bluuebunny/crossref_metadata_2025 huggingface dataset:
Monte Carlo simulations and radiation dosimetry measurements of peripherally applied HDR breast brachytherapy D‐shaped applicators
Authors: Yang Yun , Rivard Mark J.
Published: February 2009

Conformal dose coverage for accelerated partial breast irradiation or radiotherapy boost can be obtained with AccuBoost® D‐shaped brachytherapy applicators using a flattened surface positioned near the patient. Three D‐shaped applicators (D45/D53/D60) were dosimetrically characterized using Monte Carlo methods (MCNP5), air ionization chambers (Farmer and Markus), and radiochromic film (GafChromic EBT) in polystyrene and ICRU 44 breast tissue. HDR source dwell times were either constant or optimized to improve skin dose uniformity. Scatter dose decreased as depth decreased. 10 mm beyond the applicator aperture, dose reductions of 90% and 51% were observed at depths of 0 and 30 mm, respectively. Similarly, planar dose uniformity improved as depth decreased and was also due to scatter and applicator geometry. Dose uniformity inside the applicator aperture was approximately 11% and 15% for all three applicators at the skin and 30 mm deep, respectively. Depth dose measurements in polystyrene using ion chamber and radiochromic film agreed with Monte Carlo results within 2%. Discrepancies between film and Monte Carlo dose profiles at 30 mm depth were within 1%.
Static and rotational output variation of a tomotherapy unit
Authors: Francois Pascal , Mazal Alejandro
Published: February 2009

A simple device to check the machine output in rotational mode is described. Integral and instantaneous beam output in absolute dose can be measured and analyzed in a very simple manner. A method to correlate the results with the value obtained during the machine calibration in static beam and the reference value used by the treatment planning system for dose calculation in rotation beam is also described. Using this method and device, the daily output can be performed in rotational conditions which are closer to the treatment conditions. Measurement results using this device show differences in the beam output between static and rotational delivery which have to be considered carefully during the calibration process.
Field size effect of radiation quality in carbon therapy using passive method
Authors: Nose H. , Kase Y. , Matsufuji N. , Kanai T.
Published: February 2009

The authors have investigated the dependency of radiation quality and absorbed dose on radiation field size in therapeutic carbon beams. The field size of the broad beam, formed using the passive technique, was controlled from per side with a multileaf collimator. The absorbed dose and radiation quality on the beam center were evaluated at several depths in a water phantom using microdosimetric technique in experiments and Monte Carlo simulations. With an increase in the field size, the radiation quality was reduced, although the absorbed dose grew at the center of the field. This indicates that the dose and radiation quality at the center of the broad beam are influenced by particles from the off‐center region via large‐angle scattering and that such particles have relatively low radiation quality and mainly consist of fragment particles. Because such a tendency appeared to be more remarkable in the deeper region of the water phantom, it is likely that fragment particles that are born in a water phantom have a marked role in determining the field size effect.
The effect of scatter and glare on image quality in contrast‐enhanced breast imaging using an full‐field flat panel detector
Authors: Carton Ann‐Katherine , Acciavatti Raymond , Kuo Johnny , Maidment Andrew D. A.
Published: February 2009

The purpose of this study is to evaluate the performance of an antiscatter grid and its potential benefit on image quality for a full‐field digital mammography (FFDM) detector geometry at energies typical for temporal subtraction contrast‐enhanced (CE) breast imaging. The signal intensities from primary, scatter, and glare were quantified in images acquired with an FFDM detector using a Rh target and a 0.27 mm Cu filter at tube voltages ranging from 35 to 49 kV. Measurements were obtained at the center of the irradiation region of 20–80 mm thick breast‐equivalent phantoms. The phantoms were imaged with and without an antiscatter grid. Based on these data, the performance of the antiscatter grid was determined by calculating the primary and scatter transmission factors ( and ) and Bucky factors . In addition, glare‐to‐primary ratios (GPRs) and scatter‐to‐primary ratios (SPRs) were quantified. The effect of the antiscatter grid on the signal‐difference‐to‐noise ratio (SDNR) was also assessed. It was found that increases with kV but does not depend on the phantom thickness; values between 0.81 and 0.84 were measured. increases with kV and phantom thickness; values between 0.13 and 0.21 were measured. decreases with kV and increases with phantom thickness; ranges from 1.4 to 2.1. GPR is nearly constant, varying from 0.10 to 0.11. SPR without an antiscatter grid ranges from 0.35 to 1.34. decreases by approximately 9% from 35 to 49 kV for a given phantom thickness and is 3.5 times larger for an 80 mm thick breast‐equivalent phantom than for a 20 mm thick breast‐equivalent phantom. SPR with an antiscatter grid ranges from 0.06 to 0.31. increases by approximately 23% from 35 to 49 kV for a given phantom thickness; is four times larger for an 80 mm breast‐equivalent phantom than for a 20 mm breast‐equivalent phantom. When imaging a 25 mm PMMA plate at the same mean glandular dose with and without an antiscatter grid, the SDNR is 4% greater with a grid than without. For an 75mm PMMA plate, the SDNR is 20% greater with a grid. In conclusion, at the higher x‐ray energy range used for CE‐DM and CE‐DBT, an antiscatter grid significantly reduces SPR and improves SDNR. These effects are most pronounced for thick breasts.
Contributions to the floras of British Columbia and the Yukon Territory. II. Mosses and lichens
Authors: Douglas George W. , Peterson W. L.
Published: February 2009

