bluuebunny/crossref_metadata_2025 huggingface dataset:
Public Policy Implications of Changing Student Attendance Patterns
Authors: Longanecker David A. , Blanco Cheryl D.
Published: April 2003

Public policy is likely to remain more reactive than proactive, and more iterative than creative, in responding to the needs and concerns of students with new attendance patterns. Swirling students will likely swirl even more among institutions, but it will take some time before our policies catch up.
Nontraditional Attendance and Persistence: The Cost of Students' Choices
Authors: King Jacqueline E.
Published: April 2003

Working more than part‐time and attending college part‐time negatively affect persistence, especially among low‐income students. Such choices also impede the ability of institutions to shorten time‐to‐degree, improve graduation rates, and accommodate larger numbers of students. Judicious use of student loans can help students reduce hours at work and finance full‐time attendance.
Rethinking Policy, Process, and Planning to Redefine Quality and Enhance Student Success
Authors: Passaro Joanne , Lapovsky Lucie , Feroe Louise H. , Metzger James R.
Published: April 2003

Combining broad access with academic excellence requires academic and support strategies and practices that pinpoint student needs and target appropriate resources effectively. Mercy College, a private comprehensive institution of ten thousand students in New York, has undertaken a series of policy and programmatic changes to support both access and excellence among nontraditional students.
Best Practices in Providing Nontraditional Students With Both Academic and Financial Support
Authors: Hart Natalia K.
Published: April 2003

Efforts begun at Ohio State to address the interspections of finance and academics benefit all students, but especially nontraditional students with complex life circumstances. These efforts have centered on keeping students out of the financial aid office and in the classroom, and on designing programs and services that address financial and academic concerns in an integrated way.
Changing U. S. Demographics and American Higher Education
Authors: Anderson Eugene L.
Published: April 2003

Higher education in the United States is more diverse today because of dramatic shifts in the general population and increased attendance among adults. These trends will continue as more adults begin or return to college and as the Baby Boom Echo generation enters college. Whereas persons of color will become the new majority in several states, many states will remain mostly white.
Swirling and Double‐Dipping: New Patterns of Student Attendance and Their Implications for Higher Education
Authors: McCormick Alexander C.
Published: April 2003

It is increasingly common for students to attend multiple institutions, and this involves more than transfer between institutions. Although sophisticated bureaucratic mechanisms for dealing with course‐taking at other institutions have been developed, there is an urgent need to understand its educational implications and to develop ways to enhance educational coherence.
Beyond Access: Persistence Challenges and the Diversity of Low‐Income Students
Authors: Corrigan Melanie E.
Published: April 2003

Public policy often emphasizes access to higher education, but low‐income students face more difficult challenges on the path to degree attainment. Adult low‐income students have different obligations and goals than their younger counterparts. Institutional leaders and policymakers can encourage persistence among low‐income students with flexible policies that accommodate new enrollment patterns, diverse family structures, and differing educational and economic goals.
Threats to the estimation of benefit: are preference elicitation methods accurate?
Authors: Lloyd Andrew J
Published: April 2003

Stated preference methods are used to estimate the value that people place on health care. The data that emerges from these studies is used to guide health policy. However, relatively little is known about how individuals make decisions in a preference elicitation task. Two methods (willingness to pay and conjoint analysis) are considered within the context of the literature from psychology (and also environmental economics) regarding how people construct preferences, process information, and make decisions. There is substantial evidence that individuals employ heuristics (cognitive shortcuts) in order to simplify tasks they are presented with. The use of heuristics implies that people ignore much of the information they are presented with and make decisions which would not be considered rational in the economic sense. These stated preference methods assume that individuals trade between the different attributes of a good or service when making decisions – an assumption that other theories predict is wrong. The implications of this are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Fast Feldkamp reconstruction based on focus of attention and distributed computing
Authors: Gregor J. , Gleason S. S. , Paulus M. J. , Cates J.
Published: April 2003

The Feldkamp algorithm is widely accepted as a practical conebeam reconstruction method for three‐dimensional x‐ray computed tomography. We introduce focus of attention, an effective and simple to implement datadriven preprocessing scheme, for identifying a convex subset of voxels that include all those relevant to the object under study. By concentrating on this subset of voxels during reconstruction, we reduce the computational demands of the Feldkamp algorithm correspondingly. To achieve further speed‐up, all computations are distributed across a cluster of inexpensive, dual‐processor PCs. We present experimental work based on mouse data obtained from the MicroCAT which is a high‐resolution x‐ray computed tomography system for small animal imaging. This work shows that focus of attention can cut the overall computation time in half without affecting the image quality. The method is general by nature and can easily be adapted to apply to other geometries and modalities as well as to iterative reconstruction algorithms. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 12, 229–234, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10027
An automatic focusing algorithm
Authors: Lin Sheng‐Fuu , Lin You‐Tasi , Su Chien‐Kun
Published: April 2003

