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Background Enteric infections are a major public health issue in developing countries. Antimicrobial resistance is also a problem for enteric infection. OPS-2071 is a novel quinolone antibiotic with low oral absorption and potent antibacterial activity against Clostridioides difficile. Objectives This study was conducted to confirm the antimicrobial activity of OPS-2071 against major enteropathogenic bacteria and to evaluate the risk of emergence of drug resistance. Methods The antibacterial activity was evaluated by the agar dilution method. The inhibitory activity against DNA gyrase and topoisomerase IV was determined by supercoiling assay and decatenation assay, respectively. The mutant prevention concentration and frequency of spontaneous resistance were determined by inoculation on drug-containing agar. Results Compared with the reference drugs, the antibacterial activity of OPS-2071 was more potent against Gram-positive bacteria and Campylobacter jejuni, including quinolone-resistant strains. Against other Gram-negative bacteria, OPS-2071 was comparable to existing quinolones. The inhibitory activities against DNA gyrase with quinolone-resistant mutations closely correlated with the antibacterial activity. Spontaneous resistance to OPS-2071 was not observed in Staphylococcus aureus and Escherichia coli and was lower than that of existing quinolones and higher than that of azithromycin in C. jejuni. The mutant prevention concentration of OPS-2071 was lower than that of tested compounds in S. aureus and C. jejuni and slightly higher than that of existing quinolones in E. coli. Conclusions The broad and potent in vitro antibacterial activity and lower risk of drug resistance suggested that OPS-2071 may be useful for enteric infections caused by major pathogens including quinolone-resistant Campylobacter.

Background One of the growth mechanisms of castration-resistant prostate cancer (CRPC) is de novo androgen synthesis from intracellular cholesterol, and statins may be able to inhibit this mechanism. In addition, statins have been reported to suppress the expression of androgen receptors (ARs) in prostate cancer cell lines. In this study, we investigated a combination therapy of novel AR antagonists and statin, simvastatin, for CRPC. Methods LNCaP, 22Rv1, and PC-3 human prostate cancer cell lines were used. We developed androgen-independent LNCaP cells (LNCaP-LA). Microarray analysis was performed, followed by pathway analysis, and mRNA and protein expression was evaluated by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. Cell viability was determined by MTS assay and cell counts. All evaluations were performed on cells treated with simvastatin and with or without AR antagonists (enzalutamide, apalutamide, and darolutamide). Results The combination of darolutamide and simvastatin most significantly suppressed proliferation in LNCaP-LA and 22Rv1 cells. In a 22Rv1-derived mouse xenograft model, the combination of darolutamide and simvastatin enhanced the inhibition of cell proliferation. In LNCaP-LA cells, the combination of darolutamide and simvastatin led to reduction in the mRNA expression of the androgen-stimulated genes, KLK2 and PSA; however, this reduction in expression did not occur in 22Rv1 cells. The microarray data and pathway analyses showed that the number of differentially expressed genes in the darolutamide and simvastatin-treated 22Rv1 cells was the highest in the pathway termed "role of cell cycle." Consequently, we focused our efforts on the cell cycle regulator polo-like kinase 1 (PLK1), cyclin-dependent kinase 2 (CDK2), and cell cycle division 25C (CDC25C). In 22Rv1 cells, the combination of darolutamide and simvastatin suppressed the mRNA and protein expression of these three genes. In addition, in PC-3 cells (which lack AR expression), the combination of simvastatin and darolutamide enhanced the suppression of cell proliferation and expression of these genes. Conclusions Simvastatin alters the expression of many genes involved in the cell cycle in CRPC cells. Thus, the combination of novel AR antagonists (darolutamide) and simvastatin can potentially affect CRPC growth through both androgen-dependent and androgen-independent mechanisms.

