bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributory Factors in Traffic Congestions in the 2nd District of Albay, Philippines: Basis for Traffic Management Framework
Authors: Balla Domingo , Macabeo Manny
Published: March 2024

The global concern over traffic safety conditions has escalated due to the growing number of vehicles and pedestrians. Governments are putting significant efforts into implementing systems to alleviate and reduce traffic congestion. This study aimed to identify the factors contributing to traffic congestion in the 2nd district of Albay through quantitative research. It examined traffic congestion status in terms of Data Traffic Volume, Rush Hour, Classification of Vehicles, and Road Users. The research pinpointed key contributors to congestion, including insufficient road infrastructure, high vehicle density, rapid population growth, poor public transport, and road quality. A survey questionnaire was administered to personnel from Camalig MPS, Daraga MPS, and Legazpi City Police Station, as well as Public Safety Officers from the mentioned areas. The community, representing riders and commuters in the Poblacion area, also participated. The findings revealed that traffic congestion is prevalent in the 2nd district of Albay, primarily driven by traffic volume, rush hour, vehicles, and road users. As a result, the study emphasizes the need for a standardized traffic management framework to be implemented. This framework aims to coordinate stakeholders' perceptions regarding the factors contributing to traffic congestion, serving as a guide for effective traffic management in the region.
Compliance with Health Care Quality Standards in Government Accredited Hospitals in the Province of Albay
Authors: Altavano Ryan , Betiz Jeymar
Published: March 2024

Global health systems operate within ever-evolving local and global environments, influenced by various factors, including economic shifts, demographic dynamics, and technological advancements, among other variables. A study was conducted to determine the Health Care Quality Standards among the government-accredited hospitals in the province of Albay. Specifically, it identified the status of Health Care Quality Standards in the Province of Albay along with Policies and Procedures, Services, Human Resources, Budget, and Logistical Resources. It determines the Health Care Quality Standards among the government-accredited hospitals in the province of Albay regarding Patient Care Management, Human Resource Management, Information Management, and Safe Practice and Environment. The quantitative method was used to gather responses from respondents. The respondents of the study are personnel from the top and middle management and selected patients in the three hospitals. Hence, the study revealed that the Health Care Quality Standards among the government-accredited hospitals in the province of Albay are complied with based on the requirements set forth by the hospitals among the four components. Thus, it ensures that health services are responsive to the needs of targeted individuals and communities and encourages the role of communities as co-producers of health. The study recommends a sustainable healthcare management framework to strengthen and sustain comprehensive healthcare services, thus improving the community's quality of life.
Reading Proficiency Levels in English among the Intermediate Graders in Manito District SY 2022-2023
Authors: Obar Maria Jellie
Published: March 2024

This study aimed to determine the reading proficiency levels in English among intermediate graders in the Manito District, as well as the factors that affect these levels. The research design utilized for this study is descriptive-correlational, which describes the relationship between the factors and the reading proficiency in English of the intermediate graders. The four categories of factors that were explored in this study were pupil factors, teacher factors, home factors, and curriculum factors. The research findings indicated that pupil factors such as vocabulary, comprehension, and word recognition impact intermediate graders’ reading proficiency levels in English. Home factors such as parental involvement, access to reading materials, and socioeconomic status also contribute to the development of reading proficiency. Teacher and curriculum factors had no significant relationship with reading proficiency levels in English. By addressing the identified factors, parents can be provided with support, and pupils can be given reading materials to create a home learning environment that promotes literacy development. A contextualized illustrated short stories and workbook as supplementary reading material was developed to improve reading proficiency levels in English among intermediate pupils.
Estimación del área de inundación por tsunamis a partir del principio de conservación de energía
Authors:   , Estrada Carrasco María Fernanda
Published: March 2024

El análisis de la amenaza de tsunamis mediante enfoques probabilísticos es de vital importancia para la planificación urbana y planes de evacuación en zonas costeras. Sin embargo, el uso de modelos computacionales precisos implica costos prohibitivamente altos. En este contexto, este estudio se propone implementar y evaluar un modelo simplificado que se basa en el uso de perfiles topobatimétricos (multi-1D) para la generación de mapas de inundación por tsunami. El enfoque se construye a partir de la metodología de la ASCE (2022), que estima las profundidades de inundación a lo largo de perfiles topobatimétricos a partir de la cota máxima de inundación. Se propone modificar la metodología invirtiendo el proceso, calculando las distancias de inundación máxima a partir de las profundidades de inundación en la línea de costa con el objetivo de estimar mapas de inundación con un muy bajo costo computacional. La metodología modificada se implementó en tres ciudades de la Reión de Valparaíso y se comparó con simulaciones de tsunami completas, que abordan la inundación desde la zona de ruptura hasta el punto de runup, integrando las ecuaciones no lineales de aguas someras. Durante esta evaluación, se identificaron limitaciones relacionadas con las pendientes del perfil topográfico cercanas a la línea de costa, las cuales contribuyen a la sobrestimación de las inundaciones. En respuesta, se proponen ajustes a la metodología para abordar estas limitaciones y mejorar la precisión. Además, la metodología modificada se calibra usando los resultados de las simulaciones completas de tsunami, lo que permitió reducir los errores en el cálculo de área de inundación en las ciudades de estudio a menos del 10%. En conclusión, la metodología propuesta es aplicable y ofrece errores acotados, lo que la hace adecuada para la construcción de mapas de inundación. Su capacidad para reducir el tiempo computacional de simulaciones de meses a horas la posiciona como una opción viable para un enfoque probabilístico. Además, ofrece una alternativa eficiente para explorar escenarios relacionados con cambios en el nivel del mar.
Discapacidad y utilización de servicios de salud y rehabilitación en la comuna de Cerro Navia
Authors:   , Fowler Madeline
Published: March 2024

