bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Visualization Skills of Engineering Graphics Students Using Simple JavaScript Web Based Games
Authors: Crown Stephen W.
Published: January 2013

A number of web‐based games were created using simple JavaScript code to teach visualization skills needed for a course in engineering graphics. The games are part of a comprehensive multimedia instructional CD‐ROM/web page that consists of an integrated web site with links to hours of tutorial movies, lecture presentations of class lectures, and a series of interactive web‐based quizzes. The web‐based games provide an interactive graphics based introduction to engineering graphics and a class design project. In addition, several games are devoted to the development of visualization skills in the areas of multiview drawings and pictorials, auxiliary views, the manipulation of objects and coordinate systems in a 3‐D coordinate space, and dimensioning and tolerancing. The games provide an interactive learning experience for students where tutorial animations specific to the students needs are interjected into the games. The feedback based on student input in the games allows the students to learn and apply new concepts simultaneously. The impact of the game pages on student understanding and the development of visualization skills have been positive as evidenced by improved performance on exams and positive feedback on surveys. The overall effectiveness of the instructional CD has also been positive, and this continues to be used and expanded.
Innovative First Year Aerospace Design Course at MIT
Authors: Newman Dava J. , Amir Amir R.
Published: January 2013

Students at MIT typically take major‐specific courses beginning with their second year of studies. For the first year students eager to begin their aerospace education and to help those students unsure about selecting aerospace engineering as their major field, the MIT Department of Aeronautics and Astronautics offers an elective course, Introduction to Aerospace and Design. The course makes use of the new opportunities offered by the World Wide Web and provides students a real engineering experience through the hands‐on, Lighter‐Than‐Air (LTA) vehicle design project. The course teaches the basic concepts of aeronautics, includes lectures on design, and gives an overview of astronautics. The flexibility inherent in the World Wide Web allows us to accommodate the needs of students who require a review of the fundamentals in addition to in‐ class lecture material and the needs of others who desire to learn advanced material beyond what is presented in lecture. A Web‐based Discussion Forum greatly facilitated interaction among students, resulting in better vehicle designs and a friendlier classroom environment. The course culminates in an LTA vehicle design competition in which teams of five to six students design and build radio‐controlled blimps measuring up to 5 meters in length. The vehicles are flown around the perimeter of a basketball court with the objective of carrying a maximum amount of payload in a minimum amount of time. The students are introduced to real‐world engineering practice through oral presentations of their preliminary designs and critical designs in front of a faculty jury. Towards the end of the course, the students are required to submit a design portfolio showing how their LTA vehicles took shape via their individual and team efforts. The students are permitted to examine previous designs and improve upon them, yielding better vehicles every year. Results from a survey indicated that the freshmen felt much more comfortable working on technical problems with no clear answers as well as designing and building a device from an assortment of given parts.
Cooperative Learning Instructional Activities in a Capstone Design Course
Authors: Pimmel Russ
Published: January 2013

In developing our capstone design course, we decided to include instruction in design methodology, project management, engineering communications, and professional ethics, along with a comprehensive design project. As this course evolved over a number of years, we found that active and cooperative learning was critical for effective instruction in these topics and we developed a series of instructional activities using this methodology. These activities consisted of short presentations (mini‐lectures) with interspersed team exercises. We describe our course, these instructional activities, and some evaluation data showing that our students found them effective and important. Our experiences convinced us that the cooperative learning approach both enhanced our students' understanding of these topics and encouraged them to incorporate the associated skills into their working skill set. Including team exercises that dealt with various steps in the design process provided a “jump‐start” on these unfamiliar activities in a structured, short duration exercise environment in class. Listening to presentations by other teams and reviewing and discussing another team's results as a part of the team exercises provided an opportunity to see and think about different formulations of the problem they just considered.
Generic Skills Teaching in Materials Science and Engineering
Authors: Hoddinott John , Young David
Published: January 2013

University education has been very effective in preparing graduates to be discipline experts but there has been an increased emphasis on students becoming more generalist in their abilities. This paper examines the opinions that instructors and students have about the teaching of generic skills in a School of Materials Science and Engineering in Australia. In interviews, both groups demonstrated a limited understanding of what constituted generic skills, but classroom observation found broad evidence of a range of such skills being taught and practiced. We conclude that it would be an advantage for the students, and their subsequent employers, if instructors worked to make the teaching and practice of generic skills more explicit in their course materials.
Globalization and the Undergraduate Manufacturing Engineering Curriculum
Authors: SWEARENGEN J.C. , BARNES SPENCER , COE STEVEN , REINHARDT CARSTEN , SUBRAMANIAN K.
Published: January 2013

At an ASME panel on manufacturing engineering education, industry representatives emphasized preparation for globalization. The concept has not yet had widespread impact on undergraduate engineering curricula. In this paper the industry updates are summarized, especially as they pertain to undergraduate engineering education for a globalized economy, and synthesized with the literature on the subject. Objectives for manufacturing engineering education are derived and possible ways of introducing the subject into an undergraduate curriculum without lengthening the program are suggested. The findings should be applicable to manufacturing, mechanical, and industrial engineering.
Fire‐Fighting Robot Contest: Interdisciplinary Design Curricula in College and High School
Authors: Verner Igor M. , Ahlgren David J.
Published: January 2013