One moss taxon and five lichen taxa new to British Columbia and eight moss taxa new to the Yukon are reported. In addition, four other rare British Columbia or Yukon species are discussed.
Alpine lichen-dominated communities in Alberta and the Yukon
Authors: See Marianne G. , Bliss L. C.
Published: February 2009

Alpine lichen-dominated vegetation is described with emphasis upon floristic composition, quantitative structure, and distribution of lichen communities. Macrolichens and vascular plants were quantitatively sampled using stratified random quadrats (10 cm × 40 cm) in 40 stands (30 m × 5 m) in west-central Alberta and north central Yukon Territory. Comparable acid and basic substrates, and glaciated and unglaciated sites were sampled in each region. Bray-Curtis and reciprocal averaging ordinations were used to analyze vegetation data. For both macrolichens and vascular plants, floristic similarity is greater within each region than on equivalent substrates in different regions. Three alpine macrolichen communities are described in each region which exhibit pronounced regional differences. Cetraria tilesii and Thamnolia subuliformis characterize driest sites in both regions, while Cetraria cucullata indicates mesic habitats. Cladonia spp. dominate acidic Yukon sites; Stereocaulon alpinum and Peltigera aphthosa characterize equivalent Alberta habitats. Vascular plant communities are dominated by Dryas integrifolia and D. octopetala in Alberta and Yukon areas, respectively, with dwarf willow and heath in acidic, mesic sites. Distribution of alpine communities of macrolichens and corresponding vascular plants is more strongly correlated with substate pH and moisture, than with glaciation history. Comparison with other northern studies suggests that these macrolichen communities may be found throughout the Canadian Cordillera where equivalent habitats are present.
Influence of increasing soil phosphorus levels on interactions between vesicular–arbuscular mycorrhizae and Rhizobium in soybeans
Authors: Asimi S. , Gianinazzi-Pearson V. , Gianinazzi S.
Published: February 2009

Growth and yield increases, obtained in nodulated soybeans growing in unamended sterile soil by inoculation with the vesicular–arbuscular (VA) mycorrhizal fungus Glomus mosseae, were accompanied by improved P uptake, lower root to shoot ratios, better nodulation with higher nitrogenase activity, and modifications in the pattern of the latter during plant growth. Stimulation of nitrogenase activity occurred early in plant development and preceded plant growth responses by about 2 weeks. Phosphate fertilization increased yield, percent P but not percent N of both mycorrhizal and nonmycorrhizal soybeans, and also modified the pattern and amount of nitrogenase activity during plant growth. Additions of 0.25 g KH2PO4/kg to the soil eliminated the mycorrhizal effect on plant growth, but nodule formation and nitrogenase activity were still significantly stimulated by the mycorrhizal infection. Mycorrhizal effects on nodulation were eliminated with 0.5 g KH2PO4 and on nitrogenase activity with the addition of 1.0 g KH2PO4. These higher levels of phosphate fertilization considerably diminished infection and, in particular, fungal spread within the roots.
EFFECTIVE CONSTRAINTS FOR QUANTUM SYSTEMS
Authors: BOJOWALD MARTIN , SANDHÖFER BARBARA , SKIRZEWSKI AURELIANO , TSOBANJAN ARTUR
Published: February 2009

An effective formalism for quantum constrained systems is presented which allows manageable derivations of solutions and observables, including a treatment of physical reality conditions without requiring full knowledge of the physical inner product. Instead of a state equation from a constraint operator, an infinite system of constraint functions on the quantum phase space of expectation values and moments of states is used. The examples of linear constraints as well as the free non-relativistic particle in parametrized form illustrate how standard problems of constrained systems can be dealt with in this framework.
BINARY REPRESENTATIONS OF ALGEBRAS WITH AT MOST TWO BINARY OPERATIONS: A CAYLEY THEOREM FOR DISTRIBUTIVE LATTICES
Authors: MOVSISYAN YU. M.
Published: February 2009

The notion of binary representation of algebras with at most two binary operations is introduced in this paper, and the binary version of Cayley theorem for distributive lattices is given by hyperidentities. In particular, we get the binary version of Cayley theorem for DeMorgan and Boolean algebras.
HEIGHTS ON THE FINITE PROJECTIVE LINE
Authors: NATHANSON MELVYN B.
Published: February 2009

Define the height function h(a) = min {k + (ka mod p) : k = 1, 2, …, p - 1} for a ∈ {0, 1, …, p - 1.} It is proved that the height has peaks at p, (p + 1)/2, and (p + c)/3, that these peaks occur at a = [p/3], (p - 3)/2, (p - 1)/2, [2p/3], p - 3, p - 2, and p - 1, and that h(a) ≤ p/3 for all other values of a.
RESTRICTIONS OF HILBERT MODULAR FORMS
Authors: OULED AZAIEZ NAJIB
Published: February 2009

