bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass balance of the Antarctic ice sheet
Authors: Wingham D.J , Shepherd A , Muir A , Marshall G.J
Published: May 2006

The Antarctic contribution to sea-level rise has long been uncertain. While regional variability in ice dynamics has been revealed, a picture of mass changes throughout the continental ice sheet is lacking. Here, we use satellite radar altimetry to measure the elevation change of 72% of the grounded ice sheet during the period 1992–2003. Depending on the density of the snow giving rise to the observed elevation fluctuations, the ice sheet mass trend falls in the range −5–+85 Gt yr
−1
. We find that data from climate model reanalyses are not able to characterise the contemporary snowfall fluctuation with useful accuracy and our best estimate of the overall mass trend—growth of 27±29 Gt yr
−1
—is based on an assessment of the expected snowfall variability. Mass gains from accumulating snow, particularly on the Antarctic Peninsula and within East Antarctica, exceed the ice dynamic mass loss from West Antarctica. The result exacerbates the difficulty of explaining twentieth century sea-level rise.
Recent trends in Antarctic snow accumulation from Polar MM5 simulations
Authors: Monaghan Andrew J , Bromwich David H , Wang Sheng-Hung
Published: May 2006

Polar MM5, a mesoscale atmospheric model optimized for use over polar ice sheets, is employed to simulate Antarctic accumulation in recent decades. Two sets of simulations, each with different initial and boundary conditions, are evaluated for the 17 yr period spanning 1985–2001. The initial and boundary conditions for the two sets of runs are provided by the (i) European Centre for Medium-Range Weather Forecasts 40 year Reanalysis, and (ii) National Centres for Environmental Prediction—Department of Energy Atmospheric Model Intercomparison Project Reanalysis II. This approach is used so that uncertainty can be assessed by comparing the two resulting datasets.

There is broad agreement between the two datasets for the annual precipitation trends for 1985–2001. These generally agree with ice core and snow stake accumulation records at various locations around the continent, indicating broad areas of both upward and downward trends. Averaged over the continent the annual trends are small and not statistically different from zero, suggesting that recent Antarctic snowfall changes do not mitigate current sea-level rise. However, this result does not suggest that Antarctica is isolated from the recent climate changes occurring elsewhere on Earth. Rather, these are expressed by strong seasonal and regional precipitation changes.
Ice-sheet contributions to future sea-level change
Authors: Gregory J.M , Huybrechts P
Published: May 2006

Accurate simulation of ice-sheet surface mass balance requires higher spatial resolution than is afforded by typical atmosphere–ocean general circulation models (AOGCMs), owing, in particular, to the need to resolve the narrow and steep margins where the majority of precipitation and ablation occurs. We have developed a method for calculating mass-balance changes by combining ice-sheet average time-series from AOGCM projections for future centuries, both with information from high-resolution climate models run for short periods and with a 20 km ice-sheet mass-balance model. Antarctica contributes negatively to sea level on account of increased accumulation, while Greenland contributes positively because ablation increases more rapidly. The uncertainty in the results is about 20% for Antarctica and 35% for Greenland. Changes in ice-sheet topography and dynamics are not included, but we discuss their possible effects. For an annual- and area-average warming exceeding

in Greenland and

in the global average, the net surface mass balance of the Greenland ice sheet becomes negative, in which case it is likely that the ice sheet would eventually be eliminated, raising global-average sea level by 7 m.
Integrating satellite observations with modelling: basal shear stress of the Filcher-Ronne ice streams, Antarctica
Authors: Joughin Ian , Bamber Jonathan L , Scambos Ted , Tulaczyk Slawek , Fahnestock Mark , MacAyeal Douglas R
Published: May 2006

Using inverse methods constrained by recent satellite observations, we have produced a comprehensive estimate of the basal shear stress beneath the Filchner-Ronne ice streams. The inversions indicate that a weak bed (approx. 4–20 kPa) underlies much of these ice streams. Compared to the Ross ice streams, the distribution of weak subglacial till is more heterogeneous, with ‘sticky spots’ providing much of the resistance to flow. A weak bed beneath Recovery ice stream extends several hundred kilometres inland with flow. Along this ice stream, discrepancies between thickness measurements and flux estimates suggest the existence of a deep (−1400 m) trough not resolved by existing maps of subglacial topography. We hypothesize that the presence of this and other deep troughs is a major influence on this sector of the ice sheet that is not fully incorporated in current models of ice-sheet evolution.
Evolution of the Antarctic ice sheet: new understanding and challenges
Authors: Payne Antony J , Hunt Julian C.R , Wingham Duncan J
Published: May 2006

This brief paper has two purposes. First, we gauge developments in the study of the Antarctic ice sheet over the last seven years by comparing the contents of this issue with the volume produced from an American Geophysical Union meeting, held in September 1998, on the West Antarctic ice sheet. We focus on the uptake of satellite-based observation; ice–ocean interactions; ice streams as foci of change within the ice sheet; and the time scales on which the ice sheet is thought to operate. Second, we attempt to anticipate the future challenges that the study of the Antarctic ice sheet will present.

We highlight the role of the upcoming International Polar Year in facilitating a better coverage of
in situ
climatic observations over the continent; the pressing need to understand the causes and consequences of the contemporary changes observed in the Amundsen Sea sector of West Antarctica; and the need for improved physics in predictive models of the ice sheet.
The oxygenation of the atmosphere and oceans
Authors: Holland Heinrich D
Published: May 2006

The last 3.85 Gyr of Earth history have been divided into five stages. During stage 1 (3.85–2.45 Gyr ago (Ga)) the atmosphere was largely or entirely anoxic, as were the oceans, with the possible exception of oxygen oases in the shallow oceans.

