bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and psychometric properties of a belief-based Physical Activity Questionnaire for Diabetic Patients (PAQ-DP)
Authors: Ghazanfari Zeinab , Niknami Shamsaddin , Ghofranipour Fazlollah , Hajizadeh Ebrahim , Montazeri Ali
Published: November 2010

Background

This study carried out to develop a scale for assessing diabetic patients' perceptions about physical activity and to test its psychometric properties (The Physical Activity Questionnaire for Diabetic Patients-PAQ-DP).

Methods

An item pool extracted from the Theory of Planned Behavior literature was generated. Then an expert panel evaluated the items by assessing content validity index and content validity ratio. Consequently exploratory factor analysis (EFA) was performed to indicate the scale constructs. In addition reliability analyses including internal consistency and test-retest analysis were carried out.

Results

In all a sample of 127 women with diabetes participated in the study. Twenty-two items were initially extracted from the literature. A six-factor solution (containing 19 items) emerged as a result of an exploratory factor analysis namely: instrumental attitude, subjective norm, perceived behavioral control, affective attitude, self-identity, and intention explaining 60.30% of the variance observed. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.54 to 0.8) and intraclass correlation coefficients (ranging from 0.40 to 0.92).

Conclusions

The Physical Activity Questionnaire for Diabetic Patients (PAQ-DP) is the first instrument that applies the Theory of Planned Behavior in its constructs. The findings indicated that the PAQ-DP is a reliable and valid measure for assessing physical activity perceptions and now is available and can be used in future studies.
Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells
Authors: Raghu Hari , Sodadasu Prasanna Kumar , Malla Rama Rao , Gondi Christopher S , Estes Norman , Rao Jasti S
Published: November 2010

Background

uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts.

Methods

To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts) to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling.

Results

Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. In vitro angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells.

Conclusion

Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9.
Investigating dynamic and energetic determinants of protein nucleic acid recognition: analysis of the zinc finger zif268-DNA complexes
Authors: Torella Rubben , Moroni Elisabetta , Caselle Michele , Morra Giulia , Colombo Giorgio
Published: November 2010

Background

Protein-DNA recognition underlies fundamental biological processes ranging from transcription to replication and modification. Herein, we present a computational study of the sequence modulation of internal dynamic properties and of intraprotein networks of aminoacid interactions that determine the stability and specificity of protein-DNA complexes.

Results

To this aim, we apply novel theoretical approaches to analyze the dynamics and energetics of biological systems starting from MD trajectories. As model system, we chose different sequences of Zinc Fingers (ZF) of the Zif268 family bound with different sequences of DNA. The complexes differ for their experimental stability properties, but share the same overall 3 D structure and do not undergo structural modifications during the simulations. The results of our analysis suggest that the energy landscape for DNA binding may be populated by dynamically different states, even in the absence of major conformational changes. Energetic couplings between residues change in response to protein and/or DNA sequence variations thus modulating the selectivity of recognition and the relative importance of different regions for binding.

Conclusions

The results show differences in the organization of the intra-protein energy-networks responsible for the stabilization of the protein conformations recognizing and binding DNA. These, in turn, are reflected into different modulation of the ZF's internal dynamics. The results also show a correlation between energetic and dynamic properties of the different proteins and their specificity/selectivity for DNA sequences. Finally, a dynamic and energetic model for the recognition of DNA by Zinc Fingers is proposed.
Tracking hantavirus nucleocapsid protein using intracellular antibodies
Authors: Li Jiandong , Zhang Quanfu , Wang Tao , Li Chuan , Liang Mifang , Li Dexin
Published: November 2010

Background

Hantavirus nucleocapsid (N) protein is a multifunctional viral macromolecule involved in multiple stages of the viral replication cycle. The intracellular trafficking of N protein during virus assembly remains unclear.

Methods

We used N protein-specific intracellular expressed antibodies to track the localization and distribution of Hantaan virus and Seoul virus N protein. The N protein-specific antibody single-chain variable antibody fragments (scFvs), which bind an N-terminal linear epitope (L13F3) and C-terminal conformational domain (H34), were intracellularly expressed in the endoplasmic reticulum (ER) by fusion of the SEKDEL retention signal peptide at the carboxyl terminus, and in the cytoplasm (Cyto) by deletion of the ER membrane target signal peptide. Stable Vero-E6 cell lines expressing intracellular scFvs were either infected with hantavirus or transfected with an N protein expression plasmid; virus replication and N protein intracellular localization were determined.

Result

N protein co-localized with scFvs in the ER and cytoplasm with or without viral membrane glycoproteins. Hantavirus replication was inhibited in both the scFvs-ER- and scFvs-Cyto-expressing stable cell lines.

