bluuebunny/crossref_metadata_2025 huggingface dataset:
OPTIMIZED QUBIT PHASE ESTIMATION IN NOISY QUANTUM CHANNELS
Authors: TESIO ENRICO , OLIVARES STEFANO , PARIS MATTEO G. A.
Published: March 2011

We address the estimation of phase-shifts for qubit systems in the presence of noise. Different sources of noise are considered including bit flip, bit-phase flip and phase flip. We derive the ultimate quantum limits to precision of estimation by evaluating the analytical expressions of the quantum Fisher information and assess performances of feasible measurements by evaluating the Fisher information for realistic spin-like measurements. We also propose an experimental scheme to test our results.
A structural, geomorphological and InSAR study of an active rock slope failure development
Authors: Henderson I. H. C. , Lauknes T. R. , Osmundsen P. T. , Dehls J. , Larsen Y. , Redfield T. F.
Published: March 2011

Few studies of rockslides have addressed the relationships between structures, geomorphological expression and direct evidence for movement. We employ structural geology, geomorphology and interferometric synthetic aperture radar (InSAR) to investigate the evolution of the surface features developed in response to movement of the Gamanjunni rockslide site in Troms County in northern Norway. The slide is located on a west-facing mountainside, and is bounded by two angled back scarps and a 20°–30° basal sliding plane. The volume is estimated at 24 Mm
3
and is therefore among the largest potential rockslides in Norway. InSAR provides a new method to measure the movement of potential rockslides, and thus provides a direct link between qualitative movement data and field observations. We document the relationship between variations in ground movement rates and changing back-scarp geomorphology at the Gamanjunni site as well as movement patterns within the incipient rockslide. We demonstrate that variations in InSAR documents millimetre variations in scarp displacement and that this is reflected in the evolving back-scarp geometry. We conclude that InSAR can provide important information to complement field observations. The ability of InSAR to document landslide movement patterns greatly extends our knowledge of back-scarp evolution and active landslide processes.
Valley shape influence on deformation mechanisms of rock slopes
Authors: Ambrosi Christian , Crosta Giovanni B.
Published: March 2011

Stress distribution in mountainous areas is influenced by local morphology. Valley morphology and the relationship between main and tributary valleys strongly depend on geological characteristics and evolution. They may control the evolution of slope instabilities, especially when interacting with pervasive structural features.

We performed parametric three-dimensional (3D) numerical modelling of simplified slope geometries with variable slope angle (from 21° to 35°), length, combining different orientations for different slope sectors and changing attitude of pervasive planes of anisotropy (foliation, schistosity, bedding). Data used in the 3D models are the initial slope geometry, rock mass properties and internal anisotropy. We assumed Mohr–Coulomb behaviour, with the presence of ubiquitous joints and different piezometric levels.

The model results show that plastic deformation initiates near the highest ridge just after deglaciation commences. A shear zone develops and propagates toward the toe of the slope, and its shape is strongly controlled by slope geometry, anisotropy and
in situ
stresses. The thickness of the failing mass, for model slope reliefs up to 3200 m, increases from 50 m to some hundreds of metres during glacier retreat, and it depends on geometry of slopes, anisotropy and
in situ
stresses. Results are compared to examples of deep-seated slope deformations from the Alps, which helps in the interpretation of such phenomena and in the understanding of their influence on valley evolution.
The Celentino deep-seated gravitational slope deformation (DSGSD): structural and geomechanical analyses (Peio Valley, NE Italy)
Authors: Ghirotti M. , Martin S. , Genevois R.
Published: March 2011

Deep-seated gravitational slope deformations (DSGSDs) are fairly common phenomena in the Eastern Italian Alps. The Celentino DSGSDs (Trentino–Alto Adige Region, Peio Valley) extends over an area of approximately 5 km
2
between 2400 and 1050 m a.s.l. (metres above sea level), involving metamorphic rocks. A set of parallel ridge-top trenches and antislope scarps are present in the upper part of the slope over a length of 2 km. The shear surface is inferred at 80–100 m in depth, and the involved volume is estimated to be 3.5×10
8
–4.0×10
8
m
3
. The displacement of the rock mass has diverted the Noce River for 200–250 m. Structural, geomorphological and engineering geology surveys were conducted both within and outside the DSGSDs. The evolution of the whole ridge has been modelled using the two-dimensional (2D) finite element code Phase
2
, simulating the unloading of the glacier cover and assuming a progressive damage of the rock mass. The numerical analyses demonstrate that continuum modelling can be used to examine the evolution of stresses, strains and plastic yielding, providing results consistent with field observations. Structural control due to brittle geological structures seems to be extremely important in the location, shape and extent of the DSGSDs, and post-glacial debuttressing an important predisposing factor in its development and triggering.

