bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Nutritional Intake, Body Mass Index and Glycemic Control in Patients with Type-2 Diabetes from Northern Tanzania
Authors: Hoffmeister Michael , Lyaruu Isaack A. , Krawinkel Michael B.
Published: March 2005

Background/Aims: Little information is available about the nutrition of people with diabetes from Africa. For the treatment and prevention of diabetes by nutrition, we have assessed the major local foods in a baseline study. Methods: The staple foods and meal frequencies of 53 outpatients with type-2 diabetes were assessed in a 24-hour dietary recall based on a questionnaire at a diabetes clinic in northern Tanzania in November and December 1999. In addition, data on weight and height, casual blood glucose, urinary glucose and diabetes therapy were ascertained. Results: 72% of the patients had a body mass index of ≧25 kg/m2; 64% of patients had casual blood glucose levels of >7.8 mmol/l, 47% had >11.1 mmol/l, and most of them were treated by sulfonylureas or conventional insulin therapy. The test for urinary glucose highly correlated with the blood glucose values, and was positive in 59% of patients. 36% of the patients had ≤3 meals/day. The foods stated most frequently were stiff porridge, plantains, bread, rice, beef, milk, amaranth leaves, orange and sunflower oil. The main beverages were water, tea and milk. Conclusions: The baseline data obtained enable more precise dietary assessment and emphasize the need to collect more data on local food consumption in areas where pharmacological diabetes treatment is limited.
Phase III Trial of Satraplatin, an Oral Platinum plus Prednisone vs. Prednisone alone in Patients with Hormone-Refractory Prostate Cancer
Authors: Sternberg C.N. , Whelan P. , Hetherington J. , Paluchowska B. , Slee P.H.Th.J. , Vekemans K. , van Erps P. , Theodore C. , Koriakine O. , Oliver T. , Lebwohl D. , Debois M. , Zurlo A. , Collette L.
Published: March 2005

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials [1]. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0–2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m2 for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7–28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4–23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46–1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8–13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1– 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28–0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.
Immunochemical and Biological Analysis of Allergenicity with Excretory-Secretory Products of Anisakis simplex Third Stage Larva
Authors: Kim J.S. , Kim K.H. , Cho S. , Park H.Y. , Cho S.W. , Kim Y.T. , Joo K.H. , Lee J.S.
Published: March 2005

Background:Anisakis simplex third stage larvae (L3) are parasites that frequently give rise to allergic responses. The larvae molt into fourth stage larvae (L4), and at each stage they produce L3-excretory-secretory products (L3-ESP) and L4-ESP, respectively, which are different in their main protein constituents. Although the allergenicity of L4-ESP has been investigated by several research groups, research on the allergenicity of L3-ESP has not been carried out by any researcher. In this investigation, the allergenicity and antigenicity of L3-ESP were investigated in comparison with L4-ESP, using rat sera. Methods: Rat sera were produced by L3 oral infection two times with a 9-week interval. Larvae ESP prepared by culture were concentrated and fractioned using lyophilizer and a centrifugal filter device, respectively. Immunochemical analysis was performed using both indirect ELISA and immunoblot. Biological allergenicity was analyzed by RBL-2H3 exocytosis. Results: With the indirect ELISA, the optical density (OD) value of the nonfractioned (NF)-L3ESP was only one third of that of the NF-L4ESP in both specific IgM and IgG. On measuring specific IgE, the OD of NF-L3ESP was less than one tenth of that of NF-L4ESP. In addition, neither antigen nor allergen was shown in NF-L3ESP, but it was shown in NF-L4ESP with immunoblot. However, the biological allergenicity of NF-L3ESP was comparable to that of NF-L4ESP. To demonstrate the presence of any allergen, L3-ESP was fractioned and found to carry twelve visualized allergen bands from 10 to 186 kDa by immunoblot. Conclusions: These results indicate that L3-ESP may include the important allergens necessary to induce the allergy by L3 oral infection, as compared to L4-ESP.
Increasing Prevalence of Japanese Cedar Pollinosis: A Meta-Regression Analysis
Authors: Kaneko Yoshihiro , Motohashi Yutaka , Nakamura Hiroyuki , Endo Tomohiko , Eboshida Akira
Published: March 2005

