Mechanism of Mitogenic Action of Aluminum Ion on Bone Cells : Potential Involvement of the Insulin-Like Growth Factor Regulatory System

Micromolar concentrations of aluminum ion (oxidation state of 3 +) consistently stimulated [3H]thymidine incorporation into cell DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-like cells of chicken and human origin. Although biphasic, dose-dependent stimulations were highly reproducible, the maximal stimulatory dose varied among different experiments. Mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE85 cells. In addition, the same mitogenic concentrations of aluminum ion enhanced the 1,25 dihydroxy vitamin D3-dependent stimulation of osteocalcin secretion. Together, these findings indicate that aluminum at micromolar concentrations, stimulates the proliferation, differentiation, and activity of human osteoblastic-line cells in vitro. With respect to the mechanism of its mitogenic action, the mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. Additional studies have also revealed that the mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, the mitogenic action of aluminum was unaffected by culture medium changes (/. e., it was not dependent on the presence of essential factors in the cell-conditioned media); (b) unlike fluoride, the mitogenic action of aluminum was not specific for bone cells; and (c) interaction studies with fluoride revealed that aluminum and fluoride did not share the same rate-limiting step(s) for their effects in stimulating the proliferation of osteoblastic-like cells. To test the additional hypothesis that the mitogenic action of aluminum ion is mediated through the insulin-like growth factor (IGF) regulatory system, the effects of mitogenic concentrations of aluminum on IGF-I and IGF-II production were evaluated. TE85 cells treated with aluminum ion for 48 hours showed biphasic stimulation of the synthesis/secretion of IGF-I and IGF-II into the conditioned medium (CM). The addition of IGFBP-4, an inhibitory IGF binding protein, significantly reduced the effect of aluminum to stimulate [3H]thymidine incorporation, supporting the hypothesis that the mitogenic action of aluminum was mediated by an increase in IGF production. Western ligand blot analysis revealed that mitogenic concentrations of aluminum ion also inhibited the secretion of IGF binding proteins, particularly the inhibitory IGFBP-4, an action which could lead to the potentiation of the overall activity of IGFs. Based on these findings, it is concluded that aluminum ion, at micromolar concentrations, acts directly on human bone cells to stimulate their proliferation and differentiation by a mechanism that involves increase in the production and activity of IGFs in bone cells

Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5′ flap DNA: basis of interstrand cross-link repair by FAN1

Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5′ flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domain playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5′ flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair

Sistem Informasi Pelayanan Jasa Service Pada Bengkel Cipta Prima Motor Cibitung

Abstrak: Dalam Penelitian ini membahas tentang pembuatan Sistem Informasi Pelayanan Jasa Service Pada Bengkel Cipta Prima Motor Cibitung. Saat ini proses pencatatan transaksi yang ada di Bengkel Cipta Prima Motor masih menggunakan sistem manual dalam pengolahan data transaksi pelanggan. Hal ini menimbulkan penyajian data tidak berjalan dengan baik, Terdapat kesalahan penulisan keluhan pelanggan dan kekeliruan dalam penghitungan biaya servis yang menyebabkan kerugian. Dalam penelitian ini penulis ingin membangun sebuah sistem informasi untuk membantu kasir dalam melayani pelanggan saat service kendaraan. Metode pengembangan dan penelitian ini adalah SDLC dengan model waterfall dan disertai dengan analisis SWOT serta analisa kelayakan TELOS. Hasil dari perancangan ini diharapkan dapat dibangun sistem informasi pelayanan jasa service yang mampu melayani pelanggan dengan cepat dan akurat.   Kata kunci: Service, Sistem Informasi, Waterfall   Abstract: In this study discusses about the manufacture of Service Information Systems Service Service in Bengkel Cipta Prima Motor Cibitung. Currently the process of recording transactions in Bengkel Cipta Prima Motor still use manual system in customer transaction data processing. This results in the data presentation not working properly, there is a customer misconduct error and a mistake in calculating the service charge causing the loss. In this study the authors want to build an information system to help the cashier in serving customers when service vehicles. The method of development and research is SDLC with waterfall model and is accompanied by SWOT analysis and TELOS Feasibility analysis. The results of this design is expected to be built information service system service services capable of serving customers quickly and accurately.   Keywords: Information System, Service, Waterfal

To stay or to leave? : an assessment of the social, economic, and political factors that influence international students when deciding to remain in, or leave Nova Scotia, upon graduation

xi, 127 leaves : col. ill. ; 29 cmIncludes abstract and appendices.Includes bibliographical references (leaves 103-114).This research examines critical factors graduating/recently graduated international students from Halifax Regional Municipality (HRM) universities encounter when deciding to remain in Nova Scotia, move to other provinces, or return home. The 2014 “Now or Never” report identified high rates of educated international students leaving Nova Scotia. This research uses Lee’s Push-Pull Theory of Migration to fill the gap regarding the factors that influence this phenomenon. An online survey (94 respondents) and a focus group were utilized to gather information on social and economic situations, and experiences from a mixed group of international students. The results indicate that they face a series of push factors encouraging their departure from Nova Scotia, and pull factors encouraging them to stay. In both instances, factors are related to social, political, and/or economic reasons. The research highlights that these push-pull factors are not static, and will aid in understanding how political actors can move forward