Background Recently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP). Methods From April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock. Results Regarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p p = 0.007). ROC curve for diagnosing septic shock indicated an area under the curve (AUC) of 0.881 for presepsin (vs. 0.690, 0.583, and 0.527 for PCT, CRP and WBC, respectively). Regarding the 5th day after admission, the median presepsin value on the enrollment day was significantly higher in the SIRS groups than in the non-SIRS groups (p = 0.006). On the other hand, PCT (≥ 2 ng/ml) on the enrollment day was an independent risk factor for SIRS. ROC curve for diagnosing sepsis on the fifth day indicated an AUC of 0.837 for PCT (vs. 0.817, 0.811, and 0.802 for presepsin, CRP, and WBC, respectively). Conclusions This study showed that presepsin may be a good marker for diagnosing septic shock based on admission data in patients with UTI.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although many types of drug are used, clinical outcomes are still unsatisfactory. Previous studies have suggested that intestinal bacteria are involved in the pathogenesis of IBD. Accordingly, in an IBD model we evaluated the therapeutic effects of OPS-2071, a low-absorption quinolone antibacterial agent indicated for intestinal infection, and investigated its mechanism of action. The therapeutic effects of OPS-2071 and comparison therapies were evaluated using naive CD4 + T cell-transfer IBD model mice. In vitro inhibition of LPS-induced TNF-α production and inhibitory effects on T cell responses stimulated using anti-CD3/CD28 antibody-loaded beads were evaluated using mouse splenocytes and human peripheral blood mononuclear cells. In addition, in vitro activities against bacteria implicated in IBD pathogenesis were tested. OPS-2071 dose-dependently decreased both colonic weight/length ratio and the colitis histological score as compared with the vehicle group. The therapeutic effect of OPS-2071 was equivalent to that of anti-IL-12/23 (p40) antibody. In vitro, OPS-2071 suppressed TNF-α production induced by LPS stimulation and T cell responses in a dose-dependent manner. At high concentrations, these effects were comparable to those of existing immunosuppressive agents, such as prednisolone, in both mouse and human cells. OPS-2071 also showed antibacterial activity against IBD-related bacteria. Our results suggest that OPS-2071 had both immunosuppressive and antibacterial effects. This dual effect makes OPS-2071 a unique and promising candidate for IBD.

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin., OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated C. difficile strains with a MIC of 0.125 μg/ml (MIC50) and 0.5 μg/ml (MIC90), making it more active than vancomycin on a concentration basis (MIC50, 2 μg/ml; MIC90, 4 μg/ml) and comparable to fidaxomicin (MIC50, 0.063 μg/ml; MIC90, 8 μg/ml). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and nonhypervirulent strains, while a significant difference in susceptibility to fidaxomicin was observed. Spontaneous resistance to OPS-2071 and vancomycin was not observed; however, resistance to fidaxomicin was observed at 4× MIC. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the postantibiotic effect of OPS-2071 was longer than those of fidaxomicin and vancomycin. Also, OPS-2071 showed low systemic exposure, with OPS-2071 having 2.9% oral bioavailability at 1 mg/kg in rats. Furthermore, OPS-2071 showed significant in vivo efficacy at 0.0313 mg/kg/day (50% effective doses), 39.0-fold and 52.1-fold lower than those of vancomycin and fidaxomicin, respectively, in a hamster model of C. difficile infection. OPS-2071 has the potential to become a new therapeutic option for treating C. difficile infection.

