bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent epidemiological changes in meningococcal disease may be due to the displacement of serogroup A by serogroup C in Hefei city, China
Authors: Ni J Dong , Jin Y H , Dai B , Wang X P , Liu D Q , Chen X , Zheng Y , Ye D Q
Published: March 2008

Objectives

To determine the change in epidemiological characteristics of meningococcal disease in the Hefei city area and to provide valuable information for developing timely and appropriate public health interventions.

Methods

Meningococcal disease was identified according to the National Disease Surveillance System. Data were collected using standardised questionnaires. Serological and bacteria culture testing was performed on cerebrospinal fluid and serum specimens from suspected cases for evidence of Neisseria meningitidis infection.

Results

From July 2003 to June 2007, meningococcal disease was confirmed in 386 cases in the total population. This worked out at an annual incidence of 1.19–2.86 per 100 000 population, which was significantly higher than that in 2002–3 (0.27 cases per 100 000 population). The increase in incidence was accompanied by a shift in age distribution, more cases being reported in adolescents and young adults: the median age increased to 15 years (range 2 months to 78 years). When assessed by age group, middle-school students (aged 12–17) had the highest incidence (6.57 per 100 000 population) and the highest proportion (31.4%). The N meningitidis serogroup was identified in 135 (35.0%) of the cases of meningococcal disease; all were serogroup C. No cases due to serogroup A or other strains were found during the study period. The mean case-fatality rate was 7.3%, with a peak of 16.9% in children younger than 6. Since winter 2003, a vaccination campaign has been partially implemented, but the effectiveness has been limited.

Conclusions

The incidence of meningococcal disease has substantially increased in Hefei city, which may be due to the replacement of serogroup A by serogroup C. A shift in age distribution of cases to adolescents and young adults was found.
Chemistry of Atmospheric Deposition, the Snowpack, and Snowmelt in the Turkey Lakes Watershed
Authors: Semkin R. G. , Jeffries D. S.
Published: March 2008

Bulk and wet-only deposition and the snowpack were monitored at the Turkey Lakes Watershed in northern Ontario over the winter and spring of 1986. Based on a comparison with snowpack and cumulative snowmelt, the bulk sampler overcollected major ions by factors ranging from 6 to 22%. Nitrate appeared to be preferentially collected by the bulk sampler relative to SO42− during snow events. Dry deposition was estimated to be 12 and 5% of total deposition forSO42− and NO3−, respectively. Ion budgets for cumulative bulk deposition and snowmelt supported the hypothesis that ion losses from the snowpack are insignificant during a winter having no melt episodes. Snowmelt was characterized by chemical fractionation of major ions; SO42− and H+ in initial meltwaters were 10 times more concentrated than the premelt snowpack. Preferential elution of ions in the snowmelt followed the sequence: SO42− > NO3− > H+ > Cl−. Snowmelt chemistry was used to predict changes in lake chemistry: H+, NO3−, and NH4+ levels should increase in lake waters; Ca2+ decreases through dilution by snowmelt; SO42− concentrations remain fairly constant.
Ion Mass Budgets for Lakes in the Turkey Lakes Watershed, June 1981 – May 1983
Authors: Jeffries D. S. , Semkin R. G. , Neureuther R. , Seymour M.
Published: March 2008

Ion mass budgets were determined for two water years (June – May 1981–83) for Batchawana L. South, Wishart L., Little Turkey L., and Turkey L. Water budgets balance within measurement error except for Little Turkey L. (output surplus for both water years) and Batchawana L. South (output surplus for 1982–83). Groundwater seepage is hypothesized to explain these water budget imbalances. The chemical budgets show that H+, NH4+, and NO3− are retained by the lakes to varying degrees. The major input pathway for H+ and NH4+ is via direct atmospheric deposition, while relatively weaker terrestrial retention of NO3− causes basin runoff to be the major input pathway for this parameter. All three species are playing an acidifying role on the Turkey Lakes Watershed. Chemical budgets for Mg2+, Na+, K+, SO42−, and Cl− are generally balanced for all lakes relative to the water budgets. In contrast, Ca2+ and acid-neutralizing capacity (ANC) exhibit excess output over measured plus estimated inputs. Probable unmeasured inputs of these two parameters include groundwater seepage and Ca2+ exchange with the sediments. In-lake generation of ANC by SO42− reduction is of minor importance.
Application of a Hydrological Model to the Acidified Turkey Lakes Watershed
Authors: Bobba A. G. , Lam D. C. L.
Published: March 2008

A hydrological model applied to the Turkey Lakes Watershed at different locations produced results which agreed closely with observed stream flow, groundwater flow, snowpack, and snowpack chemistry. The model results are consistent with many of the episodic events that have occurred in the watershed. The snowpack sulphate concentration is simulated with a simple sulphate model linked to the hydrological model. The different calibrated hydrological coefficients were found to vary with the geology and geomorphology at several locations in he watershed. The general applicability of these coefficients was confirmed by comparing model results with a new set of data from subsequent years.
Axle load shifts during truck braking and their implications for bridge and pavement design
Authors: Hutchinson B. G. , Rilett L. R. , Green R. , Haas R. C. G.
Published: March 2008