Let Γ ⊂ PSL (2, ℝ) be a discrete and finite covolume subgroup. We suppose that the modular curve [Formula: see text] is "embedded" in a Hilbert modular surface [Formula: see text], where ΓKis the Hilbert modular group associated to a real quadratic field K. We define a sequence of restrictions (ρn)n∈ℕof Hilbert modular forms for ΓKto modular forms for Γ. We denote by Mk1, k2(ΓK) the space of Hilbert modular forms of weight (k1, k2) for ΓK. We prove that ∑n∈ℕ∑k1, k2∈ℕρn(Mk1, k2(ΓK)) is a subalgebra closed under Rankin–Cohen brackets of the algebra ⊕k∈ℕMk(Γ) of modular forms for Γ.
Proofs, tests and continuation passing style
Authors: Guerrini Stefano , Masini Andrea
Published: February 2009

The concept of syntactical
duality
is central in logic. In particular, the duality defined by classical negation, or more syntactically by left and right in sequents, has been widely used to relate logic and computations. We study the proof/test duality proposed by Girard in his 1999 paper on the meaning of logical rules. In detail, starting from the notion of “test” proposed by Girard, we develop a notion of test for intuitionistic logic and we give a complete deductive system whose computational interpretation is the target language of the call-by-value and call-by-name continuation passing style translations.
Crowd control
Authors: Hoffmann Leah
Published: February 2009

Using crowdsourcing applications, humans around the world are transcribing audio files, conducting market research, and labeling data, for work or pleasure.
Legally speakingWhen is a "license" really a sale?
Authors: Samuelson Pamela
Published: February 2009

Can you resell software even if the package says you can't? What are the implications for copyright law of the Quanta decision discussed in the November 2008 column?
Error correction up to the information-theoretic limit
Authors: Guruswami Venkatesan , Rudra Atri
Published: February 2009

Ever since the birth of coding theory almost 60 years ago, researchers have been pursuing the elusive goal of constructing the "best codes," whose encoding introduces the minimum possible redundancy for the level of noise they can correct. In this article, we survey recent progress in
list decoding
that has led to
efficient
error-correction schemes with an
optimal
amount of redundancy, even against
worst-case errors
caused by a potentially malicious channel. To correct a proportion ρ(say 20%) of worst-case errors, these codes only need close to a proportion ρ of redundant symbols. The redundancy cannot possibly be any lower information theoretically. This new method holds the promise of correcting a factor of two more errors compared to the conventional algorithms currently in use in diverse everyday applications.
PuzzledSolutions and sources
Authors: Winkler Peter
Published: February 2009

Last month (February 2009, p. 104) we posed a trio of brain teasers concerning algorithm termination. Here, we offer some possible solutions. How did you do?
Open access publishing in science
Authors: Mann Florian , von Walter Benedikt , Hess Thomas , Wigand Rolf T.
Published: February 2009

While the evolving information society is freely opening and sharing its diaries, social networks and source codes, it remains to be seen if the same will come true for scientific knowledge. Despite strong sympathy for the idea, scientists balk at Open Access publishing. Here we shed some light on why this is so.
Going places sitting down
Authors: Haslem Wendy
Published: February 2009

This article will explore the dynamic spatial perspective created by juxtaposing giant and miniature worlds in Hiraki Sawa's
Going Places Sitting Down
(2004). In Hiraki Sawa's digital artworks, fantastic miniature worlds are layered, illuminated, and exhibited across a triptych of digital screens.

Sawa's works, particularly,
Going Places Sitting Down
(2004), but also
Dwelling
(2002) and
Spotter
(2002) reveal the proximity between human-sized and miniature worlds. Within Sawa's digital projections, imagined worlds are layered across ordinary spaces, often reinventing the home as a site of imaginary travel. A play with scale in these domestic spaces reveals miniature dynamic sites of fantasy.

Sawa uses digital technologies in the production and exhibition of miniature worlds. In
On Longing: Narratives of the Miniature, the Gigantic, the Souvenir, the Collection
, Susan Stewart draws from the publication of
Micrographia; Or Some Physiological Descriptions of Minute Bodies Made By Magnifying Glasses, With Observations and Inquiries There Upon
(1665), to reveal the inextricable link between the miniature and new technologies when she asserts that the miniature “speaks … from the invention of the microscope, the mechanical eye that can detect significance in a world the human eye is blind to” (Stewart 1983, p. 40). A similar dynamic is visible in the shift to the digital in the new millennium. Sawa uses processes of digital compositing, layering disparate worlds across the moving image triptych to uncover new worlds.
Going Places Sitting Down
provides a primary example of digital technologies that are used to destabilize, revitalize, and recreate space, investing magic in the ordinary that enchants and invites a reflective engagement across the three screens.
Flying cake
Authors: Park Anjin , Jung Keechul
Published: February 2009

In the current age of ubiquitous computing via high bandwidth networks, wearable and hand-held mobile devices with small cameras and wireless communication will become widespread in the near future. Thus, research on augmented games for mobile devices has recently attracted a lot of attention. Most existing augmented games use a traditional “backpack” system and “pattern marker”. However, ‘backpack’ systems are expensive, cumbersome, and inconvenient to use, while the use of a pattern marker means the game can only be played at a previously installed location. Hence, this article proposes an augmented game, called
Flying Cake
, where face regions are used to create virtual objects (characters) without a predefined pattern marker, plus the location of the virtual objects are measured relative to the real world on a small mobile PDA instead of using cumbersome hardware.
Flying Cake
is an augmented shooting game with two playing modes: (1) single player, where the player attacks a virtual character overlaid on images captured by a PDA camera in the physical world; and (2) two players, where each player attacks a virtual character in an image received via a wireless LAN from their opponent. The virtual character overlaps a face region obtained using a real-time face-detection technique. As a result,
Flying Cake
provides an exciting experience for players on the basis of a new game paradigm where the user interacts with both the physical world captured by a PDA camera and the virtual world.
Integrating the Wii controller with enJine
Authors: Bernardes João , Nakamura Ricardo , Calife Daniel , Tokunaga Daniel , Tori Romero
Published: February 2009

