bluuebunny/crossref_metadata_2025 huggingface dataset:
Closing the Gap: Preparing Computing Students for Employment through Embedding Work-Related Learning in the Taught Curriculum
Authors: McKinnon Sabine , McCrae June
Published: August 2012

This paper presents the findings from a pilot study which explored the impact of embedding work-related learning activities in the first-year computing curriculum at Glasgow Caledonian University. Students worked in teams on practical projects which were formally assessed and the researchers gathered student feedback using two online surveys (n=159) and focus groups (n=29). The findings indicate that 85% of the students felt that their learning on the module had improved their employability skills but that their confidence levels in most skills were lower at the end of the module. The paper suggests that first-year students' realistic awareness of their own skills gaps leads to more focused learning in their remaining years of study.
Practical Elements in Danish Engineering Programmes, Including the European Project Semester
Authors: Hansen Jørgen
Published: August 2012

In Denmark, all engineering programmes in HE have practical elements; for instance, at Bachelor's level, an internship is an integrated part of the programme. Furthermore, Denmark has a long-established tradition of problem-based and project-organized learning, and a large part of students' projects, including their final projects, is done in cooperation with industry. This interaction with industry is important because students learn about the culture of the companies with which they are involved and they usually find it very motivating to discover that the companies can benefit from their work. Given the difference between theoretical teaching at a university and practical work done in a company, internships help students to combine practice and theory. Many large projects involve teams and this offers students good learning opportunities and enables them to improve their interpersonal skills. In addition, students learn to learn, an increasingly important requirement since knowledge can rapidly become outdated. Engineers must now be able to work in an international context and to address this need a ‘European Project Semester’ (EPS) was introduced in 1995. EPS is based on experience from problem-based learning in an international context, with exchange students working in international teams. The focus is on international teamwork and intercultural communication and students not only acquire technical skills but also improve their communication skills and their international competences.
International Innovation Camps
Authors: Silva Paulino , Temple Bryan K. , Kälviäinen Mirja , Mantzalos Costas , Horký Emil , Stoklasa Michal , Orme Philip
Published: August 2012

A two-week workshop was held in Finland during February 2010 and again in Glasgow in February 2011. The events were sponsored by the European Lifelong Learning programme. Students from Portugal, Cyprus, the Czech Republic, Finland and the UK were placed in multicultural teams of five. Each team had two product designers, one graphic designer, one financial and one marketing student. They were set the task of devising new product ideas for a local company and they had two weeks in which to do it. These intensive workshops comprised lectures and practice sessions as well as ideation sessions for the new product ideas. This paper reports on the reactions to the first programme and the lessons learned.
Characterisation of the Physical and Metallurgical Properties of Natural Iron Ore for Iron Production
Authors: Muwanguzi Abraham J. B. , Karasev Andrey V. , Byaruhanga Joseph K. , Jönsson Pär G.
Published: August 2012

The blast furnace is still the dominant form of iron production, but over the years, direct reduction methods have increased due to a number of reasons. Overall, iron production methods have optimal requirements with respect to the feed materials especially iron ore. In this study, tests were carried out on Muko iron ore from Uganda to analyse its suitability to meet the feed requirements of today's dominant iron production methods. More specifically, the Tumbler, Abrasion, and Shatter Indices of the ore were determined. In addition, porosity, thermoanalysis, and reducibility tests were performed. Overall, the Muko ore was found to have good mechanical properties exemplified with tumble and shatter index data >89.0 wt% and <2.5 wt%, respectively. Furthermore, its reducibility at 0.87%/min is within the acceptable range as a natural material feed for blast furnace and direct reduction furnaces. Also, the energy requirement for heating the ore to 1100°C was found to be higher in the samples containing a wider size range of irregular grains and the largest contaminations. In summary, it is concluded that the Muko iron ore has good physical and metallurgical properties to serve as a natural material for the blast furnace and direct reduction furnaces.
The Kinetics of Joined Action of Triplet-Triplet Annihilation and First-Order Decay of Molecules in the State in the Case of Nondominant First-Order Process
Authors: Borowicz Paweł , Nickel Bernhard
Published: August 2012

This paper presents the description of triplet-triplet annihilation in the case of nondominant first-order decay of molecules in the triplet state. The kinetics of the statistical system is influenced by joined action of two processes: the first- and second-order decies. This kinetics can be described with analytical function if the rate parameter of second-order reaction is constant. The approach presented here combines the well-known Smoluchowski formula with the previously published intuitive and non-Fickian models of diffusion-controlled triplet-triplet annihilation. The kinetics of the delayed fluorescence of anthracene is used as a practical example of applicability of the model proposed. The advantages and limits of the proposed model are discussed.
Ricci Solitons in α-Sasakian Manifolds
Authors: Ingalahalli Gurupadavva , Bagewadi C. S.
Published: August 2012

We study Ricci solitons in α-Sasakian manifolds. It is shown that a symmetric parallel second order-covariant tensor in a α-Sasakian manifold is a constant multiple of the metric tensor. Using this, it is shown that if ℒVg+2S is parallel where V is a given vector field, then (g,V,λ) is Ricci soliton. Further, by virtue of this result, Ricci solitons for n-dimensional α-Sasakian manifolds are obtained. Next, Ricci solitons for 3-dimensional α-Sasakian manifolds are discussed with an example.
On Fundamental Domains for Subgroups of Isometries Acting in
Authors: Lascurain Orive Antonio , Molina Hernández Rubén
Published: August 2012