Conclusion

N protein may be expressed in the ER retention signal peptide of KDEL circulating region (ER/cis-Golgi) without the assistance of G protein, and so expression of N protein in both the cytoplasm and within the ER/cis-Golgi plays an important role in virus replication.
Sensitization of Capsaicin and Icilin Responses in Oxaliplatin Treated Adult Rat DRG Neurons
Authors: Anand Uma , Otto William R , Anand Praveen
Published: November 2010

Background:

Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons.

Results:

48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P < 0.05), compared to controls (120.3 ± 4 a.u.). Calcium imaging showed significantly enhanced capsaicin (TRPV1 agonist), responses after acute 20 μg/ml oxaliplatin treatment where the second of paired capsaicin responses increased from 80.7 ± 0.6% without oxaliplatin, to 171.26 ± 29% with oxaliplatin, (n = 6 paired t test, P < 0.05); this was reduced to 81.42 ± 8.1% (P < 0.05), by pretretreatment with the cannabinoid CB2 receptor agonist GW 833972. Chronic oxaliplatin treatment also resulted in dose related increases in capsaicin responses. Similarly, second responses to icilin (TRPA1/TRPM8 agonist), were enhanced after acute (143.85 ± 7%, P = 0.004, unpaired t test, n = 3), and chronic (119.7 ± 11.8%, P < 0.05, n = 3) oxaliplatin treatment, compared to control (85.3 ± 1.7%). Responses to the selective TRPM8 agonist WS-12 were not affected.

Conclusions:

Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.
Transmitted drug resistance associated with transmission clusters in newly diagnosed antiretroviral‐naïve patients in Northern Greece
Authors: Skoura L , Metallidis S , Buckton AJ , Mbisa JL , Pilalas D , Papadimitriou E , Papoutsi A , Haidich AB , Valagouti D , Tsachouridou O , Antoniadou ZA , Kollaras P , Nikolaidis P , Malisiovas N
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Leukocyte extract reduces HIV replication and modulates cellular factors involved in HIV infection: therapeutic meant
Authors: Fernandez‐Ortega C , Casillas D , Dubed M , Navea L , Ramirez A , Lopez L , Paneque T , Reinoso Y
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Switch to once or twice daily unboosted atazanavir in a cohort of stable HIV patients: strong differences in drug exposure and virological outcome
Authors: Baudry T , Boibieux A , Gagnieu MC , Cotte L , Livrozet JM , Miahles P , Makhloufi D , Chidiac C , Peyramond D , Ferry T
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis
Authors: Sjövall Fredrik , Morota Saori , Hansson Magnus J , Friberg Hans , Gnaiger Erich , Elmér Eskil
Published: November 2010

Introduction

Mitochondrial dysfunction has been suggested as a contributing factor to the pathogenesis of sepsis-induced multiple organ failure. Also, restoration of mitochondrial function, known as mitochondrial biogenesis, has been implicated as a key factor for the recovery of organ function in patients with sepsis. Here we investigated temporal changes in platelet mitochondrial respiratory function in patients with sepsis during the first week after disease onset.

Methods

Platelets were isolated from blood samples taken from 18 patients with severe sepsis or septic shock within 48 hours of their admission to the intensive care unit. Subsequent samples were taken on Day 3 to 4 and Day 6 to 7. Eighteen healthy blood donors served as controls. Platelet mitochondrial function was analyzed by high-resolution respirometry. Endogenous respiration of viable, intact platelets suspended in their own plasma or phosphate-buffered saline (PBS) glucose was determined. Further, in order to investigate the role of different dehydrogenases and respiratory complexes as well as to evaluate maximal respiratory activity of the mitochondria, platelets were permeabilized and stimulated with complex-specific substrates and inhibitors.

Results

Platelets suspended in their own septic plasma exhibited increased basal non-phosphorylating respiration (state 4) compared to controls and to platelets suspended in PBS glucose. In parallel, there was a substantial increase in respiratory capacity of the electron transfer system from Day 1 to 2 to Day 6 to 7 as well as compared to controls in both intact and permeabilized platelets oxidizing Complex I and/or II-linked substrates. No inhibition of respiratory complexes was detected in septic patients compared to controls. Non-survivors, at 90 days, had a more elevated respiratory capacity at Day 6 to 7 as compared to survivors. Cytochrome c increased over the time interval studied but no change in mitochondrial DNA was detected.