The goal of the work described here is to integrate a 3D input device, the Wii controller, and enJine, a didactic engine, motivated by the growing use of 3D interfaces. This article discusses how this increases enJine's didactic and technological potential, and details the adopted solution as a layered architecture. Two interaction styles were tested with the implemented solution. Test results show a variety of data about the controller, confirming that this solution works as desired and that using it to modify a game so it can use the WiiMote as its input device is a simple task.
Greedy heuristics for the bounded diameter minimum spanning tree problem
Authors: Julstrom Bryant A.
Published: February 2009

Given a connected, weighted, undirected graph
G
and a bound
D
, the bounded diameter minimum spanning tree problem seeks a spanning tree on
G
of minimum weight among the trees in which no path between two vertices contains more than
D
edges. In Prim's algorithm, the diameter of the growing spanning tree can always be known, so it is a good starting point from which to develop greedy heuristics for the bounded diameter problem. Abdalla, Deo, and Gupta described such an algorithm. It imitates Prim's algorithm but avoids edges whose inclusion in the spanning tree would violate the diameter bound. Running the algorithm from one start vertex requires time that is
O
(
n
3
).

A modification of this approach uses the start vertex as the center of the spanning tree (if
D
is even) or as one of the two center vertices (if
D
is odd). This yields a simpler algorithm whose time is
O
(
n
2
). A further modification chooses each next vertex at random rather than greedily, though it still connects each vertex to the growing tree with the lowest-weight feasible edge. On Euclidean problem instances with small diameter bounds, the randomized heuristic is superior to the two fully greedy algorithms, though its advantage fades as the diameter bound grows. On instances whose edge weights have been chosen at random, the fully greedy algorithms outperform the randomized heuristic.
Purpose-Built Languages
Authors: Shapiro Mike
Published: February 2009

In my college computer science lab, two eternal debates flourished during breaks from long nights of coding and debugging: "emacs versus vi?"; and "what is the best programming language?" Later, as I began my career in industry, I noticed that the debate over programming languages was also going on in the hallways of Silicon Valley campuses. It was the ’90s, and at Sun many of us were watching Java claim significant mindshare among developers, particularly those previously developing in C or C++.
The Flaws of Nature
Authors: Kelly-Bootle Stan
Published: February 2009

Multicolumnar ideas had been lurking like Greek temples in my so-called mind as 2008 came to an end. There are so many annual journalistic clichés available, looking back at all our past-years’ mistakes and resolving never to repeat them in 2009. One annoyance that I must get off my chest here and now: Can we ban such empty constructions as "X is much worse than you may think"? Or "Y is much simpler than many suppose"? We may never have thought of X one way or the other, or made suppositions about the ease of Y, yet we tend to nod and move on as though some meaningful proposition has been asserted; and, worse, that some judgment has been validated beyond dispute. Let’s learn to recognize these sneaky-weasely variations of "proof by insinuation."
Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase
Authors: Tham Elaine , Liu Jianhua , Innis Sheila , Thompson David , Gaylinn Bruce D. , Bogarin Roberto , Haim Alon , Thorner Michael O. , Chanoine Jean-Pierre
Published: February 2009

Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes ( n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean ± SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 ± 0.2 vs. 10.2 ± 1.9 ng·ml−1·90 min−1, P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated ( r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 ± 1.9 vs. 8.6 ± 1.2 ng·ml−1·90 min−1, P = 0.005). In a second group of subjects ( n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 ± 0.5 vs. 4.5 ± 0.6 μg/ml, P = 0.029) and cholinesterase activity (705 ± 33 vs. 1,013 ± 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process. Desacyl ghrelin increases in gestational diabetes, possibly reflecting resistance to the inhibitory effect of insulin on ghrelin secretion.
Evidence that Exocytosis Is Driven by Calcium Entry Through Multiple Calcium Channels in Goldfish Retinal Bipolar Cells
Authors: Coggins Michael , Zenisek David
Published: February 2009

Ribbon-containing neurons represent a subset of neural cells that undergo graded membrane depolarizations rather than Na+-channel evoked action potentials. Bipolar cells of the retina are one type of ribbon-containing neuron and extensive research has demonstrated kinetically distinct pools of vesicles that are released and replenished in a calcium-dependent manner. In this study, we look at the properties of the fastest pool of releasable vesicles in these cells, often referred to as the immediately releasable pool (IRP), to investigate the relationships between vesicle release and calcium channels in these terminals. Using whole cell capacitance measurements, we monitored exocytosis in response to different magnitude and duration depolarizations, with emphasis on physiologically relevant step depolarizations. We find that release rate of the IRP increases superlinearly with membrane potential and that the IRP is sensitive to elevated EGTA concentrations in a membrane-potential–dependent manner across the physiological range of membrane potentials. Our results are best explained by a model in which multiple Ca2+ channels act in concert to drive exocytosis of a single synaptic vesicle. Pooling calcium entering through many calcium channels may be important for reducing stochastic noise in neurotransmitter release associated with the opening of individual calcium channels.
Proteome analysis of fatty liver in feed-deprived dairy cows reveals interaction of fuel sensing, calcium, fatty acid, and glycogen metabolism
Authors: Kuhla Björn , Albrecht Dirk , Kuhla Siegfried , Metges Cornelia C.
Published: February 2009

