bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors and prognosis of young stroke. The FUTURE study: A prospective cohort study. Study rationale and protocol
Authors: Rutten-Jacobs Loes CA , Maaijwee Noortje AM , Arntz Renate M , Van Alebeek Mayte E , Schaapsmeerders Pauline , Schoonderwaldt Henny C , Dorresteijn Lucille DA , Overeem Sebastiaan , Drost Gea , Janssen Mirian C , van Heerde Waander L , Kessels Roy PC , Zwiers Marcel P , Norris David G , van der Vlugt Maureen J , van Dijk Ewoud J , de Leeuw Frank-Erik
Published: September 2011

Background

Young stroke can have devastating consequences with respect to quality of life, the ability to work, plan or run a family, and participate in social life. Better insight into risk factors and the long-term prognosis is extremely important, especially in young stroke patients with a life expectancy of decades. To date, detailed information on risk factors and the long-term prognosis in young stroke patients, and more specific risk of mortality or recurrent vascular events, remains scarce.

Methods/Design

The FUTURE study is a prospective cohort study on risk factors and prognosis of young ischemic and hemorrhagic stroke among 1006 patients, aged 18-50 years, included in our study database between 1-1-1980 and 1-11-2010. Follow-up visits at our research centre take place from the end of 2009 until the end of 2011. Control subjects will be recruited among the patients' spouses, relatives or social environment. Information on mortality and incident vascular events will be retrieved via structured questionnaires. In addition, participants are invited to the research centre to undergo an extensive sub study including MRI.

Discussion

The FUTURE study has the potential to make an important contribution to increase the knowledge on risk factors and long-term prognosis in young stroke patients. Our study differs from previous studies by having a maximal follow-up of more than 30 years, including not only TIA and ischemic stroke but also hemorrhagic stroke, the addition of healthy controls and prospectively collect data during an extensive follow-up visit. Completion of the FUTURE study may provide better information for treating physicians and patients with respect to the prognosis of young stroke.
BglBrick vectors and datasheets: A synthetic biology platform for gene expression
Authors: Lee Taek Soon , Krupa Rachel A , Zhang Fuzhong , Hajimorad Meghdad , Holtz William J , Prasad Nilu , Lee Sung Kuk , Keasling Jay D
Published: September 2011

Background

As engineered biological systems become more complex, it is increasingly common to express multiple operons from different plasmids and inducible expression systems within a single host cell. Optimizing such systems often requires screening combinations of origins of replication, expression systems, and antibiotic markers. This procedure is hampered by a lack of quantitative data on how these components behave when more than one origin of replication or expression system are used simultaneously. Additionally, this process can be time consuming as it often requires the creation of new vectors or cloning into existing but disparate vectors.

Results

Here, we report the development and characterization of a library of expression vectors compatible with the BglBrick standard (BBF RFC 21). We have designed and constructed 96 BglBrick-compatible plasmids with a combination of replication origins, antibiotic resistance genes, and inducible promoters. These plasmids were characterized over a range of inducer concentrations, in the presence of non-cognate inducer molecules, and with several growth media, and their characteristics were documented in a standard format datasheet. A three plasmid system was used to investigate the impact of multiple origins of replication on plasmid copy number.

Conclusions

The standardized collection of vectors presented here allows the user to rapidly construct and test the expression of genes with various combinations of promoter strength, inducible expression system, copy number, and antibiotic resistance. The quantitative datasheets created for these vectors will increase the predictability of gene expression, especially when multiple plasmids and inducers are utilized.
Transnational Questing Desire in Star Cinema's Kailangan kita and Milan
Authors: Benitez Francisco
Published: September 2011

Using the hit movies Kailangan kita (I Need You, 2002) and Milan (2004) as examples, this essay explores how Philippine commercial film mediates the affective and emotional labor required to maintain flows of out-migration, despite narrative trajectories that uphold a final return to the native land. Both films posit a transnational subject that bemoans the economic plight of the nation-state while demonstrating neoliberal entrepreneurship in self-regulation. The desiring subjects of the films embark upon transnational quests for self-actualization, which in turn foreground their insertion into an international labor market where they struggle to maintain a sense of national belonging. These subjects are figured as entrepreneur-consumers, whose mediation commodifies their own affect, bodies, and labor power and uphold global structures. Featuring primarily middle-class protagonists, Kailangan kita and Milan present narratives of transnational mobility as the path to self-improvement, but also disclose the contradictions in the nation-state's relationship to other countries and its own absent workers, on whose love, loyalty, and labor it depends.
Exchange Rate Regimes in the Modern Era: Fixed, Floating, and Flaky
Authors: Rose Andrew K
Published: September 2011

This paper provides a selective survey of the incidence, causes, and consequences of a country's choice of its exchange rate regime. I begin with a critical review of Michael Klein and Jay C. Shambaugh's (2010) book Exchange Rate Regimes in the Modern Era, and then proceed to provide an alternative overview of what the economics profession knows and needs to know about exchange rate regimes. While a fixed exchange rate with capital mobility is a well-defined monetary regime, floating is not; thus, it is unclear whether it is theoretically sensible to compare countries across exchange rate regimes. This comparison is quite difficult to make empirically. It is often hard to figure out what the exchange rate regime of a country is in practice, since there are multiple conflicting regime classifications. More importantly, similar countries choose radically different exchange rate regimes without substantive consequences for macroeconomic outcomes like output growth and inflation. That is, the profession knows surprisingly little about either the causes or consequences of national choices of exchange rate regimes. But since the consequences of these choices are small, understanding their causes is of only academic interest. (JEL E52, F33)
The Origins of Endogenous Growth
Authors: Romer Paul M
Published: September 2011

