bluuebunny/crossref_metadata_2025 huggingface dataset:
Robotic Nucleic Acid Isolation Using a Magnetic Bead Resin and an Automated Liquid Handler for Biological Agent Simulants
Authors: Bailey Andrew M. , Pajak Laura , Fruchey Isaac R. , Cowan Cristopher A. , Emanuel Peter A.
Published: February 2005

The events that occurred following the mailing of Bacillus anthracis-laced envelopes through the postal system has highlighted the need to perform biological screening on large numbers of environmental samples. High-throughput screening that relies on integrated robotic systems to speed analysis has been undertaken to handle the surge in samples requiring testing in events involving weapons of mass destruction. These automated screening systems require DNA extraction methods capable of handling environmental samples that contain inhibitors and have target organisms at low concentrations. This study describes the development of a method for the detection of the biological warfare agent simulants Erwinia herbicola and Bacillus subtilis var. niger spores using paramagnetic bead-based resin with an automated liquid handler and environmental samples.
Evaluation of Automated Cell Culture Incubators
Authors: Triaud Frederique , Clenet Diane-Helene , Cariou Yves , Le Neel Tanguy , Morin Delphine , Truchaud Alain
Published: February 2005

Automated cell culture incubators generally are considered primary components of fully automated cell culture systems, which are able to monitor cell growth without human interaction. This tutorial is focused on automated cell culture incubators. It emphasizes the impact of automation on throughput and environmental controls (temperature, humidity, and CO2) and proposes some basic protocols to check these functions. In addition, it details practical aspects for switching from manual to automated cell culture incubators.
Evolution of High-Sensitivity Microarray Technology
Authors: MÜLler Uwe R.
Published: February 2005

Microarray technology is a multiplex analytical technique for the detection of many different analytes in a mixture of biomolecules. The detection limits for each of the analytes for which the array is designed depend on a multiplicity of reaction parameters, the array itself, and profoundly on the label and detection technology employed. Significant improvements in assay sensitivity have been achieved by optimizing all steps that affect the generation of signal and noise. Nanoparticle technology brings a new dimension to this technology by providing not only higher sensitivity but also improved specificity for hybridization-based microarray assay systems.
Improving Sample Analysis Throughput and Quality with a .NETTM-based, Real-Time QC Decision Support System
Authors: Staab Torsten , Shiina Toshiyuki , Miller Derek
Published: February 2005

This report describes an integrated, software-based quality control system designed to significantly improve the sample analysis throughput and quality of beryllium analysis laboratories throughout the U.S. Department of Energy complex. Originally, this system was developed to minimize the downtimes of expensive instrumentation (here: Perkin Elmer® 4300™ DV Inductively Coupled Plasma Optical Emission Spectrometers) and to automate the sample analysis quality control process. This automated software system was also expected to eliminate time-consuming and error-prone result data interpretation, which previously was done manually. To achieve these goals, Los Alamos National Laboratory recently implemented a rule-based decision support system in the C#.NET™ that continuously extracts and analyzes data from the instrument's result database as the data is being generated. Using a customer-specific expert rule base, the system is capable of detecting abnormal operating situations fully autonomously in real time. This also enables the system to perform on-the-fly quality control and automatic, electronic event notification of lab personnel via e-mail and pager.
The Adelie Blizzard: the Australasian Antarctic Expedition's neglected newspaper
Authors: Leane Elizabeth
Published: February 2005

To prevent boredom and restlessness during early Arctic and Antarctic over-wintering expeditions, leaders often encouraged ‘cultural’ activities, one of the most successful of which was the production of newspapers. Expedition members contributed poetry, short fiction, and literary criticism as well as scientific articles and accounts of their daily activities. These newspapers provide an important insight into the experiences and attitudes of the men who took part in the expeditions. In some cases, the newspaper would be published on the expedition's return, as a means of publicity, fund-raising, and memorialisation. The most famous example is the South Polar Times, the newspaper produced by Robert Falcon Scott's two expeditions. Other polar newspapers remain unpublished and unexamined. This article focuses on the Adelie Blizzard, the newspaper of the Australasian Antarctic Expedition of 1911–14, led by Douglas Mawson. Despite Mawson's efforts, the Adelie Blizzard was never published, and is rarely discussed in any detail in accounts of the expedition. The aim of this article is to address this neglect, by examining the genesis, production and attempted publication of the Adelie Blizzard.
The Norse landnám on the North Atlantic islands: an environmental impact assessment
Authors: Dugmore Andrew J. , Church Mike J. , Buckland Paul C. , Edwards Kevin J. , Lawson Ian , McGovern Thomas H. , Panagiotakopulu Eva , Simpson Ian A. , Skidmore Peter , Sveinbjarnardóttir Guðrún
Published: February 2005