The liver of dairy cows is involved in signaling the current hepatic metabolic state to the brain via metabolites and nerval afferents to control and adjust feed intake. Feed deprivation may result in mobilization of body reserves favoring hepatic steatosis. While the overall metabolic changes are well characterized, specific regulatory mechanisms are not readily understood. To identify molecular events associated with metabolic adaptation and the control of energy homeostasis, liver specimens from six ad libitum-fed and six feed-deprived cows were analyzed for selected metabolites, for the activation of AMP kinase, and for regulatory/regulated proteins using two-dimensional gel electrophoresis and MALDI-TOF-MS. Feed deprivation increased total liver fat and the calcium content, as well as augmented AMPK phosphorylation, while it decreased the contents of protein, glucose, glycogen, and cholesterol when expressed as a percentage of dry matter. Among 34 differentially expressed proteins identified, we found downregulation of proteins associated with fatty acid oxidation, glycolysis, electron transfer, protein degradation, and antigen processing, as well as cytoskeletal rearrangement. Proteins upregulated after feed deprivation included enzymes of the urea cycle, fatty acid or cholesterol transport proteins, an inhibitor of glycolysis, and previously unknown changes in calcium signaling network. Direct correlation was found between expression of glycolytic enzymes and glucose/glycogen content, whereas inverse correlation exists between expression of β-oxidative enzymes and total liver fat content. In conclusion, the regulatory response of identified proteins may help to explain development and consequences of hepatic lipidosis but also offers novel candidates potentially involved in signaling for maintaining energy homeostasis.
An Efficient Algorithm to Find Broadcast Schedule in Ad Hoc TDMA Networks
Authors: Ahmad Imtiaz , Al-Kazemi Buthaina , Das A. Shoba
Published: February 2009

The broadcast scheduling is of fundamental importance and practical concern for ad hoc network performance measures such as the communication delay and the throughput. The scheduling problem on hand involves determination of a collision‐free broadcast schedule with the minimum length TDMA frame and the maximum slot utilization by efficient distribution of slots among stations. The problem is widely known as NP‐complete, and diverse heuristic algorithms were reported to solve this problem recently. The intractable nature of the broadcast scheduling problem and its importance in ad hoc TDMA networks necessitates development of more efficient heuristic algorithms. In this paper, we developed a new heuristic approach which employs a tight lower bound derived from the maximal incompatibles and generates a search space from the set of maximal compatibles. The developed algorithm is very efficient and effective in conquering the intractable nature of the broadcast scheduling problem in the sense that it explores complex solution space in smaller CPU time. A comparison with existing techniques for the test examples reported in the literature shows that our algorithm achieves a collision‐free broadcast with minimum frame length and the maximum slot utilization in relatively shorter time.
Luteinized Ovarian Thecoma in a Postmenopausal Women Presenting with Virilization
Authors: Kaluarachchi Athula , Marasinghe Jeevan P. , Batcha Thuwan M. , Agunawela Preethika
Published: February 2009

We report a case of luteinizing thecoma in a 58-year-old postmenopausal woman who presented with progressive androgenic features and hypertension of one year duration. She did not notice a significant change in her body weight or appetite. Her total serum testosterone level was 4.5 ng/mL. Ultrasound scan revealed a normal-sized uterus and a right-sided solid ovarian mass of 5 cm 5 cm. Left ovary was normal. She had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and an omentectomy performed. Histological examination confirmed the diagnosis of luteinized thecoma. This case illustrates the necessity to consider the rare possibility of luteinized ovarian thecoma as a cause for virilization in a menopausal woman.
EphA2 Reexpression Prompts Invasion of Melanoma Cells Shifting from Mesenchymal to Amoeboid-like Motility Style
Authors: Parri Matteo , Taddei Maria Letizia , Bianchini Francesca , Calorini Lido , Chiarugi Paola
Published: February 2009

Eph tyrosine kinases instruct cell for a repulsive behavior, regulating cell shape, adhesion, and motility. Beside its role during embryogenesis, neurogenesis, and angiogenesis, EphA2 kinase is frequently up-regulated in tumor cells of different histotypes, including prostate, breast, colon, and lung carcinoma, as well as melanoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 is still debated. Here, we showed that EphA2 reexpression in B16 murine melanoma cells, which use a defined mesenchymal invasion strategy, converts their migration style from mesenchymal to amoeboid-like, conferring a plasticity in tumor cell invasiveness. Indeed, in response to reexpression and activation of EphA2, melanoma cells activate a nonproteolytic invasive program that proceeds through the activation of cytoskeleton motility, the retraction of cell protrusions, a Rho-mediated rounding of the cell body, and squeezing among three-dimensional matrix, giving rise to successful lung and peritoneal lymph node metastases. Our results suggest that, among the redundant mechanisms operating in tumor cells to penetrate the anatomic barriers of host tissues, EphA2 plays a pivotal role in the adaptive switch in migration pattern and mechanism, defining and distinguishing tumor cell invasion strategies. Thus, targeting EphA2 might represent a future approach for the therapy of cancer dissemination. [Cancer Res 2009;69(5):2072–81]
Unsupervised Analysis of Transcriptomic Profiles Reveals Six Glioma Subtypes
Authors: Li Aiguo , Walling Jennifer , Ahn Susie , Kotliarov Yuri , Su Qin , Quezado Martha , Oberholtzer J. Carl , Park John , Zenklusen Jean C. , Fine Howard A.
Published: February 2009

