Efficacy of tiotropium and indacaterol monotherapy and their combination on dynamic lung hyperinflation in COPD: a random open-label crossover study

Background and objective: The difference in efficacy of long-acting muscarinic antagonists (LAMAs) and long-acting beta(2)-agonists (LABAs) for dynamic lung hyperinflation (DLH) in COPD is unclear. The purpose of this study was to elucidate the difference in efficacy of LAMA and LABA alone and the combination thereof for DLH. Subjects and methods: Thirty stable patients were enrolled and randomly divided into two groups following baseline measurements. One group was treated with 5 mu g tiotropium (Respimat inhaler) for 4 weeks following a 4-week treatment with 150 mu g indacaterol, while the other group was treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium. For both groups, these treatments were followed by a combination of the two drugs for 4 weeks. Pulmonary function tests, including DLH evaluated by metronome-paced incremental hyperventilation and exercise tolerance evaluated by the shuttle-walk test, were performed at the end of each treatment period. Results: In total, 23 patients completed this study. Both tiotropium and indacaterol alone significantly increased forced expiratory volume in 1 second, exercise tolerance, and improved health status. Tiotropium significantly improved DLH, but indacaterol did not. The combination therapy resulted in further improvements in lung function and exercise tolerance, but not in DLH. Conclusion: The efficacy of tiotropium in inhibiting DLH following metronome-paced incremental hyperventilation may be superior to that of 150 mu g indacaterol, although the effects on airflow obstruction were the same, and the combination therapy showed further improvement in airflow obstruction, but not in DLH.ArticleINTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE.12:3195-3201(2017)journal articl

Magnetic properties of terminal iodinated nitroxide radical liquid crystals

We designed and synthesized terminal iodinated nitroxide radical liquid crystalline compounds (NR-LCs) with octyloxy side chain (±)-8-I and dodecyloxy side chain (±)-12-I to understand the substitution effects of an iodine atom on the phase transition behavior and on the magnetic properties in crystalline (Cr), liquid crystalline (LC) and isotropic (Iso) phases. These NR-LCs show monotropic nematic phases because the iodine atom is too short and apolar as a terminal group to stabilize LC phases. Furthermore, the SQUID magnetometry and electron paramagnetic resonance (EPR) spectroscopy indicate that the magnetic properties in the Cr phase depend on the length of the alkoxy side chain; antiferromagnetic interactions occur in (±)-8-I, whereas ferromagnetic interactions occur in (±)-12-I, and the paramagnetic susceptibility of (±)-8-I slightly decreases (J¯0) at each of the Cr-to-Iso phase transitions. These results suggest that the most frequent type of the magnetic interactions in LC and Iso phases is similar to those in the Cr phases among the various types of intermolecular magnetic interactions induced by the inhomogeneous intermolecular contacts.Akita T., Yamazaki T., Uchida Y., et al. Magnetic properties of terminal iodinated nitroxide radical liquid crystals. Polyhedron 136, 79 (2017); https://doi.org/10.1016/j.poly.2017.02.030

Large negative magneto-LC effects induced by racemic dimerization of liquid crystalline nitroxide radicals with a terminal cyano group

This article reports the synthesis and mesomorphism of new nitroxide radical compounds with a terminal cyano group and discusses the magneto-LC effects in the new compounds; one of the new compounds shows the largest decrease of paramagnetic susceptibility at the crystalline-to-liquid crystalline (LC) phase transition (negative magneto-LC effects) in the all-organic LC radicals reported thus far. The origins of the phenomenon are rationalized on the basis of the racemic magnetic dipolar interaction model using electron paramagnetic resonance (EPR) spectroscopy; the temperature dependences of the Lorentzian and Gaussian components of the line widths obtained by fitting EPR spectra with Voigt function provide important insights.Akita T., Kiyohara D., Yamazaki T., et al. Large negative magneto-LC effects induced by racemic dimerization of liquid crystalline nitroxide radicals with a terminal cyano group. Journal of Materials Chemistry C 5, 12457 (2017); https://doi.org/10.1039/c7tc04699e

Fairness Scheduling in Dense User-Centric Cell-Free Massive MIMO Networks

We consider a user-centric scalable cell-free massive MIMO network with a total of $LM$ distributed remote radio unit antennas serving $K$ user equipments (UEs). Many works in the current literature assume $LM\gg K$, enabling high UE data rates but also leading to a system not operating at its maximum performance in terms of sum throughput. We provide a new perspective on cell-free massive MIMO networks, investigating rate allocation and the UE density regime in which the network makes use of its full capability. The UE density $K$ approximately equal to $\frac{LM}{2}$ is the range in which the system reaches the largest sum throughput. In addition, there is a significant fraction of UEs with relatively low throughput, when serving $K>\frac{LM}{2}$ UEs simultaneously. We propose to reduce the number of active UEs per time slot, such that the system does not operate at ``full load'', and impose throughput fairness among all users via a scheduler designed to maximize a suitably defined concave componentwise non-decreasing network utility function. Our numerical simulations show that we can tune the system such that a desired distribution of the UE throughput, depending on the utility function, is achieved