The Norse colonisation or landnám of the North Atlantic islands of the Faroes, Iceland, and Greenland from the ninth century AD onwards provides opportunities to examine human environmental impacts on ‘pristine’ landscapes on an environmental gradient from warmer, more maritime conditions in the east to colder, more continental conditions in the west. This paper considers key environmental contrasts across the Atlantic and initial settlement impacts on the biota and landscape. Before landnám, the modes of origin of the biota (which resulted in boreo-temperate affinities), a lack of endemic species, limited diversity, and no grazing mammals on the Faroes or Iceland, were crucial in determining environmental sensitivity to human impact and, in particular, the impact of introduced domestic animals. Gathering new data and understanding their geographical patterns and changes through time are seen as crucial when tackling fundamental questions about human interactions with the environment, which are relevant to both understanding the past and planning for the future.
Multiple constraints on regional CO2 flux variations over land and oceans
Authors: Peylin Philippe , Bousquet Philippe , Le Quéré Corinne , Sitch Stephen , Friedlingstein Pierre , McKinley Galen , Gruber Nicolas , Rayner Peter , Ciais Philippe
Published: February 2005

To increase our understanding of the carbon cycle, we compare regional estimates of CO2 flux variability for 1980–1998 from atmospheric CO2 inversions and from process‐based models of the land (SLAVE and LPJ) and ocean (OPA and MIT). Over the land, the phase and amplitude of the different estimates agree well, especially at continental scale. Flux variations are predominantly controlled by El Niño events, with the exception of the post‐Pinatubo period of the early 1990s. Differences between the two land models result mainly from the response of heterotrophic respiration to precipitation and temperature. The “Lloyd and Taylor” formulation of LPJ [Lloyd and Taylor, 1994] agrees better with the inverse estimates. Over the ocean, inversion and model results agree only in the equatorial Pacific and partly in the austral ocean. In the austral ocean, an increased CO2 sink is present in the inversion and OPA model, and results from increased stratification of the ocean. In the northern oceans, the inversions estimate large flux variations in line with time‐series observations of the subtropical Atlantic, but not supported by the two model estimates, thus suggesting that the CO2 variability from high‐latitude oceans needs further investigation.
Regional‐scale climate change detection using a Bayesian decision method
Authors: Min Seung‐Ki , Hense Andreas , Kwon Won‐Tae
Published: February 2005

We use Bayesian statistics for a regional climate change detection problem and show an application for the East Asian surface air temperature (SAT) field. Detection variables are constructed from a data‐independent advection‐diffusion model for SAT. Two scenario cases, namely a control scenario (CTL) and a CO2‐induced climate change scenario (G), are derived from model integrations. The Bayesian decision process starts from prior probabilities, goes through the likelihood function where the observations enter, and finally produces posterior probabilities. We select the scenario of larger posterior probability given the observations, by which the theoretical decision error becomes a minimum. The application results for the East Asian SAT reveal strong G signals since 1990s insensitive to prior probabilities. The signal is carried on temporal scales longer than 1 year and spatial scales larger than 6000 km.
Comment on “First principles electrochemistry: Electrons and protons reacting as independent ions” [J. Chem. Phys. 117, 10193 (2002)]
Authors: Rockwood Alan L.
Published: February 2005

The entropy of the electron gas used by Llano and Eriksson (LE) in the definition they used for an absolute half-cell potential (AHCP) is indeterminate. This AHCP is therefore not based on a thermodynamically well-defined process and cannot easily be extended to other thermodynamic functions such as entropy. An alternative approach to the AHCP avoids these difficulties. The present comment also corrects statements and concepts presented by LE about the temperature coefficient of the Fermi level and surface charge of the electrolyte solution.
Response to “Comment on ‘First principles electrochemistry: Electrons and protons reacting as independent ions’ ” [J. Chem. Phys. 122, 087103 (2005)]
Authors: Llano Jorge , Eriksson Leif A.
Published: February 2005

We present a critical analysis of the thermodynamic description of fermion gases concerning its compatibility with the International Union of Pure and Applied Chemistry recommended definition of the absolute electrode potential. The approximations enabling to separate the molecular problem of a half reaction out of the interfacial problem are discussed.
Direct patterning of conductive water-soluble polyaniline for thin-film organic electronics
Authors: Lee Kwang Seok , Blanchet Graciela B. , Gao Feng , Loo Yueh-Lin
Published: February 2005

We report a simple and low-cost technique for directly patterning conductive water-soluble polyaniline. This technique exploits the hydrophilic nature of polyaniline that was synthesized on a polymer acid template. To create conductive features, aqueous polyaniline solutions are directly spun cast onto substrates previously patterned with hydrophilic and hydrophobic regions. Polyaniline selectively adsorbs in the hydrophilic regions thereby resulting in features as small as 5 μm with an average conductivity of 0.3 S/cm over large areas. Polyaniline contacts for thin-film transistors were fabricated; such devices show on characteristics that are quantitatively similar to those of reference devices with gold electrodes.
Large low-field magnetoresistance effect in Sr2FeMoO6 homocomposites
Authors: Huang Y. H. , Lindén J. , Yamauchi H. , Karppinen M.
Published: February 2005