Objetivos: Las personas con discapacidad (PcD) en Chile utilizan más servicios de salud que las sin discapacidad (PsD). Sin embargo, PcD se enfrentan con mayores barreras a la atención. El estudio actual tiene como objetivo describir y analizar el uso de servicios de salud y rehabilitación en los últimos 12 meses para adultos con y sin discapacidad en Cerro Navia y sus factores asociados. Métodos: Se realizó un estudio transversal con datos secundarios del Primer Estudio Comunal de Discapacidad en Cerro Navia, una comuna de alta vulnerabilidad en Chile. Se crearon modelos de regresión logística para estimar el efecto de factores asociados con la utilización en PcD y PsD. Resultados: PcD presentan mayor prevalencia de utilización de servicios de salud en los últimos 12 meses que PsD, y ambos presentan mayores tasas de utilización que al nivel nacional. La presencia de más comorbilidades, depresión o ansiedad, y utilización de un dispositivo de apoyo se asoció con mayor utilización de servicios de salud en PcD. Depresión o ansiedad, limitación física o de movilidad, dificultad con barreras en espacios públicos para socializar, y nivel educacional aparte de “básica completa” se asociaron con mayor uso de rehabilitación en PcD. Finalmente, dificultad con barreras en espacios públicos para socializar se asoció con menor frecuencia de rehabilitación. Conclusión: Estos hallazgos pueden motivar profesionales a identificar condiciones de salud mental, dispositivos de apoyo, y accesibilidad de espacios públicos como potenciales focos de intervención para apoyar la salud de PcD en comunas vulnerables como Cerro Navia.
Tooth loss and depression: epidemiological evidence of causality from the Chilen population
Authors:   , Ortuño Borroto Duniel
Published: March 2024

En este estudio, se evaluó la asociación entre pérdida dentaria y depresión con diferentes diseños y poblaciones en Chile. En el marco muestral MAUCO se realizó un análisis longitudinal, con regresiones logísticas binarias y multinomial. Se encontró que los individuos con 19 o menos dientes podrían tener mayor riesgo de depresión, con diferencias entre hombres y mujeres. El edentulismo se asoció a mayor incidencia de depresión a los 4 años de seguimiento, y con mayores niveles de severidad de los síntomas depresivos en mujeres. En los individuos edéntulos al inicio del estudio, el riesgo para cada una de las comparaciones "leve vs no", "moderada vs no", ”moderada severa vs no" y ”severa vs no" fue mayor comparado con aquellos con ≥ 20 dientes. Utilizando el marco muestral ENS 2016-2017, se realizó un análisis de mediación para evaluar el rol de las funciones orales en la asociación entre pérdida de dientes, incluyendo anteriores, y depresión en individuos de 15 años o más. El deterioro de las funciones orales fue un mediador en la asociación entre la pérdida de dientes y el autorreporte o la sospecha de depresión. La sensación de incomodidad al hablar o la incomodidad al comer fueron los mediadores más significativos.
Total Knee Arthroplasty in a Patient with Bilateral Fused Hip due to Seronegative Arthritis: A Case Report
Authors: Chaudhari Tushar , Solunke Swaroop , Nair Abhishek , Gundecha Pratik
Published: March 2024

Degenerative changes in other joints secondary to hip fusion occur due to changes in the relative biomechanical forces acting on those joints. At present, there are no standard protocols to aid the decision-making process of joint replacement surgery in patients with hip fusion due to secondary arthritis causes. Each patient requires tailored management planned by the surgeon to optimise treatment plan and achieve the highest degree of functional improvement. Total Knee Arthroplasty (TKA) is a welldocumented, common, and cost-effective procedure in the management of morbidities associated with joint degeneration due to wear and tear of the cartilage. TKA in patients with hip fusion is relatively rare, and there are few case reports and studies indicating a standardised approach and treatment protocols for the same. In this case report, TKA due to symptomatic knee arthritis in a patient with a 15-year history of spontaneous bilateral hip fusion due to seronegative arthritis is discussed. Postoperatively, the patient’s condition was stable, with good Range Of Motion (ROM) at the knee and without aseptic features as determined by recent radiologic investigations.
On Some Recurrence Relations Connected with Generalized Fermat Numbers and Some Properties of Divisibility for these Numbers
Authors: Ipek Ahmet
Published: March 2024

As a result of nice properties of Fermat numbers and their interesting applications, these numbers have recently seen a variety of developments and extensions. Within this framework, this paper contributes. The purpose of this paper is to obtain some recurrence relations connected with generalized Fermat numbers \(\mathcal{F}\)\(\mathcal{n}\) = \(\mathcal{a}\)2\(\mathcal{n}\) + 1 for \(\mathcal{a}\); \(\mathcal{n}\) \(\epsilon\) \(\mathbb{Z}\) and \(\mathcal{n}\) \(\geq\) 0 and as a result of these recurrent relations, to get some properties of divisibility for generalized Fermat numbers.
Chemical and Functional Properties of Pasting Producing from Plantain, Mesquite Seed Flours and Rice Bran
Authors: Emojorho Ernest Eguono , Udeh Charles Chiedu , Anene Maryann Nkemakonam , Aphiar Agnes , Nwosu Adaora Ngozi , Ochimana Titus Onucheojo
Published: March 2024

