bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient‐specific motion artifacts in 4DCT
Authors: Watkins W. Tyler , Li Ruijiang , Lewis John , Park Justin C. , Sandhu Ajay , Jiang Steve B. , Song William Y.
Published: June 2010

Purpose

Four‐dimensional computed tomography (4DCT) has enhanced images of the thorax and upper abdomen during respiration, but intraphase residual motion artifacts will persist in cine‐mode scanning. In this study, the source and magnitude of projection artifacts due to intraphase target motion is investigated.

Methods

A theoretical model of geometric uncertainty due to partial projection artifacts in cine‐mode 4DCT was derived based on ideal periodic motion. Predicted artifacts were compared to measured errors with a rigid lung phantom attached to a programmable motion platform. Ideal periodic motion and actual patient breathing patterns were used as input for phantom motion. Reconstructed target dimensions were measured along the direction of motion and compared to the actual, known dimensions.

Results

Artifacts due to intraphase residual motion in cine‐mode 4DCT range from a few mm up to a few cm on a given scanner, and can be predicted based on target motion and CT gantry rotation time. Errors in ITV and GTV dimensions were accurately characterized by the theoretical uncertainty at all phases when sinusoidal motion was considered, and in 96% of 300 measurements when patient breathing patterns were used as motion input. When peak‐to‐peak motion of 1.5 cm is combined with a breathing period of 4 s and gantry rotation time of 1 s, errors due to partial projection artifacts can be greater than 1 cm near midventilation and are a few mm in the inhale and exhale phases. Incorporation of such uncertainty into margin design should be considered in addition to other uncertainties.

Conclusions

Artifacts due to intraphase residual motion exist in 4DCT, even for ideal breathing motions (e.g., sine waves). It was determined that these motion artifacts depend on patient‐specific tumor motion and CT gantry rotation speed. Thus, if the patient‐specific motion parameters are known (i.e., amplitude and period), a patient‐specific margin can and should be designed to compensate for this uncertainty.
Clinical application of Varian OBI CBCT system and dose reduction techniques in breast cancer patients setup
Authors: Ueltzhöffer Stefan , Zygmanski Piotr , Hesser Jürgen , Högele Wolfgang , Wong Julia , Bellon Jennifer R. , Lyatskaya Yulia
Published: June 2010

Purpose

To characterize the standard modes of Varian on board imaging (OBI) v1.4 system and identify techniques to further optimize imaging parameters, in particular, for breast treatment setup.

Methods

A male anthropomorphic torso phantom was used for image quality assessment and a simpler thorax phantom for dose measurements. Both phantoms had artificial breasts attached. Doses were measured with an ion chamber in seven locations in the thorax and the breast. Evaluation of image quality was performed in terms of contrast‐to‐noise ratio (CNR) and in combination with the dose‐to‐contrast‐to‐noise (CNRD) parameter. The effect of kVp and mAs on the image quality, dose, and CNRD parameter was analyzed. In addition, image geometry with noncentral isocenter location with start and stop imaging angles adjusted for greater sparing of the contralateral breast was evaluated in terms of image quality and dose.

Results

The measurements showed doses between 0.02 and 1.6 cGy for the three full‐fan modes and 0.6–3.2 cGy for half‐fan modes. This is a reduction of over 80% and 30%–50% compared to OBI v.1.3 modes for full‐fan and half‐fan modes, respectively. The CNRD is the highest for both low dose modes (low dose thorax and low dose head). Optimal ranges for an averaged sized thorax are tube voltages not higher than 100 kVp and current‐time products between 100 and 400 mAs . For the contralateral breast and lung, a dose less than 0.03 cGy per scan was measured for the optimized image geometry with the noncentral isocenter location.

Conclusions

The OBI v1.4 system allows for imaging with a larger variety of imaging parameters compared to previous OBI v1.3 systems. The largest doses (up to 4 cGy) were measured in a phantom when OBI v1.4 system was used for imaging with half‐fan modes. Using full‐fan modes resulted in the doses less than 1.6 cGy. Further decrease in dose may be achieved by reducing mAs while preserving acceptable image quality. Organ specific sparing (e.g., contralateral breast) may be achieved by proper selection of the start and stop angles. For thorax imaging, the use of Low Dose Thorax mode is recommended.
Staphylococcus aureus
Nonribosomal Peptide Secondary Metabolites Regulate Virulence
Authors: Wyatt Morgan A. , Wang Wenliang , Roux Christelle M. , Beasley Federico C. , Heinrichs David E. , Dunman Paul M. , Magarvey Nathan A.
Published: June 2010

Golden Regulator

Staphylococcus aureus
is a common cause of intractable infections that are exacerbated by an array of toxins and virulence factors. The
agr
pheromone has been thought to represent the master regulator of virulence in this pathogen, but it is not always expressed and is also found in many nonpathogenic cocci. A strictly conserved, nonribosomal peptide synthetase has now been found by

Wyatt
et al.