The axle load shifts of four truck types during braking are estimated using theoretical braking models and the implications of these axle load shifts for bridge and pavement design are explored. The truck types examined are a three-axle straight truck, a five-axle tractor semi-trailer, a seven-axle tractor semi-trailer with two air-lift belly axles, and a seven-axle B-train tractor-double trailer, each loaded to legal Ontario limits with weigh-out commodities. Each of the truck types experienced a substantial load transfer to the front steering axles under braking, mainly from the rear tandem axle groups, where the front axle load increase varied from 38 to 48%. The bridge design implications of the load shifts are examined in terms of the Ontario Bridge Formula and the moments induced in simple-span bridges compared with the moments induced by a reference design truck. For the braking model used, the decelerations and associated shifts in axle load do not lead to higher forces for bridge design and evaluation. The pavement damage implications are analyzed in terms of load equivalency functions derived from some load tests conducted at a number of pavement sites across Canada in 1986. These equivalencies increased up to 50% of the static values for the three-axle truck at maximum braking. It is suggested that the major damage implications are at intersections in urban areas and that increased structural sections could be designed to handle the increased equivalencies. Key words: bridge design, pavement design, truck braking, truck loads, pavement damage, bridge damage.
Combined flexure and torsion of I-shaped steel beams
Authors: Driver Robert G. , Kennedy D. J. Laurie
Published: March 2008

Design standards provide little information for the design of I-shaped steel beams not loaded through the shear centre and therefore subjected to combined flexure and torsion. In particular, methods for determining the ultimate capacity, as is required in limit states design standards, are not presented. The literature on elastic analysis is extensive, but only limited experimental and analytical work has been conducted in the inelastic region. No comprehensive design procedures, applicable to limit states design standards, have been developed.From four tests conducted on cantilever beams, with varying moment–torque ratios, it is established that the torsional behaviour has two distinct phases, with the second dominated by second-order geometric effects. This second phase is nonutilizable because the added torsional restraint developed is path dependent and, if deflections had been restricted, would not have been significant. Based on the first-phase behaviour, a normal and shearing stress distribution on the cross section is proposed. From this, a moment–torque ultimate strength interaction diagram is developed, applicable to a number of different end and loading conditions. This ultimate limit state interaction diagram and serviceability limit states, based on first yield and on distortion limitations, provide a comprehensive design approach for these members. Key words: beams, bending moment, flexure, inelastic, interaction diagram, I-shaped, limit states, serviceability, steel, torsion, torque, ultimate.
Intercity auto trip estimation for Sri Lanka using entropy maximization
Authors: Ratnayake L. L.
Published: March 2008

Recently, techniques such as calibration of demand models and entropy maximization have been used to estimate origin–destination (O–D) matrices. To the author's knowledge, there has been no reported work on an O–D estimation for a nationwide network. This paper describes a methodology to estimate intercity auto traffic for Sri Lanka using entropy maximization. Some of these results are then compared with the values obtained from a known demand model and the actual data. Key words: O–D matrices, entropy maximization, Sri Lanka, link volume, intercity.
Productivity growth in the paper and paperboard industries: a variable cost function approach
Authors: Borger Bruno De , Buongiorno Joseph
Published: March 2008

Annual indices of total productivity growth were calculated for the paper and paperboard industries of the United States between 1958 and 1981. The procedure relied on the hypothesis that each industry minimizes variable costs, conditional on the level of the remaining inputs. The variable cost functions revealed short-run economies of scale but long-run diseconomies, suggesting inefficient capacity expansion. Derived demands for energy, labor, and materials were inelastic. Demand for energy was much more responsive to price than labor and materials. There were substantial substitution possibilities between energy and materials and between labor and materials, but none between labor and energy. The productivity indices that were computed showed a slightly increasing rate of productivity growth between 1958 and 1973, with a marked slowdown thereafter. This slowdown was explained by the rise in the price of energy. Average productivity growth was three to four times faster in the paper than in the paperboard industry between 1958 and 1981. This difference was partly explained by higher energy intensiveness and lower labor productivity growth in the paperboard industry.
A new method for evaluating decay: the effect of oxygen on Polyporuscompactus in red oak
Authors: Hall T. J. , Leben Curt
Published: March 2008