Gliomas are the most common type of primary brain tumors in adults and a significant cause of cancer-related mortality. Defining glioma subtypes based on objective genetic and molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications based on gene expression data have been attempted in the past with varying success and with only some concordance between studies, possibly due to inherent bias that can be introduced through the use of analytic methodologies that make a priori selection of genes before classification. To overcome this potential source of bias, we have applied two unsupervised machine learning methods to genome-wide gene expression profiles of 159 gliomas, thereby establishing a robust glioma classification model relying only on the molecular data. The model predicts for two major groups of gliomas (oligodendroglioma-rich and glioblastoma-rich groups) separable into six hierarchically nested subtypes. We then identified six sets of classifiers that can be used to assign any given glioma to the corresponding subtype and validated these classifiers using both internal (189 additional independent samples) and two external data sets (341 patients). Application of the classification system to the external glioma data sets allowed us to identify previously unrecognized prognostic groups within previously published data and within The Cancer Genome Atlas glioblastoma samples and the different biological pathways associated with the different glioma subtypes offering a potential clue to the pathogenesis and possibly therapeutic targets for tumors within each subtype. [Cancer Res 2009;69(5):2091–9]
Regulatory T Cells Recruited through CCL22/CCR4 Are Selectively Activated in Lymphoid Infiltrates Surrounding Primary Breast Tumors and Lead to an Adverse Clinical Outcome
Authors: Gobert Michael , Treilleux Isabelle , Bendriss-Vermare Nathalie , Bachelot Thomas , Goddard-Leon Sophie , Arfi Vanessa , Biota Cathy , Doffin Anne Claire , Durand Isabelle , Olive Daniel , Perez Solène , Pasqual Nicolas , Faure Christelle , Ray-Coquard Isabelle , Puisieux Alain , Caux Christophe , Blay Jean-Yves , Ménétrier-Caux Christine
Published: February 2009

Immunohistochemical analysis of FOXP3 in primary breast tumors showed that a high number of tumor-infiltrating regulatory T cells (Ti-Treg) within lymphoid infiltrates surrounding the tumor was predictive of relapse and death, in contrast to those present within the tumor bed. Ex vivo analysis showed that these tumor-infiltrating FOXP3+ T cells are typical Treg based on their CD4+CD25highCD127lowFOXP3+ phenotype, their anergic state on in vitro stimulation, and their suppressive functions. These Ti-Treg could be selectively recruited through CCR4 as illustrated by (a) selective blood Treg CCR4 expression and migration to CCR4 ligands, (b) CCR4 down-regulation on Ti-Treg, and (c) correlation between Ti-Treg in lymphoid infiltrates and intratumoral CCL22 expression. Importantly, in contrast to other T cells, Ti-Treg are selectively activated locally and proliferate in situ, showing T-cell receptor engagement and suggesting specific recognition of tumor-associated antigens (TAA). Immunohistochemical stainings for ICOS, Ki67, and DC-LAMP show that Ti-Treg were close to mature DC-LAMP+ dendritic cells (DC) in lymphoid infiltrates but not in tumor bed and were activated and proliferating. Furthermore, proximity between Ti-Treg, CD3+, and CD8+ T cells was documented within lymphoid infiltrates. Altogether, these results show that Treg are selectively recruited within lymphoid infiltrates and activated by mature DC likely through TAA presentation, resulting in the prevention of effector T-cell activation, immune escape, and ultimately tumor progression. This study sheds new light on Treg physiology and validates CCR4/CCL22 and ICOS as therapeutic targets in breast tumors, which represent a major health problem. [Cancer Res 2009;69(5):2000–9]
Telomere Dysfunction and DNA-PKcs Deficiency: Characterization and Consequence
Authors: Williams Eli S. , Klingler Rebekah , Ponnaiya Brian , Hardt Tanja , Schrock Evelin , Lees-Miller Susan P. , Meek Katheryn , Ullrich Robert L. , Bailey Susan M.
Published: February 2009