The goal of the study was to see whether plantain flour could be blended with rice bran and mesquite flour to produce composite flour that might be included in the diet of some people with health issues. According to the findings, the chemical composition of the top-rated enriched composite flour showed 10.41 to 14.70 % moisture, 3.37 to 11.70 % protein, 62.79 to 80.74 % carbohydrate, 1.35 to 1.71 % ash, 3.68 to 0.37 % fibre and 0.30 to 0.58 % fat. Mineral composition showed calcium 3.08 to 4.00 mg/100g, potassium 5.03 to 6.65 mg/100g, zinc 0.038 to 0.053 mg/100g, iron 0.029 to 0.038 mg/100g and sodium 0.51 to 0.80 mg/100g. Functional properties showed swelling capacity 3.85 g/g to 4.26 g/g, bulk density 0.40 to 0.44 g/cm3, solubility 6.94 to 17.35 %  , water absoption capacity 58.00 to 59.80 %.  Therefore, adding up to 30% of rice bran and mesquite flour to the composite flour mix would enhance its nutritional value.
Evaluation of Germplasm for Seedling Stage Salinity Tolerance in Rice (Oryza Sativa L.)
Authors: Pranaya J , Roja V , Rao P Venkata Ramana , Rani M Girija , Ramesh D
Published: March 2024

Salinity affects rice growth and development. Mostly all growth stages from germination to maturity are affected by the salinity. Among all the stages, seedling and reproductive stages are the most sensitive stages to salinity, which results in considerable yield losses. Development of salt tolerant varieties is most feasible approach for improving the production of rice in salt affected soils as seedling stage is necessary for better crop improvement. Overall 76 rice germplasm lines were evaluated at RARS, Maruteru, West Godavari, A.P during Kharif 2020 for salinity tolerance at seedling stage. The different parameters like root length, shoot length, shoot Na+ content, shoot  K+ content, Na+/K+ content and SIS (salt injury score) at 10th and 16th day were studied under hydroponics subjecting to electrical conductivity of 6 and 12 dSm-1, at a pH of 5.0. Salinity scoring during seedling stage was noted as per the modified standard evaluation score (SES) of IRRI, revealed that four genotypes FL478, MTU1290, MTU1061 and MCM109 as tolerant, 23 genotypes as moderately tolerant, 42 were susceptible and remaining seven genotypes namely BPT2848, BPT3140, Hallabhatta, MTU1271, MTU1121, BPT2846 and Krishnahamsa are highly susceptible. The phenotypic study signified that Na+/K+ ratio is the key note for salinity tolerance.
Soil Nutrient Based Mobile App for Crop-wise Fertilizer Recommendation: A “SoilNutro” Application
Authors: Birla Lalit , Lal S. B. , Chaturvedi K K , Farooqi Mohammad Samir , Sharma Anu , Bharadwaj Anshu , Naik Banoth Jagdish , Patel Lal Dhari
Published: March 2024

Agriculture is the most important occupation for most Indian families in India. A relatively larger Indian population lives in rural areas. The majority of rural people depend on agriculture for their livelihood. Therefore, it is the responsibility of the government and information technology to provide relevant information related to agricultural technologies for better crop production so that farmers can feed India's growing population. Soil fertility refers to the ability of soil to sustain agricultural plant growth. The farmer needs to know the soil fertility of soil of their farm holding that soil is either capable of better crop production or not. Therefore, it is very necessary to know soil health for increasing crop production and reduce the cost of production. The available nutrient content is an important parameter to determine soil health. Nitrogen (N), Phosphorus (P), and Potassium (k) are major nutrients that are needed in the crop field with large amounts in the form of fertilizers. In the technology front, we all are aware that the mobile phones have become one of the major sources of communication technologies in developed and developing countries in the last few decades. With the realization of this fact about the use of smartphones, the development of a mobile application called ‘SoilNutro’ has been done. SoilNutro app has been developed to achieve the nutrient status of a specific location of users. It also recommends the combination of fertilizer doses required for crops based on current nutrient status for efficient use of various fertilizers. ‘SoilNutro’ app has been developed using minimum SDK version of API 24: Android 7 on the android platform. The developed Android application 'SoilNutro' will be of great use to provide farmers with a specific location of nutrients and recommend crop-wise fertilizer based on the available nutrient.
Review of Abstinence Syndrome: A Comprehensive Analysis of Current Practices and Recommendations
Authors: Siddhartha Lolla , Charan Jemini , Saraswathi Nanna , Deepika Todima , Shireesha Kolupula , Rachana Sunkari
Published: March 2024

Alcohol use disorder is frequently accompanied with the diverse and sometimes fatal consequence of alcohol withdrawal syndrome (AWS). Many patients with AUD may develop AWS during their Emergency Department stay, and AUD is one of the top causes of death worldwide. This study summarizes the etiology, epidemiology, and emergency management of Alcohol Withdrawal Syndrome and Alcohol Use Disorder.The influence of AWS on the therapy of ED is highlighted, along with its temporal course. Once AWS is diagnosed, the most common therapy is still symptom- triggered benzodiazepine injection; however, patients who have significant medical or psychiatric comorbidities or are about to be discharged may not be good candidates for this approachIn these circumstances, emergency department doctors can consider employing alternative regimens based on state-of-the-art anticonvulsants or shorter barbiturate durations. For clinical practice, specific treatment procedures are described. Lastly, in addition to managing acute patients' AWS, emergency physicians also need to provide the groundwork for effective AUD therapy. A strategy for the patient with AUD's disposition is offered.
An Economic Analysis of Cropping Pattern, Marketing Chains and Food Security Status of Farm Households in Rural-Urban Interface of Bengaluru, India
Authors: Ashwini B. C.  , Nayana, H. N.  , Umesh K. B. , Gaddi, G. M.  , Ramu, M. S.
Published: March 2024

