Classification tasks using input driven nonlinear magnetization dynamics in spin Hall oscillator.

The inherent nonlinear magnetization dynamics in spintronic devices make them suitable candidates for neuromorphic hardware. Among spintronic devices, spin torque oscillators such as spin transfer torque oscillators and spin Hall oscillators have shown the capability to perform recognition tasks. In this paper, with the help of micromagnetic simulations, we model and demonstrate that the magnetization dynamics of a single spin Hall oscillator can be nonlinearly transformed by harnessing input pulse streams and can be utilized for classification tasks. The spin Hall oscillator utilizes the microwave spectral characteristics of its magnetization dynamics for processing a binary data input. The spectral change due to the nonlinear magnetization dynamics assists in real-time feature extraction and classification of 4-binary digit input patterns. The performance was tested for the classification of the standard MNIST handwritten digit data set and achieved an accuracy of 83.1% in a simple linear regression model. Our results suggest that modulating time-driven input data can generate diverse magnetization dynamics in the spin Hall oscillator that can be suitable for temporal or sequential information processing.

Efficacy and safety of equine anti-thymocyte immunoglobulin (eATG) in three Japanese patients with moderate to very severe aplastic anemia: a case series.

Aplastic anemia results from lymphocyte-mediated destruction of hematopoietic stem cells. Immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is the standard front-line treatment for patients with severe aplastic anemia who are not suitable candidates for stem cell transplants. PF-06462700 is a potent equine ATG that targets T-lymphocytes and has been approved as a treatment for aplastic anemia outside of Japan for over 30 years. Due to the high medical need for PF-06462700, the Ministry of Health, Labor and Welfare requested its development for Japanese patients with aplastic anemia. In this case series, the efficacy and safety of PF-06462700, administered intravenously at 40 mg/kg/day for 4 days, were assessed over a 24-week period. This was as an open-label, single-arm, multicenter clinical study designed to enroll a minimum of three Japanese participants with aplastic anemia. Two participants met the primary outcome of hematologic response at week 12 and improvements in disease severity were observed. No deaths or serious adverse events were reported. The efficacy results from this case series suggest that administration of PF-06462700 is generally well-tolerated and produces a hematologic response in Japanese patients with aplastic anemia, which should be further evaluated in real-world studies.ClinicalTrials.gov identifier: NCT04350606.

Ruthenium-Catalyzed Intramolecular Double Hydrofunctionalization of Alkynes. Synthesis of Spirocyclic Hemiaminal Ethers and Their Lewis Acid-Mediated Cleavage/Nucleophilic Addition.

[RuCl2(p-cymene)]2/AgNO3-catalyzed intramolecular double hydrofunctionalization of internal alkynes having nitrogen and oxygen nucleophilic groups at appropriate positions provided a series of spirocyclic hemiaminal ether derivatives in good to excellent yields. The product spiro-hemiaminal ethers underwent Lewis acid-mediated chemoselective cleavage, and in situ-generated iminium/oxocarbenium ions could be trapped with nucleophiles to afford a range of nitrogen and oxygen heterocycles.

Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo-controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease.

INTRODUCTION: Symptomatic anti-Alzheimer's disease (AD) drugs have been commonly used for the treatment of AD. Knowing the natural courses of patients with AD on placebo is highly relevant for clinicians to understand their efficacy and for investigators to design clinical studies. METHODS: The data on rating scales for dementia such as Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Severe Impairment Battery were extracted from eight previous Japanese Phase II and III studies. Natural courses of Japanese AD patients in placebo groups were evaluated and statistically analyzed in a pooled and retrospective fashion. RESULTS: Decreases in ADAS-cog and Severe Impairment Battery was larger at week 22 or 24 than at week 12. Scores of ADAS-cog appeared to deteriorate faster in moderate AD than in mild AD. DISCUSSION: The present data will provide clinicians following up patients with AD with helpful information on how to manage AD patients and investigators with instruction for clinical study design.

Allele frequencies and forensic genetic parameters of 10 supplementary and two CODIS loci in a Japanese population genotyped using an Investigator HDplex Kit.

A total of 344 unrelated Japanese adults were genotyped to determine allele frequencies and evaluate forensic parameters for 10 autosomal supplementary non-CODIS loci and 2 autosomal CODIS loci using an Investigator® HDplex Kit for complex relationship testing.

Increased expression of CysLT2 receptors in the lung of asthmatic mice and role in allergic responses.

