Functional Analysis of CCR4-NOT Complex in Pancreatic β Cell

Functional analysis of CCR4-NOT complex in pancreatic β cellPancreatic β cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Therefore, defects in pancreatic β cell function lead to hyperglycemia and diabetes mellitus. While extensive research has focused on signaling, transcriptional, and epigenetic regulation in β cells, how post-transcriptional mechanisms influence the β cell gene expression program is largely unknown. The carbon catabolite repression 4 (CCR4)–negative on TATA-less (NOT) complex (CCR4-NOT complex), a major deadenylase conserved in eukaryotes, catalyzes mRNA deadenylation which is the rate limiting step in mRNA decay pathway. The CCR4-NOT complex has been implicated in the development of metabolic diseases. However, whether the CCR4-NOT complex affects β cell function is not addressed. In this thesis, I aim to understand the importance of post-transcriptional regulation in β cells by generating mice lacking the Cnot3 gene, which encodes an essential CCR4-NOT complex subunit, in β cells. Suppression of CNOT3 in β cells caused β cell dysfunction and diabetes. This was associated with the decreased expression of β cell-specific genes and increased expression of genes specifically repressed in β cells, called “β cell disallowed genes”. By combining whole transcriptome and proteome analyses and subsequent validations using quantitative PCR (qPCR) and immunoblot analyses, I found that mRNA and protein expression patterns were largely different from normal β cells upon CNOT3 suppression, which was clearly relevant to the observed phenotypes. I also found that some β cell disallowed genes were stabilized in the absence of CNOT3, suggesting that their expression was maintained at low levels under the control of the CCR4-NOT complex. Together, this study uncovered mRNA deadenylation by CCR4-NOT complex as a novel molecular mechanism by which β cell identity and function are regulated.Okinawa Institute of Science and Technology Graduate Universit

堆砂による物理的目詰まりが土壌と貯水池の水理的性能に及ぼす影響

京都大学新制・課程博士博士(工学)甲第23172号工博第4816号新制||工||1753(附属図書館)京都大学大学院工学研究科都市社会工学専攻(主査)教授 角 哲也, 准教授 竹門 康弘, 准教授 Sameh Kantoush学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDGA

Avaliação da eficácia da carragenana e da goma arábica na manutenção da supersaturação do efavirenz

TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências da Saúde. Farmácia.O efavirenz é um fármaco pertencente à classe II do Sistema de Classificação Biofarmacêutica e compõe uma das principais associações preconizadas pelo Ministério da Saúde para o tratamento da infecção pelo HIV-1. Assim, sua baixa solubilidade em água é o principal fator limitante para melhor biodisponibilidade oral deste fármaco. Diversas tecnologias vêm sendo estudadas com o intuito de promover aumento na solubilidade dos fármacos pertencentes à essa classe. Um exemplo é a composição de dispersões sólidas, onde o fármaco é disperso em um material hidrofílico, geralmente inerte, sendo os polímeros frequentemente utilizados nesta composição. A λ-carragenana e a goma arábica são polímeros aniônicos e de origem natural amplamente utilizados pela indústria farmacêutica, mas pouco explorados na composição de dispersões sólidas. Neste estudo, avaliou-se a capacidade desses polímeros em manter a supersaturação do efavirenz, a qual foi gerada pelo método de solvent-shift. Observou-se que nenhum desses polímeros foi capaz de prolongar a supersaturação do fármaco, provavelmente devido a ocorrência de interações entre as cargas dos polímeros (aniônicos) e do fármaco (ácido fraco) no estado líquido, uma vez que a ocorrência de interações no estado sólido foi descartada. No entanto, ainda que não tenham sido eficazes em prolongar a supersaturação, a adição desses polímeros foi capaz de promover melhora significativa na solubilidade do fármaco. Mesmo assim, é necessário investigar se a substituição destes polímeros por outros, de natureza catiônica, pode acarretar em melhor desempenho na manutenção da supersaturação e/ou promover aumento ainda mais expressivo na solubilidade do efavirenz.Efavirenz is a drug that belongs to class II of the Biopharmaceutical Classification System and composes one of the main associations chosen by the Brazilian Ministry of Health to treat HIV type-1 infections. Thus, its low solubility in water is the major issue involved in achieving the greatest values to oral bioavailability. Many strategies is been used to promote higher solubility of drugs that belong to this class. Development of solid dispersions is one of these strategies, in which the drug is dispersed in a hydrophilic material, usually inert, and polymers are often chosen for this composition. Arabic gum and λ-carrageenan are anionic polymers commonly used by the pharmaceutical industry, but little explored in the composition of solid dispersions. In this study, the capacity of these polymers in maintaining a supersaturated solution of efavirenz, generated by the solvent-shift method, was evaluated. It was observed that none of these polymers were effective in extend the supersaturation of the drug, probably due to presence of interactions between the charges of these polymers (which are anionic) and the drug (a weak acid) on the liquid phase, once the occurrence of solid-state interaction was rejected. However, even that carrageenan and arabic gum were not able to maintain supersaturation state of the drug, the addition of these polymers was effective in promoting a significant increase in the solubility of this drug. Even so, it is necessary investigate if the replacement of these polymers by cationic polymers can lead to a better performance in prolonging the supersaturation or even promote a more expressive increases in efavirenz solubility

