bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic compression of mouse dorsal root ganglion alters voltage-gated sodium and potassium currents in medium-sized dorsal root ganglion neurons
Authors: Fan Ni , Donnelly David F. , LaMotte Robert H.
Published: September 2011

Chronic compression (CCD) of the dorsal root ganglion (DRG) is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the DRG, spinal nerve, or root. Previously, we examined electrophysiological changes in small-diameter lumbar level 3 (L3) and L4 DRG neurons treated with CCD; the present study extends these observations to medium-sized DRG neurons, which mediate additional sensory modalities, both nociceptive and non-nociceptive. Whole-cell patch-clamp recordings were obtained from medium-sized somata in the intact DRG in vitro. Compared with neurons from unoperated control animals, CCD neurons exhibited a decrease in the current threshold for action potential generation. In the CCD group, current densities of TTX-resistant and TTX-sensitive Na+current were increased, whereas the density of delayed rectifier voltage-dependent K+current was decreased. No change was observed in the transient or “A” current after CCD. We conclude that CCD in the mouse produces hyperexcitability in medium-sized DRG neurons, and the hyperexcitability is associated with an increased density of Na+current and a decreased density of delayed rectifier voltage-dependent K+current.
Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor
Authors: Leiva-Salcedo Elias , Coddou Claudio , Rodríguez Felipe E. , Penna Antonello , Lopez Ximena , Neira Tanya , Fernández Ricardo , Imarai Mónica , Rios Miguel , Escobar Jorge , Montoya Margarita , Huidobro-Toro J. Pablo , Escobar Alejandro , Acuña-Castillo Claudio
Published: September 2011

The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance.
Gas Turbine Engine Control Design Using Fuzzy Logic and Neural Networks
Authors: Bazazzadeh M. , Badihi H. , Shahriari A.
Published: September 2011

This paper presents a successful approach in designing a Fuzzy Logic Controller (FLC) for a specific Jet Engine. At first, a suitable mathematical model for the jet engine is presented by the aid of SIMULINK. Then by applying different reasonable fuel flow functions via the engine model, some important engine-transient operation parameters (such as thrust, compressor surge margin, turbine inlet temperature, etc.) are obtained. These parameters provide a precious database, which train a neural network. At the second step, by designing and training a feedforward multilayer perceptron neural network according to this available database; a number of different reasonable fuel flow functions for various engine acceleration operations are determined. These functions are used to define the desired fuzzy fuel functions. Indeed, the neural networks are used as an effective method to define the optimum fuzzy fuel functions. At the next step, we propose a FLC by using the engine simulation model and the neural network results. The proposed control scheme is proved by computer simulation using the designed engine model. The simulation results of engine model with FLC illustrate that the proposed controller achieves the desired performance and stability.
Mild Solutions of Neutral Stochastic Partial Functional Differential Equations
Authors: Govindan T. E.
Published: September 2011

This paper studies the existence and uniqueness of a mild solution for a neutral stochastic partial functional differential equation using a local Lipschitz condition. When the neutral term is zero and even in the deterministic special case, the result obtained here appears to be new. An example is included to illustrate the theory.
Seismic Imaging and Seismicity Analysis in Beijing-Tianjin-Tangshan Region
Authors: Yu Xiangwei , Zhang Wenbo , Chen Yun-tai
Published: September 2011

In this study a new tomographic method is applied to over 43,400 high-quality absolute direct P arrival times and 200,660 relative P arrival times to determine detailed 3D crustal velocity structures as well as the absolute and relative hypocenter parameters of 2809 seismic events under the Beijing-Tianjin-Tangshan region. The inferred velocity model of the upper crust correlates well with the surface geological and topographic features in the BTT region. In the North China Basin, the depression and uplift areas are imaged as slow and fast velocities, respectively. After relocation, the double-difference tomography method provides a sharp picture of the seismicity in the BTT region, which is concentrated along with the major faults. A broad low-velocity anomaly exists in Tangshan and surrounding area from 20 km down to 30 km depth. Our results suggest that the top boundary of low-velocity anomalies is at about 25.4 km depth. The event relocations inverted from double-difference tomography are clusted tightly along the Tangshan-Dacheng Fault and form three clusters on the vertical slice. The maximum focal depth after relocation is about 25 km depth in the Tangshan area.
Current Immunotherapeutic Approaches in Pancreatic Cancer
Authors: Koido Shigeo , Homma Sadamu , Takahara Akitaka , Namiki Yoshihisa , Tsukinaga Shintaro , Mitobe Jimi , Odahara Shunichi , Yukawa Toyokazu , Matsudaira Hiroshi , Nagatsuma Keisuke , Uchiyama Kan , Satoh Kenichi , Ito Masaki , Komita Hideo , Arakawa Hiroshi , Ohkusa Toshifumi , Gong Jianlin , Tajiri Hisao
Published: September 2011

