Session-Based Programming for Parallel Algorithms: Expressiveness and Performance

This paper investigates session programming and typing of benchmark examples to compare productivity, safety and performance with other communications programming languages. Parallel algorithms are used to examine the above aspects due to their extensive use of message passing for interaction, and their increasing prominence in algorithmic research with the rising availability of hardware resources such as multicore machines and clusters. We contribute new benchmark results for SJ, an extension of Java for type-safe, binary session programming, against MPJ Express, a Java messaging system based on the MPI standard. In conclusion, we observe that (1) despite rich libraries and functionality, MPI remains a low-level API, and can suffer from commonly perceived disadvantages of explicit message passing such as deadlocks and unexpected message types, and (2) the benefits of high-level session abstraction, which has significant impact on program structure to improve readability and reliability, and session type-safety can greatly facilitate the task of communications programming whilst retaining competitive performance

Choreographies with Secure Boxes and Compromised Principals

We equip choreography-level session descriptions with a simple abstraction of a security infrastructure. Message components may be enclosed within (possibly nested) "boxes" annotated with the intended source and destination of those components. The boxes are to be implemented with cryptography. Strand spaces provide a semantics for these choreographies, in which some roles may be played by compromised principals. A skeleton is a partially ordered structure containing local behaviors (strands) executed by regular (non-compromised) principals. A skeleton is realized if it contains enough regular strands so that it could actually occur, in combination with any possible activity of compromised principals. It is delivery guaranteed (DG) realized if, in addition, every message transmitted to a regular participant is also delivered. We define a novel transition system on skeletons, in which the steps add regular strands. These steps solve tests, i.e. parts of the skeleton that could not occur without additional regular behavior. We prove three main results about the transition system. First, each minimal DG realized skeleton is reachable, using the transition system, from any skeleton it embeds. Second, if no step is possible from a skeleton A, then A is DG realized. Finally, if a DG realized B is accessible from A, then B is minimal. Thus, the transition system provides a systematic way to construct the possible behaviors of the choreography, in the presence of compromised principals

Mononuclear Cell Clusters Observed in Pars Intermedius of Human Hypophysis

We observed cell clusters morphologically resembling lymphocytes in the pars intermedius of human hypophyses, and investigated their immunohistochemical properties. These morphologically lymphocyte-like cells were not immunostained by any of the antibodies to hormones known to be present in the adenohypophysis or antidody to S-100 protein. However, immunostaining using antibodies to T cell membrane and B cell membrane showed that the cells were mainly stained by anti-B cell membrane antibodies. To investigate the stage of maturity of these B cell membrane-positive cells, we performed immunostaining using antibodies to IgG, 1gM and IgA, and obtained negative results for all three. However, the present study did not answer the questions of why these cells are found only in the pars intermedius, why they are mainly B cells, and what functions they possess. Although there is so far no evidence suggesting a relationship between this cell cluster and functions of the pars intermedius in the hypophysis, the pars intermedius in human is considered more degenerate compared to amphibians, birds and rodents, and is likely to possess some yet undiscovered functions

Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus

Introduction: Two studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy. Materials and Methods: In the trial involving add‐on to sulfonylureas (study 03‐1), patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for a 24‐week double‐blind period, followed by a 28‐week open‐label period. In the open‐label trial involving add‐on to other OADs; that is, biguanides, dipeptidyl peptidase‐4 inhibitors, thiazolidinediones, glinides and α‐glucosidase inhibitors (study 03‐2), patients received luseogliflozin for 52 weeks. Results: In study 03‐1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24‐week double‐blind period compared with the placebo (–0.88%, P < 0.001), and glycated hemoglobin reduction from baseline at week 52 was –0.63%. In study 03‐2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (–0.52 to –0.68%, P < 0.001 for all OADs). Bodyweight reduction was observed in all add‐on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double‐blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable. Conclusions: Add‐on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI‐111507; add on to other OADs: JapicCTI‐111508)

Notable underlying mechanism for pancreatic β-cell dysfunction and atherosclerosis: Pleiotropic roles of incretin and insulin signaling

Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run. In the diabetic state, expression levels of insulin gene transcription factors and incretin receptors are downregulated, which we think is closely associated with β-cell failure. These data also suggest that it would be better to use incretin-based drugs at an early stage of diabetes when incretin receptor expression is preserved. Indeed, it was shown that incretin-based drugs exerted more protective effects on β-cells at an early stage. Furthermore, it was shown recently that endothelial cell dysfunction was also associated with pancreatic β-cell dysfunction. After ablation of insulin signaling in endothelial cells, the β-cell function and mass were substantially reduced, which was also accompanied by reduced expression of insulin gene transcription factors and incretin receptors in β-cells. On the other hand, it has been drawing much attention that incretin plays a protective role against the development of atherosclerosis. Many basic and clinical data have underscored the importance of incretin in arteries. Furthermore, it was shown recently that incretin receptor expression was downregulated in arteries under diabetic conditions, which likely diminishes the protective effects of incretin against atherosclerosis. Furthermore, a series of large-scale clinical trials (SPAED-A, SPIKE, LEADER, SUSTAIN-6, REWIND, PIONEER trials) have shown that various incretin-related drugs have beneficial effects against atherosclerosis and subsequent cardiovascular events. These data strengthen the hypothesis that incretin plays an important role in the arteries of humans, as well as rodents.Kaneto, H.; Obata, A.; Kimura, T.; Shimoda, M.; Sanada, J.; Fushimi, Y.; Katakami, N.; Matsuoka, T.; Kaku, K. Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling. Int. J. Mol. Sci. 2020, 21, 9444

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.</p

Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients