bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of specific airway resistance to assess bronchodilator response in children
Authors: MAHUT BRUNO , PEIFFER CLAUDINE , BOKOV PLAMEN , DELCLAUX CHRISTOPHE , BEYDON NICOLE
Published: March 2011

Background and objective:  Changes in specific airway resistance (ΔsRaw) after bronchodilation, as measured by plethysmography and FEV1, are frequently considered to be interchangeable indices of airway obstruction. However, the baseline relationship between these two indices is weak, and the value of ΔsRaw that best predicts FEV1 reversibility in children has yet to be determined. The aim of this study was (i) to establish the sRaw cut‐off value that best distinguishes between positive and negative bronchodilator responses, as measured by FEV1 reversibility; (ii) to determine whether the discrepancy between ΔsRaw and ΔFEV1 might be explained by independent correlations between ΔFEV1 and both ΔsRaw (mainly airway obstruction) and ΔFVC (airway closure); and (iii) to assess the effect of height and age on the relationship between ΔsRaw and ΔFEV1.

Methods:  A retrospective study was performed in 481 children (median age 10.5 years, range 6.1–17.6) with actual or suspected asthma, for whom sRaw and spirometry data were obtained at baseline and after administration of a bronchodilator.

Results:  The sRaw cut‐off value that best predicted FEV1 reversibility was a 42% decrease from baseline (P = 0.0001, area under the curve 0.70, sensitivity 55%, specificity 77%) and was independent of height and age. Changes in FEV1 were significantly but independently related to ΔsRaw and ΔFVC (index of air trapping) (r = 0.40, P < 0.0001 and r = 0.39, P < 0.0001, respectively).

Conclusions:  A 42% decrease in sRaw predicted FEV1 reversibility reasonably well, whereas a smaller decrease in sRaw failed to detect approximately one out of two positive responses detected by FEV1, with no influence of height or age.
Nocturia as a manifestation of systemic disease
Authors: Gulur Dev Mohan , Mevcha Amit M. , Drake Marcus J.
Published: March 2011

What’s known on the subject? and What does the study add?

Waking at night to pass urine, nocturia, is widely regarded as urological, but many medical conditions can be responsible. Overproduction of urine overnight on the frequency volume chart, “nocturnal polyuria”, is a key feature signifying possible contribution of systemic disease; renal, endocrine, neurological, or cardiovascular malfunction may be responsible.

Failure to evaluate the potential medical basis risks poor treatment outcomes for a bothersome symptom. Inappropriately instigating surgical treatment, such as TURP, can lead to harm in a patient whose nocturia is caused by nocturnal polyuria. Global and nocturnal polyuria should be fully investigated, in case a potentially serious illness is responsible.

Nocturia is commonly referred to urologists, but the mechanisms underlying the problem, together with the appropriate clinical assessment and management, may lie outside the ordinary scope of the specialty. Some serious conditions may manifest nocturia as an early feature, often as a consequence of nocturnal polyuria (NP). Voiding frequency is influenced by rate of urine output, reservoir capacity of the bladder, lower urinary tract (LUT) sensation and psychological response. Polyuria can result from polydipsia or endocrine dysfunction. NP can result from endogenous fluid and solute shifts, cardiovascular and autonomic disease, obstructive sleep apnoea, and chronic kidney disease. Nocturia without polyuria occurs in the presence of LUT pathology, pelvic masses and sleep disturbance. Drug intake can contribute to, or counteract, each of these problems. In assessing nocturia, clinicians need to consider an undiagnosed serious condition that may manifest nocturia as an early feature, or suboptimal management of a known condition. The frequency‐volume chart is a key tool in categorizing the basis of nocturia, identifying those patients with global polyuria or NP, for whom involvement of other specialties is often necessary for assessment and management. Treatment should be directed at the cause of the problem, with a view to improving long‐term health and health‐related quality of life. Simple steps should be undertaken by all patients, including improvement of the sleep environment and behaviour modification. Evaluation of treatment response requires objective data to corroborate subjective impressions. Some mechanisms of nocturia do not reliably improve with treatment, leading to refractory symptoms.
INTERNATIONAL INTEGRATION AND REGIONAL INEQUALITIES: HOW IMPORTANT IS NATIONAL INFRASTRUCTURE?*
Authors: BEHRENS KRISTIAN
Published: March 2011

I investigate how international trade and national infrastructure interact to affect the regional distribution of economic activity within a country involved in a process of economic integration. Building on a new economic geography model I show that, in general, there is no simple relationship between regional inequality and changes in trade costs. Whereas trade liberalization in developing countries with poor infrastructure and mostly autarkic regions may well exacerbate spatial inequalities, countries with better infrastructure and larger volumes of interregional trade may experience a more balanced spatial development through the redispersion of economic activity.
Therapeutic hypothermia during neonatal transport
Authors: O’Reilly Kathleen M , Tooley James , Winterbottom Sharon
Published: March 2011

Aim:  To compare the effectiveness of different cooling methods used during neonatal transport in maintaining target temperature.

Methods:  Retrospective review of transport data for all infants centralized for therapeutic hypothermia between April 2008 and October 2009.

