bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischaemic Contracture in an Infant’s Forearm – A Case Report
Authors: ISSHIKI H. , NAKAMURA T. , TAKAYAMA S. , TOYAMA Y.
Published: August 2004

We present a case of a gradually developing ischaemic contracture of the forearm muscles of an infant who developed without any trauma or acute gangrene at birth. Release of the middle and ring finger digitorum profundus muscles and pronator quadratus at 2 years of age corrected the deformity. Histopathology showed no evidence of fibromatosis or any other tumor. Although a dynamic splint was used to maintain the range of motion, the range of the middle finger motion deteriorated gradually 2 years after surgery. Though the pathogenesis of this problem was unclear, we assume that it was caused by fibrosis of muscles as a result of bleeding before or during delivery.
Hand Muscle Pathology after Long-Term Vibration Exposure
Authors: NECKING LARS E. , LUNDBORG GÖRAN , LUNDSTRÖM RONNIE , THORNELL LARS-ERIC , FRIDÉN JAN
Published: August 2004

The morphology of the abductor pollicis brevis muscle was studied in 20 patients suffering from hand–arm vibration syndrome. The main morphological changes observed were centrally located myonuclei and fibre type grouping (found in all 20 muscle biopsies), angulated muscle fibres (found in 19 biopsies), ring fibres and regenerating fibres (found in 18 biopsies) and fibrosis (found in 17 biopsies). The observed abnormalities are believed to reflect damage to both the muscle fibres and the motor nerve. The changes were related to different vibration exposure parameters. The number of fibres demonstrating centrally located nuclei correlated significantly with the cumulative vibration exposure, while the number of angulated fibres correlated significantly with the total vibration exposure time. This indicates that the vibrating tools may cause direct damage to muscle fibres as well as nerves.
Volatiles in glasses from the HSDP2 drill core
Authors: Seaman Caroline , Sherman Sarah Bean , Garcia Michael O. , Baker Michael B. , Balta Brian , Stolper Edward
Published: August 2004

H2O, CO2, S, Cl, and F concentrations are reported for 556 glasses from the submarine section of the 1999 phase of HSDP drilling in Hilo, Hawaii, providing a high‐resolution record of magmatic volatiles over ∼200 kyr of a Hawaiian volcano's lifetime. Glasses range from undegassed to having lost significant volatiles at near‐atmospheric pressure. Nearly all hyaloclastite glasses are degassed, compatible with formation from subaerial lavas that fragmented on entering the ocean and were transported by gravity flows down the volcano flank. Most pillows are undegassed, indicating submarine eruption. The shallowest pillows and most massive lavas are degassed, suggesting formation by subaerial flows that penetrated the shoreline and flowed some distance under water. Some pillow rim glasses have H2O and S contents indicating degassing but elevated CO2 contents that correlate with depth in the core; these tend to be more fractionated and could have formed by mixing of degassed, fractionated magmas with undegassed magmas during magma chamber overturn or by resorption of rising CO2‐rich bubbles by degassed magmas. Intrusive glasses are undegassed and have CO2 contents similar to adjacent pillows, indicating intrusion shallow in the volcanic edifice. Cl correlates weakly with H2O and S, suggesting loss during low‐pressure degassing, although most samples appear contaminated by seawater‐derived components. F behaves as an involatile incompatible element. Fractionation trends were modeled using MELTS. Degassed glasses require fractionation at p ≈ 5–10 bars. Undegassed low‐SiO2 glasses require fractionation at p ≈ 50 bars. Undegassed and partially degassed high‐SiO2 glasses can be modeled by coupled crystallization and degassing. Eruption depths of undegassed pillows can be calculated from their volatile contents assuming vapor saturation. The amount of subsidence can be determined from the difference between this depth and the sample's depth in the core. Assuming subsidence at 2.5 mm/y, the amount of subsidence suggests ages of ∼500 ka for samples from the lower 750 m of the core, consistent with radiometric ages. H2O contents of undegassed low‐SiO2 HSDP2 glasses are systematically higher than those of high‐SiO2 glasses, and their H2O/K2O and H2O/Ce ratios are higher than typical tholeiitic pillow rim glasses from Hawaiian volcanoes.
Air‐sea CO2 exchange in the equatorial Pacific
Authors: McGillis Wade R. , Edson James B. , Zappa Christopher J. , Ware Jonathan D. , McKenna Sean P. , Terray Eugene A. , Hare Jeffrey E. , Fairall Christopher W. , Drennan William , Donelan Mark , DeGrandpre Michael D. , Wanninkhof Rik , Feely Richard A.
Published: August 2004