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vast majority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer.
Shift Unitary Transform for Constructing Two‐Dimensional Wavelet Filters
Authors: Li Fei , Yang Jianwei
Published: September 2011

Due to the difficulty for constructing two‐dimensional wavelet filters, the commonly used wavelet filters are tensor‐product of one‐dimensional wavelet filters. In some applications, more perfect reconstruction filters should be provided. In this paper, we introduce a transformation which is referred to as Shift Unitary Transform (SUT) of Conjugate Quadrature Filter (CQF). In terms of this transformation, we propose a parametrization method for constructing two‐dimensional orthogonal wavelet filters. It is proved that tensor‐product wavelet filters are only special cases of this parametrization method. To show this, we introduce the SUT of one‐dimensional CQF and present a complete parametrization of one‐dimensional wavelet system. As a result, more ways are provided to randomly generate two‐dimensional perfect reconstruction filters.
Dermoid Cysts of the Floor of the Mouth: Two Case Reports
Authors: Makos Christos , Noussios George , Peios Marinos , Gougousis Spyridon , Chouridis Pantelis
Published: September 2011

Dermoid cysts in the floor of the mouth may be congenital or acquired. The congenital form, according to the main theory, originates from embryonic cells of the 1st and 2nd branchial arch. The acquired form may be due to traumatic or iatrogenic causes and as a result of the occlusion of a sebaceous gland duct. Its occurrence is less and is estimated to be from 1.6 to 6.4% of the dermoid cysts of the body in adults and 0.29% of the head and neck tumors occurring in children. They may also be classified as anatomical and histological. Anatomically, they are divided into median genioglossal, median geniohyoid, and lateral cysts, while histologically they are divided into epidermoid, dermoid cysts and teratomas. Clinically, a distinction between supra and inferior type as well as between central and lateral type is proposed in relation to themylohyoidmuscle and themidline, respectively. Histologically, an estimation of dermoid, epidermoid, and teratoid cysts is reported. Enucleation via intraoral and/or extraoral approach is the method of treatment. Two case reports of dermoid cysts in the floor of the mouth are presented in this paper, and an evaluation with regard to pathology, clinical findings, differential diagnosis, and treatment is discussed.
Prioritizing Signaling Information Transmission in Next Generation Networks
Authors: Baraković Jasmina , Bajrić Himzo , Kos Mladen , Baraković Sabina , Husić Amir
Published: September 2011

Next generation transport network is characterized by the use of in-band signaling, where Internet Protocol (IP) packets carrying signaling or media information are mixed in transmission. Since transport resources are limited, when any segment of access or core network is congested, IP packets carrying signaling information may be discarded. As a consequence, it may be impossible to implement reachability and quality of service (QoS). Since present approaches are insufficient to completely address this problem, a novel approach is proposed, which is based on prioritizing signaling information transmission. To proof the concept, a simulation study was performed using Network Simulator version 2 (ns-2) and independently developed Session Initiation Protocol (SIP) module. The obtained results were statistically processed using Statistical Package for the Social Sciences (SPSS) version 15.0. Summarizing our research results, several issues are identified for future work.
High-Performance 3D Compressive Sensing MRI Reconstruction Using Many-Core Architectures
Authors: Kim Daehyun , Trzasko Joshua , Smelyanskiy Mikhail , Haider Clifton , Dubey Pradeep , Manduca Armando
Published: September 2011

Compressive sensing (CS) describes how sparse signals can be accurately reconstructed from many fewer samples than required by the Nyquist criterion. Since MRI scan duration is proportional to the number of acquired samples, CS has been gaining significant attention in MRI. However, the computationally intensive nature of CS reconstructions has precluded their use in routine clinical practice. In this work, we investigate how different throughput-oriented architectures can benefit one CS algorithm and what levels of acceleration are feasible on different modern platforms. We demonstrate that a CUDA-based code running on an NVIDIA Tesla C2050 GPU can reconstruct a 256 × 160 × 80 volume from an 8-channel acquisition in 19 seconds, which is in itself a significant improvement over the state of the art. We then show that Intel's Knights Ferry can perform the same 3D MRI reconstruction in only 12 seconds, bringing CS methods even closer to clinical viability.
Effects of Chinese Economic Stimulus Package on Economic Growth in the Post‐Crisis China
Authors: Zhou Shenglv , Shi Minjun , Li Na , Yuan Yongna
Published: September 2011

This paper aims to simulate the contribution of investment expansion policy after financial crisis as well as describe the possible economic perspectives in the post‐crisis period by using scenario simulation method based on Chinese dynamic economic CGE (computable general equilibrium) model. Energy consumption and CO2 emission are also considered in order to access the possible negative effects owing to investment enlargement. The results show that expanding investment response to financial crisis increases economic growth rate by 6.74% from 2.36% in 2009. It can relieve the fluctuation in economy and bring the economic growth close to baseline level in the near post‐crisis period. However, higher energy consumption intensity and CO2 emission intensity compared to baseline owing to the increasing investment make energy saving and CO2 mitigation more difficult.
Differential Effect of Calsequestrin Ablation on Structure and	Function of Fast and Slow Skeletal Muscle Fibers
Authors: Paolini Cecilia , Quarta Marco , D′Onofrio Laura , Reggiani Carlo , Protasi Feliciano
Published: September 2011