Background Recently, presepsin is reported to be a biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients, but there are few reports about urinary-tract infections. The objective of this study is to evaluate whether presepsin is a recent marker for detecting severe sepsis, and whether it can predict the therapeutic course in UTI when compared with procalcitonin (PCT) and C-reactive protein (CRP), already used markers.Methods From April 2014 to December 2016, a total of 50 patients, who were admitted into Gunma university hospital with urinary-tract infections, were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC), causative diseases of urinary-tract infections and other data were evaluated at the enrollment, third and fifth days. The patients were divided into two groups; with (n=11) or without (n=39) septic shock at the enrollment day, and with (n=7) or without (n=43) sepsis at the fifth day, respectively. Presepsin was evaluated for systemic inflammatory response syndrome (SIRS) or septic shock. Results Concerning the enrollment day, there was no significant difference of presepsin between SIRS and non-SIRS groups (p=0.276). The median presepsin (pg/mL) was significantly higher in the septic shock group (pConclusions This study shows that presepsin may be a good marker for diagnosis of severe patients who need vasopressor therapy at the data of admission, and PCT may be a good marker for predicting hard-to-treat cases in UTI.

Background/Aim: There are several treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) in the world. In recent years, the use of docetaxel, abiraterone, enzalutamide, and apalutamide has been used for mHSPC, but combined androgen blockade (CAB) therapy using first-generation antiandrogens has been widely used in Japan. There is a background. We performed a consecutive study of patients who received combined androgen blockade (CAB) at a single institute to determine the prognostic factors for mHSPC. Patients and Methods: We conducted a consecutive study of 237 mHSPC patients treated with CAB from 2003 to 2017 at the Gunma University Hospital. Prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The associations between pre-treatment risk factors and the PSA response 3 months after starting CAB, PSA-PFS, and OS were evaluated by the Cox proportional hazards model. Results: Among the 237 cases, the median PSA-PFS and OS times were 63.0 and 91.4 months, respectively. The median PSA-PFS and OS times of M1 cases (174 cases, 73.4% of all 237 cases) were 36.1 and 75.9 months, respectively. The Eastern Cooperative Oncology Group performance status (ECOG PS) score, hemoglobin (Hb), lactate dehydrogenase, extent of disease, visceral metastasis (no vs. yes), and PSA response after 3 months were significant predictors of OS according to Cox regression analysis of prognostic factors in M1 patients. The ECOG PS, Hb, visceral metastasis (no vs. yes), and PSA response after 3 months predicted OS high-risk patients in LATITUDE criteria. The OS was 92.1 months in the low-risk group (0-1 risk factors), 48.2 months in the intermediate-risk group (2 risk factors), and 16.9 months in the high-risk group (3-4 risk factors). Conclusion: CAB should be considered as a treatment option for strictly selected patients with mHSPC, even though novel treatments are available.

The hammering sound inspection for pieces plays the Digital Twin part in the Hybrid Twin approach. The map generated by Self-Organizing Map (SOM) algorithm makes it possible to cluster the pieces into defected and non-defected groups by checking the corresponding hammering sounds. However, the applicability of map generated by SOM has not yet been discussed. This paper suggests a procedure how to improve a map generated by SOM algorithm. It shows that if the hammering sound of a piece is mapped on the boundary between the areas corresponding to defected and non-defected products, the map cannot be applied to inspect this piece and another map must be generated by repeating the training including the hammering sounds of such pieces by SOM algorithm. By executing the procedure some number of times, it is likely that the improved map will be used for hammering sound inspection.

Background/aim The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reversed cabazitaxel resistance in castration-resistant prostate cancer (CRPC). Materials and methods Cabazitaxel resistance was induced in the castration-resistant prostate cancer cell line, 22Rv1-CR. In vitro and in vivo models were used to test the efficacy of YM155 and cabazitaxel. Results Survivin gene expression was significantly higher in 22Rv1-CR than its parent cells (22Rv1). In 22Rv1-CR cells, YM155 significantly reduced expression of the survivin gene in a concentration-dependent manner. YM155 alone was poorly effective; however, it significantly enhanced the anticancer effects of cabazitaxel on 22Rv1-CR in vitro and in vivo. Conclusion Inhibition of survivin by YM155 overcomes cabazitaxel resistance in CRPC cells.