A simple and effective automatic focusing algorithm is proposed in this article. The principle of the proposed automatic focusing algorithm is based on that, for the radial test pattern, a best‐focused image should have the smallest blurred region in the middle of the acquired image, and hence, should have the smallest equivalent radius. The circular Hough transform has became a common method in numerous image‐processing applications for circle detection. Various modifications to the basic circular Hough transform have been suggested, such as: the inclusion of edge orientation, simultaneous consideration of a range of circle radii, the use of a complex accumulator array with the phase proportional to the log of the radius, or for filter operations. The purpose of this work is to show that a radius of a circular region extracted by a normalized circular Hough transform is a possible solution for determining the sharpness of images. To acquire high quality images with a given CCD camera, it is crucial that the camera be located exactly at the back length of the lens, i.e., the focus position of the lens. In the best conditions, the contours of the acquired images are of the sharpest, with none of the blurring effects associated with unfocused images. Acquiring such high quality images by these means is the main goal of the automatic focusing algorithm proposed in this article. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 12, 235–238, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10029
A novel blind super‐resolution technique based on the improved Poisson maximuma posteriorialgorithm
Authors: Pan Min‐Cheng
Published: April 2003

Image restoration has received considerable attention. In many practical situations, unfortunately, the blur is often unknown, and little information is available about the true image. Therefore, the true image is identified directly from the corrupted image by using partial or no information about the blurring process and the true image. In addition, noise will be amplified to induce severely ringing artifacts in the process of restoration. This article proposes a novel technique for the blind super‐resolution, whose mechanism alternates between de‐convolution of the image and the point spread function based on the improved Poisson maximuma posteriorisuper‐resolution algorithm. This improved Poisson MAP super‐resolution algorithm incorporates the functional form of a Wiener filter into the Poisson MAP algorithm operating on the edge image further to reduce noise effects and speed restoration. Compared with that based on the Poisson MAP, the novel blind super‐resolution technique presents experimental results from 1‐D signals and 2‐D images corrupted by Gaussian point spread functions and additive noise with significant improvements in quality. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 12, 239–246, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10032
Pyramid‐based super‐resolution of the undersampled and subpixel shifted image sequence
Authors: Lu Yao , Imamura Minoru
Published: April 2003

The existing methods for the reconstruction of a super‐resolution image from the undersampled and subpixel shifted image sequence have to solve a large ill‐condition equation group by approximately finding the inverse matrix or performing many iterations to approach the solution. The former leads to a big burden of computation, and the latter causes the artifacts or noise to be overstressed. So they are rarely implemented in practical use. In order to solve these problems, in this article, we consider applying pyramid structure to the super‐resolution of the image sequence and present a suitable pyramid framework, called Super‐Resolution Image Pyramid (SRIP), and determine the pyramid back‐projection. Pyramid structure and methods are widely used in image processing and computer vision. But we have not found their applications to the super‐resolution in literatures. We give a complete description for SRIP. As an example, the Iterative Back‐Projection (IBP) suggested by Peleg (1991, 1993) is integrated in this pyramid framework. The experiments and the error analysis are performed to show the effectiveness of this framework. The image resolution can be improved better even in the case of severely undersampled images. In addition, the other general super‐resolution methods can be easily integrated in this framework so that they can be done in parallel so as to meet the need of real‐time processing. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol 12, 254–263, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10033
Neural network‐based image restoration using scaled residual with space‐variant regularization
Authors: Salari E. , Zhang S.
Published: April 2003

Image restoration is aimed to recover the original scene from its degraded version. This paper presents a new method for image restoration. In this technique, an evaluation function which combines a scaled residual with space‐variant regularization is established and minimized using a Hopfield network to obtain a restored image from a noise corrupted and blurred image. Simulation results demonstrate that the proposed evaluation function leads to a more efficient restoration process which offers a fast convergence and improved restored image quality. © 2003 Wiley Periodicals, Inc. Int J Imaging Syst Technol 12, 247–253, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10034
Brackish water subirrigation for vegetables
Authors: Patel R. M. , Prasher S. O. , Goel P. K. , Madramootoo C. A. , Broughton R. S.
Published: April 2003

As freshwater resources for irrigation are being depleted rapidly, recent emphasis has been on the development of nonconventional water sources: reuse of agricultural drainage water, use of industrial or municipal wastewater, and use of brackish water for irrigation. Experiments conducted in field lysimeters over three seasons sought to investigate the feasibility of using brackish water for growing moderately sensitive crops. Brackish waters, with salinity levels of 1, 5 and 9 dS m−1, were used. In 1993 the effects of a factorial combination of three subirrigation water salinity levels, two water table depths and four NPK fertilizer combinations on salt buildup in an initially nonsaline soil and on green pepper (Capsicum annuum L.) performance were assessed. A gradual increase in soil solution salinity (ECsw) from the water table to the soil surface was evident; however, throughout the growing season, the ECsw did not reach a level that could seriously damage the crop. There was no significant difference in pepper yields due to either salinity of subirrigation water or water table depth. In 1994, two potato (Solanum tuberosum L.) cultivars were grown in the soil, which was salinized with 3.5 dS m−1 water before planting tubers. The salt buildup pattern was similar to that observed in 1993; however, the ECsw levels were higher in 1994 due to the higher initial soil salinity. Moreover, a decrease in ECsw was observed near the water table in lysimeters subirrigated with 1 dS m−1 water. For both cultivars, no significant difference in tuber yield was observed due to either water table depth or subirrigation water salinity. In 1995, three potato cultivars were grown in a nonsaline soil as well as a soil presalinized with 2 dS m−1 water. In the topsoil layer, higher rate of increase in ECsw was observed in the saline soil compared to the nonsaline soil. No significant difference in total tuber yield was observed due to either the initial soil salinity levels or subirrigation water salinity levels. Brackish water with salinity levels of up to 9 dS m−1, when applied through subirrigation, could be used to successfully produce green peppers and potatoes under semiarid to arid conditions. Copyright © 2002 John Wiley & Sons, Ltd.
The role of controlled drainage under drought conditions in an irrigated area in NWFP, Pakistan
Authors: Daraz Khan Gul , Latif Muhammad , Hassan Sibtul
Published: April 2003

