bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidation of the Rotavirus NSP4-Caveolin-1 and -Cholesterol Interactions Using Synthetic Peptides
Authors: Schroeder Megan E. , Hostetler Heather A. , Schroeder Friedhelm , Ball Judith M.
Published: March 2012

Rotavirus (RV) NSP4, the first described viral enterotoxin, is a multifunctional glycoprotein that contributes to viral pathogenesis, morphogenesis, and replication. NSP4 binds both termini of caveolin-1 and is isolated from caveolae fractions that are rich in anionic phospholipids and cholesterol. These interactions indicate that cholesterol/caveolin-1 plays a role in NSP4 transport to the cell surface, which is essential to its enterotoxic activity. Synthetic peptides were utilized to identify target(s) of intervention by exploring the NSP4-caveolin-1 and -cholesterol interactions. NSP4112–140that overlaps the caveolin-1 binding domain and a cholesterol recognition amino acid consensus (CRAC) motif and both termini of caveolin-1 (N-caveolin-12–20,  19–40and C-caveolin-1161–180) were synthesized. Direct fluorescence-binding assays were employed to determine binding affinities of the NSP4-caveolin-1 peptides and cholesterol. Intracellular cholesterol alteration revealed a redistribution of NSP4 and disintegration of viroplasms. These data further imply interruption of NSP4112–140-N-caveolin-119–40and cholesterol interactions may block NSP4 intracellular transport, hence enterotoxicity.
Sex Differences in Facial, Prosodic, and Social Context Emotional Recognition in Early-Onset Schizophrenia
Authors: Ramos-Loyo Julieta , Mora-Reynoso Leonor , Sánchez-Loyo Luis Miguel , Medina-Hernández Virginia
Published: March 2012

The purpose of the present study was to determine sex differences in facial, prosodic, and social context emotional recognition in schizophrenia (SCH). Thirty-eight patients (SCH, 20 females) and 38 healthy controls (CON, 20 females) participated in the study. Clinical scales (BPRS and PANSS) and an Affective States Scale were applied, as well as tasks to evaluate facial, prosodic, and within a social context emotional recognition. SCH showed lower accuracy and longer response times than CON, but no significant sex differences were observed in either facial or prosody recognition. In social context emotions, however, females showed higher empathy than males with respect to happiness in both groups. SCH reported being more identified with sad films than CON and females more with fear than males. The results of this study confirm the deficits of emotional recognition in male and female patients with schizophrenia compared to healthy subjects. Sex differences were detected in relation to social context emotions and facial and prosodic recognition depending on age.
Effects of Artificial Flooding for Hydroelectric Development on the Population ofMansonia humeralis(Diptera: Culicidae) in the Paraná River, São Paulo, Brazil
Authors: Paula Marcia Bicudo de , Gomes Almério de Castro , Natal Delsio , Duarte Ana Maria Ribeiro de Castro , Mucci Luís Filipe
Published: February 2012

The closure of two phases of the dam at the Porto Primavera Hydroelectric Plant on the Paraná River flooded a flawed system located in the Municipality of Presidente Epitácio, São Paulo state, favoring the proliferation of aquatic weeds. This study aimed to observe the population ofMansonia humeralisin the area, monitoring the richness, diversity, and dominance of this species both before and during different phases of reservoir flooding as well as evaluate its possible consequences concerning human and animal contact. Adult mosquitoes were collected monthly in the following periods: at the original level, after the first flood, and after the maximum level had been reached between 1997 and 2002. Collection methods used were an aspirator, a Shannon trap, and the Human Attractive Technique. A total of 30,723 mosquitoes were collected,Ma. humeralisaccounting for 3.1% in the preflood phase, 59.6% in the intermediate, and 53.8% at maximum level. This species is relevant to public health, since the prospect of continued contact betweenMa. humeralisand the human population enhances the dam’s importance in the production of nuisance mosquitoes, possibly facilitating the transmission of arboviruses. Local authorities should continue to monitor culicid activity through sustainable entomological surveillance.
A Predator‐Prey Model with Functional Response and Stage Structure for Prey
Authors: Sun Xiao-Ke , Huo Hai-Feng , Zhang Xiao-Bing
Published: March 2012

A predator‐prey system with Holling type II functional response and stage structure for prey is presented. The local and global stability are studied by analyzing the associated characteristic transcendental equation and using comparison theorem. The existence of a Hopf bifurcation at the positive equilibrium is also studied. Some numerical simulations are also given to illustrate our results.
A Jointly Optimized VariableM-QAM and Power Allocation Scheme for Image Transmission
Authors: El-Tarhuni Mohamed , Hassan Mohamed , Bin Sediq Akram
Published: February 2012

