scholarly journals MPINet: Metabolite Pathway Identification via Coupling of Global Metabolite Network Structure and Metabolomic Profile

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Feng Li ◽  
Yanjun Xu ◽  
Desi Shang ◽  
Haixiu Yang ◽  
Wei Liu ◽  
...  
Keyword(s):  
Network Structure ◽  
Gas Chromatography Mass Spectrometry ◽  
Metabolomic Profile ◽  
Cancer Dataset ◽  
Unique Character ◽  
Metabolomic Data ◽  
Different Types ◽  
Application Fields ◽  
Experimental Technology

High-throughput metabolomics technology, such as gas chromatography mass spectrometry, allows the analysis of hundreds of metabolites. Understanding that these metabolites dominate the study condition from biological pathway perspective is still a significant challenge. Pathway identification is an invaluable aid to address this issue and, thus, is urgently needed. In this study, we developed a network-based metabolite pathway identification method, MPINet, which considers the global importance of metabolites and the unique character of metabolomic profile. Through integrating the global metabolite functional network structure and the character of metabolomic profile, MPINet provides a more accurate metabolomic pathway analysis. This integrative strategy simultaneously captures the global nonequivalence of metabolites in a pathway and the bias from metabolomic experimental technology. We then applied MPINet to four different types of metabolite datasets. In the analysis of metastatic prostate cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of the two type 2 diabetes datasets, we show that MPINet has the potentiality for identifying novel pathways related with disease and is reliable for analyzing metabolomic data. Finally, we extensively applied MPINet to identify drug sensitivity related pathways. These results suggest MPINet’s effectiveness and reliability for analyzing metabolomic data across multiple different application fields.

FUNCTIONAL STATUS AND ADAPTIVE POTENTIAL IN FOREIGN STUDENTS WITH DIFFERENT TYPES OF VEGETATIVE REGULATION DURING TUITION

2020 ◽  
pp. 118-126
Author(s):  
A.M. Satarkulova
Keyword(s):  
Heart Rate ◽  
Foreign Students ◽  
Autonomic Regulation ◽  
The Body ◽  
Functional Changes ◽  
Different Types ◽  
Type 3 ◽  
Adaptive Abilities

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.

scholarly journals Gundelia tournefortii: Fractionation, Chemical Composition and GLUT4 Translocation Enhancement in Muscle Cell Line

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3785
Author(s):  
Sleman Kadan ◽  
Sarit Melamed ◽  
Shoshana Benvalid ◽  
Zipora Tietel ◽  
Yoel Sasson ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Rapid Development ◽  
Muscle Cells ◽  
Flash Chromatography ◽  
Glucose Disposal ◽  
Gas Chromatography Mass Spectrometry ◽  
Glut4 Translocation ◽  
Toxic Concentrations ◽  
L6 Muscle Cells

Type 2 diabetes (T2D) is a chronic metabolic disease, which could affect the daily life of patients and increase their risk of developing other diseases. Synthetic anti-diabetic drugs usually show severe side effects. In the last few decades, plant-derived drugs have been intensively studied, particularly because of a rapid development of the instruments used in analytical chemistry. We tested the efficacy of Gundelia tournefortii L. (GT) in increasing the translocation of glucose transporter-4 (GLUT4) to the myocyte plasma membrane (PM), as a main strategy to manage T2D. In this study, GT methanol extract was sub-fractionated into 10 samples using flash chromatography. The toxicity of the fractions on L6 muscle cells, stably expressing GLUTmyc, was evaluated using the MTT assay. The efficacy with which GLUT4 was attached to the L6 PM was evaluated at non-toxic concentrations. Fraction 6 was the most effective, as it stimulated GLUT4 translocation in the absence and presence of insulin, 3.5 and 5.2 times (at 250 μg/mL), respectively. Fraction 1 and 3 showed no significant effects on GLUT4 translocation, while other fractions increased GLUT4 translocation up to 2.0 times. Gas chromatography–mass spectrometry of silylated fractions revealed 98 distinct compounds. Among those compounds, 25 were considered anti-diabetic and glucose disposal agents. These findings suggest that GT methanol sub-fractions exert an anti-diabetic effect by modulating GLUT4 translocation in L6 muscle cells, and indicate the potential of GT extracts as novel therapeutic agents for T2D.