GasEx‐2001, a 15‐day air‐sea carbon dioxide (CO2) exchange study conducted in the equatorial Pacific, used a combination of ships, buoys, and drifters equipped with ocean and atmospheric sensors to assess variability and surface mechanisms controlling air‐sea CO2 fluxes. Direct covariance and profile method air‐sea CO2 fluxes were measured together with the surface ocean and marine boundary layer processes. The study took place in February 2001 near 125°W, 3°S in a region of high CO2. The diurnal variation in the air‐sea CO2 difference was 2.5%, driven predominantly by temperature effects on surface solubility. The wind speed was 6.0 ± 1.3 m s−1, and the atmospheric boundary layer was unstable with conditions over the range −1 < z/L < 0. Diurnal heat fluxes generated daytime surface ocean stratification and subsequent large nighttime buoyancy fluxes. The average CO2 flux from the ocean to the atmosphere was determined to be 3.9 mol m−2 yr−1, with nighttime CO2 fluxes increasing by 40% over daytime values because of a strong nighttime increase in (vertical) convective velocities. The 15 days of air‐sea flux measurements taken during GasEx‐2001 demonstrate some of the systematic environmental trends of the eastern equatorial Pacific Ocean. The fact that other physical processes, in addition to wind, were observed to control the rate of CO2 transfer from the ocean to the atmosphere indicates that these processes need to be taken into account in local and global biogeochemical models. These local processes can vary on regional and global scales. The GasEx‐2001 results show a weak wind dependence but a strong variability in processes governed by the diurnal heating cycle. This implies that any changes in the incident radiation, including atmospheric cloud dynamics, phytoplankton biomass, and surface ocean stratification may have significant feedbacks on the amount and variability of air‐sea gas exchange. This is in sharp contrast with previous field studies of air‐sea gas exchange, which showed that wind was the dominating forcing function. The results suggest that gas transfer parameterizations that rely solely on wind will be insufficient for regions with low to intermediate winds and strong insolation.
Recurrence of volcanic activity along the Roman Comagmatic Province (Tyrrhenian margin of Italy) and its tectonic significance
Authors: Marra F. , Taddeucci J. , Freda C. , Marzocchi W. , Scarlato P.
Published: August 2004

The Roman Comagmatic Province (RCP) developed along the NW‐SE striking extensional Tyrrhenian margin of Italy since middle Pleistocene and includes ultrapotassic small eruptive centers and large volcanic districts. By means of a review and statistical analysis of a large data set of radiometric ages we demonstrate that in the RCP, major eruptive cycles occurred at different volcanic districts almost simultaneously and with an almost constant recurrence time. Our analysis started with the Alban Hills Volcanic District, where a detailed 40Ar/39Ar chronology of the eruptive cycles has been recently achieved, and then extended to include a database of 264 radiometric ages of the RCP volcanics published since 1980. Statistical treatment of the data set shows a marked non‐Poissonian behavior of volcanic activity through the whole magmatic province, with climax of each major eruptive cycle occurring simultaneously at the different districts approximately every 48 kyr. The concomitant eruption of many volcanic districts spreading over a 250‐km‐long chain implies a control mechanism acting at a regional scale. After discussing the possible relationship between tectonics, sea level changes, and volcanic activity we hypothesize that constant rates of slab retreat during middle Pleistocene could have been a key factor controlling the rate of magma upwelling and the major cycles of recharge of the magma chambers. As a working hypothesis, we propose that the duration of the cycles may be related to (1) progressive weakening of the crust due to magma underplating or (2) cyclic injection of convective plumes into the mantle wedge.
Do the western Himalayas defy global warming?
Authors: Yadav Ram R. , Park Won‐Kyu , Singh Jayendra , Dubey Bhasha
Published: August 2004

Observational records and reconstructions from tree rings reflect premonsoon (March to May) temperature cooling in the western Himalaya during the latter part of the 20th century. A rapid decrease of minimum temperatures at around three times higher rate, as compared to the rate of increase in maximum temperatures found in local climate records is responsible for the cooling trend in mean premonsoon temperature. The increase of the diurnal temperature range is attributed to large scale deforestation and land degradation in the area and shows the higher influence of local forcing factors on climate in contrast to the general trend found in higher latitudes of the northern Hemisphere.
Projected temperature changes along the American cordillera and the planned GCOS network
Authors: Bradley Raymond S. , Keimig Frank T. , Diaz Henry F.
Published: August 2004

Analysis of 7 GCM simulations with 2x CO2 levels shows large and statistically significant free air temperature changes (compared to controls) along the axis of the American Cordillera (from Alaska to southern Chile). At all latitudes, the modeled change in temperature increases with elevation. Temperature increases are especially large in boreal summer months from ∼35–50°N, and year‐round in the high mountains of Peru, Bolivia and northern Chile. If these models are correct, mountain ranges that extend high into the lower troposphere are likely to experience significant warming, with implications for glacier mass balance and water resources, montane ecosystems and high elevation agricultural activities. There are few high elevation meteorological stations to validate the model projections, or to monitor future changes. The planned GCOS (Global Climate Observing System) surface network is not adequate to address the critical issues raised by these model simulations; additional high elevation observing stations are needed.
Multi‐scale probability distributions of solar wind speed fluctuations at 1 AU described by a generalized Tsallis distribution
Authors: Burlaga L. F. , F.‐Viñas A.
Published: August 2004