We introduce an improved image transmission scheme over wireless channels with flat Rayleigh fading. The proposed scheme jointly optimizes bit power and modulation level to maximize the peak signal-to-noise ratio (PSNR) of the reconstructed image and hence improves the perceptual quality of the received image. In this optimization process, the significance of bits with regard to the overall quality of the image is exploited. The optimality of the proposed algorithm is demonstrated using the Lagrange method and verified through an iterative offline exhaustive search algorithm. For practical implementation, a look-up table is used at the transmitter for assigning the bit power and modulation level to each bit stream according to the received signal-to-noise ratio (SNR) observed at the receiver. The proposed scheme has low complexity since the look-up table is computed offline, only once, and used for any image which makes it suitable for devices with limited processing capability. Analytical and simulation results show that the proposed scheme with jointly optimized bit power and variable modulation level provides an improvement in PSNR of about 10 to 20 dB over fixed power fixed modulation (16-QAM). A further reduction in complexity is achieved by using the average signal-to-noise ratio rather than the instantaneous SNR in selecting the system parameters.
Managing the Morbidity Associated with Respiratory Viral Infections in Children with Congenital Heart Disease
Authors: Geskey Joseph M. , Cyran Stephen E.
Published: February 2012

Children with congenital heart disease (CHD) are at risk for increased morbidity from viral lower respiratory tract infections because of anatomical cardiac lesions than can worsen an already compromised respiratory status. Respiratory syncytial virus (RSV) remains an important pathogen in contributing toward the morbidity in this population. Although the acute treatment of RSV largely remains supportive, the development of monoclonal antibodies, such as palivuzumab, has reduced the RSV-related hospitalization rate in children with CHD. This review highlights the specific cardiac complications of RSV infection, the acute treatment of bronchiolitis in patients with CHD, and the search for new therapies against RSV, including an effective vaccine, because of the high cost associated with immunoprophylaxis and its lack of reducing RSV-related mortality.
Ethanol Electrooxidation on Pt with Lanthanum Oxide as Cocatalyst in a DAFC
Authors: Santoro T. A. B. , Neto A. Oliveira , Forbicini C. A. L. G. de O. , Linardi M. , Rodríguez J. L. , Pastor E.
Published: March 2012

Electrocatalytic activity toward ethanol electrooxidation of Pt particles in PtLa/C catalysts with different Pt : La ratios has been studied with different electrochemical and spectroscopic techniques, and the results were compared to those of Pt/C catalyst. Significant enhancement in the electrocatalytic activity has been achieved by depositing the Pt particles with lanthanum oxides/hydroxides using an alcohol reduction method. Compared to Pt/C catalyst, PtLa/C materials exhibit a lower onset potential and a higher electron-transfer rate constant for the investigated reaction. These studies illustrate the possibility of utilizing Pt/C with La oxides/hidroxides as electrocatalyst for direct alcohol fuel cells (DAFCs).
A Lightweight Lap Time Measurement System for Alpine Ski Sport Using a TDMA-Based Linear Wireless Sensor Network
Authors: Lee Hyung-Bong , Kwon Ki-Hyeon , Park Lae-Jeong , Chung Tae-Yun , Wu Qishi
Published: February 2012

In Alpine ski sport, traditional lap time measurement systems record a skier's departure and arrival using time-of-day timers through wires, which is not cost effective in unofficial or training games. This paper develops a lightweight lap time measurement system using a wireless sensor network, which employs a practical TDMA-based linear wireless sensor network protocol for multihop communications in long strap-shaped environments where sensor nodes are linearly deployed. We evaluate the performance of this protocol through the implementation and deployment of the lap time measurement system. The experimental results show that the proposed protocol transmits data at a success rate of 99.66% and maintains the time synchronization errors between two adjacent nodes within 183  μs without using any other time synchronization protocols. In an experimental deployment for a 1.5 km ski slope covered by 31 nodes, the system provides lap time measurements with a measurement error of 1.255 ms, which satisfies the official measurement error of 5.0 ms.
Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with DisseminatedMycobacterium avium-intracellulareInfection
Authors: Ablanedo-Terrazas Yuria , Ormsby Christopher E. , Reyes-Terán Gustavo
Published: March 2012

ActinomycesandMycobacterium avium-intracellulareare facultative intracellular organisms, members of the bacterial order actinomycetales. AlthoughActinomycescan behave as copathogen when anatomic barriers are compromised, its coinfection withMycobacterium avium-intracellularehas not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject.
Convex Image Segmentation Model Based on Local and Global Intensity Fitting Energy and Split Bregman Method
Authors: Yang Yunyun , Wu Boying
Published: March 2012

We propose a convex image segmentation model in a variational level set formulation. Both the local information and the global information are taken into consideration to get better segmentation results. We first propose a globally convex energy functional to combine the local and global intensity fitting terms. The proposed energy functional is then modified by adding an edge detector to force the active contour to the boundary more easily. We then apply the split Bregman method to minimize the proposed energy functional efficiently. By using a weight function that varies with location of the image, the proposed model can balance the weights between the local and global fitting terms dynamically. We have applied the proposed model to synthetic and real images with desirable results. Comparison with
other models also demonstrates the accuracy and superiority of the proposed model.
Gas Compressor Station Economic Optimization
Authors: Kurz Rainer , Lubomirsky Matt , Brun Klaus
Published: March 2012

