressive and tensile bending with a range of bending radii and repeated bending cycles. Under both compressive and tensile bending with Rb = 16.5 mm, no significant degradation was observed for both the crystalline and amorphous films up to 300 bending cycles. For a smaller bending radius, the amorphous film shows much less electrical degradation than the crystalline films under compressive bending due to less film delamination at the bending sites. On the other hand, for a small bending radius (<16 mm), both crystalline and amorphous films degrade after repeated tensile bending, most likely due to the development of microcracks in the films. To demonstrate the application of amorphous Cd1-xInxO1+δ alloy in photovoltaics, we fabricated perovskite and bulk-heterojunction organic solar cells (OSCs) on glass and flexible PET utilizing amorphous Cd1-xInxO1+δ layers as transparent electrodes. The organic-inorganic hybrid perovskite solar cells (PSCs) exhibit a power conversion efficiency (PCE) of ∼11 to 12% under both front and back illumination, demonstrating good bifacial performance with bifaciality factor >90%. The OSCs fabricated on an amorphous Cd1-xInxO1+δ-coated flexible PET substrate achieve a promising PCE of 12.06%. Our results strongly suggest the technological potentials of amorphous Cd1-xInxO1+δ as a reliable and effective transparent conducting material for flexible and organic optoelectronic devices.

Effects of oxygen flow ratio and thermal annealing on defect evolution of aluminum doped zinc oxide thin films by reactive DC magnetron sputtering.

Al doped ZnO (AZO) is a promising transparent conducting oxide to replace the expensive Sn doped In2O3(ITO). Understanding the formation and evolution of defects in AZO is essential for its further improvement. Here, we synthesize transparent conducting AZO thin films by reactive DC magnetron sputtering. The effects of oxygen flow ratio as well as the rapid thermal annealing (RTA) in different conditions on their structural and optoelectrical properties were investigated by a variety of analytical techniques. We find that AZO thin films grown in O-rich conditions exhibit inferior optoelectrical performance as compared with those grown in Zn-rich conditions, possibly due to the formation of excessive native acceptor defects and/or secondary phases (e.g. Al2O3). Temperature-dependent Hall measurements indicate that mobilities of these highly degenerate AZO films withN> 1020 cm-3are primarily limited by ionized and neutral impurities, while films with relatively lowN∼ 1019 cm-3exhibit a temperature-activated mobility owing to the grain-barrier scattering. AsNincreases, the optical band gap of AZO thin film increases as a result of Burstein-Moss shift and band gap narrowing. RTA treatments under appropriate conditions (i.e. at 500 °C for 60 s in Ar) can further improve the electrical properties of AZO thin film, with low resistivity of ∼6.2 × 10-4Ω cm achieved, while RTA at high temperature with longer time can lead to the formation of substantial sub-gap defect states and thus lowers the electron mobility. X-ray photoelectron spectroscopy provides further evidence on the variation of Al (Zn) content at the surface of AZO thin films with different processing conditions.

Using a single parameter to describe time-activity curves.

Time-activity uptake curves [u(t) in % injected dose per gram of tissue] may be described by different--often complicated--functional forms. Because of the need to readily compare sequences of engineered radiopharmaceuticals, it is efficient to use mean residence time (MRT) as a one-parameter descriptor. In applying this computation to a sequence of five cognate anti-carcinoembryonic antigen (CEA) antibodies, it was found that the intact form had the longest MRT in the blood with the other four cognates having values less by approximately a factor of 10 or more. This difference probably follows from the lack of an intact Fc segment on the latter engineered molecules. MRT values for a sequence of six scFv-Fc engineered fragments demonstrated that the double mutant had the shortest blood residence time--30-fold less compared with the wild type. Whereas it is not possible to directly apply the MRT to nonbolus (tumor or organ) curves, a residence time (τ) may be assigned using the uptake function. Using τ, it was found that the intact (natural) form of the anti-CEA cognate set had the longest time at the tumor site in the human xenograft model in nude mice. The MRT and τ concept are proposed to also allow comparison of possible relative blood and tissue exposures, respectively, for cognate sets of unlabeled engineered antibodies used to treat malignancies although no data are yet available in the literature for this application.

A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma.

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.

Rapid purification of a new humanized single-chain Fv antibody/human interleukin-2 fusion protein reactive against HER2 receptor.

Human embryonic kidney 293 cells were transfected with plasmid pcDNA-H520C9scFv-rhIL-2 containing a chimeric cDNA encoding the humanized 520C9 scFv/recombinant human IL-2 fusion protein (H520C9scFv-rhIL-2). The transfected cells in plateau growing phase were cultured in serum-free medium for three days. The supernatant was collected, concentrated and purified using an affinity column packed with CNBr-activated Sepharose 4B coupled with anti-rhIL-2 mouse monoclonal antibody. The purified fusion protein was analyzed by ELISA, SDS-PAGE and Western blot. The fusion protein showed only one band in both silver stained electrophoresis gel and Western blot developed by ECL chemiluminescence system. Its molecular weight was confirmed to be about 45 kD. This fusion protein possessed binding specificity against p185 positive SKOV3 and B16/neu cells, and it might stimulate IL-2-dependent CTLL-2 cell proliferation as well.

Pilot trial evaluating an 123I-labeled 80-kilodalton engineered anticarcinoembryonic antigen antibody fragment (cT84.66 minibody) in patients with colorectal cancer.