The effects of oxygen decay (weight loss) incited by Polyporuscompactus Overh. was studied using small fresh and dried wood blocks containing both sapwood and heartwood of similar radial position and age. A manifold was used to deliver hydrated gas mixtures of 1.0, 4.2, or 21% (ambient air) oxygen at constant pressure and continuous flow to jars containing inoculated or noninoculated blocks. Means (P = 0.05) for dry weight losses in inoculated blocks at 1.0, 4.2, and 21% oxygen were 3.3, 8.9, and 21.4%, respectively; losses may be comparable to decay by other white rot fungi using the soil-block procedure. Losses in noninoculated blocks at the above oxygen levels were 2.0, 4.6, and 7.0%, respectively. Differences in dry weight losses between fresh and dry blocks were found. In particular, losses in inoculated fresh blocks were significantly less than losses in inoculated dry blocks in ambient air. Native inhabitants occurring in fresh wood appear to interfere with the decay processes of P. compactus. Losses in noninoculated fresh blocks were significantly greater than in noninoculated dry blocks at 21% oxygen but not at 1.0 or 4.2% oxygen; losses were attributed to natural inhabitants in fresh wood.
Genotype–nitrogen interactions in full-sib seedlings of black spruce
Authors: Mullin T. J.
Published: March 2008

Genotype–environment interactions were investigated in 40 full-sib black spruce (Piceamariana (Mill.) B.S.P.) families grown in a greenhouse for 25 weeks under three levels of nitrogen fertility. Large general combining ability components of variance indicated that much of the genetic variance was additive. Heritability estimates were also high, with narrow-sense heritabilities of 0.35 for 25-week height growth and 0.15 for ovendry weight. Specific combining ability, reciprocal, and maternal effects were negligible for all but very early seed and growth characters. Statistically significant family × nitrogen interaction components were detected for all growth variables. Stability analysis using regression suggested that these interactions were due more to differences in degree of expression of genetic variation than to extreme changes in rank. Generally, the families that ranked in the top 10% at the highest nitrogen level were above average at all other levels.
The distribution of Endocronartiumharknessii and Cronartiumquercuum on jack pine in Minnesota
Authors: Dietrich R. A. , Blanchette R. A. , Croghan C. F. , Phillips S. O.
Published: March 2008

In 1984, a survey was done to determine the distribution of pine–pine gall rust (Endocronartiumharknessii (J. P. Moore) Y. Hiratsuka) and pine–oak gall rust (Cronartiumquercuum (Berk) Miyabe ex Shirai f.sp. banksianae Burdsall and Snow) on jack pine (Pinusbanksiana Lamb.) throughout its range in Minnesota. Sporulating globose galls (960 galls from 257 stands) were collected in May and June and the pathogens were identified on the basis of aeciospore germ tube morphology. The relative usefulness of aeciospore germination characteristics that have been used to separate these rusts was examined. Endocronartiumharknessii predominated in the northeastern and Cronartiumquercuum in the southwestern portions of the range of jack pine. This information will be useful in selecting and growing rust-resistant trees and for monitoring changes in the distribution of these rusts in the future.
Mycorrhizal responsiveness of Thuja, Calocedrus, Sequoia, and Sequoiadendron species of western North America
Authors: Kough J. L. , Molina Randy , Linderman R. G.
Published: March 2008

Four western conifers inoculated or not inoculated with three species of vesicular–arbuscular mycorrhizal fungi were grown in pasteurized soil and maintained at 11 or 43 ppm phosphorus. Compared with controls, vesicular–arbuscular mycorrhizal colonization increased biomass more of younger than older seedlings. In young seedlings, species with large seeds responded less to phosphate addition or vesicular–arbuscular mycorrhizal colonization than smaller seeded species. Vesicular–arbuscular mycorrhizal seedlings with low phosphorus were always larger than noninoculated low phosphorus controls and comparable in size or larger than nonmycorrhizal controls at moderate phosphorus. Vesicular–arbuscular mycorrhizal plants produced from 100 to 2000% more biomass than noninoculated plants at low phosphorus, and from equality to 500% at moderate phosphorus. Vesicular–arbuscular mycorrhizal fungal species did not differ in plant growth enhancement or root colonization at any seedling age or phosphorus fertility examined. Tree species' responsiveness ranged as follows: Thujaplicata > Sequoiasempervirens > Calocedrusdecurrens > Sequoiadendrongiganteum. Vesicular–arbuscular mycorrhizal fungi enhanced seedling uniformity and size in all the tree species.
The effects of acidic deposition on cation leaching from three deciduous forest canopies
Authors: Lovett Gary M. , Lindberg Steven E. , Richter Daniel D. , Johnson Dale W.
Published: March 2008

Canopy leaching or retention of all major ions was determined for three deciduous forests in eastern Tennessee that are currently receiving wet and dry acidic deposition. For all three canopies, the retention of atmospherically deposited cations (H+ and [Formula: see text]) exceeded retention of deposited anions [Formula: see text] on a charge-equivalent basis. Charge balance was maintained by ion exchange between the deposited cations and K+, Ca2+, and Mg2+ on the canopy surfaces. It was found that 40–60% of the leaching of K+, Ca2+, and Mg2+ from these canopies results from this exchange process, with the remainder attributable to coleaching with plant-derived anions. Because the cation exchange can be largely attributed to retention of deposited H+, we interpret it as a measure of the acidic deposition effect on foliar cation leaching. Dry deposition was found to be an important input for most of the major cations and anions. The data indicate that organic anions may be important counter ions to cation leaching, especially in the absence of acidic deposition, and that acid–base reactions in the canopy can obscure the true H+-exchange reactions between the deposition and the canopy.
Development of vesicular–arbuscular mycorrhizae in a young sweetgum plantation
Authors: Kormanik Paul P.
Published: March 2008

