bluuebunny/crossref_metadata_2025 huggingface dataset:
TH‐B‐217A‐01: Calculations for the Release of Radioactive Patients From Radiation Safety Restrictions
Authors: Wendt R
Published: June 2012

Radioactive patients may safely be released from radiation safety restrictions when the most exposed person is unlikely to receive more than 5 mSv (500 mrem) according to the United States Nuclear Regulatory Commission. NUREG 1556 Volume 9 Appendix U Revision 2 presents regulatory guidance that may be used to assure compliance with this limit. Although this risk‐based approach is a big step forward from the prior activity‐based release criteria, the methods in the regulatory guidance are arguably still quite conservative. Work such as that by the Radiation Dose Assessment Resource (RADAR) members shows that more realistic calculations may be used to release patients under the regulatory limit with less stringent restrictions.

Learning Objectives:

1. Perform the calculations in the regulatory guidance

2. Characterize the conservatism in those calculations

3. Perform more realistic calculations
TH‐C‐BRA‐01: A New Method & Schema for Real‐Time Prostate Tracking during VMAT Delivery
Authors: Zhuang L , Yan D , Li J
Published: June 2012

Purpose: To create a method and schema for intra‐treatment prostate motion tracking using simultaneous kV imaging during the VMAT treatment delivery. Methods: Intra‐treatment prostate motion is monitored using the visicoils' position manifested on continuous kV projection images. Instead of using intensity based image registration, we extract the points' representation of the visicoils for alignment. Real‐time prostate displacement is determined by minimizing the distance between the visicoil points' positions on the planning CT and their corresponding positions extracted from a sub‐arc of projection images. In the clinical operation, kV imaging keeps on continuously during the VMAT delivery, and the prostate instantaneous motion, as well as the corresponding systematic and random components within a fixed time window, is determined in real‐time. Following the delivery, the projection images will be reconstructed to a Cone‐Beam (CB) CT. The visicoils' position in the CBCT is compared to the average position of the visicoils determined from the kV projections for verification purpose. The performance of our method was evaluated using a computer simulated phantom under four typical prostate motion patterns. The imaging and detection schema was tested during hypo‐fractionated (20 fractions) VMAT treatment of prostate cancer patient. Results: Based on the simulated experiments, the root mean square error between the detected trajectories and the ground truth is (0.1, 0.4, 0.6) mm. The reconstructed mean position is (0.0±0.1, 0.2±0.1, 0.2±0.2) mm from actual value. Based on the patient experiment, the average visicoils' position determined from the real‐time projection image is (−0.6±0.4,0.6±0.8, −0.4±0.5) mm away from the position detected in the CBCT. Conclusions: A practical detection method and imaging schema were developed and implemented in clinic for monitoring target motion during VMAT delivery of prostate cancer treatment. Phantom and clinical evaluation showed its feasibility for clinical use. Research Supported by Elekta
TH‐C‐BRA‐02: A Novel Technology for Volume‐Of‐Interest KV Cone Beam CT
Authors: Robar J
Published: June 2012

Purpose: In this work we describe the development of a new technology allowing volume‐of‐interest (VOI) kV CBCT. A device for dynamic kV beam collimation is described and initial imaging and dosimetric results are given. Methods: We have manufactured a prototype of an iris aperture capable of tracking a chosen VOI during kV CBCT imaging. The aperture and housing is compact and occupies an area comparable to the bow‐tie filter when mounted to the source of an on‐board imaging system. The system allows two‐dimensional translation of the aperture as a function of gantry angle and dynamic adjustment of iris diameter. Iris leaves are non‐overlapping and therefore can be made sufficiently thick to attenuate higher energy kV beams used. The device was tested for functionality on a Varian OBI system. Dose reduction in the VOI was measured and compared to full‐field imaging, for planar and CBCT imaging protocols, as a function of iris dimension. Initial projection and CBCT images of a head phantom were acquired. Results: The system provides a versatile tool for dynamic collimation of the kV beam during CBCT. While dose reduction in VOI CBCT is achieved primarily by blocking of non‐VOI anatomy, the dose inside the imaged VOI is also reduced substantially, by 5% to 60% for 20 cm and 2 cm iris diameters, respectively. The magnitude of dose reduction increases slightly with increased tube potential, between 65 and 125 kVp. Projection images demonstrate that the iris produces effective collimation with minimal leakage. Reconstructed CBCT images are affected by truncation artefact, but this may be remedied by data filling techniques or other (e.g. pi‐line) reconstruction algorithms. Conclusions: The technology presented is a novel approach to kV CBCT, localizing imaging dose to a chosen VOI while, compared to full‐field CBCT, reducing dose both inside and outside of the VOI. No conflict of interest exists.
TH‐C‐217BCD‐02: Ultrasound Texture Analysis of Radiation‐Induced Parotid‐Gland Injury in Post‐Radiotherapy Head‐And‐Neck Patients: Feasibility Study
Authors: Yang X , Tridandapani S , Beitler J , Yu D , Henry S , Chen H , Curran W , Liu T
Published: June 2012

