bluuebunny/crossref_metadata_2025 huggingface dataset:
Abatement of CF4 and CHF3 byproducts using low-pressure plasmas generated by annular-shaped electrodes
Authors: Hur Min , Lee Jae O. K. , Hoon Song Young , Yoo Hoon A.
Published: February 2012

Three different driving schemes are tested for a plasma reactor designed to abate the greenhouse gases emitted by the semiconductor industry. The reactor and electrodes all have a concentric annular shape, which allows them to be easily connected to pre-existing pipelines without any disturbance to the exhaust stream. The destruction and removal efficiencies are measured for CF4 by varying the O2/CF4 ratio and pressure. The influences of adding O2 and H2O to the byproducts of the CHF3 abatement process are investigated by analyzing the spectra resulting from Fourier transform infrared spectroscopy measurements. Based on the experimental results we suggest an appropriate combination of driving scheme and reactant gas species for efficient and economical abatement of a mixture of CHF3 and CF4. Then, the optimal flow rate of the reactant gas is presented. Finally, the reduction rates for global warming emissions are estimated to demonstrate the feasibility of using our device for abatement of greenhouse gases emitted by the semiconductor industry.
SiCl4/Cl2 plasmas: A new chemistry to etch high-k materials selectively to Si-based materials
Authors: Bodart Paul , Cunge Gilles , Joubert Olivier , Lill Thorsten
Published: February 2012

Plasma etching of ultrathin layers of high-k materials is one critical step in the fabrication of gate transistors. The main challenge in this process is to achieve an infinite etching selectively between the high-k and the Si (or SiO2 covered silicon) substrate to prevent damaging the source and drain regions of the transistor. State of the art high-k etching plasmas use BCl3 chemistries, sometime at high wafer temperature. However, the process window in which an infinite high-k/Si selectivity can be achieved is very narrow and several issues remain associated with these processes. In this work, we introduced a new high-k plasma etching chemistry: SiCl4/Cl2. It can be used to etch Hf-based and Al-based high-k materials with an infinite selectivity towards Si, SiO2 and SiON, and with a much wider process window than BCl3 plasmas. XPS analyses indicate that the selectivity mechanism relies on the formation of a SiClx deposit selectively on Si-containing materials, which prevent them from being etched. By contrast SiClx radicals and ions are directly involved in the etching of the metallic oxide layer by forming volatile products (most probably SiOClx and HfClx). This new chemistry may replace valuably BCl3-based plasmas for future high-k etching processes and it may also be interesting for other applications.
Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage
Authors: Crane Justin D. , Ogborn Daniel I. , Cupido Colleen , Melov Simon , Hubbard Alan , Bourgeois Jacqueline M. , Tarnopolsky Mark A.
Published: February 2012

Beneficial effects of massage on tired muscles work through anti-inflammatory and mitochondrial biogenesis pathways.
CXCL12-Induced Monocyte-Endothelial Interactions Promote Lymphocyte Transmigration Across an in Vitro Blood-Brain Barrier
Authors: Man Shumei , Tucky Barbara , Cotleur Anne , Drazba Judith , Takeshita Yukio , Ransohoff Richard M.
Published: February 2012

An in vitro model of the human blood-brain barrier provides insights into how chemokine receptors regulate the transmigration of leukocytes into brain tissue.
Geomapping Health-Related Data
Authors: Sayani Saleem
Published: February 2012

Geographical information systems can be used to analyze health data and drive improvements.
A GENERALIZED FIXED POINT FREE AUTOMORPHISM OF PRIME POWER ORDER
Authors: ERCAN GÜLİN , GÜLOĞLU İSMAİL Ş.
Published: February 2012

Let G be a finite group and α be an automorphism of G of order pn for an odd prime p. Suppose that α acts fixed point freely on every α-invariant p′-section of G, and acts trivially or exceptionally on every elementary abelian α-invariant p-section of G. It is proved that G is a solvable p-nilpotent group of nilpotent length at most n + 1, and this bound is best possible.
AN EXPLANATION FACILITY FRAMEWORK FOR RULE-BASED SYSTEMS
Authors: TOMIĆ BOJAN , HORVAT BORIS , JOVANOVIĆ NEMANJA
Published: February 2012

Rule engines, business rule management systems and other rule-based systems used today widely utilize methods, techniques and technologies from the era of expert systems. Unfortunately, this doesn't seem to be the case when it comes to explanation facilities. Nowadays, the use of explanation facilities seems more important than ever. Business rule management systems control or constrain the behavior of business processes through business rules and an explanation of the inference process intended for the end user would be more than welcome. An explanation facility framework which was created in order to remedy this situation is presented in this paper. It is written in Java and is supposed to be a generic solution for modern rule-based systems. Besides being free and open-source, it is simple to use and can generate explanations in the form of natural language like sentences. Internationalization is also supported and explanations can be saved as textual, XML or PDF reports.
RESONANT ENHANCEMENT OF NUCLEAR REACTIONS AS A POSSIBLE SOLUTION TO THE COSMOLOGICAL LITHIUM PROBLEM
Authors: CYBURT RICHARD H. , POSPELOV MAXIM
Published: February 2012