The probability distributions of changes in the solar speed observed at 1 AU by ACE during 1999 on scales from 1 hour to 171 days and at a scale of 64 sec can be described by a single distribution function. The function is a simple generalization of the Tsallis q‐distribution, a probability distribution that was derived from nonextensive statistical mechanics. The fluctuations in speed are related to (1) intermittent turbulence and shocks on the smallest scales; (2) ejecta, corotating streams, slow flows, interaction regions, etc. on intermediate scales; and (3) systems of interacting flows involving all of these features, on scales greater than the solar rotation period.
Seasonal cycles of nonmethane hydrocarbons and methyl chloride, as derived from firn air from Dronning Maud Land, Antarctica
Authors: Kaspers K. A. , van de Wal R. S. W. , de Gouw J. A. , Hofstede C. M. , van den Broeke M. R. , Reijmer C. H. , van der Veen C. , Neubert R. E. M. , Meijer H. A. J. , Brenninkmeijer C. A. M. , Karlöf L. , Winther J.‐G.
Published: August 2004

This paper presents atmospheric concentrations of ethane, propane, acetylene, and methyl chloride, inferred from firn air by using a numerical one‐dimensional firn diffusion model. The firn air was collected on the Antarctic plateau in Dronning Maud Land during the Norwegian Antarctic Research Expedition (NARE) 2000/2001. The influences of seasonal variations in temperature and pressure and the variation in accumulation rate were studied and are not negligible, but appear to cancel each other out if all variability is taken into account. This paper also demonstrates that firn air from the uppermost firn layer (30 m) can be used to derive seasonal cycles of these trace gases, without needing a year‐round facility. These cycles display higher atmospheric mixing ratios during the Antarctic winter and lower atmospheric mixing ratios in summer. The cycles for the year 2000 show amplitudes of 140 ± 25 ppt for ethane, 30 ± 10 ppt for propane, 24 ± 6 ppt for acetylene, and 40 ± 20 ppt for methyl chloride. For ethane and propane the amplitudes and months of maximum atmospheric concentration (phase) are in reasonable agreement with year‐round measurements at the South Pole and Baring Head (New Zealand). The amplitudes for methyl chloride and acetylene are significantly greater than seen in year‐round measurements at the South Pole and at Neumayer (Antarctica), although the phase is in line. While biomass burning and removal by OH radicals can partially explain these large amplitudes, the exact cause still remains unclear for methyl chloride and acetylene.
Olympus Mons aureole deposits: New evidence for a flank failure origin
Authors: McGovern P. J. , Smith J. R. , Morgan J. K. , Bulmer M. H.
Published: August 2004

The origin of the rough‐textured aureoles that surround the immense Olympus Mons volcano on Mars is controversial. We present data from the Mars Global Surveyor and Mars Odyssey missions to demonstrate that at least two of the aureole lobes are derived from the volcano's flanks in large and probably catastrophic mass movement events, leaving behind headwalls that constitute the basal scarp. This evidence stems from the morphology and internal structure of aureole blocks, which exhibit remnants of volcanic flow units on their surfaces. Our claim is supported by plausible reconstructions of the prefailure flanks. Structural analogs to known flank failure events at Hawaiian volcanoes suggest that repeated cycles of flank growth and collapse at Olympus Mons allow generation of the observed aureoles from a protoedifice similar in size and shape to the present one.
Robustness properties of circadian clock architectures
Authors: Stelling Jörg , Gilles Ernst Dieter , Doyle Francis J.
Published: August 2004

Robustness, a relative insensitivity to perturbations, is a key characteristic of living cells. However, the specific structural characteristics that are responsible for robust performance are not clear, even in genetic circuits of moderate complexity. Formal sensitivity analysis allows the investigation of robustness and fragility properties of mathematical models representing regulatory networks, but it yields only local properties with respect to a particular choice of parameter values. Here, we show that by systematically investigating the parameter space, more global properties linked to network structure can be derived. Our analysis focuses on the genetic oscillator responsible for generating circadian rhythms in
Drosophila
as a prototypic dynamical cellular system. Analysis of two mathematical models of moderate complexity shows that the tradeoff between robustness and fragility is largely determined by the regulatory structure. Rank-ordered sensitivities, for instance, allow the correct identification of protein phosphorylation as an influential process determining the oscillator's period. Furthermore, sensitivity analysis confirms the theoretical insight that hierarchical control might be important for achieving robustness. The complex feedback structures encountered
in vivo
, however, do not seem to enhance robustness
per se
but confer robust precision and adjustability of the clock while avoiding catastrophic failure.
Mapping activation and repression domains of the vnd/NK-2 homeodomain protein
Authors: Stepchenko Alexander , Nirenberg Marshall
Published: August 2004