Results:  A total of 46 infants were retrieved for therapeutic hypothermia during the study period. During transport, 10 infants were passively cooled, 17 infants were actively cooled with adjuncts and 19 infants were actively cooled with a purpose‐built cooling machine. On arrival at the tertiary unit, 84% of infants who were actively cooled with a purpose‐built cooling machine had temperatures within the therapeutic range compared with 47% of infants who were actively cooled with adjuncts and 20% of infants who were passively cooled.

Conclusion:  Passive cooling and cooling with adjuncts often fail to achieve temperatures within the desired therapeutic range. Therapeutic hypothermia during transport can be reliably achieved using a purpose‐built cooling machine. We recommend that cooling during transport should only be undertaken using a purpose‐built cooling machine.
Relational regulation in the Brazilian Ministério Publico: The organizational basis of regulatory responsiveness
Authors: Coslovsky Salo V.
Published: March 2011

Recent research on regulatory enforcement has been showing that the best way to enforce protective regulations is to thoroughly adapt the remedy to the problem at hand. Unfortunately, this is far from easy, as organizations and work environments all too often encourage street‐level bureaucrats to standardize and simplify their practices. In an attempt to bridge this gap, many scholars equate responsiveness to preprogrammed escalation. This article analyzes how the Brazilian Ministério Público (MP) promotes a more ambitious form of responsiveness, here called relational regulation. While most of the formal features of the MP encourage routinization, groups of reformist prosecutors identify important cases, recruit external allies, and jointly devise innovative and context‐specific solutions to problems of non‐compliance. Crucially, this mode of action is not an anomaly, the result of individual proclivities or specific and formal job assignments. Rather, it is systematically produced by a mostly parallel and covert organization that operates within and expands beyond the MP itself. These two logics – routinized and custom‐made responses – compete, cooperate, interpenetrate, and find common ground within the same organizational umbrella, and through their interaction they create an enforcement agency that is more robust, reliable, and responsive than allowed by current theory.
Population growth and colonization of Steller sea lions in the Glacier Bay region of southeastern Alaska: 1970s–2009
Authors: Mathews Elizabeth A. , Womble Jamie N. , Pendleton Grey W. , Jemison Lauri A. , Maniscalco John M. , Streveler Greg
Published: March 2011

Abstract

We estimated trends in numbers of Steller sea lions in the Glacier Bay region of the eastern population from the 1970s to 2009. We documented the colonization of several new haul‐outs and the transition of one haul‐out (Graves Rocks) to a rookery, assessed seasonal patterns in distribution, and compared counts from different observation platforms. Sea lions increased in the region by 8.2%/yr (95%CI = 6.4%–10.0%), with the most growth at South Marble Island in Glacier Bay (16.6%/yr, 1991–2009) and rapid growth in Cross Sound. Seasonal patterns in the distribution of sea lions were likely influenced by new breeding opportunities and the seasonal availability of prey. Factors that likely contributed to the exceptional growth include availability of new habitat following deglaciation, immigration, redistribution, decreases in mortality, and ecosystem‐level changes. The rapid increase in sea lion numbers in this region is of particular interest in light of dramatic declines in the western population and evidence that Steller sea lions from both the eastern and western populations colonized the Graves Rocks rookery. The colonization and rookery development in this dynamic area may signal the reversal of the reproductive isolation of the two populations.
Group‐Based Shame and Guilt: Emerging Directions in Research
Authors: Lickel Brian , Steele Rachel R. , Schmader Toni
Published: March 2011

Research on the role of emotion in social identity, group processes, and intergroup conflict is burgeoning. This paper examines recent research on group‐based shame and guilt and describes important themes in this research. Guilt and shame are distinguished by different appraisals and motivations in intergroup contexts. Group‐based shame is associated with threats to group‐image and motivations to protect and repair that image. In contrast, group‐based guilt is associated with efforts to repair and apologize for ingroup wrongdoing. Current research is expanding in several important directions. First, the scope of emotions is expanding beyond that of shame and guilt to consider the roles of emotions such as ingroup‐directed anger in situations that may also provoke group‐based shame and guilt. Second, people’s motivations to avoid feeling group‐based shame and guilt are becoming better understood, particularly in relation to different aspects of social identification. Finally, we argue that dynamic processes in emotion expression and experience, particularly due to the relation between perpetrator and victim groups, are an important future direction in research on group‐based shame and guilt.
A measure for describing and comparing postreproductive life span as a population trait
Authors: Levitis Daniel A , Lackey Laurie Bingaman
Published: March 2011

1. While classical life‐history theory does not predict postreproductive life span (PRLS), it has been detected in a great number of taxa, leading to the view that it is a broadly conserved trait and attempts to reconcile theory with these observations. We suggest an alternative: the apparently wide distribution of significant PRLS is an artefact of insufficient methods.

2. PRLS is traditionally measured in units of time between each individual’s last parturition and death, after excluding those individuals for whom this interval is short. A mean of this measure is then calculated as a population value. We show this traditional population measure (which we denote PrT) to be inconsistently calculated, inherently biased, strongly correlated with overall longevity, uninformative on the importance of PRLS in a population’s life history, unable to use the most commonly available form of relevant data and without a realistic null hypothesis. Using data altered to ensure that the null hypothesis is true, we find a false‐positive rate of 0·47 for PrT.