Conclusions

The results indicate the presence of a soluble plasma factor in the initial stage of sepsis inducing uncoupling of platelet mitochondria without inhibition of the electron transfer system. The mitochondrial uncoupling was paralleled by a gradual and substantial increase in respiratory capacity. This may reflect a compensatory response to severe sepsis or septic shock, that was most pronounced in non-survivors, likely correlating to the severity of the septic insult.
Seismic Risk Assessment of Masonry Buildings in Istanbul for Effective Risk Mitigation
Authors: Erberik M. Altug
Published: November 2010

Unreinforced and non-engineered masonry buildings are highly vulnerable to seismic hazard and constitute a significant percentage of earthquake losses, including both casualties and economic losses. This study presents an engineering application on seismic safety assessment of unreinforced masonry (URM) buildings in Istanbul, Turkey, a metropolitan city under very high seismic risk. Nearly 20,000 masonry buildings were examined through a two-stage assessment procedure in order to identify the addresses of those buildings which are under high seismic risk. Furthermore, the obtained database can be employed in the preparation of an earthquake mitigation strategy for the expected major earthquake in Istanbul. In the first-stage evaluation, buildings are examined visually from the street by considering their basic structural parameters and they are ranked within a priority list in terms of the calculated seismic risk. Next, the buildings identified with higher risk are evaluated in the second stage by using a more detailed procedure. The developed procedure is both an optimal and a practical tool in the seismic risk assessment of large masonry building stocks in a short period of time with limited resources.
Post-Earthquake Housing Recovery in Bachhau, India: The Homeowner, the Renter, and the Squatter
Authors: Mukherji Anuradha
Published: November 2010

This paper looks at post-earthquake housing recovery in Bachhau, a town close to the epicenter of the 2001 Gujarat earthquake in western India. This research examines the difference in housing recovery outcomes among homeowners, squatters, and renters in Bachhau, in order to understand why single-family homeowners and squatters were able to rebuild and improve their housing conditions whereas low-income renters continued to struggle toward housing recovery. This paper shows that communities in Bachhau did not have the resources or capacities to rebuild themselves and that appropriate public assistance was critical for housing recovery. While public assistance was mainly targeted to meet the needs of homeowners, local government officials in Bachhau pursued a squatter housing recovery program crafted to meet the needs of low-income squatters. In contrast, public policy failed to understand the needs of renter households, resulting in their marginalization from the housing recovery process in Bachhau.
Evaluation of Design Review Process and Requirements for Seismic-Isolated Buildings
Authors: Ryan Keri L. , Arendt Lucy A. , Larsen Desiray
Published: November 2010

A telephone survey was conducted to determine design professionals' experiences and opinions of the design review process for seismic isolated buildings. Participants agreed that the review process is beneficial in concept, but the benefit can sometimes be obscured by poor implementation. Best practice recommendations include: (1) the review team should be organized and the review process should be planned at the onset of design; (2) all parties should mutually agree on the scope and level of detail of review; and (3) a process for conflict resolution should be pre-negotiated. Most of the discussion and recommendations generated by this study are applicable to design reviews in general. The specific code requirements for design review of isolated buildings were found to be in need of updating, but the concept of exempting certain structures from the review process, favored by some engineers, was not found to have widespread support.
Seismic Hazard Mapping of California considering Site Effects
Authors: Kalkan Erol , Wills Chris J. , Branum David M.
Published: November 2010

In this paper, we have combined the U.S. Geological Survey's National Seismic Hazard Maps model with the California geologic map showing 17 generalized geologic units that can be defined by their VS30. We regrouped these units into seven VS30 values and calculated a probabilistic seismic hazard map for the entire state for each VS30 value. By merging seismic hazard maps based on the seven different VS30 values, a suite of seismic hazard maps was computed for 0.2 and 1.0 s spectral ordinates at 2% probability of exceedance (PE) in 50 years. The improved hazards maps explicitly incorporate the site effects and their spatial variability on ground motion estimates. The spectral acceleration (SA) at 1.0 s map of seismic shaking potential for California has now been published as California Geological Survey Map Sheet 48.
Exploring the Proximity of Ground-Motion Models Using High-Dimensional Visualization Techniques
Authors: Scherbaum Frank , Kuehn Nicolas M. , Ohrnberger Matthias , Koehler Andreas
Published: November 2010

Logic trees have become a popular tool to capture epistemic uncertainties in seismic hazard analysis. They are commonly used by assigning weights to models on a purely descriptive basis (nominal scale). This invites the creation of unintended inconsistencies regarding the weights on the corresponding hazard curves. On the other hand, for human experts it is difficult to confidently express degrees-of-beliefs in particular numerical values. Here we demonstrate for ground-motion models how the model and the value-based perspectives can be partially reconciled by using high-dimensional information-visualization techniques. For this purpose we use Sammon's (1969) mapping and self-organizing mapping to project ground-motion models onto a two-dimensional map (an ordered metric set). Here they can be evaluated jointly according to their proximity in predicting similar ground motions, potentially making the assignment of logic tree weights consistent with their ground motion characteristics without having to abandon the model-based perspective.
Minimization of Trigger Error in Cat-in-a-Box Parametric Earthquake Catastrophe Bonds with an Application to Costa Rica
Authors: Franco Guillermo
Published: November 2010