Homocomposites consisting of two single-phase Sr2FeMoO6 components with different grain sizes were prepared by a sol-gel method. Large low-field magnetoresistance (LFMR) effect was achieved for the composites. Experimental results show that the LFMR strongly depends on both the relative amounts of the two components and their grain sizes. The magnetoresistance value is found to be proportional to the square of the relative magnetization (M∕Ms). We suggest that the LFMR enhancement in the homocomposites compared with parent Sr2FeMoO6 has its origin in the enhanced intergranular effects.
Modification of GaAs Schottky diodes by thin organic interlayers
Authors: Vearey-Roberts A. R. , Evans D. A.
Published: February 2005

Control of the interfacial potential barrier for metal∕n-GaAs diodes has been achieved using thin interlayers of the organic semiconductor, tin phthalocyanine (SnPc). The current–voltage (I–V) characteristics for organic-modified Ag∕S:GaAs diodes indicate a change from rectifying to almost ohmic behavior as the thickness of the SnPc interlayer is increased. Modeling reveals thermionic emission to be the dominant transport mechanisms for all diodes (ideality factors, n<1.3). Unlike other organic interlayers in similar device structures, SnPc reduces the effective barrier height by influencing the space charge region of the GaAs. The change in barrier height deduced from the I–V characteristics [(0.26±0.02)V] is similar to the band-bending measured using core-level photoelectron spectroscopy for SnPc growth on the S-passivated n-GaAs(001) surface [(0.22±0.04)eV] and is much larger than previously reported for other similar systems.
Four-dimensional optical manipulation of colloidal particles
Authors: Rodrigo Peter John , Daria Vincent Ricardo , Glückstad Jesper
Published: February 2005

We transform a TEM00 laser mode into multiple counterpropagating optical traps to achieve four-dimensional simultaneous manipulation of multiple particles. Efficient synthesis and dynamic control of the counterpropagating-beam traps is carried out via the generalized phase contrast method, and a spatial polarization-encoding scheme. Our experiments genuinely demonstrate real-time, interactive particle-position control for forming arbitrary volumetric constellations and complex three-dimensional trajectories of multiple particles. This opens up doors for cross-disciplinary cutting-edge research in various fields.
Stable charge storage in granular thin films
Authors: Xu Fengting T. , Thaler Sean M. , Lopez Carlos A. , Barnard John A. , Butera Alejandro , Weston James L.
Published: February 2005

Highly stable local charge storage by scanning probe microscopy methods has been observed in Fe–SiO2 (and Co–SiO2) granular thin films (5nm metal granules embedded in SiO2) with decay times as much as two orders of magnitude longer than previously reported for heterogeneous films. Charge dissipation is well described as occurring in two regimes, a comparatively fast regime at short times (decay times of thousands of seconds) and a much slower regime at longer times (decay times of tens of thousands of seconds). Negative charging occurs more readily in these systems but positive charges are significantly more stable. Based on the results presented here, granular thin films have great potential as a new class of stable, tunable electrets suitable for nanoscale charge patterning and electrostatically directed assembly of complex nanostructures from discrete charged/polarized nanoparticles and macromolecules.
All-MgB2 tunnel junctions with aluminum nitride barriers
Authors: Shimakage Hisashi , Tsujimoto Kazuya , Wang Zhen , Tonouchi Masayoshi
Published: February 2005

All-MgB2 tunnel junctions were fabricated on a C-plane sapphire substrate. The current-voltage characteristics showed both quasiparticle and Josephson tunneling currents and a clear gap structure. The current density was 115A∕cm2 for a 20×20μm2 junction with a 0.14-nm-thick AlN layer, and the ratio of the subgap resistance and normal resistance was 3.3. The gap voltages of lower and upper MgB2 electrodes were estimated to be 2.2 and 1.5mV, respectively. The temperature dependence of the Josephson current indicated that a normal layer existed between the AlN and the MgB2 electrodes. The Josephson tunneling currents were clearly modulated by applying an external magnetic field.
Folate supplementation increases genomic DNA methylation in the liver of elder rats
Authors: Choi Sang-Woon , Friso Simonetta , Keyes Mary K. , Mason Joel B.
Published: February 2005