There is a significant discrepancy between the current theoretical prediction of the cosmological lithium abundance, mostly produced as 7 Be during the Big Bang, and its observationally inferred value. We investigate whether the resonant enhancement of 7 Be burning reactions may alleviate this discrepancy. We identify one narrow nuclear level in 9 B , E5/2+ ≃ 16.7 MeV that is not sufficiently studied experimentally, and being just ~ 200 keV above the 7 Be +d threshold, may lead to the resonant enhancement of 7 Be (d, γ)9 B and 7 Be (d, p)αα reactions. We determine the relationship between the domain of resonant energies Er and the deuterium separation width Γd that results in the significant depletion of the cosmological lithium abundance and find that (Er, Γd)≃(170-220, 10-40) keV can eliminate the current discrepancy. Such a large width at this resonant energy can be only achieved if the interaction radius for the deuterium entrance channel is very large, a27 ≥ 10 fm . New nuclear experimental and theoretical work is needed to clarify the role this resonance plays on the BBN prediction of the lithium abundance. Alternatively, the most liberal interpretation of the allowed parameters of 16.7 MeV resonance can significantly increase the errors in predicted lithium abundance: [7 Li/H ] BBN = (2.5-6) × 10-10.
AN ELECTRICALLY TUNABLE FOCUSING PICO PROJECTION SYSTEM BASED ON A LIQUID CRYSTAL LENS ADOPTING A LIQUID CRYSTAL AND POLYMER COMPOSITE FILM
Authors: LIN HUNG-CHUN , CHEN MING-SYUAN , LIN YI-HSIN
Published: February 2012

An electrically tunable liquid-crystal-on-silicon (LCOS)-based pico projection system based on a liquid crystal lens adopting a liquid crystal and polymer composite film (LCPCF) is demonstrated. The LC lens consists of two built-in sub-lenses: one is an electrically tunable focusing lens controlled by a LC layer and the other is a fixed focused LCPCF lens. The electrically tunable focusing range of the pico projection system is 200 cm to ~7 cm when the voltage is from 0 to 35 Vrms. The image performance is also demonstrated. The related optical analysis is discussed. This study opens a new window for electrically tunable focusing pico projection system.
ENHANCED OPTICAL THIRD HARMONIC GENERATION IN THICK ORGANIC FILMS
Authors: CHOI HEE-JOO , CHA MYOUNGSIK
Published: February 2012

In order to enhance optical third-harmonic generation (THG) in polymer films, we investigated linear and nonlinear optical properties of polymer films containing ethyl-violet with varying thickness. The THG intensity increased monotonically with thickness, as opposed to the theory for non-phase-matched THG in films thicker than the coherence length. By measuring the refractive indices, we found that the difference between the indices of the fundamental and the third-harmonic was smaller in thicker films. Thus, the coherence lengths for thicker films were evaluated to be larger than those for the thin films, explaining the monotonic increase of the THG signal with thickness.
'YOU CAN RUN, BUT YOU CANNOT HIDE': TRACKING OBJECTS THAT LEAVE THE FIELD-OF-VIEW
Authors: HAUENSTEIN JACOB , TINAZTEPE RAMAZAN , AYGUN RAMAZAN S.
Published: February 2012

In the past, there has been significant research on tracking objects based on features that characterize objects. However, once the features to detect the object are not available from the position of a tracker, it is not clear how to track the object. Our goal in this paper is to track an object even though the object leaves the field-of-view. In this paper, we first describe the problems related to this type of tracking. We then explain our approach that has two phases: Real object tracking and virtual object tracking. We mostly focus on virtual object tracking that requires reorientation, distance estimation, traveling the computed distance, estimating the direction for turn, and turning into the direction. We show our results by building a robot that achieves these.
AN ANALYSIS OF THE INFLUENCE OF DISPERSION OF VALUATIONS ON FINANCIAL MARKETS THROUGH AGENT-BASED MODELING
Authors: TAKAHASHI HIROSHI
Published: February 2012

This research analyzes the influence of dispersion of valuations on financial markets, taking several aspects of real financial market into consideration (such as financial constraints, investment strategies and so on). As a result of intensive experiments in the market, we made the following findings: (1) Dispersion of fundamentalists' valuations has little effect on the market when financial constraints are absent; (2) When financial constraints — such as short-sale constraints — are introduced, certain situations arise in which deviations from fundamental values become larger, according to the level of the dispersion of valuations; (3) A passive investment strategy, as is consistent with traditional financial theory, is valid even when the introduction of financial constraints causes market prices to deviate significantly from fundamental values. These results contribute to clarifying the mechanism of price fluctuations in financial markets and are notable from both academic and practical view points.
TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice
Authors: Iwasaki Hitoshi , Naka Ayano , Iida Kaoruko Tada , Nakagawa Yoshimi , Matsuzaka Takashi , Ishii Kiyo-aki , Kobayashi Kazuto , Takahashi Akimitsu , Yatoh Shigeru , Yahagi Naoya , Sone Hirohito , Suzuki Hiroaki , Yamada Nobuhiro , Shimano Hitoshi
Published: February 2012