This paper describes the Trinity College Fire‐Fighting Home Robot Contest and contest‐related curricular developments at the college level and the high school level. We discuss the learning processes related to team‐based robot design projects and present findings obtained from the contest surveys, pertaining to learning subjects, activities and motivation of the participants.
The Academic Bookshelf
Authors: Rover Diane T.
Published: January 2013

Interdisciplinary Teaching and Learning: What, Why, and How Interdisciplinary Courses and Team Teaching: New Arrangements for Learning by James R. Davis
A Retrospective on Undergraduate Engineering Success for Underrepresented Minority Students
Authors: May Gary S. , Chubin Daryl E.
Published: January 2013

This paper examines the various factors that contribute to the success of minority students in engineering programs by exploring past and current paradigms promoting success and analyzing models for advancing the participation of members of these populations. Included is a literature review of articles, government reports, Web sites, and archives published since 1980. Student success is correlated to several indicators, including pre‐college preparation, recruitment programs, admissions policies, financial assistance, academic intervention programs, and graduate school preparation and admission. This review suggests that the problem of minority underrepresentation and success in engineering is soluble given the appropriate resources and collective national “will” to propagate effective approaches.
Engineering Design: Examining the Impact of Gender and the Team's Gender Composition
Authors: Laeser Melissa , Moskal Barbara M. , Knecht Robert , Lasich Debra
Published: January 2013

This project used Eberhardt's team functions as an observational protocol to examine the team process as it occurred in the Engineering Practices Introductory Course Sequence (EPICS) at the Colorado School of Mines. A design report scoring rubric was used to evaluate the quality of the team‐produced final report. The results of this study suggest that the gender composition of the teams impacted both the interactions that took place during the team process and the quality of the team's final report.

Members of majority male teams were more likely to be witnessed clarifying and standard setting during team interactions than were members of majority female teams. During the first course, the final reports that were produced by majority male teams on average were judged to be of higher quality than were those that were produced by majority female teams. The reverse was found to be true in the second course.
Developing an Observation System to Capture Instructional Differences in Engineering Classrooms
Authors: HARRIS ALENE H. , COX MONICA FARMER
Published: January 2013

In 1999, bioengineering and learning science faculties at four research universities began collaboration on a National Science Foundation‐supported Engineering Research Center. The Vanderbilt‐Northwestern‐Texas‐Harvard/MIT Engineering Research Center for Bioengineering Education and Technology is the first such Center to have a specific focus on postsecondary education. Within this project, educators, learning scientists, and bioengineers collaborated to develop the VaNTH Observation System, an assessment tool to capture quantitatively teaching and learning experiences of the bioengineering classroom. The four components of the instrument address the professor's interaction with students, students' lesson engagement, narrative notes, and research‐based measures of effective teaching. As professors redesigned lessons to incorporate current learning theory as a guide, observers measured differences in bioengineering classroom experiences resulting from these innovations. Results indicate that the observation instrument captures differences in classroom experiences, and these differences relate to a lesson's incorporation of current learning theory.
The Evolution of Curricular Change Models within the Foundation Coalition
Authors: CLARK M. CAROLYN , FROYD JEFFREY , MERTON PRUDENCE , RICHARDSON JIM
Published: January 2013

This paper examines one aspect of the curricular change process undertaken by the Foundation Coalition (FC); specifically, how understanding about curricular change held by the FC leaders evolved as they moved through the process of establishing a new curriculum at their institutions. The initial change model was similar to that used for product development and emphasized the role of a pilot program. However, as the curriculum moved beyond the pilot stage to adoption and full‐scale implementation, and then into the final stage where sustaining the new curriculum was the focus, the change model became more complex. Those complexities reflect a parallel evolution in their understanding of what constitutes a curriculum, from their initial conceptualization of it as a product to be carefully designed towards an understanding of it as a dynamic entity whose growth must be sustained.
Engineering Concepts and Communication: A Two‐Quarter Course Sequence
Authors: LENGSFELD CORINNE S. , EDELSTEIN GERALD , BLACK JANET , HIGHTOWER NANCY , ROOT MELISSA , STEVENS KIRA , WHITT MARGARET
Published: January 2013

Together the departments of engineering and English designed and implemented a course sequence that sustains first‐year enrollment in engineering while teaching engineering design and fundamental communication skills. The sequence integrates the goals of four formally separate courses: Critical Reading and Writing, Argument and Research, Engineering Concepts I and II. Linking the courses did not detract from the original course goals nor burden the limited time resources of the participating faculty. We found that the linked courses have increased our first to second year retention rate by up to 30 percent.
Evaluation of a Challenge‐based Human Metabolism Laboratory for Undergraduates
Authors: Linsenmeier R.A. , Kanter D.E. , Smith H.D. , Linsenmeier K.A. , McKenna A.F.
Published: January 2013