During stage 2 (2.45–1.85 Ga) atmospheric oxygen levels rose to values estimated to have been between 0.02 and 0.04 atm. The shallow oceans became mildly oxygenated, while the deep oceans continued anoxic.

Stage 3 (1.85–0.85 Ga) was apparently rather ‘boring’. Atmospheric oxygen levels did not change significantly. Most of the surface oceans were mildly oxygenated, as were the deep oceans.

Stage 4 (0.85–0.54 Ga) saw a rise in atmospheric oxygen to values not much less than 0.2 atm. The shallow oceans followed suit, but the deep oceans were anoxic, at least during the intense Neoproterozoic ice ages. Atmospheric oxygen levels during stage 5 (0.54 Ga–present) probably rose to a maximum value ofca0.3 atm during the Carboniferous before returning to its present value. The shallow oceans were oxygenated, while the oxygenation of the deep oceans fluctuated considerably, perhaps on rather geologically short time-scales.
Measuring the burden of major cancers due to smoking in Korea
Authors: Lee Heeyoung , Yoon Seok‐Jun , Ahn Hyeong‐Sik
Published: May 2006

Morbidity and mortality are classically used to measure disease burden. However, the allocation of limited health‐care resources demands an agreed rational allocation principle and, consequently, the setting of priorities is of considerable importance. We collected data from the national death certificate database, and the national health insurance claim database and life tables. Using this data, we calculated disability adjusted life year (DALY) and health life year (HeaLY) values for smoking‐related cancer. The burden of cancer due to smoking was estimated by multiplying the population attributable risk due to smoking by the DALY and HeaLY results for cancers. The burden of cancer due to smoking for Korean men was 1930.1 person‐years by DALY and 1681.3 person‐years by HeaLY per 100 000 people. Similarly, the burden of cancer due to smoking for Korean women was 352.6 person‐years for DALY and 313.6 person‐years for HeaLY per 100 000 people. Priority rankings for cancer burden due to smoking was somewhat different by DALY and HeaLY. The largest health gap for men was stomach cancer by DALY and lung cancer by HeaLY, whereas for women it was lung cancer by both methods. This study provides a rational basis for national cancer policy planning by presenting the priority burden of cancers caused by smoking. (Cancer Sci 2006; 97: 530 – 534)
Genetic polymorphisms of glutathione S‐transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta‐analysis
Authors: Saadat Mostafa
Published: May 2006

The association between glutathione S‐transferase T1 (GSTT1) polymorphism and gastric cancer risk has been both confirmed and refuted in a number of published studies. Most of these studies were based on small sample sizes. We carried out a meta‐analysis of the research published up to August 2005 to obtain more precise estimates of gastric cancer risk associated with GSTT1 polymorphism. In the present study, 16 case‐control studies (with a total of 6717 subjects) were eligible for meta‐analysis. There was no evidence of heterogeneity between the studies. The GSTT1 null genotype conferred a 1.06‐fold increased risk of gastric cancer, which was not significant (95% confidence interval [CI]: 0.94–1.19). However, in the analysis of ethnic groups, we observed distinct differences associated with GSTT1 status. Restricting analyses to ethnic groups, the pooled odd ratios for the GSTT1 genotype were 1.27 in Caucasians (95% CI: 1.03–1.57) and 0.98 in Asians (95% CI: 0.86–1.13). Glutathione S‐transferase M1 (GSTM1) and GSTT1 are involved in detoxification of a variety of compounds, some that overlap between enzymes and some that are highly specific. To investigate whether the profile of glutathione S‐transferase genotypes was associated with risk of gastric cancer, further analyses combining the GSTT1 and GSTM1 genotypes were also carried out. There was a significant trend in risk associated with zero, one and two putative high‐risk genotypes (χ2 = 9.326, d.f. = 1, P = 0.0023). Those who had null genotypes of GSTM1 and GSTT1 had an increased gastric cancer risk compared with those who had both active genes (odds ratio = 2.08, 95% CI: 1.42–3.10). (Cancer Sci 2006; 97: 505–509)
Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy
Authors: Szatmári Tünde , Lumniczky Katalin , Désaknai Szilvia , Trajcevski Stéphane , Hídvégi Egon J. , Hamada Hirofumi , Sáfrány Géza
Published: May 2006