Background: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. Methods: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. Results: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R2 = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson’s r = 0.70, p < 0.001). Conclusions: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization.
FK506 Aerosol Locally Inhibits Antigen-Induced Airway Inflammation in Guinea Pigs
Authors: Morishita Yoshihiko , Hirayama Yoshitaka , Miyayasu Kikuo , Tabata Kenji , Kawamura Akio , Ohkubo Yoshitaka , Mutoh Seitaro
Published: March 2005

Background: Eosinophilic airway inflammation is a common pathological feature of asthma. It has been shown that FK506 given systemically suppresses antigen-induced airway inflammation in animal models. However, it is unknown whether inhaled FK506 can suppress the airway allergic inflammation/immune response and whether it acts locally or systemically. Methods: We tested the effects of oral FK506 and inhaled FK506 on antigen-induced airway inflammation in guinea pigs. The tissue and blood concentrations of FK506 given via both routes were compared. The effect of inhaled FK506 on the expression of cytokine mRNA in lung and bronchoalveolar lavage fluid (BALF) cells was also tested. Results: Both routes of administration of FK506 suppressed the airway eosinophilia in egg albumin (EA)-sensitized and -challenged animals. The effect of three inhaled puffs was almost equal to that of 1 mg/kg administered by the oral route. Following inhalation of three puffs, FK506 concentration in blood (AUC0–24 h) was approximately 1/21 of that following oral FK506 (1 mg/kg). After EA challenge, mRNA expression of interleukin (IL)-5, eotaxin and IL-1β in BALF cells and IL-5 in the lung increased significantly. FK506 aerosol markedly inhibited IL-5 mRNA expression in the lung. In situ hybridization indicated that in the BALF IL-5 mRNA expression by lymphocyte-like cells was inhibited by FK506 aerosol. In addition, anti-IL-5 antibody injected intratracheally almost completely abolished eosinophilia in this model. Conclusion: Inhaled FK506 can suppress airway inflammation in guinea pigs, where the local action, presumably the inhibition of T-cell activation/function in the lung and airways, was primarily important.
Idiopathic CD4+ Lymphocytopenia May Be due to Decreased Bone Marrow Clonogenic Capability
Authors: Isgrò Antonella , Sirianni Maria Caterina , Gramiccioni Claudia , Mezzaroma Ivano , Fantauzzi Alessandra , Aiuti Fernando
Published: March 2005

Background: Idiopathic CD4+ lymphocytopenia is defined by a stable decrease of CD4+ T cells in the absence of any known cause of immune deficiency. The mechanisms responsible for the immunological impairment are still unknown, but a regenerative failure of hematopoietic stem/progenitor cells has been hypothesized. Methods: We evaluated in the bone marrow (BM) of 5 patients with idiopathic CD4+ lymphocytopenia the phenotype of BM progenitor cells, their differentiation capacity with colony-forming cells and long-term culture-initiating cell assays, in parallel with the spontaneous IL-7 production in the patient sera. Results: Compared with controls, a regenerative failure of hematopoietic stem cells has been observed, both in ‘committed’ and in ‘uncommitted’ progenitor cells, despite high IL-7 serum levels. The percentage of phenotypically primitive CD34+CD38–DR+ cells (this includes the lymphoid precursor cells) was decreased, suggesting an involvement of the more primitive BM compartment in the de novo T cell generation. Conclusions: Despite the low number of patients, due to the low incidence of the disease, the decrease of primitive precursors sustains the possibility that diminished stem cell precursors might contribute to the development of CD4+ T cell depletion.
The Value of Interleukin-8, Interleukin-6 and Interleukin-1β in Vaginal Wash as Predictors of Preterm Delivery
Authors: González Bosquet Eduardo , Ferrer Imma , Valls Carme , Borrás Miquel , Lailla Josep M.
Published: March 2005

Aims: To study the value of interleukin (IL)-8, IL-6 and IL-1β in vaginal wash as predictors of preterm delivery. Methods: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1β, IL-6 and IL-8 concentrations. Results: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1β, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1β, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. Conclusion: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1β, IL-6 and IL-8 as a predictor clinically.
Multi-Tasking RGS Proteins in the Heart
Authors: Riddle Evan L. , Schwartzman Raúl A. , Bond Meredith , Insel Paul A.
Published: March 2005