The River Swat is the source of irrigation for the entire irrigation system of Mardan, Nowshera and Charsadda districts. Reductions of water and overdrainage have influenced the yield of major crops. The impact of reduced supply at the inlet from the source, drought conditions and overdrainage from the area have lowered the groundwater to a disastrous level. Thus the present groundwater level cannot contribute to the crops. A subsurface collector at its exit in drainage unit 106 was controlled to raise the watertable. The study area was divided into 10 zones. Each zone was separately assessed to analyze the groundwater impact in response to the controlled technique adopted for mitigating drought in different strategies of the canal operation. The interaction of groundwater level with irrigation depth, crop yield, water use efficiency and water saving were also studied. During the rotational period of the canal, irrigations applied in section II raised the water level by nearly 1 m. The upslope area of section III also needed a large irrigation depth. The groundwater level on the downslopes of the lateral drains in sections I and V was at the design depth of 1.1 m during the rotational strategy, while it decreased only slightly on the upslopes of the lateral drains for the same positions. Because of effective control by the collector, the watertable on the downslopes of the laterals in sections II and III was affected less while in the respective upslope area of section III it dropped more than 2 m. The water levels in section IV (both in the upslope and downslope areas along the laterals) remained very close to the design level. A significant contribution of seepage in the upslope of the collector drain considerably reduced the irrigation depths. During the canal closure period, the watertables in the study area dropped to the limit from 2.3 to 3.25 m. After the reopening of the canal, the watertables in sections II, III and IV were raised from 2.55 to 0.70 m. During this period the water levels near the canal reached the design level. The maximum yield of 6.5 tons ha−1 on the downslopes of the lateral drains in section II was obtained, resulting in maximum water use efficiency of 0.93 kg m−3. However, the minimum yield of 3.5 tons ha−1 on the upslopes of the lateral drains in section I was obtained, resulting in the lowest water use efficiency of 0.35 kg m−3 near the deep surface drain (5 m). The impact of controlled subsurface drainage in zones 2, 3 and 7 resulted in the best maintenance of optimum groundwater level and moisture content. Therefore large amounts of extra irrigation water applied (ranging from 23 to 129% of that actually required) in different zones of the controlled area can be saved for drought conditions. Copyright © 2003 John Wiley & Sons, Ltd.
Critical role of the transcription factor AP‐1 for the constitutive and interferon‐induced expression of IFI 16
Authors: Clarke C.J.P. , Apostolidis V. , Hii L.L.P. , Gough D.J. , Trapani J.A. , Johnstone R.W.
Published: April 2003

IFI 16 is a member of the HIN‐200 family of transcriptional regulators that suppress cell growth, modulate the cell cycle and have been linked to cellular differentiation. We hypothesized that the activity of IFI 16 depends on its level of expression and therefore studied the transcriptional activity of the IFI 16 promoter. A discrete sequence within the 5′ untranslated region was required for constitutive activity of the promoter and the functional motif within this region was shown to be a consensus AP‐1 site. Interestingly, this AP‐1 site was also critical for IFN‐induced activation of the promoter and consistent with these observations, treatment of cells with IFNγ resulted in a rapid and robust induction of AP‐1 activity that preceded expression of IFI 16. These experiments define the transcriptional mechanisms of IFI 16 gene regulation and provide evidence suggesting that AP‐1 activation may be an important event in IFN signaling. J. Cell. Biochem. 89: 80–93, 2003. © 2003 Wiley‐Liss, Inc.
Effects of mobile phone radiation on reproduction and development in Drosophila melanogaster
Authors: Weisbrot David , Lin Hana , Ye Lin , Blank Martin , Goodman Reba
Published: April 2003

In this report we examined the effects of a discontinuous radio frequency (RF) signal produced by a GSM multiband mobile phone (900/1,900 MHz; SAR ∼ 1.4 W/kg) on Drosophila melanogaster, during the 10‐day developmental period from egg laying through pupation. As found earlier with low frequency exposures, the non‐thermal radiation from the GSM mobile phone increased numbers of offspring, elevated hsp70 levels, increased serum response element (SRE) DNA‐binding and induced the phosphorylation of the nuclear transcription factor, ELK‐1. The rapid induction of hsp70 within minutes, by a non‐thermal stress, together with identified components of signal transduction pathways, provide sensitive and reliable biomarkers that could serve as the basis for realistic mobile phone safety guidelines. J. Cell. Biochem. 89: 48–55, 2003. © 2003 Wiley‐Liss, Inc.
Molecular cloning of the cell surface antigen identified by the osteoprogenitor‐specific monoclonal antibody, HOP‐26
Authors: Zannettino Andrew C.W. , Harrison Kate , Joyner Clive J. , Triffitt James T. , Simmons Paul J.
Published: April 2003

