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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract whose occurrence is attributed to various factors, including genetic factors, immune response, microbial changes, and oxidative stress. Microbial-targeted therapy has emerged as an alternative to immunosuppressive therapy for IBD. Methods The effects of an atypical commensal Escherichia coli strain harboring an additional catalase gene (compared to typical E. coli strain) on dextran sulfate sodium (DSS)-induced colitis were explored in mice. Results The atypical E. coli (atEc) significantly restored body weight, reduced disease activity score, and improved histological scores in mice with colitis. Hydrogen peroxide levels in colitis mice were noticeably decreased when the mice were administered atEc. The proinflammatory cytokine levels were decreased and regulatory T cell numbers were increased after the administration of atEc. The abundance of Firmicutes was significantly recovered, while that of Proteobacteria decreased in atEc -treated mice compared with that in vehicle-treated wild-type mice. To investigate the role of interleukin (IL)-17A in mediating the anti-inflammatory effects of the atEc, IL-17A‒knockout mice were orally administered atEc. Clinical and immune responses and microbial composition were significantly reduced in IL-17A‒knockout mice compared with those in wild-type mice. Conclusions atEc ameliorates colonic inflammation by controlling hydrogen peroxide levels, immune responses (including regulatory T cells and IL-17A), and microbial composition. atEc could be a novel candidate of probiotic for IBD treatment.

Soil-dwelling predatory mites are natural enemies of various soil pest insects and mites. Both Gaeolaelaps aculeifer (Canestrini) and Stratiolaelaps scimitus (Womersley) are commercialized natural enemies of thrips, but there is little information on the predation rate of these predatory mites on different thrips species. We compared their predation capacities on three thrips species, Frankliniella occidentalis, F. intonsa, and Thrips palmi, which are major pests of various horticultural plants. The predatory rate of G. aculeifer was higher than that of S. scimitus. Both predator species fed on more T. palmi thrips than F. occidentalis or F. intonsa thrips, which may be attributable to the smaller body size of T. palmi than the other thrips. Predation rates of female adults were 2.6–2.8 times higher than those of deutonymphs in both species. Predation rates were not separated according to the various developmental stages (i.e., second instar larva, pupa, or adult) of thrips; however, deutonymphs fed on fewer adults than larvae or pupae of F. occidentalis. Our results suggest that both G. aculeifer and S. scimitus are active predators that can prey during any of their developmental stages and on any species of thrips tested.

Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC.Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004-2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors.Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals.Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT.

Mechanochemical synthesis of the Ce3Al11 powder was performed through a reaction among CeCl3, AlCl3 and NaH powders. α-Ce3Al11 particles with an average size of 250 nm were obtained. The catalytic effect of the synthesized Ce3Al11 on the hydrogen sorption properties of NaAlH4 was investigated. The hydrogen absorption kinetics of NaAlH4 with Ce3Al11 was significantly enhanced and the hydrogen capacity was improved compared to those properties of NaAlH4 with CeCl3. This can be attributed to the fine distribution of the Ce3Al11 catalyst in NaAlH4 during ball milling. Although the volume of the NaAlH4 pellets generally tends to increase during the hydrogen sorption cycles, the volume expansion of the pellet of NaAlH4 with Ce3Al11 was relatively low with a small pore fraction compared to that of the pellet of NaAlH4 with conventional chloride catalysts such as CeCl3, TiCl3 and TiCl4. The use of a nonchloride catalyst appears to provide an effective approach for suppressing the volume expansion of NaAlH4 pellets during the hydrogen sorption cycles.

Class C G protein–coupled receptors (GPCRs) are obligatory dimers that are particularly important for neuronal responses to endogenous and environmental stimuli. Ligand recognition through large extracellular domains leads to the reorganization of transmembrane regions to activate G protein signaling. Although structures of individual domains are known, the complete architecture of a class C GPCR and the mechanism of interdomain coupling during receptor activation are unclear. By screening a mutagenesis library of the human class C sweet taste receptor subunit T1R2, we enhanced surface expression and identified a dibasic intracellular retention motif that modulates surface expression and co-trafficking with its heterodimeric partner T1R3. Using a highly expressed T1R2 variant, dimerization sites along the entire subunit within all the structural domains were identified by a comprehensive mutational scan for co-trafficking with T1R3 in human cells. The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2–T1R3 dimer in living cells, which predicts a twisted arrangement of domains around the central axis, and a continuous folded structure between transmembrane domain loops and the cysteine-rich domains. These insights have implications for how conformational changes between domains are coupled within class C GPCRs.