(p.
294
, published online 3 June) by genome mining. The enzyme assembles valine and tyrosine into cyclic dipeptides called aureusimines that are expressed by all sequenced strains of
S. aureus
, including the “superbug” MRSA (Methicillin-resistant
Staphylococcus aureus
). Microarray analysis showed a striking effect of mutation in the synthetase locus on the production of immunomodulators, hemolysins, and other exotoxins by the pathogen. Indeed, mice infected systemically with the mutant strain showed a restricted spread of infection compared with the wild type.
Allergen and endotoxin exposure in a companion animal hospital
Authors: Samadi Sadegh , Heederik Dick J J , Krop Esmeralda J M , Jamshidifard Ali-Reza , Willemse Ton , Wouters Inge M
Published: June 2010

Background

Exposure to allergens, both in general and occupational environments, is known to result in sensitisation and exacerbation of allergic diseases, while endotoxin exposure might protect against allergic diseases. This may be important for veterinarians and co-workers. However, exposure levels are mostly unknown.

Objective

We investigated the allergen and endotoxin exposure levels of veterinary medicine students and workers in a companion animal hospital.

Methods

Airborne and surface dust was collected using various sampling methods at different locations. Allergen levels in extracts were measured with sandwich ELISAs and/or the multiplex array for indoor allergens (MARIA). Endotoxin was determined by limulus amebocyte lysate (LAL) assay.

Results

Fel d 1 (Felis domesticus), Can f 1 (Canus familiaris) and endotoxin were detected in all except stationary samples. The geometric mean (GM) level of personal inhalable dust samples for Fel d 1 was 0.3 ng/m3(range: below lower limit of detection (<LOD) to 9.4), for Can f 1 3.6 ng/m3(<LOD to 73.3) and for endotoxin 4.4 EU/m3(<LOD to 75). Exposure levels differed significantly between job titles, with highest allergen exposure for student assistants in the intensive care unit (Fel d 1, GM 1.5 ng/m3; Can f 1, GM 18.5 ng/m3), and highest endotoxin exposure for students (GM 10.1 EU/m3). Exposure levels in dust captured by diverse sampling methods correlated with each other (p<0.05).

Conclusion

Allergen exposure likely occurs during veterinary practice, with relatively low endotoxin levels. Future research should investigate dose–response relationship between airborne allergen exposure and health effects.
Comparison of the effectiveness of collaborative groups and peer instruction in a large introductory physics course for science majors
Authors: Kalman Calvin S. , Milner-Bolotin Marina , Antimirova Tetyana
Published: June 2010

We report on an experiment comparing examinations of concepts using slightly modified peer instruction (MPI) interventions with a conceptual conflict strategy based on collaborative groups (CG). Four interventions were utilized in two sections of an introductory physics course for science students. Both instructors and strategies were alternated in the two classes so that instructor dependence could be factored out and so that each class could serve as both an experimental and a control group. The gain on the Force Concept Inventory (FCI) used as a pre- and post-test is essentially the same in both classes. The instructors were experienced in use of MPI, but this was the first time that these instructors had used a collaborative group activity in their classes and only used it for the two interventions in each class described in this paper. CG appears to be more effective as a teaching method than PI. It also should be noted that the effectiveness of both teaching methods seems to be instructor independent as long as the instructors followed the same protocol.
Clonal evaluation for fusiform rust disease resistance: effects of pathogen virulence and disease escape
Authors: Kayihan Gögçe C. , Nelson C. Dana , Huber Dudley A. , Amerson Henry V. , White Timothy L. , Davis John M.
Published: June 2010

We evaluated the precision of phenotypic classification for fusiform rust resistance of Pinus taeda L. in a clonally propagated population segregating for the pathotype-specific resistance gene Fr1. In all marker-defined Fr1/fr1 clones screened with low complexity or ambient inoculum, marker–trait cosegregation was complete with no exceptions. Uncommon exceptions (4 of 30) in which marker-defined Fr1/fr1 clones screened with high complexity inoculum were diseased were probably due to a low frequency of spores virulent to Fr1 resistance. Marker–trait cosegregation for fr1/fr1 clones was less reliable, as all ramets of a few clones (5 of 29, 3 of 25, and 4 of 16) remained disease-free with low complexity, high complexity, or ambient inoculum, respectively. We termed disease-free fr1/fr1 ramets “escapes”, since the genetics of the host–pathogen interaction predicted them to be diseased. For nonmarker-defined materials, we considered escapes to be disease-free ramets within clones that had at least one diseased ramet. Narrow-sense heritability estimates for escape rate were 29% and 23% for the low and high complexity inocula, respectively, suggesting that genetic variation in the host is an important component of this resistance mechanism.
Geographical and historical determinants of microsatellite variation in Eucalyptus pilularis
Authors: Shepherd Mervyn , Sexton Timothy R. , Thomas Dane , Henson Michael , Henry Robert J.
Published: June 2010

Geographically distributed genetic variation is expected in species that have wide latitudinal and habitat ranges, like Eucalyptus pilularis Sm. Coastal and inland ecotypes of this tall forest tree have been distinguished in genecological studies, but patterns of regionally distributed quantitative variation are weak. At the coarsest level, variation of 12 microsatellite markers divided a rangewide sample of 424 E. pilularis trees into two zones: the region to the south of Sydney forming one zone and regions to the north forming another. Genetic structuring did not correspond with ecotypes but rather with a biogeographic division, suggesting an imprint of historical isolation. Typical and uniform levels of genetic diversity (He= 0.78 ± 0.02 (mean ± SE)) were found across 10 geographic regions. Genetic structuring by regions (PhiRT = 3%), by localities within regions (PhiPT = 2%), between coastal and inland provenances (PhiPT = 2%), or due to isolation by distance was subtle. These observations, along with the lack of evidence for bottlenecks, suggested genetic cohesion within zones due to gene flow and historically large population sizes. The low levels of diversity and poor growth performance of the Fraser Island ecotype were better explained by recent colonization and adaptation than by genetic isolation, since there was no evidence of inbreeding.
Spatial distributions of species in an old-growth temperate forest, northeastern China
Authors: Wang Xugao , Ye Ji , Li Buhang , Zhang Jian , Lin Fei , Hao Zhanqing
Published: June 2010