When considering gas compressor stations for pipeline projects, the economic success of the entire operation depends to a significant extent on the operation of the compressors involved. In this paper, the basic factors contributing to the economics are outlined, with particular emphasis on the interaction between the pipeline and the compressor station. Typical scenarios are described, highlighting the fact that pipeline operation has to take into account variations in load.
A Classification of a Totally Umbilical SlantSubmanifold of Cosymplectic Manifolds
Authors: Uddin Siraj , Ozel Cenap , Khan Viqar Azam
Published: February 2012

We study slant submanifolds of a cosymplectic manifold.
It is shown that a totally umbilical slant submanifold M of a cosymplectic
manifold is either an anti‐invariant submanifold or a 1−dimensional
submanifold. We show that every totally umbilical proper slant submanifold
of a cosymplectic manifold is totally geodesic.
H3e/H4e Ratio in Olivines from Linosa, Ustica, and Pantelleria Islands (Southern Italy)
Authors: Fourré Elise , Allard Patrick , Jean-Baptiste Philippe , Cellura Dario , Parello Francesco
Published: March 2012

We report helium isotope data for 0.03–1 Ma olivine-bearing basaltic hawaiites from three volcanoes of the southern Italy magmatic province (Ustica, Pantelleria, and Linosa Islands). Homogenous H3e/H4e ratios (range: 7.3–7.6 Ra) for the three islands, and their similarity with the ratio of modern volcanic gases on Pantelleria, indicate a common magmatic end-member. In particular, Ustica (7.6±0.2 Ra) clearly differs from the nearby Aeolian Islands Arc volcanism, despite its location on the Tyrrhenian side of the plate boundary. Although limited in size, our data set complements the large existing database for helium isotope in southern Italy and adds further constraints upon the spatial extent of intraplate alkaline volcanism in southern Mediterranea. As already discussed by others, the He-Pb isotopic signature of this magmatic province indicates a derivation from a mantle diapir of a OIB-type that is partially diluted by the depleted upper mantle (MORB mantle) at its periphery.
Magnesium and Vascular Changes in Hypertension
Authors: Cunha Ana Rosa , Umbelino Bianca , Correia Margarida L. , Neves Mario Fritsch
Published: February 2012

Many factors have been implicated in the pathogenesis of hypertension, including changes in intracellular concentrations of calcium, sodium, potassium, and magnesium. There is a significant inverse correlation between serum magnesium and incidence of cardiovascular diseases. Magnesium is a mineral with important functions in the body such as antiarrhythmic effect, actions in vascular tone, contractility, glucose metabolism, and insulin homeostasis. In addition, lower concentrations of magnesium are associated with oxidative stress, proinflammatory state, endothelial dysfunction, platelet aggregation, insulin resistance, and hyperglycemia. The conflicting results of studies evaluating the effects of magnesium supplements on blood pressure and other cardiovascular outcomes indicate that the action of magnesium in the vascular system is present but not yet established. Therefore, this mineral supplementation is not indicated as part of antihypertensive treatment, and further studies are needed to better clarify the role of magnesium in the prevention and treatment of cardiovascular diseases.
Distribution‐Based Identification of Yield Coefficients in a Baker’s Yeast Bioprocess
Authors: Sendrescu Dorin
Published: March 2012

A distribution‐based identification procedure for estimation of yield coefficients in a baker’s yeast bioprocess is proposed. This procedure transforms a system of differential equations to a system of algebraic equations with respect to unknown parameters. The relation between the state variables is represented by functionals using techniques from distribution theory. A hierarchical structure of identification is used, which allows obtaining a linear algebraic system of equations in the unknown parameters. The coefficients of this algebraic system are functionals depending on the input and state variables evaluated through some test functions from distribution theory. First, only some state equations are evaluated throughout test functions to obtain a set of linear equations in parameters. The results of this first stage of identification are used to express other parameters by linear equations. The process is repeated until all parameters are identified. The performances of the method are analyzed by numerical simulations.
Challenges in the Management of HIV-Infected Malnourished Children in Sub-Saharan Africa
Authors: Trehan Indi , O'Hare Bernadette A. , Phiri Ajib , Heikens Geert Tom
Published: March 2012

Infection with HIV, and oftentimes coinfection with TB, complicates the care of severely malnourished children in sub-Saharan Africa. These superimposed infections challenge clinicians faced with a population of malnourished children for whose care evidence-based guidelines have not kept up. Even as the care of HIV-uninfected malnourished children has improved dramatically with the advent of community-based care and even as there are hopeful signs that the HIV epidemic may be stabilizing or ameliorating, significant gaps remain in the care of malnourished children with HIV. Here we summarize what is currently known, what remains unknown, and what remains challenging about how to treat severely malnourished children with HIV and TB.
Improving Streaming Capacity in Multi-Channel P2P VoD Systems via Intra-Channel and Cross-Channel Resource Allocation
Authors: He Yifeng , Guan Ling
Published: February 2012