3. We propose an alternative population measure, using life‐table methods. Postreproductive representation (PrR) is the proportion of adult years lived which are postreproductive. We briefly derive PrR and discuss its properties. We employ a demographic simulation, based on the null hypothesis of simultaneous and proportional decline in survivorship and fecundity, to produce a null distribution for PrR based on the age‐specific rates of a population.

4. In an example analysis, using data on 84 populations of human and nonhuman primates, we demonstrate the ability of PrR to represent the effects of artificial protection from mortality and of humanness on PRLS. PrR is found to be higher for all human populations under a wide range of conditions than for any nonhuman primate in our sample. A strong effect of artificial protection is found, but humans under the most adverse conditions still achieve PrR of >0·3.

5. PrT should not be used as a population measure and should be used as an individual measure only with great caution. The use of PrR as an intuitive, statistically valid and intercomparable population life‐history measure is encouraged.
Effects of channel dimensions on performance of a-InGaZnO4 thin-film transistors
Authors: Heo Young-Woo , Cho Kwang-Min , Sun Sang-Yun , Kim Se-Yun , Lee Joon-Hyung , Kim Jeong-Joo , Norton D. P. , Pearton S. J.
Published: March 2011

The authors report an investigation of the effects of channel dimensions on the properties of amorphous-InGaZnO4 (a-IGZO) thin-film transistors (TFTs) that are associated with surface depletion and surface/volume ratio. As the channel width decreased below a critical value of around 100 nm, the on current abruptly decreased and the threshold voltage abruptly increased. The magnitude of hysteresis behavior also depended on the channel size. Both of these effects result from the change of channel resistance that can be explained by surface changes due to adsorption of oxygen or water vapor. The authors also investigated short channel a-IGZO TFTs and observed short channel effects below a critical value of channel length of 900 nm. The breakdown electric field of a-IGZO was found to be in the range of 0.4–0.8 MV/cm.
Prevention and management of knee osteoarthritis and knee cartilage injury in sports
Authors: Takeda Hideki , Nakagawa Takumi , Nakamura Kozo , Engebretsen Lars
Published: February 2011

Articular cartilage defects in the knee of young or active individuals remain a problem in orthopaedic practice. These defects have limited ability to heal and may progress to osteoarthritis. The prevalence of knee osteoarthritis among athletes is higher than in the non-athletic population. The clinical symptoms of osteoarthritis are joint pain, limitation of range of motion and joint stiffness. The diagnosis of osteoarthritis is confirmed by the symptoms and the radiological findings (narrowing joint space, osteophyte formation and subchondral sclerosis). There is no strong correlation between symptoms and radiographic findings. The aetiology of knee osteoarthritis is multifactorial. Excessive musculoskeletal loading (at work or in sports), high body mass index, previous knee injury, female gender and muscle weakness are well-known risk factors. The high-level athlete with a major knee injury has a high incidence of knee osteoarthritis. Cartilage injuries are frequently observed in young and middle-aged active athletes. Often this injury precedes osteoarthritis. Reducing risk factors can decrease the prevalence of knee osteoarthritis. The prevention of knee injury, especially anterior cruciate ligament and meniscus injury in sports, is important to avoid progression of knee osteoarthritis.
Engineering Applications of Biomolecular Motors
Authors: Hess Henry
Published: March 2011

Biomolecular motors, in particular motor proteins from the kinesin and myosin families, can be used to explore engineering applications of molecular motors in general. Their outstanding performance enables the experimental study of hybrid systems, where bio-inspired functions such as sensing, actuation, and transport rely on the nanoscale generation of mechanical force. Scaling laws and theoretical studies demonstrate the optimality of biomolecular motor designs and inform the development of synthetic molecular motors.
Progress and Prospects for Stem Cell Engineering
Authors: Ashton Randolph S. , Keung Albert J. , Peltier Joseph , Schaffer David V.
Published: March 2011

Stem cells offer tremendous biomedical potential owing to their abilities to self-renew and differentiate into cell types of multiple adult tissues. Researchers and engineers have increasingly developed novel discovery technologies, theoretical approaches, and cell culture systems to investigate microenvironmental cues and cellular signaling events that control stem cell fate. Many of these technologies facilitate high-throughput investigation of microenvironmental signals and the intracellular signaling networks and machinery processing those signals into cell fate decisions. As our aggregate empirical knowledge of stem cell regulation grows, theoretical modeling with systems and computational biology methods has and will continue to be important for developing our ability to analyze and extract important conceptual features of stem cell regulation from complex data. Based on this body of knowledge, stem cell engineers will continue to develop technologies that predictably control stem cell fate with the ultimate goal of being able to accurately and economically scale up these systems for clinical-grade production of stem cell therapeutics.
Silencing or Stimulation? siRNA Delivery and the Immune System
Authors: Whitehead Kathryn A. , Dahlman James E. , Langer Robert S. , Anderson Daniel G.
Published: March 2011