Regulator of G-protein–signaling (RGS) proteins play a key role in the regulation of G-protein–coupled receptor (GPCR) signaling. The characteristic hallmark of RGS proteins is a conserved ≈120-aa RGS region that confers on these proteins the ability to serve as GTPase-activating proteins (GAPs) for G
α
proteins. Most RGS proteins can serve as GAPs for multiple isoforms of G
α
and therefore have the potential to influence many cellular signaling pathways. However, RGS proteins can be highly regulated and can demonstrate extreme specificity for a particular signaling pathway. RGS proteins can be regulated by altering their GAP activity or subcellular localization; such regulation is achieved by phosphorylation, palmitoylation, and interaction with protein and lipid-binding partners. Many RGS proteins have GAP-independent functions that influence GPCR and non-GPCR–mediated signaling, such as effector regulation or action as an effector. Hence, RGS proteins should be considered multifunctional signaling regulators. GPCR-mediated signaling is critical for normal function in the cardiovascular system and is currently the primary target for the pharmacological treatment of disease. Alterations in RGS protein levels, in particular RGS2 and RGS4, produce cardiovascular phenotypes. Thus, because of the importance of GPCR-signaling pathways and the profound influence of RGS proteins on these pathways, RGS proteins are regulators of cardiovascular physiology and potentially novel drug targets as well.
Kosovo: Boundaries and the Liberal Dilemma
Authors: Johanson Märta
Published: March 2005

A common position adopted by international lawyers on State borders is that they should be changed as little as possible, as allowing too much scope for changes to borders risks opening up a Pandora's box of unending claims. The liberal position on international boundaries posits that the location of a State's external boundaries matters little anyway, as the liberal State can function within any borders. The article attempts to provide a critique of these positions, and argues that another approach to borders, and particularly to boundaries at the dissolution of States, is needed. The liberal assumption does not adequately respond to boundary changes in non-liberal States. Differences between borders, and the importance attached to these differences in different contexts, have attracted little attention by international lawyers. Because the same solution often tends to lead to different results in different contexts, attempting to apply Public International Law rules, such as a modern version of uti possidetis, to boundaries in all cases of State dissolutions and new State formations, forms not only an insuf ficient response, but might in fact risk contravening obligations under the UN Charter to maintain international peace and security. The con flicts over the republican boundaries of the Socialist Federal Republic of Yugoslavia (SFRY) in the early 1990s exemplify that an automatic conversion of federal boundaries into international ones risks undermining long-term peaceful solutions. The final status of Kosovo, and the issue of its borders, remains a challenge for the international community. In light of the recent tensions in Kosovo existing territorial and political assumptions need to be reexamined, in order that the solution adopted for the territory accord with international obligations set out under the UN Charter.
Is Environmental CAPE Important in the Determination of Maximum Possible Hurricane Intensity?
Authors: Persing John , Montgomery Michael T.
Published: March 2005

In numerical simulations using an axisymmetric, cloud-resolving hurricane model, hurricane intensity shows quasi-steady-state behavior. This quasi-steady intensity is interpreted as the maximum possible intensity (MPI) of the model.

Within the literature, numerical demonstrations have confirmed theoretically anticipated influences on hurricane intensity such as sea surface temperature, outflow temperature, and surface exchange coefficients of momentum and enthalpy. Here these investigations are extended by considering the role of environmental convective available potential energy (CAPE) on hurricane intensity. It is found that environmental CAPE (independent of changes to the outflow level) has no significant influence on numerically simulated maximum hurricane intensity. Within this framework, MPI theories that are sensitive to environmental CAPE should be discarded.
Atmospheric Stability in a Generalized Barotropic Model
Authors: Mitas Christos M. , Robinson Walter A.
Published: March 2005

An empirical modification of conventional barotropic dynamics is implemented to study the low-frequency variability (LFV) of the upper troposphere. Using the conservation of potential vorticity, generalized spectral barotropic operators that apply at single isentropic levels are constructed. In initial value calculations the empirical model shows improvement in skill compared to the conventional barotropic model, but it does not do significantly better than persistence. For short times, however, the empirically modified model shows a much closer resemblance to the observed streamfunction tendency. Overall, it is a significantly more accurate representation of the atmosphere than the conventional barotropic model.

