The design and synthesis of nuclear localization signal (NLS) mimics

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references: leaves 28-29.Nuclear import of proteins is a carefully controlled process that is critical for cellular function and regulation. A protein is marked for nuclear entry by a nuclear localization signal (NLS), a peptide motif, which typically consists of one or two small clusters rich in basic amino acids (lysine or arginine). Transport occurs through pores that span the nuclear envelope by a receptor mediated, energy-dependent process. The goal of this study is to synthesize mimics of the NLS from aminoalkylated dihydroxybenzene fragments joined with linkers of various length, rigidity, and directional constraint. The project is part of a larger effort to understand the molecular recognition in nuclear protein import; its emphasis is to study the role of charge placement, orientation, and linker features in NLS recognition. Modeled after the NLS of the HIV-1 matrix protein, the proposed molecules can mimic the side chain placement of the NLS template. Candidates are evaluated for inhibition in an in vitro nuclear import assay. Inhibition was not observed for all the candidates despite the presence of positively charged clusters. The results suggest inhibition is not solely based on the presence of positive charge and confirms the hypothesis that other factors, such as orientation, are important

Sustainable development of peri-urban agriculture in South-East Asia project. Strategies of stakeholders in vegetable commodity chain supplying Hanoi market

The objectives of this specific study are: - To understand the situation of some vegetables areas supplying Hanoi, - To describe the flows supplying Hanoi vegetable market, - To understand the roles and relationships of the stakeholders of the commodity chains supplying Hanoi vegetable market, - To understand the advantages and constraints of each stakeholder. The study focuses on 4 product flows from 4 different supplying regions: - The safe vegetable flow from Dong Anh - the main safe vegetable supplier of supermarkets, stores of state-owned and private companies, canteens of schools and kindergardens. - The normal vegetable flow from Me Linh - the important vegetable supplier of Dich Vong wholesale market. - The vegetable flow from Gia lam- the main vegetable supplier of Bac Qua-Long Bien wholesale market. - The vegetable flow from Thanh Tri - the main vegetable supplier of Mo and Nga Tu So market. The relation between the producing areas and markets depends on the distance from producing region to markets, and the strategies as regards quality management. The safe vegetable channel is characterised by close relationship between stakeholders. The retailers are the stakeholders regulating the chain. They inform the stakeholders upstream the chain about the demands of the market and induce them to widen their scale in order to be more efficient. The biggest limit of this flow is that consumers have little confidence in the product quality. The demand for safe vegetables is increasing but producers cannot find regular outlets for their safe vegetables. In the normal vegetable flows, the assignment of the different actors is relatively clear; however, in almost all the three flows, the relationships among them are very loose as illustrated by the commodity chain from Me Linh to Hanoi. The participation of the farmers in the market is relatively frequent, especially for farmers from Thanh Tri and Gia Lam. The irregular involvement of many farmers in the market makes the flows less centralized. That is the reason why the information from the market to producing regions is very scattered. This affects the income of the stakeholders. Product quality is one of the factors connecting market and production levels. This is a tool to connect the actors participating in commodity chain. This is clearly expressed in the safe vegetable flow. Nowadays, in peri-urban districts, the pressure of urbanization and the cultivated area reduction have led the farmers to change their strategies. They choose vegetables giving more profitability and improve the quality to raise the income per area unit. On the other hand, to make customers willing to buy at higher prices, it is important to make them trust that the bought products have the quality mentioned on the labels. So it is necessary to help consumers to have means to check the products quality. The first step is to help actors building the standard of product quality. In any case, the state should act as a referee to make actors respect the regulations. (Résumé d'auteur

Adaptation options for agricultural cultivation systems in the South Central Coast under the context of climate change: Assessment Report.

This report highlights the results of consultation meetings and field visits organized by the Department of Crop Production and the CGIAR Research Program on Climate Change, Agriculture and Food Security in Southeast Asia in association with the three offices of the Department of Agriculture and Rural Development in the South Central Coast provinces of Binh Thuan, Ninh Thuan, and Khanh Hoa, in combination with consultation with the provinces in the conference: “Summing up crops production in the Winter-Spring season in 2018-2019, implementing the Summer-Autumn season, Main rice season in 2019 for the South Central Coast and the Central Highlands” held by the Ministry of Agriculture and Rural Development in Tam Ky City, Quang Nam Province on 12 April 2019. The meetings underlined the progress made by the provinces on climate change adaptation and mitigation, options for risk reductions in agricultural production, and conversion of crop structure as results of implementing the guidelines of the provinces and the Sector, especially, solutions for reservation and efficient and economic use of water under the context of climate change. This assessment report also reviews some issues related to the agricultural transformation of the region in adapting to risks caused by climate change. They are based on comparative advantages in terms of geographical location and market of key agricultural products. This report also points out shortcomings in using land and unreasonable points in managing and using important natural resources, especially water, and provides recommendations for the agricultural transformation and inter-regional connection with the Central Highlands and the Southeast. The team also introduces climate-related risks maps and adaptation plans (CS MAP) which is applied in the five provinces in the Mekong Delta Region, and hopes this solution’s expansion shall be supported by the Ministry of Agriculture and Rural Development and the provinces