Since its inception more than a decade ago, the field of short interfering RNA (siRNA) therapeutics has demonstrated potential in the treatment of a wide variety of diseases. The power behind RNA interference (RNAi) therapy lies in its ability to specifically silence target genes of interest. As more biological data have become available, it has become evident that, in addition to mediating RNAi, siRNA molecules have the potential to potently induce the innate immune system. One of the significant challenges facing the field today is the differentiation between therapeutic effects caused by target-specific, RNAi-mediated gene silencing and those caused by nonspecific stimulation of the innate immune system. Unless appropriate experimental measures are taken to control for RNA-induced immunostimulation, genetic manipulation can be confused with immune activation. This review attempts to provide an accessible background in siRNA-relevant immunology and to highlight the ways in which siRNA can be engineered to avoid or provoke an innate immune response.
Diffusion Imaging, White Matter, and Psychopathology
Authors: Thomason Moriah E. , Thompson Paul M.
Published: March 2011

The functional significance of the brain's white matter was not fully appreciated until new imaging methods were developed to visualize fiber pathways and connections in the living brain. Rapid advances in diffusion tensor imaging (DTI) have led to substantial insights into human brain development and disease processes and have thrust white matter into the focus of researchers and clinicians alike. The full clinical potential of this relatively new technique remains to be determined, but early indicators suggest that DTI will be a significant new technology in mapping mechanisms of human health and disease. Here we review brain changes that have been studied with DTI over the human lifespan and findings in a variety of neuropsychiatric disorders. We also suggest future areas where DTI is likely to have significant impact.
Disordered Gambling: Etiology, Trajectory, and Clinical Considerations
Authors: Shaffer Howard J. , Martin Ryan
Published: March 2011

Gambling-related research has advanced rapidly during the past 20 years. As a result of expanding interest in pathological gambling (PG), stakeholders (e.g., clinicians, regulators, and policy makers) have a better understanding of excessive gambling, including its etiology (e.g., neurobiological/neurogenetic, psychological, and sociological factors) and trajectory (e.g., initiation, course, and adaptation to gambling exposure). In this article, we examine these advances in PG-related research and then consider some of the clinical implications of these advances. We consider criteria changes for PG recently proposed by the DSM-V Impulse Control Work Group for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). We also review how clinicians can more accurately and efficiently diagnose clients seeking help for gambling-related problems by utilizing brief screens. Finally, we consider the importance of future research that can identify behavioral markers for PG. We suggest that identifying these markers will allow clinicians to make earlier diagnoses, recommend targeted treatments, and advance secondary prevention efforts.
Uranium Series Accessory Crystal Dating of Magmatic Processes
Authors: Schmitt Axel K.
Published: March 2011

Complex and protracted crystallization histories over geologic timescales are recorded in accessory minerals (e.g., zircon, allanite). Although magmatic crystallization was traditionally assumed to occur essentially instantaneously for the purposes of interpreting mineral geochronometers with low absolute time resolution for ancient samples, it emerged relatively recently that magmatic crystallization can occur over extended durations. This discovery arose from applying high-spatial-resolution accessory mineral dating techniques for uranium series isotopes to young volcanic and cognate plutonic rocks. The emerging pattern from these studies is that individual crystals and crystal populations record crystallization episodes lasting from <1,000 to many hundreds of thousands of years. Accessory mineral dating of volcanic rocks and cognate plutonic xenoliths opens new research avenues for crystal age fingerprinting that correlates pyroclastic deposits, lavas, and plutonic rocks by using characteristic age distributions. It also provides direct observations on magmatic accumulation and residence times, and the preeruptive configuration of subterraneous magma bodies and intrusive complexes with implications for the forecasting of volcanic eruptions. Awareness of potentially protracted crystallization in igneous rocks should guide the interpretation of accessory mineral ages.
Climate of the Neoproterozoic
Authors: Pierrehumbert R.T. , Abbot D.S. , Voigt A. , Koll D.
Published: March 2011

The Neoproterozoic is a time of transition between the ancient microbial world and the Phanerozoic, marked by a resumption of extreme carbon isotope fluctuations and glaciation after a billion-year absence. The carbon cycle disruptions are probably accompanied by changes in the stock of oxidants and connect to glaciations via changes in the atmospheric greenhouse gas content. Two of the glaciations reach low latitudes and may have been Snowball events with near-global ice cover. This review deals primarily with the Cryogenian portion of the Neoproterozoic, during which these glaciations occurred. The initiation and deglaciation of Snowball states are discussed in light of a suite of general circulation model simulations designed to facilitate intercomparison between different models. Snow cover and the nature of the frozen surface emerge as key factors governing initiation and deglaciation. The most comprehensive model discussed confirms the possibility of initiating a Snowball event with a plausible reduction of CO2. Deglaciation requires a combination of elevated CO2 and tropical dust accumulation, aided by some cloud warming. The cause of Neoproterozoic biogeochemical turbulence, and its precise connection with Snowball glaciations, remains obscure.
Scaling Up in Ecology: Mechanistic Approaches
Authors: Denny Mark , Benedetti-Cecchi Lisandro
Published: March 2011