The DSGSDs are common phenomena in areas of high relief energy, associated with orogenic history and mountain unroofing where tectonics is still active.
Controlling factors for deep-seated gravitational slope deformation (DSGSD) in the Aosta Valley (NW Alps, Italy)
Authors: Martinotti G. , Giordan D. , Giardino M. , Ratto S.
Published: March 2011

Deep-seated gravitational slope deformation (DSGSD) is a common and widespread type of large slope instability in the Alps. In the Aosta Valley region in NW Italy, DSGSDs occupy at least 13.5% of the regional territory. In this study, regional distribution analyses have been coupled with local detailed geological and geomorphological surveys of individual phenomena to detect the controlling factors, deformation processes and evolution stages of DSGSD. Data and maps from field and remote-sensing investigations have been supported by drill data and geomechanical and hydrogeochemical analyses from project studies for hydroelectric plants and tunnels. Several phenomena related to DSGSD have been studied thoroughly: gravity-induced stresses, tectonic–metamorphic setting, morphostructural relations, glacial and periglacial morphodynamics, recent tectonic evolution, hydrogeological conditions and karst phenomena have been generically indicated as controlling factors. In the studied area three of the controlling factors were crucial in differentiating the form and evolution of DSGSDs: deep dissolution, surface tectonics, and tectonostructural setting. They are presented as possible end members of a classification scheme for DSGSDs.
Palaeostress analysis of a giant Holocene rockslide near Boaco and Santa Lucia (Nicaragua, Central America)
Authors: Baron̆ Ivo , Kernstocková Markéta , Novotný Roman , Buriánek David , Hradecký Petr , Havlic̆ek Pavel , Melichar Rostislav
Published: March 2011

A giant rockslide occurred on the southern side of an Upper Tertiary shield volcano in central Nicaragua in the Holocene. The failure caused tectonic-like deformation of rock masses and changed the local stress regime. The lower, compressional part of the rockslide produced a stress field with the axis of maximum stress (σ
1
) parallel to the displacement vector of the main body. The upper part of the rockslide was gravity-driven with σ
1
vertical and σ
3
horizontal, and oriented SE–NW. The mass tended to move SE. In the crown, the stress field had a subvertical σ
1
steeply dipping towards the west. Data at the base of the Santa Lucia Depression, where east- and west-dipping reverse and thrust faults developed, showed that the compressional stress, σ
1
, was nearly horizontal and east–west oriented, the horizontal σ
2
was north–south oriented, and the σ
3
was subvertical. These compressional conditions resulted from the collapse of the crown after the main slope failure phase. Simultaneously, along with the gravity relaxation of the main displaced mass, the slopes and mountain slopes along the main scarp depression underwent deep-seated sliding, sagging and flowing.
The relationship between pulsatile GnRH secretion and cAMP production in immortalized GnRH neurons
Authors: Frattarelli John L. , Krsmanovic Lazar Z. , Catt Kevin J.
Published: March 2011

In perifused immortalized GnRH neurons (GT1–7), simultaneous measurements of GnRH and cAMP revealed that the secretory profiles for both GnRH and cAMP are pulsatile. An analysis of GnRH and cAMP pulses in 16 independent experiments revealed that 25% of pulses coincide. Inversion of the peak and nadir levels was found in 33% and random relationship between GnRH and cAMP found in 42% of analyzed pulses. The random relation between GnRH and cAMP pulse resets to synchronous after an inverse relation between pulses occurred during the major GnRH release, indicating that GnRH acts as a switching mechanism to synchronize cAMP and GnRH release in perifused GT1–7 neurons. Activation of GnRH receptors with increasing agonist concentrations caused a biphasic change in cAMP levels. Low nanomolar concentrations increased cAMP production, but at high concentrations the initial increase was followed by a rapid decline to below the basal level. Blockade of the GnRH receptors by peptide and nonpeptide antagonists generated monotonic nonpulsatile increases in both GnRH and cAMP production. These findings indicate that cAMP positively regulates GnRH secretion but does not participate in the mechanism of pulsatile GnRH release.
Effect of sodium oxybate on growth hormone secretion in narcolepsy patients and healthy controls
Authors: Donjacour Claire E. H. M. , Aziz N. Ahmad , Roelfsema Ferdinand , Frölich Marijke , Overeem Sebastiaan , Lammers Gert Jan , Pijl Hanno
Published: March 2011

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.
Percutaneous Transfistulous Interventions for Intractable Pancreatic Fistula
Authors: Hirota Masahiko
Published: March 2011