Sweetgum seedlings with vesicular–arbuscular mycorrhizae formed by Glomusetunicatum or Glomusdeserticola in nursery soil with 30 ppm available phosphorus (P) and nonmycorrhizal seedlings grown in nursery soil with 800 ppm available P were outplanted and whole trees were excavated periodically over the next 5 years in the plantation to follow mycorrhizal development. Four months after outplanting, roots of all initially nonmycorrhizal seedlings had formed vesicular–arbuscular mycorrhizae and the degree of root colonization was comparable to that of initially vesicular–arbuscular mycorrhizal seedlings. New feeder roots did not develop on seedlings of any treatment until almost 5 months after planting. By the end of the first growing season and for the remainder of the study, vesicular–arbuscular mycorrhizae development was approximately the same on all seedlings. The proportion of feeder roots colonized by vesicular–arbuscular mycorrhizal fungi stabilized at 65 to 70%; approximately 56% of the cortical tissues of all feeder roots were colonized with arbuscles, vesicles, and hyphae. Periodic assays of the soil in the plantation showed that vesicular–arbuscular mycorrhizal fungal spores gradually declined from an initial high of 3600 spores to 620 spores per 100-cm3 soil sample after 5 years. This decline was probably caused by crown closure of the sweetgum trees which gradually suppressed understory vegetation.
Embryogenesis in subcultured callus of Larixdecidua
Authors: Nagmani R. , Bonga J. M.
Published: March 2008

Megagametophytes were excised from immature ovules of Larixdecidua Mill. Archegonia, proembryos or embryos, and suspensors were removed from these gametophytes and the remaining tissue was then cultured on media with various auxins, cytokinins, and organic nitrogen sources. After 8–9 weeks, a few of the cultures produced callus. When subcultured on hormone-free medium, this callus grew rapidly and produced a large number of embryoids with suspensors. Embryogenesis was intense through six to eight successive transfers and then slowed down in subsequent transfers. Many of the embryoids formed plantlets, the ploidy of which still remains to be determined.
The prediction of understory vegetation by environmental factors for the purpose of site classification in forestry: an example from northern Ontario using residual ordination analysis
Authors: Carleton T. J. , Jones R. K. , Pierpoint G.
Published: March 2008

Problems arise in the use of understory vegetation as an indicator of site condition in that impermanent factors such as microclimate, succession, and chance may play significant roles in determining local composition. Residual ordination analysis is a method which facilitates quantification of the sources of variation in understory vegetation over a landscape. Here it is applied to survey data, representing 250 stands upon which the forest ecosystem classification programme for the Clay Belt portion of northeastern Ontario is based, to test the premise that vegetation types will differentiate soil conditions for forestry purposes. Ordination of the data by detrended correspondence analysis yielded a bivariate scatterplot which, through visual appraisal, seemed readily interpretable in terms of site-related nutrient and moisture gradients. Formal exploration, using canonical redundancy analysis, yielded the following predictive model: understory vegetation (detrended correspondence analysis axes 1 and 2) = soils (67%) + canopy (8%) + succession (1%) + error (24%). Extraction of residual ordinations confirmed this general model and demonstrated that although canopy and successional influences are minor in the data, they are significant. Because the nonsite-related, predictable components account for only 9% of the variation at most, the premise of the existing forest ecosystem classification system is judged to be sound insofar as the data upon which it is based adequately describe the range of commercial stand conditions normally encountered. The results are discussed in relation to vegetation survey design and the performance of residual ordination analysis on a large data set is assessed.
Tree size, biomass, and volume growth of twelve 34-year-old Ontario jack pine provenances
Authors: Magnussen S. , Smith V. G. , Yeatman C. W.
Published: March 2008

Tree size and aboveground biomass in twelve 34-year-old Ontario jack pine (Pinusbanksiana Lamb.) provenances growing at Petawawa National Forestry Institute (Chalk River, Ontario) was negatively correlated with latitude of origin. The best provenance exceeded the local provenance in tree height and diameter by approximately 10%. The pattern of geographical variation was stable over time, making general and sound predictions of provenance growth based on juvenile performance feasible. Persistent differences among some geographically close provenances indicated the potential for genetic improvement by selecting the best populations within site regions. The results demonstrated have important implications for jack pine breeding and improvement strategies at the provenance level. The provenance averages of aboveground ovendry weight per tree ranged from 44 to 79 kg. The aboveground tree biomass was distributed as follows in seven analyzed provenances: stem wood, 78%; stem bark, 8%; branch wood, 8%; needles, 5%; cones, 1%. Variation in average stemwood mass among provenances was less than the variation in average stem volume because of a strong negative correlation on a single tree basis between stem volume and stem wood density. The mean annual volume and biomass accretion per hectare in the best provenances averaged 10 m3 and 4 t, respectively. Total stem volume production per hectare varied exponentially with tree height. Mean annual stem volume increment of the best provenances exceeded that of the slowest growing provenances by 22–40%.
Comparing treatment means correctly and appropriately
Authors: Mize Carl W. , Schultz Richard C.
Published: March 2008