The availability of folate is implicated as a determinant of DNA methylation, a functionally important feature of DNA. Nevertheless, when this phenomenon has been examined in the rodent model, the effect has not always been observed. Several reasons have been postulated for the inconsistency between studies: the rodent is less dependent on folate as a methyl source than man; juvenile animals, which most studies use, are more resistant to folate depletion than old animals; methods to measure genomic DNA methylation might not be sensitive enough to detect differences. We therefore examined the relationship between folate and genomic DNA methylation in an elder rat model with a newly developed method that can measure genomic DNA methylation sensitively and precisely. Thirty-nine 1-year-old rats were divided into three groups and fed a diet containing 0, 4·5 or 18 μmol folate/kg (folate-deplete, -replete and -supplemented groups, respectively). Rats were killed at 8 and 20 weeks. At both time points, mean liver folate concentrations increased incrementally between the folate-deplete, -replete and -supplemented rats (Pfor trend <0·001) and by 20 weeks hepatic DNA methylation also increased incrementally between the folate-deplete, -replete and -supplemented rats (Pfor trend=0·025). At both time points folate-supplemented rats had significantly increased levels of DNA methylation compared with folate-deplete\ rats (P<0·05). There was a strong correlation between hepatic folate concentration and genomic DNA methylation in the liver (r0·48,P=0·004). In the liver of this animal model, dietary folate over a wide range of intakes modulates genomic DNA methylation.
Globalization and Fiscal Federalism: Does Openness Constrain Subnational Budget Imbalances?
Authors: De Mello Luiz R.
Published: February 2005

Recent research has shown that more globalized countries—defined as those with stronger international trade and financial linkages—tend to have larger governments. The empirical evidence reported in this paper shows that globalization is also associated with the government's fiscal stance, nationally and subnationally. Greater access to external sources of finance, which can be facilitated through globalization, is associated with increased market scrutiny over policies, resulting in a higher premium on fiscal discipline.
Simultaneous detection of Macrobrachium rosenbergii nodavirus and extra small virus by a single tube, one‐step multiplex RT‐PCR assay
Authors: Yoganandhan K , Sri Widada J , Bonami J R , Sahul Hameed A S
Published: February 2005

Post‐larvae of Macrobrachium rosenbergii infected with white tail disease were collected from hatcheries and nursery ponds in India. The causative organisms have been identified as Macrobrachium rosenbergii nodavirus (MrNV) and extra small virus (XSV). A one‐step multiplex reverse transcriptase‐polymerase chain reaction (RT‐PCR) has been developed to detect these viruses simultaneously in naturally and experimentally infected prawns. Several parameters were assayed in order to optimize the protocol for simultaneous detection. Naturally and experimentally infected prawns showed two prominent bands of 681 and 500 bp for MrNV and XSV, respectively, as in separate RT‐PCR assays. Experimentally infected adult prawns showed two bands for these two viruses in all the organs, except hepatopancreas and eyestalk, as seen in normal RT‐PCR. The sensitivity test carried out on the primer sets of MrNV and XSV revealed that these primers could simultaneously detect the two viruses at a level of 25 fg of total RNA prepared from infected samples using this multiplex RT‐PCR protocol.
Synthesis of 10‐ and 9‐membered dilactams derived from aspartic and glutamic acids
Authors: Chulin A. N. , Rodionov I. L. , Ivanov V. T.
Published: February 2005

Abstract:  9‐ and 10‐membered bridged dipeptides derived from l‐aspartic acid and l‐ or d‐glutamic acid were synthesized using aminoacyl incorporation reaction. Key intermediates containing internal pyroglutamyl moiety were prepared via side chain to backbone cyclization of related protected dipeptide derivatives of glutamic acid.
Transcatheter closure of a complex postmyocardial infarction ventricular septal defect after surgical patch dehiscence
Authors: Cutfield N. J. , Ruygrok P. N. , Wilson N. J. , Raudkivi P. J. , Greaves S. C. , Gentles T. L. , Kerr A. J.
Published: February 2005

Abstract

Ventricular septal defect (VSD) complicating acute myocardial infarction is a rare but serious event carrying a high mortality. Residual shunting after emergency surgical repair is common, adversely affects prognosis and can necessitate reoperation. We describe the successful transcatheter VSD closure with the Amplatzer occluder in a 75‐year old man after earlier emergency surgical repair of a VSD complicating an acute myocardial infarction. The technique and positioning of the device in a tortuous infero‐apical VSD are described. (Intern Med J 2005; 35: 128–130)
Organizational Attributes Valued by Hospital, Home Care, and District Nurses in the United States and New Zealand
Authors: Flynn Linda , Carryer Jenny , Budge Claire
Published: February 2005

Purpose:

To determine whether hospital‐based, home care, and district nurses identify a core set of organizational attributes in the nursing work environment that they value as important to the support of professional practice.

Design:

Survey data, collected in 2002–2003 from 403 home care nurses in the United States (US) and 320 district nurses in New Zealand (NZ), were pooled with an existing data set of 669 hospital‐based nurses to conduct this descriptive, nonexperimental study.