The role of transcription factor E3 (TFE3), a bHLH transcription factor, in immunology and cancer has been well characterized. Recently, we reported that TFE3 activates hepatic IRS-2 and hexokinase, participates in insulin signaling, and ameliorates diabetes. However, the effects of TFE3 in other organs are poorly understood. Herein, we examined the effects of TFE3 on skeletal muscle, an important organ involved in glucose metabolism. We generated transgenic mice that selectively express TFE3 in skeletal muscles. These mice exhibit a slight acceleration in growth prior to adulthood as well as a progressive increase in muscle mass. In TFE3 transgenic muscle, glycogen stores were more than twofold than in wild-type mice, and this was associated with an upregulation of genes involved in glucose metabolism, specifically glucose transporter 4, hexokinase II, and glycogen synthase. Consequently, exercise endurance capacity was enhanced in this transgenic model. Furthermore, insulin sensitivity was enhanced in transgenic mice and exhibited better improvement after 4 wk of exercise training, which was associated with increased IRS-2 expression. The effects of TFE3 on glucose metabolism in skeletal muscle were different from that in the liver, although they did, in part, overlap. The potential role of TFE3 in regulating metabolic genes and glucose metabolism within skeletal muscle suggests that it may be used for treating metabolic diseases as well as increasing endurance in sport.
Differential regulation of stimulated glucose transport by free fatty acids and PPARα or -δ agonists in cardiac myocytes
Authors: Asrih Mohamed , Lerch René , Papageorgiou Irène , Pellieux Corinne , Montessuit Christophe
Published: February 2012

Stimulation of glucose transport in response to insulin or metabolic stress is an important determinant of cardiac myocyte function and survival, particularly during ischemia-reperfusion episodes. The impact of dyslipidemia and its consequence PPAR activation on stimulated glucose transport in cardiac myocytes remains unknown. Isolated adult rat cardiac myocytes were chronically exposed to free fatty acids (FFA) or PPAR agonists. Insulin- (ISGT) and oligomycin-stimulated glucose transport (OSGT) and related cell signaling were analyzed. Exposure of cardiac myocytes to FFA reduced both ISGT and OSGT. Exposure to either PPARα or PPARδ agonists, but not to a PPARγ agonist, reduced ISGT but not OSGT and increased fatty acid oxidation (FAO). The reduction in ISGT was associated with impaired insulin signaling and, in the case of PPAR stimulation, overexpression of SOCS-3, a protein known to hinder proximal insulin signaling. In contrast, the reduction of OSGT could not be explained by a reduced activity of the cellular energy-sensing system, as assessed from the maintained phosphorylation state of AMPK. Inhibition of FAO at the level of mitochondrial acylcarnitine uptake restored OSGT but not ISGT. Seemingly paradoxically, further stimulation of FAO with PPARα or PPARδ agonists also restored OSGT but not ISGT. Together, these results suggest that inhibition of OSGT occurs downstream of energy gauging and is caused by some intermediate(s) of fatty acid oxidation, which does not appear to be acylcarnitines. The results indicate that the mechanisms underlying FFA-mediated inhibition of ISGT and OSGT differ remarkably.
Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice
Authors: Lizunov Vladimir A. , Stenkula Karin G. , Lisinski Ivonne , Gavrilova Oksana , Yver Dena R. , Chadt Alexandra , Al-Hasani Hadi , Zimmerberg Joshua , Cushman Samuel W.
Published: February 2012

Insulin regulates glucose uptake into fat and muscle by modulating the subcellular distribution of GLUT4 between the cell surface and intracellular compartments. However, quantification of these translocation processes in muscle by classical subcellular fractionation techniques is confounded by contaminating microfibrillar protein; dynamic studies at the molecular level are almost impossible. In this study, we introduce a muscle-specific transgenic mouse model in which HA-GLUT4-GFP is expressed under the control of the MCK promoter. HA-GLUT4-GFP was found to translocate to the plasma membrane and T-tubules after insulin stimulation, thus mimicking endogenous GLUT4. To investigate the dynamics of GLUT4 trafficking in skeletal muscle, we quantified vesicles containing HA-GLUT4-GFP near the sarcolemma and T-tubules and analyzed insulin-stimulated exocytosis at the single vesicle level by total internal reflection fluorescence and confocal microscopy. We found that only 10% of the intracellular GLUT4 pool comprised mobile vesicles, whereas most of the GLUT4 structures remained stationary or tethered at the sarcolemma or T-tubules. In fact, most of the insulin-stimulated exocytosis emanated from pretethered vesicles, whereas the small pool of mobile GLUT4 vesicles was not significantly affected by insulin. Our data strongly suggest that the mobile pool of GLUT4 vesicles is not a major site of insulin action but rather locally distributed. Most likely, pretethered GLUT4 structures are responsible for the initial phase of insulin-stimulated exocytosis.
Inhibition and Termination of Physiological Responses by GTPase Activating Proteins
Authors: Ligeti Erzsébet , Welti Stefan , Scheffzek Klaus
Published: February 2012