Purpose: Xerostomia (dry mouth), resulting from radiation damage to the parotid glands, is one of the most common and distressing side effects of head‐and‐neck cancer radiotherapy. We have developed a family of sonographic texture features to evaluate the morphologic and microstructural integrity of the parotid glands, and investigate the feasibility of quantitative evaluation of radiotherapy‐induced parotid‐gland injury. Methods: In this pilot study, 12 post‐radiotherapy head‐and‐neck cancer patients and 7 healthy volunteers were enrolled. Each participant underwent one ultrasound study, and longitudinal (vertical) ultrasound scans were performed of the bilateral parotids. The averaged follow‐up time for the post‐radiotherapy patients was 17.2 months and the median radiation dose was 32.3 Gy. Eight grey level co‐occurrence matrix (GLCM) features were derived from the B‐mode images. The associated parameters for texture features can be summarized as follows: 1. Inverse differential moment (IDM): local homogeneity; 2. Contrast: difference of gray‐scale through continuous pixels of the image; 3. Angular second moment (ASM): homogenous texture; 4. Entropy: disorder of the image. 5. Variance: heterogeneity; 6. Correlation: linear relationship between the gray‐scale of pixel pairs; 7. Cluster shade and 8. Cluster prominence: the perceptual concepts of uniformity and proximity. Results: Significant differences (p<0.05) were observed in 8 sonographic features, between normal and irradiated parotid glands. IDM value decreased from 7.88±1.14E‐2 (normal) to 6.93±1.54E‐2 (irradiated); Contrast value increased from 3.41±1.11E+2 to 8.45±3.46E+2; ASM value decreased from 6.06±1.72E‐4 to 3.02±0.87E‐4; Entropy value increased from 7.66±0.34 to 8.47±0.23; Variance value increased from 2.84±1.01E+2 to 9.30±3.53E+2; Correlation value decreased from 1.35±0.45E‐3 to 6.22±2.09E‐4; Cluster shade value increased from 1.20±1.24E+4 to 1.51±1.27E+5; Cluster prominence value increased from 3.11±2.50E+6 to 3.74±3.11E+7. Conclusions: This work has demonstrated the feasibility of ultrasonic texture evaluations of the parotid glands, and the sonographic features may serve as imaging signatures to assess radiation‐induced parotid damage.
The Tides of Titan
Authors: Iess Luciano , Jacobson Robert A. , Ducci Marco , Stevenson David J. , Lunine Jonathan I. , Armstrong John W. , Asmar Sami W. , Racioppa Paolo , Rappaport Nicole J. , Tortora Paolo
Published: June 2012

Getting to Know Titan

Gravity-field measurements provide information on the interior structure of planets and their moons.

Iess
et al.

(p.
457
; published online 28 June) analyzed gravity data from six flybys of Saturn's moon, Titan, by the Cassini spacecraft between 2006 and 2011. The data suggest that Titan's interior is flexible on tidal time scales with the magnitude of the observed tidal deformations being consistent with the existence of a global subsurface water ocean.
Landscape of Somatic Retrotransposition in Human Cancers
Authors: Lee Eunjung , Iskow Rebecca , Yang Lixing , Gokcumen Omer , Haseley Psalm , Luquette Lovelace J. , Lohr Jens G. , Harris Christopher C. , Ding Li , Wilson Richard K. , Wheeler David A. , Gibbs Richard A. , Kucherlapati Raju , Lee Charles , Kharchenko Peter V. , Park Peter J. ,   The Cancer Genome Atlas Research Network
Published: June 2012

Movement in the Cancer Genome

Transposable elements are genetic sequences that can replicate and move within the genome. The factors that make an element mobile are unknown but are generally considered rare in mammals.

Lee
et al.

(p.
967
, published online 28 June) analyzed five cancer types occurring among several individuals and found that three types of epithelial tumors exhibited high rates of element movement relative to brain and blood cancers. Furthermore, these somatically acquired, tumor-specific elements targeted genes in colorectal cancer that, when disrupted, impact gene expression and thus may be a factor in the progression of the cancers.
Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair
Authors: Tsai Hui-Hsin , Li Huiliang , Fuentealba Luis C. , Molofsky Anna V. , Taveira-Marques Raquel , Zhuang Helin , Tenney April , Murnen Alice T. , Fancy Stephen P. J. , Merkle Florian , Kessaris Nicoletta , Alvarez-Buylla Arturo , Richardson William D. , Rowitch David H.
Published: June 2012

Born to Stay Together

For as many neurons as there are in the brain, there are many more astrocytes. These backstage workers perform a variety of functions, such as sustaining the blood-brain barrier and providing a stabilized environment for neurons. Diversity of astrocyte function is reflected in different molecular expression profiles.

Tsai
et al.