Normal, optimal, and singular modes of the modified model are calculated. The modes of the empirically modified model are more stable and more difficult to excite than those of the barotropic model. These results are consistent with previous studies that found barotropic dynamics deficient for the quantitative description of LFV. The singular modes of the modified operator have very similar patterns but explain less variance than those of the barotropic operator, which is consistent with the difficulty in detecting optimal patterns in observations. The modified barotropic operator is also more normal than the barotropic operator, and thus less variable.
A Parameterization of the Effective Layer Emission for Infrared Radiation Calculations
Authors: Chou Ming-Dah , Lee Kyu-Tae
Published: March 2005

The impact of the vertical integration of radiative transfer on cooling rate calculations is studied for different numerical schemes. One involves the effective emitting temperature of a layer (scheme A), and the other involves temperatures at the interface between layers (scheme B). It is found that when there are large variations of temperature and humidity in the lower troposphere, the cooling rate profiles computed with the different schemes exhibit little resemblance. When the mean layer temperature is used for the effective emitting temperature (scheme A2), the cooling rate oscillates greatly from one layer to the next. On the other hand, the cooling rate computed with scheme B varies very little with height even for the case with large vertical variations of temperature and humidity. The reason for the large cooling rate oscillation in scheme A2 is due to the use of a single effective emitting temperature for both upward and downward fluxes, which is true only for an isothermal layer. The overly smoothed cooling profile for scheme B is caused by the interpolation of level temperatures from layer temperatures. The interpolation has a smoothing effect on the vertical distribution of temperature and, hence, cooling rate.

The transmission function averaged over a spectral band decreases exponentially with the square root of absorber amount. Based on this relationship, the effective emitting temperature of a layer is parameterized separately for computing upward and downward fluxes (scheme A1). Using the parameterization, the large oscillation of the cooling rate profile of scheme A2 is substantially reduced, while the problem of overly smoothing when using scheme B is eliminated. In addition, to be more accurate, the speed of computation using scheme A2 is higher than that using scheme B.
Shear Instability Wave along a Snowband: Instability Structure, Evolution, and Energetics Derived from Dual-Doppler Radar Data
Authors: Kawashima Masayuki , Fujiyoshi Yasushi
Published: March 2005

This article presents a detailed analysis of a meso-γ-scale (∼17 km wavelength) shear instability wave along a snowband using a series of dual-Doppler radar data. The wave developed along a low-level shear line that formed under the strain wind field caused by an adjacent mesoscale vortex. The horizontal wind shear across the line was largest at lower levels, and the eddy-component horizontal winds and the retrieved pressure anomaly showed a bottom-intensified structure as well. The resultant vertical pressure gradient force was found to be responsible for the enhancement of alternating updrafts and downdrafts that were subsequently related to the formation of the reflectivity core/gap structure of the wave.

Eddy kinetic energy (EKE) budgets of the evolving disturbance were investigated using time series of retrieved kinematic and thermodynamic data. The wave grew at an approximately constant growth rate for about 40 min from its onset. The EKE in this quasi-linear growth period was primarily generated by the horizontal shear that decreased with height. The pressure work was found to remove about two-thirds of this generation in the layer below 1 km, while in the upper layer it was constructive to EKE generation and comparable to the generation of EKE by horizontal shear. These results indicate that the source of EKE was basically located at low levels and the energy was transported upward mainly by the pressure work. After the quasi-linear growth period, horizontal shear generation rapidly decreased and EKE peaked. The buoyancy generation of EKE was small but positive in the quasi-linear growth period, then became negative because of the development of thermally indirect circulations.
Holes and Entrainment in Stratocumulus
Authors: Gerber H. , Frick G. , Malinowski S. P. , Brenguier J-L. , Burnet F.
Published: March 2005

Aircraft flights through stratocumulus clouds (Sc) during the Dynamics and Chemistry of Marine Stratocumulus II (DYCOMS-II) study off the California coast found narrow in-cloud regions with less liquid water content (LWC) and cooler temperatures than average background values. The regions are named cloud holes and are assumed to be a result of water evaporated by the entrainment of dryer air from above the Sc. While such features have been noted previously, this study provided a unique opportunity to investigate in much greater detail the nature of the holes, as well as their relationship to the entrainment rate, because high-speed temperature and LWC probes with maximum spatial resolution of 10 cm were flown together for the first time. Nine long-duration flights were made through mostly unbroken Sc for which conditional sampling was used to identify the location and size of the holes. The holes are concentrated near cloud top, their average width near cloud top is about 5 m, their relative length distribution is nearly constant for all flights, and they can penetrate hundreds of meters deep into the Sc before being lost by mixing. Entrainment velocities at cloud top are estimated from measurements of fluxes of reduced LWC and vapor mixing ratios in holes, the fraction of cloud area covered by holes, and the total water jump between cloud top and the free atmosphere. Rates as large as 10 mm s−1 are found for nocturnal flights, and these rates are about 3 times larger than for daytime flight segments. The rates correlate best with the size of the buoyancy jump above the Sc; the present conditional-sampling approach for measuring the rates gives larger rates than the “flux jump” rates determined by others for the same flights by a factor of about 2. The stability criterion for all Sc predicts thinning and breakup of the Sc, which does not occur. The minimal amount of cloud-top evaporative cooling caused by entrainment contributes little to the top-down convection dominated by radiative cooling during nocturnal flights; however, evaporative cooling caused by the mixing of holes as they subduct with the large-scale eddy circulation in the Sc may contribute, but with an as-of-yet unknown amount.
Prevalence of Co-Occurring Disorders Among Juveniles Committed to Detention Centers
Authors: Abrantes Ana M. , Hoffmann Norman G. , Anton Ronald
Published: March 2005