We compared structure and function of EDL and Soleus muscles in adult (4–6 m) mice lacking both Calsequestrin (CASQ) isoforms, the main SR Ca2+‐binding proteins. Lack of CASQ induced ultrastructural alterations in ~30% of Soleus fibers, but not in EDL. Twitch time parameters were prolonged in both muscles, although tension was not reduced. However, when stimulated for 2 sec at 100 hz, Soleus was able to sustain contraction, while in EDL active tension declined by 70–80%. The results presented in this paper unmask a differential effect of CASQ1&2 ablation in fast versus slow fibers. CASQ is essential in EDL to provide large amount of Ca2+ released from the SR during tetanic stimulation. In contrast, Soleus deals much better with lack of CASQ because slow fibers require lower Ca2+ amounts and slower cycling to function properly. Nevertheless, Soleus suffers more severe structural damage, possibly because SR Ca2+ leak is more pronounced.
Idiopathic Superior Mesenteric Vein Thrombosis Resulting in Small Bowel Ischemia in a Pregnant Woman
Authors: Lin Hao , Lin Chih-Che , Huang Wan-Ting
Published: September 2011

Background. Small bowel ischemia due to superior mesenteric vein thrombosis (MVT) is rare during pregnancy. However, additional precipitating factors should usually be identified.Case. A 31-year-old woman, pregnant at 34 weeks, was sent to the emergency department because of acute peritonitis. An emergency exploration revealed a segmental gangrene of the small intestine without any mechanical obstruction. Together with the termination of pregnancy, resection of the damaged small bowel was performed, and an end-to-end enterostomy was followed. Based on the operative and pathological findings, small bowel ischemia might be attributed to superior mesenteric vein thrombosis.Conclusion. Hypercoagulation state normally found in pregnant women is believed to lead to this catastrophic condition without other precipitating factors.
Antifungal Activities of Peptides Derived from Domain 5 of High-Molecular-Weight Kininogen
Authors: Sonesson Andreas , Nordahl Emma Andersson , Malmsten Martin , Schmidtchen Artur
Published: September 2011

In both immunocompromised and immunocompetent patients,CandidaandMalasseziaare causing or triggering clinical manifestations such as cutaneous infections and atopic eczema. The innate immune system provides rapid responses to microbial invaders, without requiring prior stimulation, through a sophisticated system of antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and components of the contact system have previously been reported to bind toCandidaand other pathogens, leading to activation of the contact system. A cutaneousCandidainfection is characterized by an accumulation of neutrophils, leading to an inflammatory response and release of enzymatically active substances. In the present study we demonstrate that antifungal peptide fragments are generated through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK, D5-derived peptides, as well as hydrophobically modified D5-derived peptides efficiently killedCandidaandMalassezia. Furthermore, the antifungal activity of modified peptides was studied at physiological conditions. Binding of a D5-derived peptide, HKH20 (His479-His498), to the fungal cell membrane was visualized by fluorescence microscopy. Our data disclose a novel antifungal activity of D5-derived peptides and also show that proteolytic cleavage of HMWK results in fragments exerting antifungal activity. Of therapeutic interest is that structurally modified peptides show an enhanced antifungal activity.
A Novel Design of Microstrip Arrays for Relay-Based Wireless Network
Authors: Petropoulos Ioannis , Voudouris Konstantinos , Abd-Alhameed Raed A. , Jones Steve M. R. , Athanasopoulos Nikos
Published: September 2011

A relay station (RS) is a smart transceiver used under a 4G wireless network in order to extend network's coverage and capacity. It uses an antenna system that includes an antenna for connecting the relay with the end users (access link) and the RS with the base station (backhaul link). In this paper, a 7.9 dBi access and 11.4 dBi backhaul antennas are presented for the frequency range of 3.3 to 3.8 GHz. The antennas are simulated and fabricated, and relevant measured results in terms of return loss and radiation pattern are presented and analyzed. Considering that the planes of those two antennas are positioned in an angle (omega), two antenna configuration geometries are tested in terms of coupling. The experimental results of for several values of the angle show that the interaction between the radiating elements is dependent on their relative position. Simulated and experimental results are in good agreement, showing coupling typically less than −40 dB. A comparison in terms of coupling between the proposed antennas and commercial ones proves that the suggested antennas provide 10 dB lower coupling.
Basal Cell Carcinoma of the Head and Neck Region in Ethnic Chinese
Authors: Chow Velda Ling Yu , Chan Jimmy Yu Wai , Chan Richie Chiu Lung , Chung Joseph Hon Ping , Wei William Ignace
Published: September 2011

