bluuebunny/crossref_metadata_2025 huggingface dataset:
TOTAL FACTOR PRODUCTIVITY AND R&D IN THE PRODUCTION FUNCTION
Authors: REIKARD GORDON
Published: January 2012

A production function is used to estimate total factor productivity and the contribution of R&D to growth. The impact of R&D is found to be higher than in most prior studies, for two reasons. First, the R&D stock is larger, due to the use of a longer time series with base values starting in 1921, and the assumption of no technical depreciation of knowledge. Second, the elasticity of R&D increases over time. In accounting for post-WWII growth, the results for 1948–1980 are consistent with earlier findings. Technical advance accelerated dramatically in the 1960s, but collapsed in the mid-1970s. Starting in the early 1980s, however, the production function suggests a new interpretation. There was a stronger rebound in total factor productivity, lasting roughly through 2000. Thereafter, total factor productivity decelerated sharply in 2001–2007. The contribution of R&D to growth has varied over time. The largest effect occurred in 1948–1960. The impact of R&D fell off in the 1970s, and picked up to a smaller but still significant effect starting in the 1980s. Despite the larger stock and the increasing elasticity, R&D is found to have contributed on average less than half of total factor productivity.
THE DYNAMIC PRICE-QUALITY DECISION MODEL FOR TWO SUCCESSIVE GENERATIONS OF TECHNOLOGY INNOVATION
Authors: CHANDA UDAYAN
Published: January 2012

As most of the high-technology companies are trying to be more demand driven, technological innovation and diffusion become important forces in markets today. They critically affect the fortunes of consumers, firms, and nations. Despite research across many disciplines, many important questions remain unanswered. Effects of fluctuating price and quality on the consumer adoption decision for multi-generation innovation are some of such important research areas in this field. High-technology product comes in generations that consist of substitutable product ranges; consumers' preferences tend to reflect external and internal factors that change over time. Often, two successive generations under the same product category compete in the market. It is anticipated by the consumers that the later generation possesses more advance features. Yet it becomes difficult for the marketing managers to decide on the optimum-level values of marketing mix variables for two competing products under its stable. This paper studies optimal control policies for quality and price when two technology generations are present in a dynamic market and also suggest a policy for the optimal launching time of an advanced generation. Lots of work has already been done to study the optimal policies on explanatory variables such as price, promotional effort, quality, and time for new products. In comparison high-technology products have received less attention. The profit functional used for optimal control in this paper combines well-known diffusion models and the cost function that is capable of estimating the future profit trends. The diffusion model uses the relationship between the repeat purchasers and the new purchasers to study the overall diffusion of a new technology over multiple generations.
PRODUCT DEVELOPMENT IN OPEN DESIGN COMMUNITIES: A PROCESS PERSPECTIVE
Authors: RAASCH CHRISTINA
Published: January 2012

Open source (OS) has raised significant attention in industrial practice and in scholarly research as a new and successful mode of product development. This paper is among the first to study open source development processes outside their original context, the software industry. In particular, we investigate the development of tangible products in so-called open design projects. We study how open design projects address the challenges usually put forward in the literature as barriers to the open development of tangible products. The analysis rests on the comparative qualitative investigation of four cases from different industries. We find that, subject to certain contingencies, open design processes can be organized to resemble OSS development processes to a considerable degree. Some practices are established specifically to uphold OS principles in the open design context, while others starkly differ from those found in OSS development. Our discussion focusses on different aspects of modularity as well as the availability of low-cost tools.
Vasopressin and oxytocin excite MCH neurons, but not other lateral hypothalamic GABA neurons
Authors: Yao Yang , Fu Li-Ying , Zhang Xiaobing , van den Pol Anthony N.
Published: January 2012

Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na+/Ca2+ exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na+/Ca2+ exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg8]vasotocin, the selective V1aR agonist [Phe2]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.
Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle
Authors: Pandorf Clay E. , Jiang Weihua , Qin Anqi X. , Bodell Paul W. , Baldwin Kenneth M. , Haddad Fadia
Published: January 2012

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.
Both cyclin I and p35 are required for maximal survival benefit of cyclin-dependent kinase 5 in kidney podocytes
Authors: Taniguchi Yoshinori , Pippin Jeffrey W. , Hagmann Henning , Krofft Ronald D. , Chang Alice M. , Zhang Jiong , Terada Yoshio , Brinkkoetter Paul , Shankland Stuart J.
Published: January 2012