Functional Outcomes of Surgical Management for Spinal Epidural Masses in an Egyptian Tertiary Hospital

BACKGROUND: The spinal epidural space, covering the dural sac, is located along the posterior longitudinal ligament anteriorly, the ligamentum flavum and the periosteum of laminae posteriorly, and the pedicles of the spinal column by the intervertebral foramina containing their neural elements laterally. It could be affected variably by different types of diseases, either as primary lesions or as an extension from a disease process in the nearby tissues and organs. AIM: We aimed to present clinically and surgically patients with spinal epidural masses operated in the Neurosurgery Department of Cairo University Hospitals, Cairo, Egypt, along a time interval of one year. METHODS: In this prospective cohort study, we analysed motor deficits, sensory deficits, and bowel and bladder dysfunction. We have performed decompressive laminectomy on 19 patients with spinal epidural masses together with mass excision as long as the tumour was accessible, with or without fixation. RESULTS: All patients were radiologically assessed by MRI over the affected side of the spine. D10 was the commonest site in our study to be affected in 10 cases of our participants (23%), followed by D5, D7, and D12 each of them was affected in 6 cases (14%), in another word spinal segments by order of frequency to be affected were dorsal followed by lumbar spine. All patients included in this study (100%) showed an obvious improvement as regard pain and tenderness. CONCLUSION: Surgical interventions have improved the quality of life for our patients with spinal epidural masses

The effect of combining laser and nanohydroxy-apatite on the surface properties of enamel with initial defects

The aim of this study was to evaluate the effect of combining fractional CO2 LASER and nanohydroxy apatite on surface microhardness and color of enamel with initial defects. Two types of nano hydroxylapatite (nHAP) was prepared; Pure hydroxyapatite (nHA) and Fluoro hydroxyapatite (nFHA), Sixty extracted premolar teeth without visible caries or structural defects on enamel surface were used, immersed in 10 ml of a demineralizing solution for 2 weeks to create artificial white spot lesions, they were randomly allocated into two groups; Group 1: nHA, Group 2: nFHA, each group is then subdivided into 2 subgroups (A and B) where two different in vitroremineralization procedures have been performed, the first procedure utilizes a 10?wt% nHA aqueous slurries only, the second was first exposed to irradiation from a fractional CO2 laser then (nHAP) was applied. Microhardness and color were measured using a micro-Vickers hardness tester and spectrophotometer respectively. Laser treated teeth in both groups showed the highest mean hardness and lowest color difference where ?E was less than 3.3 units, in both tests the pure type of nanohydroxyapatite gave better results than the nanofluroapatite type. Nano-hydroxyapatite has remarkable remineralizing effects on initial lesions of enamel, certainly higher when combined with laser application

Highlight of Grid-connected PV systems in administrative buildings in Egypt

Solar energy applications are becoming increasingly common in Egypt. The abundant sunshine in Egypt, as well as the increasing competitiveness of solar energy systems including- but not limited to photovoltaic (PV), – predicts that these technologies could be weighed to be raised in Egypt.PV systems are installed on roof tiles or other parts of building structures to supplement grid utility, reduce electric bills, and provide emergency back–up energy. Moreover, they simultaneously reduce significant amounts of CO2 emissions. It is foreseen, a number of residential and public buildings in Egypt are using solar power to cut electric utility bills significantly. The approximately payback period to recover the investment costs for PV systems is up to about 5 years.  In addition, it is more economical to use PV system than grid utility systems. The two components that determine the total initial price of a grid- connected PV system are the modules and the balance of systems (BOS). The BOS includes different components such as mounting frames, inverters and site- specific installation hardware.The Government of Egypt (GOE) has endorsed the deployment of PV systems through three approaches. It started with a prime minister decree to install PV projects on one-thousand of the governmental buildings. This was followed by as an initiative called "Shamsk ya Masr", and finally the Feed-in Tariff (FiT) projects.Following the prime minster decree the Egyptian Electricity Holding Company (EEHC) and its affiliated companies took the lead to install PV systems at the top roof of their administrative buildings and interconnect these systems to the electricity network where the suitable locations have been selected for mounting them. About 90 PV systems have been already mounted with about a capacity of 9 MW. On the other hand, "Shamsk ya Masr" has considered energy efficiency (EE) so as to complement the PV systems, which will be installed on administrative buildings. Cost- effective EE measures should be implemented prior to or at the same time as implemented PV program. The amount of electricity that a PV system produces depends on the system type, orientation and the available solar resource. In 2014, the GOE issued the Feed-in Tariff program to further promote RE technologies in general and PV in particular. Egyptian Electric Utility and Consumer Protection Regulatory Authority (Egypt ERA) has set the regulations, promotion and awareness for PVs. This approach has been applied for administrative buildings as well.The paper highlights the impact of the previously mentioned mechanisms in deploying PV technologies through small scale projects. It also represents a cost- benefit analysis for the installed systems taking into account the measured value for PV parameters (kWh/kWp, PSH) and daily load profiles of the selected administrative buildings.</p

