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BackgroundBimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. In a phase 2b study, BKZ showed rapid and sustained efficacy and was well tolerated up to 156 weeks (wks) in patients (pts) with active ankylosing spondylitis (AS).1,2ObjectivesTo assess efficacy and safety of BKZ vs placebo (PBO) in pts with active AS up to Wk 24 in the ongoing pivotal phase 3 study, BE MOBILE 2.MethodsBE MOBILE 2 (NCT03928743) comprises a 16-wk double-blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 yrs, met modified New York criteria and had active AS (BASDAI ≥4, spinal pain ≥4) at BL. Pts were randomised 2:1, BKZ 160 mg Q4W:PBO. From Wk 16, all pts received BKZ 160 mg Q4W. Primary and secondary efficacy endpoints were assessed at Wk 16.ResultsOf 332 randomised pts (BKZ: 221; PBO: 111), 322 (97.0%) completed Wk 16 and 313 (94.3%) Wk 24. BL characteristics were comparable between groups: mean age 40.4 yrs, symptom duration 13.5 yrs; 72.3% pts male, 85.5% HLA-B27+, 16.3% TNFi-experienced. At Wk 16, the primary (ASAS40: 44.8% BKZ vs 22.5% PBO; pTable 1.Efficacy at Wks 16 and 24BLWk 16Wk 24PBO N=111BKZ 160 mg Q4W N=221PBO N=111BKZ 160 mg Q4W N=221p valuePBO→BKZ 160 mg Q4W N=111BKZ 160 mg Q4W N=221Ranked endpoints in hierarchical orderASAS40* [NRI] n (%)--25 (22.5)99 (44.8)63 (56.8)119 (53.8)ASAS40 in TNFi-naïve† [NRI] n (%)--22 (23.4)a84 (45.7)b56 (59.6)a100 (54.3)bASAS20† [NRI]n (%)--48 (43.2)146 (66.1)85 (76.6)159 (71.9)BASDAI CfB† [MI] mean (SE)6.5 (0.1)6.5 (0.1)–1.9 (0.2)–2.9 (0.1)–3.3 (0.2)–3.3 (0.1)ASAS PR† [NRI]n (%)--8 (7.2)53 (24.0)28 (25.2)56 (25.3)ASDAS-MI† [NRI] n (%)--6 (5.4)57 (25.8)43 (38.7)67 (30.3)ASAS 5/6† [NRI]n (%)--16 (14.4)94 (42.5)57 (51.4)107 (48.4)BASFI CfB† [MI] mean (SE)5.2 (0.2)5.3 (0.2)–1.1 (0.2)–2.2 (0.1)–2.2 (0.2)–2.4 (0.2)Nocturnal spinal pain CfB† [MI]mean (SE)6.8 (0.2)6.6 (0.1)–1.9 (0.2)–3.3 (0.2)–3.7 (0.3)–3.8 (0.2)ASQoL CfB† [MI] mean (SE)8.5 (0.4)9.0 (0.3)–3.2 (0.3)–4.9 (0.3)–4.9 (0.4)–5.4 (0.3)SF-36 PCS CfB† [MI] mean (SE)34.6 (0.8)34.4 (0.6)5.9 (0.8)9.3 (0.6)10.6 (0.8)10.8 (0.6)BASMI CfB† [MI] mean (SE)3.8 (0.2)3.9 (0.1)–0.2 (0.1)–0.5 (0.1)0.005–0.5 (0.1)–0.6 (0.1)Other endpointsnEnthesitis-free state†c [NRI]n (%)--22 (32.8)d68 (51.5)e-33 (49.3)d70 (53.0)eASAS40 in TNFi-experienced [NRI]n (%)--3 (17.6)f15 (40.5)g---ASDAS-CRP CfB [MI]mean (SE)3.7 (0.1)3.7 (0.1)–0.7 (0.1)–1.4 (0.1)-–1.7 (0.1)–1.6 (0.1)hs-CRP (mg/L) [MI] geometric mean (median)6.7 (6.3)6.5 (8.2)6.0 (6.3)2.4 (2.4)-1.9 (2.2)2.1 (2.3)MRI spine Berlin CfBh [OC] mean (SD)3.3 (4.9)i3.8 (5.3)j0.0 (1.4)k–2.3 (3.9)l---SPARCC MRI SIJ score CfBh [OC] mean (SD)5.8 (7.7)i7.4 (10.7)m1.1 (6.9)k–5.6 (9.9)l---Randomised set. *Primary endpoint; †Secondary endpoint; an=94; bn=184; cMASES=0 in pts with BL MASES >0; dn=67; en=132; fn=17; gn=37; hIn pts in MRI sub-study; in=45; jn=82; kn=43; ln=79; mn=83; nNominal p values not shown.Over 16 wks, 120/221 (54.3%) BKZ pts had ≥1 TEAE vs 48/111 (43.2%) PBO; three most frequent on BKZ were nasopharyngitis (BKZ: 7.7%; PBO: 3.6%), headache (4.1%; 4.5%) and oral candidiasis (4.1%; 0%). No systemic candidiasis was observed. Up to 16 wks, incidence of SAEs was low (1.8%; 0.9%); no MACE or deaths were reported; 2 (0.9%) IBD cases occurred in pts on BKZ.ConclusionDual inhibition of IL-17A and IL-17F with BKZ in pts with active AS resulted in rapid, clinically relevant improvements in efficacy outcomes vs PBO. No new safety signals were observed.1,2References[1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491.AcknowledgementsThis study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of InterestsDésirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Employee of: Imaging Rheumatology BV (Director), Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Merck, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Matt Brown Speakers bureau: Novartis, Consultant of: Pfizer, Clementia, Ipsen, Regeneron, Grey Wolf Therapeutics, Grant/research support from: UCB Pharma, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Filip van den Bosch Speakers bureau: AbbVie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Nigil Haroon Consultant of: AbbVie, Amgen, Janssen, Merck, Novartis and UCB Pharma, Huji Xu: None declared, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis, and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis, and Pfizer, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis, Pfizer, and UCB Pharma; paid to institution, Marga Oortgiesen Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, Atul Deodhar Speakers bureau: Janssen, Novartis, and Pfizer; consultant of AbbVie, Amgen, Aurinia, BMS, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB Pharma.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Rydberg atoms, with their enormous electronic orbitals, exhibit dipole–dipole interactions reaching the gigahertz range at a distance of a micrometre, making them a prominent contender for realizing ultrafast quantum operations. However, such strong interactions between two single atoms have so far never been harnessed due to the stringent requirements on the fluctuation of the atom positions and the necessary excitation strength. Here we introduce novel techniques to explore this regime. First, we trap and cool atoms to the motional quantum ground state of holographic optical tweezers, which allows control of the inter-atomic distance down to 1.5 μm with a quantum-limited precision of 30 nm. We then use ultrashort laser pulses to excite a pair of these nearby atoms to a Rydberg state simultaneously, far beyond the Rydberg blockade regime, and perform Ramsey interferometry with attosecond precision. This allows us to induce and track an ultrafast interaction-driven energy exchange completed on nanosecond timescales—two orders of magnitude faster than in any other Rydberg experiments in the tweezers platform so far. This ultrafast coherent dynamics gives rise to a conditional phase, which is the key resource for a quantum gate, opening the path for quantum simulation and computation operating at the speed limit set by dipole–dipole interactions with this ultrafast Rydberg platform.