Cyclin-dependent kinase (Cdk)-5 is activated by both cyclin I and the noncyclin activator p35 in terminally differentiated cells such as kidney podocytes and neurons. Cyclin I and p35 are restricted to podocytes in the kidney, and each limit podocyte apoptosis by activating Cdk5. To determine whether both activators are necessary, or whether they serve backup roles, a double cyclin I-p35 null mouse was generated. Experimental glomerular disease characterized by podocyte apoptosis was then induced by administering an anti-podocyte antibody. The results showed that under nonstressed conditions double mutants had normal kidney structure and function and were indistinguishable from wild-type, cyclin I−/−, or p35−/−mice. In contrast, when stressed with disease, podocyte apoptosis increased fourfold compared with diseased cyclin I−/−or p35−/−mice. This resulted in a more pronounced decrease in podocyte number, proteinuria, and glomerulosclerosis. Under normal states and nephritic states, levels for the prosurvival protein Bcl-2 were lower in double cyclin I−/−p35−/−mice than the other mice. Similarly, levels of Bcl-xL, another prosurvival member, were lower in normal and nephritic double cyclin I−/−p35−/−mice but similar to single-cyclin I−/−mice. Moreover, levels of ERK1/2 and MEK1/2 activation were lower in nephritic double cyclin I−/−p35−/−mice but similar to single-cyclin I−/−mice. The results demonstrate that the activators of Cdk5, p35, and cyclin I are not required for normal kidney function. However, they play pivotal coordinated roles in maintaining podocyte survival during stress states in disease.
Predicting other people's action goals with low-level motor information
Authors: Falck-Ytter Terje
Published: January 2012

In support for the direct-matching hypothesis, Ambrosini et al. (2011) recently reported that goal-directed saccades during action observation were modulated by manipulations of basic motor information. This finding indicates that motor programs, activated by low-level visual descriptions of others' actions, are involved in predicting other people's action goals. Here, I put this result into a broader context, review alternative interpretations, and suggest strategies for future studies.
Some Asymptotic Theory for Functional Regression and Classification
Authors: Ruymgaart Frits , Wang Jing , Wei Shih-Hsuan , Yu Li
Published: January 2012

Exploiting an expansion for analytic functions of operators, the asymptotic distribution of an estimator of the functional regression parameter is obtained in a rather simple way; the result is applied to testing linear hypotheses. The expansion is also used to obtain a quick proof for the asymptotic optimality of a functional classification rule, given Gaussian populations.
Proteomics Shows New Faces for the Old Penicillin ProducerPenicillium chrysogenum
Authors: Barreiro Carlos , Martín Juan F. , García-Estrada Carlos
Published: January 2012

Fungi comprise a vast group of microorganisms including the Ascomycota (majority of all described fungi), the Basidiomycota (mushrooms or higher fungi), and the Zygomycota and Chytridiomycota (basal or lower fungi) that produce industrially interesting secondary metabolites, such as β-lactam antibiotics. These compounds are one of the most commonly prescribed drugs world-wide. Since Fleming's initial discovery ofPenicillium notatum80 years ago, the role ofPenicilliumas an antimicrobial source became patent. After the isolation ofPenicillium chrysogenumNRRL 1951 six decades ago, classical mutagenesis and screening programs led to the development of industrial strains with increased productivity (at least three orders of magnitude). The new “omics” era has provided the key to understand the underlying mechanisms of the industrial strain improvement process. The review of different proteomics methods applied toP. chrysogenumhas revealed that industrial modification of this microorganism was a consequence of a careful rebalancing of several metabolic pathways. In addition, the secretome analysis ofP. chrysogenumhas opened the door to new industrial applications for this versatile filamentous fungus.
Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly-Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin
Authors: D'Annessa Ilda , Tesauro Cinzia , Fiorani Paola , Chillemi Giovanni , Castelli Silvia , Vassallo Oscar , Capranico Giovanni , Desideri Alessandro
Published: January 2012

Topoisomerases I are ubiquitous enzymes that control DNA topology within the cell. They are the unique target of the antitumor drug camptothecin that selectively recognizes the DNA-topoisomerase covalent complex and reversibly stabilizes it. The biochemical and structural-dynamical properties of the Asp677Gly-Val703Ile double mutant with enhanced CPT sensitivity have been investigated. The mutant displays a lower religation rate of the DNA substrate when compared to the wild-type protein. Analyses of the structural dynamical properties by molecular dynamics simulation show that the mutant has reduced flexibility and an active site partially destructured at the level of the Lys532 residue. These results demonstrate long-range communication mechanism where reduction of the linker flexibility alters the active site geometry with the consequent lowering of the religation rate and increase in drug sensitivity.
Assessing the Population Status of a Tree Species Using Distance Sampling:Aquilaria crassna(Thymelaeaceae) in Northern Laos
Authors: Jensen Anders , Meilby Henrik
Published: January 2012