Given a fundamental polyhedron for the action of , a classical
kleinian group, acting in -dimensional hyperbolic space, and , a finite index
subgroup of , one obtains a fundamental domain for pasting copies of
by a Schreier process. It also generalizes the side pairing
generating theorem for exact or inexact polyhedra. It is proved
as well that the general Möbius group acting in
is transitive on “-spheres”. Hence, describing the hyperbolic -planes in the upper half space
model intrinsically, and providing also an alternative proof of the transitive
action on them. Some examples are given in
detail, derived from the classical modular group and the Picard group.
Quality of Life Assessment in Patients with Multiple Sclerosis Receiving Interferon Beta-1a: A Comparative Longitudinal Study of Avonex and Its Biosimilar CinnoVex
Authors: Abolfazli R. , Hosseini A. , Gholami Kh. , Javadi M. R. , Torkamandi H. , Emami S.
Published: August 2012

Background. Multiple sclerosis (MS) is an autoimmune inflammatory disease of central nervous system (CNS). MS affects quality of Life (QOL) due to physical disability and other associated problems. Disease-modifying agents like interferon beta (IFNB) have been widely utilized in this patient population; however, their frequency, route of administration, side effects, high cost, and also the question of whether they are truly beneficial for longer-term outcomes and QOL need to be further investigated. Objectives. To assess QOL in patients with multiple sclerosis receiving interferon beta-1a (Avonex or CinnoVex) and in order to compare QOL in groups receiving Avonex and CinnoVex, respectively, also, to evaluate whether the more cost-effective biosimilar form of IFNB (CinnoVex) has the same effect on QOL and can be substituted for Avonex. Methods. We conducted a 30-month, nonrandomized longitudinal study and recruited a total of 92 patients diagnosed with relapsing-remitting MS. The patients were distributed in Avonex and CinnoVex groups with 46 patients in each group. Quality of life was assessed by means of MSQOL-54 questionnaire, four times a year, at baseline and at months 4, 8, and 12 of the study. Results. Mean age ± SD was 30.5 ± 8.9 and 32.3 ± 9.0 years in Avonex and CinnoVex groups, respectively, and P value of gender was different (P value : 0.036). The physical health composite scores were 61.8 and 59.8 (P values 0.677 and 0.884) for Avonex and CinnoVex groups, in that order. The results of the study revealed no significant difference between the two groups with regard to physical health, health perception, energy, and role limitations due to physical problems, pain, sexual and social function, and physical health distress scores. Further, interferon therapy did not significantly impact patients’ QOL after a year of treatment with either Avonex or CinnoVex. Conclusions. According to the present study, treatment with IFNB (Avonex or CinnoVex) did not affect QOL during a year of therapy. Further studies with longer follow-up periods are required to assess the value of interferons on long-term outcomes and patient’s QOL.
Real-Time PCR-Coupled CE-SELEX for DNA Aptamer Selection
Authors: Ruff Patrick , Pai Rekha B. , Storici Francesca
Published: August 2012

Aptamers are short nucleic acid or peptide sequences capable of binding to a target molecule with high specificity and affinity. Also known as “artificial antibodies,” aptamers provide many advantages over antibodies. One of the major hurdles to aptamer isolation is the initial time and effort needed for selection. The systematic evolution of ligands by exponential enrichment (SELEX) is the traditional procedure for generating aptamers, but this process is lengthy and requires a large quantity of target and starting aptamer library. A relatively new procedure for generating aptamers using capillary electrophoresis (CE), known as CE-SELEX, is faster and more efficient than SELEX but requires laser-induced fluorescence (LIF) to detect the aptamer-target complexes. Here, we implemented an alternative system without LIF using real-time- (RT-) PCR to indirectly measure aptamer-target complexes. In three rounds of selection, as opposed to ten or more rounds common in SELEX protocols, a specific aptamer for bovine serum albumin (BSA) was obtained. The specificity of the aptamer to BSA was confirmed by electrophoretic mobility shift assays (EMSAs), an unlabeled competitor assay, and by a supershift assay. The system used here provides a cost effective and a highly efficient means of generating aptamers.
Das Strukturrisiko von Finanzderivaten
Authors: Keßler Oliver
Published: August 2012

Sowohl die eigenmittelbezogene als auch die kapitalmarktrechtliche Regulierung von Finanzderivaten haben in der Vergangenheit falsche Anreize gesetzt. Der Autor betrachtet vor diesem Hintergrund grenzüberschreitende OTC-Derivateverträge, bestimmt deren wechselwirkende Risiken („Strukturrisiko“) und den aufsichtsrechtlichen Umgang damit. Ein besonderer Schwerpunkt liegt auf der Erörterung der Risiken, die durch die Verwendung von Standard-Rahmenverträgen (ISDA oder DRV) entstehen, wenn es zur Anwendung konfligierender Rechtssysteme kommt. Unter Berücksichtigung des Strukturrisikos wird das Verhältnis der Marktteilnehmer untereinander, das häufig durch unterschiedlich ausgeprägte Expertise im Umgang mit Finanzderivaten geprägt ist („strukturelles Ungleichgewicht“), betrachtet. Der Autor löst das strukturelle Ungleichgewicht auf, indem er die institutionelle, aufsichtsrechtliche Kompetenz der Marktteilnehmer im Rahmen des „Modells typisierter Information“ fruchtbar macht. Der Autor ist Rechtsanwalt in Frankfurt am Main sowie Lehrbeauftragter an der GGS – German Graduate School of Management and Law in Heilbronn.
Flying High with the Bird Tetrahedron
Authors: Gjøvik Øistein
Published: August 2012