The Practical Adolescent Diagnostic Interview (PADDI), a structured diagnostic interview designed to gather basic information about substance use disorders, mental health conditions, and related experiences, was used in routine evaluation of all adolescents committed to two juvenile detention centers. Anonymous data from 252 consecutively admitted adolescents were analyzed to assess the prevalence and severity of problem areas and to provide a preliminary exploration of interrelationships among those problems. Results demonstrated that a majority of adolescents manifested multiple problems. Whereas prevalence rates were high across gender, females displayed significantly greater mental health problems and maltreatment histories.
The Function of Self-Harm Behavior in a Forensic Population
Authors: Jeglic Elizabeth L. , Vanderhoff Holly A. , Donovick Peter J.
Published: March 2005

This article examines the functions of self-injurious behavior (SIB) in forensic populations. The cases of four individual offenders who have engaged in SIB are presented. These cases depict the four main functions of self-harm behaviors including (a) suicidal intent, (b) manipulation of the environment, (c) emotion regulation, and (d) a response to psychotic delusions or hallucinations. Assessment and treatment implications are discussed.
The Impact of Sex Offender Residence Restrictions: 1,000 Feet From Danger or One Step From Absurd?
Authors: Levenson Jill S. , Cotter Leo P.
Published: March 2005

Several states have enacted public policies that prohibit sex offenders who have abused children from living within close proximity to a school, park, day care center, or school bus stop. The purpose of this exploratory study was to describe the impact of residence restrictions on sex offender reintegration and to better understand sex offenders' perceptions of these laws. A survey of 135 sex offenders in Florida was conducted. Most of the molesters who responded to the survey indicated that housing restrictions increased isolation, created financial and emotional stress, and led to decreased stability. Respondents also indicated that they did not perceive residence restrictions as helpful in risk management and, in fact, reported that such restrictions may inadvertently increase triggers for reoffense. Implications for policy and practice are discussed.
Exocytosis and Endocytosis of Synaptic Vesicles and Functional Roles of Vesicle Pools: Lessons from the Drosophila Neuromuscular Junction
Authors: Kuromi Hiroshi , Kidokoro Yoshiaki
Published: March 2005

To maintain synaptic transmission during intense neuronal activities, the synaptic vesicle (SV) pool at release sites is effectively replenished by recruitment of SVs from the reserve pool and/or by endocytosis. The authors have studied dynamics of SVs using a fluorescence dye, FM1-43, which is incorporated into SVs during endocytosis and released by exocytosis. Drosophila is one of the most suitable preparations for genetic and pharmacological analyses, and this provides a useful model system. The authors found at the neuromuscular junctions of Drosophila that exocytosis and endocytosis of SVs are triggered by Ca2+ influx through distinct routes and that selective inhibition of exocytosis or endocytosis resulted in depression of synaptic transmission with a distinct time course. They identified two SV pools in a single presynaptic bouton. The exo/endo cycling pool (ECP) is loaded with FM1-43 during low-frequency stimulation and locates close to release sites in the periphery of boutons, whereas the reserve pool (RP) is loaded and unloaded only during high-frequency stimulation and resides primarily in the center of boutons. The size of ECP closely correlates with the quantal content of evoked release, suggesting that SVs in the ECP are primarily involved in synaptic transmission. SVs in the RP are recruited to synaptic transmission by a process involving the cAMP/PKA cascade during high-frequency stimulation. Cytochalasin D blocked this recruitment process, suggesting involvement of filamentous actin. Endocytosed SVs replenish the ECP during stimulation and the RP after tetanic stimulation. Replenishment of the ECP depends on Ca2+ influx from external solutions, and that of the RP is initiated by Ca2+ release from internal stores. Thus, SV dynamics is closely involved in modulation of synaptic efficacy and influences synaptic plasticity.
The Development of Branch Libraries in Leicester
Authors: Fox Rachel , Feather John
Published: March 2005

