bluuebunny/crossref_metadata_2025 huggingface dataset:
Rules and Heuristics during Sentence Comprehension: Evidence from a Dual-task Brain Potential Study
Authors: Martín-Loeches Manuel , Schacht Annekathrin , Casado Pilar , Hohlfeld Annette , Abdel Rahman Rasha , Sommer Werner
Published: August 2008

Whether syntactic and semantic processes during sentence comprehension follow strict sets of rules or succumb to context-dependent heuristics was studied by recording event-related potentials in a dual-task design. In one condition, sentence-extraneous acoustic material was either semantically congruent or incongruent relative to an adjective in the visually presented sentence, the latter being either semantically correct or incorrect within the sentence context. Homologous syntactic (gender) manipulations were performed in another condition. Syntactic processing within the sentence appeared to be blind to the syntactic content of the second task. In contrast, semantically incongruous material of the second task induced fluctuations typically associated with the detection of within-sentence semantic anomalies (N400) even in semantically correct sentences. Subtle but extant differences in topography between this N400 and that obtained with within-sentence semantic violations add to recent proposals of separate semantic subsystems differing in their specificity for sentence structure and computational procedures. Semantically incongruous material of the second task also influenced later stages of the processing of semantically incorrect adjectives (P600 component), which are traditionally assumed to pertain to the syntactic domain. This result is discussed in the light of current proposals of a third combinatorial stream in sentence comprehension.
Russian National Legal Tradition: Svod versus Ulozhenie in Nineteenth-century Russia
Authors: Borisova Tatiana
Published: August 2008

The article describes and analyses the competing approaches to codification in Russia during the first decades of the nineteenth century following Napoleon (and his Code Civil) and its evaluation in the late nineteenth century. Based on recent methodology—the history of notions (Begriffsgeschichte)—this article presents the history of codification through the perspective of the emergence and development of the Russian legal terms 'svod' (compilation/digest) and 'ulozhenie' (system/code). These terms represented the 'battle flags' of the two parties: on one hand, those whom one might characterize as rationalist, universalist, Enlightenment-oriented, based on the French Revolution and inspired by the Code Napoleon; and, on the other, those who might better be described as history-oriented, traditionalist, romantic, nationalist. Speranskii, initially the prime representative of the first tendency, was ultimately successful as the leader of a Russian codification movement by claiming an original national approach to codification, while in practice combining the two elements. The article seeks to demonstrate that the categories of 'national', 'traditional', 'original'—as well as their opposites, 'universalistic', 'rationalist'—which were used in the political and academic discourse on codification in nineteenth-century Russia, may be analyzed as a rhetorical means of argument skillfully applied by the ambitious drafters of new codes (as well as by their opponents). Contextual analysis of both the Russian and European political background of codification discussions are applied in this work, which leads to conclusions on the construction (and deconstruction) of a national mythology of legal traditions. My view of the creation of a new code of laws (ulozhenie)—during the first three decades of the nineteenth century—is one of the completion of a Russian national project. It became such rather suddenly in the spring of 1812 as a result of both major forces and of chance circumstances, the movement of armies, global ideas and the passions of historical figures. The combination of a number of factors resulted in a situation whereby the political struggle over the new code was conducted through the language of nationalism by contrasting the 'national spirit of the law' with 'foreign principles'. In the struggle for a new code, the opposing sides not only used 'national rhetoric' introduced from outside but, also, changed the Russian language, inventing new 'national' meanings for legal concepts.
Precipitation Regimes during Cold-Season Central U.S. Inverted Trough Cases. Part II: A Comparative Case Study
Authors: Schumacher Philip N. , Frosig Gregory , Selzler Jason L. , Weisman Robert A.
Published: August 2008

This is the second of two papers that examine the organization of the precipitation field during central U.S. cold-season cyclones involving inverted troughs (ITs). The first paper (Part I) used a climatology and composites to find synoptic-scale differences between storms with precipitation located ahead of the IT (ahead cases) and those with precipitation located behind the IT (behind cases). This paper expands the conclusions in Part I through the use of a comparative case study between two cyclones. The first cyclone, on 29 October 1996, was an ahead case that produced heavy rainfall and was associated with a potential vorticity (PV) anomaly moving across the central plains. The IT formed in the lee of the Rockies prior to 0600 UTC 29 October and moved east into the northern plains over the next 18 h. The trough itself was coincident with the limiting streamline, which separated moist air rising over the warm front from dry air subsiding behind the cyclone. The second cyclone, on 17–18 January 1996, had precipitation on both sides of the IT and was associated with heavy snow and blizzard conditions in the northern plains and significant ice accumulation in the western Great Lakes. The IT was associated with large frontogenesis over the snow area. The ascent was further enhanced by a jet streak moving across southern Canada. Dynamically, the IT resembled a warm front, with veering winds with height and a strong frontal inversion.