Background To investigate the association between androgen deprivation therapy (ADT) and changes in the estimated glomerular filtration rate (eGFR) in male Japanese prostate cancer patients, based on post-hoc analysis of data from a previous prospective study.Methods From among 103 prostate cancer patients in whom renal function changes were tracked over 5 years, 88 were divided into a group who completed ADT within 3 years (short ADT group; n = 47) and a group who continued with ADT for more than 5 years (continuous ADT group; n = 41). We compared the groups in terms of the eGFR, calculated based on age and serum creatinine (mg/dL), before ADT initiation and every other year over the next 5 years. This study was approved by the Ethics Committee for Clinical Studies of Gunma University Hospital (Approval No: 8 − 5).Results The eGFR decreased by 4.91 and 2.89 ml/min in the short and continuous ATD groups, respectively, over the 5-year period following ADT initiation. The respective decreases in the eGFR were 0.98 and 0.58 ml/min/year. No significant difference in the eGFR was observed between the two groups at any measurement point.Conclusions ADT patients showed a decrease in the eGFR of 0.58–0.98 ml/min/y over a 5-year period, which is about twice as high as that of normal Japanese males. No significant difference in the eGFR by ADT duration was observed.

INTRODUCTION AND OBJECTIVE:Urinary-tract infections are common diseases, and sometimes progress to sepsis or septic shock which can be lethal. Therefore, the diagnosis and severity of sepsis are im...

236 Background: We mainly perform Robotic-Assisted laparoscopic Radical Prostatectomy (RARP) and Carbon Ion Radiotherapy (CIRT) as curative treatment for prostate cancer. Several factors such as cancer control and quality of life after treatment are considered to be important, but there are few reports comparing sexual function changes before and after treatment between RARP and CIRT. We performed retrospective study comparing the evaluation of sexual function after RARP and CIRT cases using the propensity score matching method. Methods: 127 patients treated by RARP from 2014 to 2018 and 190 patients treated by CIRT monotherapy from 2010 to 2019 were evaluated. We evaluated Expanded Prostate Cancer Index Composite (EPIC) score before and after treatment. The EPIC was compared before, 12 months, and 24 months after treatment. Propensity score matching was performed using the age at treatment, PSA value, T stage, and pretreatment EPIC comprehensive score of sexual function as covariates. A cohort of 101 patients in each group was prepared and examined. This study was approved by the Institutional Review Board of Gunma University Hospital (No. IRB2020-050, 1839). Results: The mean ± standard deviation of each of the RARP and CIRT groups were age; 65.1 ± 5.9, 65.3 ± 6.5 years, PSA value; 6.31 ± 2.07, 6.34 ± 2.46 ng/ ml, pretreatment EPIC sexual function overall score; 46.4 ± 15.6, 48.2 ± 16.2. In both groups, T1N0M0 was 16%, T2N0M0 was 83%, and T3N0M0 was 1%. The total EPIC sexual function scores before, 12 months, and 24 months after treatment were 46.4, 27.9, 28.2 in the RARP group, and 48.2, 41.4, 41.6 in the CIRT group, respectively. In both groups, there was a significant decrease in score after 12 months and 24 months compared to before treatment (p < 0.05). At 12 and 24 months, the total EPIC sexual function score in the CIRT group was significantly higher than RARP group (p < 0.001). Conclusions: In prostate cancer cases adjusted by propensity score matching, the decrease in EPIC sexual function score was significantly smaller in the CIRT group than RARP group. The results of this study seemed to be useful information for decision making with patients.