Physiological processes are strictly organized in space and time. However, in cell physiology research, more attention is given to the question of space rather than to time. To function as a signal, environmental changes must be restricted in time; they need not only be initiated but also terminated. In this review, we concentrate on the role of one specific protein family involved in biological signal termination. GTPase activating proteins (GAPs) accelerate the endogenously low GTP hydrolysis rate of monomeric guanine nucleotide-binding proteins (GNBPs), limiting thereby their prevalence in the active, GTP-bound form. We discuss cases where defective or excessive GAP activity of specific proteins causes significant alteration in the function of the nervous, endocrine, and hemopoietic systems, or contributes to development of infections and tumors. Biochemical and genetic data as well as observations from human pathology support the notion that GAPs represent vital elements in the spatiotemporal fine tuning of physiological processes.
Dyspnea Caused by Atlantoaxial Subluxation in a Patient with Rheumatoid Arthritis
Authors: Lin Hsin-Yi , Chen Chien-Chih , Lee Yi-Kung , Su Yung-Cheng
Published: February 2012

Atlantoaxial subluxation is a well-known but poorly recognized disease in rheumatoid patients. We report a patient with rheumatoid arthritis whose chief complaint was dyspnea on arrival to the emergency department (ED). After further investigation, spinal cord compression caused by atlantoaxial subluxation was diagnosed. This is an uncommon but important case that ED physicians should be aware of.
Electric-Field-Directed Self-Assembly of Active Enzyme-Nanoparticle Structures
Authors: Hsiao Alexander P. , Heller Michael J.
Published: February 2012

A method is presented for the electric-field-directed self-assembly of higher-order structures composed of alternating layers of biotin nanoparticles and streptavidin-/avidin-conjugated enzymes carried out on a microelectrode array device. Enzymes included in the study were glucose oxidase (GOx), horseradish peroxidase (HRP), and alkaline phosphatase (AP); all of which could be used to form a light-emitting microscale glucose sensor. Directed assembly included fabricating multilayer structures with 200 nm or 40 nm GOx-avidin-biotin nanoparticles, with AP-streptavidin-biotin nanoparticles, and with HRP-streptavidin-biotin nanoparticles. Multilayered structures were also fabricated with alternate layering of HRP-streptavidin-biotin nanoparticles and GOx-avidin-biotin nanoparticles. Results showed that enzymatic activity was retained after the assembly process, indicating that substrates could still diffuse into the structures and that the electric-field-based fabrication process itself did not cause any significant loss of enzyme activity. These methods provide a solution to overcome the cumbersome passive layer-by-layer assembly methods to efficiently fabricate higher-order active biological and chemical hybrid structures that can be useful for creating novel biosensors and drug delivery nanostructures, as well as for diagnostic applications.
Correlation between the Magnetoresistance, IR Magnetoreflectance, and Spin-Dependent Characteristics of Multilayer Magnetic Films
Authors: Kravets V. G.
Published: February 2012

We present the experimental results on magnetorefractive effect (MRE) in ferromagnetic metal-metal and metal-insulator multilayer films of different composition and different type of magnetoresistive effects. The shape and magnitude of the MRE dependences are found to be very sensitive to the spin-dependent scattering parameters and the effective polarization of the electron density of state around the Fermi level. A study of an MRE in multilayered films is shown to be sufficient for direct extracting of the spin-dependent relaxation times of electron (for GMR-like samples) and energy dependence of the tunnel spin-polarization density of states near the Fermi level for layered TMR films. It is proposed to use the magnetorefractive effect as a noncontact probe of magnetoresistive effects in thin magnetic films through investigations of the field-dependent reflection behaviors of multilayered films in the IR region.
A Remark on Wavelet Bases in Weighted Spaces
Authors: Wojciechowska Agnieszka
Published: February 2012

The paper deals with unconditional wavelet bases in weighted spaces. Inhomogeneous wavelets of Daubechies type are considered. Necessary and sufficient conditions for weights are found for which the wavelet system is an unconditional basis in weighted spaces in dependence on .
A Two-Study Comparison of Clinical and MRI Markers of Transition from Mild Cognitive Impairment to Alzheimer’s Disease
Authors: Devanand D. P. , Liu Xinhua , Brown Patrick J. , Huey Edward D. , Stern Yaakov , Pelton Gregory H.
Published: February 2012