The Impact of Pazopanib on the Cardiovascular System

Background: Pazopanib was FDA-approved in 2009 and has become the first line of treatment for renal cell carcinoma. Pazopanib is a tyrosine kinase inhibitor that slows tumor growth and angiogenesis by its action on vascular endothelial and platelet-derived growth factor receptors. Unfortunately, the efficacy of this drug is limited by its cardiovascular toxicity, including hypertension. Goal: Gain a greater understanding of the mechanism of these side effects in order to: 1) identify patients who are at higher risk; 2) develop strategies to mitigate cardiovascular toxicity; and 3) aid in future drug development. Hypothesis: The hypertensive effects of pazopanib are due to sustained activation of the renin-angiotensin-aldosterone system (RAAS). Methods: Wild type mice were dosed with 30 mg/kg of pazopanib twice daily for 42 days. Cardiac-specific beta-II spectrin knockout mice and flox control mice were dosed with 100 mg/kg once daily for 22 days, and an additional cohort was co-treated with Lisinopril (RAAS inhibitor). Blood pressures were monitored throughout treatment. Electrophysiological studies were conducted on isolated cardiomyocytes. Results: Pazopanib treatment led to an increase in blood pressure in all mice that received pazopanib. After 42 days, precursors to ventricular arrhythmias, such as delayed afterdepolarizations and prolonged action potential duration, were detected in cardiomyocytes. In mice that received 100 mg/kg of pazopanib, lisinopril co-treatment attenuated pazopanib-induced blood pressure rise and enlargement of the heart. Discussion: These results support our hypothesis regarding the involvement of the RAAS pathway, and validate the use of lisinopril for mitigating the hypertensive effects of pazopanib. Notably, the mechanism by which various tyrosine kinase inhibitors lead to hypertension may vary. Conclusion: Lisinopril is effective at attenuating the hypertensive effects of pazopanib, and it is worth determining whether the cardioprotective qualities of lisinopril are dependent upon blood pressure.Pelotonia Undergraduate Research Fellowship ProgramAcademic Major: Biochemistr

GIS-based modeling of rainfall-induced landslides using data mining-based functional trees classifier with AdaBoost, Bagging, and MultiBoost ensemble frameworks

The main objective of this study is to propose and verify a novel ensemble methodology that could improve prediction performances of landslide susceptibility models. The proposed methodology is based on the functional tree classifier and three current state-of-the art machine learning ensemble frameworks, Bagging, AdaBoost, and MultiBoost. According to current literature, these methods have been rarely used for the modeling of rainfall-induced landslides. The corridor of the National Road 32 (Vietnam) was selected as a case study. In the first stage, the landslide inventory map with 262 landslide polygons that occurred during the last 20 years was constructed and then was randomly partitioned into a ratio of 70/30 for training and validating the models. Second, ten landslide conditioning factors were prepared such as slope, aspect, relief amplitude, topographic wetness index, topographic shape, distance to roads, distance to rivers, distance to faults, lithology, and rainfall. The model performance was assessed and compared using the receiver operating characteristic and statistical evaluation measures. Overall, the FT with Bagging model has the highest prediction capability (AUC = 0.917), followed by the FT with MultiBoost model (AUC = 0.910), the FT model (AUC = 0.898), and the FT with AdaBoost model (AUC = 0.882). Compared with those derived from popular methods such as J48 decision trees and artificial neural networks, the performance of the FT with Bagging model is better. Therefore, it can be concluded that the FT with Bagging is promising and could be used as an alternative in landslide susceptibility assessment. The result in this study is useful for land use planning and decision making in landslide prone areas

Mobilizations And Strengthening For Radiating Hip And Anterior Knee Pain: A Case Report