Three techniques for the treatment of intractable pancreatic fistula: percutaneous transfistulous pancreatic duct drainage (PTPD), percutaneous transfistulous pancreatojejunostomy (PTPJ), and percutaneous transfistulous pancreatic duct embolization (PTPE) are presented as treatment options for intractable pancreatic fistula. PTPD is effective for most cases of intractable fistula that communicate with the main pancreatic duct. However, PTPD itself is not enough in some specific cases. PTPJ and PTPE are applicable in such cases.
Comment on "A Strong Convergence of a Generalized Iterative Method for Semigroups of Nonexpansive Mappings in Hilbert Spaces"
Authors: Golkarmanesh Farman , Naseri Saber
Published: March 2011

Piri and Vaezi (2010) introduced an iterative scheme for finding a common fixed point of a semigroup of nonexpansive mappings in a Hilbert space. Here, we present that their conclusions are not original and most parts of their paper are picked up from Saeidi and Naseri (2010), though it has not been cited.
Proteomic Analysis of Soybean Roots under Aluminum Stress
Authors: Duressa Dechassa , Soliman Khairy , Taylor Robert , Senwo Zachary
Published: March 2011

Toxic levels of aluminum (Al) in acid soils inhibit root growth and cause substantial reduction in yields of Al-sensitive crops. Aluminum-tolerant cultivars detoxify Al through multiple mechanisms that are currently not well understood at genetic and molecular levels. To enhance our understanding of the molecular mechanisms involved in soybean Al tolerance and toxicity, we conducted proteomic analysis of soybean roots under Al stress using a tandem combination of 2-D-DIGE, mass spectrometry, and bioinformatics tools and Al-tolerant (PI 416937) and Al-sensitive (Young) soybean genotypes at 6, 51 or 72 h of Al treatment. Comparison of the protein profile changes revealed that aluminum induced Al tolerance related proteins and enzymes in Al-tolerant PI 416937 but evoked proteins related to general stress response in Al-sensitive Young. Specifically, Al upregulated: malate dehydrogenase, enolase, malate oxidoreductase, and pyruvate dehydrogenase, in PI 416937 but not in Young. These enzymes contribute to increased synthesis of citrate, a key organic acid involved in Al detoxification. We postulate that simultaneous transgenic overexpression of several of these enzymes would be a robust genetic engineering strategy for developing Al-tolerant crops.
Unsteady Magnetohydrodynamic Heat Transfer in a Semi-Infinite Porous Medium with Thermal Radiation Flux: Analytical and Numerical Study
Authors: Bég O. Anwar , Zueco J. , Ghosh S. K. , Heidari Alireza
Published: March 2011

The unsteady, buoyancy-induced, hydromagnetic, thermal convection flow in a semi-infinite porous regime adjacent to an infinite hot vertical plate moving with constant velocity, is studied in the presence of significant thermal radiation. The momentum and energy conservation equations are normalized and then solved using both the Laplace transform technique and Network Numerical Simulation. Excellent agreement is obtained between both analytical and numerical methods. An increase in Hartmann number (M2) strongly decelerates the flow and for very high strength magnetic fields (M2=20), the flow is reversed after a short time interval. The classical velocity overshoot is also detected close to the plate surface for low to intermediate values of M2 at both small and large times; however this overshoot vanishes for larger strengths of the transverse magnetic field (M2=10). An increase in radiation-conduction parameter (Kr) significantly increases temperature throughout the porous regime at both small and larger times, adjacent to the plate, but decreases the shear stress magnitudes at the plate. Temperature gradient is reduced at the plate surface for all times, with a rise in radiation-conduction parameter (Kr). Shear stress is reduced considerably with an increase in Darcian drag parameter (Kp).
The Curious Question of Exercise-Induced Pulmonary Edema
Authors: Bates Melissa L. , Farrell Emily T. , Eldridge Marlowe W.
Published: March 2011

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking.
Randomized Controlled Trial of Clozapine and CBT for First-Episode Psychosis with Enduring Positive Symptoms: A Pilot Study
Authors: Edwards J. , Cocks J. , Burnett P. , Maud D. , Wong L. , Yuen H. P. , Harrigan S. M. , Herrman-Doig T. , Murphy B. , Wade D. , McGorry P. D.
Published: March 2011

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria () were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.
Nicotinic Acetylcholine Receptor Signaling in Tumor Growth and Metastasis
Authors: Singh Sandeep , Pillai Smitha , Chellappan Srikumar
Published: March 2011

Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer.
Anesthesic Management for Escobar Syndrome: Case Report
Authors: Arpaci Ayse Hande , Bozkirli Fusun , Konuk Onur
Published: March 2011

Escobar syndrome is a rare autosomal recessive disorder which is characterized by growth retardation, axillary, antecubital, popliteal digital, and intercrural joint flexion contracture, pterygium in the eyes, cleft palate, decreased lung capacity, genital abnormalities, and spinal deformity. In this case, we presented the anesthesic management of a 2-year-old child undergoing frontal sling operation for ptosis and amblyopia etiology exploration.
A Parallel Stochastic Framework for Reservoir Characterization and History Matching
Authors: Thomas Sunil G. , Klie Hector M. , Rodriguez Adolfo A. , Wheeler Mary F.
Published: March 2011