An origami activity can lead to rich tasks in several branches of mathematics.
Assessment Can Support Reasoning & Sense Making
Authors: Suurtam Christine
Published: August 2012

Teachers can use data from a research project to enhance their classroom assessment practices.
Using Disks as Models for Proofs of Series
Authors: Somchaipeng Tongta , Kruatong Tussatrin , Panijpan Bhinyo
Published: August 2012

Students use balls and disks to prove the general formulas for sums of squares and cubes.
Using Radioactive Decay to Investigate Exponential Functions
Authors: Bryan Joel A.
Published: August 2012

During the thirteen years that I taught high school physics and mathematics, I found that my physics students typically came to class excited to learn. As in all science classes, they interacted with fellow classmates while performing laboratory investigations and other group activities requiring higher-order thinking skills. To create a similar experience for my mathematics students, I developed a laboratory investigation for my precalculus class. These students responded just as favorably as my physics students to hands-on data collection activities.
Mathematics Autobiographies
Authors: Yow Jan A.
Published: August 2012

Mathematics anxiety among students and their parents has been documented for years (Fiore 1999; Jackson and Leffingwell 1999). As a classroom teacher, I saw it often in the eyes of my students on the first day of class. Now, as a mathematics teacher educator, I see a passion for mathematics in the eyes of my preservice teachers. How students feel about mathematics makes a difference in how they will learn and how they will teach (Hembree 1990). As a result of research and my own experience, the first assignment that I give students each year is to write a mathematics autobiography. In addition, I ask their parents to write a letter that introduces me to their son or daughter.
Informing Practice: Developing Symbol Sense for the Minus Sign
Authors: Lamb Lisa L. , Pierson Bishop Jessica , Philipp Randolph A. , Schappelle Bonnie P. , Whitacre Ian , Lewis Mindy
Published: August 2012

Research on how students make sense of and use the minus sign indicates that students struggle to understand the multiple meanings of this symbol. Teachers can support students in developing a robust understanding of each interpretation.
GAISEing into the Common Core of Statistics
Authors: Groth Randall E. , Bargagliotti Anna E.
Published: August 2012

Two recent sets of guidelines that intersect statistics and complement each other can be used to plot an orderly progression of study.
Discourse: Simple Moves That Work
Authors: Rothermel Rawding Molly , Wills Theresa
Published: August 2012

Analyze discourse strategies and dissect simple classroom tools to maximize student engagement and excitement about math.
Back-to-school shopping
Authors: Phillippi Kevin
Published: August 2012

As students prepare to return to class, back-to-school advertisements feature sales on clothing, backpacks, and supplies. The following problem involves a real-life scenario about making purchases with discount coupons—a wonderful context for teaching problem solving and critical thinking.
Une amnésie des combats ? Présence et absence du xixe siècle libéral et radical dans la revue Cité libre (1950-1966)
Authors: Livernois Jonathan
Published: August 2012

Même si on a souvent reproché à Cité libre (1950-1966) son absence de perspective historique, il est tout à fait pertinent d’analyser les récupérations multiples, dans les pages de la revue, du libéralisme radical du xixe siècle au Canada français. En portant une attention particulière aux écrits de Pierre Elliott Trudeau et à ceux de Pierre Vadeboncoeur, Jean-Charles Falardeau et Fernand Dumont, nous constatons qu’il existe un rapport entre la capacité ou l’incapacité de saisir le néonationalisme et la récupération de l’héritage combatif du xixe siècle. Si Pierre Elliott Trudeau ne voit pas très bien et très loin derrière Wilfrid Laurier, Pierre Vadeboncoeur, par une série de procédés littéraires, réussit à irriguer son présent avec des traits et des événements oubliés.
High‐Strength Laminated Copper Matrix Nanocomposites Developed from a Single‐Walled Carbon Nanotube Film with Continuous Reticulate Architecture
Authors: Niu Zhiqiang , Ma Wenjun , Li Jinzhu , Dong Haibo , Ren Yan , Zhao Duan , Zhou Weiya , Xie Sishen
Published: August 2012

A critical challenge in nanocomposite fabrication by adding SWCNTs as reinforcement is to realize an effective transfer of the excellent mechanical properties of the SWCNTs to the macroscale mechanical properties of the matrix. Using directly grown SWCNT films with continuous reticulate structure as the template, Cu/SWCNTs/Cu laminated nanocomposites are fabricated by an electrodepositing process. The resulting Cu/SWCNTs/Cu laminated nanocomposites exhibit extremely high strength and Young's modulus. The estimated Young's modulus of the SWCNT bundles in the composite are between 860 and 960 GPa. Such a high strength and an effective load‐transfer capacity are ascribed to the unique continuous reticulate architecture of SWCNT films and the strong interfacial strength between the SWCNTs and Cu matrix. Raman spectroscopy is used to characterize the loading status of the SWCNTs in the strained composite. It provides a route to investigate the load transfer of SWCNTs in the metal matrix composites.
Effects of Varied Substituents on the Antibacterial Activity of Triazolylmethyl Oxazolidinones
Authors: Phillips Oludotun A. , Udo Edet E. , Abdel‐Hamid Mohammed E. , Varghese Reny
Published: August 2012