The mechanism that appeared to control the different precipitation organization between the two systems was the orientation of the PV anomalies and the airstreams associated with their secondary circulations. This resulted in a differing orientation of the baroclinicity north and east of the cyclone. In the ahead case, the rising branches of the secondary circulations forced by the northern and southern anomalies remained separate. This allowed the baroclinicity to develop along the traditional warm front, while the IT never developed a thermal gradient as it moved east. In the both sides case, the southern stream anomaly helped to fix the northern anomaly-forced jet streak in place, so that a strong temperature gradient developed along the IT with strong frontogenesis and warm-air advection observed behind the IT. As the frontal circulation developed, the direct circulation associated with the right entrance region of a jet streak enhanced the ascent to the west of the IT.

A conceptual model is proposed based upon the case studies and the results of Part I. This model can be used by forecasters to differentiate between the precipitation regimes in cyclones associated with ITs.
A Snow-Ratio Equation and Its Application to Numerical Snowfall Prediction
Authors: Byun Kun-Young , Yang Jun , Lee Tae-Young
Published: August 2008

This study 1) presents a logistic regression equation of the snow ratio (SR) for use in a conversion of numerically predicted precipitation amounts into snowfall depths and 2) examines the quality of snowfall-depth forecasts using the proposed SR equation.

A logistic regression equation of SR has been derived with surface air temperature as the predictor, using observed 3-h snow ratio and surface air temperature. It is obtained for each of several ranges of the precipitation rate to reduce the large variability of SR. The proposed scheme is found to reproduce the observed SRs better than other schemes, according to verification against an independent observation dataset.

Predictions of precipitation and snowfall using the Weather Research and Forecasting (WRF) model and the proposed SR equation have shown some skill for a low threshold [1 mm (6 h)−1 and 1 cm (6 h)−1 for precipitation and snowfall depth, respectively]: the 10-case mean threat scores (TSs) are 0.47 and 0.43 for precipitation and snowfall forecasts, respectively. For higher thresholds [5 mm (6 h)−1 and 5 cm (6 h)−1 for precipitation and snowfall depth, respectively], however, TSs for snowfall forecasts tend to be significantly lower than those for the precipitation forecasts. Examination indicates that the poor predictions of relatively heavy snowfall are associated with incorrect prediction(s) of precipitation amount and/or surface air temperature, and the errors of the estimated SRs. The proposed SR equation can be especially useful for snowfall prediction for an area where the spatial variation of precipitation type (e.g., wet or dry snow) is significant.
Sensitivity of WRF Forecasts for South Florida to Initial Conditions
Authors: Etherton Brian , Santos Pablo
Published: August 2008

This study presents results from an experiment conducted to measure the impact of locally initializing a numerical weather prediction model on that model’s ability to predict precipitation and other surface parameters. The study consisted of quantifying the impact of initializing the Weather and Research Forecast (WRF) model with the Advanced Weather Interactive Processing System (AWIPS) Local Analysis and Prediction System (LAPS) diagnostic analyses. In the experiment, WRF was run for two different initial times: 0600 and 1800 UTC. For each initial time, the model was run twice, once using LAPS for the initial conditions, and once using the North American Mesoscale model (NAM; also known as the Eta Model at the time of the experiment). The impact of the local LAPS initialization on the model forecast of surface parameters is presented. Additionally, the model’s quantitative precipitation forecast (QPF) skill is compared for three different model configurations: 1) WRF initialized with LAPS, 2) WRF initialized with NAM, and 3) the standard NAM/Eta Model. The experiment ran from 1 June 2005 to 31 July 2005.

Results show that WRF forecasts initialized by LAPS have a more accurate representation of convection in the short range. LAPS-initialized forecasts also offer more accurate forecasts of 2-m temperature and dewpoint, 10-m wind, and sea level pressure, particularly in the short range. Most significantly, precipitation forecasts from WRF runs initialized by LAPS are more accurate than WRF runs initialized by NAM. WRF initialized with LAPS also demonstrates higher QPF skill than does the NAM/Eta Model, particularly in the short range when the precipitation thresholds are higher (0.25 in. in 3 h versus 0.10 in. in 3 h), and when forecasts are initialized at 0600 UTC rather than initialized at 1800 UTC.
Modeling the Distribution of Precipitation Forecasts from the Canadian Ensemble Prediction System Using Kernel Density Estimation
Authors: Peel Syd , Wilson Laurence J.
Published: August 2008

Kernel density estimation is employed to fit smooth probabilistic models to precipitation forecasts of the Canadian ensemble prediction system. An intuitive nonparametric technique, kernel density estimation has become a powerful tool widely used in the approximation of probability density functions. The density estimators were constructed using the gamma kernels prescribed by S.-X. Chen, confined as they are to the nonnegative real axis, which constitutes the support of the random variable representing precipitation accumulation.