Summary In lithium-sulfur (Li-S) batteries, the insulating nature of sulfur and lithium sulfide (Li2S) results in large polarization and low sulfur utilization while the soluble polysulfides lead to internal shuttle upon cycling. Furthermore, the redox reaction via the dissolution-precipitation route destroys the electrode architecture by passivating the active interface responsible for the redox reaction, and thus the performance deteriorates with cycling. Here, we employ the redox chemistry of quinone to realize efficient, fast, and stable operation of Li-S batteries using Li2S microparticles. By adding a quinone derivative with tailored properties (e.g., oxidation potential, solubility, and electrochemical stability) to an electrolyte as a redox mediator (RM), initial charging of Li2S electrodes occurs below 2.5 V at 0.5C, and the subsequent discharge capacity is as high as 1,300 mAh gs−1. Moreover, deposition of dead Li2S, which was the primary cause of increasing polarization and decreasing capacity upon cycling, is effectively prevented with the RM.

In this study, the stability of the total nitrogen removal efficiency (TNRE) was modeled using an artificial neural network (ANN)-based binary classification model for the anaerobic ammonium oxidation (AMX) process under saline conditions. The TNRE was stabilized to 80.2 ± 11.4% at the final phase under the salinity of 1.0 ± 0.02%. The results of terminal restriction fragment length polymorphism (T-RFLP) analysis showed the predominance of Candidatus Jettenia genus. Real-time quantitative PCR analysis revealed the average abundance of Ca. Jettenia and Kuenenia spp. increased in 3.2 ± 5.4 × 10

This study seeks to contribute to the growing body of research in crisis communication by exploring how two types of empathy; cognitive empathy and affective empathy, affect organizational reputation and publics’ forgiveness for an organization that is in a crisis. An online three (crisis type: victim vs. accidental vs. preventable) × two (response strategy: rebuilding vs. denial) between-subjects experiment was conducted with 648 participants (N = 648) recruited through Amazon’s research tool MTurk. The results of the study reveal that crisis type affects both cognitive and affective empathy and people are more likely to feel empathetic toward an organization that uses rebuilding strategies than an organization that denies the existence of a crisis. Theoretical and practical implications of empathy on corporate reputation and forgiveness are discussed.

Translocation renal cell carcinoma (tRCC) is a poorly-characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKI) are worse than those treated with immune checkpoint inhibition (ICI). Using multiparametric immunofluorescence, we find that the tumors are infiltrated with CD8(+) T cells, though the T cells harbor an exhaustion immunophenotype distinct from that of clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.

Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

Objective Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation. Methods We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants. Results The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity. Conclusions Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans., Highlights • Sweet taste receptors (STR) have functional roles beyond taste perception. • The TAS1R2 gene of STR is highly polymorphic, suggesting nutrient-dependent adaptive roles. • The Ile191Val variant of TAS1R2 gene causes a partial STR loss-of-function. • Val carriers have reduced glucose excursions mirroring TAS1R2-KO mice.

To increase the discrimination power of human identification in forensic and to evaluate expanded short tandem repeat (STR) loci, we examined a Korean sample population of 2000 unrelated individuals using both GlobalFiler™ PCR Amplification kit and PowerPlex® Fusion System. Allele frequencies for the 20 STR loci (D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, D2S441, D19S433, TH01, FGA, D22S1045, D5S818, D13S317, D7S820, D10S1248, D1S1656, D12S391, and D2S1338) were calculated. Allele frequencies of the 20 STR loci would be useful for personal identification and paternity testing in forensics and as a standard reference database in Korea.

Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors.One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6min walk distance from baseline to post-intervention.After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1±14.7MET-h/wk. to 26.6±21.7MET-h/wk. in the exercise group, with no change in the control group (p0.01 for group and time interaction). Circulating insulin level decreased by 1μU/ml (6.0±3.9 vs. 5.0±3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-α (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction).The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors.

High-risk localized prostate cancer (HRLPC) is associated with a substantial risk of recurrence and prostate cancer-specific mortality1. Recent clinical trials have shown that intensifying anti-androgen therapies administered prior to prostatectomy can induce pathologic complete responses (pCR) or minimal residual disease (MRD) (SPOP mutation and SPOPL copy number loss were exclusively observed in ER, while TP53 mutation and PTEN copy number loss were exclusively observed in NR. These alterations were clonal in all tumor phylogenies per patient. Additionally, transcriptional programs involving androgen signaling and TGFβ signaling were enriched in ER and NR, respectively. The presence of these alterations in routine biopsies from patients with HRLPC may inform the prospective identification of responders to neoadjuvant anti-androgen therapies to improve clinical outcomes and stratify other patients to alternative biologically informed treatment strategies.

Recently, a method of identifying body fluids using DNA methylation has been developed (Frumkin et al., 2011). An existing multiplex assay using 9 CpG markers could differentiate 5 body fluids: semen, blood, saliva, menstrual blood, and vaginal fluid. To validate this technique, we evaluated the previously described body fluid identification method by means of single base extension (SBE). DNA methylation was applied to 22 samples in 18 forensic cases; seven of these were semen, three were blood, eight were saliva, three were vaginal fluid, and one was menstrual blood. Total of 18 samples were tested, the DNA methylation profiles were coincident from preliminary tests (acid phosphatase (AP), leucomalachite green (LMG, Sigma Aldrich, St Louis, MO, USA) and SALIgAE®) except one sample which displayed an all-negative result. After applying the DNA methylation method to forensic samples, we determined that it could be very useful for differentiating vaginal secretions from menstrual blood, for which there is no conventional preliminary testing method.

We report our findings of a detailed investigation into the frequent failures of ethylene furnace radiant tubes at a petrochemical plant. One of the failed samples having gas tungsten arc welded joint between Kanthal-APMT(Fe-based) and KHR45A(Ni-based) which had served for 2 years at 950 °C as an actual ethylene furnace tube was analyzed and turned out to have fracture occurred at the welding interface between the different metals. The detailed microstructural study revealed that the failure was induced by the massive formation of NiAl intermetallic phase and Cr23C6 carbide along the weld interface. To further discuss the failure mechanism, three additional specimens were made in as-welded and heat-treated (at 950 °C for 170 and 1000 h) conditions. Microstructural observation on the additional specimens revealed the enhanced diffusion of Al from APMT weld metal into KHR45A and, as a result, the early-stage precipitation of NiAl intermetallic phase in Al-enriched KHR45A side almost covering the weld interface was successfully detected, which plausibly explains the premature failures in the petrochemical plant.

The rhodium(III)-catalyzed C−H alkylations of indolines with enones and enals is described. This reaction can proceed through 1,4-conjugate addition and protonation process providing β-indolinic ketone compounds, which are known to be crucial scaffolds of biologically active compounds.

The long-term precipitation of the σ phase in a 304H austenitic stainless steel, which had been used for an oil refinery system at 720 °C for 18 years, was investigated in terms of both the base and weld metals using experimental and computational methods. The microstructure was quantitatively analyzed using the electron backscattered diffraction (EBSD) technique, which clearly revealed a substantial amount of σ phase formed at the expense of δ ferrite during the service. Whereas the amount of σ phase precipitated after service corresponded to the fraction of the initial δ ferrite in the base metal, the fraction of the σ phase significantly exceeded the initial amount of δ ferrite in the weld metal. The simulation of long-term precipitation kinetics using MatCalc indicated that the nucleation of the σ phase occurred only in the δ ferrite in both the base and weld metals. The subsequent growth of the σ phase after the nucleation in δ ferrite was predicted to actively occur in austenite during the service. The simulation results also implied that the precipitation behavior of the σ phase was very sensitive to the Cr content.

