Simultaneous Enhancement of Efficiency and Operational-Stability of Mesoscopic Perovskite Solar Cells via Interfacial Toughening.

The combined effects of compact TiO2 (c-TiO2 ) electron-transport layer (ETL) are investigated without and with mesoscopic TiO2 (m-TiO2 ) on top, and without and with an iodine-terminated silane self-assembled monolayer (SAM), on the mechanical behavior, opto-electronic properties, photovoltaic (PV) performance, and operational-stability of solar cells based on metal-halide perovskites (MHPs). The interfacial toughness increases almost threefold in going from c-TiO2 without SAM to m-TiO2 with SAM. This is attributed to the synergistic effect of the m-TiO2 /MHP nanocomposite at the interface and the enhanced adhesion afforded by the iodine-terminated silane SAM. The combination of m-TiO2 and SAM also offers a significant beneficial effect on the photocarriers extraction at the ETL/MHP interface, resulting in perovskite solar cells (PSCs) with power-conversion efficiency (PCE) of over 24% and 20% for 0.1 and 1 cm2 active areas, respectively. These PSCs also have exceptionally long operational-stability lives: extrapolated T80 (duration at 80% initial PCE retained) is ≈18 000 and 10 000 h for 0.1 and 1 cm2 active areas, respectively. Postmortem characterization and analyses of the operational-stability-tested PSCs are performed to elucidate the possible mechanisms responsible for the long operational-stability.

CanISO: a database of genomic and transcriptomic variations in domestic dog (Canis lupus familiaris).

BACKGROUND: The domestic dog, Canis lupus familiaris, is a companion animal for humans as well as an animal model in cancer research due to similar spontaneous occurrence of cancers as humans. Despite the social and biological importance of dogs, the catalogue of genomic variations and transcripts for dogs is relatively incomplete. RESULTS: We developed CanISO, a new database to hold a large collection of transcriptome profiles and genomic variations for domestic dogs. CanISO provides 87,692 novel transcript isoforms and 60,992 known isoforms from whole transcriptome sequencing of canine tumors (N = 157) and their matched normal tissues (N = 64). CanISO also provides genomic variation information for 210,444 unique germline single nucleotide polymorphisms (SNPs) from the whole exome sequencing of 183 dogs, with a query system that searches gene- and transcript-level information as well as covered SNPs. Transcriptome profiles can be compared with corresponding human transcript isoforms at a tissue level, or between sample groups to identify tumor-specific gene expression and alternative splicing patterns. CONCLUSIONS: CanISO is expected to increase understanding of the dog genome and transcriptome, as well as its functional associations with humans, such as shared/distinct mechanisms of cancer. CanISO is publicly available at https://www.kobic.re.kr/caniso/ .

Selective Control of Novel TiO2 Nanorods: Excellent Building Blocks for the Electron Transport Layer of Mesoscopic Perovskite Solar Cells.

Novel TiO2 nanorods (NRs) with various lengths of 70-200 nm and uniform widths of 46-48 nm are selectively synthesized by a solvothermal reaction under a basic environment. The length of TiO2 NRs is reproducibly tuned by varying the concentration of tetramethylammonium hydroxide (TMAH), while the NRs in the pure anatase phase are grown in the [001] direction, caused by the preferential binding affinity of TMAH to the TiO2 (101) facet. TiO2 NRs of various lengths are then applied to form the electron transporting layer (ETL) of mesoscopic perovskite solar cells (PSCs). We found that PSC devices with NRs exhibit superior photovoltaic (PV) performance to those with conventional 46 nm-sized TiO2 nanoparticles (NP46). Particularly, the PSC with TiO2 NRs of 110 nm length (NR110) exhibits the optimum PV conversion efficiency (PCE): the average PCE is 22.64% with a VOC of 1.137 V, a JSC of 24.60 mA·cm-2, and a FF of 80.96%, while the champion PCE is 23.18%. In addition, the PSC with NR110 (PSC-NR110) reveals significantly improved long-term stability in air with a relative humidity of 40-50%. In 1000 h, its PCE is reduced by only 9% whereas that of PSC with NP46 decreases by 25%. The PSC properties analyzed by impedance spectroscopy and J-V curve measurements under dark conditions and at various light intensities provide evidence that PSC-NR110 has fewer defects and shows significantly reduced charge recombination. We discuss the advantages of NR structures in preparing the ETL of PSC devices and also explain why the charge recombination is suppressed.

Formation of Highly Efficient Perovskite Solar Cells by Applying Li-Doped CuSCN Hole Conductor and Interface Treatment.