Lack of reliable and accurate field data affect assessments of population status of tree species, especially tropical taxa with broad distributions. Use of distance sampling techniques may help to overcome the problem. This paper describes a method for estimation of absolute density of a rare tree species with scattered and clumped distribution, using line transect distance sampling. The method was applied to previously harvested populations ofAquilaria crassnaPierre ex H. Lec. (Thymelaeaceae) at four sites in Northern Laos. This species is destructively harvested to yield agarwood, probably the world’s most valuable nontimber forest product and categorised as ”critically endangered“. The average density of felledA. crassnatrees at the four sites was 2.2 ha−1, indicating that harvesting has been extensive. However, the estimated densities of living saplings, 10.9 ha−1, small trees (DBH < 10 cm), 10.6 ha−1, and larger trees (DBH ≥ 10 cm), 1.7 ha−1, suggest that populations are not wiped flat. The survey method should stand a good chance of wider use as a tool in management and conservation of a wide range of tree species. Results of the present case study could suggest that the conservation status ofA. crassnashould be re-categorised.
Kadec-Klee Properties of Calderón-Lozanovskiĭ Function Spaces
Authors: Kolwicz Paweł
Published: January 2012

We study Kadec-Klee properties with respect to global (local) convergence in measure. First, we present some results concerning Köthe spaces and Orlicz functions. Next, we shall give full criteria for Kadec-Klee properties with respect to global (local) convergence in measure in Calderón-Lozanovskiĭ function spaces. In particular, we obtain the full characterizations of Kadec-Klee properties in Orlicz-Lorentz function spaces, which have not been presented until now.
Transfer Matrix Method for Natural Vibration Analysis of Tree System
Authors: He Bin , Rui Xiaoting , Zhang Huiling
Published: January 2012

The application of Transfer matrix method (TMM) ranges from linear/nonlinear vibration, composite structure, and multibody system to calculating static deformation, natural vibration, dynamical response, and damage identification. Generally TMM has two characteristics: (1) the TMM formulae share similarity to the chain mechanics model in terms of topology structure; then TMM often is selected as a powerful tool to analyze the chain system. (2) TMM is adopted to deal with the problems of the discrete system, continuous system, and especial discrete/continuous coupling system with the uniform matrix form. In this investigation, a novel TMM is proposed to analyze the natural vibration of the tree system. In order to make the TMM of the tree system have the two above advantages of the TMM of the chain system, the suitable state vectors and transfer matrices of the typical components of the tree system are constructed. Then the topology comparability between the mechanics model and its corresponding formulae of TMM can be adopted to assembling the transfer matrices and transfer equations of the global tree system. Two examples of natural vibration problems validating the method are given. The formulation of the proposed TMM is mathematically intuitive and can be held and applied by the engineers easily.
A Family of Three‐Point Methods of Ostrowski′s Type for Solving Nonlinear Equations
Authors: Džunić Jovana , Petković Miodrag S.
Published: January 2012

A class of three‐point methods for solving nonlinear equations of eighth order is constructed.
These methods are developed by combining two‐point Ostrowski′s fourth‐order methods and a
modified Newton′s method in the third step, obtained by a suitable approximation of the first
derivative using the product of three weight functions. The proposed three‐step methods have
order eight costing only four function evaluations, which supports the Kung‐Traub conjecture
on the optimal order of convergence. Two numerical examples for various weight functions are
given to demonstrate very fast convergence and high computational efficiency of the proposed
multipoint methods.
Chromosomal Damage and Apoptosis in Exfoliated Buccal Cells from Individuals with Oral Cancer
Authors: Dórea Lavínia Tércia Magalhães , Meireles José Roberto Cardoso , Lessa Júlia Paula Ramos , Oliveira Márcio Campos , de Bragança Pereira Carlos Alberto , Polpo de Campos Adriano , Cerqueira Eneida de Moraes Macílio
Published: January 2012

This study aimed to investigate cytological abnormalities indicative of chromosome damage (micronuclei) and apoptosis (karyorrhexis, pyknosis, and condensed chromatin) in exfoliated cells from the buccal mucosa of patients with oral cancer and control subjects. The sample included twenty individuals with oral cancer and forty individuals with normal buccal mucosa. Material was collected from the cheek epithelium in areas with lesions and areas without abnormalities. A minimum of one thousand cells was analyzed. Micronuclei were found significantly more frequently in cells collected from lesions than in cells from normal areas, independent of the presence/absence of cancer (P<0.0001). They were also significantly more frequent in smokers and in mouthwash users (P<0.0001). Apoptosis occurred significantly less frequently in individuals with oral cancer (P<0.0001). These results show that oral cancer is associated with higher frequency of chromosomal damage and suggest that apoptosis is compromised in the buccal cells of individuals with this kind of neoplasia.
Comparative Efficacy of Three Forms of Parenteral Iron
Authors: Dillon Richard , Momoh Ibrahim , Francis Yvonne , Cameron Laura , Harrison Claire N. , Radia Deepti
Published: January 2012