Multi-channel Peer-to-Peer (P2P) Video-on-Demand (VoD) systems can be categorized intoindependent-channelP2P VoD systems andcorrelated-channelP2P VoD systems. Streaming capacity for a channel is defined as the maximal streaming rate that can be received by every user of the channel. In this paper, we study the streaming capacity problem in multi-channel P2P VoD systems. In an independent-channel P2P VoD system, there is no resource correlation among channels. Therefore, we can find the average streaming capacity for the independent-channel P2P VoD system by finding the streaming capacity for each individual channel, respectively. We propose a distributed algorithm to solve the streaming capacity problem for a single channel in an independent-channel P2P VoD system. The average streaming capacity for a correlated-channel P2P VoD system depends on both the intra-channel and cross-channel resource allocation. To better utilize the cross-channel resources, we first optimize the server upload allocation among channels to maximize the average streaming capacity and then propose cross-channel helpers to enable cross-channel sharing of peer upload bandwidths. We demonstrate in the simulations that the correlated-channel P2P VoD systems with both intra-channel and cross-channel resource allocation can obtain a higher average streaming capacity compared to the independent-channel P2P VoD systems with only intra-channel resource allocation.
Sonography of the Primary Cutaneous Melanoma: A Review
Authors: Wortsman Ximena
Published: March 2012

The diagnosis and management of primary cutaneous melanoma have traditionally relied on clinical and histological characteristics. Nevertheless, in recent years there has been a significant growth in the usage of ultrasound for studying the cutaneous layers. Thus, the present paper focuses on the primary lesion, its sonographic characteristics, the potential benefits of early imaging, and the new developments on the ultrasound field applied to cutaneous melanoma.
Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease
Authors: Ambade Aditya , Mandrekar Pranoti
Published: March 2012

Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative stress and inflammation and highlight signaling intermediates regulated by oxidative stress that provokes proinflammatory responses in alcoholic liver disease.
Enhancing Photocatalytic Performance through Tuning the Interfacial Process between -Assembled and Pt-Loaded Microspheres
Authors: Zhang Jun , Li Liping , Li Guangshe
Published: March 2012

This work reports on a simple two-step approach to rutile TiO2-assembled microspheres loaded by Pt with an aim to tune semiconductor-metal interfacial processes for enhancing the photocatalytic performance. Systematic sample characterizations and structural analysis indicate that Pt loading did not produce any significant influences on the lattice structure of TiO2-assembled microspheres. Instead, upon Pt loading, Schottky barrier was formed in the interfaces between microspheres and Pt nanoparticles, which inhabited efficiently the recombination of photo-generated electron-hole pairs essential for the photocatalytic activities. In addition, TiO2microspheres also showed a capacity of electrons storage and releasing as represented by a high dielectric constant, which increased the utility rate of photogenerated electrons. All these structural advantages contribute to the excellent photocatalytic activity under ultraviolet light irradiation. The interfacial process between microspheres and Pt nanoparticles was further tuned through adjusting the loading Pt content of metal Pt. As a consequence, the best photocatalytic activity on TiO2was obtained at 0.85 wt% Pt loading, above or below which photocatalytic activity was apparently decreased.
Corrosion Behaviour of Heat-Treated Aluminum-Magnesium Alloy in Chloride and EXCO Environments
Authors: Adeosun S. O. , Sekunowo O. I. , Balogun S. A. , Obiekea V. D.
Published: March 2012

Machines designed to operate in marine environment are generally vulnerable to failure by corrosion. It is therefore imperative that the corrosion susceptibility of such facilities is evaluated with a view to establishing mechanism for its mitigation. In this study, the corrosion behaviour of as-cast and retrogression-reagion (RRA) specimens of aluminum alloy containing 0.4–2.0 percent magnesium additions in NaCl, FeCl3, and EXCO solutions was investigated. The corrosion simulation processes involved gravimetric and electrochemical techniques. Results show substantial inducement of Mg2Si precipitates at a relatively higher magnesium addition, 1.2–2.0 percent, giving rise to increased attack. This phenomenon is predicated on the nature of the Mg2Si crystals being anodic relative to the alloy matrix which easily dissolved under attack by chemical constituents. Formation of Mg2Si intermetallic without corresponding appropriate oxides like SiO2and MgO, which protect the precipitates from galvanic coupling with the matrix, accentuates susceptibility to corrosion.
A Power‐Efficient Soft‐Output Detector for Spatial‐Multiplexing MIMO Communications
Authors: Wang Hsiao-Chi , Liu Tung-Lin , Wu Yuan-Wei , Ma Hsi-Pin
Published: March 2012