The public library system developed slowly in Leicester and encountered much opposition before it began. With the eventual success of its central library, the establishment of branch libraries was mooted. Despite the failure of the very first branch, subsequent branches were successful and answered a very definite need for localized provision of public library services at a time when the central library was inadequate to cope with a rapid growth in demand.
Manchester and Liverpool: (1) the Manchester Free Library, And (2) George Chandler, Librarian
Authors: Glasgow Eric
Published: March 2005

The first of these papers looks again at the opening of Manchester's first public library in 1852, and the celebrities who attended. Though the library was intended for the working classes, the latter had no role to play at the occasion. Secondly, a sketch is provided of the career of George Chandler, chief librarian of Liverpool's public libraries between 1952 and 1974.
PHACCS, an online tool for estimating the structure and diversity of uncultured viral communities using metagenomic information
Authors: Angly Florent , Rodriguez-Brito Beltran , Bangor David , McNairnie Pat , Breitbart Mya , Salamon Peter , Felts Ben , Nulton James , Mahaffy Joseph , Rohwer Forest
Published: March 2005

Background

Phages, viruses that infect prokaryotes, are the most abundant microbes in the world. A major limitation to studying these viruses is the difficulty of cultivating the appropriate prokaryotic hosts. One way around this limitation is to directly clone and sequence shotgun libraries of uncultured viral communities (i.e., metagenomic analyses). PHACCS http://phage.sdsu.edu/phaccs, Phage Communities from Contig Spectrum, is an online bioinformatic tool to assess the biodiversity of uncultured viral communities. PHACCS uses the contig spectrum from shotgun DNA sequence assemblies to mathematically model the structure of viral communities and make predictions about diversity.

Results

PHACCS builds models of possible community structure using a modified Lander-Waterman algorithm to predict the underlying contig spectrum. PHACCS finds the most appropriate structure model by optimizing the model parameters until the predicted contig spectrum is as close as possible to the experimental one. This model is the basis for making estimates of uncultured viral community richness, evenness, diversity index and abundance of the most abundant genotype.

Conclusion

PHACCS analysis of four different environmental phage communities suggests that the power law is an important rank-abundance form to describe uncultured viral community structure. The estimates support the fact that the four phage communities were extremely diverse and that phage community biodiversity and structure may be correlated with that of their hosts.
Using equilibrium frequencies in models of sequence evolution
Authors: Knudsen Bjarne , Miyamoto Michael M
Published: March 2005

Background

The f factor is a new parameter for accommodating the influence of both the starting and ending states in the rate matrices of "generalized weighted frequencies" (+gwF) models for sequence evolution. In this study, we derive an expected value for f, starting from a nearly neutral model of weak selection, and then assess the biological interpretation of this factor with evolutionary simulations.

Results

An expected value of f = 0.5 (i.e., equal dependency on the starting and ending states) is derived for sequences that are evolving under the nearly neutral model of this study. However, this expectation is sensitive to violations of its underlying assumptions as illustrated with the evolutionary simulations.

Conclusion

This study illustrates how selection, drift, and mutation at the population level can be linked to the rate matrices of models for sequence evolution to derive an expected value of f. However, as f is affected by a number of factors that limit its biological interpretation, this factor should normally be estimated as a free parameter rather than fixed a priori in a +gwF analysis.
Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1
Authors: Karavasilis Vasilis , Malamou-Mitsi Vasiliki , Briasoulis Evangelos , Tsanou Elena , Kitsou Evangelia , Kalofonos Haralambos , Fountzilas George , Fotsis Theodore , Pavlidis Nicholas
Published: March 2005

Background

Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets.

Methods

Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data.

Results

VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1.

Conclusion

Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.
Orientation determination by wavelets matching for 3D reconstruction of very noisy electron microscopic virus images
Authors: Saad Ali Samir
Published: March 2005

Background

In order to perform a 3D reconstruction of electron microscopic images of viruses, it is necessary to determine the orientation (Euler angels) of the 2D projections of the virus. The projections containing high resolution information are usually very noisy. This paper proposes a new method, based on weighted-projection matching in wavelet space for virus orientation determination. In order to speed the retrieval of the best match between projections from a model and real virus particle, a hierarchical correlation matching method is also proposed.