Bone is a highly organized structure comprising a calcified connective tissue matrix formed by mature osteoblasts, which develop from the proliferation and differentiation of osteoprogenitor cells. The osteogenic cell lineage is thought to arise from a population of uncommitted multipotential stromal precursor cells (SPC) which reside close to all bone surfaces, in the bone marrow spaces and the surrounding connective tissue. These SPC also give rise to related cell lineages which form cartilage, smooth muscle, fat, and fibrous tissue. Due to the lack of well defined cell surface markers, little is known of the precise developmentally regulated changes in phenotype which occur during the differentiation and maturation of human osteoprogenitor cells into functional osteoblasts and ultimately, terminally differentiated osteocytes. In order to identify antibody reagents with greater specificity for osteoprogenitors we generated a series of antibodies following immunization with freshly isolated human bone marrow stromal fibroblasts. One such antibody, HOP‐26, reacts with a cell surface antigen expressed by SPC and developing bone cells. We now demonstrate that this mAb identifies a member of the tetraspan family of cell surface glycoproteins, namely CD63. Western blot analysis of human bone marrow stromal cells (HBMSC) has revealed that like a well defined CD63 mAb 12F12, HOP‐26 interacts with a heavily glycosylated cell surface protein with an apparent molecular weight of 50–60 kD. J. Cell. Biochem. 89: 56–66, 2003. © 2003 Wiley‐Liss, Inc.
Proteins that mediate the nuclear entry of the goat uterine estrogen receptor activation factor (E‐RAF): Identification of a molecular basis for the inhibitory effect of progesterone on estrogen action
Authors: Govind Anitha P. , Sreeja S. , Thampan Raghava Varman
Published: April 2003

A 66 kDa transport protein, tp66, has been identified as the protein that mediates the nuclear transport of the estrogen receptor activation factor (E‐RAF). Indirect evidence shows that tp66 influences the transport of E‐RAF mainly by recognizing the nuclear localization signals (NLS) on the latter. A 38 kDa nuclear pore complex protein (npcp38) has been identified to which tp66–E‐RAF complex gets ‘docked’ prior to the nuclear entry of E‐RAF. Progesterone binding to E‐RAF serves to dissociate E‐RAF from the tp66 thereby inhibiting the nuclear entry of E‐RAF. The demonstration of the high affinity progesterone binding property of E‐RAF adds credibility to the above findings. A change in conformation of E‐RAF being brought about by progesterone binding is evident from the results of the circular dichroism (CD) analysis. This appears to be the fundamental reason behind the dissociation of the tp66–E‐RAF complex under progesterone influence and provides a molecular basis for the estrogen ‘antagonistic’ action of progesterone. A nuclear run‐on transcription assay clearly demonstrates the transcription‐activation function of E‐RAF II, also reaffirming the functional role of tp66 in the nuclear entry of E‐RAF. J. Cell. Biochem. 89: 108–119, 2003. © 2003 Wiley‐Liss, Inc.
Estradiol dependent anchoring of the goat uterine estrogen receptor activation factor (E‐RAF) at the endoplasmic reticulum by a 55 kDa anchor protein (ap55)
Authors: Govind Anitha P. , Sreeja S. , Thampan Raghava Varman
Published: April 2003

The primary intracellular site of localization of the estrogen receptor activation factor (E‐RAF) is shown here to be the endoplasmic reticulum where the protein remains anchored through an estrogen dependent mechanism. The retention of E‐RAF by the endoplasmic reticulum is facilitated by two proteins: (1) a 55 kDa anchor protein (ap55) which is an integral membrane protein of the endoplasmic reticulum. ap55 is a high affinity estrogen binding protein. A conformational change induced by estrogen binding is thought to favor the anchoring process. (2) The anchoring of E‐RAF by ap55 is mediated by yet another protein. This is the 66 kDa transport protein (tp66) which recognizes ap55 on the one hand and E‐RAF on the other. The presence of estradiol that saturates the hormone binding sites on ap55 appears to favor the anchoring of tp66–E‐RAF complex to ap55. This interaction appears to be weakened by levels of estradiol below 7 nM concentration leading to the dissociation of the tp66–E‐RAF complex from ap55. The tp66—E‐RAF complex moves towards the nucleus. J. Cell. Biochem. 89: 94–107, 2003. © 2003 Wiley‐Liss, Inc.
Expression of lactate dehydrogenase A and B genes in different tissues of rats adapted to chronic hypobaric hypoxia
Authors: Rossignol Fabrice , Solares Magali , Balanza Elfride , Coudert Jean , Clottes Eric
Published: April 2003