Ecologists have long grappled with the problem of scaling up from tractable, small-scale observations and experiments to the prediction of large-scale patterns. Although there are multiple approaches to this formidable task, there is a common underpinning in the formulation, testing, and use of mechanistic response functions to describe how phenomena interact across scales. Here, we review the principles of response functions to illustrate how they provide a means to guide research, extrapolate beyond measured data, and simplify our conceptual grasp of reality. We illustrate these principles with examples of mechanistic approaches ranging from explorations of the ecological niche, random walks, and macrophysiology to theories dealing with scale transition, self-organization, and the prediction of extremes.
Sparse High-Dimensional Models in Economics
Authors: Fan Jianqing , Lv Jinchi , Qi Lei
Published: March 2011

This article reviews the literature on sparse high-dimensional models and discusses some applications in economics and finance. Recent developments in theory, methods, and implementations in penalized least-squares and penalized likelihood methods are highlighted. These variable selection methods are effective in sparse high-dimensional modeling. The limits of dimensionality that regularization methods can handle, the role of penalty functions, and their statistical properties are detailed. Some recent advances in sparse ultra-high-dimensional modeling are also briefly discussed.
Large-Eddy-Simulation Tools for Multiphase Flows
Authors: Fox Rodney O.
Published: March 2011

Multiphase flows occurring in nature and in technological applications are often turbulent. The large range of length scales and timescales in turbulent multiphase flows makes direct numerical simulation of the microscale governing equations intractable for many applications. In this article we review a systematic approach for developing large-eddy-simulation (LES) tools for dispersed multiphase flows starting from the microscale model. A key intermediate step is the mesoscopic model for the dispersed phase, formulated in terms of kinetic equations, that contains the physical models for the flow. Owing to the phase-space variables, direct solution of the mesoscopic model is usually intractable, and additional mathematical approximations are introduced to arrive at a macroscopic model. We show that self-conditioned LES models can be derived for both the mesoscopic and macroscopic models, but the former is preferred to ensure consistency and physical accuracy. The principal difficulties and open challenges in closing the LES model equations are highlighted.
Electrocaloric Materials
Authors: Scott J.F.
Published: March 2011

Electrocaloric materials are reviewed through a discussion of ferroelectric crystals used to achieve refrigeration via adiabatic depolarization. Related thermodynamics is briefly summarized, but emphasis is on experiments and materials.
The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism
Authors: Moore Kathryn J. , Rayner Katey J. , Suárez Yajaira , Fernández-Hernando Carlos
Published: March 2011

MicroRNAs (miRNAs) represent an elegant mechanism of posttranscriptional control of gene expression that serves to fine-tune biological processes. These tiny noncoding RNAs (20–22 nucleotide) bind to the 3′ untranslated region of mRNAs, thereby repressing gene expression. Recent advances in the understanding of lipid metabolism have revealed that miRNAs, particularly miR-122 and miR-33, play major roles in regulating cholesterol and fatty acid homeostasis. miR-122, the most abundant miRNA in the liver, appears to maintain the hepatic cell phenotype, and its inhibition decreases total serum cholesterol. miR-33, an intronic miRNA located with the sterol response element-binding protein (SREBP)-2 gene, regulates cholesterol efflux, fatty acid β oxidation, and high-density lipoprotein metabolism. These findings have highlighted the complexity of lipid homeostasis and the important role that miRNAs play in these processes, potentially opening new avenues for the treatment of dyslipidemias.
Genetic Variation and Clinical Heterogeneity in Cystic Fibrosis
Authors: Drumm Mitchell L. , Ziady Assem G. , Davis Pamela B.
Published: March 2011

Cystic fibrosis (CF), a lethal genetic disease, is characterized by substantial clinical heterogeneity. Work over the past decade has established that much of the variation is genetically conferred, and recent studies have begun to identify chromosomal locations that identify specific genes as contributing to this variation. Transcriptomic and proteomic data, sampling hundreds and thousands of genes and their products, point to pathways that are altered in the cells and tissues of CF patients. Genetic studies have examined more than half a million polymorphic sites and have identified regions, and probably genes, that contribute to the clinical heterogeneity. The combination of these approaches has great potential because genetic profiling identifies putative disease-modifying processes, and transcript and protein profiling is shedding light on the biology involved. Such studies are providing new insights into the disease, such as altered apoptotic responses, oxidative stress dysregulation, and neuronal involvement, all of which may open new therapeutic avenues to exploration.
Toll-Like Receptor–Gut Microbiota Interactions: Perturb at Your Own Risk!
Authors: Carvalho Frederic A. , Aitken Jesse D. , Vijay-Kumar Matam , Gewirtz Andrew T.
Published: March 2011