A transient transfection assay using
Drosophila S2
tissue culture cells and WT and mutant
Drosophila
vnd/NK-2 homeobox cDNAs was used to localize repression and activation domains of vnd/NK-2 homeodomain protein. A repression domain was identified near the N terminus of vnd/NK-2 homeodomain protein (amino acid residues 154–193), which contains many hydrophobic amino acid residues. The major determinants of the repression domain were shown to be amino acid residues F155, W158, I161, L162, L163, and W166. Truncated protein consisting of the N-terminal repression domain and the DNA-binding homeodomain repressed transcription as efficiently as WT vnd/NK-2 protein. An activation domain was identified between the tinman domain and the homeodomain (amino acid residues 277–543), which consists of a glutamine-rich subdomain and two acidic subdomains. No effect was detected of the tinman domain or the NK-2-specific domain on either activation or repression of a β-galactosidase reporter gene.
Gene-based vaccines and immunotherapeutics
Authors: Liu Margaret , Acres Bruce , Balloul Jean-Marc , Bizouarne Nadine , Paul Stephane , Slos Philippe , Squiban Patrick
Published: August 2004

DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies, and cancer; plasmids encoding normal human proteins are likewise being tested as vaccines and treatments for autoimmune diseases. Examples of
in vivo
prophylaxis and immunotherapy, based on different types of immune responses (humoral and cellular), in a variety of disease models and under evaluation in early phase human clinical trials are presented. Viral vectors continue to show better levels of expression than those achieved by DNA plasmid vectors. We have focused our clinical efforts, at this time, on the use of recombinant viral vectors for both vaccine as well as cytokine gene transfer studies. We currently have four clinical programs in cancer immunotherapy. Two nonspecific immunotherapy programs are underway that apply adenoviral vectors for the transfer of cytokine genes into tumors
in situ
. An adenovirus-IFNγ construct (TG1042) is currently being tested in phase II clinical trials in cutaneous lymphoma. A similar construct, adenovirus-IL2 (TG1024), also injected directly into solid tumors, is currently being tested in patients with solid tumors (about one-half of which are melanoma). Encouraging results are seen in both programs. Two cancer vaccine immunotherapy programs focus on two cancer-associated antigens: human papilloma virus E6 and E7 proteins and the epithelial cancer-associated antigen MUC1. Both are encoded by a highly attenuated vaccinia virus vector [modified vaccinia Ankara (MVA)] and both are coexpressed with IL-2. Encouraging results seen in both of these programs are described.
Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1)
Authors: Shi Song-Hai , Cox Daniel N. , Wang Denan , Jan Lily Yeh , Jan Yuh-Nung
Published: August 2004

Development of both dendrites and axons is important for the formation of neuronal circuits, because dendrites receive information and the axon is responsible for sending signals. In the past decade, extensive studies have revealed many molecules underlying axonal outgrowth and pathfinding. In contrast, much less is known about the molecular mechanisms that control dendrite development. Here we report the identification of an evolutionarily conserved Ig superfamily member, dendrite arborization and synapse maturation 1 (Dasm1), which plays a critical role in dendrite development. Dasm1 contains five Ig domains and two fibronectin III domains in the extracellular N terminus, a single transmembrane domain, and an intracellular C-terminal tail with a type I PDZ domain binding motif at the end. It is highly expressed in the brain and localized at the dendrites. Suppression of Dasm1 expression in hippocampal neurons via RNA interference or expression of Dasm1 without its cytoplasmic tail specifically impairs dendrite, but not axon, outgrowth. Together with its orthologues in other species, Dasm1 defines a family of molecules likely involved specifically in dendrite arborization.
Plasma malondialdehyde is induced by smoking: a study with balanced antioxidant profiles
Authors: Lykkesfeldt Jens , Viscovich Michael , Poulsen Henrik E.
Published: August 2004

It has been reported that smokers have higher plasma malondialdehyde concentrations compared with non-smokers. However, smokers have also consistently been shown to have a lower intake of fruits and vegetables as well as lower plasma antioxidant concentrations. Since both the latter issues may well influence the malondialdehyde concentration, we wanted to investigate if the observed difference between smokers and non-smokers was a result of differences in antioxidant status or if a more direct effect of smoking could also be isolated. In the present study, the plasma malondialdehyde and antioxidant profiles of a cohort of smokers (n48) and non-smokers (n32) were compared. While there was no significant difference in the major plasma antioxidants measured, i.e. ascorbic acid, α- and γ-tocopherol and uric acid, we found a significant effect of smoking on plasma malondialdehyde (P=0·0003). Consequently, the present study suggests that lipid peroxidation as measured by plasma malondialdehyde is induced by smokingper se. While poor antioxidant status presumably also affects lipid peroxidation, it is only partly responsible for the increased level found in smokers in general.
Effect of a nutritional intervention promoting the Mediterranean food pattern on electrophoretic characteristics of low-density lipoprotein particles in healthy women from the Québec City metropolitan area
Authors: Goulet Julie , Lamarche Benoît , Charest Amélie , Nadeau Geneviève , Lapointe Annie , Desroches Sophie , Lemieux Simone
Published: August 2004