Methods:

The importance of organizational attributes in the nursing work environment was measured using the Nursing Work Index‐Revised (NWI‐R). Frequency distributions and analysis of variance were used to analyze the data.

Findings:

At least 80% of hospital‐based, home care, and district nurses either agreed or strongly agreed that 47 of the 49 items comprising the NWI‐R represented organizational attributes they considered important to the support of their professional nursing practice. Mean importance scores among home care nurses, however, were significantly lower than were those of the other two groups.

Conclusions:

Overall, hospital‐based, home care, and district nurses had a high level of agreement regarding the importance of organizational traits to the support of their professional practice. The intensity of the attributes' importance was less among home care nurses. Further research is needed to determine whether this set of organizational traits, measured using the NWI‐R, is associated with positive nurse and patient outcomes in home care and district nursing practice, as has been shown in acute care settings.
Optical Imaging of Neuronal Populations During Decision-Making
Authors: Briggman K. L. , Abarbanel H. D. I. , Kristan W. B.
Published: February 2005

We investigated decision-making in the leech nervous system by stimulating identical sensory inputs that sometimes elicit crawling and other times swimming. Neuronal populations were monitored with voltage-sensitive dyes after each stimulus. By quantifying the discrimination time of each neuron, we found single neurons that discriminate before the two behaviors are evident. We used principal component analysis and linear discriminant analysis to find populations of neurons that discriminated earlier than any single neuron. The analysis highlighted the neuron cell 208. Hyperpolarizing cell 208 during a stimulus biases the leech to swim; depolarizing it biases the leech to crawl or to delay swimming.
Inflationary Cosmology: Exploring the Universe from the Smallest to the Largest Scales
Authors: Guth Alan H. , Kaiser David I.
Published: February 2005

Understanding the behavior of the universe at large depends critically on insights about the smallest units of matter and their fundamental interactions. Inflationary cosmology is a highly successful framework for exploring these interconnections between particle physics and gravitation. Inflation makes several predictions about the present state of the universe—such as its overall shape, large-scale smoothness, and smaller scale structure—which are being tested to unprecedented accuracy by a new generation of astronomical measurements. The agreement between these predictions and the latest observations is extremely promising. Meanwhile, physicists are busy trying to understand inflation's ultimate implications for the nature of matter, energy, and spacetime.
Refuge from Berlin's Bustle
Authors: Bohannon John
Published: February 2005

Einstein's Summer House in Caputh
. Einstein Forum, Am Neuen Markt 7, 14467 Potsdam, Germany.
www.einsteinforum.de

Einstein's retreat in the village of Caputh will be opened for tours once renovations are completed this spring;. photographs from the three years Einstein enjoyed the house are currently on display in Potsdam.
"ProC Global": A functional screening test that predicts recurrent venous thromboembolism
Authors: Bates Shannon , Johnston Marilyn , McRae Simon , Ginsberg Jeffrey , Grand’Maison Anne
Published: February 2005

Abnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.
Effect of age on the performance of a diagnostic strategy based on clinical probability, spiral computed tomography and venous compression ultrasonography
Authors: Couturaud Francis , Parent Florence , Meyer Guy , Girard Philippe , Le Gal Grégoire , Musset Dominique , Simonneau Gérald , Mottier Dominique , Leroyer Christophe
Published: February 2005

As the prevalence of PE increases with age, the effect of age on the diagnostic work-up in front of a clinical suspicion of PE deserves exploration. In this retrospective analysis, we used the data from 1041 consecutive suspected PE patients. The patients were divided into three groups according to tertiles of age: under 54 years, 54 to 73 years and above 73 years. The prevalence of PE in patients with respectively low, intermediate and high pretest clinical probability was expressed within each age group. We studied the effect of age on the results observed in three main groups of patients, after performing CT scan and ultrasonography (CUS): (1) patients with inconclusive results; (2) patients with negative findings on both exams and non high pretest clinical probability;(3) patients with positive findings. The prevalence of PE increased significantly with age, in overall, as well as in patients with low or intermediate pretest clinical probability. An analysis according to the three main diagnostic groups showed that: (1) the distribution of inconclusive spiral CT or CUS examinations was not different between age groups;(2) no thromboembolic event occurred in untreated patients with low or intermediate clinical probability aged under 54 years of age, whereas 7 events were diagnosed in patients aged over 73 years (p< 0.001); (3) a higher proportion of older patients had a positive result at both spiral CT and CUS examinations. The percentage of positive CT scans in the case of negative or inconclusive CUS results was not different between age groups; conversely, in the case of a negative or inconclusive CT scan, the percentage of positive CUS was higher in older patients. In conclusion, management of elderly suspected PE patients appears to be different from both the work-up and the outcome perspectives.
Cost-effectiveness of low-molecular-weight heparin for secondary prophylaxis of cancer-related venous thromboembolism
Authors: Smith Kenneth , Cornuz Jacques , Roberts Mark , Aujesky Drahomir
Published: February 2005