Intravenous iron therapy is a useful treatment for the rapid correction of iron deficiency anaemia and can be used to avoid or reduce the requirement for allogeneic blood transfusion. Several intravenous iron preparations are available commercially which differ in cost, mode of administration and side effect profile. There are few data directly comparing the efficacy of these preparations. In this retrospective single-centre study, we present the results from two hundred and eight patients treated using three different iron preparations (iron dextran, iron sucrose and ferric carboxymaltose) and compare the effect on haemoglobin levels and other measures of iron deficiency six weeks after treatment. Within the limitations of our study design, we show a statistically and clinically significant difference in efficacy between these preparations.
Production of Chemoenzymatic Catalyzed Monoepoxide Biolubricant: Optimization and Physicochemical Characteristics
Authors: Salimon Jumat , Salih Nadia , Abdullah Bashar Mudhaffar
Published: January 2012

Linoleic acid (LA) is converted to per-carboxylic acid catalyzed by an immobilized lipase fromCandida antarctica(Novozym 435). This per-carboxylic acid is only intermediate and epoxidized itself in good yields and almost without consecutive reactions. Monoepoxide linoleic acid 9(12)-10(13)-monoepoxy 12(9)-octadecanoic acid (MEOA) was optimized using D-optimal design. At optimum conditions, higher yield% (82.14) and medium oxirane oxygen content (OOC) (4.91%) of MEOA were predicted at 15 μL of H2O2, 120 mg of Novozym 435, and 7 h of reaction time. In order to develop better-quality biolubricants, pour point (PP), flash point (FP), viscosity index (VI), and oxidative stability (OT) were determined for LA and MEOA. The results showed that MEOA exhibited good low-temperature behavior with PP of−41°C. FP of MEOA increased to128°Ccomparing with115°Cof LA. In a similar fashion, VI for LA was 224 generally several hundred centistokes (cSt) more viscous than MEOA 130.8. The ability of a substance to resist oxidative degradation is another important property for biolubricants. Therefore, LA and MEOA were screened to measure their OT which was observed at 189 and168°C, respectively.
The Evolving Role of Selenium in the Treatment of Graves' Disease and Ophthalmopathy
Authors: Duntas Leonidas H.
Published: January 2012

Graves' disease (GD) and ophthalmopathy (GO) are organ-specific autoimmune-inflammatory disorders characterized by a complex pathogenesis. The inflammatory process is dominated by an imbalance of the antioxidant-oxidant mechanism, increased production of radical oxygen species (ROS), and cytokines which sustain the autoimmune process and perpetuate the disease. Recently, selenium, which is a powerful antioxidant, has been successfully applied in patients with mild GO, slowing the progression of disease, decreasing the clinical activity score, and appreciably improving the quality of life. The mechanisms of selenium action are variable. The aim of this review is to summarize the actions of selenium in GD and GO. Selenium as selenocysteine is incorporated in selenoproteins, such as glutathione peroxidase which catalyzes the degradation of hydrogen peroxide and lipid hydroperoxide that are increasingly produced in hyperthyroidism. Moreover, selenium decreases the formation of proinflammatory cytokines, while it contributes, in synergy with antithyroid drugs, to stabilization of the autoimmune process in GD and alleviation of GO. It is now to be clarified whether enforced nutritional supplementation has the same results and whether prolonging selenium administration may have an impact on the prevention of disease.
Imaging an Adapted Dentoalveolar Complex
Authors: Herber Ralf-Peter , Fong Justine , Lucas Seth A. , Ho Sunita P.
Published: January 2012

Adaptation of a rat dentoalveolar complex was illustrated using various imaging modalities. Micro-X-ray computed tomography for 3D modeling, combined with complementary techniques, including image processing, scanning electron microscopy, fluorochrome labeling, conventional histology (H&E, TRAP), and immunohistochemistry (RANKL, OPN) elucidated the dynamic nature of bone, the periodontal ligament-space, and cementum in the rat periodontium. Tomography and electron microscopy illustrated structural adaptation of calcified tissues at a higher resolution. Ongoing biomineralization was analyzed using fluorochrome labeling, and by evaluating attenuation profiles using virtual sections from 3D tomographies. Osteoclastic distribution as a function of anatomical location was illustrated by combining histology, immunohistochemistry, and tomography. While tomography and SEM provided past resorption-related events, future adaptive changes were deduced by identifying matrix biomolecules using immunohistochemistry. Thus, a dynamic picture of the dentoalveolar complex in rats was illustrated.
Nasu-Hakola Syndrome: An Unusual Cause of Pathological Fractures
Authors: Panchmatia Jaykar R. , Jiwa Natasha , Soneji Neil , Murphy John Paul
Published: January 2012