Results

A data set of 600 HSV-1 capsid particle images in different orientations was used to test the proposed method. An initial model of about 40 Å resolutions was used to generate projections of an HSV-1 capsid. Results show that a significant improvement, in terms of accuracy and speed, is obtained for the initial orientation estimates of noisy herpes virus images. For the bacteriophage (P22), the proposed method gave the correct reconstruction compared to the model, while the classical method failed to resolve the correct orientations of the smooth spherical P22 viruses.

Conclusion

This paper introduces a new method for orientation determination of low contrast images and highly noisy virus particles. This method is based on weighted projection matching in wavelet space, which increases the accuracy of the orientations. A hierarchical implementation of this method increases the speed of orientation determination. The estimated number of particles needed for a higher resolution reconstruction increased exponentially. For a 6 Å resolution reconstruction of the HSV virus, 50,000 particles are necessary. The results show that the proposed method reduces the amount of data needed in a reconstruction by at least 50 %. This may result in savings 2 to 3 man-years invested in acquiring images from the microscope and data processing. Furthermore, the proposed method is able to determine orientations for some difficult particles like P22 with accuracy and consistency. Recently a low PH sindbis capsid was determined with the proposed method, where other methods based on the common line fail.
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial
Authors: Escudier Bernard , Dorval Thierry , Chaput Nathalie , André Fabrice , Caby Marie-Pierre , Novault Sophie , Flament Caroline , Leboulaire Christophe , Borg Christophe , Amigorena Sebastian , Boccaccio Catherine , Bonnerot Christian , Dhellin Olivier , Movassagh Mojgan , Piperno Sophie , Robert Caroline , Serra Vincent , Valente Nancy , Le Pecq Jean-Bernard , Spatz Alain , Lantz Olivier , Tursz Thomas , Angevin Eric , Zitvogel Laurence
Published: March 2005

Background

DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome.

Patients and methods

Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression.

Results

The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood.

Conclusion

The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.
New York City HIV superbug: fear or fear not?
Authors: Smith Stephen M
Published: March 2005

On February 11, 2005, the New York City Department of Health and Mental Hygiene announced that a city resident had recently been infected with a multi-drug resistant form of HIV and rapidly progressed to AIDS. The Health Commissioner, Thomas R. Frieden, called for increased vigilance against this new strain. Is this situation an emerging crisis or simply an unusual case report of rapid HIV progression?
Retrovirology highlights a quarter century of HTLV-I research
Authors: Jeang Kuan-Teh
Published: March 2005

In 1977, Takatsuki and co-workers described in Japan a human malignant disease termed adult T-cell leukemia (ATL). Three years later, in 1980, Gallo and colleagues reported the identification of the first human retrovirus, human T-cell leukemia virus type I (HTLV-I), in a patient with cutaneous T-cell lymphoma. This month, Retrovirology commemorates these two land mark findings by publishing separate personal recollections by Takatsuki and Gallo respectively on the discovery of ATL and HTLV.
Dengue fever: new paradigms for a changing epidemiology
Authors: Guha-Sapir Debarati , Schimmer Barbara
Published: March 2005

Dengue is the most important arthropod-borne viral disease of public health significance. Compared with nine reporting countries in the 1950s, today the geographic distribution includes more than 100 countries worldwide. Many of these had not reported dengue for 20 or more years and several have no known history of the disease. The World Health Organization estimates that more than 2.5 billion people are at risk of dengue infection. First recognised in the 1950s, it has become a leading cause of child mortality in several Asian and South American countries.

This paper reviews the changing epidemiology of the disease, focusing on host and societal factors and drawing on national and regional journals as well as international publications. It does not include vaccine and vector issues. We have selected areas where the literature raises challenges to prevailing views and those that are key for improved service delivery in poor countries.

Shifts in modal age, rural spread, and social and biological determinants of race- and sex-related susceptibility have major implications for health services. Behavioural risk factors, individual determinants of outcome and leading indicators of severe illness are poorly understood, compromising effectiveness of control programmes. Early detection and case management practices were noted as a critical factor for survival. Inadequacy of sound statistical methods compromised conclusions on case fatality or disease-specific mortality rates, especially since the data were often based on hospitalised patients who actively sought care in tertiary centres.

