Generalized theoretical method for the interaction between arbitrary nonuniform electric field and molecular vibrations: Toward near-field infrared spectroscopy and microscopy.

A theoretical method to compute infrared absorption spectra when a molecule is interacting with an arbitrary nonuniform electric field such as near-fields is developed and numerically applied to simple model systems. The method is based on the multipolar Hamiltonian where the light-matter interaction is described by a spatial integral of the inner product of the molecular polarization and applied electric field. The computation scheme is developed under the harmonic approximation for the molecular vibrations and the framework of modern electronic structure calculations such as the density functional theory.

Endoscopic Submucosal Dissection is Feasible for Very Elderly Patients with Early Gastric Cancer : Comparison of Short-Term and Long-Term Outcomes in Very Elderly and Non-Elderly Patients.

Background/aims: Endoscopic submucosal dissection (ESD) has become a standard procedure for the resection of early gastric cancer (EGC). However, the feasibility of ESD for very elderly patients, aged ≥ 80 years, has not been determined.

Methodology: The study population included 67 non-elderly (NE) patients aged ≤ 65 years (80 lesions) and 22 very elderly (VE) patients ≥ 80 years (26 lesions) with EGC who underwent ESD and met the criteria for absolute or expanded indications.

A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

Purpose: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting.

Methods: VS-6063 was administered orally twice daily (b.

Effects of chronic DHEA treatment on central and peripheral reproductive parameters, the onset of vaginal opening and the estrous cycle in female rats.

The neonatal and/or prepubertal androgen milieu affects sexual maturation and reproductive function in adulthood. However, the effects of chronic dehydroepiandrosterone (DHEA) treatment on reproductive functions have not been fully elucidated. Therefore, the reproductive phenotypes and parameters of rats that had been subjected to chronic DHEA treatment were evaluated in this study.

Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.

The advancement of the onset of vaginal opening in female rats subjected to chronic testosterone treatment occurs independently of hypothalamic Kiss1 and RFRP expression.

Objective: The neonatal and/or prepubertal androgen milieu affects sexual maturation. In rodents, neonatal chronic testosterone treatment, which is used as a model of polycystic ovary syndrome (PCOS), results in the onset of vaginal opening occurring earlier in the pubertal period.

Design: In the present study, the changes in hypothalamic Kiss1 (a gonadotropin-releasing hormone (GnRH)-stimulating factor) and RF-amide related peptide (RFRP; a GnRH inhibitory factor) mRNA expression induced by testosterone treatment were examined in order to clarify whether these factors are involved in the testosterone-induced acceleration of sexual maturation.

Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome.

The conventional Δ5 and Δ4 steroidogenic pathways mediate androgen production in females. While multiple non-conventional pathways to dihydrotestosterone (DHT) have recently been postulated in humans, the functional significance of these pathways remains to be elucidated. The aim of this study was to clarify the origin of androgens in healthy women and in patients with polycystic ovary syndrome (PCOS), a multifactorial disorder characterized by androgen overproduction.

Successful human epidermal growth receptor 2-targeted therapy beyond disease progression for extramammary Paget's disease.

Extramammary Paget's disease is a malignant intraepithelial carcinoma, which constitutes less than 1 % of all vulvar malignancies. Surgical resection is the first treatment of choice and standard chemotherapy has not been established for advanced or recurrent disease. Experimental and clinical studies have identified human epidermal growth receptor 2 as a potential therapeutic target.

Developmental changes in the hypothalamic mRNA levels of nucleobindin-2 (NUCB2) and their sensitivity to fasting in male and female rats.

Nesfatin-1 is a central anorectic peptide derived from the precursor protein nucleobindin-2 (NUCB2). In the present study, the changes in hypothalamic NUCB2 mRNA expression and their responses to food deprivation during the neonatal to pre-pubertal period (postnatal days 10, 20, and 30) were evaluated in male and female rats. The rats' serum leptin levels were also measured because NUCB2 mRNA expression is positively regulated by leptin.

The expression of orexigenic and anorexigenic factors in middle-aged female rats that had been subjected to prenatal undernutrition.

Fetal growth retardation, which affects short- and long-term fetal brain development, is associated with metabolic, hematological, and thermal disturbances, which can increase the risk of metabolic syndrome later in life. Orexigenic and anorexigenic factors regulate food intake and energy expenditure. We studied how the expression of these factors was affected by food deprivation (FD) in middle-aged female rats that had been subjected to prenatal undernutrition.

Prenatal undernutrition results in greater lipopolysaccharide-induced changes in hypothalamic TNF-α expression, but does not affect the equivalent changes in the serum levels of luteinizing hormone and testosterone, in adult male rats.

Immune stress can cause reproductive dysfunction. Some hypothalamic factors such as pro-inflammatory cytokines play pivotal roles in reproductive disorders under immune stress conditions. Recently, it has been reported that prenatal undernutrition affects not only metabolic functions, but also the responses of physiological functions to immune stress in adulthood.

Synergistic effect of ATP for RuvA-RuvB-Holliday junction DNA complex formation.

The Escherichia coli RuvB hexameric ring motor proteins, together with RuvAs, promote branch migration of Holliday junction DNA. Zero mode waveguides (ZMWs) constitute of nanosized holes and enable the visualization of a single fluorescent molecule under micromolar order of the molecules, which is applicable to characterize the formation of RuvA-RuvB-Holliday junction DNA complex. In this study, we used ZMWs and counted the number of RuvBs binding to RuvA-Holliday junction DNA complex.

Afatinib-refractory brain metastases from EGFR-mutant non-small-cell lung cancer successfully controlled with erlotinib: a case report.