VLSI implementation of a configurable power‐efficient MIMO detector is proposed to support 4 × 4 spatial multiplexing and modulation from QPSK to 64‐QAM. A novel tree search algorithm is proposed to enable the detector to provide soft outputs and to be implemented in parallel and pipelined hardware architecture. The frame error rate (FER) of the detector approaches the quasi‐optimal sphere decoder, with 0.5‐dB degradation. Moreover, the proposed detector can operate at the optimal voltage under different configurations and detect/recover timing error at run time by a novel adaptive voltage scaling technique with double sampling circuitry. The proposed detector, using TSMC 0.18 μm single‐poly six‐metal CMOS process with a core area of 1.17 × 1.17 mm2, provides fixed throughput of 45 Mbps in 64‐QAM configuration, 120 Mbps in 16‐QAM configuration, and 60 Mbps in QPSK configuration. The normalized power efficiency of the design for 64‐QAM and 16‐QAM configurations is 1.56 Mbps/mW and 2.53 Mbps/mW, respectively. Compared with the conservative margin‐based design, the proposed design achieves a 48.8% power saving.
Closed Relative Trajectoriesfor Formation Flying with Single‐Input Control
Authors: Guerman Anna , Ovchinnikov Michael , Smirnov Georgi , Trofimov Sergey
Published: March 2012

We study the problem of formation shape control under the constraints on the thrust direction.
Formations composed of small satellites are usually subject to serious limitations for
power consumption, mass, and volume of the attitude and orbit control system (AOCS). If
the purpose of the formation flying mission does not require precise tracking of a given relative
trajectory, AOCS of satellites may be substantially simplified; however, the capacity of
AOCS to ensure a bounded or even periodic relative motion has to be studied first. We consider
a formation of two satellites; the deputy one is equipped with a passive attitude control
system that provides one‐axis stabilization and a propulsion system that consists of one or two
thrusters oriented along the stabilized axis. The relative motion of the satellites is modeled by
the Schweighart‐Sedwick linear equations taking into account the effect of J2 perturbations. We
prove that both in the case of passive magnetic attitude stabilization and spin stabilization for
all initial relative positions and velocities of satellites there exists a control guaranteeing their
periodic relative motion.
Mammary Ductal Carcinoma In Situ: A Fresh Look at Architectural Patterns
Authors: Scripcaru Gabriel , Zardawi Ibrahim M.
Published: February 2012

Mammary ductal carcinoma in-situ (DCIS), a malignant appearing lesion on cytological and histological grounds, is in fact a non-obligate precancer. DCIS is difficult to manage and is sometimes treated more aggressively than invasive carcinoma. Although most DCIS classifications take into account the architectural growth pattern, when it comes to architecture, the literature is full of contradictory information. We examined 289 breast cancers and found DCIS in 265 of the cases. The majority of the DCIS cases were seen in the setting of invasive cancer and only 9% of the cases represented pure DCIS with no invasive cancer. The DCIS commonly displayed a mixed pattern with micropapillary, cribriform and solid components with the micropapillary type being the rarest, occurring seldom on its own. A continuum of growth with a micropapillary pattern evolving into a cribriform type could be seen in some of the cases. This may explain some of the conflicting information, in the literature, regarding the different architectural types of DCIS. The comedo-pattern of necrosis could be seen in all types of DCIS. We therefore conclude that the study of the determinants of growth pattern in DCIS would be the key to unravelling the diverse, often non-concordant evidence one encounters in the literature.
The Cyclin-Dependent Kinase Inhibitor Flavopiridol Potentiates Doxorubicin Efficacy in Advanced Sarcomas: Preclinical Investigations and Results of a Phase I Dose-Escalation Clinical Trial
Authors: Luke Jason J. , D'Adamo David R. , Dickson Mark A. , Keohan Mary Louise , Carvajal Richard D. , Maki Robert G. , de Stanchina Elisa , Musi Elgilda , Singer Samuel , Schwartz Gary K.
Published: February 2012

Purpose: Dysregulated cyclin-dependent kinases are important to the growth of some sarcomas. Flavopiridol is a pan-CDK inhibitor that has been shown to potentiate chemotherapy. As such, we explored the potentiation of doxorubicin by flavopiridol in sarcoma, in vitro and in vivo, and conducted a phase I trial of flavopiridol with doxorubicin in patients with advanced sarcomas.

Experimental Design: Sarcoma cell lines and xenografts were treated with flavopiridol alone and in combination with doxorubicin. In the phase I study, doxorubicin and flavopiridol were administered on two flavopiridol schedules; a 1-hour bolus and split dosing as a 30-minute bolus followed by a 4-hour infusion.

Results: Preclinically, flavopiridol potentiated doxorubicin. In vivo, doxorubicin administered 1 hour before flavopiridol was more active than doxorubicin alone. Clinically, 31 patients were enrolled on protocol and flavopiridol was escalated to target dose in two schedules (90 mg/m2 bolus; 50 mg/m2 bolus + 40 mg/m2 infusion) both in combination with doxorubicin (60 mg/m2). Dose-limiting toxicities were neutropenia, leukopenia, and febrile neutropenia but no maximum tolerated dose was defined. Flavopiridol pharmacokinetics showed increasing Cmax with increasing dose. Response Evaluation Criteria in Solid Tumors (RECIST) responses included two partial responses, however, stable disease was seen in 16 patients. Of 12 evaluable patients with progressive well- and dedifferentiated liposarcoma, eight had stable disease greater than 12 weeks.