Compared with CysLT1 receptors, the functional role of CysLT2 receptors in asthma has not been clarified. The purpose of this study was to determine 1) whether CysLT2 receptors are expressed in the lung of mice and if expression increases in asthmatic mice, and 2) whether CysLT2 receptors are involved in allergic leukocyte infiltration into the lung and in the development of airway remodeling in asthmatic mice. BALB/c mice were sensitized with ovalbumin (OVA) + Al(OH)3, and intratracheally challenged with OVA 4 times. Lung tissue was isolated before and after the 4th OVA challenge for detection of CysLT2 receptors by immunohistochemistry and flow cytometry. The effect of a CysLT2 receptor antagonist BayCysLT2RA on multiple antigen challenge-induced leukocyte infiltration into the lung and the development of airway remodeling was evaluated. Even in non-challenged mice, CysLT2 receptors were expressed in bronchial smooth muscle. After multiple challenges, expression was also observed in leukocytes infiltrating into alveolar spaces. CysLT2R+ leukocytes included alveolar macrophages, conventional dendritic cells, and eosinophils. BayCysLT2RA significantly inhibited multiple antigen challenge-induced increases in eosinophils and mononuclear cells in the lung. The development of airway remodeling was tended to be suppressed by CysLT2 receptor antagonist. In conclusion, CysLT2 receptors were constitutively expressed in the lung, and expression was strengthened in asthmatic mice. Activation of CysLT2 receptors was functionally involved in allergic leukocyte infiltration into the lung. The CysLT2 receptor can be a molecular target for the development of new pharmacotherapies for asthma.

Regulation of allergic airway inflammation by adoptive transfer of CD4+ T cells preferentially producing IL-10.

Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4+ T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-ß for 7 days. After the 7-day culture, the CD4+ T cells were purified using a murine CD4 magnetic beads system. When the induced CD4+ T cells were stimulated by OVA in the presence of antigen-presenting cells, IL-10 was preferentially produced in vitro. When CD4+ T cells were adoptively transferred to OVA-sensitized mice followed by intratracheal OVA challenges, IL-10 was preferentially produced in the serum and bronchoalveolar lavage fluid in vivo. IL-10 production coincided with the inhibition of eosinophilic airway inflammation and epithelial mucus plugging. Most of the IL-10-producing CD4+ T cells were negative for Foxp3 and GATA-3, transcription factors of naturally occurring regulatory T cells and Th2 cells, respectively, but double positive for LAG-3 and CD49b, surface markers of inducible regulatory T cells, Tr1 cells. Collectively, most of the induced IL-10-producing CD4+ T cells could be Tr1 cells, which respond to the antigen to produce IL-10, and effectively suppressed allergic airway inflammation. The induced Tr1 cells may be useful for antigen-specific cellular immunotherapy for atopic diseases.

Identification of a common single nucleotide polymorphism at the primer binding site of D2S1360 that causes heterozygote peak imbalance when using the Investigator HDplex Kit.

Phenomena known as null alleles and peak imbalance can occur because of mutations in the primer binding sites used for DNA typing. In these cases, an accurate statistical evaluation of DNA typing is difficult. The estimated likelihood ratio is incorrectly calculated because of the null allele and allele dropout caused by mutation-induced peak imbalance. Although a number of studies have attempted to uncover examples of these phenomena, few reports are available on the human identification kit manufactured by Qiagen. In this study, 196 Japanese individuals who were heterozygous at D2S1360 were genotyped using an Investigator HDplex Kit with optimal amounts of DNA. A peak imbalance was frequently observed at the D2S1360 locus. We performed a sequencing analysis of the area surrounding the D2S1360 repeat motif to identify the cause for peak imbalance. A point mutation (G>A transition) 136 nucleotides upstream from the D2S1360 repeat motif was discovered in a number of samples. The allele frequency of the mutation was 0.0566 in the Japanese population. Therefore, human identification or kinship testing using the Investigator HDplex Kit requires caution because of the higher frequency of single nucleotide polymorphisms at the primer binding site of D2S1360 locus in the Japanese population.

A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease.

AIM: To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm(2) and titrated to 10 cm(2) after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm(2) and titrated by 2.5 cm(2) every 4 weeks to 10 cm(2)). METHODS: A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. RESULTS: Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was -3.6% (95% confidence interval: -17.0, 9.6), falling within the prespecified acceptance range. CONCLUSION: The tolerability of two different titration schemes was similar in Japanese patients with AD.

Effects of siRNAs targeting the spacer sequence of plant RNAi vectors on the specificity and efficiency of RNAi.

Small interfering RNAs (siRNAs) generated from the spacer region of hairpin RNAs were not detected in the RNA interference (RNAi) plants targeting the fatty acid desaturase gene. The expression of the desaturase gene was stably suppressed even when siRNAs targeting the spacer sequences were introduced into this plant.