Objectives.This study aims to report our experience in the management of HNBCC in ethnic Chinese over a 10-year period.Methods.A retrospective review of all ethnic Chinese patients with HNBCC treated in a tertiary centre from 1999 to 2009.Results.From 1999 to 2009, 225 patients underwent surgical excision for HNBCC. Majority were elderly female patients. Commonest presentation was a pigmented (76.2%) ulcer (64.8%) over the nose (31.6%). Median skin margin taken on tumour excision was 2.0 mm; primary skin closure was achieved in 51.8%. Postresection skin margin was clear in 75.4%. Of those with inadequate skin margins, 56.7% opted for further treatment, 43.4% for observation. Recurrence rates were 2.6% and 13.8%, respectively (). Overall recurrence rate was 5.5%.Conclusions.HNBCC commonly presented as pigmented ulcers over the nose of elderly female patients in our locality. Adequate tumour excision ± reconstruction offered the best chance of cure. Reexcision of those with inadequate skin margins improved local tumour control.
Use of the Stingray Re-Entry System in Two Complex Cases of Occluded Superficial Femoral Arteries
Authors: Galbraith Erin M. , Del Rosario Marc , Niazi Khusrow
Published: September 2011

Totally occluded infrainguinal arterial disease presents formidable challenges to endovascular revascularization. A variety of devices have been made available to make the crossing of these lesions more amenable to endovascular techniques. We discuss the novel use of a device that has been developed for crossing occluded coronary arteries, the Stingray Re-Entry System.
Eosinophilic Esophagitis in Pediatrics: The Worst of all Possible Allergy Worlds?
Authors: Hopp Russell J.
Published: September 2011

Eosinophilic esophagitis (EoE) is a relatively uncommon allergic disease. Presenting with variable gastrointestinal symptoms, the definitive diagnosis is made after esophageal visualization and histological confirmation of excessive esophageal eosinophils. The scientific discovery of the pathophysiology of EoE has been aided by its relationship to other common and well-recognized allergic diseases. Similarities and important differences have emerged to distinguish EoE as a significant pediatric allergic disease with unique medical care requirements.
Facile Synthesis of Colloidal CuO Nanocrystals for Light‐Harvesting Applications
Authors: Lim Yee-Fun , Choi Joshua J. , Hanrath Tobias
Published: September 2011

CuO is an earth‐abundant, nontoxic, and low band‐gap material; hence it is an attractive candidate for application in solar cells. In this paper, a synthesis of CuO nanocrystals by a facile alcohothermal route is reported. The nanocrystals are dispersible in a solvent mixture of methanol and chloroform, thus enabling the processing of CuO by solution. A bilayer solar cell comprising of CuO nanocrystals and phenyl‐C61‐butyric acid methyl ester (PCBM) achieved a power conversion efficiency of 0.04%, indicating the potential of this material for light‐harvesting applications.
Phonon Spectra of Small Colloidal II-VI Semiconductor Nanocrystals
Authors: Dzhagan Volodymyr , Valakh Mykhailo , Mel'nik Nikolai , Rayevska Olexandra , Lokteva Irina , Kolny-Olesiak Joanna , Zahn Dietrich R. T.
Published: September 2011

Resonant Raman spectroscopy has been employed to explore the first- and higher-order phonon spectra of several kinds of II-VI nanocrystals (NCs), with the aim of better understanding of the nature of phonon modes and forming a unified view onto the vibrational spectrum of semiconductor NCs. Particularly, besides the previously discussed TO, SO, LO, and 2LO modes, the combinational modes of TO+LO and SO+LO can be assumed to account for the lineshape of the spectrum below 2LO band. No trace of 2TO or 2SO band was detected, what can be the result of the dominance of Fröhlich mechanism in electron-phonon coupling in II-VI compounds. The resonant phonon Raman spectrum of NCs smaller than 2 nm is shown to be dominated by a broad feature similar to the SO mode of larger NCs or phonon density of states of a bulk crystal.
Canonical and Singular Propagation of Ultrashort Pulses in a Nonlinear Medium
Authors: Glasner Karl , Kolesik Miroslav , Moloney Jerome V. , Newell Alan C.
Published: September 2011

We examine the two types of singular behaviors of ultrashort pulses in a nonlinear medium, pulse steepening if the weak longitudinal dispersion is normal and collapse if it is anomalous. Connections with analogous behaviors of wave packets of almost monochromatic waves in strongly dispersive media are discussed.
Phase Behavior at High Pressure of the Ternary System: CO2, Ionic Liquid and Disperse Dye
Authors: Mazzer Helen R. , Santos José C. O. , Cabral Vladimir F. , Dariva Claudio , Kunita Marcos H. , Rubira Adley F. , Aznar Martin , Cardozo-Filho Lucio
Published: September 2011

High pressure phase behavior experimental data have been measured for the systems carbon dioxide (CO2) + 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] [PF6]) and carbon dioxide (CO2) + 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] [PF6]) + 1-amino-2-phenoxy-4-hydroxyanthraquinone (C.I. Disperse Red 60). Measurements were performed in the pressure up to 18 MPa and at the temperature (323 to 353 K). As reported in the literature, at higher concentrations of carbon dioxide the phase transition pressure increased very steeply. The experimental data for the binary and ternary systems were correlated with good agreement using the Peng-Robinson equation of state. The amount of water in phase behavior of the systems was evaluated.
Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions
Authors: López-Pedrera Chary , Pérez-Sánchez Carlos , Ramos-Casals Manuel , Santos-Gonzalez Monica , Rodriguez-Ariza Antonio , José Cuadrado Ma
Published: September 2011

Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as systemic inflammation mediators, including cytokines, chemokines, proteases, autoantibodies, adhesion receptors, and others, have been implicated in the development of these vascular pathologies. Yet, the characteristics of vasculopathies may significantly differ depending on the underlying disease. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been further detected. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Epigenetic regulatory mechanisms comprise DNA methylation, histone modifications, and microRNA activity, all of which act upon gene and protein expression levels. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, not only showing differences between AID patients and healthy controls, but also showing how one disease differs from another and even how the expression of key proteins involved in the development of each disease is regulated.
rILYd4, a Human CD59 Inhibitor, Enhances Complement-Dependent Cytotoxicity of Ofatumumab against Rituximab-Resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia
Authors: Ge Xiaowen , Wu Lin , Hu Weiguo , Fernandes Stacey , Wang Chun , Li Xu , Brown Jennifer R. , Qin Xuebin
Published: September 2011

Purpose: Ofatumumab is an anti-CD20 antibody recently approved for treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL); it mediates much stronger complement-dependent cytotoxicity (CDC) than rituximab. Human CD59, a key membrane complement regulator that inhibits CDC, is highly expressed in B-cell malignancies and its upregulation is an important determinant of the sensitivity of B-cell malignancies to rituximab treatment. Previously, we have shown that the potent CD59 inhibitor rILYd4 sensitizes rituximab-resistant lymphoma cells to rituximab-mediated CDC. Here, we further investigated whether rILYd4 can sensitize B-cell malignancies to ofatumumab-mediated CDC and whether either ofatumumab-mediated CDC or rILYd4-enhanced ofatumumab-mediated CDC correlates with CD20 or CD59 expression, known biomarkers involved in rituximab activity.

Experimental Design: Rituximab-resistant cell lines and primary CLL cells were used to investigate the antitumor efficacy of the combination of rILYd4 with ofatumumab or rituximab. Propidium iodide staining or alamarBlue assay were used to evaluate the CDC effect. The levels of CD20 and CD59 on the cell membrane were analyzed by flow cytometry.

Results: rILYd4 enhanced CDC effects mediated by ofatumumab or rituximab on rituximab-resistant lymphoma cells and primary CLL cells in vitro. The sensitivity to CDC effects mediated by ofatumumab positively correlated with the ratio of CD20/CD59 and negatively correlated with CD59 levels on CLL cells. The degree to which rILYd4 enhanced CDC correlated positively with the CD59 levels on CLL cells.

Conclusions: These data suggest that rILYd4 may enhance the anticancer activity of ofatumumab and rituximab in B-cell malignancies that have relapsed after prior antibody-based therapies. Clin Cancer Res; 17(21); 6702–11. ©2011 AACR.
Common Cancer Stem Cell Gene Variants Predict Colon Cancer Recurrence
Authors: Gerger Armin , Zhang Wu , Yang Dongyun , Bohanes Pierre , Ning Yan , Winder Thomas , LaBonte Melissa J. , Wilson Peter M. , Benhaim Leonor , Paez David , El-Khoueiry Rita , El-Khoueiry Anthony , Kahn Michael , Lenz Heinz-Josef
Published: September 2011

Purpose: Recent evidence suggests that cancer stem cells (CSC) are responsible for key elements of colon cancer progression and recurrence. Germline variants in CSC genes may result in altered gene function and/or activity, thereby causing interindividual differences in a patient's tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of CSC genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer.

Experimental Design: A total of 234 patients treated with 5-fluorouracil–based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for germline polymorphisms in genes that have been previously associated with colon CSC (CD44, Prominin-1, DPP4, EpCAM, ALCAM, Msi-1, ITGB1, CD24, LGR5, and ALDH1A1) by PCR-RFLP or direct DNA-sequencing.

Results: The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35–0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33–0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12–0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71–16.63, P < 0.001).