PURPOSE: The chimeric T84.66 (cT84.66) minibody is a novel engineered antibody construct (V(L)-linker-V(H)-C(H)3; 80 kDa) that demonstrates bivalent and high affinity (4 x 10(10) m(-1)) binding to carcinoembryonic antigen (CEA). The variable regions (V(L) and V(H)) assemble to form the antigen-combining sites, and the protein forms dimers through self-association of the C(H)3 domains. In animal models, the minibody demonstrated high tumor uptake, approaching that of some intact antibodies, substantially faster clearance than intact chimeric T84.66, and superior tumor-to-blood ratios compared with the cT84.66 F(ab')(2) fragment, making it attractive for further evaluation as an imaging and therapy agent. The purpose of this pilot clinical study was to determine whether (123)I-cT84.66 minibody demonstrated tumor targeting and was well tolerated as well as to begin to evaluate its biodistribution, pharmacokinetics, and immunogenicity in patients with colorectal cancer. EXPERIMENTAL DESIGN: Ten patients with biopsy-proven colorectal cancer (6 newly diagnosed, 1 pelvic recurrence, 3 limited metastatic disease) were entered on this study. Each received 5-10 mCi (1 mg) of (123)I-labeled minibody i.v. followed by serial nuclear scans and blood and urine sampling over the next 48-72 h. Surgery was performed immediately after the last nuclear scan. RESULTS: Tumor imaging was observed with (123)I-labeled minibody in seven of the eight patients who did not receive neoadjuvant therapy before surgery. Two patients received neoadjuvant radiation and chemotherapy, which significantly reduced tumor size before surgery and minibody infusion. At surgery, no tumor was detected in one patient and only a 2-mm focus was seen in the second patient. (123)I-labeled minibody tumor targeting was not seen in either of these pretreated patients. Mean serum residence time of the minibody was 29.8 h (range, 10.9-65.4 h). No drug-related adverse reactions were observed. All 10 patients were evaluated for immune responses to the minibody, with no significant responses observed. CONCLUSION: This pilot study represents one of the first clinical efforts to evaluate an engineered intermediate-molecular-mass radiolabeled antibody construct directed against CEA. cT84.66 minibody demonstrates tumor targeting to colorectal cancer and a faster clearance in comparison with intact antibodies, making it appropriate for further evaluation as an imaging and therapy agent. The mean residence time of the minibody in patients is longer than predicted from murine models. We therefore plan to further evaluate its biodistribution and pharmacokinetic properties with minibody labeled with a longer-lived radionuclide, such as (111)In.

A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer.

PURPOSE: Targeted systemic radiation therapy using radiolabeled antibodies results in tumor doses sufficient to produce significant objective responses in the radiosensitive hematological malignancies. Although comparable doses to tumor are achieved with radioimmunotherapy (RIT) in solid tumors, results have been modest primarily because of their relative lack of radiosensitivity. For solid tumors, as with external beam radiotherapy, RIT should have a more important clinical role if combined with other systemic, potentially radiation-enhancing chemotherapy agents and if used as consolidative therapy in the minimal tumor burden setting. The primary objective of this trial was to evaluate the feasibility and toxicities of systemic 90Y-chimeric T84.66 (cT84.66) anti-carcinoembryonic antigen RIT in combination with continuous infusion 5-fluorouracil (5-FU). EXPERIMENTAL DESIGN: Patients with chemotherapy-refractory metastatic colorectal cancer were entered. The study was designed for each patient to receive 90Y-cT84.66 anti-carcinoembryonic antigen at 16.6 mCi/m2 as an i.v. bolus infusion combined with 5-FU delivered as a 5-day continuous infusion initiated 4 h before antibody infusion. Cohorts of patients were entered at 5-FU dose levels of 700, 800, 900, and 1000 mg/m2/day. Upon reaching the highest planned dose level of 5-FU, a final cohort received 90Y-cT84.66 at 20.6 mCi/m2 and 5-FU at 1000 mg/m2/day. For all patients, Ca-diethylenetriaminepentaacetic acid at 125 mg/m2 every 12 h was administered for the first 72 h after 90Y-cT84.66. Patients were eligible to receive up to three cycles of 90Y-cT84.66/5-FU every 6 weeks. RESULTS: Twenty-one patients were treated on this study. All had been heavily pretreated with 19 having previously received 5-FU and 16 having failed two to four chemotherapy regimens. A maximum-tolerated dose of 16.6 mCi/m2 90Y-cT84.66 combined with 1000 mg/m2/day 5-FU was reached. These dose levels are comparable with maximum-tolerated dose levels of each agent alone. Thirteen patients received one cycle and 8 patients two cycles of therapy. Hematopoietic toxicity was dose-limiting and reversible. RIT did not appear to increase nonhematopoietic toxicities associated with 5-FU. Two of 19 patients assayed developed a human anti-chimeric antibody immune response after the first cycle of therapy, which is significantly less than that observed in a previous trial evaluating 90Y-cT84.66 alone. No objective responses were observed. However, 11 patients with progressive disease entering the study demonstrated radiological stable disease of 3-8 months duration and 1 patient demonstrated a mixed response. CONCLUSIONS: Results from this trial are encouraging and demonstrate the feasibility and possible advantages of combining continuous infusion 5-FU with 90Y-cT84.66 RIT. The addition of 5-FU does not appear to significantly enhance hematological toxicities of the radiolabeled antibody. In addition, 5-FU reduces the development of human anti-chimeric antibody response, permitting multicycle therapy in a larger number of patients. Future efforts should continue to focus on integrating radiation therapy delivered by radiolabeled antibodies into established 5-FU regimens.