A published predictor model in a single-site cohort study (questionable dementia, QD) that contained episodic verbal memory (SRT total recall), informant report of function (FAQ), and MRI measures was tested using logistic regression and ROC analyses with comparable measures in a second multisite cohort study (Alzheimer’s Disease Neuroimaging Initiative, ADNI). There were 126 patients in QD and 282 patients in ADNI with MCI followed for 3 years. Within each sample, the differences in AUCs between the statistical models were very similar. Adding hippocampal and entorhinal cortex volumes to the model containing AVLT/SRT, FAQ, age and MMSE increased the area under the curve (AUC) in ADNI but not QD, with sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%. Conversely, adding episodic verbal memory (SRT/AVLT) and FAQ to the model containing age, Mini Mental State Exam (MMSE), hippocampal and entorhinal cortex volumes increased the AUC in ADNI and QD, with sensitivity increasing by 17% in ADNI and 10% in QD for 80% specificity. The predictor models showed similar differences from each other in both studies, supporting independent validation. MRI hippocampal and entorhinal cortex volumes showed limited added predictive utility to memory and function measures.
Structure of Colloidal Flocs in relation to the Dynamic Properties of Unstable Suspension
Authors: Adachi Yasuhisa , Kobayashi Azusa , Kobayashi Motoyoshi
Published: February 2012

Dynamic behaviors of unstable colloidal dispersions are reviewed in terms of floc formation. Geometrical structure of flocs in terms of chemical conditions and formation mechanics is a key to predict macroscopic transportation properties. The rate of sedimentation and rheological properties can be described with the help of fractal dimension (D) that is the function of the number of contacts between clusters (Nc). It is also well known that the application of water soluble polymers and polyelectrolytes, which are usually used as a conditioner or flocculants in colloidal dispersions, critically affects the process of flocculation. The resulted floc structure is also influenced by the application of polymer. In order to reveal the roles of the polymers, the elementary rate process of polymer reaching to colloidal interface and subsequent reconformation process into more stable adsorption state are needed to be analyzed. The properties of permeable flocs and adsorbed polymer (polyelectrolyte) layers formed on the colloidal surfaces remain to be worked out in relation to inhomogeneous porous structure and electrokinetics in the future.
Against Lung Cancer Cells: To Be, or Not to Be, That Is the Problem
Authors: Okumura Naoko , Yoshida Hitomi , Kitagishi Yasuko , Nishimura Yuri , Iseki Shio , Matsuda Satoru
Published: February 2012

Tobacco smoke and radioactive radon gas impose a high risk for lung cancer. The radon-derived ionizing radiation and some components of cigarette smoke induce oxidative stress by generating reactive oxygen species (ROS). Respiratory lung cells are subject to the ROS that causes DNA breaks, which subsequently bring about DNA mutagenesis and are intimately linked with carcinogenesis. The damaged cells by oxidative stress are often destroyed through the active apoptotic pathway. However, the ROS also perform critical signaling functions in stress responses, cell survival, and cell proliferation. Some molecules enhance radiation-induced tumor cell killing via the reduction in DNA repair levels. Hence the DNA repair levels may be a novel therapeutic modality in overcoming drug resistance in lung cancer. Either survival or apoptosis, which is determined by the balance between DNA damage and DNA repair levels, may lender the major problems in cancer therapy. The purpose of this paper is to take a closer look at risk factor and at therapy modulation factor in lung cancer relevant to the ROS.
Lipid-Laden Alveolar Macrophages and pH Monitoring in Gastroesophageal Reflux-Related Respiratory Symptoms
Authors: Kitz R. , Boehles H. J. , Rosewich M. , Rose M. A.
Published: February 2012

Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER). This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL). Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed.
Hierarchical Matrices Method and Its Application in Electromagnetic Integral Equations
Authors: Guo Han , Hu Jun , Shao Hanru , Nie Zaiping
Published: February 2012

Hierarchical (H-) matrices method is a general mathematical framework providing a highly compact representation and efficient numerical arithmetic. When applied in integral-equation- (IE-) based computational electromagnetics,H-matrices can be regarded as a fast algorithm; therefore, both the CPU time and memory requirement are reduced significantly. Its kernel independent feature also makes it suitable for any kind of integral equation. To solveH-matrices system, Krylov iteration methods can be employed with appropriate preconditioners, and direct solvers based on the hierarchical structure ofH-matrices are also available along with high efficiency and accuracy, which is a unique advantage compared to other fast algorithms. In this paper, a novel sparse approximate inverse (SAI) preconditioner in multilevel fashion is proposed to accelerate the convergence rate of Krylov iterations for solvingH-matrices system in electromagnetic applications, and a group of parallel fast direct solvers are developed for dealing with multiple right-hand-side cases. Finally, numerical experiments are given to demonstrate the advantages of the proposed multilevel preconditioner compared to conventional “single level” preconditioners and the practicability of the fast direct solvers for arbitrary complex structures.
Antifungal and Antioxidant Activities of Pyrrolidone Thiosemicarbazone Complexes
Authors: Al-Amiery Ahmed A. , Kadhum Abdul Amir H. , Mohamad Abu Bakar
Published: February 2012

Metal complexes of (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L) with Cu(II), Co(II), and Ni(II) chlorides were tested against selected types of fungi and were found to have significant antifungal activities. The free-radical-scavenging ability of the metal complexes was determined by their interaction with the stable free radical 2,2′′-diphenyl-1-picrylhydrazyl, and all the compounds showed encouraging antioxidant activities. DFT calculations of the Cu complex were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms.
Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease
Authors: Constantin Myrna , Choi Alexander J. S. , Cloonan Suzanne M. , Ryter Stefan W.
Published: February 2012