Studying spatial distributions of species can provide important insights into processes and mechanisms that maintain species richness. We used the relative neighborhood density Ω based on the average density of conspecific species in circular neighborhoods around each species to quantify spatial distributions of species with ≥10 individuals in a fully mapped 25 ha temperate plot at Changbaishan, northeastern China. Our results show that spatial aggregation is a dominant pattern of species in the Changbaishan temperate forests. However, the percentage of significantly aggregated species decreases with spatial scale, especially for rare species. Rare species are more aggregated than intermediate and common species. The aggregation intensity declines with increasing size class (diameter at breast height), i.e., species become more regularly spaced as species grow, which is consistent with the predictions of self-thinning and Janzen–Connell spacing effects. Species functional traits (canopy layer, seed dispersal ability, shade tolerant, etc) also havea significant effect on the spatial distributions of species. Our results partially conform to the prediction that better dispersal reduces aggregation. Consequently, dispersal limitation, self-thinning, Janzen–Connell spacing effects, and habitat heterogeneity may primarily contribute to spatial distributions of species in the temperate forests.
Habitat preferences of an arboreal forage lichen in a Sierra Nevada old-growth mixed-conifer forest
Authors: Rambo Thomas R.
Published: June 2010

The arboreal forage lichen Bryoria fremontii (Tuck.) Brodo & D.Hawksw. appears sensitive to conditions of prolonged hydration in wet forests of British Columbia. I estimated the abundance of this lichen in mixed-conifer forest canopy in the contrasting Mediterranean climate of the southern Sierra Nevada in relationship to the vertical gradient of vapor pressure deficit. Abundance was estimated by biomass in 5 m strata from the ground to the tops of 50 trees. Transplants of Bryoria thalli were installed in 18 fir trees for 1 year to assess their growth relative to distance from perennial streams. VPD generally increased with height, being significantly greater at 45 m than 5 m. Bryoria biomass averaged across tree heights was estimated as 15.9, 0.60, 0.15, 0.25, and 0.19 g·m–1in red fir (Abies magnifica A.Murray), white fir (Abies concolor (Gordon & Glend.) Hildebr. var. lowiana (Gordon) Lemmon), incense cedar (Calocedrus decurrens (Torr.) Florin), Jeffrey pine (Pinus jeffreyi Balf.), and sugar pine (Pinus lambertiana Douglas), respectively. Transplant growth was significantly greater in trees <25 m from water (11.4%) than in trees >25 m from water (9.7%). Bryoria had strong positive associations with red fir, proximity to streams, and decreasing VPD. The sensitivity of Bryoria to prolonged hydration does not appear to be important in this climate characterized by extended summer dryness.
On the efficiency of line intersect distance sampling
Authors: Affleck David L.R.
Published: June 2010

Sampling strategies commonly used for coarse woody debris (CWD) inventories, including line intersect sampling (LIS), typically require large sample sizes to estimate aggregate volume with reasonable precision. Line intersect distance sampling (LIDS) is a recently developed strategy based on a probability proportional-to-volume design and a linear sampling unit. In principle, the design augments the precision of volume estimators by increasing the intensity with which bulkier particles are sampled, while the transect-based protocol facilitates the search for qualifying particles. This study reports on the relative performances of LIDS and LIS in seven stands in Montana, USA. Particles selected by LIDS were consistently less numerous but larger in cross section than those selected at the same locations by LIS. In timed field trials, LIDS required more time than LIS, but CWD volume estimates from LIDS were generally more precise, more than offsetting the time differential. Conversely, aggregate length and abundance of CWD were generally estimated more efficiently with LIS. Results suggest that LIDS permits more efficient use of survey resources than LIS where CWD inventories focus on parameters relating to volume, biomass, or carbon. However, the constant volume factor design of LIDS is not advantageous where CWD frequency is of central interest.
Advantages of long-term measurement of fine root demographics with a minirhizotron at two balsam fir sites
Authors: Krasowski M.J. , Lavigne M.B. , Olesinski J. , Bernier P.Y.
Published: June 2010

We used 15 site-years of minirhizotron observations (1998–2006 at one site; 1998–2000 and 2004–2006 at second site) from two mature balsam fir ( Abies balsamea (L.) Mill.) sites to quantify interannual variability in fine root demography and assess the accuracy of estimates from early years of observation. Annual production varied fourfold at Forêt Montmorency (FM) (5.8–26.5 roots·100 cm–2) and twofold at Green River (GR) (7.2–14.2 roots·100 cm–2). Annual mortality varied more than 30-fold at the two sites (FM: 0.7–23.2 roots·100 cm–2; GR: 0.3–10.9 roots·100 cm–2), year-end standing crops varied two- to eight-fold (FM: 3.6–28.4 roots·100 cm–2; GR 8.5–18.6 roots·100 cm–2), and median life-span of annual cohorts varied from 180 to 540 days at FM and from 350 to 577 days at GR. This variation illustrates that root demography estimates from short-term studies may differ widely from long-term means. Annual mortality and standing crops were lowest in the first year of observation and tended to increase for two or more years at both sites, whereas these trends were not observed for annual production. Our results indicate that minirhizotron tubes must be in place for more than 2 years to accurately estimate fine root demography at balsam fir sites.
A height-growth and site-index model for interior spruce in the Sub-Boreal Spruce biogeoclimatic zone of British Columbia
Authors: Hu Zhengjun , García Oscar
Published: June 2010