The neutron lifetime has been measured by comparing the decay rate with the reaction rate of $^3$He nuclei of a pulsed neutron beam from the spallation neutron source at the Japan Proton Accelerator Research Complex (J-PARC). The decay rate and the reaction rate were determined by simultaneously detecting electrons from the neutron decay and protons from the $^3$He(n,p)$^3$H reaction using a gas chamber of which working gas contains diluted $^3$He. The measured neutron lifetime was $898\,\pm\,10\,_{\rm stat}\,^{+15}_{-18}\,_{\rm sys}\,$s., 28 pages, 20 figures, will be submitted to PTEP

A neutron lifetime measurement conducted at the Japan Proton Accelerator Research Complex (J-PARC) is counting the number of electrons from neutron decays with a time projection chamber (TPC). The $\gamma$ rays produced in the TPC cause irreducible background events. To achieve the precise measurement, the inner walls of the TPC consist of $^6$Li-enriched lithium-fluoride ($^6$LiF) tiles to suppress the amount of $\gamma$ rays. In order to estimate the amount of $\gamma$ rays from the $^{6}{\rm LiF}$ tile, prompt gamma ray analysis (PGA) measurements were performed using germanium detectors. We reconstructed the measured $\gamma$-ray energy spectrum using a Monte Carlo simulation with the stripping method. Comparing the measured spectrum with a simulated one, the number of $\gamma$ rays emitted from the$^{6}{\rm LiF}$ tile was $(2.3^{+0.7}_{-0.3}) \times 10^{-4}$ per incident neutron. This is $1.4^{+0.5}_{-0.2}$ times the value assumed for a mole fraction of the $^{6}{\rm LiF}$ tile. We concluded that the amount of $\gamma$ rays produced from the $^{6}{\rm LiF}$ tile is not more twice the originally assumed value., Comment: 14 pages, 11 figures, will be submitted to JINST

Background Carotid body tumors are rare, neurogenic tumors arising from the periadventitial chemoreceptive tissue of the carotid body. The purpose of this study is to ascertain the presentation and preoperative risk factors associated with surgical resection. Methods A single-center retrospective review of 25 carotid body tumor resections from 2002 to 2019. Demographics, periprocedural details, and postoperative outcomes were analyzed using Stata (Stata Corporation, College Station, TX). Results Among 25 patients, 64% were women, 84% were asymptomatic, and the mean age was 49 years (range 21–79). Forty-four percent of tumors were Shamblin III. Nine patients underwent preoperative embolization but did not correlate with decreased blood loss (299 cm3 vs 205 cm3, P = .35). The 30-day death, stroke, and cranial nerve injury rates were 0%, 8%, and 32%, respectively. Cranial nerve injuries included 20% vagus, 4% hypoglossal, 4% facial, and 4% glossopharyngeal, with permanent deficits in 4% (n = 1). Mean length of stay was 3.0 days (range 1–9 days). At a mean follow-up of 12 months (range 1–63 months), there has been no recurrence. Conclusion Although carotid body tumors are uncommon in the Midwest, complete surgical resection is curative of these typically hormonally inactive tumors. Preoperative embolization did not affect blood loss, and the incidence of death, stroke, and permanent cranial nerve injury rates remained very low.

Electroluminescence (EL) of MOS devices with rare-earth related oxide layer, which were fabricated with the mixtures of organic liquid sources of (Ce + Pr) and Gd spin-coated on the Si substrate and annealed, are reported. UV and visible white EL were observed. The spectral peaks of the EL correspond to radiative transitions of Pr3+, Ce3+, and Gd3+ ions. Effects of compounding ratios of (Ce + Pr) and Gd devices on EL characteristics are analyzed.