Conclusions: The sequential combination of doxorubicin followed by flavopiridol is well tolerated on both schedules. Disease control was observed in well- and dedifferentiated liposarcoma specifically, a disease in which CDK4 is known to be amplified. Clin Cancer Res; 18(9); 2638–47. ©2012 AACR.
Aortic Function: From the Research Laboratory to the Clinic
Authors: Boudoulas Konstantinos Dean , Vlachopoulos Charalambos , Raman Subha V. , Sparks Elizabeth A. , Triposciadis Filippos , Stefanadis Christodoulos , Boudoulas Harisios
Published: February 2012

For many years, much of the pioneering research on aortic function was carried out by a small group of investigators frequently working away from the clinical environment in the research laboratory. The evaluation of aortic function using aortic pulse wave velocity, aortic distensibility, or other practical indices had yet to reach clinical threshold. It was necessary for the clinicians to take over and to apply these indices to the clinic. In this Odyssey, the work by the basic scientist was important to define the fundamental mechanisms of aortic function; however, it was the vision of the clinical investigator who recognized the importance of aortic function and introduced it into clinical practice. In the near future, the clinical investigator will introduce aortic function in daily clinical practice as the measurement of left ventricular function is used today. A close collaboration between the clinical and the basic investigator will be necessary in order to define the molecular mechanisms related to aortic wall synthesis and degradation of collagen and elastin. Application of these findings by the clinical investigator may help to delay or prevent aortic dysfunction related to aging or other conditions and diseases.
PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations
Authors: AlSaleh Aseel , Frost Gary S. , Griffin Bruce A. , Lovegrove Julie A. , Jebb Susan A. , Sanders Thomas A.B. , O’Dell Sandra D. ,   on behalf of the RISCK Study investigators
Published: February 2012

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.
Cardiac Magnetic Resonance Imaging in Danon Disease
Authors: Nucifora Gaetano , Miani Daniela , Piccoli Gianluca , Proclemer Alessandro
Published: February 2012

Danon disease is a rare X-linked dominant metabolic disorder caused by a primary deficiency in lysosome-associated membrane protein 2. It is characterized by the development of cardiac disease, skeletal myopathy and cognitive disorder. Due to the rarity of Danon disease, physicians may be unfamiliar with the phenotype, confusing it with hypertrophic cardiomyopathy or other causes of left ventricular hypertrophy. The present report demonstrates the clinical value of cardiac magnetic resonance imaging for the diagnostic work-up of Danon disease.
Mortality of Inherited Arrhythmia Syndromes
Authors: Nannenberg Eline A. , Sijbrands Eric J.G. , Dijksman Lea M. , Alders Marielle , van Tintelen J. Peter , Birnie Martijn , van Langen Irene M. , Wilde Arthur A.M.
Published: February 2012

Background—

For most arrhythmia syndromes, the risk of sudden cardiac death for asymptomatic mutation carriers is ill defined. Data on the natural history of these diseases, therefore, are essential. The family tree mortality ratio method offers the unique possibility to study the natural history at a time when the disease was not known and patients received no treatment.

Methods and Results—

In 6 inherited arrhythmia syndromes caused by specific mutations, we analyzed all-cause mortality with the family tree mortality ratio method (main outcome measure, standardized mortality ratio [SMR]). In long-QT syndrome (LQTS) type 1, severely increased mortality risk during all years of childhood was observed (1–19 years), in particular during the first 10 years of life (SMR, 2.9; 95% CI, 1.5–5.1). In LQTS type 2, we observed increasing SMRs starting from age 15 years, which just reached significance between age 30 and 39 (SMR, 4.0; 95% CI, 1.1–10.0). In LQTS type 3, the SMR was increased between age 15 and 19 years (SMR, 5.8; 95% CI, 1.2–16.9). In the SCN5A overlap syndrome, excess mortality was observed between age 10 and 59 years, with a peak between 20 and 39 years (SMR, 3.8; 95% CI, 2.5–5.7). In catecholaminergic polymorphic ventricular tachycardia, excess mortality was restricted to ages 20 to 39 years (SMR, 3.0; 95% CI, 1.3–6.0). In Brugada syndrome, excess mortality was observed between age 40 and 59 (SMR, 1.79; 95% CI, 1.2–2.4), particularly in men.

Conclusions—

We identified age ranges during which the mortality risk manifests in an unselected and untreated population, which can guide screening in these families.
Improving Thromboprophylaxis Using Atrial Fibrillation Diagnostic Capabilities in Implantable Cardioverter-Defibrillators
Authors: Boriani Giuseppe , Santini Massimo , Lunati Maurizio , Gasparini Maurizio , Proclemer Alessandro , Landolina Maurizio , Padeletti Luigi , Botto Giovanni Luca , Capucci Alessandro , Bianchi Stefano , Biffi Mauro , Ricci Renato Pietro , Vimercati Marco , Grammatico Andrea , Lip Gregory Y.H.
Published: February 2012

Background—

Atrial fibrillation (AF) is a well-established risk factor for stroke and thromboembolism and is a frequent comorbid arrhythmia in patients with implantable cardioverter-defibrillators (ICDs). The Anticoagulation Use Evaluation and Life Threatening Events Sentinels (ANGELS) of AF project was a medical care program aimed at supporting adherence to oral anticoagulation (OAC) guidelines for thromboprophylaxis through the use of ICD AF diagnostics.