Although extended secondary prophylaxis with low-molecular-weight heparin was recently shown to be more effective than warfarin for cancer-related venous thromboembolism, its cost-effectiveness compared to traditional prophylaxis with warfarin is uncertain. We built a decision analytic model to evaluate the clinical and economic outcomes of a 6-month course of low-molecular-weight heparin or warfarin therapy in 65-year-old patients with cancer-related venous thromboembolism. We used probability estimates and utilities reported in the literature and published cost data. Using a US societal perspective, we compared strategies based on quality-adjusted life-years (QALYs) and lifetime costs. The incremental cost-effectiveness ratio of low-molecular-weight heparin compared with warfarin was $149, 865/QALY. Low-molecular-weight heparin yielded a quality-adjusted life expectancy of 1.097 QALYs at the cost of $15, 329. Overall, 46% ($7108) of the total costs associated with low-molecular-weight heparin were attributable to pharmacy costs. Although the low-molecular-weigh heparin strategy achieved a higher incremental quality-adjusted life expectancy than the warfarin strategy (difference of 0.051 QALYs), this clinical benefit was offset by a substantial cost increment of $7,609. Cost-effectiveness results were sensitive to variation of the early mortality risks associated with low-molecular-weight heparin and warfarin and the pharmacy costs for low-molecular-weight heparin. Based on the best available evidence, secondary prophylaxis with low-molecular-weight heparin is more effective than warfarin for cancer-related venous thromboembolism. However, because of the substantial pharmacy costs of extended low-molecular-weight heparin prophylaxis in the US, this treatment is relatively expensive compared with warfarin.
Clustering the annotation space of proteins
Authors: Kunin Victor , Ouzounis Christos A
Published: February 2005

Background

Current protein clustering methods rely on either sequence or functional similarities between proteins, thereby limiting inferences to one of these areas.

Results

Here we report a new approach, named CLAN, which clusters proteins according to both annotation and sequence similarity. This approach is extremely fast, clustering the complete SwissProt database within minutes. It is also accurate, recovering consistent protein families agreeing on average in more than 97% with sequence-based protein families from Pfam. Discrepancies between sequence- and annotation-based clusters were scrutinized and the reasons reported. We demonstrate examples for each of these cases, and thoroughly discuss an example of a propagated error in SwissProt: a vacuolar ATPase subunit M9.2 erroneously annotated as vacuolar ATP synthase subunit H. CLAN algorithm is available from the authors and the CLAN database is accessible at http://maine.ebi.ac.uk:8000/cgi-bin/clan/ClanSearch.pl

Conclusions

CLAN creates refined function-and-sequence specific protein families that can be used for identification and annotation of unknown family members. It also allows easy identification of erroneous annotations by spotting inconsistencies between similarities on annotation and sequence levels.
Expression of human dopamine receptor in potato (Solanum tuberosum) results in altered tuber carbon metabolism
Authors: Skirycz Aleksandra , Świędrych Anna , Szopa Jan
Published: February 2005

Background

Even though the catecholamines (dopamine, norepinephrine and epinephrine) have been detected in plants their role is poorly documented. Correlations between norepinephrine, soluble sugars and starch concentration have been recently reported for potato plants over-expressing tyrosine decarboxylase, the enzyme mediating the first step of catecholamine synthesis. More recently norepinephrine level was shown to significantly increase after osmotic stress, abscisic acid treatment and wounding. Therefore, it is possible that catecholamines might play a role in plant stress responses by modulating primary carbon metabolism, possibly by a mechanism similar to that in animal cells. Since to date no catecholamine receptor has been identified in plants we transformed potato plants with a cDNA encoding human dopamine receptor (HD1).

Results

Tuber analysis of transgenic plants revealed changes in the activities of key enzymes mediating sucrose to starch conversion (ADP-glucose phosphorylase and sucrose synthase) and sucrose synthesis (sucrose phosphate synthase) leading to altered content of both soluble sugars and starch. Surprisingly the catecholamine level measured in transgenic plants was significantly increased; the reason for this is as yet unknown. However the presence of the receptor affected a broader range of enzyme activities than those affected by the massive accumulation of norepinephrine reported for plants over-expressing tyrosine decarboxylase. Therefore, it is suggested that the presence of the exogenous receptor activates catecholamine cAMP signalling in plants.