In a neutron lifetime measurement at the Japan Proton Accelerator Complex, the neutron lifetime is calculated from the neutron decay rate and the incident neutron flux. The flux is obtained by counting the protons emitted from the neutron absorption reaction of ${}^{3}{\rm He}$ gas, which is diluted in a mixture of working gas in a detector. Hence, it is crucial to determine the amount of ${}^{3}{\rm He}$ in the mixture. In order to improve the accuracy of the number density of the ${}^{3}{\rm He}$ nuclei, we have suggested using the ${}^{14}{\rm N}({\rm n},{\rm p}){}^{14}{\rm C}$ reaction as a reference because this reaction involves similar kinetic energy to the $^3$He(n,p)$^3$H reaction and a smaller reaction cross section to introduce reasonable large partial pressure. The uncertainty of the recommended value of the cross section, however, is not satisfied with our requirement. In this paper we report the most accurate experimental value of the cross section of the $^{14}$N(n,p)$^{14}$C reaction at a neutron velocity of 2200 m s$^{-1}$, measured relative to the $^3$He(n,p)$^3$H reaction. The result was 1.868 $\pm$ 0.003 (stat.) $\pm$ 0.006 (sys.) b. Additionally, the cross section of the $^{17}$O(n,$\alpha$)$^{14}$C reaction at the neutron velocity is also redetermined as 249 $\pm$ 6 mb.

The decay lifetime of free neutrons (∼880 s) is an important parameter of the weak interaction and for Big Bang Nucleosynthesis. However, results of measurements currently show discrepancies depending on the method used. As most experiments nowadays employ ultra cold neutrons, we have developed a new cold-beam experiment which we perform at the Japan Proton Accelerator Research Complex. As a special feature, a polarized neutron beam is bunched by a spin flip chopper. A time projection chamber operated with He and CO2gas, including a well-controlled amount of3He, is used for detection of the beta-decays and simultaneous determination of the beam intensity. Using the data between 2014 and 2016, we evaluated our first, preliminary result of the neutron lifetime as 896 ± 10(stat.)−10+14(sys.) s. We plan several upgrades to achieve our precision goal of 1 s.

We have carried out a powder X-ray diffraction investigation on antiferromagnetic Kondo semiconductorsCeRu2Al10 and CeOs2Al10 at low temperatures and under high pressures as well as the structural investigationon single crystal of these compounds. The results of powder X-ray studies of CeRu2Al10 and CeOs2Al10 indicatethat these compounds do not have structural transition at its antiferromagnetic ordering temperature. The resultsof single crystal structural refinement indicate that the b-axis of this crystal structure is insensitive not only topressure but also to temperature and that the effect of cooling to Ce–Ce distance for CeRu2Al10 is the same asthat for CeOs2Al10.

We attempted to produce nanocrystalline soft magnetic powders with a high saturation magnetic flux density (Bs) and containing large-sized particles using a modified water atomization system named “HPWA/YK.” Almost fully amorphous powders containing particles with median diameters of 15 μm and composed of Fe83.3Si4B8P4Cu0.7 were obtained. These results indicate that HPWA/YK reached a higher quenching rate than conventional water atomization systems. The powder circularity reached a value of 0.78 by changing the ratio of the gas to water pressure; moreover, after annealing at 713 K, the powders presented good magnetic properties (Bs = 1.66 T; Hc = 155 A/m).

A new time projection chamber (TPC) was developed for neutron lifetime measurement using a pulsed cold neutron spallation source at the Japan Proton Accelerator Research Complex (J-PARC). Managing considerable background events from natural sources and the beam radioactivity is a challenging aspect of this measurement. To overcome this problem, the developed TPC has unprecedented features such as the use of polyether-ether-ketone plates in the support structure and internal surfaces covered with $^6$Li-enriched tiles to absorb outlier neutrons. In this paper, the design and performance of the new TPC are reported in detail., 33 pages, 10 figures

The excellent jet energy resolution required for precise physics measurements at ILC is achievable using a Particle Flow Method and highly granular calorimeters. As it was shown by CALICE international R&D collaboration, the silicon-tungsten imaging electromagnetic calorimeter provides the best granularity, stability and resolution of jet energy measurement. After proving the calorimeter concept with physical prototypes in 2005–2011, an emphasis is now moved to building a technological prototype satisfying challenging requirements. All chosen technologies should be reliable and scalable for a mass production of a future detector. We report on the current status of R&D, in particular, on beam and charge injection tests of the technological prototype and on the tests of ECAL mechanical structure. We also report on our plans to build a realistic prototype detector and test it together with an existing carbon fiber-tungsten mechanical structure. A similar silicon-tungsten calorimeter technology has been recently proposed for the Phase 2 upgrade of CMS end-cap calorimeter and future high energy circular collider projects.