This paper discusses an effort to enhance the learning and affective experience of students in a laboratory module in metabolism through the use of the “How People Learn” framework, which is grounded in educational theory and research. The laboratory, which was a component of a systems physiology course in biomedical engineering, was modified such that some students had educational experiences informed by How People Learn principles while other students encountered a more traditional laboratory. Students were compared on a number of dimensions including knowledge acquisition, ability to use information to solve problems, transfer, and perceptions of their course experience. Several differences were observed between groups, with students in the “How People Learn” group out‐performing controls on measures that required a deeper ability to use the material, but not differing in basic acquisition of information. Implications for the development of similar laboratories are discussed.
An Investigation of Students' Conceptual Understanding in Related Sophomore to Graduate‐Level Engineering and Mechanics Courses
Authors: Montfort Devlin , Brown Shane , Pollock David
Published: January 2013

Interviews were conducted with students from a sophomore‐level mechanics of materials class, a sophomore/junior‐level structures class, a senior‐level steel design class and a graduate‐level advanced steel design class to investigate students' conceptual understanding of bending and normal stress. The graduate students generally demonstrated higher computational skill and confidence but they were not significantly different from the sophomores in terms of conceptual understanding. Interestingly, the seniors showed markedly lower confidence in their ability to solve the problems posed in the interviews. Common difficulties include a conceptual definition of stress and reasoning involving the normal stresses developed under bending.
Engaging and Supporting Problem Solving in Engineering Ethics
Authors: Jonassen David H. , Shen Demei , Marra Rose M. , Cho Young‐Hoan , Lo Jenny L. , Lohani Vinod K.
Published: January 2013

Learning to solve ethical problems is essential to the education of all engineers. Engineering ethics problems are complex and ill structured with multiple perspectives and interpretations to address in their solution. In two experiments, we examined alternative strategies for engaging ethical problem solving. In Experiment 1, students studied two versions of an online learning environment consisting of everyday ethics problems. Students using question hypertext links to navigate applied more perspectives and canons and wrote stronger overall solutions to ethics problems than those using embedded hypertext links. In Experiment 2, students engaged in a more generative task, evaluating alternative arguments for solutions to the cases or generating and supporting their own solutions. Both groups better supported their solutions and generated more counterclaims than control students. These studies focused on solving realistic case‐based ethics problems as an effective method for addressing ABET's ethics criteria.
An Analysis of Motivation Constructs with First‐Year Engineering Students: Relationships Among Expectancies, Values, Achievement, and Career Plans
Authors: Jones Brett D. , Paretti Marie C. , Hein Serge F. , Knott Tamara W.
Published: January 2013

Background

Researchers have identified many factors affecting undergraduate engineering students' achievement and persistence. Yet, much of this research focuses on persistence within academia, with less attention to career plans after graduation. Furthermore, the relative influence of expectancy‐versus value‐related beliefs on students' achievement and career plans is not fully understood.

Purpose (Hypothesis)

To address these gaps, we examined the relationships among the following motivation constructs for female and male first‐year engineering students: (a) expectancy‐related constructs that included engineering self‐efficacy (i.e., a judgment of one's ability to perform a task in engineering) and expectancy for success in engineering (i.e., the belief in the possibility of success in engineering); (b) value‐related constructs that included identification with engineering (i.e., the extent to which one defines the self through a role or performance in engineering) and engineering values (i.e., beliefs related to engineering interest, importance, and usefulness); (c) engineering achievement; and (d) engineering career plans.

Design/Method

Participants included 363 first‐year engineering students at a large state university. The students completed an online survey instrument in the first and second semester of their first year.

Results

Students' expectancy‐ and value‐related beliefs decreased over the first year for both men and women. Men reported higher levels for expectancy‐related beliefs than women. Expectancy‐related constructs predicted achievement better than the value‐related constructs, whereas value‐related constructs predicted career plans better for both men and women.

Conclusions

Expectancy‐ and value‐related constructs predicted different outcomes. Thus, both types of constructs are needed to understand students' achievement and career plans in engineering.
Beliefs and Expectations about Engineering Preparation Exhibited by High School STEM Teachers
Authors: Nathan Mitchell J. , Tran Natalie A. , Atwood Amy K. , Prevost Amy , Phelps L. Allen
Published: January 2013

Background

If we are to effect change in teacher practices and decision making regarding instruction, college preparation, and career success in engineering, then knowledge of teachers' beliefs and expectations about engineering needs to be understood.

Purpose (Hypothesis)

The primary purpose was to develop a statistically reliable survey instrument to document teachers' beliefs and expectations about pre‐college engineering instruction, college preparation, and career success in engineering, called the Engineering Education Beliefs and Expectations Instrument (EEBEI), and to compare teachers' views.