(p.
358
, published online 28 June) selectively labeled astrocytes that originated from different domains of the mouse spinal cord and found that not all astrocytes are created equal: Neighborhoods of astrocytes were defined by shared birthplaces.
Primary liposarcoma of liver: a rare case and literature review
Authors: Binesh Fariba , Akhavan Ali , Kargar Saeed , Navabii Hossein
Published: June 2012

Primary liposarcoma of the liver is extremely rare. Because of its rarity, the knowledge of the clinical course, management and prognosis of it are limited. Here we report a case of primary myxoid liposarcoma of the liver in an 83-year-old Iranian woman.
Unusual association of diseases/symptoms
Authors: Rourke Thomas , Pankhania Miran , Hettige Roland , Draper Mark R
Published: June 2012

Cicatricial pemphigoid is a chronic, systemic, immunobullous disorder affecting mucous membranes. Nasal manifestations of cicatricial pemphigoid are less common than in the rest of the upper aero-digestive tract, and may prove difficult to diagnose and manage effectively. We report one such case presenting with isolated nasal symptoms, in which diagnosis, treatment and ongoing management of the underlying cause was particularly challenging. A literature review was performed to ascertain the incidence of cicatricial pemphigoid and to establish the best evidence-based investigation and treatment.
Amyloid heart disease: a brief review of treatment options
Authors: Dubrey Simon W
Published: June 2012

Heart involvement by amyloid deposition remains the most challenging of all organ sytems that may become involved, in what is generally a systemic disease. The correct diagnosis of amyloid type is critical to selection of the appropriate and wide range of therapies. The treatment of amyloid heart disease comprises two strategies: conventional management of a restrictive cardiomyopathy, and varied therapies aimed at the underlying amyloidogenic process. In light chain (AL) amyloidosis, many of the most efficacious therapies involve chemotherapeutic agents with their own inherent toxicities to the heart and bone marrow. In the case of the hereditary amyloidosis, major surgery in the form of liver transplantation is usually required. Moreover, consideration should be given to screening of family members for a potentially hereditary disease. Several types of amyloidosis may require one or more, of heart, liver and/or kidney transplantation, sometimes in addition to high-dose chemotherapy. The objective is to provide a schematic overview of available therapies in the management of AL, hereditary, senile systemic, isolated atrial and secondary forms of amyloidosis.
Canopy and edge activity of bats in a quaking aspen (Populus tremuloides) forest
Authors: Pettit T.W. , Wilkins K.T.
Published: June 2012

Characteristics of edges affect the behavior of species that are active in and near edges. Forest canopies may provide edge-like habitat for bats, though bat response to edge orientation has not been well examined. We sampled bat activity in quaking aspen ( Populus tremuloides Michx.) forest canopies and edges in Heber Valley, Utah, during summer 2009 using Anabat detectors. Categorization and regression tree (CART) analysis of echolocation characteristics (e.g., frequency, duration) identified two guilds based on characteristic frequency (i.e., high- and low-frequency guilds). We used linear regression to compare characteristics of canopy and edge vegetation (e.g., tree height, diameter at breast height) to bat activity levels. Activity levels of high-frequency bats did not respond differentially to edge vegetation; low-frequency bat activity seemed to respond to canopy height. Activity levels of high-frequency bats were significantly greater than low-frequency bats in both edges and canopies. We detected significantly more bat activity in forest edges than in forest canopies, indicating the importance of edges to bats in forests.
Ribeiroia ondatrae causes limb abnormalities in a Canadian amphibian community
Authors: Roberts C.D. , Dickinson T.E.
Published: June 2012

A parasitic flatworm ( Ribeiroia ondatrae Price, 1931) is known to cause severe limb abnormalities and high mortality levels in American amphibian populations. The distributional pattern of this parasite—its main dispersal agent being birds—correlates with the boundaries of migratory flyways in the USA. Yet thus far, R. ondatrae have not been found in Canadian amphibians, which is surprising, considering that said flyways extend well into northern Canada. In this study, we report on a lake in British Columbia that is known to support amphibians with abnormalities similar to those induced by R. ondatrae. To determine if the parasite was present and if it was the cause of the abnormalities, we collected and necropsied metamorphs of the Columbia Spotted Frog ( Rana luteiventris Thompson, 1913) and the Pacific Chorus Frog ( Pseudacris regilla (Baird and Girard, 1852)), and we set up field enclosures to protect larvae from R. ondatrae. Abnormality levels were high in both species (>20%), with the vast majority being found in close proximity to the metacercariae of R. ondatrae. Moreover, the types of abnormalities closely matched those previously recorded in field and laboratory exposures of amphibians to R. ondatrae. Finally, larvae that developed in the same lake, but were protected from R. ondatrae by an enclosure, did not develop abnormalities. Collectively, these results demonstrate that R. ondatrae are both present in an amphibian community in Canada and responsible for causing limb abnormalities.
Longitudinal changes and consistency in male physical and behavioural traits have implications for mating success in the grey seal (Halichoerus grypus)
Authors: Lidgard D.C. , Bowen W.D. , Boness D.J.
Published: June 2012