The study was taken in rural-urban interface of Bangalore to examine the participation of households in different marketing chains and production diversification on food insecurity status among selected households. Herfindahl-Hirschman (HH) index was used to estimate the crop diversification in both north and south transect. To analyze the household food security status, Food Security Index (FSI) was employed. The results indicated that, south transect was more crop diversified than north transect and the food security status was also high in south transect compared to north transect, hence crop diversity is having positive influence on household food security status in the study area. Among the different crops cultivated in the study area, percentage of area under ragi was the highest followed by maize in both the transects. In case of both maize and ragi, majority of the farm households sold their produce in the regulated markets. But ragi producers realized higher price (Rs. 2350/q) in farmers market (producer to consumers) and maize producers realized higher price (Rs. 1550/q) in regulated markets. Food security can be enhance through crop diversification and better price realization can be achieved by encouraging to adopt direct marketing or selling farmers produce through regulated markets.
Design and Development of an Android-based Remote Cardiac Monitoring Device for Continuous Real-time ECG Signal Acquisition, Transmission, and Analysis
Authors: Adeolu Olawuni , Abayomi Babalola
Published: March 2024

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, necessitating innovative solutions for early detection and continuous monitoring. This research aims to develop an Android-based remote cardiac monitoring device for real-time electrocardiogram (ECG) signal acquisition, transmission, and analysis. The system comprises hardware for acquiring ECG signals, algorithms for processing and machine learning models for anomaly classification. The hardware unit captures ECG data using electrodes and sensors. The signals are filtered, processed, and transmitted to the cloud infrastructure enabling real-time monitoring and analysis. Machine learning models including support vector machines, ensemble methods and Artificial neural networks are trained on ECG datasets to classify signals and detect cardiac abnormalities. Comprehensive testing validates the system's capabilities in real-time signal acquisition, processing, anomaly detection and data transmission. The integration of hardware, algorithms and machine learning enables round-the-clock monitoring of cardiac activity, facilitating prompt interventions and improved patient outcomes. This affordable and user-friendly system demonstrates potential for enhanced accessibility and effectiveness of preventive cardiac care.
Assessment of Variability for Herbage Yield and Its Component Traits in Genotypes of Kalmegh (Andrographis paniculata) (Burm. f.) Wall. ex Nees
Authors: Dharshini M. S. , Geetha K. A.
Published: March 2024

The study was conducted during the 2019 Kharif with the goals of estimating variability, heritability and genetic advance among all the genotypes in a Randomized Block Design with three replications. Based on variability studies, it could be concluded that the characters viz., plant height (9.93% & 81.81%), leaf width (15.06% & 80.05%), leaf area (10.62% & 81.91%), number of secondary branches (17.29% & 56.59%), total length of primary branches per plant (15.19% & 75.81%), canopy spread (12.81% & 75.33%), length of internodes (13.59% & 79.01%), angle of primary branch (66.32% & 94.01%),  all the yield parameters except leaf dry matter content (9.33% & 69.82%) and stem dry matter content (6.82% & 59.22%) and all the chemical parameters had sufficient amount of variability, high heritability respectively. Therefore, simple selection methods will be more effective for improvement of these characters.
Taylor Mason e possibilidades de representação
Authors: Ferreira Schreiner Natália , Roso Adriane , Goya Pierry Larissa , Porto Giacomelli Daniela
Published: March 2024

A expressão de gênero não binária refere-se às pessoas transgêneras que não se identificam com o gênero designado ao nascer e nem como integrantes das categorias homem e mulher, parcial ou totalmente, sendo termo guarda-chuva que contempla outras categorias de gênero. Consideramos as mídias como veículos de (re)produção de representações sociais sobre a população LGBTQIA+ e que a primeira personagem não binária na grande mídia foi Taylor Mason, da série Billions. Sob a perspectiva da Psicologia Social Crítica, da Teoria das Representações Sociais, dos Estudos de Gênero e do Feminismo Interseccional, objetivamos explorar as relações entre as personagens diante da introdução de Taylor. Especificamente, analisar como se dá a narrativa de gênero na série. Concluímos que Billions apresenta possibilidades de ancoragem e objetivação para construção de representações sobre não binariedade e que esta é tratada com espontaneidade, dando importância à personagem para além das questões de gênero.
Pode a pessoa não binária ocupar espaços?
Authors: Grassine Felipe
Published: March 2024

A não binaridade é uma luta muito cara para mim e por isso, num sopro de coragem me coloco nesse texto narrativo com três relatos de agressão que sofri ao longo desse processo de viver/morrer. Me intenciono nessa escrita para colaborar com presentes e futuras reflexões sobre como a binaridade aliada a regulação de gênero, torna corpos transgêneros abjetos. Na minha pela, foi nela que senti a mão de um ‘cistêma’ (cisgênero + sistema) pesando, vigiando e punindo, e relembrando esses ocorridos crio forças para continuar por uma luta de sobrevivência e de ajudar na nossa expectativa de viver enquanto corpos dissidentes. A escrita deriva da minha dissertação e usa métodos e referenciais narrativos/ilustrativos para geração de reflexão dentro do campo do design e dos estudos de gênero.
Além dos binarismos
Authors: Pombo Mariana Ferreira
Published: March 2024