Methods and Results—

Fifty Italian cardiology clinics followed 3438 patients with ICDs. In a subgroup of 15 centers (the ANGELS of AF centers), cardiologists attending to follow-up visits were supplied with specific reports describing stroke risk factors and risk scores (American College of Chest Physicians and CHADS
2
[congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack]), AF occurrence and duration, and current antithrombotic therapy for patients with AF, especially those with a CHADS
2
score >0 and not on OAC therapy. The remaining centers represented a control group of patients as a comparison of OAC use. In the ANGELS of AF centers, 709 (36%) patients had AF described either in their clinical history (n=426 [22%]) or as new-onset AF (n=257 [14%]). Among 683 (96%) patients with CHADS2 score >0, 209 (30.6%) were not taking an OAC. Appropriate OAC therapy was prescribed in 10% (22/209) of patients after evaluation of ANGELS of AF reports. The percentage of patients on OAC therapy, as indicated by guidelines, increased during follow-up from 46.1% at baseline, to 69.4% at the stroke risk evaluation phase, to up to 72.6% at the end of the observation period. In control centers, corresponding figures were 46.9% at baseline and 56.8% at the end of the observation period (
P
<0.001 versus ANGELS of AF group).

Conclusions—

The ANGELS of AF project demonstrates the possibility to improve OAC use in accordance with available guidelines for stroke risk reduction in AF by supplying attending physicians with reports about patients risk factors and AF information from continuous ICD monitoring.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01007474.
Gene Therapy for Heart Failure
Authors: Tilemann Lisa , Ishikawa Kiyotake , Weber Thomas , Hajjar Roger J.
Published: March 2012

Congestive heart failure accounts for half a million deaths per year in the United States. Despite its place among the leading causes of morbidity, pharmacological and mechanic remedies have only been able to slow the progression of the disease. Today's science has yet to provide a cure, and there are few therapeutic modalities available for patients with advanced heart failure. There is a critical need to explore new therapeutic approaches in heart failure, and gene therapy has emerged as a viable alternative. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within reach of gene-based therapy. The recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a), along with the start of more recent phase 1 trials, opens a new era for gene therapy for the treatment of heart failure.
Decoding the Cardiac Message
Authors: Dorn Gerald W.
Published: March 2012

This review reflects and expands on the contents of my presentation at the Thomas W. Smith Memorial Lecture at American Heart Association Scientific Sessions, 2011. “Decoding the cardiac message” refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for, and consequences of, messenger RNA (mRNA) regulation in the heart. First, I provide a brief historical perspective of the field of molecular genetics, touching on seminal research that paved the way for modern molecular cardiovascular research and helped establish the foundation for current concepts of mRNA regulation in the heart. I follow with some interesting details about the specific research that led to the discovery and appreciation of microRNAs as highly conserved pivotal regulators of RNA expression and translation. Finally, I provide a personal viewpoint as to how agnostic genome-wide techniques for measuring microRNAs, their mRNA targets, and their protein products can be applied in an integrated multisystems approach to uncover direct and indirect effects of microRNAs. Experimental designs integrating next-generation sequencing and global proteomics have the potential to address unanswered questions regarding microRNA–mRNA interactions in cardiac disease, how disease alters mRNA targeting by specific microRNAs, and how mutational and polymorphic nucleotide variation in microRNAs can affect end-organ function and stress response.
Interplay Between Heart and Skeletal Muscle Disease in Heart Failure
Authors: McNally Elizabeth M. , Goldstein Jeffery A.
Published: March 2012

The study of single gene disorders often provides insight for more complex human disease. Mutations in the genes encoding the dystrophin protein complex cause muscular dystrophy and cardiomyopathy by destabilizing the plasma membrane of skeletal myofibers and cardiomyocytes. In these diseases, progressive skeletal muscle degeneration and weakness contribute to cardiac dysfunction. Moreover, the pace and pattern of muscle weakness, along with onset of cardiomyopathy, is highly variable even when associated with the same identical mutation. Using a mouse model of muscular dystrophy and cardiomyopathy, we identified genetic loci that modify muscle pathology and cardiac fibrosis. Distinct genetic modifiers were identified for diaphragm and abdominal musculature, and these genetic intervals differ from those that regulate pathology in the skeletal muscle of the limbs and the heart. One modifier gene was identified and highlights the importance of the transforming growth factor-β pathway in the pathogenesis of muscular dystrophy and cardiomyopathy. We determined that canonical transforming growth factor-β signaling contributes to heart and muscle dysfunction using a
Drosophila
model. Together, these studies demonstrate the value of using a genetically sensitized model to uncover pathways that regulate heart failure and muscle weakness.
Exposing Global Cloud Biases in the Community Atmosphere Model (CAM) Using Satellite Observations and Their Corresponding Instrument Simulators
Authors: Kay J. E. , Hillman B. R. , Klein S. A. , Zhang Y. , Medeiros B. , Pincus R. , Gettelman A. , Eaton B. , Boyle J. , Marchand R. , Ackerman T. P.
Published: March 2012