Catastrophe bonds are used by the insurance and reinsurance industry and by national governments to cede catastrophic risks to the financial markets. Triggers whose outcomes depend only on the earthquake parameter data published by respected third parties can be implemented to determine without moral hazard whether the bond principal is paid for a certain event. Sensitivity analyses to different design assumptions show that these transactions are often affected by trigger error, unless a sufficiently dense geographic discretization is selected to define the trigger zones. A process of general application to any geography is developed to minimize the trigger error. The methodology is illustrated with the design of a hypothetical cat bond for Costa Rica.
Reconnaissance Observation on Bridge Damage Caused by the 2008 Wenchuan (China) Earthquake
Authors: Lin Chu-Chieh Jay , Hung Hsiao-Hui , Liu Kuang-Yen , Chai Juin-Fu
Published: November 2010

Following the 2008 Wenchuan (China) earthquake, the civil engineers association from Taiwan immediately dispatched a team to the affected region to collect information about the structural and geotechnical damage, and to provide information for seismic assessment, retrofitting and reconstruction planning. This team reached the damaged areas close to the epicenter—including Chengdu, Dujiangyan, Pongzhou, Xiaoyudong, Mianzhu, Zhiulong, Wudu, Hanwang, Hsuanko, Yingxiu (epicenter), and Highway 213—to survey the affected schools, hospitals, residential buildings, landslides, and bridges. More than 5,000 photos were taken to document the damage that resulted from the catastrophic earthquake ( http://www.ncree.gov.tw/eng/index.htm ). It is hoped that the information obtained can help us to develop a disaster mitigation plan. This paper focuses on the damage to different types of bridges, including those with simple support, arch, and continuous elements. The information shared in this study can help us build a community that will be safer in the future.
Seismic Rehabilitation of Welded Steel Beam-to-Box Column Connections Utilizing Internal Flange Stiffeners
Authors: Chou Chung-Che , Jao Chih-Kai
Published: November 2010

This work investigates the seismic performance of rehabilitated steel moment connections using internal flange stiffeners (IFSs) welded to the face of a built-up box column and a beam flange inner side. The objective is to provide a rehabilitation scheme that excludes interference from the composite slab and story height limitation in an existing steel building. Five rehabilitated moment connections with different IFSs were tested according to AISC (2005) loading protocol to validate their cyclic performance. Two rehabilitated moment connections had excellent performance; no welded joint fractures were found in the connections with a drift in excess of 4%. The specimens were modeled using the computer program ABAQUS to further verify the effectiveness of the IFSs in transferring beam moments to a column and to investigate potential sources of connection failure. Design guidelines for the rehabilitation scheme are provided based on test and analytical results.
An Empirical Model for Global Earthquake Fatality Estimation
Authors: Jaiswal Kishor , Wald David
Published: November 2010

We analyzed mortality rates of earthquakes worldwide and developed a country/region-specific empirical model for earthquake fatality estimation within the U.S. Geological Survey's Prompt Assessment of Global Earthquakes for Response (PAGER) system. The earthquake fatality rate is defined as total killed divided by total population exposed at specific shaking intensity level. The total fatalities for a given earthquake are estimated by multiplying the number of people exposed at each shaking intensity level by the fatality rates for that level and then summing them at all relevant shaking intensities. The fatality rate is expressed in terms of a two-parameter lognormal cumulative distribution function of shaking intensity. The parameters are obtained for each country or a region by minimizing the residual error in hindcasting the total shaking-related deaths from earthquakes recorded between 1973 and 2007. A new global regionalization scheme is used to combine the fatality data across different countries with similar vulnerability traits.
Binational Unions: New Hope for Guest Workers
Authors: Hill Jennifer
Published: November 2010

Agricultural guest workers have organized in recent years, but building viable unions to represent guest workers is challenging. To effectively represent guest workers, a union must address problems throughout the work cycle in both home and host countries. The Farm Labor Organizing Committee (FLOC) is one union that has organized guest-worker units in recent years. FLOC is experimenting with outreach, education, and representation activities in Mexico, the home country for members of their guest-worker bargaining unit. To be successful, FLOC and other guest-worker unions must use the advantages available in each country's legal and political regimes to advance the interests of its members. In Mexico, legal requirements for an employment relationship and restrictions on foreign union officials might stand in the way of union recognition. Neither is insuperable in principle, but they point to the legal and political minefield into which a guest-worker union might fall. Nevertheless, experiments aimed at developing new transnational forms and tools is a worthwhile venture because purely domestic forms of organization will not adequately serve workers in a world where both labor and capital cross borders.
Cdx1 refines positional identity of the vertebrate hindbrain by directly repressingMafbexpression
Authors: Sturgeon Kendra , Kaneko Tomomi , Biemann Melissa , Gauthier Andree , Chawengsaksophak Kallayanee , Cordes Sabine P.
Published: November 2010