Este artigo pretende, inicialmente, analisar criticamente o paradigma da diferença sexual, já em crise, como defende Paul B. Preciado, denunciando seus efeitos violentos sobre os sujeitos que não se adequam em suas categorias binárias. Em seguida, almeja se debruçar sobre a não binariedade, positivando sua potência subversiva tanto do ponto de vista individual, no sentido da possibilidade de novos devires e trilhamentos subjetivos, como do ponto de vista político, no sentido da transformação do regime de inteligibilidade social dos corpos.
Prenatal diagnosis using cell‐free nucleic acids in maternal body fluids: A decade of progress
Authors: Maron Jill L. , Bianchi Diana W.
Published: February 2007

The ability to detect cell‐free fetal nucleic acids in pregnant women has greatly evolved over the past decade. Dozens of papers have explored the biology, kinetics, and clinical significance of both cell‐free fetal DNA and mRNA in the maternal circulation. As a result, our overall understanding of fetal nucleic acid trafficking has expanded. To date, two applications, gender determination and fetal RhD status, have translated into clinical medicine. However, with advanced molecular techniques such as mass spectrometry, real‐time quantitative polymerase chain reaction, and gene expression arrays, the ease with which fetal genes can be detected within the mother has greatly improved. Newly identified placental and fetal mRNA transcripts as well as an epigenetically modified placental DNA marker, maspin, have universal applicability. Global expression analyses of fetal mRNA in both amniotic fluid and blood provide new insights into fetal development and pathology. Prenatal diagnosis is poised to evolve from detection of aneuploidy to detection of deviation from normal development, which should provide novel opportunities for fetal treatment. © 2007 Wiley‐Liss, Inc.
Ratiometric and Near‐Infrared Molecular Probes for the Detection and Imaging of Zinc Ions
Authors: Carol Priya , Sreejith Sivaramapanicker , Ajayaghosh Ayyappanpillai
Published: February 2007

The detection and imaging of Zn2+ in biological samples are of paramount interest owing to the role of this cation in physiological functions. This is possible only with molecular probes that specifically bind to Zn2+ and result in changes in emission properties. A “turn‐on” emission or shift in the emission color upon binding to Zn2+ should be ideal for in vivo imaging. In this context, ratiometric and near‐IR probes are of particular interest. Therefore, in the area of chemosensors or molecular probes, the design of fluorophores that allow ratiometric sensing or imaging in the near‐IR region is attracting the attention of chemists. The purpose of this Focus Review is to highlight recent developments in this area and stress the importance of further research for future applications.
An Improved Ruthenium Catalyst for the Environmentally Benign Amination of Primary and Secondary Alcohols
Authors: Hollmann Dirk , Tillack Annegret , Michalik Dirk , Jackstell Ralf , Beller Matthias
Published: February 2007

The N‐alkylation of amines in the presence of different ruthenium catalysts generated in situ was investigated. Among the various catalysts tested, the combination of [Ru3(CO)12] and N‐phenyl‐2‐(dicyclohexylphosphanyl)pyrrole showed the best performance. By applying this novel catalyst, a variety of functionalized alcohols and amines were converted into the corresponding secondary amines in high yield.
Gender difference in the pharmacokinetic interaction between oral warfarin and oxolamine in rats: inhibition of CYP2B1 by oxolamine in male rats
Authors: Zhu Xuan , Lee Dae Y. , Shin Wan G.
Published: February 2007

The possible reason for the significantly greater AUC of oral warfarin with oral oxolamine in male Sprague−Dawley rats was evaluated. After oral administration of warfarin at a dose of 2 mg/kg to male rats with oxolamine at doses of 10 and 50 mg/kg, the AUC values of warfarin were significantly greater than the controls (254 and 330 versus 180 µg h/ml). However, the AUC values of warfarin were not affected by oxolamine in female rats. This could be due to inhibition of CYP2B1, 2C11 and 3A2 by oxolamine in male rats, since warfarin was metabolized via CYP1A1, 2B1, 2C6, 2C11 and 3A2 in rats and CYP2B1 is male dominant, and CYP2C11 and 3A2 are male specific. Therefore, phenytoin, torasemide and clarithromycin (mainly metabolized via CYP2B1/2, 2C11 and 3A2 in rats, respectively) were administered intravenously to male rats with or without oral oxolamine. After oral oxolamine at doses of 10 and 50 mg/kg, the AUC of phenytoin was significantly greater (1280 and 1640 versus 938 µg min/ml), however, the AUC values of torasemide and clarithromycin were independent of oxolamine. The above data suggest that the significantly greater AUC of oral warfarin with oral oxolamine could be due to inhibition of CYP2B1/2 by oxolamine in male rats. Copyright © 2007 John Wiley & Sons, Ltd.
Recent advances in pharmacokinetic modeling
Authors: Ahmad Alaa M.
Published: February 2007

A major part of the science of pharmacokinetics is the modeling of the underlying processes that contribute to drug disposition. The purpose of pharmacokinetic models is to summarize the knowledge gained in preclinical and clinical studies at various stages in drug development and to rationally guide future studies with the use of adequately predictive models. This review highlights a variety of recent advances in mechanistic pharmacokinetic modeling. It is aimed at a broad audience, and hence, an attempt was made to maintain a balance between technical information and practical applications of pharmacokinetic modeling. It is hoped that drug researchers from all disciplines would be able to get a flavor of the function and capacity of pharmacokinetic modelers and their contribution to drug development. While this review is not intended to be a technical reference on modeling approaches, the roles of statistical applications and population methodologies are discussed where appropriate. Copyright © 2007 John Wiley & Sons, Ltd.
Role of plasma as activator and cofactor in phosphorylation catalyzed by protein kinase C
Authors: Kang Jeong‐Hun , Asai Daisuke , Oishi Jun , Kawamura Kenji , Toita Riki , Jiang Yuhua , Mori Takeshi , Niidome Takuro , Katayama Yoshiki
Published: February 2007