AERA postcolonial studies and education SIG

This is a brief overview of the proceedings of AERA Postcolonial Studies and Education SIG which took place on Sunday, April 15 2012 at the Vancouver Convention Center with 20 members and guests participating.peer-reviewe

PolarLight: a CubeSat X-ray Polarimeter based on the Gas Pixel Detector

The gas pixel detector (GPD) is designed and developed for high-sensitivity astronomical X-ray polarimetry, which is a new window about to open in a few years. Due to the small mass, low power, and compact geometry of the GPD, we propose a CubeSat mission Polarimeter Light (PolarLight) to demonstrate and test the technology directly in space. There is no optics but a collimator to constrain the field of view to 2.3 degrees. Filled with pure dimethyl ether (DME) at 0.8 atm and sealed by a beryllium window of 100 micron thick, with a sensitive area of about 1.4 mm by 1.4 mm, PolarLight allows us to observe the brightest X-ray sources on the sky, with a count rate of, e.g., ~0.2 counts/s from the Crab nebula. The PolarLight is 1U in size and mounted in a 6U CubeSat, which was launched into a low Earth Sun-synchronous orbit on October 29, 2018, and is currently under test. More launches with improved designs are planned in 2019. These tests will help increase the technology readiness for future missions such as the enhanced X-ray Timing and Polarimetry (eXTP), better understand the orbital background, and may help constrain the physics with observations of the brightest objects.Comment: Accepted for publication in Experimental Astronom

ARTICULATED DIFFICULTIES OF GRADE 11 STUDENTS AT TAYTAY SENIOR HIGH SCHOOL (TSHS) IN ENGLISH PROFICIENCY

English has been the medium of instruction since the beginning of the 20th century in the Philippines during the arrival of the Americans. This has been incorporated holistically in the society through the educational system, communication, mass media, publications and social media. It is given therefore that Filipino learners are bilingual-- i.e., speaking both Filipino (the native tongue) and English as Second Language (ESL). After a century though, proficiency in the language is still a difficulty and an anxiety, especially from public school learners. In Taytay Senior High School (a public senior high school), Grade 11 students were observed of certain levels of difficulties in reading, writing, speaking and listening. In this study, the researchers probed deeper into the following: a.) the difficulties experienced by grade 11 students b.) the factors that led to such difficulties and c.) the articulated ways to help them overcome such difficulties in English proficiency. As a descriptive study, the researchers used pre-survey, survey, FGD and extensive literature review as methodologies. The survey results revealed problematic stages on vocabulary, training and knowledge, confidence and self-esteem and interest. Articulated in the FGD furthermore were issues of generation, practice/articulation, and system as factors that led to difficulties in reading writing, speaking and listening. On the other hand, Grade 11 students underscored power of mind, the use of native language and practice as methodical solutions to the problem. Further directions of this study could include elaboration of the FGD results that pertain to issues of generation, practice/articulation and system. The use of native language could also be expounded on future studies

ARTICULATED DIFFICULTIES OF GRADE 11 STUDENTS AT TAYTAY SENIOR HIGH SCHOOL (TSHS) IN ENGLISH PROFICIENCY

English has been the medium of instruction since the beginning of the 20th century in the Philippines during the arrival of the Americans. This has been incorporated holistically in the society through the educational system, communication, mass media, publications and social media. It is given therefore that Filipino learners are bilingual-- i.e., speaking both Filipino (the native tongue) and English as Second Language (ESL). After a century though, proficiency in the language is still a difficulty and an anxiety, especially from public school learners. In Taytay Senior High School (a public senior high school), Grade 11 students were observed of certain levels of difficulties in reading, writing, speaking and listening. In this study, the researchers probed deeper into the following: a.) the difficulties experienced by grade 11 students b.) the factors that led to such difficulties and c.) the articulated ways to help them overcome such difficulties in English proficiency. As a descriptive study, the researchers used pre-survey, survey, FGD and extensive literature review as methodologies. The survey results revealed problematic stages on vocabulary, training and knowledge, confidence and self-esteem and interest. Articulated in the FGD furthermore were issues of generation, practice/articulation, and system as factors that led to difficulties in reading writing, speaking and listening. On the other hand, Grade 11 students underscored power of mind, the use of native language and practice as methodical solutions to the problem. Further directions of this study could include elaboration of the FGD results that pertain to issues of generation, practice/articulation and system. The use of native language could also be expounded on future studies

Hill-Hayne Aera-Aetna Iron Works Records - Accession 392

This collection consists of microfilm copies of a minute book of the Hill-Hayne Aera- Aetna Iron Works started and owned by Colonel William Hill (1741-1816) and Colonel Isaac Hayne (1745-1781). The ironworks were built in 1776 on Allison Creek in York County, SC. It was destroyed during the American Revolution by British Captain Christian Huck in June 1780 and was rebuilt after the war in 1878-1788. Also included are papers dealing with transactions made by William E. Hayne as sheriff of York District.https://digitalcommons.winthrop.edu/manuscriptcollection_findingaids/1499/thumbnail.jp