Overloaded Pilot Assignment with Pilot Decontamination for Cell-Free Systems

The pilot contamination in cell-free massive multiple-input-multiple-output (CF-mMIMO) must be addressed for accommodating a large number of users. In previous works, we have investigated a decontamination method called subspace projection (SP). The SP separates interference from co-pilot users by using the orthogonality of the principal components of the users' channel subspaces. Non-overloaded pilot assignment (PA), where each radio unit (RU) does not assign the same pilot to different users, limits the spectral efficiency (SE) of the system, since SP channel estimation is able to deal with co-pilot users that have nearly orthogonal subspaces. Motivated by this limitation, this paper introduces overloaded PA methods adjusted for the decontamination in order to improve the sum SE of CF systems. Numerical simulations show that the overloaded PA methods give higher SE than that of non-overloaded PA at a high user density scenario.Comment: 7 pages, 2 figures, this paper was submitted to IEEE WCNC 202

Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.

We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis

High accumulation of plasminogen and tissue plasminogen activator at the flow surface of mural fibrin in the human arterial system

AbstractPurpose: We assessed the fibrinolytic activity of the organized mural thrombus lining of aneurysms and prosthetic grafts. Methods: Between May 1995 and April 1998, the full-thickness mural thrombi of aneurysms and the pseudointima lining of vascular grafts were obtained from 12 patients, ranging from 55 to 78 years in age, who underwent elective surgery. These included five aortic arch aneurysms, four abdominal aortic aneurysms, and three patent synthetic vascular grafts. The specimens were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot and immunohistochemistry for human plasmin/plasminogen, tissue plasminogen activator (tPA), and fibrin degradation product (D-dimer). Results: In the SDS-PAGE/immunoblot, 25- and 27-kd bands appeared specifically in experimental fibrin plates after limited digestion by plasmin and were also recognized in the mural thrombi. The presence of bands at 25 and 27 kd, which were most prominent in sections near the flow surface layer, was consistent with the hypothesis that the mural fibrin was digested by the endogenous plasmin. Apparent immunoreactivity was found at the flow surface of the masses at a thickness of 10 to 400 μm, suggesting the presence of a plasminogen and tPA-rich layer, with D-dimer as a consequential product of fibrinolysis. Conclusion: The hypothesis that fibrin surfaces in the arterial system acquire fibrinolytic activity because of digestion by circulating endogenous plasmin was confirmed; this may contribute to the antithrombogenicity of these flow surfaces. (J Vasc Surg 2000;32:374-82.

Maternal GABAergic and GnRH/corazonin pathway modulates egg diapause phenotype of the silkworm Bombyx mori

Diapause represents a major developmental switch in insects and is a seasonal adaptation that evolved as a specific subtype of dormancy in most insect species to ensure survival under unfavorable environmental conditions and synchronize populations. However, the hierarchical relationship of the molecular mechanisms involved in the perception of environmental signals to integration in morphological, physiological, behavioral, and reproductive responses remains unclear. In the bivoltine strain of the silkworm Bombyx mori, embryonic diapause is induced transgenerationally as a maternal effect. Progeny diapause is determined by the environmental temperature during embryonic development of the mother. Here, we show that the hierarchical pathway consists of a gamma-aminobutyric acid (GABA)ergic and corazonin signaling system modulating progeny diapause induction via diapause hormone release, which may be finely tuned by the temperature-dependent expression of plasma membrane GABA transporter. Furthermore, this signaling pathway possesses similar features to the gonadotropin-releasing hormone (GnRH) signaling system for seasonal reproductive plasticity in vertebrates.ArticleProceedings of The National Academy of Sciences of The United States of America 118(1) : e2020028118-(2021)journal articl

A complete dietary review of Japanese birds with special focus on molluscs

Birds often hold important positions in the food webs of ecosystems. As a result, interactions between birds and their prey have attracted attention not only in ecology, but also in fields like agriculture and conservation. Avian food resources are well researched in Japan, however there is no database critically reviewing molluscs as a food resource for birds. Here, we present a new database reviewing dietary information for all Japanese bird species. In addition to addressing general diet categories and specific food habits for each bird, we include detailed data on the molluscan prey observed for all species that consume them. The information within this database was collected through intense literary review to provide a complete look at bird species historically present around the country. We also include new information on snail species found in the upper digestive tract of harvested wild birds. This database is publicly available in the Zenodo repository. The information should aid research around the Japanese archipelago, especially projects involving birds or molluscs