To study the effect of different polymer binders on the electrochemical performance of tin electrodes for rechargeable lithium-ion batteries, poly(vinylidene fluoride) (PVDF), conventional polyimide (PI-OB), and synthesized polyimide containing amino benzoquinone (PI-AQOB) were used as the polymer binders for electrodes consisting of commercial powdered Sn particles and Super P. PI-AQOB was converted from polyamic acid (PA-AQOB) synthesized from 2,5-bis(4,4’-oxydianiline)-1,4-benzoquinone (AQODA) and 4,4’-biphthalic dianhydride (BPDA) by condensation polymerization and characterized by Fourier-transform infrared analysis. Compared to the electrode employing the traditional PVDF binder, those with the PI-AQOB binder exhibited significantly enhanced electrochemical performance in terms of rate capability, specific capacity, and cycling behavior. PI-AQOB provided a high initial lithiation capacity of 1529 mAh/g at a current density of 50 mA/g. After 50 cycles, the PI-AQOB electrode maintained a higher specific capacity of 332 mAh/g than the Sn/PVDF electrode (only 65 mAh/g at a current density of 200 mA/g). Furthermore, the Sn/PI-AQOB electrode exhibited good volume restoration compared to the electrodes with Sn/PVDF and Sn/PI, as indicated by scanning electron microscopic analysis. The PI-AQOB binder increased the mechanical and adhesive strength of the electrode by suppressing pulverization of the Sn anode during expansion/contraction of Sn particles in the lithiation/delithiation process.

The ruthenium(II)-catalyzed site-selective acylation of indolinic C−H bonds with ethyl glyoxalate is described. A cationic ruthenium catalyst in the presence of copper(II) acetate was found to be an optimal catalytic system for the construction of C7-indolinyl ketoesters. In this process, C−H addition reaction first takes place, and subsequent oxidation of alcohol intermediates occur in-situ. The formed C7−functionalized indolines can be a crucial array towards the construction of novel bioactive molecules.

Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator that activates cellular respiration and generates a proton motive force by stimulating the tricarboxylic acid (TCA) cycle. In contrast, we find that glyoxylate induces phenotypic tolerance by inhibiting cellular respiration with acetyl-coenzyme A diversion through the glyoxylate shunt, despite drug import. Collectively, this work demonstrates that TCA cycle activity is important for both aminoglycoside uptake and downstream lethality and identifies a potential strategy for potentiating aminoglycoside treatment of P. aeruginosa infections. Keyword: aminoglycoside susceptibility; Pseudomonas aeruginosa; TCA cycle; respiration; electron transport chain; fumarate; glyoxylate; biochemical persistence; LC-MS metabolomics, Defense Threat Reduction Agency (DTRA) (Grant HDTRA1-15-1-0051), National Institutes of Health (U.S.) (Grant NIH K99GM118907)

The assembly and installation tools for the ITER Tokamak machine are special tools which are used to assemble and install ITER Tokamak machine components such as magnets, vessels and thermal shields. The sector sub-assembly tool, requiring six adjustable motions capable of movements in three directions and three-axis rotations for fine and precise alignments of the components of these tools, is a major and very large assembly tool with which to assemble vacuum vessels, thermal shields and two toroidal field coils in a 40° sector that forms the basic unit for the ITER Tokamak machine. To complete the 40° sector, the tool must maintain a sufficient degree of stiffness to support and handle heavy components which weigh up to 1200 tonnes. To meet the tooling requirements, the feasibility of the alignment system with regard to component adjustments in the sector sub-assembly tool was reviewed and verified in a mock-up test. In addition, a structural analysis using ANSYS to verify the structural stability levels under various analysis conditions was also carried out considering the safety factors and seismic load conditions according to the load specifications and codes. The sector sub-assembly sequence and the final design considering the results of the mock-up test and the structural analysis are presented.