We examined age-related changes and consistency in physical and behavioural traits of 20 male grey seals ( Halichoerus grypus (Fabricius, 1791)) and implications for a proxy of mating success (number of oestrous females attended) over four successive breeding seasons on Sable Island, Canada. Across the study, young males (10–15 years) gained body mass, while old males (23–31 years) lost body mass. Body length was an important determinant of tenure (time spent at a site among females) and males of all ages exhibited a high level of consistency in duration of tenure (r = 0.40–0.50). In young males, our proxy of success showed a strong relationship with arrival body mass and also exhibited a high level of consistency (r = 0.50). None of the physical traits measured explained variation in success by exhibiting mating tactics that did not involve tenure, which is likely due to the opportunistic nature of those tactics. Whereas young male grey seals exhibited age-dependent improvements in success owing to changes in their physical state, later in life physical traits were less influential and suggest that nonphysical traits may compensate for a deteriorating physical state and its impact on male success.
Dispersal, home-range size, and habitat use of an endangered land snail, the Oregon forestsnail (Allogona townsendiana)
Authors: Edworthy A.B. , Steensma K.M.M. , Zandberg H.M. , Lilley P.L.
Published: June 2012

Terrestrial molluscs have declined globally, often as a result of habitat loss and fragmentation. Many land snails are poor dispersers and exist in isolated habitat patches. The Oregon forestsnail ( Allogona townsendiana (I. Lea, 1838)) coincides with the most densely populated region of British Columbia and is listed as endangered in Canada. To investigate the dispersal distances and habitat-use patterns of Oregon forestsnails, we tagged and tracked 21 adult snails at Langley, British Columbia, for up to 3 years (2005–2008). The maximum daily dispersal distance for a snail was 4.5 m and the maximum displacement that we observed for a snail was 32.2 m during 3 years. Snails occupied home-range areas of 18.4–404.4 m2, often overlapping both forest and meadow habitat. Their home-range sizes were smaller in habitats with high availability of stinging nettle ( Urtica dioica L.), which may be an indicator of high-quality habitat. Our results suggest that the Oregon forestsnail is a relatively sedentary species with limited dispersal ability in its adult stage. Although Oregon forestsnails are likely unable to colonize suitable habitat independently, remnant forest–meadow mosaic patches such as our study site provide valuable habitat for Oregon forestsnail, which are supplementary to large tracts of intact forest where most of their populations are found.
Top–down influence of resident and overwintering Bald Eagles (Haliaeetus leucocephalus) in a model marine ecosystem
Authors: Harvey C.J. , Good T.P. , Pearson S.F.
Published: June 2012

Conservation of predators presents challenges when predators affect prey populations that provide ecosystem services. Near Puget Sound, resident and overwintering populations of Bald Eagle ( Haliaeetus leucocephalus (L., 1766)) have expanded in recent decades. We modeled the potential impact of Bald Eagles on marine food-web structure. Bald Eagles caused trophic cascade dynamics through mid-level predators (seabirds) to lower trophic levels (fishes, benthic invertebrates), particularly when seabirds were more abundant in eagle diets. Resident Bald Eagles affected food-web structure more than overwintering eagles, despite the latters’ greater abundance. Predator avoidance behavior by nearshore diving birds and herbivorous birds exacerbated trophic cascade effects, but only in a narrow range of species. Variability in the number of overwintering Bald Eagles, which come to the area to feed on salmon carcasses (primarily chum salmon, Oncorhynchus keta (Walbaum in Artedi, 1792)), had little effect on the food web. Our results indicate that Bald Eagles are important to marine food-web structure, owing to their high consumption rates and the high consumption rates of their seabird prey, but uncertainty about eagle diets limits our full understanding of their impact. In systems where Bald Eagles affect large seabird breeding colonies, their role in food-web structure is likely greater.
IMPROVED LINKED DATA INTERACTION THROUGH AN AUTOMATIC INFORMATION ARCHITECTURE
Authors: BRUNETTI JOSEP MARIA , GIL ROSA , GIMENO JUAN MANUEL , GARCIA ROBERTO
Published: June 2012

Thanks to Open Data initiatives the amount of data available on the Web is rapidly increasing. Unfortunately, most of these initiatives only publish raw tabular data, which makes its analysis and reuse very difficult. Linked Data principles allow for a more sophisticated approach by making explicit both the structure and semantics of the data. However, from the user experience viewpoint, published datasets continue to be monolithic files which are completely opaque or difficult to explore by making complex semantic queries. Our objective is to facilitate the user to grasp what kind of entities are in the dataset, how they are interrelated, which are their main properties and values, etc. Rhizomer is a data publishing tool whose interface provides a set of components borrowed from Information Architecture (IA) that facilitate getting an insight of the dataset at hand. Rhizomer automatically generates navigation menus and facets based on the kinds of things in the dataset and how they are described through metadata properties and values. This tool is currently being evaluated with end users that discover a whole new perspective of the Web of Data.
TOWARDS A PAN-EUROPEAN E-PROCUREMENT PLATFORM TO AGGREGATE, PUBLISH AND SEARCH PUBLIC PROCUREMENT NOTICES POWERED BY LINKED OPEN DATA: THE MOLDEAS APPROACH
Authors: ALVAREZ JOSE MARÍA , LABRA JOSÉ EMILIO , CIFUENTES FRANCISCO , ALOR-HÉRNANDEZ GINER , SÁNCHEZ CUAUHTÉMOC , LUNA JAIME ALBERTO GUZMÁN
Published: June 2012