Performance of kernel density estimators for several different smoothing bandwidths is compared with the discrete probabilistic model obtained as the fraction of member forecasts predicting the events, which for this study consisted of threshold exceedances. A propitious choice of the smoothing bandwidth yields smooth forecasts comparable, or sometimes superior, to the discrete probabilistic forecast, depending on the character of the raw ensemble forecasts. At the same time more realistic models of the probability density are achieved, particularly in the tail of the distribution, yielding forecasts that can be optimally calibrated for extreme events.
The Application of an Evolutionary Algorithm to the Optimization of a Mesoscale Meteorological Model
Authors: O’Steen Lance , Werth David
Published: August 2008

It is shown that a simple evolutionary algorithm can optimize a set of mesoscale atmospheric model parameters with respect to agreement between the mesoscale simulation and a limited set of synthetic observations. This is illustrated using the Regional Atmospheric Modeling System (RAMS). A set of 23 RAMS parameters is optimized by minimizing a cost function based on the root-mean-square (rms) error between the RAMS simulation and synthetic data (observations derived from a separate RAMS simulation). It is found that the optimization can be done with relatively modest computer resources; therefore, operational implementation is possible. The overall number of simulations needed to obtain a specific reduction of the cost function is found to depend strongly on the procedure used to perturb the “child” parameters relative to their “parents” within the evolutionary algorithm. In addition, the choice of meteorological variables that are included in the rms error and their relative weighting are also found to be important factors in the optimization.
“Warm Rain” in the Tropics: Seasonal and Regional Distributions Based on 9 yr of TRMM Data
Authors: Liu Chuntao , Zipser Edward J.
Published: August 2008

How much precipitation is contributed by warm rain systems over the tropics? What is the typical size, intensity, and echo top of warm rain events observed by the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar over different regions of the tropics? What proportion of warm raining areas is actually attached to the edges of cold systems? Are there mesoscale warm raining systems, and if so, where and when do they occur? To answer these questions, a 9-yr TRMM precipitation feature database is used in this study. First, warm rain features in 20°S–20°N are selected by specifying precipitation features 1) with minimum infrared brightness temperature > 0°C, 2) with TRMM Precipitation Radar (PR) echo top below freezing level, or 3) without any ice-scattering signature in the microwave observations, respectively. Then, the geographical, seasonal, and diurnal variations of the rain volume inside warm rain features defined in these three ways are presented. The characteristics of warm rain features are summarized.

Raining pixels with cloud-top temperature above 0°C contribute 20% of the rainfall over tropical oceans and 7.5% over tropical land. However, about half of the warm pixels over oceans and two-thirds of the warm pixels over land are attached to cold precipitation systems. A large amount of warm rainfall occurs over oceans near windward coasts during winter. Most of the warm rain systems have small size < 100 km2 and weak radar echo with a modal maximum near-surface reflectivity around 23 dBZ. However, mesoscale warm rain systems with strong radar echoes do occur in large regions of the tropical oceans, more during the nighttime than during daytime. Though the mean height of the warm precipitation features over oceans is lower than that over land, there is no significant regional difference in its size and intensity.
Forward-Looking Assimilation of MODIS-Derived Snow-Covered Area into a Land Surface Model
Authors: Zaitchik Benjamin F. , Rodell Matthew
Published: August 2008

Snow cover over land has a significant impact on the surface radiation budget, turbulent energy fluxes to the atmosphere, and local hydrological fluxes. For this reason, inaccuracies in the representation of snow-covered area (SCA) within a land surface model (LSM) can lead to substantial errors in both offline and coupled simulations. Data assimilation algorithms have the potential to address this problem. However, the assimilation of SCA observations is complicated by an information deficit in the observation—SCA indicates only the presence or absence of snow, not snow water equivalent—and by the fact that assimilated SCA observations can introduce inconsistencies with atmospheric forcing data, leading to nonphysical artifacts in the local water balance. In this paper, a novel assimilation algorithm is presented that introduces Moderate Resolution Imaging Spectroradiometer (MODIS) SCA observations to the Noah LSM in global, uncoupled simulations. The algorithm uses observations from up to 72 h ahead of the model simulation to correct against emerging errors in the simulation of snow cover while preserving the local hydrologic balance. This is accomplished by using future snow observations to adjust air temperature and, when necessary, precipitation within the LSM. In global, offline integrations, this new assimilation algorithm provided improved simulation of SCA and snow water equivalent relative to open loop integrations and integrations that used an earlier SCA assimilation algorithm. These improvements, in turn, influenced the simulation of surface water and energy fluxes during the snow season and, in some regions, on into the following spring.
Theory and Characterization of Weather Radar Networks
Authors: Junyent Francesc , Chandrasekar V.
Published: August 2008

A dense weather radar network is an emerging concept advanced by the Engineering Research Center for Collaborative Adaptive Sensing of the Atmosphere (CASA). In a weather radar environment, the specific radar units employed and the network topology will influence the characteristics of the data obtained. To define this, a general framework is developed to describe the radar network space, and formulations are obtained that can be used for weather radar network characterization.