EVALUATION OF THE MICROSTRUCTURE OF ZIRCONIUM DIOXIDE DURING ITS PROCESSING WITH VARIOUS TYPES OF DIAMOND TOOLS FOR FIXED PROSTHETICS IN DENTISTRY

2021 ◽  
pp. 57-64
Author(s):  
Богдан Романович Шумилович ◽  
Владимир Владимирович Ростовцев ◽  
Олеся Борисовна Попова ◽  
Светлана Николаевна Крюкова ◽  
Евгений Сергеевич Станиславчук ◽  
...  
Keyword(s):  
Zirconium Dioxide ◽  
Diamond Tool ◽  
Synthetic Diamond ◽  
Mechanical Action ◽  
Structure And Properties ◽  
Single Application ◽  
Diamond Tools ◽  
Ceramic Samples ◽  
Different Types

Цель: определить характер механического воздействия на структуру образцов из керамики на основе диоксида циркония при её обработке различными алмазными инструментами, и оценка пригодности инструмента с различным способом фиксации абразива при многократном применении для дальнейшего использования. Материал и методы. Материал исследования - образцы на основе метастабильного тетрагонального диоксида циркония, изготовленные в зуботехнической лаборатории и стандартизированные по толщине (1 мм). Оценку влияния механических напряжений на структуру и свойства исходного материала проводили методом перфорации образца алмазными борами, содержащими специальный абразив для обработки циркония. Исследовались боры с различным типом фиксации абразива: № 1 - алмазный бор c синтетическим абразивом, закрепленным по типу ERA; №2 - алмазный бор с композитной фиксацией абразива импортного производства; №3 - отечественный алмазный бор с нанесением и фиксацией абразива методом гальванопластики. Методом сканирующей электронной микроскопии получали изображения результатов механического воздействия боров на образцы диоксида циркония при однократном и пятикратном использовании бора. Исследование структуру самого алмазного инструмента на предмет его пригодности для дальнейшего использования. Результаты. При однократном применении все представленные боры сохраняют микроструктуру диоксида циркония, что позволяет в дальнейшем работать с образцами с использованием адгезивной техники. При пятой обработке боры № 3 не пригодными для работы с керамическим образцом, боры № 2 остаются частично пригодными, боры №1 сохраняют свою пригодность для дальнейшего использования. Заключение. Керамические образцы на основе на основе диоксида циркония изменяются в процессе механического воздействия, что зависит от вида применяемого бора и кратности его применения. Боры с синтетическим алмазным абразивом на базе ERA остаются работоспособными даже после их пятикратного применения, боры с композитной фиксацией абразива к пятому применению остаются относительно работоспособными, а боры с гальванопластической фиксацией абразива к пятому применению приходят в полную негодность Purpose: to determine the nature of the mechanical impact on the structure of samples made of ceramides based on zirconium dioxide when it is processed with various diamond tools, and to assess the suitability of tools with different methods of fixing the abrasive with multiple applications for further use. Material and methods. The material of the study is samples based on metastable tetragonal zirconium dioxide manufactured in a dental laboratory and standardized in thickness (1 mm). The influence of mechanical stresses on the structure and properties of the source material was evaluated by perforating the sample with diamond bores containing a special abrasive for processing zirconium. Bores with different types of abrasive fixation were studied: № 1-diamond boron with synthetic abrasive fixed by ERA type; № 2-diamond boron with composite fixing of imported abrasive; № 3 - edematous diamond boron with applying and fixing the abrasive by electroplating. Scanning electron microscopy was used to obtain images of the results of mechanical action of boron on samples of zirconium dioxide with a single and five-fold use of boron. Investigation of the structure of the diamond tool itself for its suitability for further use. Results. With a single application, all the presented burs preserve the microstructure of the samples, which makes it possible to preserve the suitability of the sample for further work using adhesive technology. At the fifth processing, boron № 3 is not suitable for working with a ceramic sample, boron № 2 remains partially suitable, boron № 1 retains its suitability for further use. Conclusion. Ceramic samples based on zirconium dioxide change in the process of mechanical action, which depends on the type of boron used and the multiplicity of its application. Bores with synthetic diamond abrasives based on ERA remain workable even after their five-time application, bores with composite Abrasive fixation remain relatively workable by the fifth application, and bores with electro plastic fixation of the abrasive by the fifth application become completely unusable

COEVALNESS OF INSECT TRACE FOSSILS AND TRACE-BEARING ROCKS, A CASE STUDY FROM THE PLIO?-PLEISTOCENE OF SW SPAIN

Palaios ◽  
2021 ◽  
Vol 36 (3) ◽  
pp. 115-121
Author(s):  
EDUARDO MAYORAL ◽  
JORGE F. GENISE ◽  
FRANCISCO J. RODRÍGUEZ-TOVAR ◽  
ANA SANTOS
Keyword(s):  
Fossil Record ◽  
Field Research ◽  
Sw Spain ◽  
Modern Age ◽  
Different Types ◽  
The Matrix ◽  
Time Gap