This paper describes two strands of work that converged under the heading of ‘endogenous growth.’ One strand, which is primarily empirical, asks whether there is a general tendency for poor countries to catch up with rich countries. The other strand, which is primarily theoretical, asks what modifications are necessary to construct a theory of aggregate growth that takes the economics of discovery, innovation, and technological change seriously. The paper argues that the second strand of work will ultimately have a more significant impact on our understanding of growth and our approach to aggregate theory.
Endogenous Growth Theory: Intellectual Appeal and Empirical Shortcomings
Authors: Pack Howard
Published: September 2011

This paper examines whether the recent theoretical insights stemming from endogenous growth theory have provided a better guide to explaining actual growth experience than the neoclassical model. The paper considers the available empirical evidence on a number of related subjects, including the slowing of growth in the OECD countries over the last two decades; the acceleration of growth in several Asian countries since the early 1960s; studies of the determinants of growth in a cross-country context; and sources of the differences in international productivity levels. It concludes that the empirical confirmation, so far, of endogenous growth theory is limited.
On the Workability of Market Socialism
Authors: Bardhan Pranab , Roemer John E
Published: September 2011

Contrary to the claim of Andrei Shleifer and Robert W. Vishny (1994), it is conceivable under market socialism to take firms out of the orbit of state control and that a less narrow theory of the state than theirs allows the possibility of democratic socialism mitigating problems of economic inefficiency better than capitalism.
Corporate Diversification
Authors: Montgomery Cynthia A
Published: September 2011

This paper documents the significant presence of diversified firms in the U.S. economy and presents three views on why firms diversify. The market power view argues that firms diversify to wield conglomerate power across markets. The agency view argues that diversification is undertaken by managers pursuing their own interests at the expense of the firm's owners. The resource view argues that firms diversify in response to excess capacity in productive factors. A review of recent empirical research finds little support for the market-power view and a substantial amount of evidence that is consistent with the agency and resource views.
Economic FAQs About the Internet
Authors: MacKie-Mason Jeffrey K , Varian Hal
Published: September 2011

This is a set for frequently asked questions (and answers) about the economic, institutional, and technological structure of the Internet. The authors describe the current state of the Internet, discuss some of the pressing economic and regulatory problems, and speculate about future developments.
Competition Policy, Rivalries, and Defense Industry Consolidation
Authors: Kovacic William E , Smallwood Dennis E
Published: September 2011

Declining outlays for new weapons programs have triggered a process of consolidation that promises to shrink the U.S. defense industry drastically. Consolidation in the defense industry raises complex competition policy issues that are not amenable to conventional antitrust merger analysis. This paper presents a framework for identifying important contractor competencies, assessing rivalries in defense industry segments, and evaluating the competitive effects of mergers and other consolidation events. As applied to antitrust oversight and to Department of Defense funding, program, and acquisition strategy decisions, this framework can help preserve supply alternatives for developing state-of-the-art weapons needed to satisfy national security requirements.
Evaluation of the Quantum Blue® rapid test for faecal calprotectin
Authors: Wassell Julie , Wallage Michael , Brewer Ella
Published: September 2011

Background

Calprotectin is an acute-phase protein used extensively in the assessment of gastrointestinal inflammation. It can readily be measured by enzyme-linked immunoassay (ELISA) and recently by point-of-care testing (POCT). We evaluated the Quantum Blue® POCT in this study and compared it with our existing ELISA method.

Methods

The method comparison study used faecal samples ( n = 47) sent to the laboratory for routine calprotectin analysis. Linearity was assessed by serial dilution of extracted faeces ( n = 4). Extraction efficiency was determined by repeat extraction of three different stools. The variation in results as a consequence of reading the POCT cartridges either side of the recommended 12 min was also assessed.

Results

The assay was linear across the range stated by the manufacturer. When multiple samples were taken from the same stool, results varied from −31.3% to +31.5%. For the clinical arm of our study, strictly applying the 50 μg/g cut-off recommended for both assays as positive for gastrointestinal inflammation, there were four patients where results fell a different side of the clinical cut-off; two patients had results higher by Quantum Blue® and two higher by ELISA.

Conclusions

In our hands, the Quantum Blue® method was a suitable screening test for excluding inflammatory bowel disease. It may be of value to laboratories wishing to offer calprotectin but who do not have sufficient numbers to warrant ELISA methodology or in ‘one stop’ gastrointestinal clinics where an immediate result is required.
Identifying Good Nursing Levels: A Queuing Approach
Authors: Yankovic Natalia , Green Linda V.
Published: September 2011