Conclusions

Our data support the possible involvement of catecholamines in regulating plant carbon metabolism via cAMP signalling pathway.
Isometric force production parameters during normal and experimental low back pain conditions
Authors: Descarreaux Martin , Blouin Jean-Sébastien , Teasdale Normand
Published: February 2005

Background

The control of force and its between-trial variability are often taken as critical determinants of motor performance. Subjects performed isometric trunk flexion and extension forces without and with experiment pain to examine if pain yields changes in the control of trunk forces. The objective of this study is to determine if experimental low back pain modifies trunk isometric force production.

Methods

Ten control subjects participated in this study. They were required to exert 50 and 75% of their isometric maximal trunk flexion and extension torque. In a learning phase preceding the non painful and painful trials, visual and verbal feedbacks were provided. Then, subjects were asked to perform 10 trials without any feedback. Time to peak torque, time to peak torque variability, peak torque variability as well as constant and absolute error in peak torque were calculated. Time to peak and peak dF/dt were computed to determine if the first peak of dF/dt could predict the peak torque achieved.

Results

Absolute and constant errors were higher in the presence of a painful electrical stimulation. Furthermore, peak torque variability for the higher level of force was increased with in the presence of experimental pain. The linear regressions between peak dF/dt, time to peak dF/dt and peak torque were similar for both conditions. Experimental low back pain yielded increased absolute and constant errors as well as a greater peak torque variability for the higher levels of force. The control strategy, however, remained the same between the non painful and painful condition. Cutaneous pain affects some isometric force production parameters but modifications of motor control strategies are not implemented spontaneously.

Conclusions

It is hypothesized that adaptation of motor strategies to low back pain is implemented gradually over time. This would enable LBP patients to perform their daily tasks with presumably less pain and more accuracy.
Nutritional knowledge, food habits and health attitude of Chinese university students –a cross sectional study–
Authors: Sakamaki Ruka , Toyama Kenji , Amamoto Rie , Liu Chuan-Jun , Shinfuku Naotaka
Published: February 2005

Background

We have previously shown that irregular lifestyle of young Japanese female students are significantly related to their desire to be thinner. In the present study, we examined the nutritional knowledge and food habits of Chinese university students and compared them with those of other Asian populations.

Methods

A self-reported questionnaire was administered to 540 students, ranging in age from 19-24 years. Medical students from Beijing University (135 men and 150 women) in Northern China and Kunming Medical College in southern China (95 men and 160 women) participated in this study. The parametric variables were analyzed using the Student's t-test. Chi-square analyses were conducted for non-parametric variables

Results

Our results showed that 80.5% of students had a normal BMI and 16.6 % of students were underweight with the prevalence of BMI>30 obesity being very low in this study sample. Young Chinese female students had a greater desire to be thinner (62.0%) than males (47.4%). Habits involving regular eating patterns and vegetable intake were reported and represent practices that ought to be encouraged.

Conclusions

The university and college arenas represent the final opportunity for the health and nutritional education of a large number of students from the educator's perspective. Our findings suggest the need for strategies designed to improve competence in the area of nutrition.
Sweet proteins – Potential replacement for artificial low calorie sweeteners
Authors: Kant Ravi
Published: February 2005

Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with development of bladder cancer. Naturally occurring sweet and taste modifying proteins are being seen as potential replacements for the currently available artificial low calorie sweeteners. Interaction aspects of sweet proteins and the human sweet taste receptor are being investigated.
Association study with Wegener granulomatosis of the human phospholipase Cγ2 gene
Authors: Jagiello Peter , Wieczorek Stefan , Yu Philipp , Csernok Elena , Gross Wolfgang L , Epplen Joerg T
Published: February 2005

Background

Wegener Granulomatosis (WG) is a multifactorial disease of yet unknown aetiology characterized by granulomata of the respiratory tract and systemic necrotizing vasculitis. Analyses of candidate genes revealed several associations, e.g. with α(1)-antitrypsin, proteinase 3 and with the HLA-DPB1 locus. A mutation in the abnormal limb mutant 5 (ALI5) mouse in the region coding for the hydrophobic ridge loop 3 (HRL3) of the phospholipaseCγ2 (PLCγ-2) gene, corresponding to human PLCγ-2 exon 27, leads to acute and chronic inflammation and granulomatosis. For that reason, we screened exons 11, 12 and 13 coding for the hydrophobic ridge loop 1 and 2 (HRL1 and 2, respectively) and exon 27 of the PLCγ-2 protein by single strand conformation polymorphism (SSCP), sequencing and PCR/ restriction fragment length polymorphism (RFLP) analyses. In addition, we screened indirectly for disease association via 4 microsatellites with pooled DNA in the PLCγ-2 gene.

Results

Although a few polymorphisms in these distinct exons were observed, significant differences in allele frequencies were not identified between WG patients and respective controls. In addition, the microsatellite analyses did not reveal a significant difference between our patient and control cohort.