Height growth was modelled for spruce-dominated, even-aged stands in the Sub-Boreal Spruce biogeoclimatic zone of British Columbia, Canada, using both stem analysis (SA) and permanent sample plot (PSP) data. The model is based on a stochastic differential equation (SDE) formulation of the Bertalanffy–Richards growth equation. The SDE approach accounts for serial correlation and heterogeneous variance and makes hypothesis testing possible. Statistically significant differences in height–age trends between SA and PSP data were found that may be attributed to bias caused by dominance changes in SA trees. Error structure in SA and PSPs was also significantly different. Combining both data sources in a way that respects these different error structures reduced bias and increased precision. Four parametrizations were tested; the best was a polymorphic version. The final model fit the data well with no appreciable bias over the full range of ages and site qualities. The currently used spruce site-index model was found to underestimate growth and overestimate site index in young stands. The new model can be recommended for height prediction and site-quality assessment in interior spruce.
THE AHARONOV–CASHER SCATTERING: THE EFFECT OF THE ∇ · E TERM
Authors: AL-QAQ E. , SHIKAKHWA M. S.
Published: June 2010

In the Aharonov–Casher (AC) scattering, a neutral particle interacts with an infinitesimally thin, long charge filament resulting in a phase shift. In the original AC treatment, a ∇ · E term proportional to the charge density at the filament's position is dropped from the Hamiltonian on the basis that the particle is banned from the filament, thus, the resulting Hamiltonian compares with the Aharonov–Bohm Hamiltonian of a scalar particle. Here, we consider AC scattering with this term included. Starting from the three-dimensional nonrelativistic Aharonov–Casher (AC) Schrödinger equation with the ∇ · E term included, we find the wave functions — in particular their singular component — the phase shifts and thus compute the scattering amplitudes and cross-sections. We show that singular solutions in the AC case appear only when the delta function interaction introduced is attractive regardless of the spin orientation of the particle. We find that the inclusion of this term does not introduce a structural difference in the general form of the cross-section even for polarized particles. Its mere effect, is in shifting the parameter N (the greatest integer in α) that appears in the cross-section, in the attractive case, by one. Interesting situation appears when N = 0, thus α=δ, in the case α≻0, and N = -1, so α = 1-δ in the case α≺0: At these values of the parameter N, where αis just any fraction, the cross-section for a particle polarized in the scattering plane to scatter in a state with the same polarization, is isotropic. It also vanishes, at these values of N, for transitions between same-helicity eigenstates. For these values of the parameter N and at the special values α = ±1/2, the cross-sections for both signs of α coincide. The main differences between this model and the "mathematically equivalent" spin-1/2 AB theory are outlined.
TOPOLOGICAL BLACK HOLES OF (n+1)-DIMENSIONAL EINSTEIN–YANG–MILLS GRAVITY
Authors: BOSTANI N. , DEHGHANI M. H.
Published: June 2010

We present the topological solutions of Einstein gravity in the presence of a non-Abelian Yang–Mills field. In (n+1) dimensions, we consider the SO (n(n-1)/2-1, 1) semisimple group as the Yang–Mills gauge group, and introduce the black hole solutions with hyperbolic horizon. We argue that the four-dimensional solution is exactly the same as the four-dimensional solution of Einstein–Maxwell gravity, while the higher-dimensional solutions are new. We investigate the properties of the higher-dimensional solutions and find that these solutions in five dimensions have the same properties as the topological five-dimensional solution of Einstein–Maxwell (EM) theory although the metric function in five dimensions is different. But in six and higher dimensions, the topological solutions of EYM and EM gravities with non-negative mass have different properties. First, the singularity of EYM solution does not present a naked singularity and is spacelike, while the singularity of topological Reissner–Nordström solution is timelike. Second, there are no extreme six or higher-dimensional black holes in EYM gravity with non-negative mass, while these kinds of solutions exist in EM gravity. Furthermore, EYM theory has no static asymptotically de Sitter solution with non-negative mass, while EM gravity has.
FEATURE SELECTION FOR DATASETS WITH IMBALANCED CLASS DISTRIBUTIONS
Authors: KAMAL ABU H. M. , ZHU XINGQUAN , PANDYA ABHIJIT , HSU SAM , NARAYANAN RAMASWAMY
Published: June 2010

Feature selection for supervised learning concerns the problem of selecting a number of important features (w.r.t. the class labels) for the purposes of training accurate prediction models. Traditional feature selection methods, however, fail to take the sample distributions into consideration which may lead to poor prediction for minority class examples. Due to the sophistication and the cost involved in the data collection process, many applications, such as biomedical research, commonly face biased data collections with one class of examples (e.g., diseased samples) significantly less than other classes (e.g., normal samples). For these applications, the minority class examples, such as disease samples, credit card frauds, and network intrusions, are only a small portion of the data but deserve full attention for accurate prediction. In this paper, we propose three filtering techniques, Higher Weight (HW), Differential Minority Repeat (DMR) and Balanced Minority Repeat (BMR), to identify important features from datasets with biased sample distribution. Experimental comparisons with the ReliefF method on five datasets demonstrate the effectiveness of the proposed methods in selecting informative features for accurate prediction of minority class examples.
AN EMPIRICAL EVALUATION OF REPETITIVE UNDERSAMPLING TECHNIQUES
Authors: VAN HULSE JASON , KHOSHGOFTAAR TAGHI M. , NAPOLITANO AMRI
Published: June 2010