Nursing care is arguably the single biggest factor in both the cost of hospital care and patient satisfaction. Inadequate inpatient nursing levels have also been cited as a significant factor in medical errors and emergency room overcrowding. Yet, there is widespread dissatisfaction with the current methods of determining nurse staffing levels, including the most common one of using minimum nurse-to-patient ratios. In this paper, we represent the nursing system as a variable finite-source queuing model. We develop a reliable, tractable, easily parameterized two-dimensional model to approximate the actual interdependent dynamics of bed occupancy levels and demands for nursing. We use this model to show how unit size, nursing intensity, occupancy levels, and unit length-of-stay affect the impact of nursing levels on performance and thus how inflexible nurse-to-patient ratios can lead to either understaffing or overstaffing. The model is also useful for estimating the impact of nurse staffing levels on emergency department overcrowding.
Informatics and Translational Medical Research: Challenges and Developments
Authors: Prasser Fabian , Wurst Sebastian H. R. , Lamla Gregor , Kohlmayer Florian , Blaser Rainer , Schmelcher Dominik , Vögele Bernd , Kuhn Klaus A.
Published: September 2011

This article gives an overview of informatics challenges arising in the context of translational medical research. This research concept, which has developed during the last years, aims at transferring scientific knowledge from foundational (“bench”) to clinical research and further to clinical and medical practice (“bedside”). The reverse direction is also important: clinical data are needed for feedback and as stimuli for the generation of research hypotheses. To achieve this, collaboration is needed between separate domains with differing “cultures”, regulations and IT requirements. From the informatics perspective, novel and unique questions arise. While the scientific areas involved, biochemistry, molecular biology, medicine, statistics, epidemiology, and others, have been using informatics methods for many years, their concepts differ and communication is restricted. We will summarize the challenges in this rapidly evolving domain and present recent developments, focusing on integration architectures and concepts, on security and privacy, and on software engineering.
Review
Authors: Miestamo Matti
Published: September 2011

Norbert Cyffer, Erwin Ebermann & Georg Ziegelmeyer (eds.), Negation patterns in West African languages and beyond, (Typological Studies in Language 87), Amsterdam: John Benjamins, 2009. vi + 368 pp.
THERAPY OF ENDOCRINE DISEASE: Insulin initiation in patients with type 2 diabetes mellitus: treatment guidelines, clinical evidence and patterns of use of basal vs premixed insulin analogues
Authors: Vaag Allan , Lund Sørens
Published: September 2011

This review addresses the apparent disconnect between international guideline recommendations, real-life clinical practice and the results of clinical trials, with regard to the initiation of insulin using basal (long-acting) or premixed insulin analogues in patients with type 2 diabetes (T2D). English language guidelines vary considerably with respect to recommended glycaemic targets, the selection of human vs analogue insulin, and choice of insulin regimen. Randomised trials directly comparing insulin initiation between basal and premixed analogues are scarce, and hard endpoint outcome data are inadequate. The evidence presented suggests that a major component of the HbA1c not being attained in every day clinical practice may be a result of factors that are not adequately addressed in forced titration trials of highly motivated patients, including failure to comply with complex treatment and monitoring regimens. Enforced intensification of unrealistic complex treatment regimens and glycaemic targets may theoretically worsen the psychological well-being in some patients. More simple and sustainable treatment regimens and guidelines are urgently needed. As for the use of insulin in T2D, there is limited evidence to convincingly support that initiation of insulin using basal insulin analogues is superior to initiation using premixed insulin analogues. While awaiting improved clinical efficacy and cost-effectiveness data, practical guidance from national and international diabetes organisations should consider more carefully the importance of: i) being clear and consistent; and ii) the early implementation of sustainable and cost-effective insulin treatment regimens with an emphasis on optimising treatment ease of use and patient compliance.
Effects of Physical Activity on Teen Smoking Cessation
Authors: Horn Kimberly , Dino Geri , Branstetter Steven A. , Zhang Jianjun , Noerachmanto N , Jarrett Traci , Taylor Melissa
Published: September 2011

OBJECTIVE:

To understand the influence of physical activity on teen smoking-cessation outcomes.

METHODS:

Teens (N = 233; 14–19 years of age) from West Virginia high schools who smoked >1 cigarette in the previous 30 days were included. High schools with >300 students were selected randomly and assigned to brief intervention (BI), Not on Tobacco (N-O-T) (a proven teen cessation program), or N-O-T plus a physical activity module (N-O-T+FIT). Quit rates were determined 3 and 6 months after baseline by using self-classified and 7-day point prevalence quit rates, and carbon monoxide validation was obtained at the 3-month follow-up evaluation.

RESULTS:

Trends for observed and imputed self-classified and 7-day point prevalence rates indicated that teens in the N-O-T+FIT group had significantly higher cessation rates compared with those in the N-O-T and BI groups. Effect sizes were large. Overall, girls quit more successfully with N-O-T compared with BI (relative risk [RR]: >∞) 3 months after baseline, and boys responded better to N-O-T+FIT than to BI (RR: 2–3) or to N-O-T (RR: 1–2). Youths in the N-O-T+FIT group, compared with those in the N-O-T group, had greater likelihood of cessation (RR: 1.48) at 6 months. The control group included an unusually large proportion of participants in the precontemplation stage at enrollment, but there were no significant differences in outcomes between BI and N-O-T (z = 0.94; P = .17) or N-O-T+FIT (z = 1.12; P = .13) participants in the precontemplation stage.