Nasu-Hakola syndrome is a hereditary cause of pathological fractures. Uniquely, patients also develop neuropsychiatric symptoms and signs. The disease is ultimately fatal. We propose a management strategy for pathological fractures in sufferers based on the stage of the disease.
Targeting Pioneering Factor and Hormone Receptor Cooperative Pathways to Suppress Tumor Progression
Authors: Shah Supriya , Prasad Shikha , Knudsen Karen E.
Published: January 2012

Nuclear receptors and pioneer factors drive the development and progression of prostate cancer. In this disease, aggressive disease phenotypes and hormone therapy failures result from resurgent activity of androgen receptor (AR) and the upregulation of coactivator protein p300 and pioneer factors (e.g., GATA2 and FOXA1). Thus, a major emphasis in the field is to identify mechanisms by which castrate-resistant AR activity and pioneer factor function can be combinatorially suppressed. Here we show that the turmeric spice isoflavone curcumin suppresses p300 and CBP occupancy at sites of AR function. Curcumin reduced the association of histone acetylation and pioneer factors, thereby suppressing AR residence and downstream target gene expression. Histone deacetylase inhibitors reversed the effects of curcumin on AR activity, further underscoring the impact of curcumin on altering the chromatin landscape. These functions precluded pioneer factor occupancy, leading ultimately to a suppression of ligand-dependent and ligand-independent AR residence on chromatin. Moreover, these functions were conserved even in cells with heightened pioneer factor activity, thus identifying a potential strategy to manage this subclass of tumors. Biological relevance was further identified using in vivo xenograft models mimicking disease progression. Curcumin cooperated in vivo with androgen deprivation as indicated by a reduction in tumor growth and delay to the onset of castrate-resistant disease. Together, our results show the combinatorial impact of targeting AR and histone modification in prostate cancer, thus setting the stage for further development of curcumin as a novel agent to target AR signaling. Cancer Res; 72(5); 1248–59. ©2012 AACR.
ATR–ATRIP Kinase Complex Triggers Activation of the Fanconi Anemia DNA Repair Pathway
Authors: Shigechi Tomoko , Tomida Junya , Sato Koichi , Kobayashi Masahiko , Eykelenboom John K. , Pessina Fabio , Zhang Yanbin , Uchida Emi , Ishiai Masamichi , Lowndes Noel F. , Yamamoto Kenichi , Kurumizaka Hitoshi , Maehara Yoshihiko , Takata Minoru
Published: January 2012

ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. However, the interplay between ATR and the FA pathway has been unclear. In this study, we present evidence that their action is directly linked, gaining insights into this relationship in a DT40 mutant cell line that is conditionally deficient in the critical ATR-binding partner protein ATRIP. Using this system, we showed that ATRIP was crucial for DNA damage–induced FANCD2 monoubiquitination and FANCI phosphorylation. ATR kinase phosphorylated recombinant FANCI protein in vitro, which was facilitated by the presence of FANCD2. Mechanistic investigations revealed that the RPA region but not the TopBP1 region of ATRIP was required for FANCD2 monoubiquitination, whereas Chk1 phosphorylation relied upon both domains. Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair. Cancer Res; 72(5); 1149–56. ©2012 AACR.
Management and Pathophysiology of Functional Gastrointestinal Disorders
Authors: Fukudo Shin , Kuwano Hiroyuki , Miwa Hiroto
Published: January 2012

Since 2005, every annual meeting of the Japanese Gastroenterological Association has included a core symposium for functional gastrointestinal disorders. At the 6th annual meeting, the core symposium was ‘Pathophysiology and New Treatment’. At the 7th annual meeting, the core symposium was ‘Pathophysiology and Motility’. This review summarizes the papers presented at these meetings. At the 6th meeting, we recognized that Japanese researchers successfully produced and developed many agents that are safe and effective for the treatment of functional gastrointestinal disorders, such as 5-hydroxytryptamine receptor-associated compounds, lubiprostone, Japanese herbal medicine, and other drugs. Data were validated from a clinical as well as an experimental viewpoint. Findings included the effects of sumatriptan and nizatidine, acylated or des-acylated ghrelin, T-cell-activating anti-CD3 antibody, and transient receptor potential vanilloid-1. At the 7th meeting, not only functional dyspepsia and irritable bowel syndrome (IBS), but also non-erosive esophageal reflux disease (NERD) and chronic intestinal pseudo-obstruction were actively discussed from a motility viewpoint, including papers about sham feeding and gastric motility, genetic polymorphism and motility, the role of transient receptor potential A1 on gastric accommodation, esophageal motility and NERD, diagnosis and treatment of chronic intestinal pseudo-obstruction, immunological basis of motility in IBS, developing non-invasive colonic function test, and fecal distribution in IBS patients.
Molecular Genetic Analysis of Macular Corneal Dystrophy Patients from North India
Authors: Paliwal Preeti , Sharma Arundhati , Tandon Radhika , Sharma Namrata , Titiyal Jeevan S. , Sen Seema , Vajpayee Rasik B.
Published: January 2012