An interplay of transcription factors interprets signalling pathways to define anteroposterior positions along the vertebrate axis. In the hindbrain, these transcription factors prompt the position-appropriate appearance of seven to eight segmental structures, known as rhombomeres (r1-r8). The evolutionarily conserved Cdx caudal-type homeodomain transcription factors help specify the vertebrate trunk and tail but have not been shown to directly regulate hindbrain patterning genes. Mafb (Kreisler, Krml1, valentino), a basic domain leucine zipper transcription factor, is required for development of r5 and r6 and is the first gene to show restricted expression within these two segments. The homeodomain protein vHnf1 (Hnf1b) directly activates Mafb expression. vHnf1 and Mafb share an anterior expression limit at the r4/r5 boundary but vHnf1 expression extends beyond the posterior limit of Mafb and, therefore, cannot establish the posterior Mafb expression boundary. Upon identifying regulatory sequences responsible for posterior Mafb repression, we have used in situ hybridization, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses to determine that Cdx1 directly inhibits early Mafb expression in the neural tube posterior of the r6/r7 boundary, which is the anteriormost boundary of Cdx1 expression in the hindbrain. Cdx1 dependent repression of Mafb is transient. After the 10-somite stage, another mechanism acts to restrict Mafb expression in its normal r5 and r6 domain, even in the absence of Cdx1. Our findings identify Mafb as one of the earliest direct targets of Cdx1 and show that Cdx1 plays a direct role in early hindbrain patterning. Thus, just as Cdx2 and Cdx4 govern the trunk-to-tail transition, Cdx1 may regulate the hindbrain-to-spinal cord transition.
Caveolin limits membrane microdomain mobility and integrin-mediated uptake of fibronectin-binding pathogens
Authors: Hoffmann Christine , Berking Anne , Agerer Franziska , Buntru Alexander , Neske Florian , Chhatwal G. Singh , Ohlsen Knut , Hauck Christof R.
Published: November 2010

Staphylococcus aureus, which is a leading cause of hospital-acquired infections, binds via fibronectin to integrin α5β1, a process that can promote host colonization in vivo. Integrin engagement induces actin cytoskeleton rearrangements that result in the uptake of S. aureus by non-professional phagocytic cells. Interestingly, we found that fibronectin-binding S. aureus trigger the redistribution of membrane microdomain components. In particular, ganglioside GM1 and GPI-linked proteins were recruited upon integrin β1 engagement, and disruption of membrane microdomains blocked bacterial internalization. Several membrane-microdomain-associated proteins, such as flotillin-1 and flotillin-2, as well as caveolin, were recruited to sites of bacterial attachment. Whereas dominant-negative versions of flotillin-2 did not affect bacterial attachment or internalization, cells deficient for caveolin-1 (Cav1−/−) showed increased uptake of S. aureus and other Fn-binding pathogens. Recruitment of membrane microdomains to cell-associated bacteria was unaltered in Cav1−/− cells. However, fluorescence recovery after photobleaching (FRAP) revealed an enhanced mobility of membrane-microdomain-associated proteins in the absence of caveolin-1. Enhanced membrane microdomain mobility and increased uptake of S. aureus was repressed by expression of wild-type caveolin-1, but not caveolin-1 G83S, which harbors a point mutation in the caveolin scaffolding domain. Similarly, chemical or physical stimulation of membrane fluidity led to increased uptake of S. aureus. These results highlight a crucial role for caveolin-1 in negative regulation of membrane microdomain mobility, thereby affecting endocytosis of bacteria-engaged integrins. This process might not only limit host cell invasion by integrin-binding bacterial pathogens, but might also be physiologically relevant for integrin-mediated cell adhesion.
Regulation of cell cycle-specific gene expression in fission yeast by the Cdc14p-like phosphatase Clp1p
Authors: Papadopoulou Kyriaki , Chen Jun-Song , Mead Emma , Feoktistova Anna , Petit Claudia , Agarwal Monica , Jamal Mohhammed , Malik Asrar , Spanos Adonis , Sedgwick Steven G. , Karagiannis Jim , Balasubramanian Mohan K. , Gould Kathleen L. , McInerny Christopher J.
Published: November 2010

Regulated gene expression makes an important contribution to cell cycle control mechanisms. In fission yeast, a group of genes is coordinately expressed during a late stage of the cell cycle (M phase and cytokinesis) that is controlled by common cis-acting promoter motifs named pombe cell cycle boxes (PCBs), which are bound by a trans-acting transcription factor complex, PCB binding factor (PBF). PBF contains at least three transcription factors, a MADS box protein Mbx1p and two forkhead transcription factors, Sep1p and Fkh2p. Here we show that the fission yeast Cdc14p-like phosphatase Clp1p (Flp1p) controls M–G1 specific gene expression through PBF. Clp1p binds in vivo both to Mbx1p, a MADS box-like transcription factor, and to the promoters of genes transcribed at this cell cycle time. Because Clp1p dephosphorylates Mbx1p in vitro, and is required for Mbx1p cell cycle-specific dephosphorylation in vivo, our observations suggest that Clp1p controls cell cycle-specific gene expression through binding to and dephosphorylating Mbx1p.
Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity
Authors: Horbelt Daniel , Guo Gao , Robinson Peter N. , Knaus Petra
Published: November 2010

