bluuebunny/crossref_metadata_2025 huggingface dataset:
Central Nervous Effects of Leptin and Insulin on Hippocampal Leptin and Insulin Receptor Expression following a Learning Task in Wistar Rats
Authors: Paulus K. , Schulz C. , Lehnert H.
Published: March 2005

Insulin and leptin are well known to be involved in the regulation of food intake and body weight. Recent studies have suggested that both hormones may also affect memory and learning processes. We explored whether the intrahippocampal administration of insulin or leptin improved spatial memory formation in rats following a radial maze task and whether the insulin and leptin receptor expression in different areas of the hippocampus was affected. Animals without a learning task were also investigated in order to differentiate between the influence of spatial learning and hormone application on receptor expression. Spatial memory formation was found unaltered following the different applications. The application of insulin increased the expression of the long form of the leptin receptor in the Ammon‘s horn and dentate gyrus region of the hippocampus in the learning group only. These data clearly show that learning is a prerequisite for the effect of insulin on leptin receptor expression.
Differential Role for Mitogen-Activated Protein Kinases in IgE-Dependent Signaling in Human Peripheral Blood Basophils: In Contrast to p38 MAPK, c-Jun N-Terminal Kinase Is Poorly Expressed and Does Not Appear to Control Mediator Release
Authors: Gibbs Bernhard F. , Wolff Helmut H. , Zillikens Detlef , Grabbe Jürgen
Published: March 2005

Background: Exposure of human basophils to allergens results in a rapid secretion of histamine, LTC4, IL-4 and IL-13, which dominate both the symptomology of allergic diseases and support the underlying Th2/IgE predominance associated with these reactions. The IgE-dependent release of these mediators in basophils crucially involves PI 3-kinase and the subsequent activation of p38 MAPK and ERK1&2. Here, we investigated the role of the third major member of the mitogen activated kinase family, namely the c-Jun amino terminal kinase (JNK), which is rapidly activated following IgE receptor cross-linking in murine mast cells. Methods: Human basophils were highly purified by magnetic cell sorting. The activities of various intracellular signaling components, in basophils that had been stimulated under various conditions, were assessed by Western blotting. Mediator secretions were also determined using either spectrofluorometric analysis (histamine) or ELISA (LTC4, IL-4 and IL-13). Results: Our results show that while JNK is moderately expressed in human basophils, it is not consistently phosphorylated upon anti-IgE stimulation. Phosphorylation of the transcription factor c-Jun, a downstream target of JNK, was also undetected in contrast to p38 MAPK and ERK1&2, which were clearly activated following anti-IgE stimulation of the cells. Additionally, inhibitors of the JNK pathway failed to prevent basophil mediator release and had no effect on the phosphorylation of p38 MAPK or ERK1&2 at concentrations which were specific for JNK blockade. Conclusions: These data suggest major differences in utilizing various members of the mitogen-activated kinase family in the signal transduction cascade of IgE-receptor-bearing cells.
Comparison of the Effects of Quinapril and Losartan on Carotid Artery Intima-Media Thickness in Patients with Mild-to-Moderate Arterial Hypertension
Authors: Uchiyama-Tanaka Yoko , Mori Yasukiyo , Kishimoto Noriko , Fukui Masayoshi , Nose Atsuko , Kijima Yasuaki , Yamahara Hideki , Hasegawa Takamasa , Kosaki Atsushi , Matsubara Hiroaki , Iwasaka Toshiji
Published: March 2005

Background: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. Methods: 57 hypertensive patients were randomly assigned to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB (losartan; n = 18, group L). Results: After 1 year of treatment, a similar decrease in mean blood pressure was observed in all groups. Carotid IMT was decreased significantly in group Q (10% decrease, p < 0.05) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups. Conclusion: Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients. This effect appears unrelated to the drug’s antihypertensive action or to traditional atherosclerotic factors.
High-Grade Neuroendocrine Carcinoma of the Cervix
Authors: Baykal C. , Al A. , Tulunay G. , Bulbul D. , Güler G. , Özer S. , Küçükali T.
Published: March 2005

Neuroendocrine tumor of the uterine cervix is a rare and aggressive malignancy. Despite controversial, multimodal treatment methods, prognosis and treatment outcomes are worst in advanced stages. We report an early-stage case treated with the multimodal approach. The nomenclature proposed for this tumor type in 1997 by the College of American Pathologists still has some points of discussion. As in our case some of the tumors cannot be defined exactly into small or large cell types, and this causes confusion at least for nomenclature purposes. A ‘mixed’ type for this tumor may be appropriate.
Mary Broadfoot Walker (1888–1974): A Historic Discovery in Myasthenia gravis
Authors: Pearce J.M.S.
Published: March 2005