Purpose: To identify underlying genetic defects in the carbohydrate sulfotransferase-6 (CHST6) gene in North Indian patients with macular corneal dystrophy (MCD). Methods: 30 clinically diagnosed MCD patients from 21 families and 50 healthy normal controls were recruited in the study. Detailed clinical evaluation in the patients was undertaken followed by histopathology and ultrastructural studies in corneal tissues. DNA from blood samples was amplified for the CHST6 coding and upstream region followed by direct sequencing and in silico analysis. Results: We identified pathogenic mutations in 17 patients from 11 families. Of these 4 were novel (p.Ser54Tyr, p.Gln58Arg, p.Leu59His and p.Leu293Phe), 2 were previously reported (Arg93His and Glu274Lys) homozygous, 1 heterozygous stop codon (p.Trp123X) and 2 compound heterozygous (p.Arg93His + p.Arg97Pro; p.Leu22Arg + p.Gln58X) mutations. A missense single-nucleotide polymorphism was also identified in 11 patients. The novel mutations were conserved as shown by in silico analysis. Thirteen patients did not show any pathogenic CHST6 changes. Conclusions: This is the first report on molecular analysis of MCD in North Indian patients. All cases could not be explained by mutations in CHST6, suggesting that MCD may result from other changes in the regulatory elements of CHST6 or from genetic heterogeneity.
New Frontiers for Stroke Prevention in Atrial Fibrillation
Authors: Prasad Vinayak , Kaplan Rachel M. , Passman Rod S.
Published: January 2012

Atrial fibrillation (AF) is the most common sustained arrhythmia, affects over 2.5 million people in the USA and is responsible for one fifth of the 700,000 ischemic strokes per year. For the last 50 years, long-term anticoagulation with warfarin has been the most effective therapy for preventing stroke in patients with AF and other risk factors. However, many AF patients are poor candidates for this treatment, and management of the drug can be challenging. Such challenges include the need for frequent monitoring, interactions with food and other medications, variability in metabolism and a delayed onset of action. Antiplatelet therapy has also been evaluated, and though it is not as effective at preventing ischemic strokes, it may provide some benefit for patients who cannot tolerate warfarin. Recent clinical trials have tested pharmacologic alternatives to warfarin, and new treatment options have emerged. Of these alternatives, the direct oral thrombin inhibitor dabigatran and the oral factor Xa inhibitor rivaroxaban, which have minimal interactions and require no INR monitoring, have already been approved by the FDA. The field may soon be further expanded as the oral factor Xa inhibitor apixaban has shown promise in its recent phase 3 trial and is under consideration for FDA approval. Nonpharmacologic approaches to stroke prevention in AF are under development as well. These approaches focus on occlusion or ligation of the left atrial appendage, which is frequently the location of thrombus formation. While such procedures have been done often during other cardiac surgeries, newer methods have focused on percutaneous techniques, including ones that may not require anticoagulation afterwards. In addition, new diagnostic modalities may detect paroxysmal AF with more sensitivity, potentially expanding the population to be treated and the potential impact of stroke preventive strategies on the population. This review provides a practical guide to current treatment and diagnostic options and focuses on emerging therapies.
The Use of High-Throughput Technologies to Investigate Vascular Inflammation and Atherosclerosis
Authors: Döring Yvonne , Noels Heidi , Weber Christian
Published: January 2012

The greatest challenge of scientific research is to understand the causes and consequences of disease. In recent years, great efforts have been devoted to unraveling the basic mechanisms of atherosclerosis (the underlying pathology of cardiovascular disease), which remains a major cause of morbidity and mortality worldwide. Because of the complex and multifactorial pathophysiology of cardiovascular disease, different research techniques have increasingly been combined to unravel genetic aspects, molecular pathways, and cellular functions involved in atherogenesis, vascular inflammation, and dyslipidemia to gain a multifaceted picture addressing this complexity. Thanks to the rapid evolution of high-throughput technologies, we are now able to generate large-scale data on the DNA, RNA, and protein levels. With the help of sophisticated computational tools, these data sets are integrated to enhance information extraction and are being increasingly used in a systems biology approach to model biological processes as interconnected and regulated networks. This review exemplifies the use of high-throughput technologies—such as genomics, transcriptomics, proteomics, and epigenomics—and systems biology to explore pathomechanisms of vascular inflammation and atherosclerosis.
Leukocyte-Derived Microparticles in Vascular Homeostasis
Authors: Angelillo-Scherrer Anne
Published: January 2012

Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. When they carry tissue factor or coagulation inhibitors, they participate in hemostasis and pathological thrombosis. Both proinflammatory and anti-inflammatory processes can be affected by LMPs, thus ensuring an appropriate inflammatory response. LMPs also play a dual role in the endothelium by either improving the endothelial function or inducing an endothelial dysfunction. LMPs are implicated in all stages of atherosclerosis. They circulate at a high level in the bloodstream of patients with high atherothrombotic risk, such as smokers, diabetics, and subjects with obstructive sleep apnea, where their prolonged contact with the vessel wall may contribute to its overall deterioration. Numbering microparticles, including LMPs, might be useful in predicting cardiovascular events. LMPs modify the endothelial function and promote the recruitment of inflammatory cells in the vascular wall, necessary processes for the progression of the atherosclerotic lesion. In addition, LMPs favor the neovascularization within the vulnerable plaque and, in the ruptured plaque, they take part in coagulation and platelet activation. Finally, LMPs participate in angiogenesis. They might represent a novel therapeutic tool to reset the angiogenic switch in pathologies with altered angiogenesis. Additional studies are needed to further investigate the role of LMPs in cardiovascular diseases. However, large-scale studies are currently difficult to set up because microparticle measurement still requires elaborate techniques which lack standardization.
WIT AND UNDERSTANDING: THE VOICES OF LIDIIA GINZBURG
Authors: CARDEN PATRICIA
Published: January 2012

Theory and history of literature are not for unifying, but for differentiating phenomena, and for striving to reveal and define their specificity.1
The Key Role of the Western Boundary in Linking the AMOC Strength to the North–South Pressure Gradient
Authors: Sijp Willem P. , Gregory Jonathan M. , Tailleux Remi , Spence Paul
Published: January 2012

A key idea in the study of the Atlantic meridional overturning circulation (AMOC) is that its strength is proportional to the meridional density gradient or, more precisely, to the strength of the meridional pressure gradient. A physical basis that would indicate how to estimate the relevant meridional pressure gradient locally from the density distribution in numerical ocean models to test such an idea has been lacking however. Recently, studies of ocean energetics have suggested that the AMOC is driven by the release of available potential energy (APE) into kinetic energy (KE) and that such a conversion takes place primarily in the deep western boundary currents. In this paper, the authors develop an analytical description linking the western boundary current circulation below the interface separating the North Atlantic Deep Water (NADW) and Antarctic Intermediate Water (AAIW) to the shape of this interface. The simple analytical model also shows how available potential energy is converted into kinetic energy at each location and that the strength of the transport within the western boundary current is proportional to the local meridional pressure gradient at low latitudes. The present results suggest, therefore, that the conversion rate of potential energy may provide the necessary physical basis for linking the strength of the AMOC to the meridional pressure gradient and that this could be achieved by a detailed study of the APE to KE conversion in the western boundary current.
Audience-response devices (‘clickers’): A discussion paper on their potential contribution to alcohol education in schools
Authors: Hughes Clarissa , Roche Ann M , Bywood Petra , Trifonoff Allan
Published: January 2012

Many schools endeavour to provide effective, relevant and appealing alcohol education to students, using up-to-date technologies and resources. However, choosing an appropriate, evidence-based programme or approach is rarely straightforward given the plethora of options and limited evidence base. The alcohol education literature and findings from a recent Australian study indicate four key features of effective alcohol education approaches: interactivity, peer education, exploration of students’ opinions/knowledge, and addressing alcohol-related misperceptions. These four features are acknowledged strengths of audience-response devices (‘clickers’). Clickers are increasingly popular, supported by growing evidence of suitability for a variety of educational applications and have untapped potential in the delivery of alcohol education. Clickers can engage and empower students and their ability to elucidate misperceptions regarding prevalence and acceptance of risky alcohol use among peers corresponds with normative education approaches. Clickers are effective, fun, create valuable ‘teachable moments’ and provide potential to enhance delivery of evidence-based alcohol education.
Spectral element analysis of the axial-bending-shear coupled vibrations of composite Timoshenko beams
Authors: Jang I , Lee U
Published: January 2012

This article presents a spectral element model for the axially loaded axial-bending-shear coupled vibrations of composite laminated beams, which are represented by the Timoshenko beam models based on the first-order shear deformation theory. The variation approach is used to formulate the frequency-dependent spectral element matrix (often called exact dynamic stiffness matrix) for the present spectral element model. As the spectral element matrix is formulated from exact wave solutions satisfying the frequency domain governing equations of motion transformed by the use of discrete Fourier transform theory, the present spectral element model cannot only provide extremely accurate solutions with using only a minimum number of degrees of freedom but also contribute to improving the computation efficiency. The high accuracy of the present spectral element model is numerically verified by comparing its solutions with exact analytical solutions available from references as well as with the solutions obtained by conventional finite element method. The effects of the axial loading and damping are also numerically investigated. For the numerical verification, the finite element model is also provided for the axially loaded axial-bending-shear coupled composite laminated Timoshenko beams.
Preparation and study on the structure and properties of rare-earth luminescent fiber
Authors: Ge Mingqiao , Guo Xuefeng , Yan Yanhong
Published: January 2012