Lactate dehydrogenase (LDH) is a tetramer made up of two different subunits A and B. In cellular models, severe hypoxia increases LDH A gene expression whereas LDH B gene does not exhibit any regulation. The aim of our work was to characterise LDH expression in different tissues of rats bred at high altitude. For this purpose, we chose a Sprague–Dawley rat strain adapted to chronic hypoxia in La Paz (3700 m), Bolivia. Two normoxic control groups were bred at low altitude in Clermont‐Ferrand (350 m), France, one group was ad libitum with free access to food and water as was the hypoxic one, and the second normoxic group was nourished with the food intakes measured for the animals from La Paz. We measured total LDH specific activity, isoform distribution and LDH A and B mRNA amounts in three skeletal muscles (soleus, extensor digitorum longus (EDL), plantaris), heart and brain. Our study demonstrates that, unlike what has been shown in cellular models under severe hypoxia, LDH A gene is not systematically up‐regulated in tissues of rats living at high altitude. Furthermore, chronic hypoxia limits LDH B gene transcription or its mRNA stability in both soleus and EDL. These regulations occur at various molecular levels like gene transcription, mRNA stabilisation or translation and protein stability, depending on the tissue studied, and are partly attributed to caloric restriction provoked by high altitude. These data provide insight into LDH gene expression underlying the diverse and complex tissue‐specific response to chronic hypoxia. J. Cell. Biochem. 89: 67–79, 2003. © 2003 Wiley‐Liss, Inc.
Mesangial cells are able to produce catecholamines in vitro
Authors: Di Marco Giovana Seno , Naffah‐Mazzacoratti Maria da Graça , Vio Carlos P. , Dos Santos Oscar Fernando Pavão , Schor Nestor , Casarini Dulce Elena
Published: April 2003

Mesangial cells (MC) participate in the control of the glomerular function due to their ability to synthesize hormones and induce cell contraction. Since MC can produce various kinds of hormones, the purpose of the present study was to determine if they are able to synthesize catecholamines. For this evaluation, the levels of norepinephrine, epinephrine, dopamine, and biopterin, the enzymatic cofactor of tyrosine hydroxylase (TH), were analyzed by HPLC in the intracellular compartment and in the medium of primary cultured MC. To identify and locate the enzymes responsible for monoamine synthesis, TH, dopa decarboxylase, and dopamine β‐hydroxylase, Western blotting and immunocytochemistry were employed using monoclonal and polyclonal antibodies. Concentrations of NE = 57 ± 8, EPI = 82 ± 10, and DA = 52 ± 9 pg/mg protein (X ± SEM) were found in the cell homogenate. The culture medium showed concentrations of NE = 25 ± 3, EPI = 33 ± 3, and DA = 62 ± 15 pg/mg protein. Western blotting analysis and immunocytochemistry evidenced the presence of all enzymes. Moreover, biopterin was also detected in the intracellular compartment and in the medium (0.28 ± 0.03 and 5.70 ± 2 nmol/mg cell protein, respectively). Overall, the data indicate that MC have the biosynthetic machinery necessary to produce catecholamines, suggesting that they can act as a paracrine/autocrine hormone system, contributing to the regulation of glomerular hemodynamic and renal microcirculation. J. Cell. Biochem. 89: 144–151, 2003. © 2003 Wiley‐Liss, Inc.
Estrogen receptor‐β modulates synthesis of bone matrix proteins in human osteoblast‐like MG63 cells
Authors: Cao Lihuan , Bu Rongfa , Oakley Jennifer I. , Kalla Sara E. , Blair Harry C.
Published: April 2003

Estrogens have complex effects on the skeleton, including regulation of modeling and maintenance of bone mass, which vary with cell type and developmental stage. Osteoblasts are key regulators of skeletal matrix synthesis and degradation. However, whether osteocytes, osteoblasts or earlier progenitors mediate estrogen effects, and the importance of estrogen receptors (ERs) α and β, remain unclear. To address estrogen response in human cells closely related to secretory osteoblasts, we studied MG63 cells with ERα or ERβ reduced to low levels by stable transfection of antisense plasmids. Collagen and alkaline phosphatase expression increased with estrogen in wild‐type and ERα‐suppressed cells, but not in ERβ‐suppressed cells. Matrix secretion occurs as osteoblasts cease dividing, and, in keeping with this, cell proliferation was reduced by estrogen except in ERβ‐antisense cells. No effects of estrogen on wild type or ER‐suppressed cells were seen in expression of BMP 2, the BMP antagonist noggin, or Indian hedgehog, products that regulate differentiation of osteoblasts. In contrast to expectations that estrogen would modulate bone degradation, RANKL, CSF‐1, and osteoprotegerin did not respond measurably to estrogen, regardless of ER status. In keeping with this result, estrogen response was not observed in assays of osteoclast development from CD14 cells supported by wild‐type or ER‐silenced MG63 cells. Since estrogens are major regulators of bone degradation in vivo, estrogen effects on osteoclasts may depend on interaction with stimuli present in bone but absent in the model studied. cDNA hybridization showed that additional estrogen‐binding proteins including ERRα and BCAR3 were expressed by MG63, but estrogen effects in ERβ‐silenced cells were small, so these proteins are either minor regulators in MG63 cells, or act in concert with stimuli in addition to estrogen. We conclude that, in the MG63 cell line, estrogen increases synthesis of matrix proteins via ERβ, and that, in the absence of additional stimuli, these cells are not major mediators of estrogen effects on osteoclast differentiation. Further, ERα is probably much more important in earlier stages of skeletal development, such as growth plate response, than in osteoblasts. J. Cell. Biochem. 89: 152–164, 2003. © 2003 Wiley‐Liss, Inc.
BRCA1 splice variants exhibit overlapping and distinct transcriptional transactivation activities
Authors: McEachern Kristen A. , Archey William B. , Douville Karen , Arrick Bradley A.
Published: April 2003