Satellite observations and their corresponding instrument simulators are used to document global cloud biases in the Community Atmosphere Model (CAM) versions 4 and 5. The model–observation comparisons show that, despite having nearly identical cloud radiative forcing, CAM5 has a much more realistic representation of cloud properties than CAM4. In particular, CAM5 exhibits substantial improvement in three long-standing climate model cloud biases: 1) the underestimation of total cloud, 2) the overestimation of optically thick cloud, and 3) the underestimation of midlevel cloud. While the increased total cloud and decreased optically thick cloud in CAM5 result from improved physical process representation, the increased midlevel cloud in CAM5 results from the addition of radiatively active snow. Despite these improvements, both CAM versions have cloud deficiencies. Of particular concern, both models exhibit large but differing biases in the subtropical marine boundary layer cloud regimes that are known to explain intermodel differences in cloud feedbacks and climate sensitivity. More generally, this study demonstrates that simulator-facilitated evaluation of cloud properties, such as amount by vertical level and optical depth, can robustly expose large and at times radiatively compensating climate model cloud biases.
Climate Feedbacks in CCSM3 under Changing CO2 Forcing. Part I: Adapting the Linear Radiative Kernel Technique to Feedback Calculations for a Broad Range of Forcings
Authors: Jonko Alexandra K. , Shell Karen M. , Sanderson Benjamin M. , Danabasoglu Gokhan
Published: March 2012

Climate feedbacks vary strongly among climate models and continue to represent a major source of uncertainty in estimates of the response of climate to anthropogenic forcings. One method to evaluate feedbacks in global climate models is the radiative kernel technique, which is well suited for model intercomparison studies because of its computational efficiency. However, the usefulness of this technique is predicated on the assumption of linearity between top-of-atmosphere (TOA) radiative fluxes and feedback variables, limiting its application to simulations of small climate perturbations, where nonlinearities can be neglected. This paper presents an extension of the utility of this linear technique to large forcings, using global climate model simulations forced with CO2 concentrations ranging from 2 to 8 times present-day values. Radiative kernels depend on the model’s radiative transfer algorithm and climate base state. For large warming, kernels based on the present-day climate significantly underestimate longwave TOA flux changes and somewhat overestimate shortwave TOA flux changes. These biases translate to inaccurate feedback estimates. It is shown that a combination of present-day kernels and kernels computed using a large forcing climate base state leads to significant improvement in the approximation of TOA flux changes and increased reliability of feedback estimates. While using present-day kernels results in a climate sensitivity that remains constant, using the new kernels shows that sensitivity increases significantly with each successive doubling of CO2 concentrations.
Do Drug Courts Work? Getting inside the Drug Court Black Box
Authors: Goldkamp John S. , White Michael D. , Robinson Jennifer B.
Published: March 2012

This article argues that evaluation of drug courts will benefit not only from an organizing typology (Goldkamp, 1999a, 2000) that focuses research on the critical structural elements of the drug court model but also from an understanding of how drug courts are thought to deliver their impact. In developing a causal model of drug court impact, the analysis separates assessment of impact into two investigations: whether drug courts “work” and how they work. Data from the ongoing NIJ-supported evaluation of the Portland and Las Vegas drug courts are analyzed to answer the comparative question of whether there is an impact (and of what sort) and then to move consideration of the internal elements of the drug court (the black box of drug court treatment) through the development of successive theoretical models. The illustrative analyses guided by these models consider the relative contributions of instrumental drug court treatment functions and defendant risk attributes, which contribute importantly to drug court outcomes. The exploratory findings differ by site, but show some support for the importance of treatment, sanctions and appearances before the drug court judge—and their interaction—in lowering the prospects for subsequent rearrest and increasing likelihood of graduation.
Violent Offenders in Drug Court
Authors: Saum Christine A. , Scarpitti Frank R. , Robbins Cynthia A.
Published: March 2012

Drug courts are slowly beginning to expand their admission criteria to include more chronic and serious offenders since traditional probation and incarceration have failed to prevent drug use and crime. Drug courts have moved from providing diversion programs for first-time offenders charged with drug possession to developing tracks for more complex clients. Many of these new drug court participants have extensive criminal histories, including histories of violent crime. Drug court decision-makers thus confront the difficulty of balancing the needs of treatment versus corrections by attempting to target offenders whose criminal histories suggest that their candidacy in a drug court would not pose a risk to public safety. To date, little is known about whether drug courts are appropriate for offenders with lengthy criminal histories that often include violence. The research presented here explores correlates of drug court graduation for seriously crime-involved offenders, most of whom have a history of violence.