In order to further explain the luminous properties of rare-earth luminescent fiber and promote various-product development of the fiber, in this research, rare-earth luminescent fiber was prepared by using rare-earth strontium aluminate as the rare-earth luminescent material, fiber-forming polymer PET as the matrix. The microstructure, composition and properties of rare-earth luminescent fiber were studied systematically based on tests and analysis with luminescent fiber, rare-earth luminescent materials and polyester fiber in detail. The results showed that the crystal structure of SrAl2O4: Eu2+, Dy3+ distributed in fiber was not destroyed by the polymer matrix and that the complex manufacturing process to ensure luminous properties of fiber performed well. Meanwhile, the structure and properties of luminescent fiber with no distinct changes were similar with that of the polyester fiber. The breaking tenacity and elongation of luminescent fiber in the wet state decreased respectively compared to the dry, and the breaking tenacity of polyester fiber was higher than luminescent fiber. The endothermic melting peak and glass transition temperature of luminescent fiber were slightly higher than that of polyester fiber. Decay curves of samples were successfully fitted by the sum of three exponential components with different decay times. Characteristic decay tended to be longer in luminescent fiber, while the initial luminance intensity of SrAl2O4: Eu2+, Dy3+ was higher than that of luminescent fiber.
Is patient-centred care a good thing?
Authors: Ward Christopher D
Published: January 2012

The problem: Rehabilitation professionals recognize the need to adopt a social as well as a medical model of disability, but the full implications of a social orientation towards disability are less easily accepted. If the physical environment can both produce and alleviate disability, so also can the social environment. If disablement is not to be seen as the problem of one individual then problems in rehabilitation must be ‘owned’ not solely by a single patient but also by other people implicated in a situation. It follows that ‘patient-centred care’, where a professional directs assessments and interventions towards one person, has shortcomings in rehabilitation.

Theoretical considerations: A human systems model, shifting the focus of rehabilitation towards relationships, enables rehabilitation problems to be seen as provisional and context-dependent; the relational context of problems is clarified, and the positive and negative effects of professional power are more apparent.

Clinical implications: Rehabilitation practitioners using a systemic approach would no longer view ‘carers’ and other significant individuals as mere bystanders but would integrate them within rehabilitation’s ethical and therapeutic system. Professionals would more readily recognize their roles within such a system, and would be better positioned to manage their negative as well as their positive effects.
Bobath Concept versus constraint-induced movement therapy to improve arm functional recovery in stroke patients: a randomized controlled trial
Authors: Huseyinsinoglu Burcu Ersoz , Ozdincler Arzu Razak , Krespi Yakup
Published: January 2012

Objective:

To compare the effects of the Bobath Concept and constraint-induced movement therapy on arm functional recovery among stroke patients with a high level of function on the affected side.

Design:

A single-blinded, randomized controlled trial.

Setting:

Outpatient physiotherapy department of a stroke unit.

Subjects:

A total of 24 patients were randomized to constraint-induced movement therapy or Bobath Concept group.

Intervention:

The Bobath Concept group was treated for 1 hour whereas the constraint-induced movement therapy group received training for 3 hours per day during 10 consecutive weekdays.

Main measures:

Main measures were the Motor Activity Log-28, the Wolf Motor Function Test, the Motor Evaluation Scale for Arm in Stroke Patients and the Functional Independence Measure.

Results:

The two groups were found to be homogeneous based on demographic variables and baseline measurements. Significant improvements were seen after treatment only in the ‘Amount of use’ and ‘Quality of movement’ subscales of the Motor Activity Log-28 in the constraint-induced movement therapy group over the the Bobath Concept group ( P = 0.003; P = 0.01 respectively). There were no significant differences in Wolf Motor Function Test ‘Functional ability’ ( P = 0.137) and ‘Performance time’ ( P = 0.922), Motor Evaluation Scale for Arm in Stroke Patients ( P = 0.947) and Functional Independence Measure scores ( P = 0.259) between the two intervention groups.

Conclusions:

Constraint-induced movement therapy and the Bobath Concept have similar efficiencies in improving functional ability, speed and quality of movement in the paretic arm among stroke patients with a high level of function. Constraint-induced movement therapy seems to be slightly more efficient than the Bobath Concept in improving the amount and quality of affected arm use.