Design/Method

Using two samples of teachers, EEBEI was established as a statistically reliable survey and was used to examine the beliefs and expectations of Project Lead the Way (PLTW) and non‐PLTW teachers. The results were used to further examine teachers' decisions in advising fictional students (described in vignettes) with varying academic and socioeconomic profiles.

Results

High school STEM teachers report their instruction was influenced by students' interests, family background, and prior academic achievement. Comparisons between PLTW and non‐PLTW teachers revealed that non‐PLTW teachers agreed more strongly that an engineer must demonstrate high scholastic achievement in math and science whereas PLTW teachers were more likely to report that science and math content was integrated into engineering activities. Although teachers report that students' socioeconomic status was not influential when asked explicitly, it did influence situated decision‐making tasks using fictional student vignettes.

Conclusions

Findings address challenges of STEM integration and reveal conflicting purposes of K‐12 engineering education as being for a select few or to promote technological literacy for all students, which affects recruitment, instruction, and assessment practices.
Collaborative Learning in Engineering Students: Gender and Achievement
Authors: Stump Glenda S. , Hilpert Jonathan C. , Husman Jenefer , Chung Wen‐ting , Kim Wonsik
Published: January 2013

Background

Collaboration is an ABET accreditation required component of the engineering curriculum. Research has shown that collaborative learning positively influences student achievement. The relationship between motivation, collaborative learning strategies, and achievement is not well studied in an engineering education context.

Purpose(Hypothesis)

A set of hypotheses were tested that predicted positive relationships between students' self‐reported informal collaboration, self‐efficacy for learning course material, knowledge building behaviors, and course grade. A second set of hypotheses were tested that predicted gender similarities in reported self‐efficacy, and gender differences in reported collaborative learning activities.

Design/Method

One hundred fifty engineering students were surveyed for study 1 and 513 students were surveyed for study 2. Bivariate correlations were completed to examine relationship between study variables; multiple regression analysis was completed to examine predictive ability of variables on course grade; MANOVA was completed to examine multivariate relationship between variables.

Results

In study 1, students' reported use of collaborative learning strategies and reported self‐efficacy for learning course material were significantly predictive of their course grade. In study 2, female students reported greater use of collaboration as a learning strategy than their male classmates; among male and female students combined, those who received “B's” in their engineering course reported more collaboration than their peers who received “A's” or “C's” and lower.

Conclusion

Overall, students' self reported collaborative learning strategies were associated with increased self‐efficacy for learning course material and course grade, particularly for students who received “B's” in the course. Female students reported greater use of collaborative learning strategies than their male peers.
The Design and Experimental Evaluation of a Scaffolded Software Environment to Improve Engineering Students' Disciplinary Problem‐Solving Skills
Authors: Hundhausen Christopher , Agarwal Pawan , Zollars Richard , Carter Adam
Published: January 2013

Background

Introductory gateway engineering courses are notorious for their high attrition rates. Deficiencies in students' problem‐solving processes may contribute to their failure in these courses. In an empirical study of student problem solving, we observed that students struggle because of misconceptions regarding the basic syntax and semantics of disciplinary diagrams and corresponding mathematical equations.

Purpose(Hypothesis)

We hypothesize that a scaffolded software environment that provides dynamically‐generated feedback on the syntactic and semantic correctness of students' evolving disciplinary diagrams and mathematical equations can improve engineering students' problem‐solving abilities.

Design/Method

We iteratively developed ChemProV, a software environment to assist chemical engineering students in solving material balance problems. To evaluate ChemProV's effectiveness, we performed two between subjects experimental studies. The first study compared a preliminary version of the ChemProV to pen‐and‐paper. The second study compared a redesigned version of ChemProV with dynamic feedback to the same version of ChemProV without dynamic feedback.

Results

While it did not uncover any significant differences, the first study provided insight into how to improve ChemProV's dynamic feedback mechanism. The second study found that the “feedback” version of ChemProV promoted a statistically‐significant advantage in problem‐solving accuracy, significantly more time‐on‐task, and a transfer‐of‐training to an unscaffolded problem‐solving situation.

Conclusion

A scaffolded software environment like ChemProV can serve as a valuable aid in helping students learn engineering problem‐solving skills. Its software design approach can be used as a model for designing educationally‐effective software environments for other engineering disciplines.
Instructors' Intended Learning Outcomes for Using Computational Simulations as Learning Tools
Authors: Magana Alejandra J. , Brophy Sean P. , Bodner George M.
Published: January 2013

Background

The computational simulations used by the instructors in this study were originally developed for use as research tools by subject‐matter experts and then incorporated in advanced undergraduate and graduate courses in engineering and science. Although some research has been done on students' learning with these computational simulations, less progress has been made toward understanding instructors' goals, or affordances, for incorporating these simulations in their teaching.

Purpose (Hypothesis)

To identify how computational simulations can be effectively used in teaching and learning environments, this study examined instructors' rationale for using these simulations as learning tools. The study was based on the following research question: What were the intended learning outcomes that guided the instructors' use of computational simulations as learning tools?