Antitumor effect mechanism of statin in prostate cancer cells focusing on autophagy Background:Statins have recently been studied for their proapoptotic and antimetastatic effects. However, the exact mechanisms of their anticancer actions remain unclear. We have studied the novel castration resistant prostate cancer (CRPC) treatment with statins. Using microarrays, we discovered up-regulation of ATG4B (Autophagy related 4 homolog B) in PC-3 cells after simvastatin treatment. In this study, we evaluated the effects of simvastatin focusing on androgen-independent prostate cancer cells. Methods:PC-3, LNCaP-LA, 22RV-1-LA (taht were derived from LNCaP and 22RV1 cells and cultured in 10% charcoal-stripped fetal bovine serum for 3 months), and DU145 human prostate cancer cell lines were used. Microarrays were performed using PC-3 untreated or administered with simvastatin (0 uM versus 5 uM). Proliferation, migration, and invasion were evaluated using MTS assay, Migration assay, and Invasion assay, respectively. The increases of autophagy were detected by western blot using microtubule associated protein 1 light chain 3 (LC-3) antibody and confirmed by a fluorescence microscope with staining autophagosomes by autophagy detection kit (abcam, Cambridge, UK). Results:Using microarrays, we discovered up-regulation of ATG4B in PC-3 cells after simvastatin treatment. Simvastatin inhibited the proliferation, migration, and invasion of PC-3, LNCaP-LA, 22RV1-LA and DU145 cells. The expression level of LC-3 was up-regulated by simvastatin in PC-3, LNCaP-LA, 22RV1-LA and DU145 cells. In PC-3 cells treated with statin, a significant increase in autophagosomes was confirmed by fluorescence microscopy. The expression of LC-3 and autophagosomes were increased in a concentration-dependent manner. Conclusions:It was found that statin administration enhances autophagy induction in a prostate cell line. We plan to study the combined effect with other drugs that induce autophagy. We would like to develop CRPC treatment by inducing autophagy cell death. Citation Format: Yoshiyuki Miyazawa, Daisuke Oka, Hiroshi Nakayama, Yoshitaka Sekine, Seiji Arai, Kazuhiro Suzuki. Antitumor effect mechanism of statin in PCa cells focusing on autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1935.

Background Crohn’s disease (CD) is a form of chronic inflammatory bowel disease (IBD). Although CD is an immune-mediated condition of unknown etiology, many studies suggested that abnormal immune responses against certain intestinal bacteria may trigger development of chronic inflammation. The T cell-mediated colitis model is a well characterized adaptive transfer murine model of chronic small bowel and colonic inflammation that resembles human CD (e.g., diarrhea, a heavily inflamed colon, loss of mucus from goblet cells, Th1/Th17 dominated cytokine profile). OPS-2071, a novel agent synthesized by Otsuka Pharmaceutical Co., Ltd, has broad and strong antibacterial activity with low systemic absorption. In this study, we have evaluated the therapeutic effect of OPS-2071 on murine T cell-mediated colitis and in vitro activity on T cell activation, cytokine production and antibacterial activity. Methods T cell-mediated colitis was induced via naive T cell (CD4+CD62L+CD44-) injection into T and B cell deficient recipient mice. Two weeks following T cell transfer, OPS-2071 or vehicle solution was administered orally for 3 weeks, followed by harvesting of colon tissue and assessment of efficacy evaluation by histological score and inflammatory index (colon weight/ length). In vitro inhibitory action for TNF-α production was assayed by ELISA using LPS-stimulated human peripheral blood cells. The effect on T cell activation and cytokine production (TNF-α, IFN-γ), was examined using human peripheral blood mononuclear cells and, mouse spleen which were stimulated by anti-CD2/CD3/CD28 antibody-loaded beads. In vitro activity against bacteria considered to be the cause of IBD was also tested. Results In the murine T cell transfer model, OPS-2071 significantly reduced both histological score (control: 9.2, OPS: 2.7, p128 mg/mL, respectively. Conclusion OPS-2071 demonstrated significant therapeutic effects on colon inflammation in the murine T cell-medicated colitis model, suppressed TNF-a production in vitro and showed in vitro activity against bacteria related to CD. The dual effect of anti-inflammatory effects and antibacterial activity of the novel agent OPS-2071 demonstrated in this study, provide rationale for exploring the impact of this compound on human CD in clinical trials.