Many researchers set up an experiment, make measurements, do an analysis of variance, calculate the mean response for each treatment, and then try to decide if the treatment means are significantly different and why. Duncan's multiple-range test is frequently used to test the difference among treatment means. It is, however, only one of a number of techniques that can be used to examine treatment means. Some researchers are unaware of the different techniques and that the interpretation of the results of an experiment can be strongly influenced by the technique used. In fact, using an inappropriate technique can lead to making incorrect recommendations and to completely missing major treatment effects. Selection of the appropriate technique to use for a particular experiment depends upon the nature of the treatments and the objectives of the research. This paper discusses four techniques (ranking treatment means, multiple comparison procedures, fitting response models, and using contrasts to make planned comparisons) that can be used to examine treatment means and presents examples of each one.
Chemical composition of interstitial water in decaying lodgepole pine bole wood
Authors: Yavitt Joseph B. , Fahey Timothy J.
Published: March 2008

The chemical composition of interstitial water in highly decayed lodgepole pine (Pinuscontorta ssp. latifolia) bole wood lying on the forest floor was sampled during the spring snow melt period in 1981 and 1982. The solutions were dominated by nutrient-rich organic compounds, with more than 95% of the dissolved total N and P occurring in organically bound forms. Relatively low C: N (45: 1) and C: P (280: 1) ratios for these organic compounds were 4- and 12- fold lower than C: N and C: P ratios for the solid phase, respectively, suggesting that they were preferentially mineralized by heterotrophic microorganisms. Subsequent rapid absorption by tree roots and microbes during the snow melt period probably was responsible for maintaining the low inorganic N and P concentrations that occurred. Presence of soluble polyphenols and carbohydrates, primary components of the lignocellulose wood substrate, suggest that the dissolved organic compounds resulted in part from the incomplete oxidation of organic matter decay products. Soluble organic ligands accounted for more than 65% of the solution charge balance. Although 80% of the dissolved organic carbon was acidic in nature, solution pH values were rather high (5.4), in part because of high concentrations of base cations.
Depletion of viable seeds of Betulapubescens and Betulaverrucosa sown onto some north Swedish forest soils
Authors: Granström Anders , Fries Clas
Published: March 2008

Seeds of Betulapubescens Ehrh. and Betulaverrucosa Ehrh. were sown onto the forest floor at sites of different vegetation types in mature north Swedish coniferous forests. Subsamples of the seeded soil were taken each spring and fall and analysed for viable seeds. During the 1st year after seeding, the population of viable birch seeds in the soil declined to approximately 6% of the original. During the 2nd year, the rate of depletion was much smaller and the population of viable seeds decreased to approximately 3% of the original. Part of the material was followed over 3 years and the rate of decline was similar during the 3rd year to that during the 2nd year. There were no significant differences when comparing the proportion of seeds remaining viable in different vegetation types, nor were there any significant differences when comparing the two species. It is inferred that seeds produced in a forest stand and stored in the soil at the time of clear-cutting could give rise to Betula seedlings. These results indicate that the risk would be strongly reduced if seed-producing birch trees are removed a few years ahead of clear-cutting, when birch regeneration is undesirable.
The "trap-log" method to survey the distribution of Armillariamellea in forest soils
Authors: Mallett K. I. , Hiratsuka Y.
Published: March 2008

A technique using trembling aspen logs was tested to detect and study Armillariamellea in the soil of a young lodgepole pine stand. A total of 121 sharpened trembling aspen logs were pounded into the ground 1 m apart in a 10 × 10 m grid. Evidence of colonization by A. mellea appeared in 31 logs. A map was drawn to show relationships of colonized logs to diseased and healthy trees as well as to stumps within the plot. Eight distinctive patches were found within the plot. Isolates from positive "trap logs" and diseased trees were found to be the same biological species of the A. mellea complex.
Effect of repeated pollination upon filled seed in white spruce
Authors: Ho Rong H.
Published: March 2008

Repeated pollinations with brush had very little effect on the production of filled seed and pollen from the first pollination was most likely to accomplish fertilization in white spruce (Piceaglauca (Moench) Voss). Based on the filled seed and the number of coloured pollen on the nucellus, it was suggested that pollinated ovules would stop exuding any pollination drops.
Multistage sampling with partial replacement
Authors: Omule Stephen A. Y.
Published: March 2008

not available
POISSON GEOMETRY OF PARABOLIC BUNDLES ON ELLIPTIC CURVES
Authors: BALDUZZI DAVID
Published: March 2008

