Novel secondary metabolites from selected marine invertebrates

Chemical studies of a Northeastern Pacific tunicate and three Papua New Guinea sponges have led to the isolation of sixteen new secondary metabolites. The structures of the new compounds were determined by spectroscopic analysis and chemical interconversions. The absolute stereochemistry of imbricatine, a previously reported starfish metabolite, has also been determined. The northeastern Pacific tunicate Ritterella rubra has been found to contain a novel series of aromatic butenolides, rubrolides A-H (149-156). The structures of the rubrolides were solved by the analysis of NMR (¹H, ¹³C, COSY, nOe, HETCOR, FLOCK, HMQC and HMBC), MS and IR data combined with chemical interconversions. FLOCK, a new ¹H/¹³C long-range correlation experiment, played a key role in establishing the rubrolide carbon skeleton. The rubrolides represent the largest family of non-nitrogenous tunicate metabolites. The protein phosphatase inhibitory activity and the potent antibiotic activities of the rubrolides warrant further investigation. The absolute stereochemistry of imbricatine (179), a compound reported from the starfish Dermasterias imbricata, has been determined by comparing the optical properties of its chemical degradation products with those of model compounds. Raney nickel reduction of 179 yielded benzyltetrahydroisoquinoline 188a which was methylated to give 188b. Comparison between the CD spectrum of 188b and those of model compounds 189 and 190 solved the absolute stereochemistry of the tetrahydroisoquinoline fragment of 179. Reductive hydrolysis of 179 followed by oxidation yielded histidine disulphide 182. Comparison of the optical rotation of 182 with the reported value solved the absolute stereochemistry of the histidine fragment of 179. Attempts to study the biogenesis of 179 were unsuccessful. Examination of three Papua New Guinea sponges resulted in the isolation of eight new compounds. Six new bastadins (211-216) were isolated from Ianthella basta. The structures were elucidated by spectroscopic analysis as well as comparison with the previously reported bastadins. A Xestospongia species was found to contain xestospongin E (238), a new metabolite, and a number of known xestospongins. Both the bastadins and the xestospongins possess antibiotic and cytotoxic activities. A symmetrical enyne, callydiyne (247), was isolated from Callyspongia flammea. The structure of 247 was determined by spectroscopic studies.Science, Faculty ofChemistry, Department ofGraduat

Pose Mask: A Model-Based Augmentation Method for 2D Pose Estimation in Classroom Scenes Using Surveillance Images

Solid developments have been seen in deep-learning-based pose estimation, but few works have explored performance in dense crowds, such as a classroom scene; furthermore, no specific knowledge is considered in the design of image augmentation for pose estimation. A masked autoencoder was shown to have a non-negligible capability in image reconstruction, where the masking mechanism that randomly drops patches forces the model to build unknown pixels from known pixels. Inspired by this self-supervised learning method, where the restoration of the feature loss induced by the mask is consistent with tackling the occlusion problem in classroom scenarios, we discovered that the transfer performance of the pre-trained weights could be used as a model-based augmentation to overcome the intractable occlusion in classroom pose estimation. In this study, we proposed a top-down pose estimation method that utilized the natural reconstruction capability of missing information of the MAE as an effective occluded image augmentation in a pose estimation task. The difference with the original MAE was that instead of using a 75% random mask ratio, we regarded the keypoint distribution probabilistic heatmap as a reference for masking, which we named Pose Mask. To test the performance of our method in heavily occluded classroom scenes, we collected a new dataset for pose estimation in classroom scenes named Class Pose and conducted many experiments, the results of which showed promising performance

Mathematical Performance Evaluation Model for Mobile Network Firewall Based on Queuing

While mobile networks provide many opportunities for people, they face security problems huge enough that a firewall is essential. The firewall in mobile networks offers a secure intranet through which all traffic is handled and processed. Furthermore, due to the limited resources in mobile networks, the firewall execution can impact the quality of communication between the intranet and the Internet. In this paper, a performance evaluation mathematical model for firewall system of mobile networks is developed using queuing theory for a multihierarchy firewall with multiple concurrent services. In addition, the throughput and the package loss rate are employed as performance evaluation indicators, and discrete-event simulated experiments are conducted for further verification. Lastly, experimental results are compared to theoretically obtained values to identify a resource allocation scheme that provides optimal firewall performance and can offer a better quality of service (QoS) in mobile networks

C5a receptor inhibitor avacopan in immunoglobulin A nephropathy - an open-label pilot study

Background Improvement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody-associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin-angiotensin-aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria. Methods This open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) >1 g/g creatinine and an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2) or >45 mL/min/1.73 m(2) if eGFR has not declined >10 mL/min/1.73 m(2) over the previous 24 weeks. If the UPCR remained at >1 g/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period. Results A total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR >1 g/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of similar to 50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan. Conclusions This short-term pilot study showed an improvement in the slope of the UPCR, with similar to 50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit

Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial

CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA). CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score-CRP, individual ACR components, as well as soluble bone turnover markers. CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits. CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in R