The purpose of this study was to investigate whether plasma can influence the phosphorylation of protein kinase C (PKC). Lysate samples were prepared from normal skin or melanoma tissue and were reacted with a PKC peptide substrate in the presence or absence of plasma. In normal skin tissue lysates, the phosphorylation rates were much lower than those in melanoma tissue lysates. However, the level of phosphorylated peptide was increased in both normal skin and melanoma tissue lysates if plasma was present. Phosphorylation rates in the samples taken from the centre of B16 melanoma tissue were lower than those in samples taken from the edge. Moreover, addition of activator and/or cofactors (diacylglycerol, phosphatidylserine and/or Ca2+) of PKC, or plasma to the lysates contaminated by plasma had no effect on phosphorylation rates for the peptide substrate. These results indicate that plasma can play a role of activator and cofactor for substrate phosphorylation. Copyright © 2007 John Wiley & Sons, Ltd.
Is patent foramen ovale closure effective in reducing migraine symptoms? A controlled study
Authors: Kimmelstiel Carey , Gange Christopher , Thaler David
Published: February 2007

Objectives:

We investigated the prevalence of migraine in patients with patent foramen ovale (PFO), and the effect of PFO closure on migraine symptoms and medications.

Background:

Studies have shown an association between migraine and PFO. Data have recently suggested a reduction in migraine symptoms following PFO closure. Most of these studies had no controls.

Methods:

Subjects were divided into three groups: No PFO (Controls, n = 65), PFO with no intervention (“Open PFO”, n = 63), and PFO treated with percutaneous closure (“Closed PFO”, n = 41). We measured the frequency, severity, and impact of migraine on quality of life employing MIDAS scores. Comparisons were made preceding and 90 days after either transesophageal echocardiography (Controls and “Open PFO”) or PFO closure (“Closed PFO”). We compared the use of abortive medications between the two time points.

Results:

Migraine, especially with aura, was more prevalent in both PFO groups (P < 0.05). Migraine frequency was reduced by 83% in Closed PFO compared with 0% of Open PFO and 10% of control patients (P < 0.0001). Migraine severity and MIDAS scores were reduced by PFO closure when compared to the other two groups (P < 0.0001, P = 0.035 respectively). Reduction in abortive medications was noted in 71% after closure, 5% of Open PFO, and 10% of Controls (P < 0.001).

Conclusions:

In this controlled study, migraine, especially with aura, is more frequent in subjects with PFO. PFO closure is associated with a reduction in migraine frequency and severity, as well as an improvement in MIDAS scores. PFO closure was associated with a significant reduction in the use of abortive medications. © 2007 Wiley‐Liss, Inc.
Recurrent very late stent thrombosis after bare‐metal stent implantation
Authors: Saito T. , Asajima H.
Published: February 2007

Very late bare‐metal stent thrombosis occurring beyond 1 year after stenting is uncommon. Although much attention has been paid for late stent thrombosis, long‐term outcome of patients who developed late stent thrombosis is not clear. We report a case of recurrent very late stent thrombosis after bare‐metal stent implantation. © 2007 Wiley‐Liss, Inc.
Long Synthetic Nanotubes from Calix[4]arenes
Authors: Organo Voltaire G. , Sgarlata Valentina , Firouzbakht Farhood , Rudkevich Dmitry M.
Published: February 2007

We report the synthesis and encapsulation properties of long (up to 5 nm) molecular nanotubes 1–4, which are based on calix[4]arenes and can be filled with multiple nitrosonium (NO+) ions upon reaction with NO2/N2O4 gases. These are among the largest nanoscale molecular containers prepared to date and can entrap up to five guests. The structure and properties of tubular complexes 1⋅(NO+)2–4⋅(NO+)5 were studied by UV/Vis, FTIR, and 1H NMR spectroscopy in solution, and also by molecular modeling. Entrapment of NO+ in 1⋅(NO+)2–4⋅(NO+)5 is reversible, and addition of [18]crown‐6 quickly recovers starting tubes 1–4. The FTIR and titration data revealed enhanced binding of NO+ in longer tubes, which may be due to cooperativity. The described nanotubes may serve as materials for storing and converting NOx and also offer a promise to further develop supramolecular chemistry of molecular containers. These findings also open wider perspectives towards applications of synthetic nanotubes as alternatives to carbon nanotubes.
Inverted Supercritical Carbon Dioxide/Aqueous Biphasic Media for Rhodium‐Catalyzed Hydrogenation Reactions
Authors: Burgemeister Katja , Franciò Giancarlo , Gego Volker H. , Greiner Lasse , Hugl Herbert , Leitner Walter
Published: February 2007

An inverted supercritical carbon dioxide (scCO2)/aqueous biphasic system has been used as reaction media for Rh‐catalysed hydrogenation of polar substrates. Chiral and achiral CO2‐philic catalysts were efficiently immobilised in scCO2 as the stationary phase, while the polar substrates and products were contained in water as the mobile phase. Notably, product separation and catalyst recycling were conducted without depressurisation of the autoclave. The catalyst phase was reused several times with high conversion and product recovery of more than 85 %. Loss of rhodium and phosphorus by leaching were found to be below the detection limit after the first two cycles in the majority of repetitive experiments. The reaction conditions were optimised with a minimum of experiments by using a simplex algorithm in a sequential optimisation. Total turnover numbers (TTNs) of up to 1600, turnover frequencies (TOFs) of up to 340 h−1 and ee's up to 99 % were obtained in repetitive batch operations. The scope of the devised catalytic system has been investigated and a semicontinuous reaction setup has been implemented. The chiral ligand (R,S)‐3‐H2F6‐BINAPHOS allowed highly enantioselective hydrogenation of itaconic acid and methyl‐2‐acetamidoacrylate combined with a considerable catalyst stability in these reaction media.
The Synthesis, Structure and Reactivity of B(C6F5)3‐Stabilised Amide (MNH2) Complexes of the Group 4 Metals
Authors: Mountford Andrew J. , Clegg William , Coles Simon J. , Harrington Ross W. , Horton Peter N. , Humphrey Simon M. , Hursthouse Michael B. , Wright Joseph A. , Lancaster Simon J.
Published: February 2007