As a clinical entity, myasthenia gravis was not recognized until Samuel Wilks in 1877 described bulbar and peripheral muscular weakness. In the Lancet of June 2, 1934, the remarkable discovery of physostigmine treatment by Dr. Mary Walker was published, which was to become the mainstay of symptomatic treatment. A quiet and modest physician, she laboured with considerable success under many obstacles in her work and career.
Attenuation of Interstitial Inflammation and Fibrosis by Recombinant Human Erythropoietin in Chronic Cyclosporine Nephropathy
Authors: Lee Seung Hun , Li Can , Lim Sun Woo , Ahn Kyung Ohk , Choi Bum Soon , Kim Yong Soo , Moon In Sung , Kim Jin , Bang Byung Kee , Yang Chul Woo
Published: March 2005

Background: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury. Methods: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death. Results: Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-β1 and transforming growth factor-β1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3). Conclusion: rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.
Bigger or Better? The Role of Human Rights and Democracy in Determining Membership of the European Institutions
Authors: Duxbury Alison
Published: March 2005

This article traces the development of the role of human rights and democracy in determining admission to three European organizations: the Council of Europe, NATO and the EU. Despite the different functions that each organization performs, they have all assumed that prospective members must comply with human rights and democratic conditions. This is evident in both the organizations' constituent instruments and related membership documents, and also in the recent admission practice of the three organizations. But the membership practice also indicates that since their establishment the organizations have not always applied these conditions rigorously – thus there is a tension between the organizations' desire for homogenous universality (getting better) and heterogeneous universality (getting bigger). The admission practice also reveals a number of problems with the use of human rights and democratic criteria, including inconsistencies in the application of the criteria between applicants and existing members of the same organization, and inconsistencies in the application of the shared criteria across the three organizations. In the end, the development of the common membership criteria of human rights and democracy highlights both a degree of flexibility in admission decisions, as well as a progressive change in the functions of each organization.
The Coupled Manifold*
Authors: Navarra A. , Tribbia J.
Published: March 2005

A new method is presented to detect the portion of variability connected between two climatic fields. The method is a realization of the Procrustes problem, and it is a generalization of methods for analysis of variance such as the singular value decomposition (SVD) or canonical correlation analysis (CCA). The Procrustes formulation offers a general framework to link together variance analysis methods, and regression methods, including as special cases SVD and CCA.

Using this approach two fields can be divided into a subspace where variations of one field are connected to variations of the other field, the coupled manifold, and a subspace where variations are independent, the free manifold. The unified approach can be applied to prescribed SST experiments, in which case it recovers consistent results with other methods designed to identify the forced portion of variance, but it can now be extended also to the coupled case or to observations.

Some examples from prescribed SST simulation experiments and observations are discussed.
Equatorial Superrotation and the Factors Controlling the Zonal-Mean Zonal Winds in the Tropical Upper Troposphere
Authors: Kraucunas Ian , Hartmann Dennis L.
Published: March 2005

The response of the zonal-mean zonal winds in the tropical upper troposphere to thermal forcing in the Tropics is studied using an idealized general circulation model with 18 vertical levels and simplified atmospheric physics. The model produces a conventional general circulation, with deep easterly flow over the equator, when integrated using zonally invariant and hemispherically symmetric boundary conditions, but persistent equatorial superrotation (westerly zonal-mean flow over the equator) is obtained when steady longitudinal variations in diabatic heating are imposed at low latitudes. The superrotation is driven by horizontal eddy momentum fluxes associated with the stationary planetary wave response to the applied tropical heating. The strength of the equatorial westerlies is ultimately limited by vertical steady eddy momentum fluxes, which are downward in the tropical upper troposphere, and by the zonally averaged circulation in the meridional plane, which erodes the mean westerly shear via vertical advection.

The transition to superrotation can be prevented by specifying offsetting zonally invariant heating and cooling anomalies on either side of the equator to create a “solstitial” basic state with a single dominant Hadley cell straddling the equator. Superrotation is restricted in the solstitial climate because the strength of the mean meridional overturning is enhanced, which increases the efficiency of vertical advection, and because the cross-equatorial flow in the upper troposphere provides an easterly zonal acceleration that offsets some of the momentum flux convergence associated with tropical eddy heating. The cross-equatorial flow aloft also reduces the stationary planetary wave response in the summer hemisphere. These results suggest that hemispheric asymmetry in the mean meridional circulation is responsible for maintaining the observed mean easterly flow in the tropical upper troposphere against the westerly torques associated with tropical wave sources.
Extratropical Dry-Air Intrusions into the West African Monsoon Midtroposphere: An Important Factor for the Convective Activity over the Sahel
Authors: Roca Rémy , Lafore Jean-Philippe , Piriou Catherine , Redelsperger Jean-Luc
Published: March 2005

This paper investigates the relationship between large-scale dynamics, water vapor, and organized convection over West Africa. Making use of a simplified condensation hypothesis, a back-trajectory model fed by NCEP-analyzed winds is used to reconstruct the midtropospheric humidity field over Africa during July to August 1992. The approach documents both the moisture content and the origin of the air masses. Meteosat satellite infrared imagery is used to characterize the convective systems.

