Svanehenderson7180

Transition metal dichalcogenide (TMD) monolayers are two-dimensional semiconductors with two valleys in their band structure that can be selectively addressed using circularly polarized light. Their photoluminescence spectrum is characterized by neutral and charged excitons (trions) that form a chemical equilibrium governed by the net charge density. Here, we use chemical doping to drive the conversion of excitons into trions in [Formula see text] monolayers at room temperature, and study the resulting valley polarization via photoluminescence measurements under valley-selective optical excitation. We show that the doping causes the emission to become dominated by trions with a strong valley polarization associated with rapid non-radiative recombination. Simultaneously, the doping results in strongly quenched but highly valley-polarized exciton emission due to the enhanced conversion into trions. A rate equation model explains the observed valley polarization in terms of the doping-controlled exciton-trion equilibrium. Our results shed light on the important role of exciton-trion conversion on valley polarization in monolayer TMDs.In this study we undertook a novel combination therapy using rAd-p53 in situ gene therapy and immunotherapy with immune checkpoint inhibitor (ICI) anti-PD-1 antibody for urogenital cancers. Three mouse syngeneic tumor cell lines, TRAMP-C2 (prostate cancer derived from C57BL/6 mice), MBT-2 (bladder cancer derived from C3H mice) and Renca (kidney cancer derived from BALB/c mice) were used in this study. The highest coxsackie and adenovirus receptor (CAR) mRNA expression was observed in TRAMP-C2 cells, followed by Renca and then MBT-2 cells. Consistent with the CAR expressions, rAd-p53 at 160 multiplicity of infection (MOI) significantly inhibited the cell proliferation of TRAMP-C2 and Renca cells, but not MBT-2 cells. In in vivo experiments, the combination of intratumoral injections of rAd-p53 (1 × 109 plaque-forming units) every other day and intraperitoneal injections of anti-mouse PD-1 antibody (200 μg) twice a week suppressed tumor growth and prolonged survival compared to rAd-p53 or anti-PD-1 antibody monotherapy in both the TRAMP-C2 and Renca models. Our results encourage the clinical development of combination therapy comprised of in situ gene therapy with rAd-p53 and immunotherapy with an ICI anti-PD-1 antibody for urogenital cancers.This study aims to elucidate the carrier dynamics behind thermal droop in GaInN-based blue light-emitting diodes (LEDs) by separating multiple physical factors. To this end, first, we study the differential carrier lifetimes (DCLs) by measuring the impedance of a sample LED under given driving-current conditions over a very wide operating temperature range of 300 K-500 K. The measured DCLs are decoupled into radiative carrier lifetime (τR) and nonradiative carrier lifetime (τNR), via utilization of the experimental DCL data, and then very carefully investigated as a function of driving current over a wide range of operating temperatures. Next, to understand the measurement results of temperature-dependent τR and τNR characteristics, thermodynamic analysis is conducted, which enables to look deeply into the temperature-dependent behavior of the carriers. Selleck PF-573228 On the basis of the results, we reveal that thermal droop is originated by the complex dynamics of multiple closely interrelated physical factors instead of a single physical factor. In particular, we discuss the inherent cause of accelerated thermal droop with elevated temperature.We analyze the performance of a force detector based on balanced measurements with a Mach-Zehnder interferometer incorporating a standard optomechanical cavity. The system is driven by a coherent superposition of coherent light and squeezed vacuum field, providing quantum correlation along with optical coherence in order to enhance the measurement sensitivity beyond the standard quantum limit. We analytically find the optimal measurement strength, squeezing direction, and squeezing strength at which the symmetrized power spectral density for the measurement noise is minimized below the standard quantum limit. This force detection scheme based on a balanced Mach-Zehnder interferometer provides better sensitivity compared to that based on balanced homodyne detection with a local oscillator in the low frequency regime.Adenomyosis is defined as the presence of ectopic nests of endometrial glands and stroma within the myometrium. Adenomyosis is a common cause of dysmenorrhea, menorrhagia, and chronic pelvic pain but is often underdiagnosed. Despite its prevalence and severity of symptoms, its pathogenesis and etiology are poorly understood. Our previous study showed that aberrant activation of β-catenin results in adenomyosis through epithelial-mesenchymal transition. link2 Using transcriptomic and ChIP-seq analysis, we identified