Class imbalance is a fundamental problem in data mining and knowledge discovery which is encountered in a wide array of application domains. Random undersampling has been widely used to alleviate the harmful effects of imbalance, however, this technique often leads to a substantial amount of information loss. Repetitive undersampling techniques, which generate an ensemble of models, each trained on a different, undersampled subset of the training data, have been proposed to allieviate this difficulty. This work reviews three repetitive undersampling methods currently used to handle imbalance and presents a detailed and comprehensive empirical study using four different learners, four performance metrics and 15 datasets from various application domains. To our knowledge, this work is the most thorough study of repetitive undersampling techniques.
SPEECH EMOTION RECOGNITION METHOD BASED ON IMPROVED DECISION TREE AND LAYERED FEATURE SELECTION
Authors: MAO QIRONG , WANG XIAOJIA , ZHAN YONGZHAO
Published: June 2010

In this paper, in order to improve the classification accuracy with features as few as possible, a new hierarchical recognition method based on an improved SVM decision tree and the layered feature selection method combining neural network with genetic algorithm are proposed. The improved SVM decision tree is constructed according to confusion degrees between two emotions or those between two emotion groups. The classifier in each node of the improved decision tree is a SVM. On the emotional speech corpus recorded by our workgroup including 7 emotions, with the features and parameters gotten by the method combining neural network with genetic algorithm, improved SVM decision tree, multi-SVM, SVM-based binary decision tree, the traditional SVM-based decision directed acyclic graph and HMM are evaluated respectively. The experiments reveal that, compared with the other four methods, the proposed method in this paper appears better classification accuracy with fewer features and less time.
EFFECTS OF FOOT SHAPE ON ENERGETIC EFFICIENCY AND DYNAMIC STABILITY OF PASSIVE DYNAMIC BIPED WITH UPPER BODY
Authors: WANG QINING , HUANG YAN , ZHU JINYING , WANG LONG , LV DONGJIAO
Published: June 2010

Passive dynamic walking has been developed as a possible explanation for the efficiency of the human gait. In this paper, we investigate the effects of foot shape on energetic efficiency and dynamic stability of passivity-based bipeds with upper body. Three walking models with point feet, round feet and flat feet were presented. Each model has an upper body constrained to keep midway between legs. We use computer simulations to find which foot shapes are indeed optimal in view of energetic efficiency and dynamic stability for a passive dynamic biped with upper body. Simulation results indicate that feet improve both the energetic efficiency and dynamic stability of passive dynamic bipeds.
BIPED HOPPING CONTROL BAzSED ON SPRING LOADED INVERTED PENDULUM MODEL
Authors: TAMADDONI SEYED HOSSEIN , JAFARI FARID , MEGHDARI ALI , SOHRABPOUR SAEED
Published: June 2010

Human running can be stabilized in a wide range of speeds by automatically adjusting muscular properties of leg and torso. It is known that fast locomotion dynamics can be approximated by a spring loaded inverted pendulum (SLIP) system, in which leg is replaced by a single spring connecting body mass to ground. Taking advantage of the inherent stability of SLIP model, a hybrid control strategy is developed that guarantees a stable biped locomotion in sagittal plane. In the presented approach, nonlinear control methods are applied to synchronize the biped dynamics and the spring-mass dynamics. As the biped center of mass follows the mass of the mass-spring model, the whole biped performs a stable locomotion corresponding to SLIP model. Simulations are done to obtain a repeatable hopping for a three-link underactuated biped model. Results show that periodic hopping gaits can be stabilized, and the presented control strategy provides feasible gait trajectories for stance and swing phases.
Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas
Authors: May Randal , Sureban Sripathi M. , Lightfoot Stan A. , Hoskins Aimee B. , Brackett Daniel J. , Postier Russell G. , Ramanujam Rama , Rao Chinthalapally V. , Wyche James H. , Anant Shrikant , Houchen Courtney W.
Published: June 2010

Stem cells are critical in maintaining adult homeostasis and have been proposed to be the origin of many solid tumors, including pancreatic cancer. Here we demonstrate the expression patterns of the putative intestinal stem cell marker DCAMKL-1 in the pancreas of uninjured C57BL/6 mice compared with other pancreatic stem/progenitor cell markers. We then determined the viability of isolated pancreatic stem/progenitor cells in isotransplantation assays following DCAMKL-1 antibody-based cell sorting. Sorted cells were grown in suspension culture and injected into the flanks of athymic nude mice. Here we report that DCAMKL-1 is expressed in the main pancreatic duct epithelia and islets, but not within acinar cells. Coexpression was observed with somatostatin, NGN3, and nestin, but not glucagon or insulin. Isolated DCAMKL-1+ cells formed spheroids in suspension culture and induced nodule formation in isotransplantation assays. Analysis of nodules demonstrated markers of early pancreatic development (PDX-1), glandular epithelium (cytokeratin-14 and Ep-CAM), and isletlike structures (somatostatin and secretin). These data taken together suggest that DCAMKL-1 is a novel putative stem/progenitor marker, can be used to isolate normal pancreatic stem/progenitors, and potentially regenerates pancreatic tissues. This may represent a novel tool for regenerative medicine and a target for anti-stem cell-based therapeutics in pancreatic cancer.
Differential responses of the incretin hormones GIP and GLP-1 to increasing doses of dietary carbohydrate but not dietary protein in lean rats
Authors: Yoder Stephanie M. , Yang Qing , Kindel Tammy L. , Tso Patrick
Published: June 2010