ABSTRACT Plio?-Pleistocene outcrops located at the southwestern edge of the Guadalquivir Basin in the area of Lepe (Huelva, Spain) provide an interesting example for studying the contemporaneity of traces with the rocks that contain them. Two different types of cells compatible with the ichnogenera Celliforma (Type 1) and Palmiraichnus (Type 2) were found in these outcrops. Their walls were constructed with the same material as the matrix and our first research in the area showed no extant bees producing them suggesting that they were coeval with the trace-bearing rocks. The case of the “Palmiraichnus-like” Type 2 cells was misleading because of its similarity with Palmiraichnus described from the region in the Canary Islands and Balearic Archipelago (Spain). Two determining features were vital in clarifying this first appearance. In the Palmiraichnus-like cells we found remains of a larval cocoon in one cell that could be dated by C14, giving a modern age. In the Celliforma-like cells more field research in the area allow us to observe extant bees nesting in these rocks in autumn. Ichnological literature show a few cases of asynchronies involving extant traces found mostly in Paleozoic and Mesozoic rocks. In contrast, the case presented herein indicates the time gap between the bearing rocks and the Lepe traces was shorter (ca. 12 ky–2.6 My), enhancing the similarity of traces and rocks and thus their potential coevalness. This case may serve as a warning about other potential examples in the fossil record in which relatively short asynchronies between traces and paleosols exist.

scholarly journals Honey dressing on a leg ulcer with tendon exposure in a patient with type 2 diabetes

2018 ◽  
Vol 2018 ◽  
Author(s):  
Ilaria Teobaldi ◽  
Vincenzo Stoico ◽  
Fabrizia Perrone ◽  
Massimiliano Bruti ◽  
Enzo Bonora ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Practice ◽  
Wound Dressing ◽  
Biological Properties ◽  
Healing Time ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Scientific Interest ◽  
Different Types

Summary Honey has been used as a wound dressing for hundreds of years by ancient civilizations, but only recently it has acquired scientific interest because of its relevant biological properties. In the last decade, indeed, several trials and observational studies have reported that, compared to conventional treatment (e.g. antiseptics, polyurethane film, paraffin gauze, soframycin-impregnated gauze), honey dressings seem to be better in healing time of different types of wounds, including diabetic foot ulcers. However, to date, information about a potential favorable biological effect of honey dressings on diabetic ulcers with exposed tendon are still scarce. Notably, foot or leg ulcers with exposed tendon are serious complications in patients with type 2 diabetes, as they are associated with an increased risk of adverse outcome. Therefore, the use of effective and safe treatments to bring these lesions to timely healing is very important in clinical practice. We herein report the case of a Caucasian adult patient with type 2 diabetes presenting a chronic right posterior lower limb ulcer (Texas University Classification (TUC) 2D) with tendon exposure that was successfully treated with honey dressings (glucose oxidase (GOX) positive with peroxide activity) in addition to systemic antibiotic therapy, surgical toilette and skin graft. In our case, the use of honey dressing for treating exposed tendon tissue probably allowed the timely wound healing. Although further studies are required, such treatment may constitute part of the comprehensive management of diabetic wounds, including those with tendon exposure, and should be considered by clinicians in clinical practice. Learning points: Honey has been used as a wound dressing for hundreds of years, but only recently it has acquired scientific interest for its biological properties. Several studies have documented that, compared to conventional dressings, honey seems to be better in healing time of different types of wounds, including diabetic foot ulcers. Our case report is the first to highlight the importance to use honey dressings also for the treatment of ulcers with tendon exposure in patients with type 2 diabetes, suggesting that this kind of dressing should be considered by clinicians in clinical practice.

scholarly journals Number of cases of type 1 and 2 diabetes diagnosed in Amapá between 2007 and 2012

2020 ◽  
pp. 18-26
Author(s):  
Kauê de Melo Souza ◽  
Lucas Facco ◽  
Amanda Alves Fecury ◽  
Maria Helena Mendonça de Araújo ◽  
Euzébio de Oliveira ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Genetic Factors ◽  
Sedentary Lifestyle ◽  
High Rate ◽  
Main Risk Factor ◽  
Food Education ◽  
Different Types

Diabetes mellitus is a succession of different types of disorders in metabolism that are characterized by causing a high rate of blood sugar. Because it is a disease with genetic factors type 1 diabetes has as main risk factor heredity, while type 2 diabetes besides these factors, includes obesity, high blood pressure, poor food education and advancing age. This study aims to show the number of cases of type 1 and 2 diabetes diagnosed in Amapá with the variables gender, age group, sedentary lifestyle, overweight, smoking, between 2007 and 2012. The data for the research were taken from the computer department of SUS, DATASUS (http://datasus.saude.gov.br). Type 1 and 2 diabetes mellitus (DM1 and DM2) are diseases that are tied to disturbances in production or in the efficient use of insulin. Smoking, as well as sedentary lifestyle and overweight are important risk factors for the development of DM2. Type 2 diabetes mellitus provides the development of various organic nerve lesions. In addition, DM2, through its chronicity, enables the development of retinopathies, nephropathies and other conditions negative to the individual’s health.