The well-being of the intestine and its host requires that this organ execute its complex function amid colonization by a large and diverse microbial community referred to as the gut microbiota. A myriad of interacting mechanisms of mucosal immunity permit the gut to corral the microbiota in such a way as to maximize the benefits and to minimize the danger of living in close proximity to this large microbial biomass. Toll-like receptors and Nod-like receptors, collectively referred to as pattern recognition receptors (PRRs), recognize a variety of microbial components and, hence, play a central role in governing the interface between host and microbiota. This review examines mechanisms by which PRR-microbiota interactions are regulated so as to allow activation of host defense when necessary while preventing excessive inflammation, which can have a myriad of negative consequences for the host. Analysis of published studies performed in human subjects and a variety of murine disease models reveals the central theme that PRRs play a key role in maintaining a healthful stable relationship between the intestine and its microbiota. In contrast, although select genetic ablations of PRR signaling may protect against some chronic diseases, the overriding theme of studies performed to date is that perturbations of PRR-microbiota interactions are more likely to promote disease states associated with inflammation.
Understanding the 2007–2008 Global Financial Crisis: Lessons for Scholars of International Political Economy
Authors: Helleiner Eric
Published: March 2011

Economists have explained the 2007–2008 global financial crisis with reference to various market and regulatory failures as well as a macro-economic environment of cheap credit during the precrisis period. These developments had important political causes that scholars of international political economy (IPE) should have been well positioned to study before the crisis. How well did they anticipate the crisis? Although none foresaw all the causes, a number of IPE scholars correctly identified many of the dangers associated with new models of securitization as well as accompanying regulatory failures and the politics underlying them. IPE scholars were less successful in identifying the macroeconomic roots of the crisis, particularly the role of international capital flows in fueling the U.S. financial bubble, but some scholars did usefully explore the politics that contributed to the latter phenomenon. The study of IPE scholarship in this episode contains useful lessons for the field's future.
Modeling Dynamics in Time-Series–Cross-Section Political Economy Data
Authors: Beck Nathaniel , Katz Jonathan N.
Published: March 2011

This article deals with a variety of dynamic issues in the analysis of time-series–cross-section (TSCS) data. Although the issues raised are general, we focus on applications to comparative political economy, which frequently uses TSCS data. We begin with a discussion of specification and lay out the theoretical differences implied by the various types of dynamic models that can be estimated. It is shown that there is nothing pernicious in using a lagged dependent variable and that all dynamic models either implicitly or explicitly have such a variable; the differences between the models relate to assumptions about the speeds of adjustment of measured and unmeasured variables. When adjustment is quick, it is hard to differentiate between the various models; with slower speeds of adjustment, the various models make sufficiently different predictions that they can be tested against each other. As the speed of adjustment gets slower and slower, specification (and estimation) gets more and more tricky. We then turn to a discussion of estimation. It is noted that models with both a lagged dependent variable and serially correlated errors can easily be estimated; it is only ordinary least squares that is inconsistent in this situation. There is a brief discussion of lagged dependent variables combined with fixed effects and issues related to non-stationarity. We then show how our favored method of modeling dynamics combines nicely with methods for dealing with other TSCS issues, such as parameter heterogeneity and spatial dependence. We conclude with two examples.
Understanding and Treating Insomnia
Authors: Bootzin Richard R. , Epstein Dana R.
Published: March 2011

Sleep disturbance is intricately entwined with our sense of well-being, health, emotion regulation, performance and productivity, memory and cognitive functioning, and social interaction. A longitudinal perspective underscores the conclusion that persistent sleep disturbance, insomnia, at any time during the life span from infancy to old age has a lasting impact. We examine how insomnia develops, the evidence for competing explanations for understanding insomnia, and the evidence about psychological and behavioral treatments that are used to reduce insomnia and change daytime consequences. There are new directions to expand access to treatment for those who have insomnia, and thus a critical analysis of pathways for dissemination is becoming increasingly important.
Evidence for context sensitivity of grasp representations in human parietal and premotor cortices
Authors: Marangon Mattia , Jacobs Stéphane , Frey Scott H.
Published: March 2011

Grasp-related responses in neurons of the macaque rostral inferior parietal lobule [PF/PFG and the anterior intraparietal area (AIP)] are modulated by task context. Event-related functional MRI was used to determine whether this is true in putative homologs of the human cortex, the rostral inferior parietal lobule (rIPL) and the anterior intraparietal sulcus (aIPS). Fifteen healthy, right-handed adults were required to select prospectively the most comfortable way to grasp a horizontally oriented handle using the cued hand (left or right). In the “no-rotation” condition, the task was simply to grasp the handle, whereas in the “rotation” condition, the goal was to plan to grasp and rotate it into a vertical orientation with the cued end (medial or lateral) pointing downward. In both conditions, participants remained still and indicated their grip preferences by pressing foot pedals. As in overt grasping, participants' grip preferences were significantly influenced by anticipation of the demands associated with handle rotation. Activity within the aIPS and rIPL increased bilaterally in both the rotation and no-rotation conditions. Importantly, these responses were significantly greater in the rotation vs. no-rotation condition. Similar context effects were detected in the presupplementary motor area, caudal intraparietal sulcus/superior parietal lobule, and bilateral dorsal and left ventral premotor cortices. Grasp representations within the rIPL and aIPS are sensitive to predicted task demands and play a role in context-sensitive grip selection. Moreover, the findings provide additional evidence that areas involved in the sensorimotor control of grasp also contribute to feedforward planning.
Synthesis of β-Amino Carbonyl Compounds via the Iodine-Alumina Catalyzed Three-Component Coupling Reaction under Microwave Irradiation
Authors: Rajbangshi Mantu , Rohman Md. Rumum , Kharkongor Icydora , Mecadon Hormi , Myrboh Bekington
Published: March 2011