Summary: Early-passage human mesenchymal stem cells (hMSCs) are typically used in clinical trials because of safety and efficacy issues. However, obtaining sufficient cells for treatment is difficult and expensive. Many more late-passage hMSCs can be obtained at lower cost, although efficacy is a large hurdle in clinical trials. The use of late-passage MSCs with better efficacy would be a revolutionary solution for reducing cost and facilitating clinical trials. In the present study, glia-like cells (ghMSCs) were induced from hMSCs and used for both in vitro and in vivo models of ischemia, effectively protecting neurons from ischemia and restoring brain tissue damaged by cerebral infarction. These beneficial effects were significantly blocked by insulin-like growth factor-binding protein-4 (IGFBP-4) antibody. The current study demonstrated that late-passage hMSCs can be efficiently induced into ghMSCs with a better neuroprotective effect against ischemic stroke and that IGFBP-4 may be a key neuronal survival factor secreted by ghMSCs. Funding Statement: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C2160). Declaration of Interests: One of the corresponding authors, Mi-Sook Chang, has a patent related to this work, which is noted in the "Declaration of Interests" section of the manuscript. She obtained a Korean patent for glia-like human mesenchymal stem cells in 2012. Ethics Approval Statements: All procedures involving animals were approved by the Institutional Animal Care and Use Committee, Seoul National University (Seoul, Republic of Korea). In addition, all animal procedures were performed in accordance with the Hanyang University guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee (IACUC) of Hanyang University. In accordance with Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, all experiments were carried out in a strictly blinded fashion, inclusion and exclusion criteria were predetermined, and attrition due to mortality and other causes was reported

Alloy design is of prime importance for automotive steels to achieve desired properties, such as strength, hardenability and wear resistance. In the present study, CALPHAD-based computational techniques have been successfully utilized to develop advanced steels for automotive applications. The first part of this series describes an integrated computational approach for the compositional modification of bearing steels. A conventional 100CrMn6 bearing steel has been precisely redesigned to achieve strength enhancement with optimized cementite size distribution. The strength of the modified bearing steel was further improved by the addition of 0.2 wt% V using fine vanadium carbide precipitates. Experimental verification of the calculated results confirmed the reliability of the computational method employed in this study.

The CALPHAD-based computational techniques established in the first part of this series [1] have been applied for the development of advanced carburizing steels used for gears in vehicle transmissions. To improve the strength and hardenability of a conventional carburizing steel, the alloying composition has been modified based on the calculation of phase equilibria and the prediction of mechanical properties such as the yield and tensile strengths, hardness, and volume fractions of martensite and bainite. The size and density of carbides precipitated with V, Nb or Ti microalloying elements as well as their austenite grain size have been predicted by thermo-kinetic simulation to optimize the microstructure. The reliability of the computational results has been experimentally confirmed by comparing the austenite grain size and the hardness of the newly developed carburizing steels with those of the conventional carburizing steels.

Allele frequencies for 23 autosomal short tandem repeat loci (D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, TH01, FGA, D5S818, D13S317, D7S820, D2S441, D19S433, D22S1045, D10S1248, D1S1656, D12S391, D2S1338, SE33, Penta D, Penta E), 1 Y-chromosome short tandem repeat locus (DYS391) and Y indel were obtained from 1000 unrelated individuals of the Korean population.

The rhodium(III)-catalyzed mild and site-selective C–H allylation of 2-arylbenzo[d]thiazoles and 2-arylbenzo[d]oxazoles with allylic phosphonates and allylic carbonates is described. This transformation provides an efficient construction of C2-allylated, crotylated and prenylated 2-arylbenzo[d]thiazoles and 2-arylbenzo[d]oxazoles. In addition, this protocol can be applied to the formation of 2-arylbenzo[d]thiazole scaffolds containing an allylic alcohol group by using of 4-vinyl-1,3-dioxolan-2-one and vinyl oxirane as coupling partners.

The rhodium(III)-catalyzed ortho-C–H functionalization of 2-arylbenzo[d]thiazoles with α-diazo esters is described. This transformation provides the facile and efficient construction of C2-alkylated 2-arylbenzo[d]thiazoles in the absence of external oxidants, and releases benign N2 gas as the only byproduct.