The global changes in gene expression induced by transient increased expression of full length BRCA1 as well as the spliced variant BRCA1S were evaluated by cDNA expression array in a human non‐tumorigenic mammary epithelial cell line, MCF10A. Over 30 genes were identified that displayed an altered expression pattern in response to the expression of BRCA1 splice variants. The expression of NFκB inducing kinase was markedly down‐regulated in BRCA1L transfected cells. However, a NFκB‐responsive promoter construct yielded increased basal activity in BRCA1L transfected cells, as well as following treatment with tumor necrosis factor‐α or lymphotoxin. In addition, nuclear extracts from BRCA1L transfected cells displayed increased DNA binding to the κB consensus site. The transcriptional activity of a panel of promoter constructs was evaluated following expression of wild type or mutant BRCA1. Full length BRCA1 transactivated the estrogen receptor‐α (ERα) and BCL2 promoters as well as AP‐1, SRE, and CRE containing promoters. Transactivation activity of the exon 11‐deleted BRCA1S was more limited and usually of lower magnitude. The ability of a pathogenic mutation, 5382insC, to abrogate the transcriptional transactivation by BRCA1L and BRCA1S was also investigated. Mutant BRCA1 retained wild type levels of transcriptional activity for the ERα promoter as well as for the NFκB, AP‐1, and CRE‐responsive promoters but had reduced or no activity with the BCL2 and SRE promoters. These results show that BRCA1 isoforms have both overlapping and distinct transcriptional transactivation activity, and that a mutant form of BRCA1 implicated in carcinogenesis is not devoid of all activity. J. Cell. Biochem. 89: 120–132, 2003. © 2003 Wiley‐Liss, Inc.
AIDS‐related Kaposi's sarcoma cells rapidly internalize endostatin, which co‐localizes to tropomysin microfilaments and inhibits cytokine‐mediated migration and invasion
Authors: Mallery Susan R. , Morse Mark A. , Wilson Ralph F. , Pei Ping , Ness Gregory M. , Bradburn Jennifer E. , Renner Robert J. , Schuller David E. , Robertson Fredika M.
Published: April 2003

AIDS‐related Kaposi's sarcoma (KS) is the most common HIV‐related malignancy. In some respects, KS is analogous to other angioproliferative diseases, in that KS lesions are highly vascularized and promoted by inflammatory cytokines. However, unlike other cancers or inflammatory mediated vascular diseases, KS is unique in that the KS lesional cells both express and respond to the complete angiogenic cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Therefore, the angiogenic phenotype, which is crucial for cancer progression, is inherent to KS tumor cells. Due to the recognized importance of angiogenesis in cancer progression, numerous angiostatic agents are being investigated as potential therapeutic agents. One such agent is endostatin, which is a 20‐kDa carboxyl‐terminal fragment of collagen XVIII that has demonstrated potent angiostatic activities at both the in vivo and in vitro levels. Since endostatin is recognized as a potent angiostatic agent, the majority of in vitro endostatin studies have evaluated its effects on endothelial cells. Although KS cells are speculated to arise from endothelial cell precursors and KS lesions are highly vascularized, no previous studies have investigated endostatin–KS cell interactions. This present study evaluated endostatin's effects on KS tumor cell: (i) signal transduction (endostatin internalization and transcription factor activation), and (ii) migration and invasion (functional activity assays and tropomysin co‐localization). Our results show that KS cells rapidly internalize endostatin and that endostatin initiates activation of the transcription activating factors nuclear factor‐κB (NF‐κB) and activating protein 1 (AP‐1). Our data also show that internalized endostatin co‐localizes to tropomysin microfilaments and acts to inhibit KS cell migration and invasion in response to the clinically relevant angiogenic cytokines VEGF and bFGF. As a consequence of its combined angiostatic and antitumorigenic activities, endostatin could provide dual therapeutic benefits for patients with mucocutaneous KS. J. Cell. Biochem. 89: 133–143, 2003. Published 2003 Wiley‐Liss, Inc.
Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone
Authors: Locklin Rachel M. , Khosla Sundeep , Turner Russell T. , Riggs B. Lawrence
Published: April 2003

Parathyroid hormone (PTH) has biphasic effects on bone: continuous treatment is catabolic whereas intermittent treatment is anabolic. The mechanism(s) responsible for these differing effects are still unclear, partly because of the previous non‐availability of a model system in which effects on both formation and resorption indices could be studied concomitantly. In cultured marrow cells from 6‐week old C57BL/6 mice, we demonstrated that 4 days of intermittent PTH treatment increased mRNA for osteoblast differentiation markers (Runx2, alkaline phosphatase (AP), and type I procollagen (COL1A1) whereas continuous treatment resulted in production of large numbers of TRAP‐positive multinucleated osteoclasts. Although IGF‐I mRNA did not increase after intermittent treatment, it was consistently higher than after continuous treatment, and the addition of an anti‐IGF‐I neutralizing antibody prevented the increase in bone formation indices observed with intermittent treatment. By contrast, after continuous treatment, gene expression of RANK ligand (RANKL) was increased and that of osteoprotegerin (OPG) was decreased, resulting in a 25‐fold increase in the RANKL/OPG ratio. In this model system, the data suggest that intermittent PTH treatment enhances osteoblast differentiation through an IGF‐I dependent mechanism and continuous PTH treatment enhances osteoclastogenesis through reciprocal increases in RANKL and decreases in OPG. J. Cell. Biochem. 89: 180–190, 2003. © 2003 Wiley‐Liss, Inc.
Upstream and downstream targets of RUNX proteins
Authors: Otto Florian , Lübbert Michael , Stock Michael
Published: April 2003