A number of 1,2,3‐triazolylmethyl piperazino oxazolidinone derivatives with optionally varied substituents at the 4N‐piperazine position were synthesized and their antibacterial activity evaluated against a panel of susceptible and resistant Gram‐positive and selected Gram‐negative bacteria. Substitution with 5‐membered heteroaroyl and dinitrobenzoyl moieties potentiated activity against staphylococci and enterococci strains. Furthermore, the compounds having dinitrobenzoyl 7n, 7o, and 5‐nitrofuroyl 7t substitutions were four‐ to eightfold more potent than linezolid against M. catarrhalis. However, substitution of guanidino and other water‐solubilizing functionalities at the 4N‐piperazine position resulted in compounds that are devoid of antibacterial activity.
Synthesis and Evaluation of a Series of Piperidine‐2,6‐dione‐piperazine (piperidine) Derivatives as Multireceptor Atypical Antipsychotics
Authors: Chen Yin , Xu Xiangqing , Liu Xin , Liu Bi‐Feng , Zhang Guisen
Published: August 2012

In this paper, we report the discovery and the synthesis of novel, potential antipsychotic piperidine‐2,6‐dione derivatives combining potent dopamine D2, D3 and serotonin 5‐HT1A, 5‐HT2A, 5‐HT2C receptor properties. We describe the structure–activity relationships that led us to the promising derivative: 1‐(4‐(4‐(6‐fluorobenzo[d]isoxazol‐3‐yl)piperidin‐1‐yl)butyl)‐4‐(4‐chlorophenyl)‐piperidine‐2,6‐dione 5. The unique pharmacological features of compound 5 are a high affinity for dopamine D2, D3 and serotonin 5‐HT1A, 5‐HT2A, 5‐HT2C receptors, together with a low affinity for the H1 receptor (to reduce the risk of obesity under chronic treatment). In a behavioral model predictive of positive symptoms, compound 5 inhibited apomorphine‐induced climbing behavior and MK‐801‐induced hyperactivity with no extrapyramidal symptoms liability in mice. In particular, compound 5 was more potent than clozapine.
Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations
Authors: Sánchez Elena , Rasmussen Astrid , Riba Laura , Acevedo‐Vasquez Eduardo , Kelly Jennifer A. , Langefeld Carl D. , Williams Adrianne H. , Ziegler Julie T. , Comeau Mary E. , Marion Miranda C. , García‐De La Torre Ignacio , Maradiaga‐Ceceña Marco A. , Cardiel Mario H. , Esquivel‐Valerio Jorge A. , Rodriguez‐Amado Jacqueline , Moctezuma José Francisco , Miranda Pedro , Perandones Carlos E. , Castel Cecilia , Laborde Hugo A. , Alba Paula , Musuruana Jorge L. , Goecke I. Annelise , Anaya Juan‐Manuel , Kaufman Kenneth M. , Adler Adam , Glenn Stuart B. , Brown Elizabeth E. , Alarcón Graciela S. , Kimberly Robert P. , Edberg Jeffrey C. , Vilá Luis M. , Criswell Lindsey A. , Gilkeson Gary S. , Niewold Timothy B. , Martín Javier , Vyse Timothy J. , Boackle Susan A. , Ramsey‐Goldman Rosalind , Scofield R. Hal , Petri Michelle , Merrill Joan T. , Reveille John D. , Tsao Betty P. , Orozco Lorena , Baca Vicente , Moser Kathy L. , Gaffney Patrick M. , James Judith A. , Harley John B. , Tusié‐Luna Teresa , Pons‐Estel Bernardo A. , Jacob Chaim O. , Alarcón‐Riquelme Marta E.
Published: August 2012

Objective

American Indian–Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian–European SLE patients.

Methods

A total of 2,116 SLE patients of American Indian–European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry‐informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).

Results

The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63– 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44–0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42–0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41–0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.

Conclusion

In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.
Murine tumor necrosis factor α–induced adipose‐related protein (tumor necrosis factor α–induced protein 9) deficiency leads to arthritis via interleukin‐6 overproduction with enhanced NF‐κB, STAT‐3 signaling, and dysregulated apoptosis of macrophages
Authors: Inoue Asuka , Matsumoto Isao , Tanaka Yoko , Umeda Naoto , Tanaka Yuki , Mihara Masahiko , Takahashi Satoru , Sumida Takayuki
Published: August 2012

Objective

To elucidate the role of tumor necrosis factor α–induced adipose‐related protein (TIARP; or tumor necrosis factor α–induced protein 9 [TNFAIP‐9]) in the development and pathogenesis of arthritis.

Methods

We generated TIARP‐deficient (TIARP−/−) mice and investigated several organs in aged mice. Peritoneal macrophages were collected and cultured with lipopolysaccharide (LPS) and TNFα, and then the production of cytokines and subsequent NF‐κB signal transduction were analyzed. We also examined the susceptibility of young TIARP−/− mice to collagen‐induced arthritis (CIA). Draining lymph nodes and splenocytes were isolated and cultured, and serum levels of anti–type II collagen (anti‐CII) antibodies, interleukin‐6 (IL‐6), and TNFα on day 60 were measured. We further investigated the effects of anti–IL‐6 receptor monoclonal antibody (mAb) on the development of arthritis in TIARP−/− mice. IL‐6/STAT‐3 signaling was also analyzed using TIARP−/− macrophages.