Mutations in the gene encoding transforming growth factor-beta receptor type II (TGFBR2) have been described in patients with Loeys–Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). Here, we present a comprehensive and quantitative analysis of TGFBR2 expression, turnover and TGF-β-induced Smad and ERK signaling activity for nine mutations identified in patients with LDS, MFS2 and TAAD. The mutations had different effects on protein stability, internalization and signaling. A dominant-negative effect was demonstrated for mutations associated with LDS and MFS2. No mutation showed evidence of an immediate cell-autonomous paradoxical activation of TGF-β signaling. There were no cell biological differences between mutations described in patients with LDS and MFS2. By contrast, R460C, which has been found in familial TAAD but not in MFS2 or LDS, showed a less-severe dominant-negative effect and retained residual Smad phosphorylation and transcriptional activity. TAAD is characterized primarily by thoracic aortic aneurysms or dissections. By contrast, MFS2 is characterized by numerous skeletal abnormalities, and patients with LDS additionally can display craniofacial and other abnormalities. Therefore, our findings suggest that the balance between defects in Smad and ERK signaling might be an important determinant of phenotypic severity in disorders related to mutations in TGFBR2.
Redox Behavior and Electrochemical Catalytic Function of B12–Hyperbranched Polymer
Authors: Tahara Keishiro , Shimakoshi Hisashi , Tanaka Akihiro , Hisaeda Yoshio
Published: November 2010

The electrochemical behavior of a covalently functionalized hyperbranched polymer with a vitamin B12 derivative (B12–HBP) was investigated by cyclic voltammetry and UV–vis spectroscopy combined with bulk electrolysis in N,N-dimethylformamide. The B12–HBP showed excellent properties for a homogeneous catalyst such as the good accessibilities of the cobalt centers in B12–HBP to an electrode and substrates and the maintained supernucleophilicity of the Co(I) species to alkyl halides. The cobalt-methylated B12–HBP was newly synthesized, and its electrochemical behavior was also investigated by cyclic voltammetry. Furthermore, B12–HBP was used as an electrochemical degradation catalyst for 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT). This work presents the first electrocatalysis study of a catalytically active transition-metal complex on a homogeneous dendritic support and investigates the suitability of the present B12–HBP system for electrochemical dehalogenation.
Thin TiO2 Films Prepared via High-pressure Crystallization for Dye-sensitized Solar Cells
Authors: Ma Jeng-Shin , Lu Chung-Hsin
Published: November 2010

Well-crystallized thin TiO2 films were successfully prepared via high-pressure crystallization (HPC). The crystallization temperature of TiO2 films was significantly decreased to 200 °C using the HPC route. The energy conversion efficiency of the dye-sensitized solar cells with the HPC-derived thin films was low because of the existence of organic residuals. Through UV-irradiation to remove the organic residuals, the energy conversion efficiency of the solar cells was significantly increased.
Probabilistic Bayesian reasoning can help identifying potentially wrong immunoassays results in clinical practice: even when they appear ‘not-unreasonable’
Authors: Ismail Adel A A , Ismail Abbas A , Ismail Yasmin
Published: November 2010

Background

Immunoassays are susceptible to analytical interferences including from endogenous immunoglobulin antibodies at a rate of ∼0.4% to 4%. Hundreds of millions of immunoassay tests (>10 millions in the UK alone) are performed yearly worldwide for measurements of an array of large and small moieties such as proteins, hormones, tumour markers, rheumatoid factor, troponin, small peptides, steroids and drugs.

Methods

Interference in these tests can lead to false results which when suspected, or surmised, can be analytically confirmed in most cases. Suspecting false laboratory data in the first place is not difficult when results are gross and without clinical correlates. However, when false results are subtle and/or plausible, it can be difficult to suspect with adverse clinical sequelae. This problem can be ameliorated by using a probabilistic Bayesian reasoning to flag up potentially suspect results even when laboratory data appear “not-unreasonable”.

Results

Essentially, in disorders with low prevalence, the majority of positive results caused by analytical interference are likely to be false positives. On the other hand, when the disease prevalence is high, false negative results increase and become more significant. To illustrate the scope and utility of this approach, six different examples covering wide range of analytes are given, each highlighting specific aspect/nature of interference and suggested options to reduce it.

Conclusion

Bayesian reasoning would allow laboratorians and/or clinicians to extract information about potentially false results, thus seeking follow-up confirmatory tests prior to the initiation of more expensive/invasive procedures or concluding a potentially wrong diagnosis.
Medication Reconciliation During Internal Hospital Transfer and Impact of Computerized Prescriber Order Entry
Authors: Lee Justin Y , Leblanc Kori , Fernandes Olavo A , Huh Jin-Hyeun , Wong Gary G , Hamandi Bassem , Lazar Neil M , Morra Dante , Bajcar Jana M , Harrison Jennifer
Published: November 2010

Background:

Internal hospital transfer is a vulnerable time during which patients are at high risk of medication discrepancies that can result in clinically significant harm, medication errors, and adverse drug events.