A case study analysis reveals that very dry air patches (RH < 5%) are located in the immediate midtropospheric environment of a typical squall line. Such dry-air structures are shown to originate in the upper levels (200–250 hPa) on the anticyclonic side of the polar jet stream at 50°N. Focusing on the Sahel region, dry events are isolated using the time series of the 500-hPa relative humidity distribution during the monsoon period. These dry events are shown to be composed of extratropical air. Composite analysis of the convective activity indicator exhibits a strong positive association between dry intrusions and convection on the eastern side of the Sahelian region. Organized convective systems that are fast moving and long lasting are more likely over this region when a dry intrusion is present. This coincides with the well-established theory that midtropospheric dry air, when combined with sufficient wind shear, can maintain and intensify previously triggered deep convection through rain evaporation that feeds the cold pools, especially within squall lines. This paper suggests that the extratropical dry-air intrusions modulate the occurrence and duration of convective systems and, therefore, the mode of variability of rainfall over West Africa during the monsoon.
The Theory of Ice Nucleation by Heterogeneous Freezing of Deliquescent Mixed CCN. Part II: Parcel Model Simulation
Authors: Khvorostyanov Vitaly I. , Curry Judith A.
Published: March 2005

The new theory of ice nucleation by heterogeneous freezing of deliquescent mixed cloud condensation nuclei (CCN) presented in Part I is incorporated into a parcel model with explicit water and ice bin microphysics to simulate the process of ice nucleation under transient thermodynamic conditions. Simulations are conducted over the temperature range −4° to −60°C, with vertical velocities varying from 1 to 100 cm s−1, for varying initial relative humidities and aerosol characteristics. These simulations show that the same CCN that are responsible for the drop nucleation may initiate crystal nucleation and can be identified as ice nuclei (IN) when crystals form. The simulated nucleation rates and concentrations of nucleated crystals depend on temperature and supersaturation simultaneously, showing good agreement with observations but with noticeable differences when compared with classical temperature-only and supersaturation-only parameterizations. The kinetics of heterogeneous ice nucleation exhibits a negative feedback via water supersaturation, whereby ice nucleation depends on the water supersaturation that is diminished by ice crystal diffusional growth. This feedback is stronger than the corresponding feedback for drop nucleation, and may explain discrepancies between observed ice nuclei concentrations and ice crystal concentrations, the very small fraction of CCN that may serve as IN, and the much smaller crystal concentrations as compared to drop concentrations. The relative importance of heterogeneous versus homogeneous nucleation is examined for a variety of cloud conditions. Based on these calculations, a simple parameterization for ice crystal concentration is suggested for use in cloud models and large-scale models.
Small-Scale Drop-Size Variability: Empirical Models for Drop-Size-Dependent Clustering in Clouds
Authors: Marshak Alexander , Knyazikhin Yuri , Larsen Michael L. , Wiscombe Warren J.
Published: March 2005

By analyzing aircraft measurements of individual drop sizes in clouds, it has been shown in a companion paper that the probability of finding a drop of radius r at a linear scale l decreases as lD(r), where 0 ≤ D(r) ≤ 1. This paper shows striking examples of the spatial distribution of large cloud drops using models that simulate the observed power laws. In contrast to currently used models that assume homogeneity and a Poisson distribution of cloud drops, these models illustrate strong drop clustering, especially with larger drops. The degree of clustering is determined by the observed exponents D(r). The strong clustering of large drops arises naturally from the observed power-law statistics. This clustering has vital consequences for rain physics, including how fast rain can form. For radiative transfer theory, clustering of large drops enhances their impact on the cloud optical path. The clustering phenomenon also helps explain why remotely sensed cloud drop size is generally larger than that measured in situ.
A Refined Method of Parameterizing Absorption Coefficients among Multiple Gases Simultaneously from Line-by-Line Data
Authors: Jacobson Mark Z.
Published: March 2005