This paper aims to describe a public procurement information platform which provides a unified pan-European system that exploits the aggregation of tender notices using linking open data and semantic web technologies. This platform requires a step-based method to deal with the requirements of the public procurement sector and the open government data initiative: (1) modeling the unstructured information included in public procurement notices (contracting authorities, organizations, contracts awarded, etc.); (2) enriching that information with the existing product classification systems and the linked data vocabularies; (3) publishing relevant information extracted out of the notices following the linking open data approach; (4) implementing enhanced services based on advanced algorithms and techniques like query expansion methods to exploit the information in a semantic way. Taking into account that public procurement notices contain different kinds of data like types of contract, region, duration, total amount, target enterprise, etc., various methods can be applied to expand user queries easing the access to the information and providing a more accurate information retrieval system. Nevertheless expanded user queries can involve an extra-time in the process of retrieving notices. That is why a performance evaluation is outlined to tune up the semantic methods and the generated queries providing a scalable and time-efficient system. Moreover, this platform is supposed to be especially relevant for SMEs that want to tender in the European Union (EU), easing their access to the information of the notices and fostering their participation in cross-border public procurement processes across Europe. Finally an example of use is provided to evaluate and compare the goodness and the improvement of the proposed platform with regard to the existing ones.
REQUIREMENTS TRACEABILITY: A SYSTEMATIC REVIEW AND INDUSTRY CASE STUDY
Authors: TORKAR RICHARD , GORSCHEK TONY , FELDT ROBERT , SVAHNBERG MIKAEL , RAJA UZAIR AKBAR , KAMRAN KASHIF
Published: June 2012

Requirements traceability enables software engineers to trace a requirement from its emergence to its fulfillment. In this paper we examine requirements traceability definitions, challenges, tools and techniques, by the use of a systematic review performing an exhaustive search through the years 1997–2007. We present a number of common definitions, challenges, available tools and techniques (presenting empirical evidence when found), while complementing the results and analysis with a static validation in industry through a series of interviews.
THE ΛCDM GROWTH RATE OF STRUCTURE REVISITED
Authors: BASILAKOS SPYROS
Published: June 2012

We re-examine the growth index of the concordance Λ cosmology in the light of the latest 6dF and WiggleZ data. In particular, we investigate five different models for the growth index γ, by comparing their cosmological evolution using observational data of the growth rate of structure formation at different redshifts. Performing a joint likelihood analysis of the recent supernovae type Ia data, the Cosmic Microwave Background shift parameter, Baryonic Acoustic Oscillations and the growth rate data, we determine the free parameters of the γ(z) parametrizations and we statistically quantify their ability to represent the observations. We find that the addition of the 6dF and WiggleZ growth data in the likelihood analysis improves significantly the statistical results. As an example, considering a constant growth index we find Ωm0 = 0.273 ± 0.011 and [Formula: see text].
TEMPERATURE EFFECT ON STRUCTURAL AND ELECTRONIC PROPERTIES OF ZINC OXIDE NANOWIRES SYNTHESIZED BY CARBOTHERMAL EVAPORATION METHOD
Authors: ORVATINIA MOHAMMAD , IMANI ROGHAYEH
Published: June 2012

Zinc Oxide ( ZnO ) nanowires were synthesized on the Si substrates by carbothermal evaporation of ZnO + C at elevated temperatures. The syntheses were carried out at different temperatures from 750°C to 950°C. Characterizations of layers were performed to study the effect of synthesis temperature on morphology, crystal structure and electrical behavior of fabricated nanowires. The physical characterization was performed by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray (EDAX) methods. SEM micrograph of layers revealed that the samples grown at the lower temperatures have better quality. However, below 800°C the growth of nanowires was stopped. So the 800°C was concluded to be the optimum temperature for growth of high quality nanowires by proposed system. By recording the conductivity variations as a function of inverse temperature, 1/T, the semiconductor property of the samples was verified. It is demonstrated that two distinct factors affect the electrical conductivity of layers, which are due to the bulk and grain boundary. We experimentally proved that the activation energy corresponding to grain boundary is higher than that of the bulk. As another result we have established for the first time that by increasing synthesis temperatures, both activation energies shift to higher values.
GENERATING SERIES FOR SYMMETRIC PRODUCT SPACES
Authors: CHO YONG SEUNG
Published: June 2012

We consider the symmetric product spaces of closed manifolds. We introduce some geometric invariants and the topological properties of symmetric product spaces via the symmetric invariant ones of product spaces and apply to Gromov–Witten invariants. We examine the symmetric product spaces of the complex projective line, their Gromov–Witten invariants and compute the generating series induced by their Gromov–Witten invariants.
A RESTATEMENT OF THE ALGEBRAIC CLASSIFICATION OF AREA METRICS ON 4-MANIFOLDS
Authors: DAHL MATIAS F.
Published: June 2012