activation of TGF-β signaling in the uteri of mutant mice that expressed dominant stabilized β-catenin in the uterus. There was a strong positive correlation between β-catenin and TGF-β2 proteins in women with adenomyosis. Furthermore, treatment with pirfenidone, a TGF-β inhibitor, increased E-cadherin expression and reduced cell invasiveness in Ishikawa cells with nuclear β-catenin. Our results suggest that β-catenin activates TGF-β-induced epithelial-mesenchymal transition in adenomyosis. This finding describes the molecular pathogenesis of adenomyosis and the use of TGF-β as a potential therapeutic target for adenomyosis.We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80-63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26-155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.Negativity bias, i.e., tendency to respond strongly to negative stimuli, can be captured via behavioural and psychophysiological responses to potential threat. A virtual environment (VE) was created at room-scale wherein participants traversed a grid of ice blocks placed 200 m above the ground. Threat was manipulated by increasing the probability of encountering ice blocks that disintegrated and led to a virtual fall. Participants interacted with the ice blocks via sensors placed on their feet. Thirty-four people were recruited for the study, who were divided into High (HN) and Low (LN) Neuroticism groups. Movement data were recorded alongside skin conductance level and facial electromyography from the corrugator supercilii and zygomaticus major. Risk-averse behaviours, such as standing on 'safe' blocks and testing blocks prior to movement, increased when threat was highest. HN individuals exhibited more risk-averse behaviour than the LN group, especially in the presence of high threat. In addition, activation of the corrugator muscle was higher for HN individuals in the period following a movement to an ice block. These findings are discussed with respect to the use of room-scale VE as a protocol for emotion induction and measuring trait differences in negativity bias within VR.RAS signaling is a promising target for colorectal cancer (CRC) therapy, and a variety of selective inhibitors have been developed. However, their use has often failed to demonstrate a significant benefit in CRC patients. Here, we used patient-derived organoids (PDOs) derived from a familial adenomatous polyposis (FAP) patient to analyze the response to chemotherapeutic agents targeting EGFR, BRAF and MEK. We found that PDOs carrying KRAS mutations were resistant to MEK inhibition, while those harboring the BRAF class 3 mutation were hypersensitive. We used a systematic approach to examine the phosphorylation of RAS effectors using reverse-phase protein array (RPPA) and found increased phosphorylation of MEK induced by binimetinib. A high basal level of ERK phosphorylation and its rebound activation after MEK inhibition were detected in KRAS-mutant PDOs. link3 Notably, the phosphorylation of EGFR and AKT was more closely correlated with that of MEK than that of ERK. Transcriptome analysis identified MYC-mediated transcription and IFN signaling as significantly correlated gene sets in MEK inhibition. Our experiments demonstrated that RPPA analysis of PDOs, in combination with the genome and transcriptome, is a useful preclinical research platform to understand RAS signaling and provides clues for the development of chemotherapeutic strategies.Although splicing errors due to single nucleotide variants represent a common cause of monogenic disorders, only a few variants have been shown to create new splice sites in exons. Here, we report an MAP3K1 splice variant identified in two siblings with 46,XY disorder of sex development. The patients carried a maternally derived c.2254C>T variant. The variant was initially recognized as a nonsense substitution leading to nonsense-mediated mRNA decay (p.Gln752Ter); however, RT-PCR for lymphoblastoid cell lines showed that this variant created a new splice donor site and caused 39 amino acid deletion (p.Gln752_Arg790del). All transcripts from the variant allele appeared to undergo altered splicing. The two patients exhibited undermasculinized genitalia with and without hypergonadotropism. Testosterone enanthate injections and dihydrotestosterone ointment applications yielded only slight increase in their penile length. Dihydrotestosterone-induced APOD transactivation was less significant in patients' genital skin fibroblasts compared with that in control samples. This study provides an example of nonsense-associated altered splicing, in which a highly potent exonic splice site was created. Furthermore, our data, in conjunction with the previous data indicating the association between MAP3K1 and androgen receptor signaling, imply that the combination of testicular dysgenesis and androgen insensitivity may be a unique phenotype of MAP3K1 abnormalities.