An extension of the correlated-k distribution method that uses spectral-mapping techniques was derived to parameterize line-by-line absorption coefficients for multiple gases simultaneously for use in three-dimensional atmospheric models. In a variation from previous correlation techniques, this technique ensures exact correlation of absorption frequencies within a probability interval for all gases through all layers of the atmosphere when multiple gases are considered. The technique is physical since, in reality, gases are correlated in wavelength space. The technique, referred to as the “multiple-absorber correlated-k distribution spectral-mapping method,” was found to be accurate to <0.7% of incident radiation for 16 probability intervals per wavelength interval, integrated over 0.4–1000-μm wavelengths and accounting for 11 absorbing gases simultaneously and multiple layers, compared with an exact line-by-line solution. A method was also derived to reduce the number of probability intervals required for a radiative transfer solution without suffering the same inaccuracy as merely reducing the number of probability intervals when parameterizing the absorption coefficient. The new coefficients were tested in a global model, and results were compared with mean thermal-IR irradiance data.
Distributed Forcing of Forecast and Assimilation Error Systems
Authors: Farrell Brian F. , Ioannou Petros J.
Published: March 2005

Temporally distributed deterministic and stochastic excitation of the tangent linear forecast system governing forecast error growth and the tangent linear observer system governing assimilation error growth is examined. The method used is to determine the optimal set of distributed deterministic and stochastic forcings of the forecast and observer systems over a chosen time interval. Distributed forcing of an unstable system addresses the effect of model error on forecast error in the presumably unstable forecast error system. Distributed forcing of a stable system addresses the effect on the assimilation of model error in the presumably stable data assimilation system viewed as a stable observer. In this study, model error refers both to extrinsic physical error forcing, such as that which arises from unresolved cumulus activity, and to intrinsic error sources arising from imperfections in the numerical model and in the physical parameterizations.
Reexamining the Near-Core Radial Structure of the Tropical Cyclone Primary Circulation: Implications for Vortex Resiliency
Authors: Mallen Kevin J. , Montgomery Michael T. , Wang Bin
Published: March 2005

Recent theoretical studies, based on vortex Rossby wave (VRW) dynamics, have established the importance of the radial structure of the primary circulation in the response of tropical cyclone (TC)–like vortices to ambient vertical wind shear. Linear VRW theory suggests, in particular, that the degree of broadness of the primary circulation in the near-core region beyond the radius of maximum wind strongly influences whether a tilted TC vortex will realign and resist vertical shear or tilt over and shear apart. Fully nonlinear numerical simulations have verified that the vortex resiliency is indeed sensitive to the initial radial structure of the idealized vortex. This raises the question of how well the “true” nature of a TC’s primary circulation is represented by idealized vortices that are commonly used in some theoretical studies.

In this paper the swirling wind structure of TCs is reexamined by utilizing flight-level observations collected from Atlantic and eastern Pacific storms during 1977–2001. Hundreds of radial profiles of azimuthal-mean tangential wind and relative vorticity are constructed from over 5000 radial flight leg segments and compared with some standard idealized vortex profiles. This analysis reaffirms that real TC structure in the near-core region is characterized by relatively slow tangential wind decay in conjunction with a skirt of significant cyclonic relative vorticity possessing a negative radial gradient. This broadness of the primary circulation is conspicuously absent in some idealized vortices used in theoretical studies of TC evolution in vertical shear. The relationship of the current findings to the problem of TC resiliency is discussed.
Optimal Perturbations in the Eady Model: Resonance versus PV Unshielding
Authors: de Vries H. , Opsteegh J. D.
Published: March 2005

Using a nonmodal decomposition technique based on the potential vorticity (PV) perspective, the optimal perturbation or singular vector (SV) of the Eady model without upper rigid lid is studied for a kinetic energy norm. Special emphasis is put on the role of the continuum modes (CMs) in the structure of the SV, and on the importance of resonance to the SV evolution. The basis for the SV is formed by a number of nonmodal structures, each consisting of a superposition of one CM and one edge wave, such that the initial surface potential temperature (PT) is zero. These nonmodal structures are used as PV building blocks to construct the SV. The motivation for using a nonmodal approach is that no attempt has been made so far to include the CM residing at the steering level of the surface edge wave in the perturbation, although it is known that this CM is in linear resonance with the surface edge wave.

Experiments with one PV building block in the initial disturbance show that the SV growth is dominated by the resonance effect except for small optimization times (less than 1 day), in which case the unshielding of PV and surface PT dominates the growth of the SV. The PV–PT unshielding provides additional growth to the SV and this explains the observation that the PV resides above the resonant level.