An area metric is a [Formula: see text]-tensor with certain symmetries on a 4-manifold that represents a non-dissipative linear electromagnetic medium. A recent result by Schuller, Witte and Wohlfarth gives a pointwise algebraic classification for such area metrics. This result is similar to the Jordan normal form theorem for [Formula: see text]-tensors, and the result shows that pointwise area metrics divide into 23 metaclasses and each metaclass requires two coordinate representations. For the first 7 metaclasses, we show that only one coordinate representation is needed. For the remaining 16 metaclasses we find an additional third coordinate representation.
SUB-WEYL GEOMETRY AND ITS LINEAR CONNECTIONS
Authors: CONSTANTINESCU OANA , CRASMAREANU MIRCEA
Published: June 2012

The aim of this paper is to study from the point of view of linear connections the data [Formula: see text] with M a smooth (n+p)-dimensional real manifold, [Formula: see text] an n-dimensional manifold semi-Riemannian distribution on M, [Formula: see text] the conformal structure generated by g and W a Weyl substructure: a map [Formula: see text] such that W(ḡ) = W(g) - du, ḡ = eug;u ∈ C∞(M). Compatible linear connections are introduced as a natural extension of similar notions from Weyl geometry and such a connection is unique if a symmetry condition is imposed. In the foliated case the local expression of this unique connection is obtained. The notion of Vranceanu connection is introduced for a pair (Weyl structure, distribution) and it is computed for the tangent bundle of Finsler spaces, particularly Riemannian, choosing as distribution the vertical bundle of tangent bundle projection and as one-form the Cartan form.
EFFECTIVE MODELS FOR GENE NETWORKS AND THEIR APPLICATIONS
Authors: SHULMAN JASON , SEEMANN LARS , ROMAN GREGG W. , GUNARATNE GEMUNU H.
Published: June 2012

Networks are used to abstract large, highly-coupled sets of objects. Their analyses have included network classification into a few broad classes and selection of small substructures that perform simple yet common tasks. One issue that has received little attention is how the state of a network can be moved according to a pre-specified set of guidelines. In this paper, we address this question in the context of gene networks. In general, neither the full membership of the gene network associated with a biological process nor the precise form of interactions between nodes is known. What is available, through microarrays or sequencing, are gene expression profiles of an organism or its viable mutants. Our approach relies only on these expression profiles, and not on the availability of an accurate model for the network. The first step is to select a small set of core- or master- nodes, such as transcription factors or microRNAs, that can be used to alter the levels of many of the remaining genes in the network. We ask how the state — or solution — of the gene network changes as the levels of these master nodes are altered externally. The object of our study is, not the network, but the surface of these solutions. We argue that it can be approximated using gene expression profiles of the organism and single manipulation of master node activity. This is done through an "effective model." The effective model as well as error estimates for its predictions can be derived from experimental data. The method is validated using synthetic gene networks that have stationary solutions and those that are periodically driven, e.g., circadian networks. An effective model for the oxygen-deprivation network of E.coli is constructed using previously published gene expression profiles, and used to predict the expression levels in a double knockout mutant. Less that 30% of the predictions lie outside the 5% confidence level. We propose the use of the effective model methodology to compute how Drosophila melanogaster in the normal state can be genetically altered into a pre-defined sleep deprived-like state.
Adaptor protein 1 complexes regulate intracellular trafficking of the kidney anion exchanger 1 in epithelial cells
Authors: Almomani Ensaf Y. , King Jennifer C. , Netsawang Janjuree , Yenchitsomanus Pa-Thai , Malasit Prida , Limjindaporn Thawornchai , Alexander R. Todd , Cordat Emmanuelle
Published: June 2012

Distal renal tubular acidosis (dRTA) can be caused by mutations in the gene encoding the anion exchanger 1 (AE1) and is characterized by defective urinary acidification, metabolic acidosis, and renal stones. AE1 is expressed at the basolateral membrane of type A intercalated cells in the renal cortical collecting duct (kAE1). Two dRTA mutations result in the carboxyl-terminal truncation of kAE1; in one case, the protein trafficked in a nonpolarized way in epithelial cells. A recent yeast two-hybrid assay showed that the carboxyl-terminal cytosolic domain of AE1 interacts with adaptor protein complex 1 (AP-1A) subunit μ1A (mu-1A; Sawasdee N, Junking M, Ngaojanlar P, Sukomon N, Ungsupravate D, Limjindaporn T, Akkarapatumwong V, Noisakran S, Yenchitsomanus PT. Biochem Biophys Res Commun 401: 85–91, 2010). Here, we show the interaction between kAE1 and mu-1A and B in vitro by reciprocal coimmunoprecipitation in epithelial cells and in vivo by coimmunoprecipitation from mouse kidney extract. When endogenous mu-1A (and to a lesser extent mu-1B) was reduced, kAE1 protein was unable to traffic to the plasma membrane and was rapidly degraded via a lysosomal pathway. Expression of either small interfering RNA-resistant mu-1A or mu-1B stabilized kAE1 in these cells. We also show that newly synthesized kAE1 does not traffic through recycling endosomes to the plasma membrane, suggesting that AP-1B, located in recycling endosomes, is not primarily involved in trafficking of newly synthesized kAE1 when AP-1A is present in the cells. Our data demonstrate that AP-1A regulates processing of the basolateral, polytopic membrane protein kAE1 to the cell surface and that both AP-1A and B adaptor complexes are required for normal kAE1 trafficking.
On the role of TRPC1 in control of Ca2+ influx, cell volume, and cell cycle
Authors: Madsen C. P. , Klausen T. K. , Fabian A. , Hansen B. J. , Pedersen S. F. , Hoffmann E. K.
Published: June 2012