"Neutron Optics and Physics (NOP/ BL05)" at MLF in J-PARC is a beamline for studies of fundamental physics. The beamline is divided into three branches so that different experiments can be performed in parallel. These beam branches are being used to develop a variety of new projects. We are developing an experimental project to measure the neutron lifetime with total uncertainty of 1 s (0.1%). The neutron lifetime is an important parameter in elementary particle and astrophysics. Thus far, the neutron lifetime has been measured by several groups; however, different values are obtained from different measurement methods. This experiment is using a method with different sources of systematic uncertainty than measurements conducted to date. We are also developing a source of pulsed ultra-cold neutrons (UCNs) produced from a Doppler shifter are available at the unpolarized beam branch. We are developing a time focusing device for UCNs, a so called "rebuncher", which can increase UCN density from a pulsed UCN source. At the low divergence beam branch, an experiment to search an unknown intermediate force with nanometer range is performed by measuring the angular dependence of neutron scattering by noble gases. Finally the beamline is also used for the research and development of optical elements and detectors. For example, a position sensitive neutron detector that uses emulsion to achieve sub-micrometer resolution is currently under development. We have succeeded in detecting cold and ultra-cold neutrons using the emulsion detector., 9 pages, 5 figures, Proceedings of International Conference on Neutron Optics (NOP2017)

Turbodrill is a type of hydraulic axial turbomachine that rotates a bit by the action of the drilling fluid on turbine blades, which converts the hydraulic power provided by the high pressure from drilling fluid into mechanical power through turbine stages. The evaluation of hydraulic turbine performance characteristics are important to define feasible rotational speed and mass flow to attend the bit torque requirements during drilling through the post-salt and salt layers. As a result, optimum operational parameters are proposed for gaining the required rotational speed and torque for post-salt environments. The turbine motor presented in this study was established by design methods based on classical aeronautical turbomachinery blade profile to supply 30k Newton-meters (Nm) of torque requested by a polycrystalline diamond compact (PDC) bit to power the complex heterogeneous layer of rock. The performance evaluation of this innovative hydraulic turbine with 200 stages was carried out using computational fluid dynamics (CFD). The simulation considers two different drilling fluid types, sea water and brine. Besides, different flow rates were considered to investigate how velocity vectors, pressure profile, output power and other performance parameters are affected. Due the large amount of data, the first and second stages of the turbine have been used to predict the performance characteristics. This assumption gives interesting results and avoids too heavy computational costs. A commercial CFD solver (ANSYS CFX 15.0®) was used to calculate the governing equations based on Reynolds-Averaged Navier-Stokes (RANS equations) with the addition of turbulence model. The two-equation Shear-Stress Transport (SST) turbulence model was used to account the effects of flow eddy viscosity.

The neutron lifetime is one of the basic parameters in the weak interaction, and is used for predicting the light element abundance in the early universe. Our group developed a new setup to measure the lifetime with the goal precision of 0.1% at the polarized beam branch BL05 of MLF, J-PARC. The commissioning data was acquired in 2014 and 2015, and the first set of data to evaluate the lifetime in 2016, which is expected to yield a statistical uncertainty of O(1)%. This paper presents the current analysis results and the future plans to achieve our goal precision., Comment: 8 pages, 7 figures, 2 tables, the 26th International Nuclear Physics Conference

