Biological function of CYP-produced eicosanoids in the regulation of the pharyngeal activity in the nematode Caenorhabditis elegans

Diese Arbeit untersucht die Auswirkungen von Cytochrom P450 (CYP)-produzierten Eicosanoiden auf das Pumpen des Pharynx im Nematoden Caenorhabditis elegans und deren funktionellen Vernetzung mit dem Wirken von Neurohormonen. Bei der Erforschung der CYP-Eicosanoid-Signalübertragung konzentrierte sich diese Arbeit hauptsächlich auf die Identifizierung und Charakterisierung von Schlüsselkomponenten, welche an der Regulation der pharyngalen Aktivität des Wurms beteiligt sind, insbesondere Regio- und Stereometaboliten von EPA und AA, Neurohormone (Serotonin und Octopamin) sowie relevante GPCR. Zunächst wurde der Einfluss einer Kurzzeitbehandlung mit CYP-Eicosanoiden und Neurohormonen auf die Bildung von freien CYP-Eicosanoiden im Wildtyp und in verschiedenen Mutantenstämmen analysiert. Die Ergebnisse zeigten, dass 17,18-EEQ die stimulierende Wirkung von Serotonin zeigt, während 20-HETE mit der hemmenden Wirkung von Octopamin überlappt. Darüber hinaus erhöhte Serotonin den freien 17,18-EEQ-Spiegel, während Octopamin selektiv die Synthese von Hydroxymetaboliten induzierte. Zweitens wurde die Stereodiskriminierung von 17,18-EEQ getestet, um das wirksame Enantiomer in der stimulierenden Funktion auf die Pharynxmuskelzellen zu identifizieren. Es wurde festgestellt, dass nur 17(R),18(S)-EEQ Beeinträchtigungen des pharyngalen Pumpens beheben konnte. Darüber hinaus wurden drei Mutantenstämme, die in verschiedenen Serotonin-GPCRs defekt sind, ser-1(ok345), ser-7(tm1325) und ser-7(tm1325)ser-1(ok345), ausgewählt, um zu entschlüsseln, welcher Rezeptor am CYP-Eicosanoid-Signaltransduktionsweg beteiligt sein könnte. Tatsächlich scheint SER-7 für die 17-18-EEQ-Effekte auf die Regulierung der pharyngalen Pumpaktivität von C. elegans erforderlich zu sein. Drittens wurde mit der Identifizierung eines GPCR des vorgeschlagenen Signaltransduktionsweges stromabwärts der CYP-Eicosanoid-Produktion begonnen. NMUR-2 wurde als potenzielles Kandidaten-GPCR-Gen ausgewählt.This thesis investigated the effects of cytochrome P450 (CYP)-produced eicosanoids on the pharyngeal pumping in the nematode Caenorhabditis elegans and their cross-link with neurohormones. Within the framework of exploring CYP-eicosanoid signaling in C. elegans this work mainly focused on identifying and characterizing key components involved in worm’s pharyngeal activity, in particular regio- and stereoisomeric metabolites of EPA (eicosapentaenoic acid, 20:5 n-3) and AA (arachidonic acid, 20:4 n-6), neurohormones, (serotonin and octopamine) as well as the involvement of relevant GPCR (G protein-coupled receptors). Firstly, the impact of short-term treatment with CYP-eicosanoids and neurohormones on CYP-eicosanoid formation in wildtype and different mutant strains was analyzed. The results showed that 17,18-EEQ (17,18-epoxyeicosatetraenoic acid) mimics the stimulatory effect of serotonin while 20-HETE (20-hydroxeicosatetraenoic acid) overlapped with the inhibitory effect of octopamine. Moreover, serotonin increased free 17,18- EEQ levels, whereas octopamine selectively induced the synthesis of hydroxy-metabolites. Secondly, stereo-discrimination of 17,18-EEQ was tested to identify the effective enantiomer in the stimulatory function on pharyngeal muscle cells. Only 17(R),18(S)-EEQ was found to rescue impairments of pharyngeal pumping. Moreover, three mutant strains defective in different serotonin GPCRs, ser-1(ok345), ser-7(tm1325) and ser-7(tm1325) ser-1(ok345), were selected to decipher which receptor might be involved in the CYP-eicosanoid signaling transduction pathway. In fact, SER-7 seems to be required for the 17-18-EEQ effects on regulation of pharyngeal pumping activity in C. elegans. Third, the identification of a GPCR of the proposed signal transduction pathway down-stream of CYP-eicosanoid production was started. NMUR-2 was selected as a potential candidate GPCR gene

Alpha-mangostin attenuates oxidative stress and inflammation in adjuvant-induced arthritic rats