Design/Method

This study used qualitative methods based on the theoretical framework of phenomenography. Openended interviews were conducted with 14 instructors teaching undergraduate and graduate courses in science and engineering who were not familiar with the research literature on beneficial ways of using simulations for learning and instruction.

Results

Analysis revealed an outcome space consisting of eight qualitatively different categories that detailed ways in which the engineering and science instructors in this study conceptualized the use of simulation tools with learning activities into existing courses they taught.

Conclusions

The outcome space of instructors' goals for using computational simulations is consistent with the recommendations found in the literature based on studies of the use of simulations in more restricted research settings.
Growth differentiation factor‐15 (GDF‐15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2)
Authors: Whitson Ramon J. , Lucia Marshall Scott , Lambert James R.
Published: January 2013

Growth differentiation factor‐15 (GDF‐15) and the CCN family member, connective tissue growth factor (CCN2), are associated with cardiac disease, inflammation, and cancer. The precise role and signaling mechanism for these factors in normal and diseased tissues remains elusive. Here we demonstrate an interaction between GDF‐15 and CCN2 using yeast two‐hybrid assays and have mapped the domain of interaction to the von Willebrand factor type C domain of CCN2. Biochemical pull down assays using secreted GDF‐15 and His‐tagged CCN2 produced in PC‐3 prostate cancer cells confirmed a direct interaction between these proteins. To investigate the functional consequences of this interaction, in vitro angiogenesis assays were performed. We demonstrate that GDF‐15 blocks CCN2‐mediated tube formation in human umbilical vein endothelial (HUVEC) cells. To examine the molecular mechanism whereby GDF‐15 inhibits CCN2‐mediated angiogenesis, activation of αVβ3 integrins and focal adhesion kinase (FAK) was examined. CCN2‐mediated FAK activation was inhibited by GDF‐15 and was accompanied by a decrease in αVβ3 integrin clustering in HUVEC cells. These results demonstrate, for the first time, a novel signaling pathway for GDF‐15 through interaction with the matricellular signaling molecule CCN2. Furthermore, antagonism of CCN2 mediated angiogenesis by GDF‐15 may provide insight into the functional role of GDF‐15 in disease states. J. Cell. Biochem. 114: 1424–1433, 2013. © 2012 Wiley Periodicals, Inc.
Assessment of density functional methods for reaction energetics: Iridium‐catalyzed water oxidation as case study
Authors: Kazaryan Andranik , Baerends Evert Jan
Published: January 2013

We investigate basis set convergence for a series of density functional theory (DFT) functionals (both hybrid and nonhybrid) and compare to coupled‐cluster with single and double excitations and perturbative triples [CCSD(T)] benchmark calculations. The case studied is the energetics of the water oxidation reaction by an iridium‐oxo complex. Complexation energies for the reactants and products complexes as well as the transition state (TS) energy are considered. Contrary to the expectation of relatively weak basis set dependence for DFT, the basis set effects are large, for example, more than 10 kcal mol−1 difference from converged basis for the activation energy with “small” basis sets (DZ/6‐31G** for Ir/other atoms, or SVP) and still more than 6 kcal mol−1 for def2‐TZVPP/6‐31G**. Inclusion of the dispersion correction in DFT‐D3 schemes affects the energies of reactant complex (RC), TS, and product complex (PC) by almost the same amount; it significantly improves the complexation energy (the formation of RC), but has little effect on the activation energy with respect to RC. With converged basis, some pure GGAs (PBE‐D3, BP86‐D3) as well as the hybrid functional B3LYP‐D3 are very accurate compared to benchmark CCSD(T) calculations. © 2012 Wiley Periodicals, Inc.
Dynamic distribution of HDAC1 and HDAC2 during mitosis: Association with F‐actin
Authors: He Shihua , Khan Dilshad H. , Winter Stefan , Seiser Christian , Davie James R.
Published: January 2013

During mitosis, histone deacetylase 2 (HDAC2) becomes highly phosphorylated through the action of CK2, and HDAC1 and 2 are displaced from mitotic chromosomes. HDAC1 and 2 are components of corepressor complexes, which function with lysine acetyltransferases to catalyze dynamic protein acetylation and regulate gene expression. In this study, we show that HDAC1 and 2 associate with F‐actin in mitotic cells. Inhibition of Aurora B or protein kinase CK2 did not prevent the displacement of HDAC1 and 2 from mitotic chromosomes in HeLa cells. Further, proteins of the HDAC1 and 2 corepressor complexes and transcription factors recruiting these corepressors to chromatin were dissociated from mitotic chromosomes independent of Aurora B activity. HDAC1 and 2 returned to the nuclei of daughter cells during lamin A/C reassembly and before Sp1, Sp3, and RNA polymerase II. Our results show that HDAC1 and 2 corepressor complexes are removed from the mitotic chromosomes and are available early in the events leading to the re‐establishment of the gene expression program in daughter cells. J. Cell. Physiol. 228: 1525–1535, 2013. © 2012 Wiley Periodicals, Inc.
An integrated understanding of the physiological response to elevated extracellular phosphate
Authors: Camalier Corinne E. , Yi Ming , Yu Li‐Rong , Hood Brian L. , Conrads Kelly A. , Lee Young Jae , Lin Yiming , Garneys Laura M. , Bouloux Gary F. , Young Matthew R. , Veenstra Timothy D. , Stephens Robert M. , Colburn Nancy H. , Conrads Thomas P. , Beck George R.
Published: January 2013