Presenilin is a catalytic subunit of γ-secretase, which hydrolyzes several transmembrane proteins within the lipid bilayer, together with binding cofactors such as nicastrin, Aph-1, and Pen-2. However, the structural basis as well as molecular mechanism of this unusual proteolytic process remains unknown. We have analyzed the structure and function relationships of presenilin using the substituted-cysteine accessibility method (SCAM), which enables identification of the hydrophilic environment by the accessibility of sulfhydryl reagents to cysteine residues introduced at a desired position. In combination with small molecule inhibitors/modulators and cross-linking experiments, we were able to identify certain residues and regions of presenilin that contribute to its intramembrane-cleaving activity. In addition, we revealed the structural dynamics of the transmembrane domains of presenilin during the formation of the complex and its proteolytic process. The SCAM provides new insights into the relationship between the structure and activity of presenilin, and is useful for probing the protein dynamics of the membrane-embedded enzymes.

a b s t r a c t Objective: Periodontitis involves periodontal tissue destruction and is associated with chronic inflammation and ageing. Periodontitis has recently been recognised as a risk factor for Alzheimer’s disease (AD). We showed upregulation of molecules in the AD pathway including amyloid beta (A4) precursor protein (APP), a key gene in AD, interleukin-1 beta (IL-1b), and complement component 1 (q subcomponent, A chain) (C1QA) in periodontitis compared to healthy tissues. Here, we quantitatively analysed the expression levels of APP, IL-1b, and C1QA and determined the localisation of APP in gingival tissues. Design: Fourteen chronic periodontitis patients and 14 healthy participants were enrolled. Six samples of total RNA from two distinct sites of healthy and periodontitis-affected gingival tissues from three randomly selected patients were used for microarray analyses, and significant biological pathways in periodontitis were identified. Differential gene expression of APP, IL-1b, and C1QA, which belong to the AD pathway, were analysed with quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) using samples from these 14 chronic periodontitis patients and 14 healthy controls. APP localisation was analysed with immunohistochemistry. Results: APP, IL-1b, and C1QA mRNA levels were significantly upregulated in periodontitisaffected gingival tissues. APP was mainly localised in macrophages in gingival connective tissues underneath the epithelial layers. Conclusions: An association between AD and periodontitis was detected with microarray and computer-aided data mining analyses. qRT-PCR identified differential gene expression in periodontitis-affected gingival tissue that may be related to AD pathogenesis. Elevated APP, IL1b, and C1QA transcripts and APP-expressing macrophages in periodontitis-affected gingival tissues were observed, suggesting a relationship between periodontitis and AD pathogenesis.

Nanocrystalline soft magnetic ribbons with high saturation magnetic flux density Bs and low coercivity Hc are attracted for high power devices. Ribbon-shaped samples with compositions of Fe83.3B16-xPxCu0.7 (x=4-10) were prepared. The activation energy of the crystallization reaction was estimated by Kissinger’s plot. The value of the Hc after the crystallization reaction was measured. As a result, it was found that as the amount of phosphorus increases, the activation energy of the crystallization reaction increases and the Hc decreases, but ΔTx become smaller. Finally, it turned out that silicon substitution is effective for stabilizing the Hc after heat treatment.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Background Continuous femoral nerve block (cFNB) induces quadriceps muscle weakness, but patient-controlled femoral nerve block (PCFNB) can provide analgesia with lower consumption of local anesthetics compared to cFNB. We hypothesized that cFNB followed by PCFNB leads to accelerated recovery of quadriceps weakness after total knee arthroplasty compared to cFNB alone. Secondary outcomes were local anesthetic consumption, pain, and mobilization. Methods Fifty-six subjects received post-operative cFNB for 24 h and then randomized to receive either cFNB (basal infusion of 6 ml/h using a dummy bolus button; n = 27) or PCFNB (bolus infusion of 3 ml with a lockout time of 30 min and no basal infusion; n = 29) using 0.08% levobupivacaine for the subsequent 24 h in a double-blind manner (registration: UMIN000010105). Quadriceps strength was assessed using a hand-held dynamometer. The percentage change from baseline was compared between groups. Results Quadriceps strength at 48 h was 47.3 ± 18.3% in the cFNB group and 49.7 ± 15.7% in the PCFNB group (95% confidence interval −7.0–11.9%, P = 0.61). Local anesthetic consumption during the post-operative period was significantly lower in the PCFNB group compared to the cFNB group (102 ± 10.8 ml vs.146 ± 4.6 ml; P < 0.001). No significant differences were found in any of the other outcomes, including pain scores at rest and during knee rehabilitation. Conclusion Continuous femoral nerve block followed by PCFNB does not improve quadriceps strength recovery time compared to cFNB alone after total knee arthroplasty, but similar analgesic effects were demonstrated with reduced levobupivacaine consumption.