scholarly journals Characteristic-Aroma-Component-Based Evaluation and Classification of Strawberry Varieties by Aroma Type

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6219
Author(s):  
Lixia Sheng ◽  
Yinan Ni ◽  
Jianwen Wang ◽  
Yue Chen ◽  
Hongsheng Gao
Keyword(s):  
Solid Phase ◽  
Economic Value ◽  
Gas Chromatography Mass Spectrometry ◽  
Volatile Components ◽  
Solid Phase Micro Extraction ◽  
Ripe Fruit ◽  
Volatile Organic ◽  
Different Types ◽  
Aroma Components

The unique fruity aroma of strawberries, a popular fruit of high economic value, is closely related to all the volatile organic compounds (VOCs) contained within them. Despite extensive studies on the identification of VOCs in strawberries, systematic studies on fruit-aroma-related VOCs are few, resulting in a lack of effective standards for accurately distinguishing aroma types. In the present study, solid-phase micro extraction and gas chromatography–mass spectrometry were used to analyze and identify VOCs in the ripe fruit of each of the 16 strawberry varieties at home and abroad and to explore their characteristic aroma components and the classification of such varieties by aroma type. The results suggested remarkable variations in the types and contents of VOCs in different strawberry varieties, of which esters were dominant. The principal volatile components, consisting of four esters, three alcohols, one aldehyde, and one ketone, in 16 strawberry varieties were detected based on the absolute and relative contents of VOCs in the fruit. The characteristic aroma components in strawberries, containing nine esters, six aldehydes, and one alcohol, were determined based on the aroma values of different VOCs, and the characteristic aroma components were divided into five types further based on aroma descriptions. Sixteen strawberry varieties were finally divided into four aroma types, namely, peachy, pineapple, fruity, and floral, based on the contributions of different types. The results provided a basis and standard for classifying strawberries by aroma type, studying the hereditary regularity of the fruity aroma of strawberries, and improving aroma quality.

Abstract P270: Niacin Lowers Triglyceride-Rich Lipoprotein Apolipoprotein B-48 Secretion in Statin-Treated Type 2 Diabetics

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Jing Pang ◽  
Dick Chan ◽  
Sandy Hamilton ◽  
Vijay Tenneti ◽  
Gerald Watts ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Residual Risk ◽  
Gas Chromatography Mass Spectrometry ◽  
Cvd Risk ◽  
Triglyceride Rich Lipoprotein ◽  
Type 2 Diabetic

Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p<0.005). TRL apoB-48 concentration was lower with niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/L, p=0.03). ApoB-48 FCR was not altered with niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p=0.79). Basal apoB-48 PR (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p=0.04) and postprandial apoB-48 PR were significantly lower (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p=0.02) on niacin. Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.

scholarly journals Elevated Serum Sorbitol and not Fructose in Type 2 Diabetic Patients

2010 ◽  
Vol 5 ◽  
pp. BMI.S4530 ◽  
Author(s):  
Gregory M. Preston ◽  
Roberto A. Calle
Keyword(s):  
Elevated Serum ◽  
Fold Increase ◽  
Clinical Development ◽  
Gas Chromatography Mass Spectrometry ◽  
Diabetic Patients ◽  
Dose Selection ◽  
Type 2 Diabetic Patients ◽  
Early Proof ◽  
Proof Of Mechanism

Reductions in fasting serum fructose or erythrocyte sorbitol have been proposed as markers for early proof of mechanism in clinical development of aldose reductase (AR) inhibitors. However fructose is significantly impacted by meals and evaluation of erythrocyte sorbitol poses technical challenges. To more accurately assess the performance of these markers in biological samples, a gas chromatography-mass spectrometry assay was modified and validated. Serum was collected on three consecutive days from 13 healthy volunteers (HV) and 14 patients with type 2 diabetes mellitus (T2DM), and assayed for sorbitol and fructose using this assay. Serum fructose and sorbitol were relatively constant across the three days. Fasting fructose levels were comparable between the two groups (T2DM: 1.48 ± 0.49 mg/L; HV: 1.39 ± 0.38 mg/L, mean ± standard deviation, P = 0.61), but fasting sorbitol levels were significantly higher in diabetics (T2DM: 0.280 ± 0.163 mg/L; HV: 0.164 ± 0.044 mg/L, P = 0.02). Feeding resulted in a 5–6 fold increase in serum fructose levels, but only a 5%-10% increase in sorbitol. Only sorbitol remained significantly elevated pre- and post feeding in T2DM patients relative to HV. These data suggest that serum sorbitol may be a robust proof of mechanism biomarker and facilitate dose selection for clinical development of AR inhibitors.

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