The development of a method to easily investigate the spatial distribution of soil moisture and soil hardness in tree windbreaks is necessary because these windbreaks often decline due to inappropriate soil moisture condition and soil compaction. This research examined the applicability of ground-penetrating radar (GPR) and a combined penetrometer&ndash, moisture probe (CPMP) for evaluating the spatial distribution of soil moisture and soil hardness in four windbreaks with different soil characteristics. A GPR-reflecting interface was observed at a less permeable layer in a coastal windbreak and at a depth affected by soil compaction in an inland windbreak with andosol. The spatial distribution of the groundwater table could also be evaluated by examining the attenuation of GPR reflection in a coastal windbreak. In contrast, GPR was not applicable in an inland windbreak with peat because of high soil water content near the soil surface. The CPMP could detect vertical distributions of soil hardness and soil water content regardless of soil type. The CPMP was useful for interpreting GPR profiles, and GPR was useful for interpolating the information about the horizontal distribution of soil moisture and soil hardness between survey points made with the CPMP. Thus, the combination of GPR and a CPMP is ideal for examining the two-dimensional spatial distribution of soil moisture and soil hardness at windbreaks with soils for which both methods are applicable.

146 Background: Enzalutamide (ENZ) is commonly used to treat patients with castration resistant prostate cancer (CRPC). However, the kinetics of serum androgen levels before and after ENZ treatment are unknown. We elucidated the kinetics of serum androgens and explored the possibility of identifying a useful marker for predicting the effects of ENZ. Methods: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. 104 CRPC patients treated with ENZ were analyzed. We investigated the PSA reduction rate (50%, 90%), PSA-progression-free survival (PFS), and overall survival (OS) after administration. To measure levels of androgens accurately we measured serum androgen levels using LC-MS/MS. OS and PSA-PFS were assessed according to the PCWG 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1177). Results: The 50% and 90% PSA decline rates were 62.5% and 25.0%, respectively. Median serum testosterone (T), dihydrotestosterone (DHT), androstenedione (A-dione), and dehydroepiandrosterone-sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. Mean serum levels of T, DHT, and A-dione increased significantly 12 and 24 weeks after compared to before treatment (p < 0.05). We performed a multivariate analysis using a Cox regression to predict OS and PSA-PFS. ECOG PS (0 vs. 1–2), hemoglobin (Hb ≥ 12.5 vs. < 12.5 g/dL), albumin (≥ 3.9 vs. < 3.9 g/dL), visceral metastasis (no vs. yes), EOD (0–2 vs. 3–4), docetaxel treatment (no vs. yes), and DHT level (≥11.25 vs. < 11.25 pg/mL, 11.25 was third quartile) were significant predictors of OS (p < 0.05). Hb (≥12.5 vs. < 12.5 g/dL), docetaxel treatment (no vs. yes), and level of DHT (≥ 5.9 vs. < 5.9 pg/mL) were significant predictors of PSA-PFS (p < 0.05). As a result of the binomial logistic analysis of the predictors of fatigue and decreased appetite, the presence of visceral metastasis (yes) and low DHT (

The plasma electrolytic oxidation (PEO) process was used to deposit an alumina coating on a cold sprayed 7075 aluminum alloy to improve the surface properties. The phase compositions, microstructures, basic mechanical properties, as well as the corrosion and the dry sliding wear resistance of cold sprayed 7075 aluminum alloy before and after PEO treatment, were investigated. The results show that a single-layered dense alumina coating with a thickness of ~15–20 μm and hardness of 1353 HV0.01 is realizable on the cold sprayed 7075 aluminum alloy by PEO treatment aided by an aluminate electrolyte. The corrosion current density and wear rate of the alumina PEO coating were 6.27 × 10−7 A/cm2 and 1.22 × 10−6 mm3/N·m respectively, which were three and two orders of magnitude lower compared to the uncoated rolled 7075 aluminum alloy (T6) substrate, thus highlighting the excellent wear and corrosion resistance of the PEO treated cold sprayed Al alloy surface.