Friction welding was carried out between TiNi alloy and austenitic stainless steel with and without a Ni interlayer. When TiNi alloy was welded to stainless steel without the Ni interlayer, a large amount of brittle Fe2Ti intermetallic compound was formed at the weld interface. The formation of this brittle compound led to degradation of the joint strength. The Ni interlayer changed the microstructures at the weld interface and improved the joint strength. A fracture occurred at the interface between Ni and TiNi. The interface between Ni and TiNi was free from Fe2Ti and consisted of mainly TiNi3 and TiNi. After TiNi3 was formed as the reaction layer, a eutectic reaction occurred between the TiNi3 and TiNi base alloy. A reaction layer with a eutectic structure tends to form at the periphery, where the temperature would be higher than that of the central region.

The behavioral effects of the kappa-opioid receptor agonist U69593 were examined in lactating rats. On day 5 of lactation, animals were treated with 0.1 mg/kg of U69593 to determine whether it influences general activity and maternal latencies toward pups. Because little attention has been given to the possibility that pre-mating treatment with morphine may modulate the response to kappa-opioid receptor stimulation, another group of animals was submitted to the same acute challenge after abrupt withdrawal from repeated treatment with morphine sulfate during the pre-mating period (5 mg/kg on alternate days for a total of five doses). Acute kappa-opioid stimulation reduced total locomotion, rearing frequency, and time spent self-grooming and increased immobility duration. These kappa agonist effects were not observed in animals pretreated with morphine. Similarly, latencies to retrieve pups were longer only in animals pretreated with saline and challenged acutely with U69593. None of these effects were observed in morphine sulfate-pretreated animals. The present results suggest that pre-mating repeated exposure to morphine produces a tolerance-like effect on behavioral responses to low-dose kappa-opioid receptor stimulation in active reproductive females.

Reduced-activation martensitic steel F82H was irradiated at alternating temperatures between 230 and 350 °C to the accumulated damage level of 1.5 dpa using an irradiation capsule with temperature control independent of reactor power. Tensile tests were conducted in order to investigate the effects of the irradiation temperature variations on mechanical properties of F82H. Electron microscope observations were performed for the irradiated F82H to evaluate microstructural evolution of the specimens following varying temperature irradiation. Yield stress of the F82H irradiated at 50% alternating temperature between 230 and 350 °C was relatively large compared with the other temperature variations in this study. Size and number densities of dislocation loops were observed to be affected by changing irradiation temperature. The distinctive hardening behavior could be interpreted by the difference in the size and density of the defect clusters in terms of the effect of varying temperature.

Toxoplasma gondii is a protozoan that infects 30% of humans as intermediate hosts. T Sexual reproduction can occur only within the intestinal tract of felines, however, infection in other mammals and birds is associated with asexual replication and interconversion between the tachyzoite and bradyzoite stages. Bradyzoites are slow growing forms found in tissue cysts in latent infection. Recently, our group described the biological behavior of the EGS strain that forms thick walled cysts spontaneously in tissue culture, constituting a useful tool for examining the developmental biology of T. gondii. To further improve the usefulness of this model, we constructed genetically modified EGS parasites that express fluorescent tags under the control of stage specific promoters. The promoter regions for SAG-1 (tachyzoite specific), BAG-1 and LDH-2 (bradyzoite specific) were amplified by PCR and plasmids were constructed with mCherry (redT) and sfGFP (greenB) sequences, respectively. Strains of parasites were selected using FACS to arrive at single fluorescent and dual fluorescent strains of EGS expressing tags in a stage specific manner. In cell cultures, vacuoles labeled by immunofluorescence assay using anti-CST-1 a marker for T. gondii cyst wall contained parasites that were positive for BAG1-GFP and negative for SAG1-mCherry. Tachyzoites and bradyzoites harvested from the mice expressed stage specific mCherry and GFP proteins, respectively. These new dual fluorescent transgenic EGS strains are a promising tool to elucidate the mechanisms of Toxoplasma gondii differentiation both in vitro and in vivo.