Conclusion: This is the first study identifying common germline variants in colon CSC genes as independent prognostic markers for stage III and high-risk stage II colon cancer patients. Clin Cancer Res; 17(21); 6934–43. ©2011 AACR.
ER and PI3K Independently Modulate Endocrine Resistance in ER-Positive Breast Cancer
Authors: Van Tine Brian A. , Crowder Robert J. , Ellis Matthew J.
Published: September 2011

Endocrine therapy–resistant estrogen receptor–positive (ER+) breast cancer is the most common cause of breast cancer death. Miller and colleagues demonstrate that ligand-independent ER activity promotes the growth of breast cancer cells through CDK4/E2F. As an independent event, the phosphatidylinositol 3-kinase (PI3K) pathway is also upregulated in endocrine therapy-resistant cells. Promising preclinical evidence by several groups for the combination of an inhibitor of ligand-independent ER, fulvestrant, with PI3K inhibition, has led to the activation of trials evaluating this concept. Cancer Discovery; 1(4): 287–8. ©2011 AACR.

Commentary on Miller et al., p. 338.
Development of an Electronic Manometer for Intrapleural Pressure Monitoring
Authors: Krenke Rafał , Guć Maciej , Grabczak Elżbieta Magdalena , Michnikowski Marcin , Pałko Krzysztof Jakub , Chazan Ryszarda , Gólczewski Tomasz
Published: September 2011

Background: Measurement of intrapleural pressure is useful during various pleural procedures. However, a pleural manometer is rarely available. Objectives: The aim of this study was to (1) construct an electronic pleural manometer, (2) assess the accuracy of the measurements done with the new device, (3) calculate the costs of the manometer construction and (4) perform an initial evaluation of the device in a clinical setting. Methods: Only widely accessible elements were used to construct the device. A vascular pressure transducer was used to transform pressure into an electronic signal. Reliability of the measurements was evaluated in a laboratory setting in a prospective, single-blind manner by comparing the results with those measured by a water manometer. Functionality of the device was assessed during therapeutic thoracentesis. The cost of the new pleural manometer was calculated. Results: We built a small, portable device which can precisely measure intrapleural pressure. The measurement results showed very high agreement with those registered with a water manometer (r = 0.999; p < 0.001). The initial evaluation of the electronic manometer during therapeutic thoracentesis showed it was easy to use. The total time needed for 6 measurements after withdrawal of different volumes of pleural fluid in 1 patient did not exceed 6 min. The total cost of the device was calculated to be <2,000 EUR. Conclusions: In the face of very limited offer of commercially available pleural manometers, it is possible to successfully construct a self-made, reliable, electronic pleural manometer at modest costs. The device is easy to use and enables data display and storage in the personal computer.
Natural Surfactant Combined with Beclomethasone Decreases Lung Inflammation in the Preterm Lamb
Authors: Dani Carlo , Corsini Iuri , Burchielli Silvia , Cangiamila Valentina , Romagnoli Roberta , Jayonta Bhattacharjee , Longini Mariangela , Paternostro Ferdinando , Buonocore Giuseppe
Published: September 2011

Background: Natural surfactant combined with beclomethasone decreases pulmonary oxidative stress in preterm lambs with respiratory distress syndrome (RDS). Objectives: To test the hypothesis that this occurs through a decrease in pulmonary inflammation. Methods: Preterm lambs received 200 mg/kg of natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 µg/kg of beclomethasone. Interleukin 8 (IL-8) and macrophage migration inhibitory factor (MIF) were assayed in bronchial aspirate samples and lung mechanics were evaluated. Results: IL-8 increased in all the groups, but the increase was lower in the groups treated with surfactant plus 400 and 800 µg/kg of beclomethasone. MIF decreased in the surfactant group, did not vary in the surfactant plus 400 µg/kg beclomethasone group, and decreased in the surfactant plus 800 µg/kg beclomethasone group. MIF concentration was higher in the surfactant plus 800 µg/kg beclomethasone group than in the other groups. Conclusions: Natural surfactant combined with beclomethasone at 800 µg/kg is effective in reducing lung inflammation in an animal model of RDS, thus explaining the associated decrease in lung oxidative stress. The increase in MIF in animals treated with surfactant plus 800 µg/kg of beclomethasone might be an important maturative and protective factor for neonatal lungs.
Hemorrhagic Transformation in Acute Cerebellar Infarction
Authors: Sakamoto Yuki , Kimura Kazumi , Iguchi Yasuyuki , Shibazaki Kensaku , Aoki Junya
Published: September 2011

