The Effects of Corporate Finance on Firm Risk-taking and Performance: Theory and Evidence

Some firms may exhibit better operating performance than others because they undertake riskier projects: risk-return tradeoff. We develop a model to examine the effects of financial contracts on a firmfs choice between safer (lower risk, lower return) and riskier (higher risk, higher return) projects. The model shows that, assuming a competitive capital market (i.e., financiers with no monopoly power), three types of financial contracts (rollover loans, non-rollover loans, and new share issues) can each be an equilibrium contract, depending on conditions. While firms undertake griskierh projects when using non-rollover loans or new share issues, firms undertake gsaferh projects when using rollover loans. The model emphasizes the role of rollover loans (with passive monitoring) as a potential disciplinary device to suppress a firmfs risk-taking. The model generates several predictions about the determinants of a firmfs risk-taking and its performance. One key prediction of the model is that (risk-neutral) firms with closer bank relationships are more likely to use rollover loans and undertake gsaferh projects, even with a contestable capital market. We find novel empirical support for the modelfs predictions.corporate finance, corporate governance, firm risk-taking, firm performance, loan rollover

TLR2-Dependent Induction of IL-10 and Foxp3+CD25+CD4+ Regulatory T Cells Prevents Effective Anti-Tumor Immunity Induced by Pam2 Lipopeptides In Vivo

16 S-[2,3-bis(palmitoyl)propyl]cysteine (Pam2) lipopeptides act as toll-like receptor (TLR)2/6 ligands and activate natural killer (NK) cells and dendritic cells (DCs) to produce inflammatory cytokines and cytotoxic NK activity in vitro. However, in this study, we found that systemic injection of Pam2 lipopeptides was not effective for the suppression of NK-sensitive B16 melanomas in vivo. When we investigated the immune suppressive mechanisms, systemic injection of Pam2 lipopeptides induced IL-10 in a TLR2-dependent manner. The Pam2 lipopeptides increased the frequencies of Foxp3+CD4+ regulatory T (T reg) cells in a TLR2- and IL-10- dependent manner. The T reg cells from Pam2-lipopeptide injected mice maintained suppressor activity. Pam2 lipopeptides, plus the depletion of T reg with an anti-CD25 monoclonal antibody, improved tumor growth compared with Pam2 lipopeptides alone. In conclusion, our data suggested that systemic treatment of Pam2 lipopeptides promoted IL-10 production and T reg function, which suppressed the effective induction of anti-tumor immunity in vivo. It is necessary to develop an adjuvant that does not promote IL-10 and T reg function in vivo for the future establishment of an anti-cancer vaccine

Characterization of CYP76M5–8 Indicates Metabolic Plasticity within a Plant Biosynthetic Gene Cluster

Recent reports have revealed genomic clustering of enzymatic genes for particular biosynthetic pathways in plant specialized/secondary metabolism. Rice (Oryza sativa) carries two such clusters for production of antimicrobial diterpenoid phytoalexins, with the cluster on chromosome 2 containing four closely related/homologous members of the cytochrome P450 CYP76M subfamily (CYP76M5–8). Notably, the underlying evolutionary expansion of these CYP appears to have occurred after assembly of the ancestral biosynthetic gene cluster, suggesting separate roles. It has been demonstrated that CYP76M7 catalyzes C11α-hydroxylation of ent-cassadiene, and presumably mediates an early step in biosynthesis of the derived phytocassane class of phytoalexins. Here we report biochemical characterization of CYP76M5, -6, and -8. Our results indicate that CYP76M8 is a multifunctional/promiscuous hydroxylase, with CYP76M5 and -7 seeming to provide only redundant activity, while CYP76M6 seems to provide both redundant and novel activity, relative to CYP76M8. RNAi-mediated double knockdown of CYP76M7 and -8 suppresses elicitor inducible phytocassane production, indicating a role for these monooxygenases in phytocassane biosynthesis. In addition, our data suggests that CYP76M5, -6, and -8 may play redundant roles in production of the oryzalexin class of phytoalexins as well. Intriguingly, the preceding diterpene synthase for oryzalexin biosynthesis, unlike that for the phytocassanes, is not found in the chromosome 2 diterpenoid biosynthetic gene cluster. Accordingly, our results not only uncover a complex evolutionary history, but also further suggest some intriguing differences between plant biosynthetic gene clusters and the seemingly similar microbial operons. The implications for the underlying metabolic evolution of plants are then discussed

Model of lung cancer surgery risk derived from a Japanese nationwide web-based database of 78 594 patients during 2014–2015

OBJECTIVESUsing data obtained from a Japanese nationwide annual database with web-based data entry, we developed a risk model of mortality and morbidity after lung cancer surgery.METHODSThe characteristics and operative and postoperative data from 80 095 patients who underwent lung cancer surgery were entered into the annual National Clinical Database of Japan data sets for 2014 and 2015. After excluding 1501 patients, the development data set for risk models included 38 277 patients entering in 2014 and the validation data set included 40 317 patients entering in 2015. Receiver–operating characteristic curves were generated for the outcomes of mortality and composite mortality/major morbidity. The concordance index was used to assess the discriminatory ability and validity of the model.RESULTSThe 30-day mortality and overall mortality rates, including in-hospital deaths, were 0.4% and 0.8%, respectively, in 2014, and 0.4% and 0.8%, respectively, in 2015. The rate of major morbidity was 5.6% in 2014 and 5.6% in 2015. Several risk factors were significantly associated with mortality, namely, male sex, performance status, comorbidities of interstitial pneumonia and liver cirrhosis, haemodialysis and the surgical procedure pneumonectomy. The concordance index for mortality and composite mortality/major morbidity was 0.854 (P < 0.001) and 0.718 (P < 0.001), respectively, for the development data set and 0.849 (P < 0.001) and 0.723 (P < 0.001), respectively, for the validation data set.CONCLUSIONSThis model was satisfactory for predicting surgical outcomes after pulmonary resection for lung cancer in Japan and will aid preoperative assessment and improve clinical outcomes for lung cancer surgery

