Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest

Casein kinase 1 epsilon is identified as a potential target for developing selective anticancer reagents

Vertically aligned InGaN nanowires with engineered axial In composition for highly efficient visible light emission.

We report on the fabrication of novel InGaN nanowires (NWs) with improved crystalline quality and high radiative efficiency for applications as nanoscale visible light emitters. Pristine InGaN NWs grown under a uniform In/Ga molar flow ratio (UIF) exhibited multi-peak white-like emission and a high density of dislocation-like defects. A phase separation and broad emission with non-uniform luminescent clusters were also observed for a single UIF NW investigated by spatially resolved cathodoluminescence. Hence, we proposed a simple approach based on engineering the axial In content by increasing the In/Ga molar flow ratio at the end of NW growth. This new approach yielded samples with a high luminescence intensity, a narrow emission spectrum, and enhanced crystalline quality. Using time-resolved photoluminescence spectroscopy, the UIF NWs exhibited a long radiative recombination time (τr) and low internal quantum efficiency (IQE) due to strong exciton localization and carrier trapping in defect states. In contrast, NWs with engineered In content demonstrated three times higher IQE and a much shorter τr due to mitigated In fluctuation and improved crystal quality

Inhibition of poly(ADP-ribose)polymerase binding to DNA by thymidine dimer

AbstractThe ability of poly(ADP-ribose)polymerase to bind damaged DNA was assessed by electrophoretic mobility shift assay. DNA binding domain of poly(ADP-ribose)polymerase (PARPDBD) binds to synthetic deoxyribonucleotide duplex 10-mer. However, the synthetic deoxyribonucleotide duplex containing cys-syn thymidine dimer which produces the unwinding of DNA helix structure lost its affinity to PARPDBD. It was shown that the binding of PARPDBD to the synthetic deoxyribonucleotide duplex was not affected by O6-Me-dG which causes only minor distortion of DNA helix structure. This study suggests that the stabilized DNA helix structure is important for poly(ADP-ribose)polymerase binding to DNA breaks, which are known to stimulate catalytic activity of poly(ADP-ribose)polymerase

Joint Channel Estimation and Phase Noise Suppression for OFDM Systems

The joint channel estimation and phase noise suppression scheme for orthogonal frequency-division multiplexing (OFDM) systems is proposed for a case where channel estimation is needed symbol by symbol. In the proposed scheme, channel estimation and phase noise suppression are performed iteratively via the expectation-maximization (EM) algorithm. The proposed algorithm mitigates the performance degradation due to phase noise effectively while providing the accurate channel estimate with comparatively few pilot subcarriers so that the spectral efficiency of an OFDM system is improved

Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies

Purpose Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261). Materials and Methods Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR). Results In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%). Conclusion Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma

An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient's condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma

Sarcopenia in autoimmune and rheumatic diseases: a comprehensive review

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia

A Case of Osteoclast-like Giant Cell Tumor of the Pancreas with Ductal Adenocarcinoma: Histopathological, Immunohistochemical, Ultrastructural and Molecular Biological Studies

Osteoclast-like giant cell tumor of the pancreas is a very rare neoplasm, of which the histiogenesis remains controversial. A 63-yr-old woman was hospitalized for evaluation of epigastric pain. An abdominal computerized tomography revealed the presence of a large cystic mass, arising from the tail of pancreas. A distal pancreatectomy with splenectomy was performed. Histologically, the tumor was composed of mononuclear stromal cells intermingled with osteclast-like giant cells. In addition, there was a small area of moderately to well differentiated ductal adenocarcinoma. The final pathologic diagnosis was osteoclast-like giant cell tumor of the pancreas with ductal adenocarcinoma. Here, we describe the histopathological, immunohistochemical, ultrastructural and molecular biological findings of this tumor with review of the literature pertaining to this condition