Well-targeted operational research, such as population-based epidemiological studies with clear operational objectives, is urgently needed to make progress in control and prevention.
Reconsidering Evolved Sex Differences in Jealousy: Comment on Harris (2003)
Authors: Sagarin Brad J.
Published: March 2005

In a recent article, Harris (2003) concluded that the data do not support the existence of evolved sex differences in jealousy. Harris' review correctly identifies fatal flaws in three lines of evidence (spousal abuse, homicide, morbid jealousy), but her criticism of two other lines of evidence (self-report responses, psychophysiological measures) is based, in part, on a mischaracterization of the evolutionary psychological theory and a misunderstanding of the empirical implications of the theory. When interpreted according to the correct criterion (i.e., an interaction between sex and infidelity type), self-report studies (both forced-choice and non-forced choice) offer strong support for the existence of sex differences in jealousy. Psychophysiological data also offer some support, although these data are weakened by validity-related concerns. In addition, some refutational evidence cited by Harris (responses to real infidelity, responses under cognitive load) actually does not refute the theory. An integrative model that describes how jealousy might result from the interaction of sociocultural variables and evolved sex differences and suggestions for future research directions are discussed.
NF-κB signalling regulates the growth of neural processes in the developing PNS and CNS
Authors: Gutierrez Humberto , Hale Valerie A. , Dolcet Xavier , Davies Alun
Published: March 2005

The proper growth and elaboration of neural processes is essential for the establishment of a functional nervous system during development and is an integral feature of neural plasticity throughout life. Nuclear factor-kappa B(NF-κB) is classically known for its ubiquitous roles in inflammation,immune and stress-related responses and regulation of cell survival in all tissues, including the nervous system. NF-κB participation in other cellular processes remains poorly understood. Here we report a mechanism for controlling the growth of neural processes in developing peripheral and central neurons involving the transcription factor NF-κB. Inhibiting NF-κB activation with super-repressor IκB-α, BAY 11 7082(IκB-α phosphorylation inhibitor) or N-acetyl-Leu-Leu-norleucinal(proteosomal degradation inhibitor), or inhibiting NF-κB transcriptional activity with κB decoy DNA substantially reduced the size and complexity of the neurite arbors of sensory neurons cultured with brain-derived neurotrophic factor while having no effect on their survival. NF-κB exerted this effect during a restricted period of development following the phase of naturally occurring neuronal death when the processes and connections of the remaining neurons are extensively modified and refined. Inhibiting NF-κB activation or NF-κB transcriptional activity in layer 2 pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic arbor size and complexity. This function of NF-κB has important implications for neural development and may provide an explanation for reported involvement of NF-κB in learning and memory.
VAN3 ARF–GAP-mediated vesicle transport is involved in leaf vascular network formation
Authors: Koizumi Koji , Naramoto Satoshi , Sawa Shinichiro , Yahara Natsuko , Ueda Takashi , Nakano Akihiko , Sugiyama Munetaka , Fukuda Hiroo
Published: March 2005

Within the leaf of an angiosperm, the vascular system is constructed in a complex network pattern called venation. The formation of this vein pattern has been widely studied as a paradigm of tissue pattern formation in plants. To elucidate the molecular mechanism controlling the vein patterning process,we previously isolated Arabidopsis mutants van1 to van7, which show a discontinuous vein pattern. Here we report the phenotypic analysis of the van3 mutant in relation to auxin signaling and polar transport, and the molecular characterization of the VAN3 gene and protein. Double mutant analyses with pin1, emb30-7/gn and mp, and physiological analyses using the auxin-inducible marker DR5::GUS and an auxin transport inhibitor indicated that VAN3 may be involved in auxin signal transduction, but not in polar auxin transport. Positional cloning identified VAN3 as a gene that encodes an adenosine diphosphate (ADP)-ribosylation factor-guanosine triphosphatase (GTPase) activating protein (ARF–GAP). It resembles animal ACAPs and contains four domains: a BAR(BIN/amphiphysin/RVS) domain, a pleckstrin homology (PH) domain, an ARF–GAP domain and an ankyrin (ANK)-repeat domain. Recombinant VAN3 protein showed GTPase-activating activity and a specific affinity for phosphatidylinositols. This protein can self-associate through the N-terminal BAR domain in the yeast two-hybrid system. Subcellular localization analysis by double staining for Venus-tagged VAN3 and several green-fluorescent-protein-tagged intracellular markers indicated that VAN3 is located in a subpopulation of the trans-Golgi network (TGN). Our results indicate that the expression of this gene is induced by auxin and positively regulated by VAN3 itself, and that a specific ACAP type of ARF–GAP functions in vein pattern formation by regulating auxin signaling via a TGN-mediated vesicle transport system.