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IXα. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease.
Giant Diaphragmatic Angiosarcoma of Adult: A Case Report and Review of Literature
Authors: Ren Tao , Chen Xue-qian
Published: February 2012

Angiosarcoma is a rare vascular malignant soft tissue tumor, with highly malignant, invasive, and multifocal characteristics of biology, which is prone to local recurrence and distant metastasis, so the prognosis is extremely poor. It rarely involves the diaphragm. We present the case of an adult patient who had a primary giant angiosarcoma of the left-sided diaphragm.
A Versatile Polymer Micelle Drug Delivery System for Encapsulation and In Vivo Stabilization of Hydrophobic Anticancer Drugs
Authors: Rios-Doria Jonathan , Carie Adam , Costich Tara , Burke Brian , Skaff Habib , Panicucci Riccardo , Sill Kevin
Published: February 2012

Chemotherapeutic drugs are widely used for the treatment of cancer; however, use of these drugs is often associated with patient toxicity and poor tumor delivery. Micellar drug carriers offer a promising approach for formulating and achieving improved delivery of hydrophobic chemotherapeutic drugs; however, conventional micelles do not have long-term stability in complex biological environments such as plasma. To address this problem, a novel triblock copolymer has been developed to encapsulate several different hydrophobic drugs into stable polymer micelles. These micelles have been engineered to be stable at low concentrations even in complex biological fluids, and to release cargo in response to low pH environments, such as in the tumor microenvironment or in tumor cell endosomes. The particle sizes of drugs encapsulated ranged between 30–80 nm, with no relationship to the hydrophobicity of the drug. Stabilization of the micelles below the critical micelle concentration was demonstrated using a pH-reversible crosslinking mechanism, with proof-of-concept demonstrated in both in vitro and in vivo models. Described herein is polymer micelle drug delivery system that enables encapsulation and stabilization of a wide variety of chemotherapeutic drugs in a single platform.
Making Personalized Cancer Medicine a Reality: Challenges and Opportunities in the Development of Biomarkers and Companion Diagnostics
Authors: Parkinson David R. , Johnson Bruce E. , Sledge George W.
Published: February 2012

The origins of this article stem from discussions at the American Association for Cancer Research Clinical and Translational Cancer Research Think Tank meeting held in San Francisco in early 2010. This article synthesizes the opinions and issues considered at that meeting, and discusses many of the important events that have since occurred in the field of personalized cancer medicine. Although investigators continue to make progress in better linking individual patient biology with risk determination, diagnosis, prognosis, and treatment selection, the pace of this progress continues to be limited by many of the issues identified in the meeting. Clin Cancer Res; 18(3); 619–24. ©2012 AACR.
Impact of Genomics on Personalized Cancer Medicine
Authors: Arteaga Carlos L. , Baselga José
Published: February 2012

Recent advances in tumor genetics and drug development have led to the generation of a wealth of anticancer targeted therapies. A few recent examples indicate that these drugs are mainly, if not exclusively, active against tumors of a particular genotype that can be identified by a diagnostic test, usually by detecting a somatic alteration in the tumor DNA. However, for the majority of targeted therapies in development, there are still no clinical tools to determine which patients are most likely to benefit or, alternatively, be resistant de novo to these novel agents or drug combinations. Clin Cancer Res; 18(3); 612–8. ©2011 AACR.
Preclinical Pharmacology of AZD5363, an Inhibitor of AKT: Pharmacodynamics, Antitumor Activity, and Correlation of Monotherapy Activity with Genetic Background
Authors: Davies Barry R. , Greenwood Hannah , Dudley Phillippa , Crafter Claire , Yu De-Hua , Zhang Jingchuan , Li Jing , Gao Beirong , Ji Qunsheng , Maynard Juliana , Ricketts Sally-Ann , Cross Darren , Cosulich Sabina , Chresta Christine C. , Page Ken , Yates James , Lane Clare , Watson Rebecca , Luke Richard , Ogilvie Donald , Pass Martin
Published: February 2012

AKT is a key node in the most frequently deregulated signaling network in human cancer. AZD5363, a novel pyrrolopyrimidine-derived compound, inhibited all AKT isoforms with a potency of 10 nmol/L or less and inhibited phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μmol/L. AZD5363 monotherapy inhibited the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of 3 μmol/L or less. Cell lines derived from breast cancers showed the highest frequency of sensitivity. There was a significant relationship between the presence of PIK3CA and/or PTEN mutations and sensitivity to AZD5363 and between RAS mutations and resistance. Oral dosing of AZD5363 to nude mice caused dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts (PRAS40 phosphorylation EC50 ∼ 0.1 μmol/L total plasma exposure), reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-d-glucose (18F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 caused dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhanced the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. It is concluded that AZD5363 is a potent inhibitor of AKT with pharmacodynamic activity in vivo, has potential to treat a range of solid and hematologic tumors as monotherapy or a combinatorial agent, and has potential for personalized medicine based on the genetic status of PIK3CA, PTEN, and RAS. AZD5363 is currently in phase I clinical trials. Mol Cancer Ther; 11(4); 873–87. ©2012 AACR.
Self- and Informant Ratings of Personality in Mild Cognitive Impairment, Reviewed
Authors: Ausén Birgitta , Edman Gunnar , Almkvist Ove , Bogdanovic Nenad
Published: February 2012