The moduli space of G-bundles on an elliptic curve with additional flag structure admits a Poisson structure. The bivector can be defined using double loop group, loop group and sheaf cohomology constructions. We investigate the links between these methods and for the case SL2 perform explicit computations, describing the bracket and its leaves in detail.
Acquisition of the Temporal and Ordinal Structure of Movement Sequences in Incidental Learning
Authors: O'Reilly Jill X. , McCarthy Katharine J. , Capizzi Mariagrazia , Nobre Anna Christina
Published: March 2008

We investigated the acquisition and integration of temporal and ordinal sequence information in an incidental learning model of motor skill acquisition (the serial reaction time task). Human participants were exposed to a stimulus-response sequence that had temporal structure, ordinal structure, or both. By changing the temporal or ordinal structure, or both, we were able to ask two questions: first, does a regular temporal structure facilitate learning of an ordinal sequence and second, is a temporal sequence, presented in the context of a random ordinal sequence of finger movements, “picked up” through incidental learning? We found that a predictable temporal structure greatly facilitated the learning of an ordinal sequence but was not learned when presented in isolation. The results suggest that when motor skills are acquired under incidental learning conditions, timing is represented at a level specific to the ordinal sequence of movements rather than as an independent temporal template.
Neural Coding of Global Form in the Human Visual Cortex
Authors: Ostwald Dirk , Lam Judith M. , Li Sheng , Kourtzi Zoe
Published: March 2008

Extensive psychophysical and computational work proposes that the perception of coherent and meaningful structures in natural images relies on neural processes that convert information about local edges in primary visual cortex to complex object features represented in the temporal cortex. However, the neural basis of these mid-level vision mechanisms in the human brain remains largely unknown. Here, we examine functional MRI (fMRI) selectivity for global forms in the human visual pathways using sensitive multivariate analysis methods that take advantage of information across brain activation patterns. We use Glass patterns, parametrically varying the perceived global form (concentric, radial, translational) while ensuring that the local statistics remain similar. Our findings show a continuum of integration processes that convert selectivity for local signals (orientation, position) in early visual areas to selectivity for global form structure in higher occipitotemporal areas. Interestingly, higher occipitotemporal areas discern differences in global form structure rather than low-level stimulus properties with higher accuracy than early visual areas while relying on information from smaller but more selective neural populations (smaller voxel pattern size), consistent with global pooling mechanisms of local orientation signals. These findings suggest that the human visual system uses a code of increasing efficiency across stages of analysis that is critical for the successful detection and recognition of objects in complex environments.
Modulation of drug resistance by artificial transcription factors
Authors: Blancafort Pilar , Tschan Mario P. , Bergquist Sharon , Guthy Daniel , Brachat Arndt , Sheeter Dennis A. , Torbett Bruce E. , Erdmann Dirk , Barbas Carlos F.
Published: March 2008

The efficiency of chemotherapeutic treatments in cancer patients is often impaired by the acquisition of drug resistance. Cancer cells develop drug resistance through dysregulation of one or more genes or cellular pathways. To isolate efficient regulators of drug resistance in tumor cells, we have adopted a genome-wide scanning approach based on the screening of large libraries of artificial transcription factors (ATFs) made of three and six randomly assembled zinc finger domains. Zinc finger libraries were linked to a VP64 activation domain and delivered into a paclitaxel-sensitive tumor cell line. Following drug treatment, several ATFs were isolated that promoted drug resistance. One of these ATFs, 3ZF-1-VP, promoted paclitaxel resistance in cell lines having mutated or inactivated p53, such as MDA-MB-435 and Kaposi's sarcoma cell lines. 3ZF-1-VP also induced strong resistance to etoposide, vincristine, and cisplatinum. Linkage of a repression domain to the selected ATF resulted in enhanced sensitivity to multiple drugs, particularly vincristine, cisplatinum, and 5-fluorouracil. Small interfering RNA–mediated inhibition of p53 revealed that 3ZF-1-VP activated both p53-dependent and p53-independent mechanisms to promote survival, whereas other ATF required intact p53. Real-time expression analysis and DNA microarrays showed that several ATFs up-regulated targets of p53, such as the cyclin-dependent kinase inhibitor p21WAF1/CIP1, and genes participating in the p14ARF-MDM2-p53 tumor suppressor pathway, such as hDMP1. Thus, ATF can be used to map genes and pathways involved in drug resistance phenotypes and have potential as novel therapeutic agents to inhibit drug resistance. [Mol Cancer Ther 2008;7(3):688–97]
Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity
Authors: Goodell Vivian , Waisman James , Salazar Lupe G. , dela Rosa Corazon , Link John , Coveler Andrew L. , Childs Jennifer S. , Fintak Patricia A. , Higgins Doreen M. , Disis Mary L.
Published: March 2008

We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/neu is influenced by the level of HER-2/neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n = 70) HER-2/neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference (P < 0.001), and there were significant differences in the magnitude of the HER-2/neu-specific antibodies between groups with varying HER-2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu-specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies. [Mol Cancer Ther 2008;7(3):449–54]
Neuropathological Aspects of Alzheimer Disease, Parkinson Disease and Frontotemporal Dementia
Authors: Jellinger Kurt A.
Published: March 2008