Ultra-wideband CMOS power amplifier for wireless body area network applications: a review

A survey on ultra-wideband complementary metal-oxide semiconductor (CMOS) power amplifiers for wireless body area network (WBAN) applications is presented in this paper. Formidable growth in the CMOS integrated circuits technology enhances the development in biomedical manufacture. WBAN is a promising mechanism that collects essential data from wearable sensors connected to the network and transmitted it wirelessly to a central patient monitoring station. The ultra-wideband (UWB) technology exploits the frequency band from 3.1 to 10.6 GHz and provides no interference to other communication systems, low power consumption, low-radiated power, and high data rate. These features permit it to be compatible with medical applications. The demand target is to have one transceiver integrated circuit (IC) for WBAN applications, consequently, UWB is utilized to decrease the hardware complexity. The power amplifier (PA) is the common electronic device that employing in the UWB transmitter to boost the input power to the desired output power and then feed it to the antenna of the transmitter. The advance in the design and implementation of ultra-wideband CMOS power amplifiers enhances the performance of the UWB-transceivers for WBAN applications. A review of recently published CMOS PA designs is reported in this paper with comparison tables listing wideband power amplifiers' performance

Computerised tomography scan in multi-drug-resistant versus extensively drug-resistant tuberculosis

Purpose: Multi-drug-resistant tuberculosis (MDR-TB) is simultaneously resistant to isoniazid and rifampin. Of course, this germ may also be resistant to other anti-tuberculosis drugs. Patients with extensively drug-resistant tuberculosis (XDR-TB) are also resistant to all types of fluoroquinolone and at least one of the three injectable medications: amikacin, clarithromycin, or kanamycin, in addition to isoniazid and rifampin. Therefore, the main objective of the current study was to evaluate and compare the computed tomography (CT) scan findings of MDR-TB and XDR-TB patients. Material and methods: In this comparative descriptive cross-sectional study 45 consecutive TB patients who referred to Masih Daneshvari Hospital, Tehran, Iran from 2013 to 2019 were enrolled. TB was diagnosed based on sputum smear and sensitive molecular and microbial tests. Patients were divided into two groups (MDR-TB and XDR-TB) based on two types of drug resistance. CT scan findings were compared for cavitary, parenchymal, and non-parenchymal disorders. The early diagnostic values of these factors were also calculated. Results: Findings related to cavitary lesions including the pattern, number, size of the largest cavity, maximum thickness of the cavity, lung involvement, number of lobes involved, and the air-fluid levels in the two patient groups were similar (p > 0.05). Parenchymal findings of the lung also included fewer and more nodules of 10 mm in the MDR-TB and XDR-TB groups, respectively. Tree-in-bud, ground-glass-opacity, bronchiectasis, cicatricial emphysema, and lobar atelectasis were similar in the two patient groups (p > 0.05). Findings outside the parenchymal lung, including mediastinal lymphadenopathy and pericardial effusion, showed no statistically significant difference between the MDR-TB and XDR-TB groups (p > 0.05). Parenchymal calcification was more common in the XDR group than in the MDR group (64.7% and 28.6%, respectively) with a significant difference (p = 0.01). Conclusions: CT scan findings in patients with XDR-TB are similar to those of patients with MDR-TB for cavitary, parenchymal, and non-parenchymal lung characteristics. However, patients with XDR-TB tend to have more parenchymal calcification and left-sided plural effusion. CT characteristics overlap between XDR-TB and those with MDR-TB. It can be concluded that CT scan features are not sensitive to the diagnosis