Previous studies have shown that oral ingestion of nutrients stimulates secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); however, it is unclear whether there is a dose-dependent response between the amount of nutrient ingested and the secretion of the hormones in vivo. Using our lymph fistula rat model, we previously demonstrated that both GIP and GLP-1 responded dose dependently to increasing amounts of infused dietary lipid and that the GLP-1-secreting cells were more sensitive to changes in intestinal lipid content. In the present study, we investigated the dose-dependent relationships between incretin secretion and the two remaining macronutrients, carbohydrate and protein. To accomplish this objective, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single bolus (3 ml) of saline, dextrin, whey protein, or casein hydrolysate (0.275, 0.55, 1.1, 2.2, 4.4 kcal) via a surgically inserted duodenal or ileal feeding tube. Lymph was continuously collected for 3 h and analyzed for GIP and GLP-1 content. Both GIP and GLP-1 outputs responded dose dependently to increasing amounts of dietary carbohydrate but not protein. Additionally, we found that the GIP-secreting cells were more sensitive than the GLP-1-secreting cells to changes in intestinal carbohydrate content.
Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle
Authors: Fillmore Natasha , Jacobs Daniel L. , Mills David B. , Winder William W. , Hancock Chad R.
Published: June 2010

Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMP-activated protein kinase (AMPK), calcium, and circulating free fatty acids (FFAs). Chronic treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR), a chemical activator of AMPK, or increasing circulating FFAs with a high-fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high-fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high-fat diet (HF), AICAR injections (AICAR), or a high-fat diet and AICAR injections (HF + AICAR) for 6 wk. At the end of the treatment period, markers of mitochondrial content were examined in white quadriceps, red quadriceps, and soleus muscles, predominantly composed of unique muscle-fiber types. In white quadriceps, there was a cumulative effect of treatments on long-chain acyl-CoA dehydrogenase, cytochrome c, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) protein, as well as on citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity. In contrast, no additive effect was noted in the soleus, and in the red quadriceps only β-HAD activity increased additively. The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high-fat diet-induced posttranscriptional increase in PGC-1α protein and AMPK-mediated increase in PGC-1α protein via a transcriptional mechanism. These data show that chronic chemical activation of AMPK and a high-fat diet have a muscle type specific additive effect on markers of fatty acid oxidation, the citric acid cycle, the electron transport chain, and transcriptional regulation.
Skeletal muscle adaptations following blood flow-restricted training during 30 days of muscular unloading
Authors: Cook Summer B. , Brown Kimberly A. , DeRuisseau Keith , Kanaley Jill A. , Ploutz-Snyder Lori L.
Published: June 2010

This study evaluated the effectiveness of low-load resistance training with a blood flow restriction (LLBFR) to attenuate muscle loss and weakness after 30 days of unilateral lower limb suspension (ULLS). Sixteen subjects (ages 18–50 yr) underwent 30 days of ULLS. Measurements of muscle strength, cross-sectional area, and endurance on the knee extensors and plantar flexors were collected before and after ULLS. Plasma concentrations of IGF-1 and IGFBP-3 were also assessed. During ULLS, eight subjects (5 males, 3 females) participated in LLBFR three times per week (ULLS + Exercise) while eight subjects (4 males, 4 females) did not exercise (ULLS). The blood flow-restricted exercise consisted of dynamic knee extension at 20% of the subject's isometric maximum voluntary contraction coupled with a suprasystolic blood flow restriction. After 30 days of limb suspension, the ULLS + Exercise group experienced minimal and insignificant losses in knee extensor cross-sectional area and strength (1.2% and 2.0%, respectively; P ≤ 0.05), while the ULLS group demonstrated significant reductions in cross-sectional area and strength (7.4% and 21%, respectively). Decrements in plantar flexor strength (23.7%) and cross-sectional area (7.4%) were observed after ULLS ( P < 0.05) and were of similar magnitude between the experimental groups ( P > 0.05). Muscular endurance in the knee extensors improved 31% in the ULLS + Exercise group, while it decreased 24% in the ULLS group ( P = 0.01). No changes were seen in hormone concentrations throughout the study. In conclusion, LLBFR of the knee extensors is effective in maintaining muscle strength and size during 30 days of ULLS and results in improved knee extensor muscular endurance.
Hormonal Modulation of Two Coordinated Rhythmic Motor Patterns
Authors: Wood Debra E. , Varrecchia Melissa , Papernov Michael , Cook Denise , Crawford Devon C.
Published: June 2010