Ca+ signaling plays a crucial role in control of cell cycle progression, but the understanding of the dynamics of Ca2+ influx and release of Ca2+ from intracellular stores during the cell cycle is far from complete. The aim of the present study was to investigate the role of the free extracellular Ca2+ concentration ([Ca2+]o) in cell proliferation, the pattern of changes in the free intracellular Ca2+ concentration ([Ca2+]i) during cell cycle progression, and the role of the transient receptor potential (TRP)C1 in these changes as well as in cell cycle progression and cell volume regulation. In Ehrlich Lettré Ascites (ELA) cells, [Ca2+]i decreased significantly, and the thapsigargin-releasable Ca2+ pool in the intracellular stores increased in G1 as compared with G0. Store-depletion-operated Ca2+ entry (SOCE) and TRPC1 protein expression level were both higher in G1 than in G0 and S phase, in parallel with a more effective volume regulation after swelling [regulatory volume decrease (RVD)] in G1 as compared with S phase. Furthermore, reduction of [Ca2+]o, as well as two unspecific SOCE inhibitors, 2-APB (2-aminoethyldiphenyl borinate) and SKF96365 (1-(β-[3-(4-methoxy-phenyl)propoxyl-4-methoxyphenethyl)1H-imidazole-hydrochloride), inhibited ELA cell proliferation. Finally, Madin-Darby canine kidney cells in which TRPC1 was stably silenced [TRPC1 knockdown (TRPC1-KD) MDCK] exhibited reduced SOCE, slower RVD, and reduced cell proliferation compared with mock controls. In conclusion, in ELA cells, SOCE and TRPC1 both seem to be upregulated in G1 as compared with S phase, concomitant with an increased rate of RVD. Furthermore, TRPC1-KD MDCK cells exhibit decreased SOCE, decreased RVD, and decreased proliferation, suggesting that, at least in certain cell types, TRPC1 is regulated during cell cycle progression and is involved in SOCE, RVD, and cell proliferation.
Cell-specific expression of human HGF by alveolar type II cells induces remodeling of septal wall tissue in the lung: a morphometric study
Authors: Leuenberger Alexandra , Gazdhar Amiq , Herrmann Gudrun , Ochs Matthias , Geiser Thomas , Knudsen Lars
Published: June 2012

Hepatocyte growth factor (HGF) is involved in development and regeneration of the lungs. Human HGF, which was expressed specifically by alveolar epithelial type II cells after gene transfer, attenuated the bleomycin-induced pulmonary fibrosis in an animal model. As there are also regions that appear morphologically unaffected in fibrosis, the effects of this gene transfer to normal lungs is of interest. In vitro studies showed that HGF inhibits the formation of the basal lamina by cultured alveolar epithelial cells. Thus we hypothesized that, in the healthy lung, cell-specific expression of HGF induces a remodeling within septal walls. Electroporation of a plasmid of human HGF gene controlled by the surfactant protein C promoter was applied for targeted gene transfer. Using design-based stereology at light and electron microscopic level, structural alterations were analyzed and compared with a control group. HGF gene transfer increased the volume of distal air spaces, as well as the surface area of the alveolar epithelium. The volume of septal walls, as well as the number of alveoli, was unchanged. Volumes per lung of collagen and elastic fibers were unaltered, but a marked reduction of the volume of residual extracellular matrix (all components other than collagen and elastic fibers) and interstitial cells was found. A correlation between the volumes of residual extracellular matrix and distal air spaces, as well as total surface area of alveolar epithelium, could be established. Cell-specific expression of HGF leads to a remodeling of the connective tissue within the septal walls in the healthy lung, which is associated with more pronounced stretching of distal air spaces at a given hydrostatic pressure during instillation fixation.
Effects of exercise training on airway closure in asthmatics
Authors: Scichilone Nicola , Morici Giuseppe , Zangla Daniele , Arrigo Rita , Cardillo Irene , Bellia Vincenzo , Bonsignore Maria Rosaria
Published: June 2012

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV1): 100 ± 7.4% pred; FEV1/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline ( week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV1: 102 ± 7.0% predicted; FEV1/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 ( P = 0.03), and 11 ± 8% at week 10 ( P = 0.028). The Mch-induced reduction in FEV1 did not change with exercise ( P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.
Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease
Authors: Brun Yohann , Karachi Carine , Fernandez-Vidal Sara , Jodoin Nicolas , Grabli David , Bardinet Eric , Mallet Luc , Agid Yves , Yelnik Jerome , Welter Marie-Laure
Published: June 2012