Iodine-alumina was employed as a catalyst in the coupling reactions of aldehydes, enolizable ketones, or 1,3-dicarbonyls with methyl carbamate or aromatic amines under microwave irradiation to afford β-amino carbonyl compounds in good-to-excellent yields. The key features of this environmentally friendly methodology are its operational simplicity, mild reaction conditions, and less reaction time.
Fyn Is Downstream of the HGF/MET Signaling Axis and Affects Cellular Shape and Tropism in PC3 Cells
Authors: Jensen Ana R. , David Saito Y. , Liao Chuanhong , Dai Jinlu , Keller Evan T. , Al-Ahmadie Hikmat , Dakin-Haché Kelly , Usatyuk Peter , Sievert Margarit F. , Paner Gladell P. , Yala Soheil , Cervantes Gustavo M. , Natarajan Viswanathan , Salgia Ravi , Posadas Edwin M.
Published: March 2011

Purpose: Fyn is a member of the Src family of kinases that we have previously shown to be overexpressed in prostate cancer. This study defines the biological impact of Fyn inhibition in cancer using a PC3 prostate cancer model.

Experimental Design: Fyn expression was suppressed in PC3 cells using an shRNA against Fyn (PC3/FYN-). Knockdown cells were characterized using standard growth curves and time-lapse video microscopy of wound assays and Dunn Chamber assays. Tissue microarray analysis was used to verify the physiologic relevance of the HGF/MET axis in human samples. Flank injections of nude mice were performed to assess in vivo growth characteristics.

Results: HGF was found to be sufficient to drive Fyn-mediated events. Compared to control transductants (PC3/Ctrl), PC3/FYN- showed a 21% decrease in growth at 4 days (P = 0.05). PC3/FYN- cells were 34% longer than control cells (P = 0.018) with 50% increase in overall surface area (P < 0.001). Furthermore, when placed in a gradient of HGF, PC3/FYN- cells showed impaired directed chemotaxis down an HGF gradient in comparison to PC3/Ctrl (P = 0.001) despite a 41% increase in cellular movement speed. In vivo studies showed 66% difference of PC3/FYN- cell growth at 8 weeks using bidimensional measurements (P = 0.002).

Conclusions: Fyn plays an important role in prostate cancer biology by facilitating cellular growth and by regulating directed chemotaxis—a key component of metastasis. This finding bears particular translational importance when studying the effect of Fyn inhibition in human subjects. Clin Cancer Res; 17(10); 3112–22. ©2011 AACR.
Nonproteasomal Targets of the Proteasome Inhibitors Bortezomib and Carfilzomib: a Link to Clinical Adverse Events
Authors: Arastu-Kapur Shirin , Anderl Janet L. , Kraus Marianne , Parlati Francesco , Shenk Kevin D. , Lee Susan J. , Muchamuel Tony , Bennett Mark K. , Driessen Christoph , Ball Andrew J. , Kirk Christopher J.
Published: March 2011

Purpose: Bortezomib (Velcade), a dipeptide boronate 20S proteasome inhibitor and an approved treatment option for multiple myeloma, is associated with a treatment-emergent, painful peripheral neuropathy (PN) in more than 30% of patients. Carfilzomib, a tetrapeptide epoxyketone proteasome inhibitor, currently in clinical investigation in myeloma, is associated with low rates of PN. We sought to determine whether PN represents a target-mediated adverse drug reaction (ADR).

Experimental Design: Neurodegenerative effects of proteasome inhibitors were assessed in an in vitro model utilizing a differentiated neuronal cell line. Secondary targets of both inhibitors were identified by a multifaceted approach involving candidate screening, profiling with an activity-based probe, and database mining. Secondary target activity was measured in rats and patients receiving both inhibitors.

Results: Despite equivalent levels of proteasome inhibition, only bortezomib reduced neurite length, suggesting a nonproteasomal mechanism. In cell lysates, bortezomib, but not carfilzomib, significantly inhibited the serine proteases cathepsin G (CatG), cathepsin A, chymase, dipeptidyl peptidase II, and HtrA2/Omi at potencies near or equivalent to that for the proteasome. Inhibition of CatG was detected in splenocytes of rats receiving bortezomib and in peripheral blood mononuclear cells derived from bortezomib-treated patients. Levels of HtrA2/Omi, which is known to be involved in neuronal survival, were upregulated in neuronal cells exposed to both proteasome inhibitors but was inhibited only by bortezomib exposure.