The spatial distribution of parameters that characterize the subsurface is never
known to any reasonable level of accuracy required to solve the governing PDEs of multiphase flow
or species transport through porous media. This paper presents a numerically cheap, yet efficient,
accurate and parallel framework to estimate reservoir parameters, for example, medium permeability, using
sensor information from measurements of the solution variables such as phase pressures, phase concentrations, fluxes, and seismic and well log data. Numerical results are presented to demonstrate the
method.
A Model to Evaluate the Thermal Conductivity of the Coral Reef in Tahiti
Authors: Guarino Alessio
Published: March 2011

Ohm's law models have been used in several works in geophysical prospecting but have never been used for coral reef. We adapted such a model to the barrier reef of Papeete (Tahiti island) in order to estimate of its thermal conductivity. We found the thermal conductivity of the barrier reef is about four times greater than that of the water. The results are then validated by the mean of experimental measurements.
Solvability and Algorithms for Functional Equations Originating from Dynamic Programming
Authors: Jiang Guojing , Kang ShinMin , Kwun YoungChel
Published: March 2011

The main purpose of this paper is to study the functional equation arising in dynamic programming of multistage decision processes "Equation missing","Equation missing""Equation missing". A few iterative algorithms for solving the functional equation are suggested. The existence, uniqueness and iterative approximations of solutions for the functional equation are discussed in the Banach spaces "Equation missing" and "Equation missing" and the complete metric space "Equation missing", respectively. The properties of solutions, nonnegative solutions, and nonpositive solutions and the convergence of iterative algorithms for the functional equation and other functional equations, which are special cases of the above functional equation, are investigated in the complete metric space "Equation missing", respectively. Eight nontrivial examples which dwell upon the importance of the results in this paper are also given.
Transplantation of Porcine Hepatocytes Cultured with Polylactic Acid-O-Carboxymethylated Chitosan Nanoparticles Promotes Liver Regeneration in Acute Liver Failure Rats
Authors: Chen Zhong , Chang Renan , Guan Weijun , Cai Hongyu , Tang Fei , Zhu Wencai , Chen Jiahui
Published: March 2011

In this study, free porcine hepatocytes suspension (Group A), porcine hepatocytes embedded in collagen gel (Group B), porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C), and PLA-O-CMC nanoparticles alone (Group D) were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI) at day 1 post-HTx (P<.05). Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats.
On the Difference Equation xn+1 = xnxn−2 − 1
Authors: Kent Candace M. , Kosmala Witold , Stević Stevo
Published: March 2011

The long‐term behavior of solutions of the following difference
equation: xn+1 = xnxn−2 − 1, n ∈ ℕ0, where the initial values x−2, x−1, x0 are real numbers, is investigated in the paper.
New Algorithm for the Numerical Solutions of Nonlinear Third‐Order Differential Equations Using Jacobi‐Gauss Collocation Method
Authors: Bhrawy A. H. , Abd-Elhameed W. M.
Published: March 2011

A new algorithm for solving the general nonlinear third‐order differential
equation is developed by means of a shifted Jacobi‐Gauss collocation spectral method. The shifted
Jacobi‐Gauss points are used as collocation nodes. Numerical examples are included to demonstrate
the validity and applicability of the proposed algorithm, and some comparisons are made with the
existing results. The method is easy to implement and yields very accurate results.
Advances in Molecular Characterization and Targeted Therapy in Dermatofibrosarcoma Protuberans
Authors: Rutkowski Piotr , Wozniak Agnieszka , Switaj Tomasz
Published: March 2011

The molecular pathogenesis of dermatofibrosarcoma protuberans (DFSP) involves distinctive rearrangement of chromosomes 17 and 22 leading to formation of theCOL1A1-PDGFBfusion gene. The knowledge of molecular events underlying development of DFSP resulted in the implementation of targeted therapy with imatinib—a tyrosine kinase inhibitor (TKI), to the clinical practice. The striking efficacy of imatinib in advanced cases of DFSP has been demonstrated in a few clinical trials. Thus, imatinib is currently considered the gold standard in the treatment of inoperable and/or metastatic and/or recurrent cases of DFSP. Therapy with imatinib may potentially facilitate resection or decrease possible disfigurement related to radical surgical procedure. Following partial response on imatinib significant percentage of patients may be rendered free of the disease by surgery of the residual tumor.
Role of Heparanase in Radiation-Enhanced Invasiveness of Pancreatic Carcinoma
Authors: Meirovitz Amichay , Hermano Esther , Lerner Immanuel , Zcharia Eyal , Pisano Claudio , Peretz Tamar , Elkin Michael
Published: March 2011