More PV building blocks are added to include PV unshielding as a third growth mechanism. Which of the three mechanisms dominates during the SV evolution depends on the region of interest (interior or surface), as well as on the optimization time and on the number of building blocks used. At the surface, resonance plays a dominant role even when a large number of building blocks is used and relatively small optimization times are used. For the interior of the domain, PV unshielding becomes the dominant growth mechanism when more than two PV building blocks are used. With increasing optimization times, the PV distribution of the SV becomes increasingly more concentrated near the steering level of the edge wave. This concentration of PV is explained by the enhanced importance of resonance for long optimization times as compared to short optimization times.
Correlates and Predictors of Self-Reported Suicide Attempts Among Incarcerated Youths
Authors: Putnins Aldis L.
Published: March 2005

The correlates and predictors of suicidal behaviors among 900 young offenders in detention centers in SouthAustralia are investigated. That young offenders are a high-risk population is confirmed, with a quarter of the youths reporting recent suicidal ideation and more than a quarter reporting having made a suicide attempt. Past suicide attempts are significantly predictive of future suicide attempts. Other variables both concurrently and prospectively associated with suicidal behaviors (even after controlling for prior suicide attempt status) are substance use, prolonged dysphoric mood, attention deficit hyperactivity disorder signs, and having a bad temper. These variables not only have predictive value but should also be considered as appropriate targets when intervening to reduce suicide risk. It is suggested that impulsiveness is an underlying common factor.
Naming Oneself Criminal: Gender Difference in Offenders’ Identity Negotiation
Authors: Geiger Brenda , Fischer Michael
Published: March 2005

This qualitative research examines gender differences in offenders’ability to negotiate a positive identity once the pejorative labels of criminal, prostitute, drug dealer, and incompetent parents have been imputed onto them. In-depth semi-structured focused interviews were conducted with a purposeful information-rich sample of eight male and eight female offenders. Content analysis reveals that males were much more adept than female offenders at juggling with conventional and street norms to justify and/or resist stigmatizing labels in order to construct a favorable identity. Appeal to such personal strengths as know-how, competence, loyalty, and a code of honor allowed male offenders to challenge the boundaries between conventional and delinquent worlds. Concomitantly such an appeal gave rise to a sense of efficacy perception and an optimistic explanatory style. In contrast, even though female offenders were able to justify the labels of drug dealer, prostitute, and thief by appeal to higher loyalties and reject that of insane, all their justifications collapsed when having to negotiate the identity of incompetent mother. Female offenders’ negative internal attributions and deprivation of the normative center-motherhood resulted in apathy, anomie, and lack of confidence in their ability to do something worthwhile. Rehabilitation guidelines would build female offenders’ personal strengths while redirecting those exhibited by male offenders into lawful enterprises.
Calcium Dysregulation, IP3 Signaling, and Alzheimer’s Disease
Authors: Stutzmann Grace E.
Published: March 2005

Ca2+ ions subserve complex signaling roles in neurons, regulating functions ranging from gene transcription to modulation of membrane excitability. Ca2+ ions enter the cytosol from extracellular sources, such as entry through voltage-gated channels, and by liberation from intracellular endoplasmic reticulum (ER) stores through inositol triphosphate (IP3) receptors and/or ryanodine (RyR) receptors. Disruptions of intracellular Ca2+ signaling are proposed to underlie the pathophysiology of Alzheimer’s disease (AD), and recent studies examining AD-linked mutations in the presenilin genes demonstrate enhanced ER Ca2+ release in a variety of cell types and model systems. The development of transgenic AD mouse models provides a means to study the mechanisms and downstream effects of neuronal ER Ca2+-signaling alterations on AD pathogenesis and offers insight into potential novel therapeutic strategies. The author discusses recent findings in both the physiological functioning of the IP3-signaling pathway in neurons and the involvement of ERCa2+ disruptions in the pathogenesis of AD.
The Control of Voluntary Eye Movements: New Perspectives
Authors: Krauzlis Richard J.
Published: March 2005

Primates use two types of voluntary eye movements to track objects of interest: pursuit and saccades. Traditionally, these two eye movements have been viewed as distinct systems that are driven automatically by low-level visual inputs. However, two sets of findings argue for a new perspective on the control of voluntary eye movements. First, recent experiments have shown that pursuit and saccades are not controlled by entirely different neural pathways but are controlled by similar networks of cortical and subcortical regions and, in some cases, by the same neurons. Second, pursuit and saccades are not automatic responses to retinal inputs but are regulated by a process of target selection that involves a basic form of decision making. The selection process itself is guided by a variety of complex processes, including attention, perception, memory, and expectation. Together, these findings indicate that pursuit and saccades share a similar functional architecture. These points of similarity may hold the key for understanding how neural circuits negotiate the links between the many higher order functions that can influence behavior and the singular and coordinated motor actions that follow.
Pride and Glory: Aberdeen Public Library During The Second World War
Authors: Nolan Marie E. , Reid Peter H.
Published: March 2005