Background: Proteinopathies are a heterogenous group of neurodegenerative disorders, characterized by intra- and extracellular accumulation of abnormal filament proteins. Objective: To describe the neuropathology of specific forms of tauopathies and synucleinopathies, the overlap of morphologic features and molecular interactions. Methods: The study uses currently available morphologic criteria of different proteinopathies. Results: Alzheimer disease (AD) is featured by deposition of β-amyloid peptides, phosphorylated tau protein (3- and 4-repeat tau) and frequent α-synuclein (aSyn) deposits. Lewy body diseases (LBD), such as sporadic Parkinson disease (PD) and dementia with Lewy bodies (DLB), show aSyn-positive deposits in neurons, neurites, glia, and presynaptic terminals, while frontotemporal dementias present tau-positive and tau-negative, ubiquitin- and TDP-43-positive neuronal and glial inclusions. The latter have also been observed in AD, PD, PD dementia and motor neuron disorders. Molecular interactions between major proteins, which may occur within the same brain in various distribution patterns, cause variable phenotypes and mixed pathologies, e.g. AD with aSyn pathology in the brainstem and amygdala, PD and DLB with AD lesions, and frontotemporal dementia with a mixture of various deposits, while others are featured by one principal pathology without other lesions (e.g. tangle-predominant type of dementia, pure PD, brainstem-predominant LBD). Conclusion: Animal models and in vitro studies showing co-occurrence and mutual promotion of fibrillation of these proteins indicate their synergistic interactions in the pathogenesis of these disorders which, at least in part, are genetically influenced.
Etiology and Pathophysiology of Frontotemporal Dementia, Parkinson Disease and Alzheimer Disease: Lessons from Genetic Studies
Authors: Wider Christian , Wszolek Zbigniew K.
Published: March 2008

Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease.
Pathophysiology of Neuronal Energy Crisis in Alzheimer’s Disease
Authors: de la Torre Jack C.
Published: March 2008

A large body of evidence indicates that sporadic Alzheimer’s disease (AD) is a vascular disorder with neurodegenerative consequences and needs to be treated and managed as such. Epidemiologic studies of vascular risk factors, together with preclinical detection tools for AD are proof of concept that cerebral hypoperfusion is one of the earliest pathological signs in the development of cognitive failure. Vascular risk factors involving heart disease and stroke in the elderly individual who already possesses a dwindling cerebrovascular reserve due to advancing age contribute to further decline in cerebral blood flow (CBF) resulting in unrelenting brain hypoperfusion. Brain hypoperfusion, in turn, can reach a critically attained threshold of cerebral hypoperfusion (CATCH) giving rise to a neuronal energy crisis via reduced ATP synthesis. The ensuing metabolic energy crisis initially carves up ischemic-sensitive neurons in the hippocampus and posterior parietal cortex setting up cognitive meltdown and progressive neurodegenerative and atrophic changes in the brain. Neuronal energy compromise accelerates oxidative stress, excess production of reactive oxygen species, aberrant protein synthesis, ionic membrane pump dysfunction, signal transduction impairment, neurotransmitter failure, abnormal processing of amyloid precursor protein resulting in β-amyloid deposition and axonal microtubule disruption from tau hyperphosphorylation. The high energy metabolic changes leading to oxidative stress and cellular hypometabolism precede clinical expression of AD. Regional CBF measurements using neuroimaging techniques can predict AD preclinically at the mild cognitive impairment stage or even before any clinical manifestation of dementia is expressed. Clinical diagnostic assessment of elderly persons who could develop or already present with memory complaints can prevent, reverse or slow down AD development. Although pathologic aging is the subject of thousands of studies, the question of why the elderly (and not younger people) succumb to AD has not been adequately addressed. The explanation(s) as to why vascular risk factors, for example, can trigger AD or vascular dementia usually in the elderly and not the young should provide vital clues in the search for a strategically effective dementia treatment. This review offers inductive hypothetical darts relative to that critical question.
Biomarkers for the Early Detection of Parkinson’s and Alzheimer’s Disease
Authors: Berg Daniela
Published: March 2008

In the aging population of many countries in the world, neurodegenerative diseases like Parkinson’s disease (PD) are becoming an increasing burden. Therefore, early therapy and ultimately disease prevention is essential, which is only possible with an early diagnosis. Besides a genetic predisposition, a number of biomarkers are being discussed to indicate vulnerability to PD, some of them many years before disease manifestation. These include hyperechogenicity of the substantia nigra as well as premotor symptoms like olfactory and autonomic dysfunction, depression, REM sleep behavior disorder, and neuropsychological impairment. Moreover, first signs of affection of the substantia nigra like PET and SPECT abnormalities and slight motor signs can be included, as they may be detected before a definite diagnosis according to motor symptoms can be made. Interestingly, other frequent neurodegenerative disorders like Alzheimer’s disease (AD) are also characterized by a long preclinical period, with several biomarkers discussed as indicative for disease vulnerability including cerebrospinal fluid, serum, and neuroimaging biomarkers, olfactory dysfunction as well as subtle neuropsychological deficits. However, future studies are necessary, which establish the predictive value of these markers singularly and in combination to detect a subgroup of the population at risk for PD and AD not only to accelerate research on etiology and pathophysiology but also to promote testing for neuroprotective strategies.
Intraneuronal β-Amyloid Is a Major Risk Factor – Novel Evidence from the APP/PS1KI Mouse Model
Authors: Bayer Thomas A. , Breyhan Henning , Duan Kailai , Rettig Jens , Wirths Oliver
Published: March 2008