Treatment of the homoleptic titanium amides [Ti(NR2)4] (R=Me or Et) with the Brønsted acidic reagent H3N⋅B(C6F5)3 results in the elimination of one molecule of amine and the formation of the four‐coordinate amidoborate complexes [Ti(NR2)3{NH2B(C6F5)3}], the identity of which was confirmed by X‐ray crystallography. The reaction with [Zr(NMe2)4] proceeds similarly but with retention of the amine ligand to give the trigonal‐bipyramidal complex [Zr(NMe2)3{NH2B(C6F5)3}(NMe2H)]. Cyclopentadienyl (Cp) amidoborate complexes, [MCp(NR2)2{NH2B(C6F5)3}] (M=Ti, R=Me or Et; M=Zr, R=Me) can be prepared from [MCp(NR2)3] and H3N⋅B(C6F5)3, and exhibit greater thermal stability than the cyclopentadienyl‐free compounds. H3N⋅B(C6F5)3 reacts with nBuLi or LiN(SiMe3)2 to give LiNH2B(C6F5)3, which complexes with strong Lewis acids to form ion pairs that contain weakly coordinating anions. The attempted synthesis of metallocene amidoborate complexes from dialkyl or diamide precursors and H3N⋅B(C6F5)3 was unsuccessful. However, LiNH2B(C6F5)3 does react with the highly electrophilic reagents [MCp2Me(μ‐Me)B(C6F5)3] to give [MCp2Me(μ‐NH2)B(C6F5)3] (M=Zr or Hf). Comparison of the molecular structures of the Group 4 amidoborate complexes reveals very similar BN, TiN and ZrN bond lengths, which are consistent with a description of the bonding as a dative interaction between an {M(L)n(NH2)} fragment and the Lewis acid B(C6F5)3. Each of the structures has an intramolecular hydrogen‐bonding arrangement in which one of the nitrogen‐bonded hydrogen atoms participates in a bifurcated F⋅⋅⋅H⋅⋅⋅F interaction to ortho‐F atoms.
Optimal Attachment Position and Linker Length Promote Native‐like Character of Cavitand‐Based Template‐Assembled Synthetic Proteins (TASPs)
Authors: Seo Emily S. , Scott Walter R. P. , Straus Suzana K. , Sherman John C.
Published: February 2007

We have designed, synthesised and characterised a series of template‐assembled de novo four‐helix bundles, each differing in the linker length between the template and the peptides. The helix is based on an earlier peptide sequence: EELLKKLEELLKKLG (first‐generation sequence), which was designed to link the hydrophilic/hydrophobic interface of the helices. Increasing or decreasing the linker length by one glycine residue had a significant effect on the structure and properties of the template‐assembled synthetic proteins (TASPs). Here, the effect of the linker length is further probed by linking the peptides closer to the hydrophobic face by using the second‐generation sequence, AEELLKKLEELLKKG, in an effort to improve the packing between the helices and to better understand the helical bundles. The peptides were synthesised with 0–4 Gly linker residues and linked onto a cavitand template. The proteins were found to be α‐helical, stable to guanidine hydrochloride (GuHCl) and to unfold cooperatively. However, their stabilities toward GuHCl, propensity to self‐aggregate and structural specificity differed. The two‐glycine variant of the second‐generation series demonstrated the highest stability and most native‐like character of all the mononeric TASPs in both the first‐ and second‐generation series. The structural specificity of this two glycine variant is comparable to that of other known native‐like de novo proteins. Molecular dynamics simulations showed that the two‐glycine variant contains helices that are tilted with respect to the cavitand template and may account for its unique properties.
Synthesis and Photoinduced Intramolecular Processes of Fulleropyrrolidine–Oligothienylenevinylene–Ferrocene Triads
Authors: Oswald Frédéric , Islam D.‐M. Shafiqul , Araki Yasuyuki , Troiani Vincent , de la Cruz Pilar , Moreno Andrés , Ito Osamu , Langa Fernando
Published: February 2007

Two new triads based on N‐methylfulleropyrolidine, oligothienylenevinylenes (nTV) and ferrocene (Fc), namely C60‐nTV‐Fc (n=2, 4) have been synthesized. A HOMO–LUMO gap as low as 1.09–1.11 eV was experimentally determined by cyclic voltammetry. In both polar and nonpolar solvents, photoinduced charge‐separation (CS) processes in C60‐nTV‐Fc predominantly take place from the singlet excited states of C60 and nTV; this result was indicated by steady and time‐resolved emission spectroscopy. In the case of C60‐4TV‐Fc, the CS state was indicated by the nanosecond transient absorption spectra. In C60‐2TV‐Fc, although the CS process was also confirmed by the fluorescence quenching in nonpolar and polar solvents, the lifetimes of the CS states were shorter than those of C60‐4TV‐Fc. It was revealed that the introduction of Fc donor moiety at the end of the longer nTV chain in the C60‐nTV dyad systems effectively increases the CS efficiency and the lifetimes of CS states.
Intrinsic chiral domains enantioselectively segregated from twisted nematic cells of bent‐core mesogens
Authors: Choi Suk‐Won , Kang Sungmin , Takanishi Yoichi , Ishikawa Ken , Watanabe Junji , Takezoe Hideo
Published: February 2007