The models developed are useful for quantifying and comparing the performance of different weather radar networks. Starting with system characteristics that are used to specify individual radars, a theoretical basis is developed to extend the concept to network configurations of interest. A general network elemental cell is defined and employed as the parameterized domain over which different coverage aspects (such as detection sensitivity, beam size, and minimum beam height) are studied using analytical tools developed in the paper. Other important parameters are the number of different radars with overlapping coverage at a given point in the network domain and the coverage area and number of radars of a network and its elemental cells. A combination of analytical and numerically derived expressions is employed to obtain these parameters for several configurations.

The radar network characterization tools developed are applied to the comparison of individual radar and networked radar configurations of interest. The values used in the calculations illustrate the CASA Integrated Project 1 (IP1) radar network and are compared to other radar systems.
Detecting Source Regions of Wave Activities in the Tropical Atmosphere by Applying Beamforming to Interpolated Data Grids
Authors: Hu Qi , Liang Zhaoning , Hoffman Michael W.
Published: August 2008

Wave activities are primary sources of weather disturbances and cyclones in the tropical atmosphere. One such activity is the intraseasonal variations in wind, convection, and precipitation in the tropical Indian and western tropical Pacific region. These variations affect the intensity, break and reset, and rainfall in the Indian and the East Asian monsoons. Detecting the source regions of these wave activities is essential for understanding and for prediction of wave development. In this study, a fixed beamforming method is proposed to deduce source regions of some wave activities in the tropical atmosphere. This method is tested with simulations of single and distributed complex sources of waves and, then, fixed beamformers are applied to the ECMWF interpolated data grids to detect and identify source regions of the intraseasonal oscillations–waves in the tropical Indian and tropical Pacific Ocean region. Results show that the fixed beamforming technique can uniquely identify the source regions of the intraseasonal oscillations. Applications of this method have revealed various source regions of all major intraseasonal oscillation (ISO) events in the tropical Indian and western equatorial Pacific region during the 29 yr from 1974 to 2002. Knowing these source regions will make it possible to extract the relevant information and, thus, to better understand the development of the intraseasonal oscillations as well as their effects on the tropical weather and climate.
Program Evaluation as Professional Development
Authors: Manning Carmen , Sisserson Kendra , Jolliffe David , Buenrostro Patty , Jackson Wendy
Published: August 2008

This study focuses on an evaluation project that served as a powerful professional development experience for teachers and leaders in a network of Chicago small schools. The network of small schools led by the Chicago High School Redesign Initiative is based on the Authentic Intellectual Achievement (AIA) framework originally conceived by Fred Newmann. As teachers developed rubrics to measure AIA and scored teachers' assignments and student work collected from their own schools to establish baseline data on the schools' achievement on the AIA scales, they gained deeper understanding of the AIA framework, which served as the theory of instruction for the network of small schools. Participants' reactions to the impact of their involvement on their teaching practices are explored.
Putting the Pieces Together
Authors: Orr Margaret Terry , Berg Barbara , Shore Rima , Meier Ellen
Published: August 2008

This article presents a collaborative inquiry analysis of the school improvement experiences of four persistently low-performing schools. It draws on the experiences of three members of the Laboratory for the Design and Redesign of Schools (LDRS) consortium who helped during their planning for restructuring or restructuring phases and one regional official who oversaw their grant support and school improvement interventions. The authors explore the role of organizational change to improved teaching and learning in the schools. The schools' mixed leadership and organizational capacity and belief in their teaching efficacy limited the benefits of state, district, and regional supports and resources, which school leaders were ill-equipped to coordinate. Combining leadership and organizational development with curricular and instructional reform models would be more promising.
Visceral Nerves: Vagal and Sympathetic Innervation
Authors: Teff Karen L.
Published: August 2008

The autonomic nervous system is the primary neural mediator of physiological responses to internal and external stimuli. It is composed of 2 branches: the sympathetic nervous system, which mediates catabolic responses, and the parasympathetic nervous system, composed of the vagus nerve, which regulates anabolic responses. As the vagus nerve innervates most tissues involved in nutrient metabolism, including the stomach, pancreas, and liver, activation of vagal efferent activity has the potential to influence how nutrients are absorbed and metabolized. Vagal efferent activity is initially activated at the onset of food intake by receptors in the oropharyngeal cavity and then during food intake postprandially. Vagal efferent innervation of the pancreas contributes to early‐phase insulin release as well as to optimizing postprandial insulin release. In the absence of vagal activation, which occurs when glucose is administered intragastrically, postprandial glucose levels are higher and insulin levels blunted compared with when there is activation of oropharyngeal receptors by food. An induction of vagal efferent activity also occurs during chronic pancreatic B‐cell challenge with 48‐hour glucose infusions. Under these conditions, the compensatory increase in insulin secretion is partially mediated by an increase in vagal efferent activity. In conclusion, the vagus nerve, part of the parasympathetic nervous system, plays a critical role in the regulation of blood glucose levels and is an often overlooked factor contributing to glucose homeostasis.
Drug‐Induced Hyperphagia: What Can We Learn From Psychiatric Medications?
Authors: Jensen Gordon L.
Published: August 2008