Objective:

To identify, characterize, and assess the clinical impact of unintentional medication discrepancies during internal hospital transfer and to investigate the influence of computerized prescriber order entry (CPOE) on medication discrepancies.

Methods:

All patients transferred between 10 inpatient units at 2 tertiary care hospitals were prospectively assessed to identify discrepancies. Interfaces included transfers between (1) units that both used paper-based medication ordering systems; (2) units that both used CPOE-based systems; and (3) units that used both paper-based and CPOE-based systems (hybrid transfer). The primary endpoint was the number of patients with at least 1 unintentional medication discrepancy during internal hospital transfer. Discrepancies were identified through assessment and comparison of a best possible medication transfer list with the actual transfer orders. A multidisciplinary team of clinicians assessed the potential clinical impact and severity of unintentional discrepancies.

Results:

Overall, 190 patients were screened and 129 patients were included. Eighty patients (62.0%) had at least 1 unintentional medication discrepancy at the time of transfer, and the most common discrepancy was medication omission (55.6%). Factors that independently increased the risk of a patient experiencing at least 1 unintentional discrepancy included lack of best possible medication history, increasing number of home medications, and increasing number of transfer medications. Forty-seven patients (36.4%) had at least 1 unintentional discrepancy with the potential to cause discomfort and/or clinical deterioration. The risk of discrepancies was present regardless of the medication-ordering system (paper, CPOE, or hybrid).

Conclusions:

Clinically significant medication discrepancies occur commonly during internal hospital transfer. A structured, collaborative, and clearly defined medication reconciliation process is needed to prevent internal transfer discrepancies and patient harm.
Phenobarbital/Lamotrigine Coadministration–Induced Blood Dyscrasia in a Patient with Epilepsy
Authors: Siniscalchi Antonio , Gallelli Luca , Calabrò Giuseppina , Tolotta Grazia Angela , Sarro Giovambattista De
Published: November 2010

Objective:

To report on a patient with epilepsy who developed leukopenia and thrombocytopenia during phenobarbital/lamotrigine treatment.

Case Report:

A 45-year-old woman with a 10-year history of complex partial seizures being treated with phenobarbital 100 mg/day presented due to the development of complex partial seizure episodes (8 episodes/month in the last 6 months). Results of laboratory tests on admission showed norma! platelets (250 × 103/μL) and white blood cells (8.2 × 103/μL). After clinical evaluation, lamotrigine titrated to a final dose of 100 mg twice daily was added to the phenobarbital. About 2 months later no epileptic manifestations were reported, but hematologic tests revealed a decrease in both platelets (36 × 103/μL) and white blood cells (2.0 × 103/μL). One day later, phenobarbital was discontinued and the patient developed 2 episodes of complex partial seizure. Levetiracetam titrated to 1500 mg/day was added to lamotrigine, with a normalization of platelets (260 × 103/μL) and white blood cell (7.9 × 103/μL) counts about 20 days later. After a few days, levetiracetam was discontinued and phenobarbital rechallenge during lamotrigine treatment induced a new blood dyscrasia in about 2 weeks (platelets 80 × 103/μL; white blood cells 3.2 × 103/μL), Phenobarbital was discontinued and levetiracetam was restarted, with a recovery of normal hematopoiesis in 25 days. The patient is presently receiving treatment with both lamotrigine 200 mg/day and levetiracetam 1500 mg/day and shows no seizure symptoms, blood abnormalities, or other adverse effects.

Discussion:

Using the Horn Drug Interaction Probability Scale, we estimated a probable relationship between the drug-drug interaction and blood dyscrasia. The underlying mechanism of this interaction has not been well characterized. Cytochrome P450 enzyme induction by phenobarbital could be responsible for the production of reactive metabolites of lamotrigine that might be causative for the observed hematologic effects. A pharmacodynamic interaction between the 2 drugs is also a possible mechanism of this interaction.

Conclusions:

Our patient with epilepsy developed blood dyscrasia during lamotrigine/phenobarbital treatment. Clinicians should carefully monitor hematologic parameters during lamotrigine/phenobarbital treatment.
Sensitivity to initial values in full non‐parametric maximum‐likelihood estimation of the two‐parameter logistic model
Authors: Nader Ingo W. , Tran Ulrich S. , Formann Anton K.
Published: November 2010