Mouse glioma 261 (Gl261) cells are used frequently in experimental glioblastoma therapy; however, no detailed description of the Gl261 tumor model is available. Here we present that Gl261 cells carry point mutations in the K‐ras and p53 genes. Basal major histocompatibility complex (MHC)I, but not MHCII, expression was detected in Gl261 cells. The introduction of interferon‐γ‐encoding genes increased expression of both MHCI and MHCII. A low amount of B7‐1 and B7‐2 RNA was detected in wild‐type cells, but cytokine production did not change expression levels. Gl261 cells were transduced efficiently by adenoviral vectors; the infectivity of retroviral vectors was limited. Low numbers of transplanted Gl261 cells formed both subcutaneous and intracranial tumors in C57BL/6 mice. The cells were moderately immunogenic: prevaccination of mice with irradiated tumor cells 7 days before intracranial tumor challenge prevented tumor formation in approximately 90% of mice. When vaccination was carried out on the day or 3 days after tumor challenge, no surviving animals could be found. In vitro‐growing cells were radiosensitive: less than 2 Gy was required to achieve 50% cell mortality. Local tumor irradiation with 4 Gy X‐rays in brain tumor‐bearing mice slowed down tumor progression, but none of the mice were cured off the tumor. In conclusion, the Gl261 brain tumor model might be efficiently used to study the antitumor effects of various therapeutic modalities, but the moderate immunogenicity of the cells should be considered. (Cancer Sci 2006; 97: 546 – 553)
Possible tumor development from double positive foci for TGF‐alpha and GST‐P observed in early stages on rat hepatocarcinogenesis
Authors: Kitano Mitsuaki , Wada Jutaro , Ariki Yutaka , Kato Masanori , Wanibuchi Hideki , Morimura Keiichirou , Hidaka Takayoshi , Hosoe Kazunori , Fukushima Shoji
Published: May 2006

Expression of TGF‐α during promotion of neoplastic development from GST‐P‐positive foci in rat chemical hepatocarcinogenesis was investigated. One‐hundred male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg bodyweight) and subjected to two‐thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0 or 500 p.p.m. was fed to the rats for 46 weeks. Groups of 10 rats were killed at weeks 4, 8, 16, 32, 48 and their livers were immunohistochemically examined for expression of GST‐P and TGF‐α. TGF‐α‐positive foci and single positive cells were observed from week 4, partially overlapping with GST‐P‐positive foci but being much fewer. Numbers of TGF‐α‐positive lesions did not increase from weeks 4–48, but their areas showed increment at weeks 32 and 48, especially with PB administration. Almost all of the tumors observed at weeks 16, 32 and 48 were positive for TGF‐α (98%). In addition, epidermal growth factor receptor overexpression was observed in most TGF‐α‐positive lesions (foci and tumors). The proliferating cell nuclear antigen labeling index in double positive foci for GST‐P and TGF‐α was significantly higher than that in TGF‐α‐negative foci. In conclusion, TGF‐α may be closely related with promotion from altered foci to neoplasms in rat hepatocarcinogenesis. Our data suggest that double positive foci for GST‐P and TGF‐α in the early stages of rat hepatocarcinogenesis may develop into tumors with promotion. (Cancer Sci 2006; 97: 478 – 483)
Human T‐cell lymphotropic virus type‐1 infection and risk of cancer: 15.4 year longitudinal study among atomic bomb survivors in Nagasaki, Japan
Authors: Arisawa Kokichi , Soda Midori , Akahoshi Masazumi , Fujiwara Saeko , Uemura Hirokazu , Hiyoshi Mineyoshi , Takeda Hideo , Kashino Wataru , Suyama Akihiko
Published: May 2006

The objective of the present study was to investigate the association between human T‐lymphotropic virus type‐1 (HTLV‐1) infection and cancer risk in a longitudinal study. The study population consisted of 2729 atomic bomb survivors in Nagasaki Prefecture, Japan, who had no previous history of cancer at baseline. The baseline survey, including analysis of antibody to HTLV‐1, took place during 1985–1987 and follow‐up was performed until the end of 2001. There were 553 incident cases of malignant neoplasms during the observation period. After adjustment for sex, age and other variables, HTLV‐1 infection was not associated with the risk of developing cancers of all sites, excluding adult T‐cell leukemia (rate ratio 1.0, 95% confidence interval [CI] 0.76–1.4), stomach, colon and rectum, lung, female breast or other minor sites, but was associated with increased risk of liver cancer (rate ratio 2.1, 95%CI 1.0–4.6). The point estimate of the rate ratio for thyroid cancer was 3.0, but this was not significantly higher than 1 because of the small number of events (n = 11) and low prevalence of HTLV‐1 seropositivity. These findings support the idea that HTLV‐1 infection is not associated with an increased general cancer risk. Confounding by hepatitis C virus (HCV) and the interaction between HTLV‐1 and HCV may explain the increased risk of liver cancer among HTLV‐1 carriers. Further follow‐up may be required to determine if HTLV‐1 carriers are at increased risk of thyroid cancer. (Cancer Sci 2006; 97: 535– 539)
Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone–releasing hormone agonist
Authors: Said Mahmoud M. , Hokaiwado Naomi , Tang Mingxi , Ogawa Kumiko , Suzuki Shugo , Ghanem Hala M. , Esmat Amr Y. , Asamoto Makoto , Refaie Fawzia M. , Shirai Tomoyuki
Published: May 2006

The effects of leuprorelin acetate, a luteinizing hormone‐releasing hormone agonist (LHRH‐A), on prostate carcinogenesis in probasin/SV40 Tag transgenic rat was investigated. Fifteen weeks after administration of 0.28 and 2.8 mg/kg leuprorelin, prostate weights and serum testosterone levels were significantly decreased compared to values for transgenic controls. Histopathological findings revealed that the incidence of prostatic adenocarcinomas was significantly reduced in ventral, dorsal and lateral lobes of the prostate, correlating with decreased expression of SV40 Tag oncoprotein as well as inhibition of DNA synthesis and proliferation of epithelial cells in neoplastic lesions of the ventral prostate. Microarray analysis further showed leuprorelin acetate to significantly inhibit testicular steroidogenesis, suppressing the expression of SV40 Tag oncoprotein and altering the expression of a large number of genes which might be involved in the inhibition of prostate cancer progression in this rat model. (Cancer Sci 2006; 97: 459–467)
A model‐based approach to treatment comparison in acute migraine
Authors: Maas Hugo J. , Danhof Meindert , Della Pasqua Oscar
Published: May 2006

Aims

Currently, direct comparisons between 5‐HT1B/d receptor agonists are used to assess differences and similarities in antimigraine response. Such comparisons depend on the selected sampling time and do not allow evaluation of entire response profiles. A thorough evaluation of drug properties requires that the time course of the response be taken into account. In this investigation we show the advantages of a model‐based approach to compare the efficacy of two triptans (sumatriptan vs. naratriptan).