Recent studies have suggested that changes in serum phosphate levels influence pathological states associated with aging such as cancer, bone metabolism, and cardiovascular function, even in individuals with normal renal function. The causes are only beginning to be elucidated but are likely a combination of endocrine, paracrine, autocrine, and cell autonomous effects. We have used an integrated quantitative biology approach, combining transcriptomics and proteomics to define a multi‐phase, extracellular phosphate‐induced, signaling network in pre‐osteoblasts as well as primary human and mouse mesenchymal stromal cells. We identified a rapid mitogenic response stimulated by elevated phosphate that results in the induction of immediate early genes including c‐fos. The mechanism of activation requires FGF receptor signaling followed by stimulation of N‐Ras and activation of AP‐1 and serum response elements. A distinct long‐term response also requires FGF receptor signaling and results in N‐Ras activation and expression of genes and secretion of proteins involved in matrix regulation, calcification, and angiogenesis. The late response is synergistically enhanced by addition of FGF23 peptide. The intermediate phase results in increased oxidative phosphorylation and ATP production and is necessary for the late response providing a functional link between the phases. Collectively, the results define elevated phosphate, as a mitogen and define specific mechanisms by which phosphate stimulates proliferation and matrix regulation. Our approach provides a comprehensive understanding of the cellular response to elevated extracellular phosphate, functionally connecting temporally coordinated signaling, transcriptional, and metabolic events with changes in long‐term cell behavior. J. Cell. Physiol. 228: 1536–1550, 2013. © 2012 Wiley Periodicals, Inc.
Glycated collagen and altered glucose increase endothelial cell adhesion strength
Authors: Kemeny Steven Frank , Cicalese Stephanie , Figueroa Dannielle Solomon , Clyne Alisa Morss
Published: January 2013

Cell adhesion strength is important to cell survival, proliferation, migration, and mechanotransduction, yet changes in endothelial cell adhesion strength have not yet been examined in diseases such as diabetes with high rates of cardiovascular complications. We therefore investigated porcine aortic endothelial cell adhesion strength on native and glycated collagen‐coated substrates and in low, normal, and high glucose culture using a spinning disc apparatus. Adhesion strength increased by 30 dynes/cm2 in cells on glycated collagen as compared to native collagen. Attachment studies revealed that cells use higher adhesion strength αvβ3 integrins to bind to glycated collagen instead of the typical α2β1 integrins used to bind to native collagen. Similarly, endothelial cells cultured in low and high glucose had 15 dynes/cm2 higher adhesion strength than cells in normal glucose after 2 days. Increased adhesion strength was due to elevated VEGF release and intracellular PKC in low and high glucose cells, respectively. Thus glucose increased endothelial cell adhesion strength via different underlying mechanisms. These adhesion strength changes could contribute to diabetic vascular disease, including accelerated atherosclerosis and disordered angiogenesis. J. Cell. Physiol. 228: 1727–1736, 2013. © 2013 Wiley Periodicals, Inc.
Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated phenotype
Authors: Leimgruber Carolina , Quintar Amado Alfredo , García Luciana Noemí , Petiti Juan Pablo , De Paul Ana Lucía , Maldonado Cristina Alicia
Published: January 2013

Prostate smooth muscle cells (pSMCs) are capable of responding to inflammatory stimuli by secreting proinflammatory products, which causes pSMCs to undergo dedifferentiation. Although it has been proposed that androgens decrease proinflammatory molecules in many cells and under various conditions, the role of testosterone in the prostate inflammatory microenvironment is still unclear. Therefore, our aim was to evaluate if testosterone was able to modulate the pSMCs response to bacterial LPS by stimulating primary pSMC cultures, containing testosterone or vehicle, with LPS (1 or 10 µg/ml) for 24–48 h. The LPS challenge induced pSMCs dedifferentiation as evidenced by a decrease of calponin and alpha smooth muscle actin along with an increase of vimentin in a dose‐dependent manner, whereas testosterone abrogated these alterations. Additionally, an ultrastructural analysis showed that pSMCs acquired a secretory profile after LPS and developed proteinopoietic organelles, while pSMCs preincubated with testosterone maintained a more differentiated phenotype. Testosterone downregulated the expression of surface TLR4 in control cells and inhibited any increase after LPS treatment. Moreover, testosterone prevented IκB‐α degradation and the LPS‐induced NF‐κB nuclear translocation. Testosterone also decreased TNF‐α and IL6 production by pSMCs after LPS as quantified by ELISA. Finally, we observed that testosterone inhibited the induction of pSMCs proliferation incited by LPS. Taken together, these results indicate that testosterone reduced the proinflammatory pSMCs response to LPS, with these cells being less reactive in the presence of androgens. In this context, testosterone might have a homeostatic role by contributing to preserve a contractile phenotype on pSMCs under inflammatory conditions. J. Cell. Physiol. 228: 1551–1560, 2013. © 2012 Wiley Periodicals, Inc.
Analysis of the protein network of cholesterol homeostasis in different brain regions: An age and sex dependent perspective
Authors: Segatto Marco , Di Giovanni Annalaura , Marino Maria , Pallottini Valentina
Published: January 2013