CONCLUSIONS:

Adding physical activity to N-O-T may enhance cessation success, particularly among boys.
Pulse Oximetry in Pediatric Practice
Authors: Fouzas Sotirios , Priftis Kostas N. , Anthracopoulos Michael B.
Published: September 2011

The introduction of pulse oximetry in clinical practice has allowed for simple, noninvasive, and reasonably accurate estimation of arterial oxygen saturation. Pulse oximetry is routinely used in the emergency department, the pediatric ward, and in pediatric intensive and perioperative care. However, clinically relevant principles and inherent limitations of the method are not always well understood by health care professionals caring for children. The calculation of the percentage of arterial oxyhemoglobin is based on the distinct characteristics of light absorption in the red and infrared spectra by oxygenated versus deoxygenated hemoglobin and takes advantage of the variation in light absorption caused by the pulsatility of arterial blood. Computation of oxygen saturation is achieved with the use of calibration algorithms. Safe use of pulse oximetry requires knowledge of its limitations, which include motion artifacts, poor perfusion at the site of measurement, irregular rhythms, ambient light or electromagnetic interference, skin pigmentation, nail polish, calibration assumptions, probe positioning, time lag in detecting hypoxic events, venous pulsation, intravenous dyes, and presence of abnormal hemoglobin molecules. In this review we describe the physiologic principles and limitations of pulse oximetry, discuss normal values, and highlight its importance in common pediatric diseases, in which the principle mechanism of hypoxemia is ventilation/perfusion mismatch (eg, asthma exacerbation, acute bronchiolitis, pneumonia) versus hypoventilation (eg, laryngotracheitis, vocal cord dysfunction, foreign-body aspiration in the larynx or trachea). Additional technologic advancements in pulse oximetry and its incorporation into evidence-based clinical algorithms will improve the efficiency of the method in daily pediatric practice.
Irlen Colored Overlays Do not Alleviate Reading Difficulties
Authors: Ritchie Stuart J. , Sala Sergio Della , McIntosh Robert D.
Published: September 2011

OBJECTIVES:

To test the efficacy of Irlen colored overlays for alleviating reading difficulties ostensibly caused by Irlen syndrome, a proposed perceptual disorder with controversial diagnostic status.

PARTICIPANTS AND METHODS:

Sixty-one schoolchildren (aged 7–12 years) with reading difficulties were assessed by an Irlen diagnostician. We used a within-subject study design to examine differences in reading rate across 3 conditions: using an overlay of a prescribed color; using an overlay of a nonprescribed color; and using no overlay. In a subset of 44 children, all of whom had a diagnosis of Irlen syndrome, we also used a between-group design to test the effects of Irlen colored overlays on a global reading measure.

RESULTS:

The Irlen diagnostician diagnosed Irlen syndrome in 77% of our poor readers. We found no evidence for any immediate benefit of Irlen colored overlays as measured by the reading-rate test or the global reading measure.

CONCLUSIONS:

Our data suggest that Irlen colored overlays do not have any demonstrable immediate effect on reading in children with reading difficulties.
Laser direct writing of nanocompounds
Authors: Ostendorf Andreas , Chakif M’Barek , Guo Qingchuan
Published: September 2011

Laser direct polymerization has been proven as a powerful tool to generate microstructures. Often photosensitive polymer materials are used because they can be tuned by photoactive molecules to be susceptible to a specific wavelength of light to initiate the polymerization process. One of the main drawbacks of this technique is the lack of functional polymers, e.g. conductive, magnetic, mechanical, optical or bioactive materials. Nanocomposites (nanocompounds), i.e. polymers with inorganic nanomaterials incorporated in the matrix offer a huge variety of new functionalities. A new approach will be presented how functional nanocomposite polymers can be generated and used for laser direct writing techniques. This can open the door for completely new MEMS and MOEMS devices comprising active and passive subcomponents.
Sb2Te3 and Bi2Te3 Thin Films Grown by Molecular Beam Epitaxy at Room Temperature
Authors: Aabdin Z. , Winkler M. , Bessas D. , König J. , Peranio N. , Eibl O. , Hermann R. , Böttner H.
Published: September 2011

Nano-alloyed p-type Sb2Te3 and n-type Bi2Te3 thin films were grown on SiO2/Si and BaF2 substrates by molecular beam epitaxy (MBE) in two steps: (i) Repeated deposition of five-layer stacks with sequence Te-X-Te-X-Te (X = Sb or Bi) with elemental layer thicknesses of 0.2 nm on substrates at room temperature, (ii) annealing at 250 °C for two hours at which phase formation of Sb2Te3 or Bi2Te3 occurred. The room temperature MBE deposition method reduces surface roughness, allows the use of non lattice-matched substrates, and yields a more accurate and easier control of the Te content compared to Bi2Te3 thin films, which were epitaxially grown on BaF2 substrates at 290 °C. X-ray diffraction revealed that the thin films were single phase, poly-crystalline, and textured. The films showed grain sizes of 500 nm for Sb2Te3 and 250 nm for Bi2Te3, analyzed by transmission electron microscopy (TEM). The in-plane transport properties (thermopower S, electrical conductivity σ, charge carrier density n, charge carrier mobility μ, power factor S2σ) were measured at room temperature. The nano-alloyed Sb2Te3 thin film revealed a remarkably high power factor of 29 μW cm-1 K-2 similar to epitaxially grown Bi2Te3 thin films and Sb2Te3 single crystalline bulk materials. This large power factor can be attributed to a high charge carrier mobility of 402 cm2 V−1 s-1 similar to high-ZT Bi2Te3/Sb2Te3 superlattices. However, for the nano-alloyed Bi2Te3 thin film a low power factor of 8 μW cm−1 K-2 and a low charge carrier mobility of 80 cm2 V−1 s−1 were found. Detailed microstructure and phase analyses were carried out by energy-filtered TEM in cross-sections. Quantitative chemical analysis by energy-dispersive x−ray spectroscopy (EDS) was also applied. In Bi2Te3 thin films, few nanometer thick Bi-rich blocking layers at grain boundaries and Te fluctuations by 1.3 at.% within the grains were observed. The small charge carrier densities are explained by a reduced antisite defect density due to the low temperatures to which the thin films were exposed during annealing.
Evaluation of Segregation in Polycrystalline 10 mol% Yttria Doped Zirconia (10YSZ)
Authors: Idris Muhammad Asri , Nowotny Janusz , Li Sean S.
Published: September 2011