Methods

A Markov model was used to describe the course of a migraine attack over three clinically identified stages. Drug effects were modelled as concentration‐dependent increases in transition rates and were parameterised as potency (EC50) and maximum effect (Emax). Parameters were estimated using headache measurements from efficacy studies. Model estimates were then used to compare the pharmacodynamics of the two drugs in a time‐independent manner.

Results

Efficacy parameters could be derived, allowing for comparison between compounds. The potency ratio (EC50suma/EC50nara) for headache relief was 3.3 (0.9, 12). The ratio of maximum effects (Emaxsuma/Emaxnara) for this endpoint was 0.74 (0.55, 0.97). To interpret these efficacy measures and explore their value for the development of antimigraine drugs, results were evaluated against the reported in vitro potency at 5‐HT1B and 5‐HT1D receptors.

Conclusions

Comparison of the effects of two or more drugs based on preset sampling times does not allow proper assessment of the antimigraine properties in vivo. Disease dynamics must be considered to evaluate treatment response adequately and optimise the dosing regimen in migraine.
Gene expression analysis of B‐lymphoma cells resistant and sensitive to bortezomib*
Authors: Shringarpure Reshma , Catley Laurence , Bhole Deepak , Burger Renate , Podar Klaus , Tai Yu‐Tzu , Kessler Benedikt , Galardy Paul , Ploegh Hidde , Tassone Pierfrancesco , Hideshima Teru , Mitsiades Constantine , Munshi Nikhil C. , Chauhan Dharminder , Anderson Kenneth C.
Published: May 2006

The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in combination with conventional and other novel agents for the treatment of multiple myeloma (MM). Although bortezomib is known to be a selective proteasome inhibitor, the downstream mechanisms of cytotoxicity and drug resistance are poorly understood. However, resistance to bortezomib as a single agent develops in the majority of patients, and activity in other malignancies has been less impressive. To elucidate mechanisms of bortezomib resistance, we compared differential gene expression profiles of bortezomib‐resistant SUDHL‐4 and bortezomib‐sensitive SUDHL‐6 diffuse large B‐cell lymphoma lines in response to bortezomib. At concentrations that effectively inhibited proteasome activity, bortezomib induced apoptosis in SUDHL‐6 cells, but not in SUDHL‐4 cells. We showed that overexpression of activating transcription factor 3 (ATF3), ATF4, ATF5, c‐Jun, JunD and caspase‐3 is associated with sensitivity to bortezomib‐induced apoptosis, whereas overexpression of heat shock protein (HSP)27, HSP70, HSP90 and T‐cell factor 4 is associated with bortezomib resistance.
Methodologically controlled variations in laboratory and field pH measurements in waterlogged soils
Authors: Elberling B. , Matthiesen H.
Published: May 2006

We have tested the reliability and consistency of conventional pH measurements made on water‐soil mixtures with respect to sieving, drying, ratio of water to soil, and time of shaking prior to measurement. The focus is on a waterlogged soil where the preservation potential of archaeological artefacts is critical. But the study includes agricultural and forest soils for comparison. At a waterlogged site, laboratory results were compared with three different field methods: calomel pH probes inserted in the soil from pits, pH measurements of soil solution extracted from the soil, and pH profiles using a solid‐state pH electrode pushed into the soil from the surface. Comparisons between in situ and laboratory methods revealed differences of more than 1 pH unit. The content of dissolved ions in soil solution and field observations of O2 and CO2 concentrations were used in the speciation model PHREEQE in order to predict gas exchange processes. Changes in pH in soil solution following equilibrium in the laboratory could be explained mainly by CO2 degassing. Only soil pH measured in situ using either calomel or solid‐state probes inserted directly into the soil was not affected by gas exchange processes. Variations on the order of 0.2–0.5 pH unit in different laboratory methods could not be explained by degassing and seem to be soil‐type specific and strongly influenced by drying and shaking. Further attention should be given to standardization of pH measurements, particularly before pH measurements from different soil types are compared.
Spontaneous scratching behaviour in DS‐Nh mice as a possible model for pruritus in atopic dermatitis
Authors: Yoshioka T. , Hikita I. , Asakawa M. , Hirasawa T. , Deguchi M. , Matsutani T. , Oku H. , Horikawa T. , Arimura A.
Published: May 2006