This brief review examines hyperphagia and associated weight gain as undesirable side effects of psychiatric medications; exploring the scope of the problem, proposed mechanisms, and potential interventions. Mechanisms of action appear to include drug‐mediated effects on hypothalamic appetite pathways that have been implicated in other etiologies of obesity. There is great individual variation in response to these medications as well as variation in the degree of weight gain within drug classes. Gene polymorphisms may be a key factor in determining individual variations in response. Better understanding of the underlying mechanisms can guide useful interventions. Medication selection and dosing appear to be important strategies to minimize adverse weight gain.
Treating each and every depressed patient
Authors: Kennedy SH
Published: August 2008

Abstract

Major depressive disorder (MDD) is a prevalent condition with substantial heterogeneity in terms of clinical symptom profiles, overlapping syndromes and degree of severity. The challenge for any new antidepressant is to demonstrate efficacy across the spectrum of patient subpopulations with a diagnosis of MDD. The anxious depressed patient historically has a lower rate of response to traditional antidepressants and high pretreatment anxiety symptoms have also been shown to increase the risk of recurrence. In addition, severity based on standard antidepressant rating scale scores influences treatment outcomes. Some antidepressants display greater placebo separation at higher levels of severity while others fail to separate from placebo in more severe populations. Gender differences in antidepressant response have also been reported in several studies. In particular, women appear to experience a greater side-effect burden with current antidepressants. This is also important in treating late-life depression, where elderly patients are more prone to experiencing side effects and drug interactions. Despite the improved tolerability with SSRIs and other novel antidepressants, restoration of healthy sleep patterns has frequently been lacking. Finally, antidepressant efficacy must include demonstrated relapse prevention during placebo-controlled drug discontinuation trials. As a novel antidepressant with melatonin receptor agonist and 5HT2C antagonist properties, agomelatine has demonstrated efficacy in randomized placebo-controlled trials. Additional analyses support the benefits of agomelatine in anxious depression, increasing efficacy with greater baseline severity, including severe late-life depression. Agomelatine has also demonstrated favourable tolerability and efficacy in separate analyses of women and men and displays successful relapse prevention at doses 25 and 50 mg. Both subjective and polysomnographic measures of sleep support increased sleep efficiency and decreased awakenings during agomelatine treatment. Combining these efficacy data with favourable effects on sexual function, CNS and GI systems, there are grounds to endorse the view that agomelatine is a well-tolerated and efficacious antidepressant for a diverse range of depressed populations.
Public Perception of Sex Offender Social Policies and the Impact on Sex Offenders
Authors: Schiavone Stacey Katz , Jeglic Elizabeth L.
Published: August 2008

This study examines the public perception of sex offender policies and the perceived impact of sex offender policies on the sex offenders themselves. Specifically, this study explores how the community feels about the effectiveness of policies such as registration and community notification (Megan’s Law), and housing restrictions in reducing sexual recidivism. Data are collected from 115 participants from a nationwide online community message board. Results suggest that although most individuals support Megan’s Law, they do not feel the policy reduces recidivism. Furthermore, the majority of the participants also do not believe that housing restriction statutes are effective in reducing sexual recidivism. When questioned about the policy impact on sex offenders, the majority of respondents agree that as a consequence of Megan’s Law, sex offenders are afraid for their safety; however, they do not believe that residence restrictions hinder sex offenders’ employment opportunities. Findings from this study are discussed as they pertain to public policy and sex offender reintegration.
Short Term Equity Returns of Chinese IPOs, 1999 to 2004
Authors: Li Larry , Fowler John , Naughton Tony
Published: August 2008

Our study of 531 Initial Public Offerings (IPOs) on the two Chinese Stock Exchanges during the period 1999 to 2004 indicates initial returns to investors of approximately 114.04 per cent and these earnings were sustained through the first month of trading. High initial returns on IPOs are most often characterised as a reflection of state policy acting with a view to longer-term economic gains and sound social policy.