Enantioselective segregation has been attained in the Bx phase of a novel substituted oxadiazole achiral banana‐shaped liquid crystal (LC) without introducing any chiral species. This bent‐core molecule exhibits LC polymorphism; the higher temperature nematic (N) phase and the lower temperature banana smectic phase (Bx phase), in which spontaneous chiral segregation with (+) and (−) chiral domains occurs with equal probabilities. In twisted cell geometries, extrinsically induced twisted N structures are formed and result in intrinsically chiral conglomorate when the temperature is decreased from N to Bx. The observed optical activity in homochiral Bx phase is comparable to those theoretically predicted and is proportional to the cell thickness. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
The Natural Product Berberine is a Human Prolyl Oligopeptidase Inhibitor
Authors: Tarrago Teresa , Kichik Nessim , Seguí Josep , Giralt Ernest
Published: February 2007

Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline‐containing peptides at the carboxy terminus. This peptidase has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders, and therefore may have important clinical implications. Among the strategies used to find novel prolyl oligopeptidase inhibitors, traditional Chinese medicinal plants provide a rich source of unexplored compounds. We used 19F NMR spectroscopy to search for new prolyl oligopeptidase inhibitors in a library of traditional Chinese medicine plant extracts. Several extracts were identified as powerful inhibitors of this peptidase. The alkaloid berberine was the prolyl oligopeptidase inhibitory molecule isolated from Rhizoma coptidis extract. Berberine inhibited prolyl oligopeptidase in a dose‐dependent manner. As berberine is a natural compound that has been safely administered to humans, it opens up new perspectives for the treatment of neuropsychiatric diseases. The results described herein suggest that the initiation of clinical trials in patients with schizophrenia, bipolar affective disorder, or related diseases in which cognitive capabilities are affected should be undertaken with either the extract or pure BBR.
Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus
Authors: Barroso‐Chinea Pedro , Castle María , Aymerich María S. , Pérez‐Manso Mónica , Erro Elena , Tuñon Teresa , Lanciego José L.
Published: February 2007

Vesicular glutamate transporters (VGLUTs) are responsible for glutamate trafficking and for the subsequent regulated release of this excitatory neurotransmitter at the synapse. Three isoforms of the VGLUT have been identified, now known as VGLUT1, VGLUT2, and VGLUT3. Both VGLUT1 and VGLUT2 have been considered definitive markers of glutamatergic neurons, whereas VGLUT3 is expressed in nonglutamatergic neurons such as cholinergic striatal interneurons. It is widely believed that VGLUT1 and VGLUT2 are expressed in a complementary manner at the cortical and thalamic levels, suggesting that these glutamatergic neurons fulfill different physiological functions. In the present work, we analyzed the pattern of VGLUT1 and VGLUT2 mRNA expression at the thalamic level by using single and dual in situ hybridization. In accordance with current beliefs, we found significant expression of VGLUT2 mRNA in all the thalamic nuclei, while moderate expression of VGLUT1 mRNA was consistently found in both the principal relay and the association thalamic nuclei. Interestingly, individual neurons within these nuclei coexpressed both VGLUT1 and VGLUT2 mRNAs, suggesting that these individual thalamic neurons may have different ways of trafficking glutamate. These results call for a reappraisal of the previously held concept regarding the mutually exclusive distribution of VGLUT transporters in the central nervous system. J. Comp. Neurol. 501:703–715, 2007. © 2007 Wiley‐Liss, Inc.
Structural changes at synapses after delayed perfusion fixation in different regions of the mouse brain
Authors: Tao‐Cheng Jung‐Hwa , Gallant Paul E. , Brightman Milton W. , Dosemeci Ayse , Reese Thomas S.
Published: February 2007

We recently showed by electron microscopy that the postsynaptic density (PSD) from hippocampal cultures undergoes rapid structural changes after ischemia‐like conditions. Here we report that similar structural changes occur after delay in transcardial perfusion fixation of the mouse brain. Delay in perfusion fixation, a condition that mimics ischemic stress, resulted in 70%, 90%, and 23% increases in the thickness of PSDs from the hippocampus (CA1), cerebral cortex (layer III), and cerebellar cortex (Purkinje spines), respectively. In step with PSD thickening, the amount of PSD‐associated α‐calcium calmodulin‐dependent protein kinase II (α‐ CaMKII) label increased more in cerebral cortical spines than in Purkinje spines. Although the Purkinje PSDs thickened only slightly after delayed fixation, they became highly curved, and many formed sub‐PSD spheres ∼80 nm in diameter that labeled for CaMKII. Delayed perfusion fixation also produced more cytoplamic CaMKII clusters (∼110 nm in diameter) in the somas of pyramidal cells (from hippocampus and cerebral cortex) than in Purkinje cells. Thus a short delay in perfusion fixation produces cell‐specific structural changes at PSDs and neuronal somas. Purkinje cells respond somewhat differently to delayed perfusion fixation, perhaps owing to their lower levels of CaMKII, and CaMKII binding proteins at PSDs. We present here a catalogue of structural changes that signal a perfusion fixation delay, thereby providing criteria by which to assess perfusion fixation quality in experimental structural studies of brain and to shed light on the subtle changes that occur in intact brain following metabolic stress. J. Comp. Neurol. 501:731–740, 2007. © 2007 Wiley‐Liss, Inc.