The objective of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern in free-living conditions on LDL electrophoretic characteristics in a group of seventy-one healthy women, aged between 30 and 65 years. The 12-week nutritional intervention consisted of two courses on nutrition and seven individual sessions with a dietitian. The first course provided information on the Mediterranean food pattern and the second was a cooking lesson. LDL peak particle diameter (LDL-PPD) and cholesterol levels in small (LDL-cholesterol<255?Å) and large LDL fractions (LDL-cholesterol>260?Å) were obtained by 2–16% polyacrylamide gel electrophoresis of whole plasma. The sample was divided on the basis of baseline LDL-PPD using tertiles of the distribution (258·4 Å and 260·0 Å). Among the total sample of women, no significant change in LDL-PPD was observed in response to the nutritional intervention. However, subjects who at baseline were in the first tertile of the LDL-PPD distribution (>258·4 Å) showed a significant increase in LDL-PPD and in the proportion of LDL%>260?%uest;Åin response to the 12-week nutritional intervention (P>0·05). In contrast, LDL-PPD decreased significantly (P=0·007) among women with large LDL particles at baseline (LDL-PPD >260 Å) while the proportion of LDL%<255 Åand of LDL%>260 Åremained unchanged. To conclude, changes in the food pattern, in response to a nutritional intervention promoting the Mediterranean food pattern, were accompanied by beneficial modifications in LDL electrophoretic characteristics in women who were characterised at baseline by smaller LDL particles.
Changes over 20 years in macronutrient intake and body mass index in 11- to 12-year-old adolescents living in Northumberland
Authors: Fletcher E. S. , Rugg-Gunn A. J. , Matthews J. N. S. , Hackett A. , Moynihan P. J. , Mathers J. C. , Adamson A. J.
Published: August 2004

Monitoring adolescent diets over time enables the assessment of the effectiveness of public health messages which are particularly important in vulnerable groups such as adolescents. In 2000, 424 children aged 11–12 years old completed two 3 d estimated dietary records. On the fourth day one nutritionist interviewed each child to clarify the information in the diary and foods were quantified with the aid of food models. Nutrient intake was calculated using computerised food tables. These children attended the same seven schools in the same Northumberland area as the 11- to 12-year-old children who recorded their diet using the same method in 1980 (n405) and 1990 (n379), respectively. Height and weight, and parental occupation were recorded in all three surveys for each child. Height and weight were used to calculate BMI, weight was used to estimate BMR and parental occupation was used to determine social class. Comparing the macronutrient intakes in 2000 with 1980 and 1990, energy intakes (EI) fell in boys (to 8·45 MJ) and girls (to 7·60 MJ). This fall may, at least in part, be due to an increase in low energy reporting. For 1980, 1990 and 2000 the percentage of boys with EI:BMR below 1·1 was 6, 15 and 23%, respectively; for girls, 3, 14 and 18%, respectively. Percentage energy from fat was unchanged between 1980 and 1990 but fell to 35% (about 76 g/d) in 2000, alongside a 3% increase in percentage energy from starch (30%). Percentage energy from non-milk extrinsic sugars remained above recommendations (16%; about 82 g/d). The number of overweight and obese children increased from 11% to 30% between 1980 and 2000. Positive changes have occurred in the Northumbrian adolescent diet but social inequalities, reported in previous surveys, remain.
Endogenous amino acid flow in the avian ileum: quantification using three techniques
Authors: Ravindran V. , Hew L. I. , Ravindran G.
Published: August 2004

The aim of the present study was to compare the protein-free diet, guanidinated casein (GuC) and enzyme hydrolysed casein (EHC) methods for the quantification of endogenous amino acid (AA) flow in the avian ileum. Growing broiler chickens (5 weeks old) were used. All three assay diets were based on dextrose, and in the GuC and EHC diets GuC or EHC were the sole source of N. Endogenous AA flows determined with the use of protein-free diet were considerably lower (P>0·05) than those determined by the GuC and EHC methods. The total endogenous AA flows determined by the GuC and EHC methods were almost 3-fold greater (P>0·05) than those determined by the protein-free diet. The endogenous AA values obtained from GuC and EHC methods were similar (P<0·05), except for the flow of arginine, which was lower (P>0·05) in the EHC method. Glutamic acid, aspartic acid, threonine and glycine were the predominant endogenous AA present in digesta from the distal ileum. The contents of methionine, histidine and cystine were lower compared with other AA. The method of determination had no effect on the AA composition of endogenous protein, except for threonine, glutamic acid, lysine, arginine and cystine. The concentrations of threonine and arginine were lower (P>0·05) and that of lysine was higher (P>0·05) with the EHC method compared with the other two methods. The concentration of glutamic acid was greater (P0·05) and that of cystine was lower (P>0·05) in the EHC and GuC methods compared with the protein-free diet method. The results showed that the ileal endogenous flows of N and AA are markedly enhanced by the presence of protein and peptides, above those determined following feeding of a protein-free diet. It is concluded that the use of EHC and GuC methods enables the measurement of ileal endogenous losses in chickens under normal physiological conditions.
Urinary excretion of purine derivatives as an index of microbial protein synthesis in the camel (Camelus dromedarius)
Authors: Guerouali Abdelhai , Gass Youssef El , Balcells Joaquim , Belenguer Alvaro , Nolan John
Published: August 2004