Pancreatic cancer is characterized by very low survival rates because of high intrinsic resistance to conventional therapies. Ionizing radiation (IR)–enhanced tumor invasiveness is emerging as one mechanism responsible for the limited benefit of radiotherapy in pancreatic cancer. In this study, we establish the role of heparanase—the only known mammalian endoglycosidase that cleaves heparan sulfate—in modulating the response of pancreatic cancer to radiotherapy. We found that clinically relevant doses of IR augment the invasive capability of pancreatic carcinoma cells in vitro and in vivo by upregulating heparanase. Changes in the levels of the transcription factor Egr-1 occurred in pancreatic cancer cells following radiation, underlying the stimulatory effect of IR on heparanase expression. Importantly, the specific heparanase inhibitor SST0001 abolished IR-enhanced invasiveness of pancreatic carcinoma cells in vitro, whereas combined treatment with SST0001 and IR, but not IR alone, attenuated the spread of orthotopic pancreatic tumors in vivo. Taken together, our results suggest that combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination, observed in many IR-treated pancreatic cancer patients. Further, the molecular mechanism underlying heparanase upregulation in pancreatic cancer that we identified in response to IR may help identify patients in which radiotherapeutic intervention may confer increased risk of metastatic spread, where antiheparanase therapy may be particularly beneficial. Cancer Res; 71(7); 2772–80. ©2011 AACR.
p53 Binds to and Is Required for the Repression of Arf Tumor Suppressor by HDAC and Polycomb
Authors: Zeng Yaxue , Kotake Yojiro , Pei Xin-Hai , Smith Matthew D. , Xiong Yue
Published: March 2011

The expression of tumor suppressor Arf is tightly repressed during normal cell growth at a young age and is activated by oncogenic insults, and during aging, results in p53 activation and cell-cycle arrest to prevent hyperproliferation. The mechanisms of both transcriptional repression and activation of Arf are not understood. We show that p53 binds to and represses Arf expression and that this repression requires the function of both histone deacetylases (HDAC) and polycomb group (PcG) proteins. Inactivation of p53 leads to increased Arf transcription in both mouse embryonic fibroblasts (MEF) cultured in vitro and in tissues and organs of p53 null mice. Activation of endogenous p53 enhances Arf repression, and reintroduction of p53 back into p53 null MEFs restores Arf repression. Both DNA binding and transactivation activities of p53 are required for Arf repression. We show that p53 is required for both HDAC and PcG to repress Arf expression. Bindings of both HDAC and PcG to Arf are disrupted by inactivation of p53 and can be restored in p53 null MEFs by the reintroduction of wild-type, but not mutant, p53. These results indicate that p53 recruits both HDAC and PcG to Arf locus to repress its expression, and this repression constitutes a second feedback loop in p53 regulation. Cancer Res; 71(7); 2781–92. ©2011 AACR.
BRAFV600E and Microenvironment in Thyroid Cancer: A Functional Link to Drive Cancer Progression
Authors: Nucera Carmelo , Lawler Jack , Parangi Sareh
Published: March 2011

Papillary thyroid cancer (PTC) rates continue to increase in the United States and Europe, and, although most patients do well, some recur and die of their disease. Patients with PTC harboring the BRAFV600E mutation seem to display a more aggressive clinical behavior, but little is known about the role of this mutation in crucial processes in the tumor microenvironment, such as tumor adhesion, migration, invasion, and metastasis. The extracellular matrix (ECM) microenvironment is not merely a structural scaffold for the cellular elements of the epithelial and stromal microenvironment, but it also elicits a profound influence on cell behavior affecting viability, proliferation, adhesion, and motility. The effects of BRAFV600E on cell surface receptors (i.e., integrins) and ECM noncellular components [i.e., thrombospondin-1 (TSP-1) and fibronectin (FN)] seem to trigger different pathologic biological processes in a cell context–dependent manner. This review focuses on the recent progress in understanding the role of BRAFV600E in the regulation of some ECM noncellular components and trans-membrane receptors of the microenvironment in PTC in order to design novel targeted therapies directed at the BRAFV600E multifaceted signaling cascades. Some of these targeted therapeutics, such as ATP-competitive BRAFV600E inhibitors (i.e., orally bioavailable PLX4720 and PLX4032 compounds), are already under investigation. Cancer Res; 71(7); 2417–22. ©2011 AACR.
Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms
Authors: Holkova Beata , Perkins E. Brent , Ramakrishnan Viswanathan , Tombes Mary Beth , Shrader Ellen , Talreja Neha , Wellons Martha D. , Hogan Kevin T. , Roodman G. David , Coppola Domenico , Kang Loveleen , Dawson Jana , Stuart Robert K. , Peer Cody , Figg William D. , Kolla Sarah , Doyle Austin , Wright John , Sullivan Daniel M. , Roberts John D. , Grant Steven
Published: March 2011

Purpose: A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, and mantle cell lymphoma).