Commercial poultry is an important agricultural industry worldwide. Although dense living conditions and large flocks increase meat and egg production, they also increase the risk of disease outbreaks and zoonoses. Current pathogen identification methods mostly rely on culture-dependent techniques and, therefore, are limited to a very small number of bacteria present in the environment. Next Generation Sequencing allows for culture-independent characterization of lower respiratory microbiome of birds including the identification of novel commensals and potentially emerging pathogens. In this study, we collected tracheo-bronchoalveolar lavage of 14 birds raised at 3 different farms in the Punjab province of Pakistan. To characterize the lower respiratory microbiome of these birds, we sequenced hyper-variable regions of the 16S ribosomal subunit gene. Although dominated by bacteria belonging to a small number of taxonomic classifications, the lower respiratory microbiome from each farm was far more diverse and novel than previously known. The differences in microbiome among farms suggest that inter-farm differences affect the microbiome of birds more than breed, geographic location, or management system. The presence of potential and known pathogens in genetically similar specialty breeds of chickens kept at unnaturally high densities and under variable conditions presents an extraordinary opportunity for the selection of highly pathogenic bacteria. In some instances, opportunistic respiratory pathogens were observed in apparently healthy birds. Understanding and monitoring the respiratory microbiome of such populations may allow the early detection of future disease threats.

The rhodium(III)-catalyzed selective C–H allylations of indolines and indoles with 4-vinyl-1,3-dioxolan-2-one at room temperature are described. These transformations provide the direct and efficient formation of indolic scaffolds containing an allylic alcohol group.

The strain change near the Curie temperature was investigated during continuous heating of pure iron using two different types of dilatometers with and without a radio frequency (RF) field. Contrary to the well-known fact that the ferro- to para-magnetic transition accompanies volumetric contraction, abnormal expansion was observed near the Curie temperature only when the quench dilatometer employing the RF field for heating was used. The abnormal expansion was caused primarily by the change in electron–phonon interaction under the RF field.

The variation of the C concentration in proeutectoid ferrite (α PF ) during austenitization in hypoeutectoid steels was quantitatively investigated using the massive transformation start temperature ( T m ) of α PF to austenite (γ) measured by high-temperature confocal laser scanning microscopy and hardness of α PF . The C concentration in α PF at T m in hypoeutectoid steels increased with increasing total C concentration up to approximately 0.2 wt.% during heating. The hardness of α PF with isothermal holding time at 775 °C in S20C steel revealed C enrichment in α PF at the early stage of isothermal holding and its reduction with further holding. These results explain the redistribution of the C in α PF during austenitization as follows: free C atoms released from cementite during pearlite decomposition diffuse excessively into neighboring α PF as well as pearlitic ferrite. The supersaturated C concentration in α PF is reduced during the long-range diffusive transformation of α PF to γ. However, some of the excess C atoms still remain in α PF until α PF starts to massively transform to γ.

A rhodium-catalyzed oxidative C2-alkenylation of indoles containing a N -( p -tolyl)carboxamide group with substituted alkynes via C C bond formation and subsequent C N bond cleavage has been described. This protocol represents direct access to C2-alkenylated free (NH)-indoles, which are important building blocks in the synthesis of natural and pharmacological compounds.

Mg is a promising light-weight material that has superior hydrogen storage capacity. However H2 storage in Mg typically requires high temperature, w500e600 K. Furthermore it has been shown that there is a peculiar film thickness effect on H2 sorption in Mg films, that is thinner Mg films desorb H2 at higher temperature [1]. In this study we show that the morphology of DC magnetron sputtered Mg thin films on rigid SiO2 substrate varied from a continuous dense morphology to porous columnar structure when they grew thicker. Sputtered Mg films absorbed H2 at 373 K and evolved into a metastable orthorhombic Mg hydride phase. Thermal desorption spectroscopy studies show that thinner dense MgH2 films desorb H2 at lower temperature than thicker porous MgH2 films. Meanwhile MgH2 pillars with greater porosity have degraded hydrogen sorption performance contradictory to general wisdom. The influences of stress on formation of metastable MgH2 phase and consequent reduction of H2 sorption temperature are discussed.