In recent years, the in vivo role of the three members of the RUNX family of transcription factors has in part been elucidated. While Runx1 is essential for mature haematopoiesis and Runx2 for osteochondrogenesis, Runx3 has a function in the nervous system. Translocations and mutations affecting the RUNX1 gene are clearly implicated in leukemogenesis whereas recent data suggest that changed expression levels of RUNX3 may be involved in gastric carcinogenesis. Germ line mutations in RUNX2 have been identified in patients with an autosomal dominant skeletal disorder, cleidocranial dysplasia. While a number of pathways have been delineated that regulate RUNX activity, transcription factors binding to RUNX promoters are only beginning to be identified. A growing number of genes have been characterised that are being regulated in their transcriptional activity by different RUNX proteins. Whether a particular RUNX protein specifically targets a defined subset of downstream genes or whether there is some redundancy as to which RUNX protein activates which target promoter remains to be elucidated. J. Cell. Biochem. 89: 9–18, 2003. © 2003 Wiley‐Liss, Inc.
Modulation of PPARγ activity with pharmaceutical agents: Treatment of insulin resistance and atherosclerosis
Authors: Wang Minghan , Tafuri Sherrie
Published: April 2003

The anti‐diabetic thiazolidinediones (TZDs) are a class of compounds with insulin‐sensitizing activity that were originally discovered using in vivo pharmacological screens. In subsequent binding studies, TZDs were demonstrated to enhance insulin action by activating peroxisome proliferator‐activated receptor gamma (PPARγ). PPARγ is a member of the ligand‐activated nuclear receptor superfamily that promotes adipogenesis and enhances insulin sensitivity by controlling the expression of genes in glucose and lipid metabolism. Given the large size of the ligand binding pocket in PPARγ, novel classes of both full and partial agonists that are structurally distinct from TZDs have been discovered. These compounds have been effective tools in differentiating adipogenic and insulin‐sensitizing activities as well as tissue selectivity of PPARγ activation. This information has led to the hypothesis that one ligand can activate or inactivate PPARs depending upon the tissue in which the PPAR resides. Thus particular compounds can be designated selective PPAR modulators or SPPARMs, a concept similar to that observed with the activation of estrogen receptor (ER) by SERMS. Additionally, both preclinical and clinical data suggest that PPARγ activation is useful for the prevention of atherosclerosis. However, the effects of TZDs on plasma lipid profiles do not solely account for their anti‐atherogenic effects. Recent studies with macrophage cells and animal models for atherosclerosis indicate that TZDs reduce the size and number of lesions formed in the vessel wall by modulating foam cell formation and inflammatory responses by macrophages. Thus in addition to the treatment of type II diabetes, PPARγ agonists can be potentially employed for the treatment of atherosclerosis in general population. J. Cell. Biochem. 89: 38–47, 2003. © 2003 Wiley‐Liss, Inc.
Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells
Authors: Chaudhary Lala R. , Hruska Keith A.
Published: April 2003

Although curcumin has been shown to inhibit prostate tumor growth in animal models, its mechanism of action is not clear. To better understand the anti‐cancer effects of curcumin, we investigated the effects of curcumin on cell survival factor Akt in human prostate cancer cell lines, LNCaP, PC‐3, and DU‐145. Our results demonstrated differential activation of Akt. Akt was constitutively activated in LNCaP and PC‐3 cells. Curcumin inhibited completely Akt activation in both LNCaP and PC‐3 cells. The presence of 10% serum decreased the inhibitory effect of curcumin in PC‐3 cells whereas complete inhibition was observed in 0.5% serum. Very little or no activation of Akt was observed in serum starved DU‐145 cells (0.5% serum). The presence of 10% serum activated Akt in DU‐145 cells and was not inhibited by curcumin. Results suggest that one of the mechanisms of curcumin inhibition of prostate cancer may be via inhibition of Akt. To our knowledge this is the first report on the curcumin inhibition of Akt activation in LNCaP and PC‐3 but not in DU‐145 cells. J. Cell. Biochem. 89: 1–5, 2003. © 2003 Wiley‐Liss, Inc.
Role of Pin2/TRF1 in telomere maintenance and cell cycle control
Authors: Zhou Xiao Zhen , Perrem Kilian , Lu Kun Ping
Published: April 2003