The mechanisms by which cells accurately distinguish between DNA double-strand break (DSB) ends and telomeric DNA ends remain poorly defined. Recent investigations have revealed intriguing interactions between DNA repair and telomeres. We were the first to report a requirement for the nonhomologous end-joining (NHEJ) protein DNA-dependent protein kinase (DNA-PK) in the effective end-capping of mammalian telomeres. Here, we report our continued characterization of uncapped (as opposed to shortened) dysfunctional telomeres in cells deficient for the catalytic subunit of DNA-PK (DNA-PKcs) and shed light on their consequence. We present evidence in support of our model that uncapped telomeres in this repair-deficient background are inappropriately detected and processed as DSBs and thus participate not only in spontaneous telomere-telomere fusion but, importantly, also in ionizing radiation–induced telomere-DSB fusion events. We show that phosphorylation of DNA-PKcs itself (Thr-2609 cluster) is a critical event for proper telomere end-processing and that ligase IV (NHEJ) is required for uncapped telomere fusion. We also find uncapped telomeres in cells from the BALB/c mouse, which harbors two single-nucleotide polymorphisms that result in reduced DNA-PKcs abundance and activity, most markedly in mammary tissue, and are both radiosensitive and susceptible to radiogenic mammary cancer. Our results suggest mechanistic links between uncapped/dysfunctional telomeres in DNA-PKcs–deficient backgrounds, radiation-induced instability, and breast cancer. These studies provide the first direct evidence of genetic susceptibility and environmental insult interactions leading to a unique and ongoing form of genomic instability capable of driving carcinogenesis. [Cancer Res 2009;69(5):2100–7]
Silencing of Elongation Factor-2 Kinase Potentiates the Effect of 2-Deoxy-d-Glucose against Human Glioma Cells through Blunting of Autophagy
Authors: Wu Hao , Zhu Hua , Liu David X. , Niu Ting-Kuang , Ren Xingcong , Patel Rajesh , Hait William N. , Yang Jin-Ming
Published: February 2009

2-Deoxy-d-glucose (2-DG), a synthetic glucose analogue that acts as a glycolytic inhibitor, is currently being evaluated in the clinic as an anticancer agent. In this study, we observed that treatment of human glioma cells with 2-DG activated autophagy, a highly conserved cellular response to metabolic stress and a catabolic process of self-digestion of intracellular organelles for energy use and survival in stressed cells. The induction of autophagy by 2-DG was associated with activation of elongation factor-2 kinase (eEF-2 kinase), a structurally and functionally unique enzyme that phosphorylates eEF-2, leading to loss of affinity of this elongation factor for the ribosome and to termination of protein elongation. We also showed that inhibition of eEF-2 kinase by RNA interference blunted the 2-DG–induced autophagic response, resulted in a greater reduction of cellular ATP contents, and increased the sensitivity of tumor cells to the cytotoxic effect of 2-DG. Furthermore, the blunted autophagy and enhanced 2-DG cytotoxicity were accompanied by augmentation of apoptosis in cells in which eEF-2 kinase expression was knocked down. The results of this study indicate that the energy stress and cytotoxicity caused by 2-DG can be accelerated by inhibition of eEF-2 kinase, and suggest that targeting eEF-2 kinase–regulated autophagic survival pathway may represent a novel approach to sensitizing cancer cells to glycolytic inhibitors. [Cancer Res 2009;69(6):2453–60]
TORC-Specific Phosphorylation of Mammalian Target of Rapamycin (mTOR): Phospho-Ser2481 Is a Marker for Intact mTOR Signaling Complex 2
Authors: Copp Jeremy , Manning Gerard , Hunter Tony
Published: February 2009

The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling. S6 kinase is the best-characterized downstream effector of mTORC1. mTOR signaling complex 2 (mTORC2) has a role in regulating the actin cytoskeleton and activating Akt through S473 phosphorylation. Herein, we show that mTOR is phosphorylated differentially when associated with mTORC1 and mTORC2 and that intact complexes are required for these mTORC-specific mTOR phosphorylations. Specifically, we find that mTORC1 contains mTOR phosphorylated predominantly on S2448, whereas mTORC2 contains mTOR phosphorylated predominantly on S2481. Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Thus, phospho-S2481 on mTOR serves as a biomarker for intact mTORC2 and its sensitivity to rapamycin. [Cancer Res 2009;69(5):1821–7]
The Critical Role of the Class III Histone Deacetylase SIRT1 in Cancer
Authors: Liu Tao , Liu Pei Y. , Marshall Glenn M.
Published: February 2009

Gene expression and deacetylase activity of the class III histone deacetylase SIRT1 are up-regulated in cancer cells due to oncogene overexpression or loss of function of tumor suppressor genes. SIRT1 induces histone deacetylation and methylation, promoter CpG island methylation, transcriptional repression, and deacetylation of tumor suppressor proteins. SIRT1 may play a critical role in tumor initiation, progression, and drug resistance by blocking senescence and apoptosis, and promoting cell growth and angiogenesis. SIRT1 inhibitors have shown promising anticancer effects in animal models of cancer. Further screening for more potent SIRT1 inhibitors may lead to compounds suitable for clinical trials in patients. [Cancer Res 2009;69(5):1702–5]
RGS17, an Overexpressed Gene in Human Lung and Prostate Cancer, Induces Tumor Cell Proliferation Through the Cyclic AMP-PKA-CREB Pathway
Authors: James Michael A. , Lu Yan , Liu Yan , Vikis Haris G. , You Ming
Published: February 2009