Itching is one of the major clinical symptoms in atopic dermatitis (AD) and complicates the management of this pathological condition. An animal model of AD‐like pruritus would contribute to a better understanding of AD and could lead to the development of safe and effective antipruritic agents. DS non‐hair (DS‐Nh) mice raised under conventional conditions spontaneously develop pruritus, which is associated with a dermatitis similar to human AD. There is a significant positive correlation between disease severity and the period of scratching behaviour in DS‐Nh mice. In the present study, we found that levels of histamine and nerve growth factor (NGF) in serum and/or skin tissue were higher in DS‐Nh mice with AD‐like dermatitis than in age‐matched mice without dermatitis. The histopathological data indicated that nerve fibres extend into and mast cells infiltrate the surrounding area of the skin lesion. NGF production by XB‐2 cells, which was derived from mouse keratinocytes, was enhanced by histamine via the H1 receptor. We also found that prolonged treatment with an H1‐antagonist was effective against pruritus through depression of the production of NGF, which is thought to be generated by keratinocytes. We conclude that DS‐Nh mice can serve as a suitable model for gaining a better understanding of pruritus in AD, and that prolonged treatment with an H1‐antagonist may be beneficial in patients with AD‐associated pruritus.
Immunogenicity and protective efficacy of tuberculosis DNA vaccines combining mycolyl‐transferase Ag85A and phosphate transport receptor PstS‐3
Authors: Romano Marta , Roupie Virginie , Wang Xiao M. , Denis Olivier , Jurion Fabienne , Adnet Pierre‐Yves , Laali Rachid , Huygen Kris
Published: May 2006

DNA vaccines encoding the 32 000 MW mycolyl‐transferase Ag85A and the 40 000 MW phosphate‐binding protein PstS‐3 can elicit protective immune responses against experimental infection with Mycobacterium tuberculosis in C57BL/6 mice. Here we have analysed the vaccine potential of a combination of both antigens using plasmid vectors expressing either a fusion protein of both antigens or the separate proteins driven by two independent promoters (in pBudCE4·1 vector). Comparable levels of Ag85A specific T helper 1 (Th1) type immune responses could be induced by the two combination vaccines and the single vaccine encoding the mycolyl‐transferase, whereas induction of PstS‐3 specific Th1‐mediated responses was impaired in both combination vaccines. In contrast, magnitude of CD8+ mediated responses against the PstS‐3 protein was comparable following combination or single DNA vaccination. Antigenic competition was also observed at the antibody level; PstS‐3 specific levels being lower in mice vaccinated with the fusion vector and Ag85A specific levels being lower in mice vaccinated with the combination pBudCE4·1 vector (as compared to levels obtained following single plasmid immunization). Protection against M. tuberculosis was only modestly improved in mice vaccinated with the DNA combinations. It is possible that prior activation of Ag85A specific CD4+ T cells directed against this common mycobacterial antigen leads to cross‐competition for major histocompatibility complex class II‐restricted peptide complexes of the Pst‐3 antigen. This may have implications for future combination vaccines using Ag85.
Diabetes‐induced decrease of adenosine kinase expression impairs the proliferation potential of diabetic rat T lymphocytes
Authors: Sakowicz‐Burkiewicz Monika , Kocbuch Katarzyna , Grden Marzena , Szutowicz Andrzej , Pawelczyk Tadeusz
Published: May 2006

The proliferative response of T lymphocytes is a crucial step in cell‐mediated immunity. This study was undertaken to investigate the mechanisms leading to the impaired proliferative response of diabetic T lymphocytes. T cells that had been isolated from the spleen of normal rats and cultured in medium containing 20 mmglucose and no insulin displayed the same degree of proliferative impairment as cells isolated from diabetic rats. The rate of T‐cell proliferation, when induced with concanavalin A or anti‐CD3 and anti‐CD28 antibodies, was not affected by the inhibition of nucleoside transporters. T cells cultured at high glucose concentrations in the absence of insulin displayed decreased expression of adenosine kinase, and released measurable extracellular quantities of adenosine. Under resting conditions, the level of cAMP was 5·9‐fold higher in these cells compared to cells grown in low glucose and in the presence of insulin. Experiments with specific adenosine receptor agonists and antagonists showed that adenosine‐induced suppression of diabetic T cell proliferation was mediated by the A2Aadenosine receptor, but not by the A2Breceptor. Treatment of diabetic T cells with 10 μmH‐89, a specific protein kinase A inhibitor, restored T‐cell proliferation. These results show that suppressed proliferation of diabetic T lymphocytes is evoked by the decreased expression of adenosine kinase, leading to the outflow of adenosine from the cell. Extracellular adenosine then stimulates the A2Areceptor and induces cAMP production, leading to the activation of protein kinase A, and suppression of T‐cell proliferation.
Relative importance of evaluation criteria for enterprise systems: a conjoint study
Authors: Keil Mark , Tiwana Amrit
Published: May 2006

Abstract.  While a large body of research exists on the development and implementation of software, organizations are increasingly acquiring enterprise software packages [e.g. enterprise resource planning (ERP) systems] instead of custom developing their own software applications. To be competitive in the marketplace, software package development firms must manage the three‐pronged trade‐off between cost, quality and functionality. Surprisingly, prior research has made little attempt to investigate the characteristics of packaged software that influence management information system (MIS) managers’ likelihood of recommending purchase. As a result, both the criteria by which MIS managers evaluate prospective packaged systems and the attributes that lead to commercially competitive ERP software products are poorly understood. This paper examines this understudied issue through a conjoint study. We focus on ERP systems, which are among the largest and most complex packaged systems that are purchased by organizations. In a conjoint study, 1008 evaluation decisions based on hypothetical ERP software package profiles were completed by managers in 126 organizations. The study represents the first empirical investigation of the relative importance that managers ascribe to various factors that are believed to be important in evaluating packaged software. The results provide important insights for both organizations that acquire such systems and those that develop them. The results show that functionality, reliability, cost, ease of use and ease of customization are judged to be important criteria, while ease of implementation and vendor reputation were not found to be significant. Functionality and reliability were found to be the most heavily weighted factors. We conclude the paper with a detailed discussion of the results and their implications for software acquisition and development practice.
Differences in SCSA outcome among boars with different sperm freezability
Authors: Hernández Marta , Roca Jordi , Ballester Joan , Vázquez Juan M. , Martínez Emilio A. , Johannisson Anders , Saravia Fernando , Rodríguez‐Martínez Heriberto
Published: May 2006