The sample IPOs were found to be oversubscribed by 243 times the share offered. Such a level of excess demand is a major factor in high initial returns to Chinese IPOs. Regression analysis indicated other major factors associated with these high initial returns including company size, offer size, general market conditions in the period of lead up to the first listing, the proportion of tradable-A shares available and the signal PE ratio at the time of offer. In addition, the paper emphasises the potential for very significant wealth effects, capital formation and development of a private capital market which arises from private sector gains linked to the IPOs.
Nonresponse in the Dutch Time Use Survey: Strategies for Response Enhancement and Bias Reduction
Authors: Ingen Erik Van , Stoop Ineke , Breedveld Koen
Published: August 2008

This article describes attempts to enhance response rates in the Dutch Time Use Survey (DTUS). The authors examine what kind of nonresponse bias exists in the DTUS—with special concern for “busyness”—and they analyze whether enhanced response rates result in lower nonresponse bias. Results partly confirm the outcomes of earlier studies. First, time pressure does not seem to stop people from cooperating in the DTUS. Second, people who are participating actively in other domains (work, sports, volunteer work) and people who are more involved (political interest, reading newspapers) tend to cooperate more often in the survey than others. Surprisingly, the authors conclude that an increase in response rate does not necessarily lead to less selectiveness, which is a counterintuitive and worrisome finding. Additional field efforts resulted in more of the same kinds of people cooperating.
B lymphocytes: how they develop and function
Authors: LeBien Tucker W. , Tedder Thomas F.
Published: August 2008

The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries.
Gsk3β/PKA and Gli1 regulate the maintenance of neural progenitors at the midbrain-hindbrain boundary in concert with E(Spl) factor activity
Authors: Ninkovic Jovica , Stigloher Christian , Lillesaar Christina , Bally-Cuif Laure
Published: August 2008

Neuronal production in the midbrain-hindbrain domain (MH) of the vertebrate embryonic neural tube depends on a progenitor pool called the `intervening zone' (IZ), located at the midbrain-hindbrain boundary. The progressive recruitment of IZ progenitors along the mediolateral (future dorsoventral)axis prefigures the earlier maturation of the MH basal plate. It also correlates with a lower sensitivity of medial versus lateral IZ progenitors to the neurogenesis inhibition process that maintains the IZ pool. This role is performed in zebrafish by the E(Spl) factors Her5 and Her11, but the molecular cascades cooperating with Her5/11, and those accounting for their reduced effect in the medial IZ, remain unknown. We demonstrate here that the kinases Gsk3β and cAMP-dependent protein kinase A (PKA) are novel determinants of IZ formation and cooperate with E(Spl) activity in a dose-dependent manner. Similar to E(Spl), we show that the activity of Gsk3β/PKA is sensed differently by medial versus lateral IZ progenitors. Furthermore, we identify the transcription factor Gli1, expressed in medial IZ cells, as an antagonist of E(Spl) and Gsk3β/PKA, and demonstrate that the neurogenesis-promoting activity of Gli1 accounts for the reduced sensitivity of medial IZ progenitors to neurogenesis inhibitors and their increased propensity to differentiate. We also show that the expression and activity of Gli1 in this process are,surprisingly, independent of Hedgehog signaling. Together, our results suggest a model in which the modulation of E(Spl) and Gsk3β/PKA activities by Gli1 underlies the dynamic properties of IZ maintenance and recruitment.
Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst
Authors: Plusa Berenika , Piliszek Anna , Frankenberg Stephen , Artus Jérôme , Hadjantonakis Anna-Katerina
Published: August 2008

The first two lineages to differentiate from a pluripotent cell population during mammalian development are the extraembryonic trophectoderm (TE) and the primitive endoderm (PrE). Whereas the mechanisms of TE specification have been extensively studied, segregation of PrE and the pluripotent epiblast (EPI) has received comparatively little attention. A current model of PrE specification suggests PrE precursors exhibit an apparently random distribution within the inner cell mass of the early blastocyst and then segregate to their final position lining the cavity by the late blastocyst. We have identified platelet-derived growth factor receptor alpha (Pdgfrα) as an early-expressed protein that is also a marker of the later PrE lineage. By combining live imaging of embryos expressing a histone H2B-GFP fusion protein reporter under the control of Pdgfra regulatory elements with the analysis of lineage-specific markers, we investigated the events leading to PrE and EPI lineage segregation in the mouse, and correlated our findings using an embryo staging system based on total cell number. Before blastocyst formation, lineage-specific factors are expressed in an overlapping manner. Subsequently, a gradual progression towards a mutually exclusive expression of PrE- and EPI-specific markers occurs. Finally, cell sorting is achieved by a variety of cell behaviours and by selective apoptosis.
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
Authors: Kawaguchi Ayano , Ikawa Tomoko , Kasukawa Takeya , Ueda Hiroki R. , Kurimoto Kazuki , Saitou Mitinori , Matsuzaki Fumio
Published: August 2008

Cellular diversity of the brain is largely attributed to the spatial and temporal heterogeneity of progenitor cells. In mammalian cerebral development,it has been difficult to determine how heterogeneous the neural progenitor cells are, owing to dynamic changes in their nuclear position and gene expression. To address this issue, we systematically analyzed the cDNA profiles of a large number of single progenitor cells at the mid-embryonic stage in mouse. By cluster analysis and in situ hybridization, we have identified a set of genes that distinguishes between the apical and basal progenitors. Despite their relatively homogeneous global gene expression profiles, the apical progenitors exhibit highly variable expression patterns of Notch signaling components, raising the possibility that this causes the heterogeneous division patterns of these cells. Furthermore, we successfully captured the nascent state of basal progenitor cells. These cells are generated shortly after birth from the division of the apical progenitors, and show strong expression of the major Notch ligand delta-like 1, which soon fades away as the cells migrate in the ventricular zone. We also demonstrated that attenuation of Notch signals immediately induces differentiation of apical progenitors into nascent basal progenitors. Thus, a Notch-dependent feedback loop is likely to be in operation to maintain both progenitor populations.
Selective Partial Hydrogenation of Dinitrobenzenes to Nitroanilines Catalyzed by Ru/C
Authors: Hou Jie , Ma Yonghuan , Li Yuhan , Guo Fang , Lu Lianhai
Published: August 2008