Five experiments were carried out to extend knowledge of purine metabolism in the camel (Camelus dromedarius) and to establish a model to enable microbial protein outflow from the forestomachs to be estimated from the urinary excretion of purine derivatives (PD; i.e. xanthine, hypoxanthine, uric acid, allantoin). In experiment 1, four camels were fasted for five consecutive days to enable endogenous PD excretion in urine to be determined. Total PD excretion decreased during the fasting period to 267 (se 41·5)?μmol/kg body weight (W)0·75per d. Allantoin and xanthine+hypoxanthine were consistently 86 and 6·1?% of total urinary PD during this period but uric acid increased from 3·6?% to 7·4?%. Xanthine oxidase activity in tissues (experiment 2) was (μmol/min per g fresh tissue) 0·038 in liver and 0·005 in gut mucosa but was not detected in plasma. In experiment 3, the duodenal supply of yeast containing exogenous purines produced a linear increase in urinary PD excretion rate with the slope indicating that 0·63 was excreted in urine. After taking account of endogenous PD excretion, the relationship can be used to predict purine outflow from the rumen. From the latter prediction, and also the purine:protein ratio in bacteria determined in experiment 5, we predicted the net microbial outflow from the rumen. In experiment 4, with increasing food intake, the rate of PD excretion in the urine increased linearly by about 11·1?mmol PD/kg digestible organic matter intake (DOMI), equivalent to 95?g microbial protein/kg DOMI.
DWE: Discriminating Word Enumerator
Authors: Sumazin Pavel , Chen Gengxin , Hata Naoya , Smith Andrew D. , Zhang Theresa , Zhang Michael Q.
Published: August 2004

Motivation: Tissue-specific transcription factor binding sites give insight into tissue-specific transcription regulation.

Results: We describe a word-counting-based tool for de novo tissue-specific transcription factor binding site discovery using expression information in addition to sequence information. We incorporate tissue-specific gene expression through gene classification to positive expression and repressed expression. We present a direct statistical approach to find overrepresented transcription factor binding sites in a foreground promoter sequence set against a background promoter sequence set. Our approach naturally extends to synergistic transcription factor binding site search.

We find putative transcription factor binding sites that are overrepresented in the proximal promoters of liver-specific genes relative to proximal promoters of liver-independent genes. Our results indicate that binding sites for hepatocyte nuclear factors (especially HNF-1 and HNF-4) and CCAAT/enhancer-binding protein (C/EBPβ) are the most overrepresented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with HNF-1, HNF-4 and HNF-3β and with C/EBPβ.

Availability: Programs are available for use over the Web at http://rulai.cshl.edu/tools/dwe

Contact:  ps@cs.pdx.edu; mzhang@cshl.edu

Supplementary information: Data and omitted results are available at http://rulai.cshl.edu/tools/dwe/supp
SABmark—a benchmark for sequence alignment that covers the entire known fold space
Authors: Van Walle Ivo , Lasters Ignace , Wyns Lode
Published: August 2004

Summary: The Sequence Alignment Benchmark (SABmark) provides sets of multiple alignment problems derived from the SCOP classification. These sets, Twilight Zone and Superfamilies, both cover the entire known fold space using sequences with very low to low, and low to intermediate similarity, respectively. In addition, each set has an alternate version in which unalignable but apparently similar sequences are added to each problem.

Availability: SABmark is available from http://bioinformatics.vub.ac.be

Contact:  ivwalle@vub.ac.be
Gene name ambiguity of eukaryotic nomenclatures
Authors: Chen Lifeng , Liu Hongfang , Friedman Carol
Published: August 2004

Motivation: With more and more scientific literature published online, the effective management and reuse of this knowledge has become problematic. Natural language processing (NLP) may be a potential solution by extracting, structuring and organizing biomedical information in online literature in a timely manner. One essential task is to recognize and identify genomic entities in text. ‘Recognition’ can be accomplished using pattern matching and machine learning. But for ‘identification’ these techniques are not adequate. In order to identify genomic entities, NLP needs a comprehensive resource that specifies and classifies genomic entities as they occur in text and that associates them with normalized terms and also unique identifiers so that the extracted entities are well defined. Online organism databases are an excellent resource to create such a lexical resource. However, gene name ambiguity is a serious problem because it affects the appropriate identification of gene entities. In this paper, we explore the extent of the problem and suggest ways to address it.