Conclusion: These data show that bortezomib-induced neurodegeneration in vitro occurs via a proteasome-independent mechanism and that bortezomib inhibits several nonproteasomal targets in vitro and in vivo, which may play a role in its clinical ADR profile. Clin Cancer Res; 17(9); 2734–43. ©2011 AACR.
A Narrow Beam Spectral Radiometer to Measure Atmospheric Emission from 4 to 14.5 vm
Authors: Wardrop A. J. , Mantis H. T.
Published: March 2011

A spectral radiometer to measure atmospheric radiance has been constructed using a helium-cooledphotoconductor detector. The radiometer is of medium resolution (δλ/λ ∼ 2%) and its advantages areits narrow beam ∼10-6 sr) and accuracy in the absolute radiance measurement (1% of a blackbody atambient temperature). Some examples of spectra made with the instrument are presented.
A Four-Filter Photometer for the Measurement of Total Ozone in the Atmosphere
Authors: Leroy B.
Published: March 2011

A description is given of a photometer designed for the measurement of total ozone in the atmosphere fromthe solar light scattered by the zenith sky. The instrument uses four interference filters and a photocell. It wascompared to other photometers, specially the Dobson spectrophotometer, in a 1974 field test at Belsk,Poland. The results of the intercomparison are detailed.In agreement with the opinion of several authors, it is concluded that total ozone measurements should beassociated with other atmospheric measurements so that information can be obtained on the influence ofaerosols on the diffusion and absorption of light. Such data, even if they are unable to eliminate errors, atleast are able to identify those conditions required for getting correct measurements.
Three-Dimensional Distribution of Air Pollutants in the Los Angeles Basin
Authors: Husar Rudolf B. , Patterson David E. , Blumenthal Donald L. , White Warren H. , Smith Theodore B.
Published: March 2011

Data from a three-dimensional pollutant mapping program, conducted in the Los Angeles basin, wereanalyzed to obtain "grand average" vertical profiles sampled on 24 summer days in 1973. Morning andafternoon profiles at four locations show an erosion of the nighttime radiation inversion, increased temperatures, more intense mixing in the inland areas, and a semi-permanent subsidence inversion at higher levels.High values of primary pollutant parameters (NO, and condensation nuclei) are seen in the western part ofthe basin at Hawthorne. Secondary pollutant parameters (Os and light scattering coefficient) were dominating at the inland receptor site, Riverside. Ozone concentrations in the morning were consistently higheraloft. The deficit near the surface is attributed to ozone scavenging by primary emissions.
Averaging for Wind Speed in a Given Direction in the Concentration Equation for Pollutants
Authors: Neumann J.
Published: March 2011

In the equation for the concentration of pollutants from a steady continuous point source, in a stationaryturbulent flow, the factor 1/u enters (u is the mean wind for a given stationary situation). If we are interestedin the concentration along a given wind direction and u denotes the wind speed in that direction and if weseek the average concentration for a class of flow situations (e.g., for the class of statically stable flows),each member of the class representing an individual stationary situation, then the averaging to be appliedis to 1/u and not to u. On the assumption (verified by some examples) that the distribution of u isa "humped" gamma distribution (standard deviation σ less than the average u of u for the class as a whole),we show that the average of 1/u equals 1/(u[1-(σ/u)2]}. Thus the average of 1/u is greater than 1/uand the resulting concentration estimate is larger than the one that would be obtained by the incorrect useof 1/u.
Comparison of Predicted and Observed Solar Radiation in an Urban Area
Authors: Bergstrom Robert W. , Peterson James T.
Published: March 2011

Measurements of the downward solar radiant flux in the St. Louis, Mo., area are compared with predictionsfrom an approximate solution to the radiative transfer equation. The atmospheric aerosols were assumedto have a power size distribution, dn/dr∼r-4, and the refractive indices suggested by Fischer (1973) foran urban area. On a relatively clean day, the predictions compared well with observations. On a hazy day,the comparison was poor with the a priori choice of aerosol properties. The particles on the hazy day apparently had more submicron particles than those found in the assumed size distribution, and the particleswere considerably less absorbing than those observed by Fischer. These changes could represent the effectsof relative humidity and different air mass characteristics.
A Preliminary Analysis of Ocean-Air Interactions Along the West Coast of North America, 1965-1969
Authors: Hannes Gerald
Published: March 2011

This paper uses a multivariate statistical technique to examine the possible relationships between theatmosphere and the ocean. Fifteen upper air stations and seventeen water temperature sampling sites werefactor analyzed. Several of the west coast water stations had high factor loadings on the same factor withseveral of the upper air sites.
A Comparison of Two CCN Counters
Authors: Hudson James G. , Hoppel W. A. , Wojciechowski T. A.
Published: March 2011

A number of careful laboratory comparisons were made between two very different CCN counters. The two instruments gave consistent results which were within about 20% on the average.
JPLEX: Java Simplex Implementation With Branch-and-Bound Search for Automated Test Assembly
Authors: Park Ryoungsun , Kim Jiseon , Dodd Barbara G. , Chung Hyewon
Published: March 2011

JPLEX, short for Java simPLEX, is an automated test assembly (ATA) program. It is a mixed integer linear programming (MILP) solver written in Java. It reads in a configuration file, solves the minimization problem, and produces an output file for postprocessing. It implements the simplex algorithm to create a fully relaxed solution and branch-and-bound (BB) method to find an integer solution (Bazaraa, Jarvis, & Sherali, 1990). The input configuration file format for linear programming (LP) modeling (van der Linden, 2005) is tailored for ATA and easy to build without the help of other modeling languages. It was originally designed for midsized test assembly applications, but there is no restriction on the number of decision variables. This solver might be useful for research students who need to assemble a test from an item pool and for those who want to learn or teach LP concepts.