Accumulating evidence points to an important role of intraneuronal β-amyloid (Aβ) in the development of Alzheimer’s disease (AD), with its typical clinical symptoms like memory impairment and changes in personality. We have previously reported on the Aβ precursor protein and presenilin-1 knock-out (APP/PS1KI) mouse model with abundant intraneuronal Aβ42 accumulation and a 50% loss of CA1 neurons at 10 months of age. In addition, we observed reduced short- and long-term synaptic plasticity, hippocampal neuron loss, and reduced performance in a working memory task. These observations support a pivotal role of intraneuronal Aβ accumulation as a principal pathological trigger in AD.
Impact of Intracellular β-Amyloid in Transgenic Animals and Cell Models
Authors: Cuello A. Claudio , Canneva Fabio
Published: March 2008

The present commentary based on cell and animal models of intracellular β-amyloid (iAβ) expression indicates that low levels of microscopically undetectable iAβ could have a physiological role in the modulation of the cyclic AMP response element (CRE)-dependent gene expression and, as a consequence, a positive influence on synaptic plasticity (the ‘good’ Aβ?). On the other hand, high levels of iAβ resembling the pathological and microscopically visible accumulation of this amyloid peptide, akin to that observed in Down syndrome and Alzheimer’s disease, disrupt CRE-regulated gene expression, therefore compromising the protein synthesis-dependent component of long-term potentiation (the ‘bad’ Aβ?). Moreover, intracellular pathology would be independent and additive to the toxic effects of the extracellular Aβ burden.
β-Amyloid Oligomers Affect the Structure and Function of the Postsynaptic Region: Role of the Wnt Signaling Pathway
Authors: Dinamarca Margarita C. , Colombres Marcela , Cerpa Waldo , Bonansco Christian , Inestrosa Nibaldo C.
Published: March 2008

Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. Synaptic dysfunction is an early manifestation of AD. The cellular mechanism by which β-amyloid peptide (Aβ) affects synapses remains unclear. Aβ oligomers target synapses in cultured rat hippocampal neurons suggesting that they play a key role in the regulation of synapses. Objective: The aim of this work is to study the effect of Aβ oligomers on the central synapses and the possible role of the Wnt signaling pathway in preventing the Aβ effects. Methods: We used rat hippocampal neurons, immunofluorescence and western blot procedures to detect synaptic proteins. Results: Aβ oligomers induced a reduction of the postsynaptic density protein 95 (PSD-95) and the NMDA glutamate receptors. We found that Wnt-5a, a noncanonical Wnt ligand, prevents the decrease triggered by Aβ oligomers in the glutamate receptor and PSD-95. Conclusion: Altogether, our results suggest that Aβ oligomers decrease the synaptic responses by affecting the postsynaptic region at different levels. The Wnt signaling activation prevents synaptic damage induced by Aβ, which raises the possibility of a new therapeutic intervention for the treatment of synaptic changes observed in AD.
Potent β-Amyloid Modulators
Authors: García-Palomero E. , Muñoz P. , Usan P. , Garcia P. , Delgado E. , De Austria C. , Valenzuela R. , Rubio L. , Medina M. , Martínez A.
Published: March 2008

Currently, the potential to interfere with the pathology of β-amyloid targeting a well-known drugable enzyme, the acetylcholinesterase (AChE), is opened. Peripheral or dual binding site inhibitors of AChE may simultaneously alleviate the cognitive and behavioral deficits in Alzheimer’s disease (AD) patients and, more importantly, act as disease-modifying agents delaying amyloid plaque formation. As part of a rational drug design program directed to find dual binding site AChE inhibitors, several families of compounds have been synthesized as potent AChE inhibitors. From these series, several drug candidates were selected based on their potent and selective inhibition of AChE (subnanomolar activity) and their interference with the β-amyloid aggregation in vitro (IC50 in the low micromolar range). First in vivo data confirm our initial hypothesis. Oral treatment with NP-61 for 3 months is able to reverse the cognitive impairment (Morris water maze test) and to reduce plaque load in the brains of human amyloid precursor protein transgenic mice (Swedish mutation). These results suggest that NP-61, a potent β-amyloid modulator, is able to reverse the AD-like neurodegenerative phenotype in transgenic mice, indicating a promising disease-modifying agent for clinical application.