Ru/C was found to be a highly effective catalyst for the selective partial hydrogenation of a range of dinitrobenzenes to their corresponding nitroanilines with excellent selectivity under mild conditions. Furthermore, the effect from other substitute groups of dinitrobenzenes on partial hydrogenation was also explored in this study.
Silicon-based Synthesis of [2]Rotaxanes without Polar Functional Groups
Authors: Phan Son Thanh , Setaka Wataru , Kira Mitsuo
Published: August 2008

The synthesis of [2]rotaxanes without polar functional groups was achieved by protodesilylation of the corresponding phenylene-bridged 1,12-disilacyclodocosanes in 20–30% isolated yields. The molecular structure of rotaxane 1a showed that the wheel is not at the center of the rod but on a dimethylene group of the dumbbell. By detailed NMR analyses, facile shuttling of the wheel was found to control the geometry of the dumbbells in the rotaxanes.
Synthesis and Characterization of Starburst 9-Phenylcarbazole/Triazatruxene Hybrids
Authors: Lai Wen-Yong , He Qi-Yuan , Chen Dao-Yong , Huang Wei
Published: August 2008

Novel starburst triazatruxenes functionalized with six N-phenylated carbazole units have been synthesized and characterized. Good yields and high purity were readily obtained via an optimized microwave-enhanced six-fold Suzuki coupling methodology. High thermal stability and good amorphous properties as well as deep blue emissions (423–434 nm) were demonstrated. The introduction of six-substituted triazatruxene scaffolds could provide a new guideline for exploring novel solution-processable amorphous materials with dual functions for light-emitting and/or hole-transporting applications.
Preparation of Hydrolyzable Polyrotaxane Containing Ester Linkages and Its Degradation Behavior
Authors: Katoono Ryo , Fukuda Shin-ichiroh , Shin Hojoon , Yui Nobuhiko
Published: August 2008

A hydrolyzable polyrotaxane composed of an ester-containing poly(ethylene glycol) chain and α-cyclodextrins showed gradual degradation into its water-soluble components in aqueous conditions, based on the dissociation of the polyrotaxane triggered by the hydrolysis of the ester groups.
Effects of O3 and NO2 on Catalytic Oxidation of Diesel PM
Authors: Yamamoto Shin , Yao Shuiliang , Kodama Satoshi , Mine Chieko , Fujioka Yuichi
Published: August 2008

Oxidative activities of ten different catalysts to particulate matter (PM) emitted from a diesel engine have been compared by thermogravimetric analysis under an atmosphere containing O3 and NO2. MnO2 has been found to exceed noble metal catalysts in the PM oxidation efficiency even at 300 °C. The PM oxidative activities of transition-metal oxides possessing high formation enthalpies are enhanced by the active oxygen species owing to acceleration of redox catalytic cycles.
Incomplete laboratory request forms: the extent and impact on critical results at a tertiary hospital in South Africa
Authors: Nutt Louise , Zemlin Annalise E , Erasmus Rajiv T
Published: August 2008

Background

Research has demonstrated that most laboratory errors occur in the preanalytical phase of testing. In view of the paucity of studies examining preanalytical errors, we evaluated our laboratory request forms for the frequency and impact of incomplete data.

Methods

This study examined all request forms received at our laboratory during a five-day period. The forms were scrutinized for the presence of specific parameters. The impact of abbreviated diagnoses was analysed, as well as how lack of ward or telephone details affects the communication of critical results to clinicians.

Results

A total of 2550 request forms were analysed. Medication(s) used by the patient (89.6%) and doctor’s contact number (61.2%) were the most incomplete parameters. No diagnosis was provided on 19.1% of forms, and when a diagnosis was present it was an abbreviated form in 37.3%. This resulted in 35.5% of diagnoses not being recorded by reception staff. Incomplete ward information was found on 4.9% of forms. In a separate search, the impact of 151 request forms (collected over a period of eight months), with incomplete ward location information and corresponding to critical results was assessed. Critical results were not communicated by telephone to clinicians in 19.9% of cases.