We have identified RGS17 as a commonly induced gene in lung and prostate tumors. Through microarray and gene expression analysis, we show that expression of RGS17 is up-regulated in 80% of lung tumors, and also up-regulated in prostate tumors. Through knockdown and overexpression of RGS17 in tumor cells, we show that RGS17 confers a proliferative phenotype and is required for the maintenance of the proliferative potential of tumor cells. We show through exon microarray, transcript analysis, and functional assays that RGS17 promotes cyclic AMP (cAMP)-responsive element binding protein (CREB)-responsive gene expression, increases cAMP levels, and enhances forskolin-mediated cAMP production. Furthermore, inhibition of cAMP-dependent kinase prevents tumor cell proliferation, and proliferation is partially rescued by RGS17 overexpression. In the present study, we show a role for RGS17 in the maintenance of tumor cell proliferation through induction of cAMP signaling and CREB phosphorylation. The prevalence of the induction of RGS17 in tumor tissues of various types further implicates its importance in the maintenance of tumor growth. [Cancer Res 2009;69(5):2108–16]
The Tamoxifen Metabolite, Endoxifen, Is a Potent Antiestrogen that Targets Estrogen Receptor α for Degradation in Breast Cancer Cells
Authors: Wu Xianglin , Hawse John R. , Subramaniam Malayannan , Goetz Matthew P. , Ingle James N. , Spelsberg Thomas C.
Published: February 2009

Tamoxifen has been the most important therapeutic agent for the treatment of estrogen receptor (ER)-positive breast cancer for the past three decades. Tamoxifen is extensively metabolized by cytochrome P450 enzymes, and recent in vivo studies have shown that women with genetically impaired cytochrome P450 2D6 have reduced production of endoxifen and a higher risk of breast cancer recurrence. Despite these observations, the contribution of endoxifen to the overall drug effectiveness of tamoxifen remains uncertain. Here, we provide novel evidence that endoxifen is a potent antiestrogen that functions in part by targeting ERα for degradation by the proteasome in breast cancer cells. Additionally, we show that endoxifen blocks ERα transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation even in the presence of tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxytamoxifen. All of the effects of endoxifen are concentration dependent and do not occur at concentrations observed in human CYP2D6 poor metabolizers. These results support the theory that endoxifen is the primary metabolite responsible for the overall effectiveness of tamoxifen in the treatment of ER-positive breast cancer. [Cancer Res 2009;69(5):1722–7]
The Interleukin-11 Receptor α as a Candidate Ligand-Directed Target in Osteosarcoma: Consistent Data from Cell Lines, Orthotopic Models, and Human Tumor Samples
Authors: Lewis Valerae O. , Ozawa Michael G. , Deavers Michael T. , Wang Guiying , Shintani Tomo , Arap Wadih , Pasqualini Renata
Published: February 2009

The interleukin-11 receptor α (IL-11Rα) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11Rα as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that IL-11Rα protein is markedly expressed in primary osseus and pulmonary metastatic osteosarcoma but absent from control normal tibia and lung. Moreover, systemic administration of an IL-11Rα–targeting phage displaying the cyclic nonapeptide CGRRAGGSC resulted in strong and selective accumulation of IL-11Rα–homing phage particles in the osteosarcoma but not in several control organs. Finally, IL-11Rα expression in a large panel of human primary and metastatic osteosarcoma samples was remarkably consistent with the observations in the orthotopic mouse model. These data establish IL-11Rα as a candidate target in human osteosarcoma and provide leads for the development of novel imaging and therapeutic agents for the management of this malignant tumor. [Cancer Res 2009;69(5):1995–9]
Expression of ABCC-Type Nucleotide Exporters in Blasts of Adult Acute Myeloid Leukemia: Relation to Long-term Survival
Authors: Guo Yanping , Köck Kathleen , Ritter Christoph A. , Chen Zhe-Sheng , Grube Markus , Jedlitschky Gabriele , Illmer Thomas , Ayres Mary , Beck James F. , Siegmund Werner , Ehninger Gerhard , Gandhi Varsha , Kroemer Heyo K. , Kruh Gary D. , Schaich Markus
Published: February 2009

Purpose: Successful treatment of acute myeloid leukemia (AML) remains a therapeutic challenge, with a high percentage of patients suffering from persistent or relapsed disease. Resistance to drug therapy can develop from increased drug export and/or altered intracellular signaling. Both mechanisms are mediated by the efflux transporters ABCC4 (MRP4), ABCC5 (MRP5), and ABCC11 (MRP8), which are involved in cellular efflux of endogenous signaling molecules (e.g., cyclic adenosine 3′, 5′-monophosphate and cyclic guanosine 3′,5′-monophosphate) and nucleoside analogues. The nucleoside analogue cytosine arabinoside (AraC) is administered to all patients with AML.

Experimental Design: Expression of ABCC transporters MRP4, MRP5, and MRP8 in blast samples from 50 AML patients was investigated by real-time reverse transcription-PCR analysis and correlated with clinical outcome measures. Accumulation of radiolabeled AraC, transport of AraC metabolites, and AraC cytotoxicity were analyzed in MRP8-transfected LLC-PK1 cells.

Results: Regression analysis revealed that high expression of MRP8 is associated with a low probability of overall survival assessed over 4 years (P < 0.03). MRP8-transfected LLC-PK1 cells accumulated reduced intracellular levels of AraC (63% of the parental vector-transfected LLC-PK1 control cells) as well as AraC metabolites. Furthermore, AraC monophosphate was transported by MRP8-enriched membrane vesicles (116 ± 6 versus 65 ± 13 pmol/mg/10 minutes by control vesicles), and MRP8-transfected cells were resistant to AraC.

Conclusion: These data suggest that MRP8 is differentially expressed in AML blasts, that expression of MRP8 serves as a predictive marker for treatment outcome in AML, and that efflux of AraC metabolites by MRP8 is a mechanism that contributes to resistance of AML blasts.