Results

TIARP−/− mice developed spontaneous enthesitis and synovitis, had high serum levels of IL‐6, had increased CD11b+ cell counts in the spleen, and showed enhanced LPS‐ and TNFα‐induced IL‐6 expression in macrophages. Sustained degradation of IκBα with dysregulated apoptosis was also noted in TIARP−/− macrophages. CIA was clearly exacerbated in TIARP−/− mice, accompanied by marked neutrophil and macrophage infiltration in joints. The levels of anti‐CII antibodies in serum were unchanged, whereas autoreactive Th1 cell and Th17 cell responses were higher in TIARP−/− mice. Treatment with anti–IL‐6 receptor mAb prevented the development of CIA in TIARP−/− mice, and TIARP−/− macrophages showed increased IL‐6–induced STAT‐3 phosphorylation.

Conclusion

These findings suggest that TIARP acts as a negative regulator of arthritis by suppressing IL‐6 production, its signaling and TNFα‐induced NF‐κB signaling, resulting in enhanced apoptosis in macrophages.
Dexamethasone prodrug treatment prevents nephritis in lupus‐prone (NZB × NZW)F1 mice without causing systemic side effects
Authors: Yuan Fang , Nelson Richard K. , Tabor Dana E. , Zhang Yijia , Akhter Mohammed P. , Gould Karen A. , Wang Dong
Published: August 2012

Objective

To evaluate the potentially improved therapeutic efficacy and safety of nephrotropic macromolecular prodrugs of glucocorticoids (GCs) for the treatment of lupus nephritis.

Methods

Lupus‐prone female (NZB × NZW)F1 mice received monthly injections of N‐(2‐hydroxypropyl) methacrylamide copolymer–based dexamethasone prodrug (P‐Dex) or daily injections of dexamethasone phosphate sodium (Dex; overall dose equivalent to that of P‐Dex) for 2 months. During treatment, the mice were monitored for albuminuria, mean arterial pressure, and serum autoantibody levels. Nephritis, renal immune complex levels, and macrophage infiltration were evaluated histologically. Bone quality was analyzed using peripheral dual x‐ray absorptiometry and micro–computed tomography. The in vivo distribution of P‐Dex was investigated using optical imaging, immunohistochemistry, and fluorescence‐activated cell sorting (FACS). The antiinflammatory effect of P‐Dex was validated using lipopolysaccharide‐activated human proximal tubule epithelial (HK‐2) cells.

Results

Monthly P‐Dex injections completely abolished albuminuria in the (NZB × NZW)F1 mice; this approach was significantly more efficacious than daily Dex treatment. P‐Dex treatment did not reduce serum levels of anti–double‐stranded DNA antibodies or renal immune complexes but did decrease macrophage infiltration, which is a marker of chronic inflammation. Immunohistochemical and FACS analyses revealed that P‐Dex was primarily sequestered by proximal tubule epithelial cells, and that it could attenuate the inflammatory response in HK‐2 cell culture. In contrast to Dex treatment, P‐Dex treatment did not lead to any significant deterioration of bone quality or reduction in the level of total serum IgG.

Conclusion

Macromolecularization of GCs renders them nephrotropic. Protracted retention, subcellular processing, and activation of GC prodrugs by kidney cells would potentiate nephritis resolution, with a reduced risk of systemic toxicities.
Multicriteria evaluation on accessibility‐based transportation equity in road network design problem
Authors: Feng Tao , Zhang Junyi
Published: August 2012

This paper investigates the performance of accessibility‐based equity measurements in transportation and proposes a multiobjective optimization model to simulate the trade‐offs between equity maximization and cost minimization of network construction. The equity is defined as the spatial distribution of accessibilities across zone areas. Six representative indicators were formulated, including GINI coefficient, Theil index, mean log deviation, relative mean deviation, coefficient of variation, and Atkinson index, and incorporated into an equity maximization model to evaluate the performance sensitivity. A bilevel multiobjective optimization model was proposed to obtain the Pareto‐optimal solutions for link capacity enhancement in a stochastic road network design problem. A numerical analysis using the Sioux Falls data was implemented. Results verified that the equity indicators are quite sensitive to the pattern of network scenarios in the sense that the level of equity varies according to the amount of overall capacity enhancement as well as the assignment of improved link segments. The suggested multiobjective model that enables representing the Pareto‐optimal solutions can provide multiple options in the decision making of road network design. Copyright © 2012 John Wiley & Sons, Ltd.
The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: An open label pilot study
Authors: Mezawa Morito , Takemoto Minoru , Onishi Shunichiro , Ishibashi Ryoichi , Ishikawa Takahiro , Yamaga Masaya , Fujimoto Masaki , Okabe Emiko , He Peng , Kobayashi Kazuki , Yokote Koutaro
Published: August 2012