Conclusion

As laboratory data influences 70% of medical diagnoses, incorrect or incomplete data provided to the laboratory could significantly impact the success and cost of overall treatment.
Excessive calcium ingestion leading to milk-alkali syndrome
Authors: Bailey C S , Weiner J J , Gibby O M , Penney M D
Published: August 2008

This report describes the presentation and clinical course of a 40-year-old woman who had an emergency admission for eclampsia. During routine investigations, she was found to have profound hypercalcaemia, the cause of which was identified as milk-alkali syndrome, caused by self-medication with antacid tablets for dyspepsia. Treatment with aggressive rehydration, bisphosphonates and discontinuation of antacid tablets restored normocalcaemia. The patient made a full recovery with no long-term side-effects. Her male infant was safely delivered with no deleterious effects of exposure to high calcium concentrations in utero.
Role of conformational change in the C-terminus of β2-microglobulin in dialysis-related amyloidosis
Authors: Kim Jaemi , Motomiya Yoshihiro , Ueda Mitsuharu , Nakamura Masaaki , Misumi Yohei , Saito Shiori , Ikemizu Shinji , Misumi Shogo , Ota Kazutoshi , Shinriki Satoru , Kai Hirofumi , Ando Yukio
Published: August 2008

Background

β2-Microglobulin (β2m) has been identified as the precursor protein of dialysis-related amyloidosis (DRA), which is a serious complication for haemodialysis (HD) patients. However, mechanisms underlying β2m amyloid fibril formation remains to be elucidated. We previously demonstrated, in amyloid deposits from HD patients, a conformational isoform of β2m with an unfolded C-terminus. However, no direct experiments have previously been performed to address whether unfolded β2m in the C-terminus may be prone to form amyloid fibrils.

Methods

To evaluate roles of C-terminal amino acids in β2m-induced amyloid formation, we generated six types of recombinant β2m with amino acid substitutions in the C-terminal region. To investigate their conformational change and amyloidogenicity, we measured circular dichroism spectra, the fluorescence intensity of tryptophan and thioflavin-T (ThT) of the recombinant β2m. To analyse morphological change of β2m, we performed electron microscopy (EM) on the samples with elevated ThT fluorescence intensity. We used ultrasonication to enhance β2m destabilization of the protein.

Results

β2M Trp95Leu and Arg97Ala showed conformational changes and increased their amyloidgenicity compared with β2m wild-type (WT). With ultrasonication, β2m Trp95Leu and Arg97Ala generated more amyloid fibrils than did β2m WT even in physiological solution. EM showed that β2m formed amorphous debris containing typical amyloid fibrils at 24 hours, when ThT fluorescence intensity was three-fold lower than that at six hours.

Conclusions

Conformational changes in the C-terminus of β2m may play an important role in DRA and that ultrasonication is useful for analysis of β2m amyloidogenesis.
A survey of the ethics climate of Hong Kong public hospitals
Authors: Hui Edwin C
Published: August 2008

The main objective of the study was to survey health-care practitioners' (HCPs) perception of health-care practices that are of medical–ethical importance in Hong Kong public hospitals, and to identify the moral issues that concern them most. A total of 2718 doctors, nurses, allied health and administrative workers from 14 hospitals participated. HCPs considered that communication/conflict between patients/families and HCPs was the most important issue, followed by issues concerning patients' rights and values. The ‘ethics climate’ in Hong Kong public hospitals was found to be largely determined by two negative factors (inadequate communication and conflict issues) and two positive factors (high regard for patients' rights and the decline in family interference). Chinese cultural conventions were inferred to exert strong influence on the behaviours of HCPs and patients/families. Significant differences in perceptions between different categories of HCPs were also detected. The study was the first of its kind ever done in Hong Kong and signalled the need for institutional reorganization and medical–ethical education.
Preimplantation genetic diagnosis for familial hypercholesterolaemia: a commentary on the recent HFEA decision
Authors: Boddington Paula , Parker Michael
Published: August 2008

The Human Fertilisation and Embryology Authority have recently granted a licence to perform preimplanation genetic diagnosis (PGD) for the homozygous form of familial hypercholesterolaemia (FH), explicitly excluding its use for the heterozygous form. The grounds for such decisions centre on how serious a condition is thought to be as well as on the availability of effective treatment, and decisions are made on a case-by-case basis. The case for licensing homozygous FH is discussed and compared with other cases, and the case for making a distinction between PGD for homozygous and heterozygous FH is also examined. Testing for homozygous FH raises difficult issues of non-disclosure of results for heterozygous FH. Fears that this decision may represent a ‘slippery slope’ to more widespread testing are argued to be overstated.
Studying the mind: ethical issues and guidance in mental health research
Authors: Adshead Gwen
Published: August 2008

Freely given informed consent to participation is the ethical cornerstone of research in health care. However, in mental health settings, there are many patients who lack the capacity to give such consent to participate in research. There is an abundance of guidance now available on how researchers might think about this issue and the Royal College of Psychiatrists has also recently reviewed its guidance to members about the ethics of research. In this piece, I will discuss some of the issues that were raised during the revision process, and add some reflections of my own.