Neuromodulation is well known to provide plasticity in pattern generating circuits, but few details are available concerning modulation of motor pattern coordination. We are using the crustacean stomatogastric nervous system to examine how co-expressed rhythms are modulated to regulate frequency and maintain coordination. The system produces two related motor patterns, the gastric mill rhythm that regulates protraction and retraction of the teeth and the pyloric rhythm that filters food. These rhythms have different frequencies and are controlled by distinct mechanisms, but each circuit influences the rhythm frequency of the other via identified synaptic pathways. A projection neuron, MCN1, activates distinct versions of the rhythms, and we show that hormonal dopamine concentrations modulate the MCN1 elicited rhythm frequencies. Gastric mill circuit interactions with the pyloric circuit lead to changes in pyloric rhythm frequency that depend on gastric mill rhythm phase. Dopamine increases pyloric frequency during the gastric mill rhythm retraction phase. Higher gastric mill rhythm frequencies are associated with higher pyloric rhythm frequencies during retraction. However, dopamine slows the gastric mill rhythm frequency despite the increase in pyloric frequency. Dopamine reduces pyloric circuit influences on the gastric mill rhythm and upregulates activity in a gastric mill neuron, DG. Strengthened DG activity slows the gastric mill rhythm frequency and effectively reduces pyloric circuit influences, thus changing the frequency relationship between the rhythms. Overall dopamine shifts dependence of frequency regulation from intercircuit interactions to increased reliance on intracircuit mechanisms.
Costs of Parkinson’s Disease and Antiparkinsonian Pharmacotherapy: An Italian Cohort Study
Authors: Winter Yaroslav , von Campenhausen Sonja , Reese Jens P. , Balzer-Geldsetzer Monika , Longo Katia , Spiga Giuseppe , Boetzel Kai , Eggert Karla , Oertel Wolfgang H. , Dodel Richard , Barone Paolo
Published: June 2010

Objective: Antiparkinsonian pharmacotherapy is costly and the determinants of drug costs in Parkinson’s disease (PD) have been poorly investigated. The objective of this study was to investigate the costs of PD and antiparkinsonian drugs in an Italian cohort of patients and identify cost-driving factors of drug therapy. Methods: Seventy outpatients with idiopathic PD were recruited in the Department of Neurology, Napoli University, Italy. Data on resource utilization were collected for 6 months using a bottom-up approach. Clinical status was evaluated using the Unified Parkinson’s Disease Rating Scale. Direct and indirect costs were calculated from the societal perspective (figures of year 2009). Independent determinants of total costs and costs of antiparkinsonian drugs were identified using multivariate regression analysis. Results: The total costs of PD were EUR 8,640 (95% CI: EUR 6,700–11,240) per patient over a 6-month period. Direct costs accounted for 70% of the total costs. Antiparkinsonian drugs (EUR 1,450; 95% CI: EUR 1,220–1,760) were the primary component of costs paid by the health insurance (39.6%) and one of the most expensive components of the direct costs (24.0%). The highest copayments made by patients were for antiparkinsonian drugs and medical equipment (58%). Independent determinants of the increased costs of antiparkinsonian pharmacotherapy were younger age and occurrence of motor fluctuations. Conclusions: Antiparkinsonian pharmacotherapy is one of the major cost components of PD-related costs for health insurance. It imposes a considerable economic burden on patients and their families as well.
It Is Time for Routine Neonatal Screening by Pulse Oximetry
Authors: Hoffman Julien I.E.
Published: June 2010

Most pediatric cardiologists believe that pulse oximetry helps to diagnose critical congenital heart disease in neonates who might otherwise be discharged from the newborn nursery undiagnosed. Some of these patients develop catastrophic cardiac and multi-system failure after the ductus closes and die or suffer severe morbidity. Nevertheless, pulse oximetry is not universally used in the newborn nursery. Some pediatricians believe that they can always detect these patients from physical findings, many believe that oximeters are unreliable, and others are concerned about costs of investigating false positive tests. Recent studies, however, show that even cardiologists miss critical congenital heart defects, modern oximeters are stable and reliable, and that the false positive rate is very low, lower than the false positive rate based on physical examination. The benefits probably exceed the cost, and evidence is provided to confirm this. There is no reason not to use pulse oximetry routinely in the newborn nursery.
Cooperative Activation of CCL5 Expression by TLR3 and Tumor Necrosis Factor-α or Interferon-γ through Nuclear Factor-ĸB or STAT-1 in Airway Epithelial Cells
Authors: Homma Tetsuya , Matsukura Satoshi , Hirose Takashi , Ohnishi Tsukasa , Kimura Teruaki , Kurokawa Masatsugu , Ieki Koushi , Odaka Miho , Suzuki Shintaro , Watanabe Shin , Sato Masayuki , Kawaguchi Mio , Schleimer Robert P. , Adachi Mitsuru
Published: June 2010