Coenzyme Q10 (CoQ10) provides the energy for vital cellular functions and is known to act as an antioxidant. We conducted an open label study to examine the clinical effects of supplementation of the reduced form of CoQ10, ubiquinol, in addition to conventional glucose‐lowering agents in patients with type 2 diabetes. Nine subjects (3 males and 6 females) with type 2 diabetes and receiving conventional medication were recruited. The subjects were assigned to receive an oral dose of 200 mg ubiquinol daily for 12 weeks. The effect of ubiquinol on blood pressure, lipid profile, glycemic control, oxidative stress, and inflammation were examined before and after ubiquinol supplementation. In addition, five healthy volunteers were also assigned to receive an oral dose of 200 mg ubiquinol daily for 4 weeks to examine the effects of ubiquinol on insulin secretion. In patients with diabetes, there were no differences with respect to blood pressure, lipid profile, oxidative stress marker, and inflammatory markers. However, there were significant improvements in glycosylated hemoglobin (53.0 ± 4.3 to 50.5 ± 3.7 mmol/mol, P = 0.01) (7.1 ± 0.4 to 6.8 ± 0.4%, P = 0.03). In healthy volunteers, the insulinogenic index (0.65 ± 0.29 to 1.23 ± 0.56, P = 0.02) and the ratio of proinsulin to insulin were significantly improved (3.4 ± 1.8 to 2.1 ± 0.6, P = 0.03). The results of our study are consistent with the suggestion that the supplementation of ubiquinol in subjects with type 2 diabetes, in addition to conventional antihyperglycemic medications, improves glycemic control by improving insulin secretion without any adverse effects.© 2012 International Union of Biochemistry and Molecular Biology, Inc.
Strategic Assay Selection for analytics in high‐throughput process development: Case studies for downstream processing of monoclonal antibodies
Authors: Konstantinidis Spyridon , Kong Simyee , Chhatre Sunil , Velayudhan Ajoy , Heldin Eva , Titchener‐Hooker Nigel
Published: August 2012

During bioprocess development a potentially large number of analytes require measurement. Selection of the best set of analytical methods to deploy can reduce the analytical requirements for process investigation but currently relies on application of heuristics. This paper introduces a generic methodology, Strategic Assay Selection, for screening a large number of analytical methods to produce a subset of analytics that best suit high‐throughput studies. The methodology uses a stochastic ranking approach where analytics are ranked based on their holistic performance in a set of criteria. Strategic Assay Selection can be used to help minimizing the impact of analytics in the generation of bottlenecks often encountered during high‐throughput process development studies. This is illustrated by using a typical downstream purification process for a monoclonal antibody product. A list of assays is populated for routinely measured analytes across the different units of operation followed by the calculation of their performances in four criteria. The methodology is then applied to select analytics testing for three analytes and the results are analyzed to demonstrate how it can lead to the selection of analytical methods with the most favorable features.
Investigation of ifosfamide nephrotoxicity induced in a liver–kidney co‐culture biochip
Authors: Choucha‐Snouber Leila , Aninat Caroline , Grsicom Laurent , Madalinski Geoffrey , Brochot Céline , Poleni Paul Emile , Razan Florence , Guillouzo Christiane Guguen , Legallais Cécile , Corlu Anne , Leclerc Eric
Published: August 2012

In this article, we present a liver–kidney co‐culture model in a micro fluidic biochip. The liver was modeled using HepG2/C3a and HepaRG cell lines and the kidney using MDCK cell lines. To demonstrate the synergic interaction between both organs, we investigated the effect of ifosfamide, an anticancerous drug. Ifosfamide is a prodrug which is metabolized by the liver to isophosforamide mustard, an active metabolite. This metabolism process also leads to the formation of chloroacetaldehyde, a nephrotoxic metabolite and acrolein a urotoxic one. In the biochips of MDCK cultures, we did not detect any nephrotoxic effects after 72 h of 50 µM ifosfamide exposure. However, in the liver–kidney biochips, the same 72 h exposure leads to a nephrotoxicity illustrated by a reduction of the number of MDCK cells (up to 30% in the HepaRG‐MDCK) when compared to untreated co‐cultures or treated MDCK monocultures. The reduction of the MDCK cell number was not related to a modification of the cell cycle repartition in ifosfamide treated cases when compared to controls. The ifosfamide biotransformation into 3‐dechloroethylifosfamide, an equimolar byproduct of the chloroacetaldehyde production, was detected by mass spectrometry at a rate of apparition of 0.3 ± 0.1 and 1.1 ± 0.3 pg/h/biochips in HepaRG monocultures and HepaRG‐MDCK co‐cultures respectively. Any metabolite was detected in HepG2/C3a cultures. Furthermore, the ifosfamide treatment in HepaRG‐MDCK co‐culture system triggered an increase in the intracellular calcium release in MDCK cells on contrary to the treatment on MDCK monocultures. As 3‐dechloroethylifosfamide is not toxic, we have tested the effect of equimolar choloroacetaldehyde concentration onto the MDCK cells. At this concentration, we found a quite similar calcium perturbation and MDCK nephrotoxicity via a reduction of 30% of final cell numbers such as in the ifosfamide HepaRG‐MDCK co‐culture experiments. Our results suggest that ifosfamide nephrotoxicity in a liver–kidney micro fluidic co‐culture model using HepaRG‐MDCK cells is induced by the metabolism of ifosfamide into chloroacetaldehyde whereas this pathway is not functional in HepG2/C3a‐MDCK model. This study demonstrates the interest in the development of systemic organ–organ interactions using micro fluidic biochips. It also illustrated their potential in future predictive toxicity model using in vitro models as alternative methods. Biotechnol. Bioeng. 2013; 110: 597–608. © 2012 Wiley Periodicals, Inc.
Statistical analysis of effects of experimental variables on mass transfer coefficient in a novel hybrid bubble column using Box–Behnken design
Authors: Dhanasekaran S. , Karunanithi T.
Published: August 2012