Experimental Design: Patients received bortezomib by intravenous push on days 1, 4, 8, and 11. Patients also received alvocidib on days 1 and 8 by 30-minute bolus infusion followed by a 4-hour continuous infusion. Treatment was on a 21-day cycle, with indefinite continuation for patients experiencing responses or stable disease. Dose escalation employed a standard 3 + 3 design until the MTD was identified on the basis of DLTs. Pharmacokinetic studies and pharmacodynamic studies were conducted.

Results: Sixteen patients were treated. The MTD was established as 1.3 mg/m2 for bortezomib and 30 mg/m2 for alvocidib (both the 30-minute bolus and 4-hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common nonhematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate = 44%). Pharmacokinetic results were typical for alvocidib and pharmacodynamic studies yielded variable results.

Conclusions: The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non–Hodgkin's lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. Clin Cancer Res; 17(10); 3388–97. ©2011 AACR.
Evasion Mechanisms to Igf1r Inhibition in Rhabdomyosarcoma
Authors: Abraham Jinu , Prajapati Suresh I. , Nishijo Koichi , Schaffer Beverly S. , Taniguchi Eri , Kilcoyne Aoife , McCleish Amanda T. , Nelon Laura D. , Giles Francis G. , Efstratiadis Argiris , LeGallo Robin D. , Nowak Brent M. , Rubin Brian P. , Malempati Suman , Keller Charles
Published: March 2011

Inhibition of the insulin-like growth factor 1 receptor (Igf1r) is an approach being taken in clinical trials to overcome the dismal outcome for metastatic alveolar rhabdomyosarcoma (ARMS), an aggressive muscle cancer of children and young adults. In our study, we address the potential mechanism(s) of Igf1r inhibitor resistance that might be anticipated for patients. Using a genetically engineered mouse model of ARMS, validated for active Igf1r signaling, we show that the prototypic Igf1r inhibitor NVP-AEW541 can inhibit cell growth and induce apoptosis in vitro in association with decreased Akt and Mapk phosphorylation. However, drug resistance in vivo is more common and is accompanied by Igf1r overexpression, Mapk reactivation, and Her2 overexpression. Her2 is found to form heterodimers with Igf1r in resistant primary tumor cell cultures, and stimulation with Igf2 leads to Her2 phosphorylation. The Her2 inhibitor lapatinib cooperates with NVP-AEW541 to reduce Igf1r phosphorylation and to inhibit cell growth even though lapatinib alone has little effect on growth. These results point to the potential therapeutic importance of simultaneous targeting of Igf1r and Her2 to abrogate resistance. Mol Cancer Ther; 10(4); 697–707. ©2011 AACR.
Preparedness for the Smoking Cessation Role among Health Sciences Students in Kuwait
Authors: Waheedi Mohammad , Al-Tmimy Aisha M. , Enlund Hannes
Published: March 2011

Objective: Our aim was to assess students’ preparedness for the smoking cessation role after a teaching module on tobacco cessation and to assess the relationship between smoking status and preparedness. Methods: Pharmacy students attended a 4-hour module on the role of health professionals in smoking cessation based on the Rx for Change training program. Two years after the first introduction of the module, a questionnaire on preparedness and smoking status was filled in by 64 pharmacy students who had attended the module and 243 students from other health sciences that had not been exposed to the module. Results: Preparedness scores for the smoking cessation role for pharmacy students were significantly higher (mean = 19.5, n = 63) for the nonsmoking pharmacy students compared to other nonsmoking students in medicine (mean = 16.2, n = 149), dentistry (mean = 16.1, n = 40) and physical therapy (mean = 14.9, n = 16) (p = 0.009). The smoking prevalence was 3% among all females and 31% among all males. Smoking students were significantly less likely (p = 0.031) to agree that it is their professional responsibility to help patients quit smoking. Conclusion: Significant and long-lasting differences in students’ perception of preparedness for the smoking cessation role based on exposure to a short teaching module were demonstrated. Furthermore, our results support previous findings that smoking compromises attitude towards helping smokers to quit.
Does Nasal Hair (Vibrissae) Density Affect the Risk of Developing Asthma in Patients with Seasonal Rhinitis?
Authors: Ozturk A.B. , Damadoglu E. , Karakaya G. , Kalyoncu A.F.
Published: March 2011