Background: CCL5/RANTES contributes to prolonged eosinophilic inflammation and asthma exacerbation after a viral infection. We studied the mechanism of CCL5 expression using viral product double-stranded RNA (dsRNA), a ligand of Toll-like receptor 3 (TLR3), and inflammatory cytokines in airway epithelial cells. Methods: The airway epithelial cell line BEAS-2B was used in our in vitro study, and the levels of CCL5 mRNA and CCL5 protein expression were determined using real-time PCR and ELISA. The activity of the CCL5 promoter region and nuclear factor (NF)-ĸB was assessed by dual luciferase assay using specific luciferase reporter plasmids. We used actinomycin D to assess the stability of mRNA. Phosphorylation of signal transducer and activator of transcription 1 (STAT-1) was analyzed by Western blot. Results: Synthetic dsRNA up-regulated the expression of CCL5 mRNA and CCL5 protein. Adding TNF-α or IFN-γ to dsRNA further increased the expression of CCL5. The combination of TNF-α and dsRNA cooperatively activated the CCL5 promoter region and the NF-ĸB-specific reporter. IFN-γ did not activate these reporters. However, it increased the stability of CCL5 mRNA induced by dsRNA. IFN-γ phosphorylated STAT-1, but dsRNA did not. The effects of IFN-γ were not evident in the cells transfected with short interfering RNA for STAT-1. Conclusions: Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CCL5 in airway epithelial cells. In this mechanism, TNF-α may activate NF-ĸB, in cooperation with TLR3 signaling. IFN-γ may stabilize CCL5 mRNA up-regulated by TLR3. This mechanism may depend on STAT-1.
Role of Th2 Cells in IgG4-Related Lacrimal Gland Enlargement
Authors: Kanari Hiroko , Kagami Shin-ichiro , Kashiwakuma Daisuke , Oya Yoshihiro , Furuta Shunsuke , Ikeda Kei , Suto Akira , Suzuki Kotaro , Hirose Koichi , Watanabe Norihiko , Okamoto Yoshitaka , Yamamoto Shuichi , Iwamoto Itsuo , Nakajima Hiroshi
Published: June 2010

Background: Lacrimal gland enlargement (LGE) is one of the characteristics of Mikulicz’s disease (MD). Recently, marked serum IgG4 elevation and infiltration of IgG4-positive plasmacytes in the enlarged exocrine glands have been reported in MD patients. However, little is known about the role of CD4+ T cells and their cytokines in IgG4-related diseases. The aim of this study was to evaluate the characteristics of CD4+ T cells in patients with IgG4-related diseases. Methods: We investigated the clinical characteristics of 9 patients with LGE and elevated serum IgG4 levels (named IgG4-related LGE). We also examined mRNA expression of cytokines and transcription factors of peripheral blood CD4+ T cells in patients with IgG4-related LGE. Results: All patients with IgG4-related LGE showed elevated serum IgE levels. In addition, 5 of 9 patients with IgG4-related LGE exhibited eosinophilia and asthma-like symptoms. In patients with IgG4-related LGE, mRNA expression of IL-4, IL-5, IL-10 and GATA-3 but not IFN-γ or T-bet was enhanced on CD4+ T cells compared with that in healthy controls. Conclusions: Th2 cells may be involved in the pathogenesis of IgG4-related diseases.
Effect of Sublingual Immunotherapy on Antigen-Induced Bronchial and Nasal Inflammation in Mice
Authors: Kaminuma Osamu , Suzuki Kazuya , Mori Akio
Published: June 2010

Background: Sublingual immunotherapy (SLIT) is effective in the treatment of a variety of allergic diseases, including bronchial asthma and rhinitis. However, how this local therapy exerts such wide effects is unclear. In this study, we comparatively examined the effect of SLIT on antigen-induced airway inflammation in bronchoalveolar and nasal cavities in mice. Methods: Mice were treated sublingually with ovalbumin (OVA) once a day for 2 weeks. Subsequently, they were immunized with the corresponding antigen. Following intratracheal and nasal challenge with OVA, infiltration of inflammatory cells into the bronchoalveolar and nasal cavities was investigated in these mice. Results: Massive infiltration of eosinophils as well as neutrophils into the bronchoalveolar cavity was induced by intratracheal OVA challenge. Eosinophils accumulated in the nasal cavity, but the number of neutrophils did not significantly change in response to nasal antigen challenge. These antigen-induced airway inflammatory responses, including the increases in the numbers of eosinophils and/or neutrophils in the bronchoalveolar and nasal cavities, were clearly suppressed by SLIT. Conclusions: This animal model displaying differential inflammatory responses in the bronchoalveolar and nasal cavities may be useful to elucidate the efficacy and mechanisms of SLIT against various allergic diseases.
Results of Electrocochleography in Ménière’s Disease after Successful Vertigo Control by Single Intratympanic Gentamicin Injection
Authors: Büki Béla , Platz Michael , Haslwanter Thomas , Jünger Heinz , Avan Paul
Published: June 2010

In the last several years, a promising new approach has been suggested in the therapy of Ménière’s disease (MD): the low-dose intratympanic gentamicin therapy. By titrating the desired vestibular inhibition by single injections and infrequent administration, side effects concerning hearing can be held on an acceptably low level, while disease-related symptoms are often successfully eliminated. However, it is still unclear if endolymphatic hydrops actually decreases when the patients become symptom free. In the literature, hydrops is significantly associated with an enhanced ratio of summating potential/action potential (SP/AP). Our aim in this retrospective study was to answer the question if pathologically high SP/AP ratios normalize after successful low-dose intratympanic gentamicin treatment. Twenty-eight patients with MD received one, two or three intratympanic gentamicin injections. These injections inhibited vertigo spells without causing additional hearing loss. SP/AP ratios measured by noninvasive electrocochleography did not improve statistically when patients became symptom free. This indicates that the beneficial effect of gentamicin does not depend on the improvement of SP/AP ratios. Considering the well-established correlation between increased SP/AP and active MD, it thus seems unlikely that gentamicin treatment significantly reduces hydrops.