Aims: To examine the degree of agreement between self- and informant ratings of personality in relation to cognitive function in patients with mild cognitive impairment (MCI), subjective cognitive impairment (SCI) and healthy controls (HC). Methods: Thirty-two patients and informants with MCI, 23 with SCI and 22 HC completed the Swedish universities Scales of Personality (SSP). Correlations and incongruence between self- and informant ratings were calculated. The Mini Mental State Examination (MMSE) was used to assess cognitive function. Results: The correlations between self- and informant ratings were fair-to-moderate on a majority of SSP scales and significant in 44%. The incongruence between patients and informants was significantly larger in MCI than in HC across SSP scales. There was a significant negative correlation between the incongruence index and the MMSE for all subjects. Conclusions: Self-informant agreement on ratings of patients’ personality was reasonable. Incongruence between patients and their informants was associated with MCI but not SCI or HC. Disagreement between patients and informants indicates cognitive impairment.
Dual Effects of Statins on Aβ Metabolism: Upregulation of the Degradation of APP-CTF and Aβ Clearance
Authors: Sato Naoyuki , Shinohara Mitsuru , Rakugi Hiromi , Morishita Ryuichi
Published: February 2012

Background/Aims: Retrospective cohort studies have suggested that statin users have a lower prevalence of dementia. On the other hand, a randomized controlled study failed to show beneficial effects on the cognitive decline in Alzheimer’s disease (AD). However, a prospective cohort study demonstrated that users of statins had a lower incidence of AD. One possible interpretation might be that statins could prevent or delay the onset of AD, but not slow cognitive decline once the disease has set in. Given that statins could prevent or delay the onset of AD, what is the responsible mechanism? Methods: We investigated the effect of fluvastatin on Aβ metabolism at a clinically relevant dose in mice. Results: Fluvastatin reduced the brain Aβ level by increased trafficking of the carboxyl terminal fragment of the amyloid precursor protein (APP-CTF), which was mediated by inhibition of protein isoprenylation. Moreover, the statin reduced the brain Aβ level through enhanced Aβ clearance mediated by upregulation of low-density lipoprotein receptor-related protein 1 (LRP-1) expression. The statin increased LRP-1 expression, mediated by inhibition of protein isoprenylation. Conclusion: Statins might prevent the onset of AD through reduced Aβ production by enhancement of APP-CTF degradation and/or upregulation of Aβ clearance. We also showed that promotion of APP-CTF degradation and upregulation of Aβ clearance could be modified by a drug, suggesting possible mechanistic targets for disease-modifying drugs.
Activation of the Unfolded Protein Response Is an Early Event in Alzheimer’s and Parkinson’s Disease
Authors: Hoozemans Jeroen J.M. , van Haastert Elise S. , Nijholt Diana A.T. , Rozemuller Annemieke J.M. , Scheper Wiep
Published: February 2012

Background: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation and aggregation of misfolded proteins. Disturbed homeostasis in the endoplasmic reticulum leads to accumulation of misfolded proteins, which triggers a stress response called the unfolded protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins. Objective: In this paper, we will briefly review the early involvement of the UPR in the pathology of AD and PD. Methods: Expression of UPR activation markers was analyzed in human brain tissue using immunohistochemistry and Western blot analysis. Results: Neuropathological studies demonstrate that UPR activation markers are increased in neurons in AD and PD. In AD, UPR activation markers are observed in neurons with diffuse staining of phosphorylated tau protein. In PD, increased immunoreactivity for UPR activation markers is detected in neuromelanin containing dopaminergic neurons of the substantia nigra, which colocalize with diffuse α-synuclein staining. Conclusion: UPR activation is closely associated with the first stages of accumulation and aggregation of the toxic proteins involved in AD and PD. Studies of postmortem brain tissue indicate that UPR activation is an early event in neurodegeneration.
Neuroinflammation and Blood-Brain Barrier Changes in Capillary Amyloid Angiopathy
Authors: Carrano Anna , Hoozemans Jeroen J.M. , van der Vies Saskia M. , van Horssen Jack , de Vries Helga E. , Rozemuller Annemieke J.M.
Published: February 2012