Both afatinib and erlotinib are tyrosine kinase inhibitors that inhibit aberrant epidermal growth factor receptor (EGFR) signals in non-small-cell lung cancer (NSCLC). Afatinib is an irreversible inhibitor directed against EGFR, ErbB-2, and ErbB-4, whereas erlotinib is a reversible inhibitor directed against EGFR only. Although afatinib has been shown to be effective in the treatment for erlotinib-refractory and/or gefitinib-refractory central nervous system metastases from NSCLC, little is known about the efficacy of erlotinib for afatinib-refractory central nervous system metastases.

Left ventricular reverse remodeling with infantile dilated cardiomyopathy and pitfalls of carvedilol therapy.

Background: The left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (DCM) and the treatment with carvedilol in infants with severe heart failure remain poorly understood.

Methods: We reviewed the medical records of 5 infants around 12 months old referred to our hospital with severe heart failure due to DCM. Increased left ventricular fractional shortening (LVFS) by more than 10% and the percent of normal of left ventricular end-diastolic dimension (%LVDd) less than 120% were defined as LVRR in this study.

Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification.

Objective: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications.

Material And Methods: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria.

Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer.

Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer.

Patients And Methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts.

The pan-HER family tyrosine kinase inhibitor afatinib overcomes HER3 ligand heregulin-mediated resistance to EGFR inhibitors in non-small cell lung cancer.

Afatinib is a second generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) characterized as an irreversible pan-human EGFR (HER) family inhibitor. Afatinib remains effective for a subpopulation of patients with non-small cell lung cancer (NSCLC) with acquired resistance to first generation EGFF-TKIs such as erlotinib. Heregulin activates HER3 in an autocrine fashion and causes erlotinib resistance in NSCLC.

Microbial rhodopsins of Halorubrum species isolated from Ejinoor salt lake in Inner Mongolia of China.

Microbial rhodopsins are photoactive proteins that use a retinal molecule as the photoactive center. Because of structural simplicity and functional diversity, microbial rhodopsins have been an excellent model system for structural biology. In this study, a halophilic archaea that has three microbial rhodopsin-type genes in its genome was isolated from Ejinoor salt lake in Inner Mongolia of China.

Effects of LPS injection on the hypothalamic and testicular mRNA expression levels of reproductive factors in male rats.

Objectives: In the hypothalamus, kisspeptin and RFamide-related peptide (RFRP) regulate gonadotropin-releasing hormone expression. Kisspeptin and RFRP are also found in the testes and might play roles in steroidogenesis and spermatogenesis.

Design And Results: The present study demonstrated that the hypothalamic mRNA expression level of the kisspeptin receptor was decreased by the injection of lipopolysaccharide (LPS) (500 μg/kg) in male rats, and it was suggested that such changes might contribute to reductions in serum luteinizing hormone levels.

Developmental changes in the hypothalamic mRNA levels of prepro-orexin and orexin receptors and their sensitivity to fasting in male and female rats.

Orexin, which is also called as hypocretin (Hcrt), a product of the prepro-orexin (pp-orexin//Hcrt) gene, affects various physiological and behavioral functions, such as the sleep-wake cycle and appetite. The developmental changes in the hypothalamic mRNA levels of pp-prexin and the orexin receptors OX1R and OX2R and their sensitivity to fasting were evaluated in both male and female rats. During development, hypothalamic pp-orexin/Hcrt mRNA expression increased in both male and female rats, whereas hypothalamic OX1R mRNA expression decreased in both sexes.

Magnetic properties of magnetite synthesized by Magnetospirillum magnetotacticum MS-1 cultured with different concentrations of ferric iron.

Objective: To clarify the effect of Fe(3+) concentration on magnetite formation, Magnetospirillum magnetotacticum MS-1 was cultured at various initial concentrations of Fe(3+) and the yield and magnetic properties of the cells were investigated.

Results: Although total cell yields (g/l) were not dependent on the initial concentration of Fe(3+) (0-68 µM) in the growth medium, the percentage of magnetic cells increased as the initial Fe(3+) concentration increased. The coercivity (H c) and saturation magnetization (M s) of dried MS-1 cells increased and the blocking temperature (T B) decreased as the initial Fe(3+) concentration increased.

The role of the non-covalent β-ionone-ring binding site in rhodopsin: historical and physiological perspective.

Bleached rhodopsin regenerates by way of the Schiff base formation between the 11-cis retinal and opsin. Recovery of human vision from light adapted states follows biphasic kinetics and each adaptive phase is assigned to two distinct classes of visual pigments in cones and rods, respectively, suggesting that the speed of Schiff base formation differs between iodopsin and rhodopsin. Matsumoto and Yoshizawa predicted the existence of a β-ionone ring-binding site in rhodopsin, which has been proven by structural studies.

Heterotrimeric G protein subunits differentially respond to endoplasmic reticulum stress in Arabidopsis.

Canonical heterotrimeric G proteins in eukaryotes are major components that localize at plasma membrane and transmit extracellular stimuli into the cell. Genome of a seed plant Arabidopsis thaliana encodes at least one Gα (GPA1), one Gβ (AGB1), and 3 Gγ (AGG1, AGG2 and AGG3) subunits. The loss-of-function mutations of G protein subunit(s) cause multiple defects in development as well as biotic and abiotic stress responses.

The suppressive effect of immune stress on LH secretion is absent in the early neonatal period in rats.

Some physiological functions display weak responses to stress in the early neonatal period; i.e., they exhibit stress hyporesponse periods.