Spermatozoa from some boars sustain the process of cryopreservation poorly and yield poor fertility after artificial insemination. Poor freezability has not been disclosed using conventional semen analyses. A defective chromatin can, if present in a substantial number of spermatozoa, affect the fertilizing ability of spermatozoa. Here we tested the hypothesis that nuclear DNA instability could explain differences in freezability among boars, and complement or supersede conventional tests for sperm quality such as sperm motility or membrane assessments. Frozen–thawed (FT) spermatozoa from a total of 44 stud boars were assessed by the sperm chromatin structure assay (SCSA), in relation to computer‐assisted sperm analysis‐derived sperm motility variables and sperm viability (triple fluorescent microscopic staining), including three experiments. The first trial, including 24 boars, evaluated the relationship between the sperm motility and viability with levels of DNA integrity. The SCSA showed that most spermatozoa had intact DNA [levels of DNA fragmentation index (%DFI) ranging from 0.63% to 11.85%] significantly correlated (albeit weakly) with current sperm quality variables. The second trial, on 15 boars, assessed the influence of two different thawing rates (20 s at 37 °C vs. 8 s at 70 °C) and the post‐thaw incubation times (0, 30, 150 and 300 min) at 37 °C on FT‐boar sperm quality. The highest sperm survival (p < 0.05) and the lowest DNA damage (p < 0.01) were achieved when thawing was carried out at 70 °C for 8 s, without any change during the first 150 min of incubation. Finally, the third experiment studied if differences in sperm freezability showed by stud boar semen, as ‘good’ or ‘bad’ freezers by conventional analyses, could be attributed to differences in chromatin structure. All SCSA parameters were low, but significantly (p < 0.05–0.001) higher for ‘bad’ freezers, showing they had less homogeneous sperm chromatin than the ‘good’ freezers. The results indicate that SCSA outcome complements conventional assessment of FT‐boar spermatozoa, disclosing differences in their ability to sustain freezing and thawing. However, the low overall DNA damage observed in FT spermatozoa seems to have poor biological significance.
Local administration of 2% trimecaine affects the content of fucosylated glycoconjugates in goblet cells in rabbit tracheal epithelium
Authors: Vajner Luděk , Uhlík Jiří , Konrádová Václava , Kleščová Andrea , Adášková Jana
Published: May 2006

The proportion of fucosylated glycoconjugate‐containing rabbit tracheal goblet cells after intratracheal application of trimecaine was studied to evaluate its possible unfavourable effects. This lapine model is comparable with diagnostic findings in humans because airway epithelia in humans and rabbits are similar; tracheal epithelium is also practically identical to bronchial epithelium in both species. Local trimecaine anaesthesia caused a proportional decrease in percentage of the tracheal goblet cells containing both α(1–2)‐ and α(1–6)‐, α(1–3)‐ and α(1–4)‐fucosylated glycoconjugates as revealed 10 min postexposure using lectin histochemistry. In previous studies, only mild ultrastructural damage to the airway's epithelium was revealed, but a conspicuous decrease in sialylated glycoconjugate‐containing tracheal goblet cells and the dominance of acidic sulphated glycoconjugates were observed as after‐effects of the same treatment. Glycoconjugate changes can influence the inner environment of airways (e.g. viscoelastic properties of the airways’ mucus and mucosal barrier functions) and thus the patient's defence barriers in airways may be weakened. Concurrently, the histochemical properties of goblet cells can be altered in bronchoscopic specimens. Since trimecaine is widely used as local anaesthesia in airways in bronchoscopy, it is necessary to heed these aforementioned effects.
How best to collect demographic data for population viability analysis models
Authors: MÜNZBERGOVÁ ZUZANA , EHRLÉN JOHAN
Published: May 2006

Matrix population models have become important tools in many fields of ecology and conservation biology, and are the most commonly used method in population viability analysis (PVA). There is a large literature concerned with different aspects of matrix model analysis, but relatively little attention has been paid to how data are collected.

In most demographic population viability studies, data are sampled in permanent plots, often resulting in poor representation of some stages. It has been suggested that by using previous knowledge of species’ demography it is possible to sample demographic data more efficiently. Here we propose an alternative method that is much simpler and does not rely on any assumptions, namely sampling an equal number of individuals per stage.

By using demographic data from 32 species we showed that sampling an equal number of individuals per stage provides more precise estimates of both population growth rate and elasticity than the traditional plot‐based method. In some cases it is also better than the estimates gained using the method based on previous knowledge of the species’ demography. The conclusions of the latter method are very sensitive to the quality of the previous knowledge of the species’ demography. In contrast, collecting demographic data from an equal number of individuals per stage is independent of any assumptions.