Background: Hemorrhagic transformation (HT) is a well-known consequence of acute ischemic stroke, but little is known about HT in cerebellar infarction. Methods: Patients with acute cerebellar infarction within 48 h of onset were retrospectively recruited. MRI, including diffusion-weighted imaging (DWI) and T2*-gradient echo imaging (T2*), was performed twice (upon admission and 2 weeks after stroke onset). Infarct diameter and volume were measured by manual tracing on initial DWI. HT was evaluated with follow-up T2*, and all patients were divided into two groups according to the presence of HT (HT group and non-HT group). The frequency of HT and the factors associated with HT were investigated. Results: Ninety-six patients (64 males, median age 74 years, IQR 65–81 years, and National Institute of Health Stroke Scale score 5, IQR 1–14) were enrolled. Forty-two patients (43%) showed HT on follow-up T2* (HT group). Infarct diameter and volume were larger in the HT group than in the non-HT group (3.2 vs. 1.6 cm, respectively, p < 0.001, for infarct diameter and 8.0 vs. 1.7 cm3, respectively, p < 0.001 for infarct volume). Multivariate logistic regression analysis revealed that both infarct diameter >2.7 cm (OR 7.58, 95% CI 2.82–20.4, p < 0.001) and volume >4.5 cm3 (OR 11.5, 95% CI 3.80–34.8, p < 0.001) were independent factors associated with HT. Conclusions: Half of the patients with acute cerebellar infarcts had HT on follow-up T2*. Initial infarct diameter and volume on DWI were independent factors associated with HT.
Outcomes for Patients with Ischaemic Stroke and Atrial Fibrillation: The PRISM Study (A Program of Research Informing Stroke Management)
Authors: Gattellari Melina , Goumas Chris , Aitken Robert , Worthington John M.
Published: September 2011

Background: In the past decade the prevalence of atrial fibrillation (AF) has been increasing in ageing populations while stroke prevention and management have advanced. To inform clinician practice, health service planning and further research, it is timely to reassess the burden of AF-related ischaemic stroke. Methods: We identified patients aged 18+ years with a primary or stay diagnosis of ischaemic stroke (ICD-10-AM I63.x), from July 1, 2000 to June 30, 2006, using an administrative health dataset of all hospitalisations in New South Wales (population ∼7 million). Fact of death was determined to December 2007. Results: Of the 26,960 index cases of ischaemic stroke, 25.4% had AF recorded during admission. Median age for AF and non-AF patients was 80.4 and 75.2 years, respectively (p < 0.001). Mortality was significantly higher in patients with AF at 30 days (19.4 vs. 11.5%), 90 days (27.7 vs. 15.8%) and 365 days (38.5 vs. 22.6%) (p values <0.0001). Adjusting for age and co-morbidities reduced these differences, with 90-day mortality of 20.9% in AF patients versus 14.7% in non-AF patients (p value <0.0001). The effect of AF on outcomes appears stronger in younger stroke patients relative to patients without AF (p valueinteraction <0.0001). At 30 days, the relative risk of mortality due to AF was 3.16 (95% CI 1.92–5.25) amongst those younger than 50, 1.71 (95% CI 1.32–2.22) in patients aged 50–64 years, 1.39 (95% CI 1.16–1.66) in patients aged 65–74 years, 1.29 (95% CI 1.17–1.43) in those aged 75–84 years, and 1.23 (95% CI 1.13–1.33) in those aged 85+ years. AF patients, surviving admission, spent a median of 19.2 days (95% CI 18.4–20.1) in hospital compared with 14.5 days (95% CI 13.9–15.1) for patients without AF (p < 0.001), with differences in length of stay greatest in younger patients (p valueinteraction <0.0001). 90-Day stroke survivors with AF spent an average of 21.5 days (95% CI 20.6–22.4) in hospital versus 16.6 days (95% CI 15.9–17.2) in those without AF. AF patients accessed more in-hospital rehabilitation (36.6%; 95% CI 35.0–38.2) than patients without AF (31.8%; 95% CI 31.0–32.7) (p value <0.0001), and differences in the proportion of AF versus non-AF patients accessing rehabilitation was greatest in younger patients (p valueinteraction <0.0006). Conclusions: Ischaemicstroke patients with AF have substantially worse outcomes than patients without AF, which can be partly explained by older age and greater co-morbidities. We have quantified the large effect of AF in younger patients and our results strongly argue for new antithrombotic research in young AF patients.
Prevalence of Multiple Sclerosis in the Serbian District Sumadija
Authors: Toncev G. , Miletic Drakulic S. , Knezevic Z. , Boskovic Matic T. , Gavrilovic A. , Toncev S. , Drulovic J. , Pekmezovic T.
Published: September 2011

Background: The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in the district of Sumadija (central part of Serbia). Methods: All persons suffering from MS, with permanent residence in the region, were recruited. Prevalence was calculated on December 31, 2006, according to a standard procedure. Results: On December 31, 2006, one hundred ninety-four patients (72 males and 122 females) were found to have MS. We found a crude MS prevalence of 64.9/100,000 (49.3/100,000 for males and 79.9/ 100,000 for females). The highest prevalence rates were registered in the age group of 30–39 years for females and 40–49 years for males, although the age-specific rates were higher in females in all age groups. The mean age at onset was 34.2 ± 9.3 years. The average duration of MS was 8.9 ± 6.2 years. The median EDSS score was 3.9 ± 2.0. The course of MS was relapsing-remitting in 63.9% of patients, secondary progressive in 32.5%, and primary progressive in 3.6%. At MS onset, motor symptoms were present in 70.1% of patients, sensory in 40.7%, cerebellar in 21.1%, brainstem in 15.5%, visual in 22.2%, and bowel/bladder disturbances in 22.2%. Conclusions: Our results demonstrate that the MS prevalence registered in the Serbian district Sumadija is similar to that of other surrounding areas in Southeastern Europe.
Myocardial Uptake of 7′-(Z)-[
123
I]Iodorotenone During Vasodilator Stress in Dogs With Critical Coronary Stenoses
Authors: Broisat Alexis , Ruiz Mirta , Goodman Norman C. , Hanrahan Stephen M. , Reutter Bryan W. , Brennan Kathleen M. , Janabi Mustafa , Schaefer Saul , Watson Denny D. , Beller George A. , VanBrocklin Henry F. , Glover David K.
Published: September 2011