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4–5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.
Diversity and excitability of deep-layer entorhinal cortical neurons in a model of temporal lobe epilepsy
Authors: Pilli Jyotsna , Abbasi Saad , Richardson Max , Kumar Sanjay S.
Published: June 2012

The entorhinal cortex (ERC) is critically implicated in temporal lobe epileptogenesis—the most common type of adult epilepsy. Previous studies have suggested that epileptiform discharges likely initiate in seizure-sensitive deep layers (V–VI) of the medial entorhinal area (MEA) and propagate into seizure-resistant superficial layers (II–III) and hippocampus, establishing a lamina-specific distinction between activities of deep- versus superficial-layer neurons and their seizure susceptibilities. While layer II stellate cells in MEA have been shown to be hyperexcitable and hypersynchronous in patients and animal models of temporal lobe epilepsy (TLE), the fate of neurons in the deep layers under epileptic conditions and their overall contribution to epileptogenicity of this region have remained unclear. We used whole cell recordings from slices of the ERC in normal and pilocarpine-treated epileptic rats to characterize the electrophysiological properties of neurons in this region and directly assess changes in their excitatory and inhibitory synaptic drive under epileptic conditions. We found a surprising heterogeneity with at least three major types and two subtypes of functionally distinct excitatory neurons. However, contrary to expectation, none of the major neuron types characterized showed any significant changes in their excitability, barring loss of excitatory and inhibitory inputs in a subtype of neurons whose dendrite extended into layer III, where neurons are preferentially lost during TLE. We confirmed hyperexcitability of layer II neurons in the same slices, suggesting minimal influence of deep-layer input on superficial-layer neuron excitability under epileptic conditions. These data show that deep layers of ERC contain a more diverse population of excitatory neurons than previously envisaged that appear to belie their seizure-sensitive reputation.
The Vitamin E Analogue α-TEA Stimulates Tumor Autophagy and Enhances Antigen Cross-Presentation
Authors: Li Yuhuan , Hahn Tobias , Garrison Kendra , Cui Zhi-Hua , Thorburn Andrew , Thorburn Jacqueline , Hu Hong-Ming , Akporiaye Emmanuel T.
Published: June 2012

The semisynthetic vitamin E derivative alpha-tocopheryloxyacetic acid (α-TEA) induces tumor cell apoptosis and may offer a simple adjuvant supplement for cancer therapy if its mechanisms can be better understood. Here we report that α-TEA also triggers tumor cell autophagy and that it improves cross-presentation of tumor antigens to the immune system. α-TEA stimulated both apoptosis and autophagy in murine mammary and lung cancer cells and inhibition of caspase-dependent apoptosis enhanced α-TEA–induced autophagy. Cell exposure to α-TEA generated double-membrane–bound vesicles indicative of autophagosomes, which efficiently cross-primed antigen-specific CD8+ T cells. Notably, vaccination with dendritic cells pulsed with α-TEA–generated autophagosomes reduced lung metastases and increased the survival of tumor-bearing mice. Taken together, our findings suggest that both autophagy and apoptosis signaling programs are activated during α-TEA–induced tumor cell killing. We suggest that the ability of α-TEA to stimulate autophagy and enhance cross-priming of CD8+ T cells might be exploited as an adjuvant strategy to improve stimulation of antitumor immune responses. Cancer Res; 72(14); 3535–45. ©2012 AACR.
Trifunctional Bispecific Antibodies Induce Tumor-Specific T Cells and Elicit a Vaccination Effect
Authors: Eissler Nina , Ruf Peter , Mysliwietz Josef , Lindhofer Horst , Mocikat Ralph
Published: June 2012

A major goal of tumor immunotherapy is the induction of long-lasting systemic T-cell immunity. Bispecific antibodies (bsAbs) that lack the immunoglobulin Fc region confer T–cell-mediated killing of tumor cells but do not induce long-term memory. In contrast, trifunctional bsAbs comprise an appropriate Fc region and, therefore, not only recruit T cells but also accessory cells that bear activating Fcγ receptors (FcγR), providing additional T–cell-activating signals and securing presentation of tumor-derived antigens to T cells. In this study, we show that trifunctional bsAbs induce a polyvalent T-cell response and, therefore, a vaccination effect. Mice were treated with melanoma cells and with a trifunctional bsAb directed against the melanoma target antigen ganglioside GD2 in addition to murine CD3. The trifunctional bsAb activated dendritic cells and induced a systemic immune response that was not replicated by treatment with the F(ab′)2-counterpart lacking the Fc region. Restimulation of spleen and lymph node cells in vitro yielded T-cell lines that specifically produced interferon-γ in response to tumor. In addition, trifunctional bsAb-induced T cells recognized various specific peptides derived from melanoma-associated antigens. Moreover, these polyvalent responses proved to be tumor-suppressive and could not be induced by the corresponding bsF(ab′)2-fragment. Taken together, our findings provide preclinical proof of concept that trifunctional bsAbs can induce tumor-specific T cells with defined antigen specificity. Cancer Res; 72(16); 3958–66. ©2012 AACR.