Synthesis and applications. A central aim for management of threatened species is to develop robust and accurate methods for assessing population viability that are also efficient in terms of costs and labour. A key issue is how to collect the data on which viability assessments are based. We show that it is possible to increase considerably the accuracy and robustness of demographic PVA without increasing sampling effort, by using a simple method based on sampling an equal number of individuals per life‐cycle stage. Improved PVA model performance will be important to guide conservation efforts and to evaluate different management options.
Slowing down a pine invasion despite uncertainty in demography and dispersal
Authors: BUCKLEY YVONNE M. , BROCKERHOFF ECKEHARD , LANGER LISA , LEDGARD NICHOLAS , NORTH HEATHER , REES MARK
Published: May 2006

Management decisions regarding invasive plants often have to be made quickly and in the face of fragmentary knowledge of their population dynamics. However, recommendations are commonly made on the basis of only a restricted set of parameters. Without addressing uncertainty and variability in model parameters we risk ineffective management, resulting in wasted resources and an escalating problem if early chances to control spread are missed.

Using available data for Pinus nigra in ungrazed and grazed grassland and shrubland in New Zealand, we parameterized a stage‐structured spread model to calculate invasion wave speed, population growth rate and their sensitivities and elasticities to population parameters. Uncertainty distributions of parameters were used with the model to generate confidence intervals (CI) about the model predictions.

Ungrazed grassland environments were most vulnerable to invasion and the highest elasticities and sensitivities of invasion speed were to long‐distance dispersal parameters. However, there was overlap between the elasticity and sensitivity CI on juvenile survival, seedling establishment and long‐distance dispersal parameters, indicating overlap in their effects on invasion speed.

While elasticity of invasion speed to long‐distance dispersal was highest in shrubland environments, there was overlap with the CI of elasticity to juvenile survival. In shrubland invasion speed was most sensitive to the probability of establishment, especially when establishment was low. In the grazed environment elasticity and sensitivity of invasion speed to the severity of grazing were consistently highest. Management recommendations based on elasticities and sensitivities depend on the vulnerability of the habitat.

Synthesis and applications. Despite considerable uncertainty in demography and dispersal, robust management recommendations emerged from the model. Proportional or absolute reductions in long‐distance dispersal, juvenile survival and seedling establishment parameters have the potential to reduce wave speed substantially. Plantations of wind‐dispersed invasive conifers should not be sited on exposed sites vulnerable to long‐distance dispersal events, and trees in these sites should be removed. Invasion speed can also be reduced by removing seedlings, establishing competitive shrubs and grazing. Incorporating uncertainty into the modelling process increases our confidence in the wide applicability of the management strategies recommended here.
Identification of Dopamine, Gonadotrophin‐Releasing Hormone‐I, and Vasoactive Intestinal Peptide Neurones Activated by Electrical Stimulation to the Medial Preoptic Area of the Turkey Hypothalamus: A Potential Reproductive Neuroendocrine Circuit
Authors: Al‐Zailaie K. A. , Kang S. W. , Youngren O. M. , Thayananuphat A. , Bakken T. , Chaiseha Y. , Millam J. R. , Proudman J. A. , El Halawani M. E.
Published: May 2006

The neural and neurochemical substrates regulating reproduction in birds remain vaguely defined. The findings that electrical stimulation in the medial preoptic area (ES/MPOA) or intracerebroventricular infusion of dopamine (DA) stimulated luteinising hormone (LH) and prolactin (PRL) release in female turkeys, led to the suggestion that ES/MPOA might help to clarify the DA circuitry regulating LH and PRL. We used c‐fos mRNA and tyrosine hydroxylase immunoreactivity as measured by double in situ hybridisation/immunocytochemistry (ISH/ICC) to determine which group/subgroup of DA neurones was activated following unilateral ES/MPOA. To establish that the reproductive neuroendocrine system was activated, double ISH/ICC was also conducted on c‐fos/gonadotrophin‐releasing hormone‐I (GnRH‐I) and c‐fos/vasoactive intestinal peptide (VIP). Changes in circulating LH and PRL were determined by radioimmunoassay. Unilateral ES/MPOA (100 µA, right side) of anaesthetised laying turkeys for 30 min increased circulating LH and PRL levels. It also induced c‐fos mRNA expression on the ipsilateral side by all GnRH‐I neurones within the septopreoptic region, implying that GnRH‐I neurones in this region share similar circuitry. VIP neurones within the nucleus infundibularis were the only VIP group to show c‐fos mRNA expression, suggesting their involvement in ES/MPOA induced PRL release. c‐fos mRNA expression was also observed in a subgroup of DA neurones in the nucleus mamillaris lateralis (ML). To our knowledge, the present study is the first to show that activation of DAergic cells in the ML is associated with the activation of GnRH‐I and VIP neurones and the release of LH and PRL. It is likely that ES/MPOA activated VIP/GnRH‐I neurones via activation of DA neurones in the ML, as this was the only DA subgroup that showed c‐fos mRNA expression.
Portal fusion protein constraints on function in DNA packaging of bacteriophage T4
Authors: Baumann Richard G. , Mullaney Julienne , Black Lindsay W.
Published: May 2006