Between 1939 and 1945 Britain's public libraries often struggled to balance wartime shortages in materials and staff with an increased readership, while also being expected to contribute actively services and skills to the war effort. Government documents, committee minutes, reports, news stories and interviews have been employed in an attempt to build a picture of one particular library's experiences during this period.
Early British Public Library Annual Reports: Then and Now Part II
Authors: Peatling G.K. , Baggs Chris
Published: March 2005

This article continues the study of public library annual reports which commenced in the previous issue of this journal (vol. 20, no. 3, November 2004, pp. 223–38). This second paper assesses the value and contemporary importance of the reports in the expansion of the public library movement, considering criticisms from both then and now. It is suggested that these documents should be of wider significance than just as sources for historians of libraries.
Computational verification of protein-protein interactions by orthologous co-expression
Authors: Tirosh Itay , Barkai Naama
Published: March 2005

Background

High-throughput methods identify an overwhelming number of protein-protein interactions. However, the limited accuracy of these methods results in the false identification of many spurious interactions. Accordingly, the resulting interactions are regarded as hypothetical and computational methods are needed to increase their confidence. Several methods have recently been suggested for this purpose including co-expression as a confidence measure for interacting proteins, but their performance is still quite poor.

Results

We introduce a novel computational method for verification of protein-protein interactions based on the co-expression of orthologs of interacting partners. The performance of our method is analysed using known S. cerevisiae interactions, and is shown to overcome limitations of previous methods. We present specific examples of known and putative interactions that are detected by our method and not by previous methods, and suggest that they represent transient interactions that might have been conserved and stabilized in other species.

Conclusion

Co-expression of orthologous protein-pairs can be used to increase the confidence of hypothetical protein-protein interactions in S. cerevisiae as well as in other species. This approach may be especially useful for species with no available expression profiles and for transient interactions.
Automated migration analysis based on cell texture: method & reliability
Authors: Qin Jianfeng , Chittenden Thomas W , Gao Ling , Pearlman Justin D
Published: March 2005

Background

In this paper, we present and validate a way to measure automatically the extent of cell migration based on automated examination of a series of digital photographs. It was designed specifically to identify the impact of Second Hand Smoke (SHS) on endothelial cell migration but has broader applications. The analysis has two stages: (1) preprocessing of image texture, and (2) migration analysis.

Results

The output is a graphic overlay that indicates the front lines of cell migration superimposed on each original image, with automated reporting of the distance traversed vs. time. Expert preference compares to manual placement of leading edge shows complete equivalence of automated vs. manual leading edge definition for cell migration measurement.

Conclusion

Our method is indistinguishable from careful manual determinations of cell front lines, with the advantages of full automation, objectivity, and speed.
BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury
Authors: Bartley John , Soltau Thomas , Wimborne Hereward , Kim Sunjun , Martin-Studdard Angeline , Hess David , Hill William , Waller Jennifer , Carroll James
Published: March 2005

Background

Mechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury.

Results

Neonatal mice underwent permanent unilateral carotid ligation on the seventh postnatal day followed by exposure to 8% hypoxia for 75 minutes. The presence of new cells was determined by bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals at intervals. Brain sections were stained for BrdU in combination with neuronal, glial, endothelial and microglial stains.

We found a significant increase in BrdU-positive cells in the neonatal mouse hippocampus in the injured area compared to the non-injured area, most prominent in the dentate gyrus (DG) (154.5 ± 59.6 v. 92.9 ± 32.7 at 3 days after injury; 68.9 ± 23.4 v. 52.4 ± 17.1 at 35 days after injury, p < 0.0011). Among the cells which showed differentiation, those which were stained as either microglial or endothelial cells showed a peak increase at three days after the injury in the DG, injured versus non-injured side (30.5 ± 17.8 v. 2.7 ± 2.6, p < 0.0002). As in the adult animal, neurogenesis was significantly increased in the DG with injury (15.0 ± 4.6 v. 5.2 ± 1.6 at 35 days after injury, p < 0.0002), and this increase was subsequent to the appearance of the other dividing cells. Numbers of new oligodendrocytes were significantly higher in the DG on the non-injured side (7.0 ± 24.2 v. 0.1 ± 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis was reduced in the injured hippocampus.