Research presentation slides: Background and Purpose: The most common joint disorder in the United States is osteoarthritis (OA). Knee OA occurs in 10% men and 13% in women aged 60 years or older. Hip instability is commonly defined as hip joint unsteadiness that may cause pain. Joint restrictions and lack of hip strength may be associated with these two conditions. However, there is limited literature on hip strengthening and mobilizations on positive outcomes with hip instability. Therefore, the purpose of this case report was to utilize hip strengthening and mobilizations interventions on a patient with hip instability and knee OA. Case Description: The patient was a 71-year-old male who presented with radiating hip and knee pain. Lower extremity myotomes, range of motion (ROM), the Lower Extremity Functional Scale (LEFS), Single Limb Stance Test (SLST), and Plumb line test were used to evaluate improvements. Interventions implemented included lower extremity strengthening, stretching, manual therapy, and balance training. Outcomes: The patient attended 11 visits over 6 weeks. LEFS improved from 47/80 to 53/80 and SLST on the right leg with eyes open from 7 seconds to 10 seconds. Discussion: Although the patient showed relatively small improvements, he reported a reduction in difficulty and pain during his work and daily living activities throughout the 6-week rehabilitation process. The patient was educated on his posture and proper body mechanics, which may have contributed to his reduction in radiating hip and knee pain. Utilizing hip strengthening and mobilization interventions for treatment of hip instability and knee OA may have positive outcomes but requires further investigation. Future research should focus on lower extremity strengthening and manual therapy for knee OA and hip instability.https://dune.une.edu/pt_studcrpres/1005/thumbnail.jp

Mobilizations And Strengthening For Radiating Hip And Anterior Knee Pain: A Case Report

Background and Purpose: The most common joint disorder in the United States is osteoarthritis (OA). Knee OA occurs in 10% men and 13% in women aged 60 years or older. Hip instability is commonly defined as hip joint unsteadiness that may cause pain. Joint restrictions and lack of hip strength may be associated with these two conditions. However, there is limited literature on hip strengthening and mobilizations on positive outcomes with hip instability. Therefore, the purpose of this case report was to utilize hip strengthening and mobilizations interventions on a patient with hip instability and knee OA. Case Description: The patient was a 71-year-old male who presented with radiating hip and knee pain. Lower extremity myotomes, range of motion (ROM), the Lower Extremity Functional Scale (LEFS), Single Limb Stance Test (SLST), and Plumb line test were used to evaluate improvements. Interventions implemented included lower extremity strengthening, stretching, manual therapy, and balance training. Outcomes: The patient attended 11 visits over 6 weeks. LEFS improved from 47/80 to 53/80 and SLST on the right leg with eyes open from 7 seconds to 10 seconds. Discussion: Although the patient showed relatively small improvements, he reported a reduction in difficulty and pain during his work and daily living activities throughout the 6-week rehabilitation process. The patient was educated on his posture and proper body mechanics, which may have contributed to his reduction in radiating hip and knee pain. Utilizing hip strengthening and mobilization interventions for treatment of hip instability and knee OA may have positive outcomes but requires further investigation. Future research should focus on lower extremity strengthening and manual therapy for knee OA and hip instability

Estimating daily and diurnal variations of illicit drug use in Hong Kong: A pilot study of using wastewater analysis in an Asian metropolitan city

The measurement of illicit drug metabolites in raw wastewater is increasingly being adopted as an approach to objectively monitor population-level drug use, and is an effective complement to traditional epidemiological methods. As such, it has been widely applied in western countries. In this study, we utilised this approach to assess drug use patterns over nine days during April 2011 in Hong Kong. Raw wastewater samples were collected from the largest wastewater treatment plant serving a community of approximately 3.5 million people and analysed for excreted drug residues including cocaine, ketamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and key metabolites using liquid chromatography coupled with tandem mass spectrometry. The overall drug use pattern determined by wastewater analysis was consistent with that have seen amongst people coming into contact with services in relation to substance use; among our target drugs, ketamine (estimated consumption: 1400-1600. mg/day/1000 people) was the predominant drug followed by methamphetamine (180-200. mg/day/1000 people), cocaine (160-180. mg/day/1000 people) and MDMA (not detected). The levels of these drugs were relatively steady throughout the monitoring period. Analysing samples at higher temporal resolution provided data on diurnal variations of drug residue loads. Elevated ratios of cocaine to benzoylecgonine were identified unexpectedly in three samples during the evening and night, providing evidence for potential dumping events of cocaine. This study provides the first application of wastewater analysis to quantitatively evaluate daily drug use in an Asian metropolitan community. Our data reinforces the benefit of wastewater monitoring to health and law enforcement authorities for strategic planning and evaluation of drug intervention strategies