Telomeres are specialized structures found at the extreme ends of chromosomes, which have many functions, including preserving genomic stability, maintaining cell proliferative capacity, and blocking the activation of DNA‐damage cell cycle checkpoints. Deregulation of telomere length has been implicated in cancer and ageing. Telomere maintenance is tightly regulated by telomerase and many other telomere‐associated proteins and is also closely linked to cell cycle control, especially mitotic regulation. However, little is known about the identity and function of the signaling molecules connecting telomere maintenance and cell cycle control. Pin2/TRF1 was originally identified as a protein bound to telomeric DNA (TRF1) and as a protein involved in mitotic regulation (Pin2). Pin2/TRF1 negatively regulates telomere length and importantly, its function is tightly regulated during the cell cycle, acting as an important regulator of mitosis. Recent identification of many Pin2/TRF1 upstream regulators and downstream targets has provided important clues to understanding the dual roles of Pin2/TRF1 in telomere maintenance and cell cycle control. These results have led us to propose that Pin2/TRF1 functions as a key molecule in connecting telomere maintenance and cell cycle control. J. Cell. Biochem. 89: 19–37, 2003. © 2003 Wiley‐Liss, Inc.
Sequence requirement for nuclear localization and growth inhibition of p27Kip1R, a degradation‐resistant isoform of p27Kip1
Authors: Hirano Katsuya , Zeng Ying , Hirano Mayumi , Nishimura Junji , Kanaide Hideo
Published: April 2003

p27Kip1R is an isoform of p27Kip1, having a distinct C‐terminus. The sequences of p27Kip1R required for nuclear localization and growth inhibition were determined in HeLa cells using a green fluorescence protein (GFP) as a reporter molecule. Region 153–168 and residues K168 and I169 were determined to play a critical role in the nuclear localization of p27Kip1R. Aliphatic amino acid was found to be a substitute for the basic residue in the typical nuclear localization signal, while its functional substitution was incomplete, thereby causing a significant cytoplasmic retention of p27Kip1R. p27Kip1R is thus the first example of an atypical bipartite nuclear localization signal with aliphatic amino acid as a functional residue. Despite cytoplasmic retention, p27Kip1R inhibited the cell growth as well as p27Kip1, while GFP alone had no effect. The mutants lacking an N‐terminus containing the binding regions for cyclins and cyclin‐dependent kinases also showed a significant degree of nuclear localization, but failed to inhibit cell growth. The growth inhibition by p27Kip1R as well as p27Kip1 was thus suggested to originate in the common N‐terminal region. J. Cell. Biochem. 89: 191–202, 2003. © 2003 Wiley‐Liss, Inc.
Induction of cellular necrosis by the glutathione peroxidase mimetic ebselen
Authors: Guérin Paul J. , Gauthier Eric R.
Published: April 2003

The selenium‐based compound ebselen is a powerful antioxidant, a potent anti‐inflammatory agent and a potential neuroprotective compound. Several studies have demonstrated that part of the biological effect of ebselen is the result of the inhibition of apoptosis. We show in this report that ebselen induced the necrotic cell death of Sp2/0‐Ag14 hybridoma cells. This process was rapid, with over 90% of the cells being dead after a 2 h exposure to 50 μM ebselen. The toxic effect of ebselen could not be prevented by the caspase inhibitor Z‐VAD‐fmk but could be blocked with thiol‐containing compounds. Interestingly, ebselen addition completely prevented caspase activation in cycloheximide‐treated Sp2/O‐Ag14 cells, indicating that this antioxidant interferes with the apoptotic machinery. Our results indicate that some cell types are acutely sensitive to the toxic effect of ebselen, and that ebselen‐induced cell death interferes with apoptotic processes. These observations are of particular importance since ebselen is currently used in clinical trials for possible use as therapeutic agent for stroke. J. Cell. Biochem. 89: 203–211, 2003. © 2003 Wiley‐Liss, Inc.
Phosphatidylinositol 3‐kinase coordinately activates the MEK/ERK and AKT/NFκB pathways to maintain osteoclast survival
Authors: Gingery Anne , Bradley Elizabeth , Shaw Aubie , Oursler Merry Jo
Published: April 2003

We have examined highly purified osteoclasts that were generated in vitro from murine co‐culture of marrow precursors with stromal support cells and have found evidence of activation of the MEK/ERK and AKT/NFκB survival pathways. Many mature marrow‐derived osteoclasts survived for at least 48 h in culture whether or not they are maintained with stromal cells. Moreover, supplementing purified osteoclasts with RANKL and/or M‐CSF had no impact on their survival pattern. In addition, spleen‐derived osteoclasts generated with RANKL and M‐CSF treatment exhibited a similar survival pattern. Blocking MEK, AKT, or NFκB activity resulted in apoptosis of many, but not all, of the osteoclasts in purified marrow‐derived osteoclasts, marrow‐derived osteoclasts co‐cultured with stromal cells, and spleen‐derived osteoclasts maintained with RANKL and M‐CSF. These data support that both the MEK/ERK and AKT/NFκB pathways contribute to osteoclast survival. Since PI3K has been shown to activate either of these pathways, we have examined its role in osteoclast survival. PI3K inhibition caused apoptosis of nearly all osteoclasts in purified and co‐cultured marrow‐derived osteoclasts and spleen‐derived osteoclasts maintained with RANKL and M‐CSF. Interestingly, in marrow‐derived co‐cultures, the apoptotic response was restricted to osteoclasts as there was no evidence of stromal support cell apoptosis. PI3K inhibition also blocked MEK1/2, ERK1/2, and AKT phosphorylation and NFκB activation in purified osteoclasts. Simultaneous blockage of both AKT and MEK1/2 caused rapid apoptosis of nearly all osteoclasts, mimicking the response to PI3K inhibition. These data reveal that PI3K coordinately activates two distinct survival pathways that are both important in osteoclast survival. J. Cell. Biochem. 89: 165–179, 2003. © 2003 Wiley‐Liss, Inc.