Although a great knowledge about the patho‐physiological roles of cholesterol metabolism perturbation in several organs has been reached, scarce information is available on the regulation of cholesterol homeostasis in the brain where this lipid is involved in the maintenance of several of neuronal processes. Currently, no study is available in literature dealing how and if sex and age may modulate the major proteins involved in the regulatory network of cholesterol levels in different brain regions. Here, we investigated the behavior of 3‐hydroxy 3‐methylglutaryl coenzyme A reductase (HMGR) and low‐density lipoprotein receptor (LDLr) in adult (3‐month‐old) and aged (12‐month‐old) male and female rats. The analyses were performed in four different brain regions: cortex, brain stem, hippocampus, and cerebellum which represent brain areas characterized by different neuronal cell types, metabolism, cytoarchitecture and white matter composition. The results show that in hippocampus HMGR is lower (30%) in adult female rats than in age‐matched males. Differences in LDLr expression are also observable in old females with respect to age‐matched males: the protein levels increase (40%) in hippocampus and decrease (20%) in cortex, displaying different mechanisms of regulation. The mechanism underlying the observed modifications are ascribable to Insig‐1 and SREBP‐1 modulation. The obtained data demonstrate that age‐ and sex‐related differences in cholesterol homeostasis maintenance exist among brain regions, such as the hippocampus and the prefrontal cortex, important for learning, memory and affection. Some of these differences could be at the root of marked gender disparities observed in clinical disease incidence, manifestation, and prognosis. J. Cell. Physiol. 228: 1561–1567, 2013. © 2012 Wiley Periodicals, Inc.
Pin1 and Nuclear Receptors: A New Language?
Authors: La Montagna Raffaele , Caligiuri Isabella , Giordano Antonio , Rizzolio Flavio
Published: January 2013

Pin1 is a unique enzyme that can isomerize specific phospho‐Ser/Thr‐Pro peptide bonds, inducing a conformational change in the target protein. Such activity represents a novel and tightly controlled signaling mechanism regulating a spectrum of protein functions during the normal physiology of the cell and in pathological conditions. Our last study demonstrated that Pin1 interacts with the androgen receptor protein and that this interaction is important for its transcriptional activity. Here, we consider the activity that Pin1 plays on the N‐terminal domain of different nuclear receptors and provide an interpretation of this phenomenon. J. Cell. Physiol. 228: 1799–1801, 2013. © 2012 Wiley Periodicals, Inc.
Nck1 deficiency accelerates unloading‐induced bone loss
Authors: Aryal A.C. Smriti , Miyai Kentaro , Hayata Tadayoshi , Notomi Takuya , Nakamoto Tetsuya , Pawson Tony , Ezura Yoichi , Noda Masaki
Published: January 2013

Mechanical stress is an important signal to determine the levels of bone mass. Unloading‐induced osteoporosis is a critical issue in bed‐ridden patients and astronauts. Many molecules have been suggested to be involved in sensing mechanical stress in bone, though the mechanisms involved in this phenomenon are not fully understood. Nck1 is an adaptor protein known to mediate signaling from plasma membrane‐activated receptors to cytosolic effectors regulating actin cytoskeleton remodeling. Nck1 has also been implicated in cellular responses to endoplasmic reticulum stress. In vitro, in case of cell stress the actin cytoskeleton is disrupted and in such cases Nck1 has been reported to enter the nucleus of the cells to mediate the nuclear actin polymerization. However, the role of Nck1 in vivo during the bone response to mechanical stimuli is unknown. The purpose of this study is to examine the role of Nck1 in unloading‐induced bone loss in vivo. Sciatic and femoral nerve resection was conducted. Neurectomy‐based unloading enhanced Nck1 gene expression in bone about twofold. Using the Nck1 deficient mice and control Nck1+/+, effects of neurectomy‐based unloading on bone structure were examined. Unloading reduced bone volume in wild type mice by 30% whereas the levels in bone loss were exacerbated to 50% in Nck1 deficient mice due to neurectomy after 4 weeks. These data demonstrate that Nck1 gene deficiency accelerates the mechanical unloading‐induced bone loss suggesting Nck1 to be a crucial molecule in mechanical stress mediated regulation in bone metabolism. J. Cell. Physiol. 228: 1397–1403, 2013. © 2012 Wiley Periodicals, Inc.
Galectin‐3 deficiency protects pancreatic islet cells from cytokine‐triggered apoptosis in vitro
Authors: Saksida Tamara , Nikolic Ivana , Vujicic Milica , Nilsson Ulf J. , Leffler Hakon , Lukic Miodrag L. , Stojanovic Ivana , Stosic‐Grujicic Stanislava
Published: January 2013

Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin‐3 deficient (LGALS3−/−) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin‐3 and to delineate the underlying mechanism. Deficiency of galectin‐3, either hereditary or induced through application of chemical inhibitors, β‐lactose or TD139, supported survival and function of islet beta cells compromised by TNF‐α + IFN‐γ + IL‐1β stimulus. Similarly, inhibition of galectin‐3 by β‐lactose or TD139 reduced cytokine‐triggered apoptosis of beta cells, leading to conclusion that endogenous galectin‐3 propagates beta apoptosis in the presence of an inflammatory milieu. Exploring apoptosis‐related molecules expression in primary islet cells before and after treatment with cytokines we found that galectin‐3 ablation affected the expression of major components of mitochondrial apoptotic pathway, such as BAX, caspase‐9, Apaf, SMAC, caspase‐3, and AIF. In contrast, anti‐apoptotic molecules Bcl‐2 and Bcl‐XL were up‐regulated in LGALS3−/− islet cells when compared to wild‐type (WT) counterparts (C57BL/6), resulting in increased ratio of anti‐apoptotic versus pro‐apoptotic molecules. However, Fas‐triggered apoptotic pathway as well as extracellular signal‐regulated kinase 1/2 (ERK1/2) was not influenced by LGALS‐3 deletion. All together, these results point to an important role of endogenous galectin‐3 in beta cell apoptosis in the inflammatory milieu that occurs during diabetes pathogenesis and implicates impairment of mitochondrial apoptotic pathway as a key event in protection from beta cell apoptosis in the absence of galectin‐3. J. Cell. Physiol. 228: 1568–1576, 2013. © 2012 Wiley Periodicals, Inc.
Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration
Authors: Casablancas Antoni , Gámez Xavier , Lecina Martí , Solà Carles , Cairó Jordi J. , Gòdia Francesc
Published: January 2013

BACKGROUND

Improvement of the mammalian cell culture process is based on the implementation of culture strategies with higher productivities, such as fed‐batch or perfusion processes. The efficient development of these culture strategies depends strongly on the availability of suitable monitoring tools to determine the activity of cell culture and adjust nutrient feeding correspondingly.

RESULTS

In this study oxygen uptake rate (OUR), cell density and glucose concentration on‐line monitoring systems are applied to control fed‐batch processes. Different combinations of these monitoring systems were used to determine cell growth and metabolic activity of cell culture in order to adjust substrate feeding in a balanced manner. Application of these monitoring tools in fed‐batch processes allowed extension of the exponential growth of hybridoma cells up to 2–3‐fold and increased antibody productivity from 84 to 168% with respect to conventional batch culture.

CONCLUSIONS

The three control strategies tested have been successful in providing improvement of the fed‐batch culture of the hybridoma cell line used. Among the different alternatives studied, the use of OUR on‐line monitoring to simultaneously determine cell growth and metabolic activity appears to be the best method to adjust substrate feeding owing to its simplicity and robustness. © 2012 Society of Chemical Industry
Bioremediation of nitrate‐polluted groundwater in a microbial fuel cell
Authors: Pous Narcis , Puig Sebastià , Coma Marta , Balaguer Maria D. , Colprim Jesus
Published: January 2013

BACKGROUND

Groundwater quality is threatened by nitrate accumulation in several regions around the world. Nitrate must be removed from contaminated groundwater to use it as drinking water. Microbial fuel cells (MFCs) can be used for autotrophic denitrification. Thus, the use of MFCs is a potential alternative to using traditional methods for treating nitrate‐polluted groundwater.

RESULTS

The objective of this study was to evaluate the potential of MFC technology to treat nitrate‐polluted groundwater (28.32 ± 6.15 mgN‐NO3− L−1). The bioanode was fed with an acetate solution that permitted electron and proton flux to the biocathode. Initially, nitrite was observed in the effluent. After 97 days of operation, the denitrifying‐MFC reduced the nitrate and nitrite concentrations in the effluent (12.14 ± 3.59 mgN‐NO3− L−1 and 0.14 ± 0.13 mgN‐NO2− L−1).Thus, this method improved water quality to meet World Health Organisation standards. However, nitrous oxide emissions were deduced from the electron balance, cathode coulumbic efficiency and Tafel plots. Bioelectrochemical evolution of the biocathode was related to the denitrification nature (sequential reaction steps from NO3− to N2, through NO2− and N2O as stable intermediates) and was supported by the Tafel plots.

CONCLUSION

The bioremediation of nitrate‐polluted groundwater with a MFC biocathode is feasible. © 2012 Society of Chemical Industry