Background: Large particles entering the nose are collected by nasal hair present in the anterior nares. Increased hair density provides an improvement in the filtering efficiency of the nose, while reduced amounts of nasal hair cause a decrease in its efficiency. The amount of nasal hair can vary between individuals, which can make a difference in the filtering efficiency of the nose. Reduced filter function of the nose leads to increased exposure of the airways to allergens. The aim of this study was to determine the effect of nasal hair density on the risk of developing asthma in seasonal rhinitis (SR) patients. Methods: A standard questionnaire was filled in, and physical examination and allergy tests were performed in 233 patients. Patients were divided into 3 groups according to the amount of nasal hair [few (few or none), moderate and many]. The association between asthma and nasal hair density was assessed. Results: Asthma was detected in 75 patients (32.2%), and of these, 45 (60%) also had pollen asthma. The rate of asthma was 44.7, 26.2 and 16.7% in the few, moderate and many groups, respectively (p = 0.002). Few nasal hairs significantly increased the risk of developing asthma [odds ratio (95% confidence interval): few, reference; moderate, 0.41 (0.21–0.78); many, 0.19 (0.06–0.55); p = 0.002]. Conclusion: Our findings suggest that the amount of nasal hair providing a nose filtration function has a protective effect on the risk of developing asthma in SR patients. To the best of our knowledge, this is the first report on this subject in the literature.
Anaphylaxis to Buckwheat in an Atopic Child: A Risk Factor for Severe Allergy to Nuts and Seeds?
Authors: Varga Eva-Maria , Kollmann Dagmar , Zach Maximilian , Bohle Barbara
Published: March 2011

Common buckwheat (Fagopyrum esculentum) is known to cause severe anaphylactic reactions in adult individuals. However, type I allergy to buckwheat is rarely seen in children. We report on a 7-year-old boy who developed a grade III anaphylactic reaction after consumption of a cake containing buckwheat flour. Prior to this incident, the boy had developed severe allergic reactions to hazelnuts and suffered from an oral allergy syndrome to poppy seed. Analysis of the patient’s IgE reactivity by immunoblotting experiments revealed that he was sensitized to members of the 2S albumin and 11S globulin protein families in buckwheat. Additionally, cross-reactivity was found between the 11S globulins in buckwheat, poppy and hazelnut. IgE inhibition experiments indicated that the 11S globulin in buckwheat was the initial sensitizing protein. We conclude that 11S globulins in buckwheat have the potential to induce IgE antibodies cross-reactive with 11S globulins in other, botanically unrelated foods and may induce anaphylactic reactions.
Increased S-Nitrosothiol Levels in Nonasthmatic Eosinophilic Bronchitis Compared with Cough Variant Asthma
Authors: Lee Byung-Jae , Jeung Yun-Jin , Lee Jin-Young , Choi Dong-Chull
Published: March 2011

Background: Nonasthmatic eosinophilic bronchitis (NAEB) and cough variant asthma (CVA) are common causes of chronic cough. Both are characterized by eosinophilic inflammation in the airways. However, airway hyperresponsiveness, which is a characteristic feature of CVA, is not observed in NAEB. We hypothesized that endogenous bronchodilator S-nitrosothiol (SNO) levels are different between patients with NAEB and CVA. Methods: SNO concentrations in sputum supernatant were measured using a commercially available kit in 20 NAEB and 21 CVA patients. Results: The mean sputum eosinophil counts and exhaled nitric oxide values were similar in patients with NAEB (12.4 ± 2.3%, 80.6 ± 8.1 ppb) and CVA (15.3 ± 3.7%, 97.7 ± 9.2 ppb). By contrast, SNO levels in the airway lining fluid of NAEB patients were substantially higher than those of CVA patients (87.1 ± 9.8 vs. 46.8 ± 4.8 µM; p < 0.05). Conclusions: SNOs may be an important factor in determining the development of airway hyperresponsiveness in the presence of eosinophilic inflammation.
Clinical Impact of Pregnancy in Mastocytosis: A Study of the Spanish Network on Mastocytosis (REMA) in 45 Cases
Authors: Matito A. , Álvarez-Twose I. , Morgado J.M. , Sánchez-Muñoz L. , Orfao A. , Escribano L.
Published: March 2011