The purpose of this study was to clarify the relationship between the thickness of the roof of the glenoid fossa (RGF) and magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) disorders (TMDs).Eighty-seven patients with symptoms and indications of TMD in one or both TMJs were referred for MRI. Cone-beam CT (3DX) was used to measure the thickness of the RGF at its thinnest point. Linear measurements were made three times on the monitor by three separate investigators and the mean values obtained were used for the statistical analyses.The joints were categorised as normal (70 joints), anterior disc displacement with reduction (ADWR; 53 joints) or anterior disc displacement without reduction (ADWOR; 51 joints). The joint disorders were also categorised into the following subgroups: with osteoarthritis (OA) (21 joints), without OA (153 joints), with disc deformation (33 joints), without disc deformation (141 joints), with joint effusion (JE) (61 joints) and without JE (113 joints). The average minimum thickness of the RGF was 0.85 mm for normal joints, 0.90 mm with ADWR, 0.93 mm with ADWOR, 0.99 mm with OA, 0.87 mm without OA, 0.87 mm with disc deformation and 0.89 mm without disc deformation. There was no significant difference between these figures. There was a significant difference in the thickness of the RGF with (0.97 mm) and without (0.84 mm) JE.These results suggest that RGF thickness is influenced by JE, but is unaffected by disc position and configuration.

Effects of displacement damage and gas atoms on microstructures and mechanical properties of F82H steel were examined by some various different methods. The hardness of F82H was increased by triple beams, dual beams and single beam at 270 °C to 20 dpa and 360 °C to 50 dpa, and the increment of hardness by irradiation at 360 °C was larger than that at 270 °C. The increment of hardness due to triple, dual and single beams depended on the irradiation temperatures. The peak temperature of swelling induced by dual ion beams to 50 dpa was about 430 °C at temperatures from 360 to 600 °C and the value of swelling was about 0.6%. Strength of F82H-std steel tested at 600 and 700 °C by small punch (SP) was increased by about 84 appm helium implantation at 120 °C, and no degradation in ductility was observed. In a 0.18DCT fracture toughness test performed at 300 °C of ductile properties, the strength of F82H with helium production was rapidly decreased as compared to that with no helium production beyond a maximum strength in ductile temperature region. The cause is related to the occurrence of sub-boundary, such as lath boundaries and packed boundaries, cracking due to helium migration to sub-boundaries. From these results, the design window of safety zone of F82H steel for operation of nuclear environment systems may be modified.

A cellular-line production system consists of multiple flow shops which are individual sets composed of functionally different facilities. The cellular-line production system is carefully designed and controlled so as to group facilities that perform similar operations and balance the workload among facilities considering the planned product mix and its variations. Thus, a drastic reduction in production lead time is possible as long as all of the facilities composing cellular-lines in the system are reliable. The present paper deals with a design problem of the cellular-line production system which includes unreliable facilities. We assume that the times to failure and times to repair are exponentially distributed and that the latter is not lengthy, that is, that the times to repair are at most several times the cycle time, which is the input interval for the cellular-lines. A methodology for designing the system in a machine-failure environment is presented and the results of numerical experiments and simulation are shown to verify the usefulness of the proposed methodology. Finally, the practical significance of quantitative analysis and evaluation in the stochastic design problem is discussed.