The present work reports surface segregation in polycrystalline yttria-stabilised zirconia (cubic) including 10 mol% Y2O3 (10YSZ). The 10YSZ specimen was annealed in the range 1073 K - 1673 K in the gas phase of controlled oxygen activity. The segregation-induced intensity profiles of 89Y, 40Ca, 28Si, 27Al, 133Cs, 197Au and 90Zr was measured using secondary ion mass spectrometry (SIMS). The data obtained show that (i) annealing of 10YSZ results in the formation of segregation-induced concentration gradients of 89Y, 40Ca, 28Si, 27Al and (ii) segregation-induced profiles depend on oxygen activity.
What Can Lasers Do in the Nano-Fabrication of Carbon Nanotube Based Devices?
Authors: Zhou Yun Shen , Xiong Wei , Mahjouri-Samani Masoud , Gao Yang , Mitchell Matt , Lu Yong Feng
Published: September 2011

Numerous applications based on CNTs have been conceived and developed at laboratory scale. However, only a handful of applications have been successfully implemented due to the difficulties in controlled growth, manipulation, and integration of CNTs. In spite of countless efforts having been devoted into this field, high-performance-on-demand solution packages are still absent. In this study, we investigated applications of lasers in the controlled growth and integration of CNTs, and developed laser-based strategies to achieve nano-fabrication of CNTbased devices. By making use of unique features of lasers, we achieved 1) parallel integration of CNTs into pre-designed micro/nano-architectures in a single-step laser-assisted chemical vapor deposition (LCVD) process, 2) selective removal of metallic CNTs in open air, 3) growing CNTs of controlled-alignments, and 4) diameter modulation in individual CNTs. The laser-based strategies developed in this study suggest a laser-based solution-package to meet the challenges for the nano-fabrication of CNT-based devices and promises a reliable and scalable approach to achieve CNT-integrated devices.
The Adaptor Protein Bam32 in Human Dendritic Cells Participates in the Regulation of MHC Class I-Induced CD8+ T Cell Activation
Authors: Ortner Daniela , Grabher Daniela , Hermann Martin , Kremmer Elisabeth , Hofer Susanne , Heufler Christine
Published: September 2011

The B lymphocyte adaptor molecule of 32 kDa (Bam32) is strongly induced during the maturation of dendritic cells (DC). Most known functions of Bam32 are related to the signaling of the B cell receptor for Ag. Because DC do not express receptors specific for Ags, we aim at characterizing the role of Bam32 in human monocyte-derived DC in this study. Our results show that binding of allogeneic T cells to mature DC causes accumulation of Bam32 on the contact sites and that this translocation is mimicked by Ab-mediated engagement of MHC class I. Silencing of Bam32 in mature monocyte-derived DC results in an enhanced proliferation of CD8+ T cells in an Ag-specific T cell proliferation assay. Further studies identify galectin-1 as an intracellular binding partner of Bam32. Regulating immune responses via regulatory T cell (Treg) modulation is one of the many immunological activities attributed to galectin-1. Therefore, we assayed mixed leukocyte reactions for Treg expansion and found fewer Treg in reactions stimulated with DC silenced for Bam32 compared to reactions stimulated with DC treated with a nontarget control. Based on our findings, we propose a role for Bam32 in the signaling of MHC class I molecules in professional Ag-presenting DC for the regulation of CD8+ T cell activation. It is distinct from that of MHC class I recognized by CD8+ T cells leading to T cell death. Thus, our data pinpoint a novel level of T cell regulation that may be of biological relevance.
The Liver Kinase B1 Is a Central Regulator of T Cell Development, Activation, and Metabolism
Authors: MacIver Nancie J. , Blagih Julianna , Saucillo Donte C. , Tonelli Luciana , Griss Takla , Rathmell Jeffrey C. , Jones Russell G.
Published: September 2011

T cell activation leads to engagement of cellular metabolic pathways necessary to support cell proliferation and function. However, our understanding of the signal transduction pathways that regulate metabolism and their impact on T cell function remains limited. The liver kinase B1 (LKB1) is a serine/threonine kinase that links cellular metabolism with cell growth and proliferation. In this study, we demonstrate that LKB1 is a critical regulator of T cell development, viability, activation, and metabolism. T cell-specific ablation of the gene that encodes LKB1 resulted in blocked thymocyte development and a reduction in peripheral T cells. LKB1-deficient T cells exhibited defects in cell proliferation and viability and altered glycolytic and lipid metabolism. Interestingly, loss of LKB1 promoted increased T cell activation and inflammatory cytokine production by both CD4+ and CD8+ T cells. Activation of the AMP-activated protein kinase (AMPK) was decreased in LKB1-deficient T cells. AMPK was found to mediate a subset of LKB1 functions in T lymphocytes, as mice lacking the α1 subunit of AMPK displayed similar defects in T cell activation, metabolism, and inflammatory cytokine production, but normal T cell development and peripheral T cell homeostasis. LKB1- and AMPKα1-deficient T cells each displayed elevated mammalian target of rapamycin complex 1 signaling and IFN-γ production that could be reversed by rapamycin treatment. Our data highlight a central role for LKB1 in T cell activation, viability, and metabolism and suggest that LKB1–AMPK signaling negatively regulates T cell effector function through regulation of mammalian target of rapamycin activity.
Long-Term Respiratory Muscle Endurance Training in Patients with Myasthenia Gravis: First Results after Four Months of Training
Authors: Rassler Beate , Marx Grit , Hallebach Stephanie , Kalischewski Petra , Baumann Irene
Published: September 2011