Statistical analysis of effects of experimental variables on volumetric mass transfer coefficient in a novel hybrid rotating and reciprocating perforated plate bubble column is studied. The novel bubble column is designed indigenously using bevel gear arrangement. Agitation level, superficial gas velocity, superficial liquid velocity, perforation diameter and plate spacing are the experimental variables. Air–sodium sulphite solution system is used in this investigation. The Box–Behnken design in response surface methodology is employed for statistical analysis. The relationship between experimental variables and the desired response of volumetric mass transfer coefficient is established for this novel hybrid column. The linear, quadratic and interactive effects of experimental variables are found to be significant on the desired response of volumetric mass transfer coefficient. Results show that the data adequately fit into the second‐order polynomial model. An F‐test and P‐value show the significance of parameters on volumetric mass transfer coefficient. © 2012 Canadian Society for Chemical Engineering
Likelihood‐based and marginal inference methods for recurrent event data with covariate measurement error
Authors: Yi Grace Y. , Lawless Jerald F.
Published: August 2012

Recurrent event data arise commonly in medical and public health studies. The analysis of such data has received extensive research attention and various methods have been developed in the literature. Depending on the focus of scientific interest, the methods may be broadly classified as intensity‐based counting process methods, mean function‐based estimating equation methods, and the analysis of times to events or times between events. These methods and models cover a wide variety of practical applications. However, there is a critical assumption underlying those methods–variables need to be correctly measured. Unfortunately, this assumption is frequently violated in practice. It is quite common that some covariates are subject to measurement error. It is well known that covariate measurement error can substantially distort inference results if it is not properly taken into account. In the literature, there has been extensive research concerning measurement error problems in various settings. However, with recurrent events, there is little discussion on this topic. It is the objective of this paper to address this important issue. In this paper, we develop inferential methods which account for measurement error in covariates for models with multiplicative intensity functions or rate functions. Both likelihood‐based inference and robust inference based on estimating equations are discussed.The Canadian Journal of Statistics40: 530–549; 2012 © 2012 Statistical Society of Canada
Physico‐Chemical and Bacterial Characteristics of Water Quality in Three Villages West of Lake Nasser, Egypt
Authors: Rashed Mohamed Nageeb , Younis Magdy
Published: August 2012

The present study aims to investigate physico‐chemical and bacterial characteristics of Nasser Lake water and houses drinking water, as well as fish cultures and its wastewater, in three villages west of Lake Nasser, Egypt. Fifteen representative water samples (Nasser Lake, different drinking water, fish cultures, and wastewater sources) were collected from three villages (Garf Hussein, Bashaier, and Kalabsha) in the west of Lake Nasser. Physico‐chemical, total viable counts, and bacterial qualification of water were achieved. The obtained results indicated that the produced water, supposed to be for domestic use in the three villages, contained all the tested organisms. The investigated water samples of the lake and drinking water in the selected three villages are supposed to be chemically safe according to World Health Organization and to Egyptian standards for drinking water. Water pollution index (WPI) was used in this study and the result concluded that for irrigation canals from the lake to the agriculture site, fish cultures (both concrete and earth pond systems), and drainage canal of fish ponds need to be treated before it is discharged to the lake. It is better to reuse it after treatment for agricultural purposes or recycled it to the fish cultures.
Distinct synaptic localization patterns of brefeldin A‐resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina
Authors: Sakagami Hiroyuki , Katsumata Osamu , Hara Yoshinobu , Tamaki Hideaki , Watanabe Masahiko , Harvey Robert J. , Fukaya Masahiro
Published: August 2012

The BRAG/IQSEC is a family of guanine nucleotide exchange factors for ADP ribosylation factors, small GTPases that regulate membrane trafficking and actin cytoskeleton, and comprises three structurally related members (BRAG1–3) generated from different genes. In the mouse retina, BRAG1 (also known as IQSEC2) was previously shown to localize at synaptic ribbons of photoreceptor terminals and to form a protein complex with RIBEYE. In this study, we examined the immunohistochemical localization of BRAG2 (IQSEC1) and BRAG3 (IQSEC3) in the adult mouse retina at the light and electron microscopic levels. In the outer plexiform layer, BRAG2 showed a punctate distribution in intimate association with dystrophin and β‐dystroglycan. Immunoelectron microscopic analysis revealed that BRAG2 localized at specific subcompartments of photoreceptor terminals in both rod spherules and cone pedicles. In the inner plexiform layer, immunolabeling for both BRAG2 and BRAG3 had a punctate appearance, suggestive of synaptic labeling. Double immunostaining demonstrated that BRAG2 colocalized preferentially with PSD‐95 and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate‐type glutamate receptors (AMPARs). By contrast, BRAG3 colocalized with gephyrin and a subpopulation of inhibitory synapses expressing glycine receptors or γ‐aminobutyric acid type A receptors (GABAARs). Immunoelectron microscopic analysis revealed that BRAG2 localized to postsynaptic processes at bipolar dyads, while BRAG3 localized to postsynaptic components at conventional synapses. These findings suggest that BRAG/IQSEC family members have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. J. Comp. Neurol. 521:860–876, 2013. © 2012 Wiley Periodicals, Inc.
Sensory and sympathetic innervation of the mouse and guinea pig corneal epithelium
Authors: Ivanusic Jason J. , Wood Rhiannon J. , Brock James A.
Published: August 2012