Background OPS-2071 is a novel fluoroquinolone that is currently in Phase 2 clinical trials for the evaluation of Crohn’s disease (CD) as an add-on therapy to standard of care. OPS-2071 has broad and potent antibacterial activity with low systemic absorption. It was previously investigated for the treatment of enteric infections, including Clostridium difficile. CD is an immune-mediated condition of unknown aetiology; however, studies suggest that an abnormal immune response against certain intestinal bacteria may trigger the development of chronic inflammation. In this study, we have evaluated the effect of OPS-2071 on both the murine T-cell-mediated colitis as well as its in vitro effect on the activity of immune cells. Methods Transfer of naïve T cells (CD4+CD62L+CD44−) into immunodeficiency mice induces autoimmune colitis. Two weeks following T-cell transfer, OPS-2071, sulfasalazine and anti-IL12/23 p40 antibody were administered for 3 weeks, followed by assessment of efficacy evaluation by histological score and inflammatory index. In vitro inhibitory action for TNF-α production was assayed using LPS-stimulated human peripheral blood cells and THP-1 macrophages. The effect on T-cell activation and cytokine production (TNF-α, IFN-γ) was examined using anti-CD2/CD3/CD28 antibody-loaded beads-stimulated human peripheral blood mononuclear cells. In vitro activity against bacteria considered to be a potential cause of IBD such as M. avium sub. paratuberculosis, Klebsiella pneumonia, etc., was also tested. Results OPS-2071 and anti-IL12/23 p40 antibody significantly reduced both histological score (control: 9.0, OPS: 4.7, anti-IL12: 4.3, p < 0.01) and inflammatory index (control: 58.3 ± 3.7 mg/cm, OPS: 25.9 ± 1.4 mg/cm, anti-IL12: 41.1 ± 2.4 mg/cm, p < 0.01) at a dose of 10 and 25 mg/kg, respectively. OPS-2071 suppressed TNF-α production in T cells, as well as macrophage activity in a dose-dependent fashion. OPS-2071 also suppressed human T-cell activation and proliferation. At high OPS-2071 concentrations, these effects were comparable to prednisolone. The minimum inhibitory concentration against IBD-related bacteria for: OPS-2071, ciprofloxacin, and metronidazole were 0.015–0.5, 0.25–8 and 0.03–>128 mg/ml, respectively. Conclusion OPS-2071 demonstrated significant therapeutic effect on colonic inflammation, suppressed TNF-α production in vitro and showed in vitro activity against bacteria related to CD. From these in vitro results, it can be concluded that OPS-2071 has anti-inflammatory activity, independent of its antibacterial activity. The dual effects demonstrated by this novel agent, OPS-2071, provided a rationale for exploring the impact of this compound on human CD in clinical trials.

This paper deals with an on-line non-destructive inspection system by using hammering sounds based on the combination of support vector machine and a heuristic algorithm. In machine learning algorithms, the perfect performance is hard to attain and it is newly suggested that a heuristic algorithm redeeming this insufficiency is connected to the support vector machine as a post-process. The experimental results show that the combination of support vector machine and the heuristic algorithm attains 100% detection of defective pieces with 18.4% of erroneous determination of non-defective pieces within the upper limit of given processing time.

In conventional air-conditioning design, the comfortable range is considered to be between temperatures of 25 and 27 °C and relative humidity of 40 and 60%; these numbers vary only slightly based on a person’s race and country. However, several studies conducted in regions with hot and humid climates show that the observed thermal comfort requirements often do not agree with those obtained from European-based studies. In this chapter, the results from the questionnaire surveys and measurements in residences in the hot and humid regions of Indonesia and Malaysia are shown. It was found that the residents use air conditioning at low temperatures for sleeping and that many people consider cold condition as “comfortable” and desire “cooler” conditions even if they feel “cold” in thermal sensation.