Parameters of the two‐parameter logistic model are generally estimated via the expectation–maximization (EM) algorithm by the maximum‐likelihood (ML) method. In so doing, it is beneficial to estimate the common prior distribution of the latent ability from data. Full non‐parametric ML (FNPML) estimation allows estimation of the latent distribution with maximum flexibility, as the distribution is modelled non‐parametrically on a number of (freely moving) support points. It is generally assumed that EM estimation of the two‐parameter logistic model is not influenced by initial values, but studies on this topic are unavailable. Therefore, the present study investigates the sensitivity to initial values in FNPML estimation. In contrast to the common assumption, initial values are found to have notable influence: for a standard convergence criterion, item discrimination and difficulty parameter estimates as well as item characteristic curve (ICC) recovery were influenced by initial values. For more stringent criteria, item parameter estimates were mainly influenced by the initial latent distribution, whilst ICC recovery was unaffected. The reason for this might be a flat surface of the log‐likelihood function, which would necessitate setting a sufficiently tight convergence criterion for accurate recovery of item parameters.
Linking the demands–control–support model to innovation: The moderating role of personal initiative on the generation and implementation of ideas
Authors: Daniels Kevin , Wimalasiri Varuni , Cheyne Alistair , Story Vicky
Published: November 2010

The demands–control–support model indicates that workers can use job control and social support for problem solving. We examined whether personal initiative moderated relationships between, on the one hand, job control used for problem solving and social support used for problem solving and, on the other hand, ideas generation and implementation. We operationalized job control used for problem solving as ‘changing aspects of work activities to solve problems’. We operationalized social support used for problem solving as ‘discussing problems to solve problems’. Using an experience sampling methodology, participants provided data for up to four times a day for up to five working days (N= 89). The extent to which people ‘changed aspects of their work activities to solve problems’ was associated with higher levels of ideas generation for people with high personal initiative. The extent to which people ‘discussed problems to solve problems’ was associated with higher levels of ideas implementation for people with high personal initiative.
The impact of nonprogrammatic factors on criminal‐justice interventions
Authors: Andrews D. A.
Published: November 2010

Purpose. Palmer (1995) drew attention to a distinction between ‘programmatic’ and ‘non‐programmatic’ aspects of criminal justice interventions. While a considerable amount of research has accumulated on the former, the latter by comparison remains under‐researched. Nevertheless some advances have been made and the present article identifies the key components of this.

Methods. Following analysis of the concepts forwarded by Palmer, a methodical comparison is made between his findings on programmatic elements and those of two other major groups of meta‐analytic findings from this area. This provides further opportunity for testing of the Risk‐Needs‐Responsivity (RNR) model and an evaluation is offered of its current status in synthesizing relevant knowledge. A parallel set of comparisons is then drawn with respect to non‐programmatic factors and the paper considers the level of agreement between separate reviews of that knowledge base. This directs attention to a number of instances of intervention ‘failure’ which can be explained by insufficient attention to non‐programmatic issues.

Results. There is a generally high level of agreement between the three sets of data surveyed. There is not a complete consensus however, caused not by disagreement between data sets but by gaps in the types and range of evidence assembled. There are larger gaps remaining on non‐programmatic factors and the nature and extent of those is described. There is also discussion of some objections and proposed alternatives to RNR, and to some conceptual confusions arising from them.

Conclusions. The present state of knowledge on criminal justice interventions is a ‘work in progress’ but nevertheless can provide firm guidance on the design of such interventions, highlighting areas in which much further work is needed.
Childhood Abuse and Neglect and the Risk of STDs In Early Adulthood
Authors: Haydon Abigail A. , Hussey Jon M. , Halpern Carolyn Tucker
Published: November 2010

CONTEXT: Given the threat posed by STDs in young adulthood, identifying early predictors of STD risk is a priority. Exposure to childhood maltreatment has been linked to sexual risk behaviors, but its association with STDs is unclear.

METHODS: Associations between maltreatment by parents or other adult caregivers during childhood and adolescence and STD outcomes in young adulthood were examined using data on 8,922 respondents to Waves 1, 3 and 4 of the National Longitudinal Study of Adolescent Health. Four types of maltreatment (sexual abuse, physical abuse, supervision neglect and physical neglect) and two STD outcomes (self‐reported recent and test‐identified current STD) were assessed. Multivariate logistic regression analyses, stratified by sex, tested for moderators and mediators.

RESULTS: Among females, even after adjustment for socioeconomic and demographic characteristics, self‐report of a recent STD was positively associated with sexual abuse (odds ratio, 1.8), physical abuse (1.7), physical neglect (2.1) and supervision neglect (1.6). Additionally, a positive association between physical neglect and having a test‐identified STD remained significant after further adjustments for exposure to other types of maltreatment and sexual risk behaviors (1.8). Among males, the only association (observed only in an unadjusted model) was between physical neglect and test‐identified STD (1.6).

CONCLUSIONS: Young women who experienced physical neglect as children are at increased risk of test‐identified STDs in young adulthood, and exposure to any type of maltreatment is associated with an elevated likelihood of self‐reported STDs. Further research is needed to understand the behavioral mechanisms and sexual network characteristics that underlie these associations.