Li-doped CuSCN films of various compositions were applied as hole-transporting material (HTM) for mesoscopic perovskite solar cells (PSCs). Those films of ~60 nm thickness, spin-coated on the perovskite layer, exhibit significantly higher crystallinity and hole mobility compared with the pristine CuSCN films. Among them, 0.33% Li-doped CuSCN (Li0.33:CuSCN) shows the best performance as the HTM of mesoscopic PSC. Furthermore, by depositing a slight amount of PCPDTBT over the Li0.33:CuSCN layer, the VOC was increased to 1.075 V, resulting in an average PCE of 20.24% and 20.65% for the champion device. These PCE and VOC values are comparable to those of PSC using spiro-OMETAD (PCE: 20.61%, VOC: 1.089 V). Such a remarkable increase can be attributed to the penetration of the PCPDTBT polymer into the grain boundaries of the Li0.33:CuSCN film, and to the interface with the perovskite layer, leading to the removal of defects on the perovskite surface by paving the non-contacting parts, as well as to the tight interconnection of the Li0.33:CuSCN grains. The PSC device with Li0.33:CuSCN showed a high long-term stability similar to that with bare CuSCN, and the introduction of PCPDTBT onto the perovskite/Li0.33:CuSCN further improved device stability, exhibiting 94% of the initial PCE after 100 days.

1H NMR based urinary metabolites profiling dataset of canine mammary tumors.

The identification of efficient and sensitive biomarkers for non-invasive tests is one of the major challenges in cancer diagnosis. To address this challenge, metabolomics is widely applied for identifying biomarkers that detect abnormal changes in cancer patients. Canine mammary tumors exhibit physiological characteristics identical to those in human breast cancer and serve as a useful animal model to conduct breast cancer research. Here, we aimed to provide a reliable large-scale metabolite dataset collected from dogs with mammary tumors, using proton nuclear magnetic resonance spectroscopy. We identified 55 metabolites in urine samples from 20 benign, 87 malignant, and 49 healthy control subjects. This dataset provides details of mammary tumor-specific metabolites in dogs and insights into cancer-specific metabolic alterations that share similar molecular characteristics.

Development of a program for in silico optimized selection of oligonucleotide-based molecular barcodes.

Short DNA oligonucleotides (~4 mer) have been used to index samples from different sources, such as in multiplex sequencing. Presently, longer oligonucleotides (8-12 mer) are being used as molecular barcodes with which to distinguish among raw DNA molecules in many high-tech sequence analyses, including low-frequent mutation detection, quantitative transcriptome analysis, and single-cell sequencing. Despite some advantages of using molecular barcodes with random sequences, such an approach, however, makes it impossible to know the exact sequences used in an experiment and can lead to inaccurate interpretation due to misclustering of barcodes arising from the occurrence of unexpected mutations in the barcodes. The present study introduces a tool developed for selecting an optimal barcode subset during molecular barcoding. The program considers five barcode factors: GC content, homopolymers, simple sequence repeats with repeated units of dinucleotides, Hamming distance, and complementarity between barcodes. To evaluate a selected barcode set, penalty scores for the factors are defined based on their distributions observed in random barcodes. The algorithm employed in the program comprises two steps: i) random generation of an initial set and ii) optimal barcode selection via iterative replacement. Users can execute the program by inputting barcode length and the number of barcodes to be generated. Furthermore, the program accepts a user's own values for other parameters, including penalty scores, for advanced use, allowing it to be applied in various conditions. In many test runs to obtain 100000 barcodes with lengths of 12 nucleotides, the program showed fast performance, efficient enough to generate optimal barcode sequences with merely the use of a desktop PC. We also showed that VFOS has comparable performance, flexibility in program running, consideration of simple sequence repeats, and fast computation time in comparison with other two tools (DNABarcodes and FreeBarcodes). Owing to the versatility and fast performance of the program, we expect that many researchers will opt to apply it for selecting optimal barcode sets during their experiments, including next-generation sequencing.

Cross-species oncogenic signatures of breast cancer in canine mammary tumors.

Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.

Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients.