Myasthenia gravis (MG) is characterized by reduced muscle endurance and is often accompanied by respiratory complications. Improvement of respiratory function is therefore an important objective in MG therapy. A previous study demonstrated that respiratory muscle endurance training (RMET) over four weeks increased respiratory muscle endurance of MG patients to about 200% of baseline. The purpose of the present study was to establish an appropriate maintenance training and to test its effects over four months. Ten patients with mild to moderate MG participated in this study. During the first month, they performed five training sessions per week. For the following 3 months, training frequency was reduced to five sessions per two weeks. Myasthenia score, lung function, and respiratory endurance were determined prior to training, after the first month, and after 4 months. Myasthenia score improved from0.71±0.1to0.56±0.1(P=0.007). Respiratory endurance time increased from6.1±0.8to20.3±3.0min (P<0.001). In conclusion, this RMET maintenance program is feasible and is significantly beneficial for MG patients.
Headache Associated with Myasthenia Gravis: The Impact of Mild Ocular Symptoms
Authors: Nishimoto Yoshinori , Suzuki Shigeaki , Utsugisawa Kimiaki , Nagane Yuriko , Shibata Mamoru , Shimizu Toshihiko , Suzuki Norihiro
Published: September 2011

Myasthenia gravis (MG) patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG). We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6%) patients and 9 (4.9%) complained of migraine. Twenty-five (13.6%) complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients.
Effect of Backbone Chemical Structure of Polymers on Selective (n,m)Single‐Walled Carbon Nanotube Recognition/Extraction Behavior
Authors: Ozawa Hiroaki , Fujigaya Tsuyohiro , Niidome Yasuro , Nakashima Naotoshi
Published: September 2011

The development of a simple and facile method to extract single‐walled carbon nanotubes (SWNTs) with a specific chirality index is one of the most‐crucial issues in the fundamental study and applications of the SWNTs. We have compared the selective recognition/extraction of the SWNT chirality of poly(9,10‐dioctyl‐9,10‐dihydrophenanthrene‐2,7‐diyl) (2C8‐PPhO) to that of poly(9,9‐dioctyfluoreny1‐2,7‐diyl) (2C8‐PFO) that are able to extract specific semiconducting SWNTs free of any metallic SWNTs. Vis/NIR absorption, 2D photoluminescence, and Raman spectroscopy as well as molecular mechanical simulations were used to analyze and understand the obtained chiral selective solubilization behavior. We found that 2C8‐PPhO selectively extracts and enriches the (8,6), (8,7), and (9,7)SWNTs, whose behaviors are different from that of 2C8‐PFO, which preferentially extracts the (7,5), (7,6), (8,6), and (8,7)SWNTs. Our results indicate that 2C8‐PPhO preferably recognizes larger‐diameter SWNTs with higher chiral angles compared to those recognized by 2C8‐PFO. These findings demonstrate that the difference in the non‐aromatic ring numbers on the polymers results in different SWNT chirality recognition/extraction behaviors.
Elastin‐like recombinamers: Biosynthetic strategies and biotechnological applications
Authors: Girotti Alessandra , Fernández‐Colino Alicia , López Isabel M. , Rodríguez‐Cabello José C. , Arias Francisco J.
Published: September 2011

The past few decades have witnessed the development of novel naturally inspired biomimetic materials, such as polysaccharides and proteins. Likewise, the seemingly exponential evolution of genetic‐engineering techniques and modern biotechnology has led to the emergence of advanced protein‐based materials with multifunctional properties. This approach allows extraordinary control over the architecture of the polymer, and therefore, monodispersity, controlled physicochemical properties, and high sequence complexity that would otherwise be impossible to attain. Elastin‐like recombinamers (ELRs) are emerging as some of the most prolific of these protein‐based biopolymers. Indeed, their inherent properties, such as biocompatibility, smart nature, and mechanical qualities, make these recombinant polymers suitable for use in numerous biomedical and nanotechnology applications, such as tissue engineering, “smart” nanodevices, drug delivery, and protein purification. Herein, we present recent progress in the biotechnological applications of ELRs and the most important genetic engineering‐based strategies used in their biosynthesis.
Tuning mesomorphic properties and handedness of chiral calamitic liquid crystals by minimal modification of the effective core
Authors: Liu Anhua , Sun Qiming , Cui Jiaxi , Zheng Jia , Liu Wenjian , Wan Xinhua
Published: September 2011