Introduction: β-Amyloid (Aβ) accumulation in cortical capillaries is a variant of cerebral amyloid angiopathy (CAA) referred to as capillary CAA (capCAA). capCAA is associated with a neuroinflammatory response. In vitro studies indicate that Aβ induces reactive oxygen species (ROS) production, mainly generated through NADPH oxidase (NOX), by activated microglia. ROS in turn can induce altered expression of tight junctions (TJ), which are essential for blood-brain barrier (BBB) function. Whether the function of the BBB is affected in the brains of Alzheimer’s disease (AD) patients with comorbid capCAA remains elusive. Cases with capCAA and no other AD-related changes allow studying capCAA-associated BBB alterations independent of AD pathology. Aim: In this study, we have investigated BBB alterations in capCAA and addressed the role of the neuroinflammatory response. Methods: Human postmortem brain tissue with capCAA was analyzed by immunohistochemical staining. Results: In this study, we show for the first time a dramatic loss of TJ proteins claudin-5, occludin and ZO-1 in Aβ-laden capillaries. In addition, affected capillaries are associated with clusters of NOX-2-positive activated microglia. Disrupted BBB function was observed by increased presence of fibrinogen around the affected capillaries. Conclusions: Our data provide support for the early observation that neuroinflammatory response is involved in the altered expression of TJs in endothelial cells and loss of BBB integrity in capCAA.
Tachyphylaxis to the Sumatriptan-Induced Contractile Effect in the Human Uterine Artery but Not in Human Cerebral Blood Vessels: Pharmacological Demonstration of the 5-HT1B Receptor Functionality Loss
Authors: Silva Sónia A. , Ribeiro Carlos A. Fontes
Published: February 2012

The in vitro contractile response of the human uterine artery to sumatriptan was compared to that of human cerebral blood vessels. Artery rings were prepared for isometric contraction. Tachyphylaxis to the triptan-induced vascular contraction was observed in the uterine artery, but not in basilar and middle cerebral arteries. To evaluate 5-HT1 receptor subtypes functionality, concentration-response curves to sumatriptan were performed at 0 and 24 h after uterine artery isolation. Both 10 µmol/l cyanopindolol and 63 nmol/l SB 224,289 (5-HT1B receptor antagonists) significantly antagonized the contractile response induced by sumatriptan at 0 h but not after 24 h of uterine artery isolation. The 5-HT1B/1D receptor antagonist BRL 15,572 at 10 µmol/l significantly antagonized the sumatriptan contractile response at both experimental conditions. We conclude that the tachyphylaxis to sumatriptan observed in the non-cerebral blood vessels, and not in the cerebral ones, may be due to loss of functionality of the 5-HT1B receptor subtype, increasing the safety of triptans.
Differential Treatment Regimen-Related Effects of HU210 on CB1 and D2-Like Receptor Functionality in the Rat Basal Ganglia
Authors: Nguyen Vu H. , Wang Hongqin , Verdurand Mathieu , Zavitsanou Katerina
Published: February 2012

Background/Aims: Functional linkages between the cannabinoid CB1 and the dopaminergic systems have been reported although the observations and the mechanisms hypothesizing their interactions at the G protein-coupled receptor (GPCR) functionality level are conflicting. Methods: Administration of a potent cannabinoid agonist, HU210, at various doses (25–100 µg/kg) and treatment regimens (1- to 14-day treatment) in rats was carried out to investigate the effect of HU210 treatment on the CB1 and D2-like agonist-mediated GPCR activation. Results: The desensitizations (reduced coupling) of both D2 agonist- and CB1 agonist-mediated GPCR activation was found to be treatment duration dependent and region specific, suggesting implication of receptor tolerance and adaptation due to the cannabinoid treatment. The effect of HU210 on the CB1 agonist-mediated GPCR desensitization in all treatment groups was not dose dependent. Conclusions: The desensitization of D2-like receptors found after a cannabinoid treatment in this study strengthens the evidence that the two neurotransmitter systems interact at the intercellular level; this interaction might occur via multiple mechanisms, which also vary according to region.
Protective Effect of Amlodipine on Rat Bone Tissue after Orchidectomy
Authors: Gradosova Iveta , Zivna Helena , Palicka Vladimir , Hubena Sona , Svejkovska Klara , Zivny Pavel
Published: February 2012

Aim: Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. Methods: Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. Results: Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. Conclusions: Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis.
Review of Cerebral Microangiopathy and Alzheimer’s Disease: Relation between White Matter Hyperintensities and Microbleeds
Authors: Hommet C. , Mondon K. , Constans T. , Beaufils E. , Desmidt T. , Camus V. , Cottier J.P.
Published: February 2012

Although Alzheimer’s disease (AD) is basically considered to be a neurodegenerative disorder, cerebrovascular disease is also involved. The role of vascular risk factors and vascular disease in the progression of AD remains incompletely understood. With the development of brain MRI, it is now possible to detect small-vessel disease, whose prevalence and severity increase with age. The first types of small-vessel disease to be described were white matter hyperintensities (WMHs). More recently, small areas of signal loss on T2*-weighted images, also called microbleeds (MBs), have been reported. Cerebral MBs are focal deposits of hemosiderin that indicate prior microhemorrhages around small vessels, related to either ruptured atherosclerotic microvessels or amyloid angiopathy. Consequently, using brain MRI for the detection of microangiopathy may prove useful to improve our understanding of the impact of the vascular burden in AD pathology. The relationship between microangiopathy and the clinical course of AD or the conversion of mild cognitive impairment to AD remains questionable in terms of cognitive or affective symptoms, particularly if we consider MBs.