Architecturally conserved viral portal dodecamers are central to capsid assembly and DNA packaging. To examine bacteriophage T4 portal functions, we constructed, expressed and assembled portal gene 20 fusion proteins. C‐terminally fused (gp20–GFP, gp20–HOC) and N‐terminally fused (GFP–gp20 and HOC–gp20) portal fusion proteins assembled in vivo into active phage. Phage assembled C‐terminal fusion proteins were inaccessible to trypsin whereas assembled N‐terminal fusions were accessible to trypsin, consistent with locations inside and outside the capsid respectively. Both N‐ and C‐terminal fusions required coassembly into portals with ∼50% wild‐type (WT) or near WT‐sized 20am truncated portal proteins to yield active phage. Trypsin digestion of HOC–gp20 portal fusion phage showed comparable protection of the HOC and gp20 portions of the proteolysed HOC–gp20 fusion, suggesting both proteins occupy protected capsid positions, at both the portal and the proximal HOC capsid‐binding sites. The external portal location of the HOC portion of the HOC–gp20 fusion phage was confirmed by anti‐HOC immuno‐gold labelling studies that showed a gold ‘necklace’ around the phage capsid portal. Analysis of HOC–gp20‐containing proheads showed increased HOC protein protection from trypsin degradation only after prohead expansion, indicating incorporation of HOC–gp20 portal fusion protein to protective proximal HOC‐binding sites following this maturation. These proheads also showed no DNA packaging defect in vitro as compared with WT. Retention of function of phage and prohead portals with bulky internal (C‐terminal) and external (N‐terminal) fusion protein extensions, particularly of apparently capsid tethered portals, challenges the portal rotation requirement of some hypothetical DNA packaging mechanisms.
Virus DNA translocation: progress towards a first ascent of Mount Pretty Difficult
Authors: Maluf Nasib K. , Feiss Michael
Published: May 2006

Virion DNA molecules of large dsDNA viruses are highly condensed. To pack the DNA, an ATP hydrolysis‐powered motor translocates the DNA into a preformed empty protein shell, the prohead. The icosahedral prohead has a special fivefold vertex, the portal vertex, where the translocation machinery acts. The portal vertex contains the portal protein, a gear‐shaped dodecamer of radially disposed subunits with a central channel for DNA entry. The symmetry mismatch between the fivefold symmetry of the shell vertex and the 12‐fold symmetry of the portal protein has prompted DNA packaging models in which ATP‐driven portal protein rotation drives DNA translocation. In this issue of Molecular Microbiology, Baumann and colleagues test portal rotation models using bacteriophage T4. A fusion between the gp20 portal protein and the HOC external shell decoration protein is used to create a block to portal rotation. Finding that DNA packaging is unimpeded in proheads containing the fusion argues that portal rotation is not crucial to DNA translocation. The paper is a landmark for describing direct testing of the mechanism of DNA translocation.
The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream‐form Trypanosoma brucei is dependent on the de novo synthesis of inositol
Authors: Martin Kirstee L. , Smith Terry K.
Published: May 2006

In bloodstream‐form Trypanosoma brucei (the causative agent of African sleeping sickness) the glycosylphosphatidylinositol (GPI) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. The conundrum that GPI anchors could not be in vivo labelled with [3H]‐inositol led us to hypothesize that de novo synthesis was responsible for supplying myo‐inositol for phosphatidylinositol (PI) destined for GPI synthesis. The rate‐limiting step of the de novo synthesis is the isomerization of glucose 6‐phosphate to 1‐d‐myo‐inositol‐3‐phosphate, catalysed by a 1‐d‐myo‐inositol‐3‐phosphate synthase (INO1). When grown under non‐permissive conditions, a conditional double knockout demonstrated that INO1 is an essential gene in bloodstream‐form T. brucei. It also showed that the de novo synthesized myo‐inositol is utilized to form PI, which is preferentially used in GPI biosynthesis. We also show for the first time that extracellular myo‐inositol can in fact be used in GPI formation although to a limited extent. Despite this, extracellular inositol cannot compensate for the deletion of INO1. Supporting these results, there was no change in PI levels in the conditional double knockout cells grown under non‐permissive conditions, showing that perturbation of growth is due to a specific lack of de novo synthesized myo‐inositol and not a general inositol‐less death. These results suggest that there is a distinction between de novo synthesized myo‐inositol and that from the extracellular environment.
Two different Pseudomonas aeruginosa chemosensory signal transduction complexes localize to cell poles and form and remould in stationary phase
Authors: Güvener Zehra Tüzün , Tifrea Delia F. , Harwood Caroline S.
Published: May 2006

Pseudomonas aeruginosa has sets of sensory genes designated che and che2. The che genes are required for flagella‐mediated chemotaxis. The che2 genes are expressed in the stationary phase of growth and are probably also involved in flagella–mediated behavioural responses. P. aeruginosa also has 26 chemoreceptor genes, six of which are preferentially expressed in stationary phase. Subcellular localization experiments indicated that Che proteins form signal transduction complexes at cell poles throughout growth. Cyan fluorescent protein (CFP)‐tagged McpA, a stationary phase‐expressed chemoreceptor, appeared and colocalized with yellow fluorescent protein (YFP)‐tagged CheA when cells entered stationary phase. This indicates that P. aeruginosa chemotaxis protein complexes are subject to remoulding by chemoreceptor proteins that are expressed when cells stop growing. CheA‐CFP and CheY2‐YFP tagged proteins that were coexpressed in the same cell had separate subcellular locations, indicating that Che2 proteins do not enter into direct physical interactions with Che proteins. Che2 protein complex formation required McpB, another stationary phase induced chemoreceptor that is predicted to be soluble. This implies that Che2 complexes have a function that depends on just one chemoreceptor. Our results suggest that motile P. aeruginosa cells have signal transduction systems that are adapted to allow non‐growing cells to sense and respond to their environment differently from actively growing cells.