Background: The impact of pregnancy on mast cell (MC)-related symptoms and newborn outcome in women with mastocytosis is not well described. We report a series of 30 women who had 45 pregnancies. Methods: Patients completed a specific questionnaire concerning MC mediator release symptoms graded according to their frequency to detect clinical changes occurring during pregestation and pregnancy as well as postpartum. Information about the medications received during pregnancy and labor and about newborn medical complications was also recorded. Results: Worsening of MC-related symptoms during pregnancy was observed in 10 cases (22%); additionally, 1 woman developed skin lesions as a manifestation of indolent systemic mastocytosis (ISM) within the third trimester of pregnancy. Conversely, 15 cases (33%) experienced clinical improvement during pregnancy, with a complete resolution of pregestational symptoms in 7 cases. MC mediator release symptoms intrapartum were observed in 5 cases (11%) without any fatal outcome. Newborn medical complications (e.g. prematurity, low birth weight, and respiratory distress) were detected in 7 infants (16%) who were all successfully managed with conservative measures. One infant developed cutaneous mastocytosis several years after birth. Conclusions: Mastocytosis has a heterogeneous clinical behavior during pregnancy: the profile of MC-related symptoms remained unchanged in half of the cases, while in the other half pregnant women experienced either an improvement or an exacerbation of the symptoms, with the manifestation of ISM during pregnancy in 1 case. To prevent potential life-threatening MC-related symptoms, adequate prophylactic antimediator therapy intrapartum should be systematically administered. The absence of both maternal and infant severe complications suggests that patients with nonaggressive categories of mastocytosis should not be advised against pregnancy.
Irinotecan-Cetuximab-Bevacizumab as a Salvage Treatment in Heavily Pretreated Metastatic Colorectal Cancer Patients: A Retrospective Observational Study
Authors: Feliu Batlle J. , Cuadrado E. , Castro J. , Caldés T. , Belda C. , Sastre J. , Barriuso J. , Martínez Marín V. , Díaz-Rubio E. , González-Barón M.
Published: March 2011

Background: The objective was to evaluate the efficacy of irinotecan-cetuximab-bevacizumab in combination as a salvage treatment for heavily pretreated metastatic colorectal cancer patients. Methods: A total of 39 patients resistant to both oxaliplatin and irinotecan were included in this retrospective study. Treatment consisted of irinotecan 180/m2 every 14 days, weekly cetuximab standard dose and bevacizumab 5 mg/kg every 14 days. Results: Partial response was observed in 8 patients (20%), stable disease in 24 (61%) and progressive disease in 7 (18%). Overall response rate in KRAS wild type was 6/22 (27%) and in mutated KRAS it was 2/15 (13%). Median time to progression was 8 months (6.4–9.4) and median overall survival 12 months (10.1–13.8). Overall, grade 3–4 adverse events were observed in 24 patients (62%). Conclusions: This regimen is active and moderately well tolerated in heavily pretreated advanced colorectal patients. However, caution is advisable when interpreting these results, because they run against the findings of two large phase III trials.
Massive Hemorrhage from Spontaneous Ruptured Hepatocellular Carcinoma Controlled by Isoamyl 2-Cyanoacrylate: A Case Report
Authors: Al-Fraij Abdullah K. , Dhar Piyaray Mohan , Al-Khalejy Ayman , Abu Najem Fadi
Published: March 2011

Objective: To report a case of ruptured hepatocellular carcinoma with massive hemoperitoneum which was successfully controlled with isoamyl 2-cyanoacrylate. Clinical Presentation and Intervention: A 46-year-old Bangladeshi gentleman presented to our casualty complaining of acute abdominal pain and distension, associated with jaundice. Bedside abdominal ultrasound showed multiple focal lesions in the liver with fluid in the abdomen. The patient was vitally unstable, so he was resuscitated and underwent emergency laparotomy for massive hemoperitoneum due to a ruptured tumor nodule. Isoamyl 2-cyanoacrylate was applied to the ruptured nodule which stopped bleeding within 1–2 min. Conclusion: This case shows the effectiveness of isoamyl 2-cyanoacrylate in controlling bleeding in ruptured liver tumors.
Fragmentation and connection of frames in collaborative water governance: a case study of river catchment management in Southern Ecuador
Authors: Dewulf Art , Mancero Monica , Cárdenas German , Sucozhañay Dolores
Published: March 2011

In collaborative water governance, the variety of frames that actors bring to the discussion constitutes an important challenge. In this study, we analyse the fragmentation and connection of frames in collaborative water governance projects in the Paute catchment and its sub-catchment Tabacay in the Southern Andes of Ecuador. We rely on frame analysis of project documents, interviews and meeting recordings to analyse the initial stages of these projects. We discuss (1) the different roles of problem domain framing and issue framing in frame fragmentation; (2) the significance of scale framing to problem domain and issue framing; (3) the challenge of connecting expert frames with frames of other actors; and (4) the importance of face-to-face dialogue for connecting frames.

Points for practitioners

Professionals in public management and administration all over the world are increasingly involved in governance processes where they have to deal with a multitude of actors and perspectives. If their task involves setting up collaborative projects with other governmental agencies, civil society organizations and/or business actors, there is much to gain by paying close attention to how they themselves and other actors are framing both the problem domain and the issues involved. In processes of collaborative water governance, additional attention is required for how projects are framed with respect to water system scales and administrative scales, and for how technical framing of the issues connects to the frames and experiences of other actors.