This study used immunohistochemistry, retrograde tracing, and high‐resolution confocal microscopy to explore the structure and neurochemistry of nerve terminals in the corneal epithelium of mice and guinea pigs. In both species, sub‐basal nerves formed a plexus in the basal epithelium. Some axons had bulbar endings within the basal epithelium, but most projected perpendicularly from sub‐basal nerves to within a few micrometers of the epithelial surface. Three morphologies for these nerve terminals were identified. Simple terminals did not branch after leaving the sub‐basal nerves and ended with a single, bulbar swelling. Ramifying terminals branched in the squamous cell layer, forming horizontal fibers that ran parallel to the surface and terminated with single bulbar swellings. Complex terminals branched as they approached the epithelial surface, forming a cluster of highly branched fibers with multiple bulbar endings. Calcitonin gene‐related peptide immunolabeled (peptidergic) axons ended mostly in simple terminals, whereas transient receptor potential cation channel subfamily M member 8 immunolabeled (cold receptor) axons ended almost exclusively in complex terminals. Retrograde labeling identified discrete subpopulations of corneal afferent neurons in the trigeminal ganglion. Tyrosine hydroxylase‐immunolabeled (sympathetic) nerve terminals originating from the superior cervical ganglion occurred throughout the corneal epithelium of mice, but only in the basal epithelium of guinea pigs. These findings demonstrate that nerve terminals in the corneal epithelium of mice and guinea pigs can be distinguished on the basis of their morphology and neurochemistry, and suggest that nerve terminals with different sensory modalities can be defined on the basis of their morphology. J. Comp. Neurol. 521:877–893, 2013. © 2012 Wiley Periodicals, Inc.
Neurons with GABAergic phenotype in the visual system of Drosophila
Authors: Raghu Shamprasad Varija , Claussen Jing , Borst Alexander
Published: August 2012

The visual system of Drosophila contains ∼60,000 neurons per hemisphere that are organized in parallel, retinotopically arranged columns. The neuroanatomy of these neurons has been mapped in considerable detail at both the light and ultrastructural level. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we characterize those neurons in the Drosophila optic lobes that possibly release gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter of the insect central nervous system. We identified 26 different types of neurons of the lamina, medulla, lobula, and lobula plate. Based on the previous Golgi‐staining analysis (Fischbach and Dittrich [1989] Cell Tissue Res 258:441–475), the identified neurons are further classified into 11 major subgroups representing lamina monopolar (L), medulla intrinsic (Mi, Mt), bushy T (T), transmedullary (Tm), transmedullary Y (TmY), Y, lobula‐complex intrinsic (Lccn), lobula columnar (Lcn), lobula plate intrinsic (Lpi), and lobula tangential (Lt) cell types. This detailed map of neurons with GABAergic phenotype will contribute to the future neurogenetic dissection of information processing circuits in the fly visual system. J. Comp. Neurol. 521:252–265, 2013. © 2012 Wiley Periodicals, Inc.
Males but not females show differences in calbindin immunoreactivity in the dorsal thalamus of the mouse model of fragile X syndrome
Authors: Giráldez‐Pérez Rosa M. , Ávila M. Nieves , Feijóo‐Cuaresma Mónica , Heredia Raúl , De Diego‐Otero Yolanda , Real M. Ángeles , Guirado Salvador
Published: August 2012

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of the Fmr1 gene product, fragile X mental retardation protein. Here we analyze the immunohistochemical expression of calcium‐binding proteins in the dorsal thalamus of Fmr1 knockout mice of both sexes and compare it with that of wildtype littermates. The spatial distribution pattern of calbindin‐immunoreactive cells in the dorsal thalamus was similar in wildtype and knockout mice but there was a notable reduction in calbindin‐immunoreactive cells in midline/intralaminar/posterior dorsal thalamic nuclei of male Fmr1 knockout mice. We counted the number of calbindin‐immunoreactive cells in 18 distinct nuclei of the dorsal thalamus. Knockout male mice showed a significant reduction in calbindin‐immunoreactive cells (range: 36–67% lower), whereas female knockout mice did not show significant differences (in any dorsal thalamic nucleus) when compared with their wildtype littermates. No variation in the calretinin expression pattern was observed throughout the dorsal thalamus. The number of calretinin‐immunoreactive cells was similar for all experimental groups as well. Parvalbumin immunoreactivity was restricted to fibers and neuropil in the analyzed dorsal thalamic nuclei, and presented no differences between genotypes. Midline/intralaminar/posterior dorsal thalamic nuclei are involved in forebrain circuits related to memory, nociception, social fear, and auditory sensory integration; therefore, we suggest that downregulation of calbindin protein expression in the dorsal thalamus of male knockout mice should be taken into account when analyzing behavioral studies in the mouse model of FXS. J. Comp. Neurol. 521:894–911, 2013. © 2012 Wiley Periodicals, Inc.