Background—

There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[
125
I]iodorotenone (
125
I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of
123
I-ZIROT in an intact large-animal model.

Methods and Results—

The
123
I-ZIROT was administered during adenosine A
2A
agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal,
123
I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later.
123
I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At
123
I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g];
P
=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g];
P
<0.05). Myocardial
123
I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or
99m
Tc-sestamibi from previous studies using a similar model. Furthermore, the
123
I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09).

Conclusions—

The ability of
123
I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.
Comments on “Estimation of Tropical Cyclone Wind Hazard for Darwin: Comparison with Two Other Locations and the Australian Wind-Loading Code”
Authors: Harper Bruce A. , Holmes John D. , Kepert Jeffrey D. , Mason Luciano B. , Vickery Peter J.
Published: September 2011

Cook and Nicholls recently argued in this journal that the city of Darwin (Northern Territory), Australia, should be located in wind region D rather than in the current region C in the Australian/New Zealand Standard AS/NZS 1170.2 wind actions standard, in which region D has significantly higher risk. These comments critically examine the methods used by Cook and Nicholls and find serious flaws in them, sufficient to invalidate their conclusions. Specific flaws include 1) invalid assumptions in their analysis method, including that cyclones are assumed to be at the maximum intensity along their entire path across the sampling circle even after they have crossed extensive land areas; 2) a lack of verification that the simulated cyclone tracks are consistent with the known climatological data and in particular that the annual rate of simulated cyclones at each station greatly exceeds the numbers recorded for the entire Australian region; and 3) the apparent omission of key cyclones when comparing the risk at Darwin with two other locations. It is shown here that the number of cyclones that have affected Port Hedland (Western Australia), a site in Australia’s region D, greatly exceeds the number that have influenced Darwin over the same period for any chosen threshold of intensity. Analysis of the recorded gusts from anemometers at Port Hedland and Darwin that is presented here further supports this result. On the basis of this evidence, the authors conclude that Darwin’s tropical cyclone wind risk is adequately described by its current location in region C.
Progress on Predicting the Breadth of Droplet Size Distributions Observed in Small Cumuli
Authors: Bewley Jennifer L. , Lasher-Trapp Sonia
Published: September 2011

A modeling framework representing variations in droplet growth by condensation, resulting from different saturation histories experienced as a result of entrainment and mixing, is used to predict the breadth of droplet size distributions observed at different altitudes within trade wind cumuli observed on 10 December 2004 during the Rain in Cumulus over the Ocean (RICO) field campaign. The predicted droplet size distributions are as broad as those observed, contain similar numbers of droplets, and are generally in better agreement with the observations when some degree of inhomogeneous droplet evaporation is considered, allowing activation of newly entrained cloud condensation nuclei. The variability of the droplet growth histories, resulting primarily from entrainment, appears to explain the magnitude of the observed droplet size distribution widths, without representation of other broadening mechanisms. Additional work is needed, however, as the predicted mean droplet diameter is too large relative to the observations and likely results from the model resolution limiting dilution of the simulated cloud.
The Shi'i Concept of Imamate and Leadership in Contemporary Iran
Authors: Hashemi-Najafabadi Adel
Published: September 2011

The Imamate is one of the most important pillars in Twelver Shi’ism. However, its meaning has been greatly debated by religious modernists in recent years. In this article, the Iranian religious modernists' position on the concept of the Imamate, in contrast to the traditional view, is expounded. In addition, this work presents the major critical remarks of the religious modernists on the theory of Velayat-e Faqih (guardianship of the jurist), as an implementation of the concept of Imamate, which is in practice in contemporary Iran.

L’Imamat est l’un des piliers les plus importants dans le chiisme duodécimain. Toutefois, sa signification a été grandement débattu par les modernistes religieux dans ces dernières années. Dans cet article, la position des modernistes religieux iraniens sur le concept de l’Imamat, contrairement à la vision traditionnelle, est exposée. En outre, cet ouvrage présente les remarques principales critiques des modernistes religieux sur la théorie du velayat-e faqih (la tutelle du juriste), comme une mise en œuvre du concept de l’Imamat, qui est en pratique dans l’Iran contemporain.