Conclusion

This report does not reveal any hints for an involvement of the PLCγ-2 gene in the pathogenesis of WG in our case-control study.
Age dependent association of endometrial polyps with increased risk of cancer involvement
Authors: Hileeto Denise , Fadare Oluwole , Martel Maritza , Zheng Wenxin
Published: February 2005

Background

Endometrial polyps (EMPs) are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1) to investigate the age-group in which EMP are most commonly encountered 2) to document the age-group in which EMP are most commonly associated with malignancies 3) To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4) To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data.

Patients and methods

All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986–1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof) of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups.

Results

We identified 513 EMPs, of which 209 (41%) were from biopsy specimens and 304 (59%) from hysterectomy specimens. Sixty six (13%) of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5%) of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32%) of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p < 0.001). The most common histologic type of malignancy was endometrioid adenocarcinoma.

Conclusions

EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice. Additional studies are needed to address the histological features and immunohistochemical profiles in the context of association between endometrioid and high-grade endometrial carcinoma and endometrial polyps.
Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes
Authors: Kress Elsa , Baydoun Hicham Hachem , Bex Françoise , Gazzolo Louis , Duc Dodon Madeleine
Published: February 2005

Background

In this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1.

Results

We have previously observed that hnRNP A1 (A1) down-modulates the post transcriptional activity of Rex protein of HTLV-1. Here, we tested whether the ectopic expression of a dominant negative mutant (NLS-A1-HA) defective in shuttling activity or knockdown of the hnRNPA1 gene using RNA interference could inhibit Rex-mediated export of viral mRNAs in HTLV-1 producing C91PL T-cells. We show that the expression of NLS-A1-HA does not modify the export of Rex-dependent viral mRNAs. Conversely, inhibiting A1 expression in C91PL cells by RNA interference provoked an increase in the Rex-dependent export of unspliced and singly spliced mRNAs. Surprisingly, we also observed a significant increase in proviral transcription and an accumulation of unspliced mRNAs, suggesting that the splicing process was affected. Finally, A1 knockdown in C91PL cells increased viral production by these cells. Thus, hnRNP A1 is implicated in the modulation of the level of HTLV-1 gene expression in T cells transformed by this human retrovirus.

Conclusions

These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells.
Verknoten und Durchfädeln von Molekülen: Chemie und Chiralität molekularer Knoten und ihrer Ensembles
Authors: Lukin Oleg , Vögtle Fritz
Published: February 2005

Wie und warum durchfädelt, verstrickt oder verknotet man Moleküle? Vom Studium molekularer Knoten (Knotane) erhofft man sich Einblicke in die Mechanismen der Bildung (supra)molekularer Schablonen (Template) und in das Falten von Molekülen mit dem Ziel der Verschlingung. Die topologische Chiralität dieser faszinierenden Moleküle führt zu neuen Typen von Isomerie und weist einen Weg hin zu nanoskaligen molekularen Motoren. Ihre Herstellung und Derivatisierung stellt hohe Ansprüche an moderne Synthesemethoden und analytische Trennverfahren, wobei sich die Ansätze zum molekularen Verknoten durch ein mehr oder weniger geplantes Design von Metallkoordinations‐ oder Wasserstoffbrückenmustern auszeichnen. Dieser Aufsatz beschreibt die Entwicklung der Templattechniken für die Synthese von Knotanen über ihre Enantiomerentrennung bis hin zu ihrer selektiven Funktionalisierung und ihrem Einsatz als Bausteine zur Synthese höherer Knotenensembles. Diese können linear verzweigt oder makrocyclisch aufgebaut sein, was einerseits wegen der vielfachen topologisch stereogenen Einheiten zu bisher nicht gefundenen Isomerenzusammensetzungen führt und andererseits neue Typen künstlicher Makromoleküle jenseits der Polymere und dendritischen Moleküle definiert.
Analyzing protein complexes in Drosophila with tandem affinity purification–mass spectrometry
Authors: Veraksa Alexey , Bauer Andreas , Artavanis‐Tsakonas Spyros
Published: February 2005

We describe the application of tandem affinity purification–mass spectrometry (TAP‐MS) to the study of protein complexes in Drosophila. We have constructed vectors for inducible expression of TAP‐tagged fusion proteins in Drosophila cultured cells and in vivo. Using these vectors, we tagged, as a paradigm, several components of the Notch signaling pathway, isolated protein complexes containing the baits and associated proteins from cells and embryos, and identified the subunits by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Several known interactions involving Notch pathway elements were confirmed, and many novel potential interactions were uncovered. For some of the novel associations, we validated the interaction genetically and biochemically. We conclude that TAP, in combination with MS, can be used as an effective method for the studies of the Drosophila proteome. Developmental Dynamics 232:827–834, 2005. © 2005 Wiley‐Liss, Inc.