Conclusion

These findings demonstrate that the neonatal animal responds to brain injury with neurogenesis, much like the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia alone. This process may play a role in the recovery of the neonatal animal from H-I insult, and if so, enhancement of the process may improve recovery.
Developmental changes in abundance of the VSPβ protein following nuclear transformation of maize with the Soybean vspβ cDNA
Authors: Grando Magali F , Smith Rex L , Moreira Cristina , Scully Brian T , Shatters Robert G
Published: March 2005

Background

Developing monocots that accumulate more vegetative tissue protein is one strategy for improving nitrogen-sequestration and nutritive value of forage and silage crops. In soybeans (a dicotyledonous legume), the vspA and B genes encode subunits of a dimeric vegetative storage protein that plays an important role in nitrogen storage in vegetative tissues. Similar genes are found in monocots; however, they do not accumulate in leaves as storage proteins, and the ability of monocot leaves to support accumulation of an ectopically expressed soybean VSP is in question. To test this, transgenic maize (Zea Mays L. Hi-II hybrid) lines were created expressing soybean vspB from a maize ubiquitin Ubi-1 promoter.

Results

From 81 bombardments, 101 plants were regenerated, and plants from five independent lines produced vspB transcripts and VSPβ polypeptides. In leaves from seven-week-old plants (prior to flowering), VSPβ accumulated to 0.5% of the soluble leaf protein in primary transgenic plants (R0), but to only 0.03% in R1 plants. During seed-filling (silage-stage) in R1 plants, the VSPβ protein was no longer detected in leaves and stems despite continued presence of the vspB RNA. The RNA transcripts for this peptide either became less efficiently translated, or the VSPβ protein became unstable during seed-fill.

Conclusion

Developmental differences in the accumulation of soybean VSPβ when transgenically expressed in maize show that despite no changes in the vspB transcript level, VSPβ protein that is readily detected in leaves of preflowering plants, becomes undetectable as seeds begin to develop.
Modeling emergency department visit patterns for infectious disease complaints: results and application to disease surveillance
Authors: Brillman Judith C , Burr Tom , Forslund David , Joyce Edward , Picard Rick , Umland Edith
Published: March 2005

Background

Concern over bio-terrorism has led to recognition that traditional public health surveillance for specific conditions is unlikely to provide timely indication of some disease outbreaks, either naturally occurring or induced by a bioweapon. In non-traditional surveillance, the use of health care resources are monitored in "near real" time for the first signs of an outbreak, such as increases in emergency department (ED) visits for respiratory, gastrointestinal or neurological chief complaints (CC).

Methods

We collected ED CCs from 2/1/94 – 5/31/02 as a training set. A first-order model was developed for each of seven CC categories by accounting for long-term, day-of-week, and seasonal effects. We assessed predictive performance on subsequent data from 6/1/02 – 5/31/03, compared CC counts to predictions and confidence limits, and identified anomalies (simulated and real).

Results

Each CC category exhibited significant day-of-week differences. For most categories, counts peaked on Monday. There were seasonal cycles in both respiratory and undifferentiated infection complaints and the season-to-season variability in peak date was summarized using a hierarchical model. For example, the average peak date for respiratory complaints was January 22, with a season-to-season standard deviation of 12 days. This season-to-season variation makes it challenging to predict respiratory CCs so we focused our effort and discussion on prediction performance for this difficult category. Total ED visits increased over the study period by 4%, but respiratory complaints decreased by roughly 20%, illustrating that long-term averages in the data set need not reflect future behavior in data subsets.

Conclusion

We found that ED CCs provided timely indicators for outbreaks. Our approach led to successful identification of a respiratory outbreak one-to-two weeks in advance of reports from the state-wide sentinel flu surveillance and of a reported increase in positive laboratory test results.
Reliability and validity of the AGREE instrument used by physical therapists in assessment of clinical practice guidelines
Authors: MacDermid Joy C , Brooks Dina , Solway Sherra , Switzer-McIntyre Sharon , Brosseau Lucie , Graham Ian D
Published: March 2005

Background

The AGREE instrument has been validated for evaluating Clinical Practice Guidelines (CPG) pertaining to medical care. This study evaluated the reliability and validity of physical therapists using the AGREE to assess quality of CPGs relevant to physical therapy practice.

Methods

A total of 69 physical therapists participated and were classified as generalists, specialist or researchers. Pairs of appraisers within each category evaluated independently, a set of 6 CPG selected at random from a pool of 55 CPGs.

Results

Reliability between pairs of appraisers indicated low to high reliability depending on the domain and number of appraisers (0.17–0.81 for single appraiser; 0.30–0.96 when score averaged across a pair of appraisers). The highest reliability was achieved for Rigour of Development, which exceeded ICC> 0.79, if scores from pairs of appraisers were pooled. Adding more than 3 appraisers did not consistently improve reliability. Appraiser type did not determine reliability scores. End-users, including study participants and a separate sample of 102 physical therapy students, found the AGREE useful to guide critical appraisal. The construct validity of the AGREE was supported in that expected differences on Rigour of Development domains were observed between expert panels versus those with no/uncertain expertise (differences of 10–21% p = 0.09–0.001). Factor analysis with varimax rotation, produced a 4-factor solution that was similar, although not in exact agreement with the AGREE Domains. Validity was also supported by the correlation observed (Kendall-tao = 0.69) between Overall Assessment and the Rigour of Development domain.