Purpose: To examine the protective effect of α-mangostin on Freund’s adjuvant-induced rheumatoid arthritis (RA) in rats.Methods: Male Wistar rats were divided into four groups (n = 6). The rats were made arthritic using a single intradermal injection of 0.1 ml complete Freund's adjuvant. α-Mangostin (100 mg/kg, i.p.) was administered for 21 days. After the experimental period, the animals were sacrificed and various biochemical markers were assessed.Results: Arthritis-induced rats showed a significant (p < 0.05) increase in malondialdehyde (16.28 ± 1.43 vs 7.22 ± 1.03) and nitric oxide (3.82 ± 0.87 vs 6.12 ± 1.23) with a concomitant reduction of antioxidants in the paw tissue. α-Mangostin intervention significantly (p < 0.05) reduced malondialdehyde and nitric oxide levels and restored antioxidant levels to normalcy by mitigating oxidative stress. The arthritic rats exhibited elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) serum concentrations, upregulated TNF-α and IL–6 protein levels, and upregulated nuclear factor αB (NF-αB) mRNA expression in paw tissues. Treatment with α-mangostin significantly (p < 0.05) reduced serum levels and downregulated inflammatory markers to normalcy.Conclusion: The results suggest that α-mangostin displayed a protective effect against adjuvantinduced arthritis in rats mediated through antioxidant and anti-inflammatory effects.Keywords: Rheumatoid arthritis, Freund’s adjuvant, α-Mangostin, Oxidative stress, Inflammatio

アサイミズウミニオケルメタントアサンカチッソハイシュツノヒョウカトメカニズム

博士（工学）東京農工大

Research on AR cultural and creative design of Yangming Culture under the background of the integration of culture and technology

The integration of science and technology and culture is a general trend in today’s society, which provides more ways for cultural exchange and interaction and promotes social development. This study analyzes the application value of AR technology in the design of cultural and creative products, and reconstructs the process of AR cultural and creative products through the double drill model, and designs Yangming cultural products based on AR technology. It can be seen from the research that AR technology is gradually integrated with culture, which can bring new breakthroughs in the transmission, preservation, creation and consumption of culture. This has played a better role in the dissemination and protection of other traditional Chinese culture and even intangible cultural heritage, further broadening the design space of cultural and creative products, and making new breakthroughs in the integration of science and technology and culture

Experimental demonstrations of high-Q superconducting coplanar waveguide resonators

We designed and successfully fabricated an absorption-type of superconducting coplanar waveguide (CPW) resonators. The resonators are made from a Niobium film (about 160 nm thick) on a high-resistance Si substrate, and each resonator is fabricated as a meandered quarter-wavelength transmission line (one end shorts to the ground and another end is capacitively coupled to a through feedline). With a vector network analyzer we measured the transmissions of the applied microwave through the resonators at ultra-low temperature (e.g., at 20 mK), and found that their loaded quality factors are significantly high, i.e., up to 10^6. With the temperature increases slowly from the base temperature (i.e., 20 mK), we observed the resonance frequencies of the resonators are blue shifted and the quality factors are lowered slightly. In principle, this type of CPW-device can integrate a series of resonators with a common feedline, making it a promising candidate of either the data bus for coupling the distant solid-state qubits or the sensitive detector of single photons.Comment: Accepted by Chinese Science Bulleti

Side-channel Attacks with Multi-thread Mixed Leakage

Side-channel attacks are one of the greatest practical threats to security-related applications, because they are capable of breaking ciphers that are assumed to be mathematically secure. Lots of studies have been devoted to power or electro-magnetic (EM) analysis against desktop CPUs, mobile CPUs (including ARM, MSP, AVR, etc) and FPGAs, but rarely targeted modern GPUs. Modern GPUs feature their special and specific single instruction multiple threads (SIMT) execution fashion, which makes their power/EM leakage more sophisticated in practical scenarios. In this paper, we study side-channel attacks with leakage from SIMT systems, and propose leakage models suited to any SIMT systems and specifically to CUDA-enabled GPUs. Afterwards, we instantiate the models with a GPU AES implementation, which is also used for performance evaluations. In addition to the models, we provide optimizations on the attacks that are based on the models. To evaluate the models and optimizations, we run the GPU AES implementation on a CUDA-enabled GPU and, at the same time, collect its EM leakage. The experimental results show that the proposed models are more efficient and the optimizations are effective as well. Our study suggests that GPU-based cryptographic implementations may be much vulnerable to microarchitecture-based side-channel attacks. Therefore, GPU-specific countermeasures should be considered for GPU-based cryptographic implementations in practical applications

Seawater Dielectric Measurements at L-Band with Latest Improvements

Recently, the dielectric constant of seawater at L-band was determined by employing a resonant cavity technique. A dielectric model function has been developed based on the measurement data and the model function has been used for retrieving the ocean salinity. The results indicate that additional accuracy is still needed to resolve the bias correlated with sea surface temperature. This paper reports the improvements that have been made recently for the development of a more accurate seawater dielectric model function. The additional measurements for the open ocean will be addressed in the paper

Deep Structured Feature Networks for Table Detection and Tabular Data Extraction from Scanned Financial Document Images

Automatic table detection in PDF documents has achieved a great success but tabular data extraction are still challenging due to the integrity and noise issues in detected table areas. The accurate data extraction is extremely crucial in finance area. Inspired by this, the aim of this research is proposing an automated table detection and tabular data extraction from financial PDF documents. We proposed a method that consists of three main processes, which are detecting table areas with a Faster R-CNN (Region-based Convolutional Neural Network) model with Feature Pyramid Network (FPN) on each page image, extracting contents and structures by a compounded layout segmentation technique based on optical character recognition (OCR) and formulating regular expression rules for table header separation. The tabular data extraction feature is embedded with rule-based filtering and restructuring functions that are highly scalable. We annotate a new Financial Documents dataset with table regions for the experiment. The excellent table detection performance of the detection model is obtained from our customized dataset. The main contributions of this paper are proposing the Financial Documents dataset with table-area annotations, the superior detection model and the rule-based layout segmentation technique for the tabular data extraction from PDF files