Results: We obtained gene information from 21 organisms and quantified naming ambiguities within species, across species, with English words and with medical terms. When the case (of letters) was retained, official symbols displayed negligible intra-species ambiguity (0.02%) and modest ambiguities with general English words (0.57%) and medical terms (1.01%). In contrast, the across-species ambiguity was high (14.20%). The inclusion of gene synonyms increased intra-species ambiguity substantially and full names contributed greatly to gene-medical-term ambiguity. A comprehensive lexical resource that covers gene information for the 21 organisms was then created and used to identify gene names by using a straightforward string matching program to process 45 000 abstracts associated with the mouse model organism while ignoring case and gene names that were also English words. We found that 85.1% of correctly retrieved mouse genes were ambiguous with other gene names. When gene names that were also English words were included, 233% additional ‘gene’ instances were retrieved, most of which were false positives. We also found that authors prefer to use synonyms (74.7%) to official symbols (17.7%) or full names (7.6%) in their publications.

Contact:  lifeng.chen@dbmi.columbia.edu
Filtering of Ineffective siRNAs and Improved siRNA Design Tool
Authors: Yiu S. M. , Wong Prudence W. H. , Lam T.W. , Mui Y.C. , Kung H. F. , Lin Marie , Cheung Y. T.
Published: August 2004

Motivation: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs.

Results: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective.

Availability: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/

Contact:  smyiu@cs.hku.hk
Missing value estimation for DNA microarray gene expression data: local least squares imputation
Authors: Kim Hyunsoo , Golub Gene H. , Park Haesun
Published: August 2004

Motivation: Gene expression data often contain missing expression values. Effective missing value estimation methods are needed since many algorithms for gene expression data analysis require a complete matrix of gene array values. In this paper, imputation methods based on the least squares formulation are proposed to estimate missing values in the gene expression data, which exploit local similarity structures in the data as well as least squares optimization process.

Results: The proposed local least squares imputation method (LLSimpute) represents a target gene that has missing values as a linear combination of similar genes. The similar genes are chosen by k-nearest neighbors or k coherent genes that have large absolute values of Pearson correlation coefficients. Non-parametric missing values estimation method of LLSimpute are designed by introducing an automatic k-value estimator. In our experiments, the proposed LLSimpute method shows competitive results when compared with other imputation methods for missing value estimation on various datasets and percentages of missing values in the data.

Availability: The software is available at http://www.cs.umn.edu/~hskim/tools.html

Contact:  hpark@cs.umn.edu
Preoperative Pregnancy Testing in Ambulatory Surgery
Authors: Manley Steven , de Kelaita Grace , Joseph Ninos J. , Salem M. Ramez , Heyman Harold J.
Published: August 2004

Background

The incidence of unrecognized early pregnancy and its influence on the surgical and anesthetic course in patients presenting for elective ambulatory surgery have not been previously determined. The current study was designed to determine the incidence of unrecognized pregnancy in women presenting for ambulatory surgery. In addition, it examined how discovery of the pregnancy altered the anesthetic or surgical course.

Methods

In a prospective study over a 1-yr period, all women of childbearing potential (defined as menstruating women without prior hysterectomy or tubal ligation) were preoperatively evaluated and tested for urine or serum human chorionic gonadotropin, to determine unrecognized pregnancy. If a pregnancy was detected, the disposition of the surgical procedure and the effect on the surgical and anesthetic management was recorded.

Results

Of 2,056 women of childbearing potential presenting for ambulatory surgery, testing revealed 7 previously unrecognized pregnancies, an incidence of 0.3%. Included among these patients were two patients scheduled to undergo fertility procedures. On learning the test result and even before being advised of available options, all patients elected to cancel or postpone the surgical procedure.

Conclusions

The incidence of previously unrecognized pregnancy in menstruating women presenting for ambulatory, nonobstetric surgery was 0.3%. The knowledge of a positive test resulted in cancellation or postponement of the operative procedure. Patient desire for cancellation was the main determining factor in each case.
Prolonged Alleviation of Tactile Allodynia by Intravenous Lidocaine in Neuropathic Rats
Authors: Chaplan Sandra R. , Bach Flemming W. , Shafer Steven L. , Yaksh Tony L.
Published: August 2004

Background

Lidocaine may be useful in the treatment of neuropathic pain states. The authors hypothesized that lidocaine would reduce tactile allodynia observed in a rat nerve injury model. In an effort to determine the site of drug action, effects after intravenous, intrathecal, and regional administration were compared.

Methods

Rats underwent ligation of the left fifth and sixth lumbar spinal nerves. The 50% thresholds (g) for left hind paw withdrawal of awake rats to von Frey hairs were documented before, during, and after intravenous administration of lidocaine at programmed/documented pseudo-steady-state plasma concentrations, and correlated with measured plasma concentrations. Responses to lidocaine application intrathecally and regionally to the injured nerves were also recorded.