BACKGROUND: Aberrant mutations in KRAS play a critical role in tumor initiation and progression, and are a negative prognosis factor in lung adenocarcinoma (LUAD). RESULTS: Using genomic analysis for K-Ras isoforms (K-Ras4A and K-Ras4B) and large-scale multi-omics data, we inspected the overall survival (OS) and disease-free survival (DFS) of LUAD patients based on the abundance of transcript variants by analyzing RNA expression and somatic mutation data from The Cancer Genome Atlas (n = 516). The expression of the minor transcript K-Ras4A and its proportion were positively correlated with the presence of KRAS mutations in LUAD. We found that both K-Ras4A abundance measures (expression and proportion) have a strong association with poor OS (p = 0.0149 and p = 3.18E-3, respectively) and DFS (p = 3.03E-4 and p = 0.0237, respectively), but only in patients harboring KRAS mutations. A Cox regression analysis showed significant results in groups with low expression (hazard ratio (HR) = 2.533, 95% confidence interval (CI) = 1.380-4.651, p = 2.72E-3) and low proportion (HR = 2.549, 95% CI = 1.387-4.684, p = 2.58E-3) of K-Ras4A. CONCLUSIONS: Based on the above results, we report the possible use of abundance measures for K-Ras4A for predicting the survival of LUAD patients with KRAS mutations.

Next-generation sequencing reveals novel resistance mechanisms and molecular heterogeneity in EGFR-mutant non-small cell lung cancer with acquired resistance to EGFR-TKIs.

OBJECTIVES: Despite initial responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant non-small cell lung cancer, patients invariably develop acquired resistance. In this study, we performed next-generation sequencing in pre- and post-EGFR-TKI tumor samples to identify novel resistance mechanisms to EGFR-TKIs. MATERIAL AND METHODS: We collected tumor tissues before EGFR-TKI treatment and after progression from 19 NSCLC patients to analyze genomic alterations in 409 cancer related genes. Bioinformatics analyses were used to identify mutations in which the allele frequencies are significantly changed, or newly appeared after progression. RESULTS: Overall, mutation rates and compositions were similar between pre- and post-EGFR-TKI tumors. We identified EGFR T790M as the most common mechanism of acquired resistance (63.2%). No pre-EGFR-TKI tumor had a preexisting T790M mutation, suggesting that tumors acquired T790M mutations following progression on EGFR-TKIs. Compared to T790M-positive tumors, T790M-negative tumors showed relatively high tumor mutation burden and shorter survival, suggesting T790M-negative patients as a potential candidate for immune checkpoint inhibitors. TP53 mutation was also significantly enriched in the T790M-negative tumors. Finally, we described here for the first time a novel missense mutation (T263P), which occurred concurrently with an activating G719A mutation, in the extracellular domain II of EGFR in a patient with poor response to erlotinib. Ba/F3 cells harboring EGFR T263P/G719A mutation showed higher sensitivity to afatinib, compared to gefitinib due to inhibition of EGFR/HER2 heterodimerization. CONCLUSION: Comprehensive genomic analysis of post-EGFR-TKI tumors can provide novel insight into the complex molecular mechanisms of acquired resistance to EGFR-TKIs.

Silicotungstate, a Potential Electron Transporting Layer for Low-Temperature Perovskite Solar Cells.

Thin films of a heteropolytungstate, lithium silicotungstate (Li4SiW12O40, termed Li-ST), prepared by a solution process at low temperature, were successfully applied as electron transporting layer (ETL) of planar-type perovskite solar cells (PSCs). Dense and uniform Li-ST films were prepared on FTO glass by depositing a thin Li-ST buffer layer, followed by coating of a main Li-ST layer. The film thickness was controlled by varying the number of coating cycles, consisting of spin-coating and thermal treatment at 150 °C. In particular, by employing 60 nm-thick Li-ST layer obtained by two cycles of coating, the fabricated CH3NH3PbI3 PSC device demonstrates the photovoltaic conversion efficiency (PCE) of 14.26% with JSC of 22.16 mA cm-2, VOC of 0.993 mV and FF of 64.81%. The obtained PCE is significantly higher than that of the PSC employing a TiO2 layer processed at the same temperature (PCE = 12.27%). Spectroscopic analyses by time-resolved photoluminescence and pulsed light-induced transient measurement of photocurrent indicate that the Li-ST layer collects electrons from CH3NH3PbI3 more efficiently and also exhibits longer electron lifetime than the TiO2 layer thermally treated at 150 °C. Thus, Li-ST is considered to be a promising ETL material that can be applied for the fabrication of flexible PSC devices.

Dual-Function Au@Y2O3:Eu3+ Smart Film for Enhanced Power Conversion Efficiency and Long-Term Stability of Perovskite Solar Cells.