Thermal Infrared Imaging Experiments of C-Type Asteroid 162173 Ryugu on Hayabusa2

The thermal infrared imager TIR onboard Hayabusa2 has been developed to investigate thermo-physical properties of C-type, near-Earth asteroid 162173 Ryugu. TIR is one of the remote science instruments on Hayabusa2 designed to understand the nature of a volatile-rich solar system small body, but it also has significant mission objectives to provide information on surface physical properties and conditions for sampling site selection as well as the assessment of safe landing operations. TIR is based on a two-dimensional uncooled micro-bolometer array inherited from the Longwave Infrared Camera LIR on Akatsuki (Fukuhara et al., 2011). TIR takes images of thermal infrared emission in 8 to 12 μm with a field of view of 16×12∘ and a spatial resolution of 0.05∘ per pixel. TIR covers the temperature range from 150 to 460 K, including the well calibrated range from 230 to 420 K. Temperature accuracy is within 2 K or better for summed images, and the relative accuracy or noise equivalent temperature difference (NETD) at each of pixels is 0.4 K or lower for the well-calibrated temperature range. TIR takes a couple of images with shutter open and closed, the corresponding dark frame, and provides a true thermal image by dark frame subtraction. Data processing involves summation of multiple images, image processing including the StarPixel compression (Hihara et al., 2014), and transfer to the data recorder in the spacecraft digital electronics (DE). We report the scientific and mission objectives of TIR, the requirements and constraints for the instrument specifications, the designed instrumentation and the pre-flight and in-flight performances of TIR, as well as its observation plan during the Hayabusa2 mission

Detection of Nε-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells

Nε-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify Nε-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. Nε-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-Nε-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30–40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two Nε-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of Nε-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that Nε-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells

Changes in Plasma Metabolites Concentrations in Obese Dogs Supplemented With Anti-oxidant Compound

The aim of this study is to discuss the effect of anti-oxidant supplement (Rv-PEM01-99, Kibun Foods, Inc., Tokyo, Japan) on changes in energy metabolism in obese dogs. 200 mg/kg/day of Rv-PEM01-99 (equivalent to 5 mg kg/day of quercetin derivative) were applied for 6 weeks to the Beagle dogs fed high fat diet (HFD) or control diet (CD). In the present study, body weight (BW) decreasing effect of Rv-PEM 01-99 in obese dogs was not clear. However, plasma alkaline phosphatase (ALP) activities at the end of experiment were significantly decreased compared to those at the start of experiment in obese dogs supplemented with Rv-PEM 01-99 (paired-t test, p &lt; 0.05). In control dogs supplemented with Rv-PEM 01-99, Plasma malondialdehyde (MDA), and triglycerides (TG) levels and lactate dehydrogenase (LDH) activities were significantly decreased compared to those at the start of experiment (paired-t test, p &lt; 0.05). From these findings, Rv-PEM 01-99 seems to be not harmful for dogs. Anti-lipid peroxide effect and liver function improvement are expected in the dogs supplemented with Rv-PEM 01-99

Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages

Mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene in hematopoietic stem cells (HSCs) results in the loss of glycosylphosphatidylinositol- anchored proteins (GPI-APs) on HSCs, but minimally affects their development, and thus can be used as a clonal maker of HSCs. We analyzed GPI-APs expression on six major lineage cells in a total of 574 patients with bone marrow (BM) failure in which microenvironment itself is thought to be unaffected, including aplastic anemia (AA) or myelodysplastic syndrome (MDS). GPI-APs-deficient (GPIAPs-) cells were detected in 250 patients. Whereas the GPIAPs- cells were seen in all six lineages in a majority of patients who had higher proportion ([dbmtequ]3%) of GPIAPs- cells, they were detected in only limited lineages in 92.9% of cases in the lower proportion (<3%) group. In all 250 cases, the same lineages of GPI-APs- cells were detected even after 6-18-month intervals, indicating that the GPIAPs- cells reflect hematopoiesis maintained by a self-renewing HSC in most of cases. The frequency of clones with limited lineages seen in mild cases of AA was similar to that in severe cases, and clones with limited lineages were seen even in two health volunteer cases. These results strongly suggest most individual HSCs produce only restricted lineages even in a steady state. While this restriction could reflect heterogeneity in the developmental potential of HSCs, we propose an alternative model in which the BM microenvironment is mosaic in supporting commitment of progenitors toward distinct lineages. Our computer simulation based on this model successfully recapitulated the observed clinical data. © AlphaMed Press

Annual report by The Japanese Association for Thoracic Surgery

All data regarding cardiovascular surgery and thoracic surgery were obtained from NCD, whereas data regarding esophageal surgery were collected from survey questionnaire by The Japanese Association for Thoracic Surgery forms because NCD of esophageal surgery does not include non-surgical cases (i.e., patients with adjuvant chemotherapy or radiation alone). Based on the change in data aggregation, there are several differences between this 2015 annual report and previous annual reports: the number of institutions decreased in each category from 578 (2014) to 568 (2015) in cardiovascular, from 762 to 714 in general thoracic and from 626 to 571 in esophageal surgery. Because more than two departments in the same institute registered their data to NCD individually, we cannot calculate correct number of institutes in this survey. Then, the response rate is not indicated in the category of cardiovascular surgery (Table 1), and the number of institutions classified by the operation number is also not calculated in the category of cardiovascular surgery (Table 2)

Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy

Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management