Two pairs of calamitic liquid crystalline molecules, (+)‐2‐[4′‐(S)‐sec‐butoxyphenyl]‐5‐(4′‐hexoxyphenyl)toluene ((+)-S-1) and (+)‐2‐(4′‐hexoxyphenyl)‐5‐[4′‐(S)‐sec‐butoxyphenyl]toluene ((+)-S-2), (−)‐2‐[4′‐(R)‐sec‐butoxyphenyl]‐5‐(4′‐hexoxyphenyl)toluene ((-)-R-1) and (−)‐2‐(4′‐hexoxyphenyl)‐5‐[4′‐(R)‐sec‐butoxyphenyl]toluene ((-)-R-2), have been designed and synthesized. Each of the molecules consists of a p‐terphenyl core substituted with a methyl group on the middle ring, a chiral sec‐butoxy tail, and an achiral n‐hexoxy tail. The geometrical difference between (+)-S-1 ((-)-R-1) and (+)-S-2 ((-)-R-2) lies only in the location of the methyl group on the effective mesogenic core. Yet, such a small change in the structure gives rise to remarkable differences in mesogenic properties and handedness. Both (+)-S-1 and (-)-R-1 have an enantiotropic cholesteric phase (N*) and a monotropic twist grain boundary C* phase (TGBC*), whereas (+)-S-2 and (-)-R-2 exhibit only a monotropic N* phase. Moreover, (+)-S-1 ((-)-R-1) and (+)-S-2 ((-)-R-2) have opposite handedness in the N* phase, and (+)-S-1 and (-)-R-1 even have a helical inversion from N* to TGBC* phase through a non‐helical chiral mesophase. Chirality, 2011. © 2011 Wiley Periodicals, Inc.
Therapeutic opportunities in dengue infection
Authors: Fagundes Caio T. , Costa Vivian V. , Cisalpino Daniel , Souza Danielle G. , Teixeira Mauro M.
Published: September 2011

Infection by one of the four serotypes of the arthropod‐borne dengue virus produces a spectrum of disease manifestations, ranging from asymptomatic to life‐threatening Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). During the last several decades, dengue has spread its geographic distribution to become the most common arboviral infection of humans in the subtropical and tropical regions of the world. There is no specific treatment or vaccine approved for human use. This fact, associated with the large number of infected individuals and the lack of markers that indicate which patients will develop severe disease, place an enormous burden on health systems of affected countries. Many efforts have been made to elucidate several aspects of dengue disease, but the pathogenesis of disease is complex and remains unclear. The hallmark of severe dengue disease is a short‐lived plasma leakage that is believed to be immune mediated. Understanding the mechanism(s) that underlie the pathogenesis of dengue is critical for the development of safe therapeutics to prevent DHF/DSS. In this review, we highlight potential therapeutic alternatives to treat dengue infection and outline strategies used to develop and research anti‐dengue therapies, focusing on in vivo results obtained using the experimental animal models currently available. Within this context, we discuss the therapeutic potential of novel antiviral molecules, either targeting virus‐encoded functions or the cellular functions needed for viral replication. In addition, we discuss studies using anti‐inflammatory strategies aimed at reducing the exacerbated host response against infection and their potential as promising therapeutic alternatives in severe dengue disease. Drug Dev Res 72:480–500, 2011. © 2011 Wiley‐Liss, Inc.
Potentiometric Sensing of Lamotrigine Based on Molecularly Imprinted Polymers
Authors: Sadeghi Hayedeh Bagheri , Ebrahimi Soltan Ahmad , Tamaddon Atefeh , Bozorgvar Fatemeh , Afifinia Hadi , Almasian Nasim , Mollaei Somayeh
Published: September 2011

In the present work a novel potentiometric sensor, based on a noncovalent imprinted polymer, was developed for determination of Lamotrigine (LTG). At optimized conditions the electrode exhibited a Nernstian response (30.8±1.0 mV decade−1) in a concentration range of 1×10−6 to 1×10−3 M with a detection limit of 8×10−7 mol L−1. The potential response of the electrode was constant in the pH range of 1.0–5.0. The electrode demonstrated a response time of ∼30 s. The selectivity coefficient of the sensor toward a number of different drugs with molecular similarities and some metal ions was evaluated. The electrode was examined for determination of LTG in real samples.
Chromium(III) Potentiometric Sensor Based on Para‐Tertiary‐Butyl Calix[4]arene
Authors: Bagheri Sadeghi Hayedeh , Tamaddon Atefeh , Afifinia Hadi , Almasian Nasim , Bozorgvar Fatemeh , Mollaei Somayeh
Published: September 2011

A new chromium(III) PVC membrane sensor incorporating p‐tertiary‐butyl calix[4]arene as ionophore, potassium tetrakis as additive and dibutyl phthalate (DBP) as plasticizer was constructed. The electrode exhibited an excellent potentiometric response over a wide concentration range of 1.0×10−7–1.0×10−1 M with a Nernstian slope of 20±0.5 mV per decade. The detection limit was 5.0×10−8 M. The electrode showed a better performance over a pH range of 3.0–8.0, and had a short response time of about <15 s.The electrode was successfully applied to potentiometric titration of Cr (III) with EDTA and for direct determination of chromium(III) in waste water.
Controlling Field‐Effect Transistor Biosensor Electrical Characteristics Using Immunosorbent Assay
Authors: Vaknin Oshri , Khamaisi Bassam , Mizrahi Mordechay , Ashkenasy Nurit
Published: September 2011