In the present study, a dual-functional smart film combining the effects of wavelength conversion and amplification of the converted wave by the localized surface plasmon resonance has been investigated for a perovskite solar cell. This dual-functional film, composed of Au nanoparticles coated on the surface of Y2O3:Eu3+ phosphor (Au@Y2O3:Eu3+) nanoparticle monolayer, enhances the solar energy conversion efficiency to electrical energy and long-term stability of photovoltaic cells. Coupling between the Y2O3:Eu3+ phosphor monolayer and ultraviolet solar light induces the latter to be converted into visible light with a quantum yield above 80%. Concurrently, the Au nanoparticle monolayer on the phosphor nanoparticle monolayer amplifies the converted visible light by up to 170%. This synergy leads to an increased solar light energy conversion efficiency of perovskite solar cells. Simultaneously, the dual-function film suppresses the photodegradation of perovskite by UV light, resulting in long-term stability. Introducing the hybrid smart Au@Y2O3:Eu3+ film in perovskite solar cells increases their overall solar-to-electrical energy conversion efficiency to 16.1% and enhances long-term stability, as compared to the value of 15.2% for standard perovskite solar cells. The synergism between the wavelength conversion effect of the phosphor nanoparticle monolayer and the wave amplification by the localized surface plasmon resonance of the Au nanoparticle monolayer in a perovskite solar cell is comparatively investigated, providing a viable strategy of broadening the solar spectrum utilization.

ISOexpresso: a web-based platform for isoform-level expression analysis in human cancer.

BACKGROUND: Alternative splicing events that result in the production of multiple gene isoforms reveals important molecular mechanisms. Gene isoforms are often differentially expressed across organs and tissues, developmental stages, and disease conditions. Specifically, recent studies show that aberrant regulation of alternative splicing frequently occurs in cancer to affect tumor cell transformation and growth. While analysis of isoform expression is important for discovering tumor-specific isoform signatures and interpreting relevant genomic mutations, there is currently no web-based, easy-to-use, and publicly available platform for this purpose. DESCRIPTION: We developed ISOexpresso to provide information regarding isoform existence and expression, which can be grouped by cancer vs. normal conditions, cancer types, and tissue types. ISOexpresso implements two main functions: First, the Isoform Expression View function creates visualizations for condition-specific RNA/isoform expression patterns upon query of a gene of interest. With this function, users can easily determine the major isoform (the most expressed isoform in a sample) of a gene with respect to the condition and check whether it matches the known canonical isoform. ISOexpresso outputs expression levels of all known transcripts to check alterations of expression landscape and to find potential tumor-specific isoforms. Second, the User Data Annotation function supports annotation of genomic variants to determine the most plausible consequence of a variation (e.g., an amino acid change) among many possible interpretations. As most coding sequence mutations are effective through the subsequent transcription and translation, ISOexpresso automatically prioritizes transcripts that act as backbones for mutation effect prediction by their relative expression. By employing ISOexpresso, we could investigate the consistency between the most expressed and known canonical/principal isoforms, as well as infer candidate tumor-specific isoforms based on their expression levels. In addition, we confirmed that ISOexpresso could easily reproduce previously known isoform expression patterns: recurrent observation of a major isoform across tissues, differential isoform expression patterns in a given tissue, and switching of major isoform during tumorigenesis. CONCLUSIONS: ISOexpresso serves as a web-based, easy-to-use platform for isoform expression and alteration analysis based on large-scale cancer database. We anticipate that ISOexpresso will expedite formulation and confirmation of novel hypotheses by providing isoform-level perspectives on cancer research. The ISOexpresso database is available online at http://wiki.tgilab.org/ISOexpresso/ .

Massively parallel sequencing of the entire control region and targeted coding region SNPs of degraded mtDNA using a simplified library preparation method.

The application of next-generation sequencing (NGS) to forensic genetics is being explored by an increasing number of laboratories because of the potential of high-throughput sequencing for recovering genetic information from multiple markers and multiple individuals in a single run. A cumbersome and technically challenging library construction process is required for NGS. In this study, we propose a simplified library preparation method for mitochondrial DNA (mtDNA) analysis that involves two rounds of PCR amplification. In the first-round of multiplex PCR, six fragments covering the entire mtDNA control region and 22 fragments covering interspersed single nucleotide polymorphisms (SNPs) in the coding region that can be used to determine global haplogroups and East Asian haplogroups were amplified using template-specific primers with read sequences. In the following step, indices and platform-specific sequences for the MiSeq(®) system (Illumina) were added by PCR. The barcoded library produced using this simplified workflow was successfully sequenced on the MiSeq system using the MiSeq Reagent Nano Kit v2. A total of 0.4 GB of sequences, 80.6% with base quality of >Q30, were obtained from 12 degraded DNA samples and mapped to the revised Cambridge Reference Sequence (rCRS). A relatively even read count was obtained for all amplicons, with an average coverage of 5200 × and a less than three-fold read count difference between amplicons per sample. Control region sequences were successfully determined, and all samples were assigned to the relevant haplogroups. In addition, enhanced discrimination was observed by adding coding region SNPs to the control region in in silico analysis. Because the developed multiplex PCR system amplifies small-sized amplicons (<250 bp), NGS analysis using the library preparation method described here allows mtDNA analysis using highly degraded DNA samples.

Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus.

BACKGROUND: Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus. RESULTS: We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit. CONCLUSIONS: Regardless of different cancer types, mTOR-pathway-activating mutations confer sensitivity to everolimus. Targeted sequencing of mTOR pathway genes facilitates identification of potential candidates for mTOR inhibitors.

Massively parallel sequencing of 17 commonly used forensic autosomal STRs and amelogenin with small amplicons.

The next-generation sequencing (NGS) method has been utilized to analyze short tandem repeat (STR) markers, which are routinely used for human identification purposes in the forensic field. Some researchers have demonstrated the successful application of the NGS system to STR typing, suggesting that NGS technology may be an alternative or additional method to overcome limitations of capillary electrophoresis (CE)-based STR profiling. However, there has been no available multiplex PCR system that is optimized for NGS analysis of forensic STR markers. Thus, we constructed a multiplex PCR system for the NGS analysis of 18 markers (13CODIS STRs, D2S1338, D19S433, Penta D, Penta E and amelogenin) by designing amplicons in the size range of 77-210 base pairs. Then, PCR products were generated from two single-sources, mixed samples and artificially degraded DNA samples using a multiplex PCR system, and were prepared for sequencing on the MiSeq system through construction of a subsequent barcoded library. By performing NGS and analyzing the data, we confirmed that the resultant STR genotypes were consistent with those of CE-based typing. Moreover, sequence variations were detected in targeted STR regions. Through the use of small-sized amplicons, the developed multiplex PCR system enables researchers to obtain successful STR profiles even from artificially degraded DNA as well as STR loci which are analyzed with large-sized amplicons in the CE-based commercial kits. In addition, successful profiles can be obtained from mixtures up to a 1:19 ratio. Consequently, the developed multiplex PCR system, which produces small size amplicons, can be successfully applied to STR NGS analysis of forensic casework samples such as mixtures and degraded DNA samples.

Analysis of Whole Transcriptome Sequencing Data: Workflow and Software.

RNA is a polymeric molecule implicated in various biological processes, such as the coding, decoding, regulation, and expression of genes. Numerous studies have examined RNA features using whole transcriptome sequencing (RNA-seq) approaches. RNA-seq is a powerful technique for characterizing and quantifying the transcriptome and accelerates the development of bioinformatics software. In this review, we introduce routine RNA-seq workflow together with related software, focusing particularly on transcriptome reconstruction and expression quantification.

Population data for 30 insertion-deletion markers in a Korean population.

This study reports on the forensic parameters of 30 insertion-deletion polymorphisms (Indels) (Investigator DIPplex® kit) in 100 individuals from a Korean population. The match probability ranged from 0.353 to 0.789, and the combined power of discrimination reached 0.99999999995. The DIPplex® kit is more discriminative in Koreans than six COfiler® short tandem repeats (STRs), but less discriminative than nine Profiler Plus® STRs. This study further demonstrated that some Indels in the DIPplex® kit could be used as Asian ancestry informative markers through a comparison with other population data.

mtDNAprofiler: a Web application for the nomenclature and comparison of human mitochondrial DNA sequences.

Mitochondrial DNA (mtDNA) is a valuable tool in the fields of forensic, population, and medical genetics. However, recording and comparing mtDNA control region or entire genome sequences would be difficult if researchers are not familiar with mtDNA nomenclature conventions. Therefore, mtDNAprofiler, a Web application, was designed for the analysis and comparison of mtDNA sequences in a string format or as a list of mtDNA single-nucleotide polymorphisms (mtSNPs). mtDNAprofiler which comprises four mtDNA sequence-analysis tools (mtDNA nomenclature, mtDNA assembly, mtSNP conversion, and mtSNP concordance-check) supports not only the accurate analysis of mtDNA sequences via an automated nomenclature function, but also consistent management of mtSNP data via direct comparison and validity-check functions. Since mtDNAprofiler consists of four tools that are associated with key steps of mtDNA sequence analysis, mtDNAprofiler will be helpful for researchers working with mtDNA. mtDNAprofiler is freely available at http://mtprofiler.yonsei.ac.kr.