Conclusion

These findings suggest that the AGREE instrument is reliable and valid when used by physiotherapists to assess the quality of CPG pertaining to physical therapy health services.
Nanopores: maltoporin channel as a sensor for maltodextrin and lambda-phage
Authors: Berkane E , Orlik F , Charbit A , Danelon C , Fournier D , Benz R , Winterhalter M
Published: March 2005

Background

To harvest nutrition from the outside bacteria e.g. E. coli developed in the outer cell wall a number of sophisticated channels called porins. One of them, maltoporin, is a passive specific channel for the maltodextrin uptake. This channel was also named LamB as the bacterial virus phage Lambda mis-uses this channel to recognise the bacteria. The first step is a reversible binding followed after a lag phase by DNA injection. To date little is known about the binding capacity and less on the DNA injection mechanism. To elucidate the mechanism and to show the sensitivity of our method we reconstituted maltoporin in planar lipid membranes. Application of an external transmembrane electric field causes an ion current across the channel. Maltoporin channel diameter is around a few Angstroem. At this size the ion current is extremely sensitive to any modification of the channels surface. Protein conformational changes, substrate binding etc will cause fluctuations reflecting the molecular interactions with the channel wall. The recent improvement in ion current fluctuation analysis allows now studying the interaction of solutes with the channel on a single molecular level.

Results

We could demonstrate the asymmetry of the bacterial phage Lambda binding to its natural receptor maltoporin.

Conclusion

We suggest that this type of measurement can be used as a new type of biosensors.
Angiogenesis in male breast cancer
Authors: Frangou Evan M , Lawson Joshua , Kanthan Rani
Published: March 2005

Background

Male breast cancer is a rare but aggressive and devastating disease. This disease presents at a later stage and in a more advanced fashion than its female counterpart. The immunophenotype also appears to be distinct when compared to female breast cancer. Angiogenesis plays a permissive role in the development of a solid tumor and provides an avenue for nutrient exchange and waste removal. Recent scrutiny of angiogenesis in female breast cancer has shown it to be of significant prognostic value. It was hypothesized that this holds true in invasive ductal carcinoma of the male breast. In the context of male breast cancer, we investigated the relationship of survival and other clinico-pathological variables to the microvascular density of the tumor tissue.

Methods

Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Agency over a period of 26 years. Forty-seven cases of invasive ductal carcinoma of the male breast had formalin-fixed paraffin-embedded tissue blocks that were suitable for this study. All cases were reviewed. Immunohistochemical staining was performed for the angiogenic markers (cluster designations 31 (CD31), 34 (CD34) and 105 (CD105), von Willebrand factor (VWF), and vascular endothelial growth factor (VEGF)). Microvascular density (MVD) was determined using average, centre, and highest microvessel counts (AMC, CMC, and HMC, respectively). Statistical analyses compared differences in the distribution of survival times and times to relapse between levels of MVD, tumor size, node status and age at diagnosis. In addition, MVD values were compared within each marker, between each marker, and were also compared to clinico-pathological data.

Results

Advanced age and tumor size were related to shorter survival times. There were no statistically significant differences in distributions of survival times and times to relapse between levels of MVD variables. There was no significant difference in MVD between levels of the different clinico-pathological variables. MVD was strongly and significantly correlated between AMC, CMC and HMC for CD31, CD34, and CD105 (p < 0.01) and remained moderate to weak for VWF and VEGF.

Conclusion

Microvascular density does not appear to be an independent prognostic factor in male breast cancer. However, the likelihood of death for men with breast cancer is increased in the presence of increased age at diagnosis and advanced tumor size. This is perhaps linked to inherent tumor vasculature, which is strongly related throughout a tumor section.
The discovery of the first human retrovirus: HTLV-1 and HTLV-2
Authors: Gallo Robert C
Published: March 2005

I describe here the history leading up to and including my laboratory's discovery of the first human retrovirus, HTLV-I, and its close relative, HTLV-II. My efforts were inspired by early work showing a retroviral etiology for leukemias in various animals, including non-human primates. My two main approaches were to develop criteria for and methods for detection of viral reverse transcriptase and to identify growth factors that could support the growth of hematopoietic cells. These efforts finally yielded success following the discovery of IL-2 and its use to culture adult T cell lymphoma/leukemia cells.