A method to modulate the signal of field‐effect transistor biosensors using an immunosorbent assay is described. A model system is used to show that binding of a secondary antibody, to which highly charged gold colloids are attached, to an analyte on the device floating gate can be used to induce strong electrostatic effects, which affect the device threshold voltage and source‐drain current. This process may be used for signal amplification, with the secondary binding specificity allowing for improved signal to noise ratio, which is of great importance for early disease detection.
Can cytogenetics explain the possible association between exposure to extreme low‐frequency magnetic fields and Alzheimer's disease?
Authors: Maes Annemarie , Verschaeve Luc
Published: September 2011

Recently, a number of epidemiological studies have suggested that occupational as well as residential exposure to extreme low‐frequency electromagnetic fields (ELF‐EMFs) may be a risk factor for Alzheimer's disease. This is not proven yet and there are no known biological mechanisms to explain this alleged association. Alzheimer's disease is characterized by a number of events that have, at least partially, a genetic origin. In particular, trisomy of chromosomes 17 and 21 seems to be involved. Overall ELF‐EMFs have not been identified as genotoxic agents, but there are some papers in the scientific literature that indicate that they may enhance the effects of agents that are known to induce mutations or tumors. There are also some indications that ELF‐EMFs may induce aneuploïdy. This opens some perspectives for investigating the alleged association between ELF‐EMFs and Alzheimer's. This paper reviews the possibility of a cytogenetic association between the electromagnetic fields and Alzheimer's disease. Copyright © 2011 John Wiley & Sons, Ltd.
Facile micropatterning of dual hydrogel systems for 3D models of neurite outgrowth
Authors: Curley J. Lowry , Moore Michael J.
Published: September 2011

Understanding how microenvironmental factors influence neurite growth is important to inform studies in nerve regeneration, plasticity, development, and neurophysiology. In vitro models attempting to more accurately mimic the physiological environment by provision of a 3D growth matrix may provide useful foundations. Some limitations of thick 3D culture models include hampered solute transport, less‐robust neurite growth than on 2D substrates, and difficulty in achieving spatial control of growth. To this end, we describe a 3D dual hydrogel model for embryonic rat day 15 dorsal root ganglion tissue explant growth using a digital micromirror device for dynamic mask projection photolithography. The photolithography method developed allowed simple, reproducible, one‐step fabrication of thick hydrogel constructs on a variety of substrates, including permeable cell culture inserts. The relationships between projected mask size, crosslinked hydrogel resolution, and gel thickness were characterized, and resolution was found generally to decrease with increasing gel thickness. Cell viability in thick (481 μm) hydrogel constructs was significantly greater on permeable supports than glass, suggesting transport limitations were somewhat alleviated. The observed neurite growth was abundant and occurred in a spatially controlled manner throughout the 3D environment, a crucial step in the quest for a more effective biomimetic model of neurite outgrowth. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011.
Switchable Supramolecular Crosslinking of Cyclodextrin‐Modified Hyperbranched Polyethylenimine via Anthraquinone Dyes
Authors: Böhm Indra , Kreth S. Katharina , Ritter Helmut , Branscheid Robert , Kolb Ute
Published: September 2011

Two anthraquinone dyes, 5,8‐di‐N‐adamantylamino‐1,4‐dihydroxyanthraquinone (AQ‐OH) and 1,4‐di‐N‐adamantylaminoanthraquinone (AQ‐H), are synthesized. The combination of AQ‐OH and AQ‐H with hyperbranched polyethylenimine (PEI) bearing covalently attached β‐cyclodextrin spontaneously formed host–guest complexes with hydrodynamic diameters of about 260 nm. Even enlarged structures of the trifunctional AQ‐H were observed via DLS. Repeated measurements show that their assembly and disassembly is reversible with a critical point at 26 °C and therefore switchable via temperature. Also superstructures up to 100 μm were detected via TEM, cryo‐TEM‐, and SEM. Hence, a smart colored network of switchable size consisting of a supramolecular approach involving an organic dye is described.
Fractal dimension of an intrinsically disordered protein: Small‐angle X‐ray scattering and computational study of the bacteriophage λ N protein
Authors: Johansen Daniel , Trewhella Jill , Goldenberg David P.
Published: September 2011

Small‐angle X‐ray scattering (SAXS) was used to characterize the bacteriophage λ N protein, a 107 residue intrinsically disordered protein (IDP) that functions as a transcriptional antitermination factor. The SAXS data were used to estimate both the average radius of gyration and the fractal dimension, a measure of the protein's internal scaling properties, under a variety of solution conditions. In the absence of denaturants, the radius of gyration was 38 ± 3.5 Å and the fractal dimension was 1.76 ± 0.05, slightly larger than the value predicted for a well‐solvated polymer with excluded volume (1.7). Neither the radius of gyration nor the fractal dimension changed significantly on the addition of urea, further indicating that the protein is extensively unfolded and well solvated in the absence of denaturant. The addition of NaCl or D2O was found to promote aggregation, but did not appear to affect the properties of the monomeric form. The experimental SAXS profiles were also compared with those predicted by a computational model for a random‐coil polypeptide, with an adjustable solvation energy term. The experimental data were well fit to the model with the solvation energy close to zero. These results indicate that the λ N protein is among the more expanded members of the broad class of IDPs, most likely because of its high content of charged residues and a large net charge (+15 at neutral pH). The expanded nature of the conformational ensemble may play a role in facilitating the interactions of the protein with other components of the dynamic transcriptional complex.