Results

In rats with tactile allodynia, intravenous lidocaine yielded 66 +/- 11% of the maximal possible effect on thresholds (100% = normal threshold), versus -1.3 +/- 2.7% for saline infusion. Twenty-one days after lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold increases depended on plasma concentration, rather than quantity of drug administered: rats receiving 15 mg/kg with higher plasma concentrations (1.2 +/- 0.1 micrograms/ml) showed significant allodynia suppression throughout 7 days of follow-up, whereas rats receiving 15 mg/kg at a slower rate with lower plasma concentrations (0.6 +/- 0.1 microgram/ml) did not. The EC50 for acute allodynia suppression was 0.75 microgram/ml. No such allodynia suppression was seen after intrathecal or regional administration of lidocaine despite transient neural blockade.

Conclusions

Intravenous, but not intrathecal or regionally applied, lidocaine produces dose-dependent suppression of allodynia associated with nerve injury. The effects far outlast plasma concentrations of lidocaine. The mechanism of these prolonged effects is unknown.
α2-Adrenergic Receptors in Human Dorsal Root Ganglia
Authors: Ongjoco Rita R. S. , Richardson Charlene D. , Rudner Xiaowen L. , Stafford-Smith Mark , Schwinn Debra A.
Published: August 2004

Background

Nonselective alpha2-adrenergic receptor (alpha2AR) agonists (e.g., clonidine) mediate antinociception in part through alpha2ARs in spinal cord dorsal horn; however, use of these agents for analgesia in humans is limited by unwanted sedation and hypotension. The authors previously demonstrated alpha2a approximately alpha2b > > > alpha2c mRNA in human spinal cord dorsal horn cell bodies. However, because 20% of dorsal horn alpha2ARs derive from cell bodies that reside in the associated dorsal root ganglion (DRG), it is important to evaluate alpha2AR expression in this tissue as well. Therefore, the authors evaluated the hypothesis that alpha2b mRNA, alpha2c mRNA, or both are present in human DRG.

Methods

Molecular approaches were used to determine alpha2AR expression in 28 human DRGs because of low overall receptor mRNA expression and small sample size. After creation of synthetic competitor cDNA and establishment of amplification conditions with parallel efficiencies, competitive reverse transcription polymerase chain reaction was performed using RNA isolated from human DRG.

Results

Overall expression of alpha2AR mRNA in DRG is low but reproducible at all spinal levels. alpha2b and alpha2cAR subtype mRNAs predominate (alpha2b approximately alpha2c), accounting for more than 95% of the total alpha2AR mRNA in DRG at all human spinal nerve root levels.

Conclusions

Predominance of alpha2b and alpha2cAR mRNA in human DRG is distinct from alpha2AR mRNA expression in cell bodies originating in human spinal cord dorsal horn, where alpha2a and alpha2b predominate with little or absent alpha2c expression. These findings also highlight species heterogeneity in alpha2AR expression in DRG. If confirmed at a protein level, these findings provide an additional step in unraveling mechanisms involved in complex neural pathways such as those for pain.
Reliability of Pharmacodynamic Analysis by Logistic Regression
Authors: Lu Wei , Bailey James M.
Published: August 2004

Background

Many pharmacologic studies record data as binary yes-or-no variables, and analysis is performed using logistic regression. This study investigates the accuracy of estimation of the drug concentration associated with a 50% probability of drug effect (C50) and the term describing the steepness of the concentration-effect relation (gamma).

Methods

The authors developed a technique for simulating pharmacodynamic studies with binary yes-or-no responses. Simulations were conducted assuming either that each data point was derived from the same patient or that data were pooled from multiple patients in a population with log-normal distributions of C50 and gamma. Coefficients of variation were calculated. The authors also determined the percentage of simulations in which the 95% confidence intervals contained the true parameter value.

Results

The coefficient of variation of parameter estimates decreased with increasing n and gamma. The 95% confidence intervals for C50 estimation contained the true parameter value in more than 90% of the simulations. However, the 95% confidence intervals of gamma did not contain the true value in a substantial number of simulations of data from multiple patients.

Conclusion

The coefficient of variation of parameter estimates may be as large as 40-50% for small studies (n < or = 20). The 95% confidence intervals of C50 almost always contain the true value, underscoring the need for always reporting confidence intervals. However, when data from multiple patients is naively pooled, the estimates of gamma may be biased, and the 95% confidence intervals may not contain the true value.
A Dose-ranging Study of Rapacuronium in Pediatric Patients
Authors: Meakin George H. , Meretoja Olli A. , Motsch Johann , Taivainen Tomi , Wirtavuori Kari , Schönstedt Rüdiger , Perkins Russell , McCluskey Anthony
Published: August 2004

Background

The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children.

Methods

Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph.

Results

Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious.

Conclusions

Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.