bluuebunny/crossref_metadata_2025 huggingface dataset:
SOLITON INTERACTION OF THE ZAKHAROV–KUZNETSOV EQUATIONS IN PLASMA DYNAMICS
Authors: ZHEN HUI-LING , TIAN BO , WANG PAN , LIU RONG-XIANG , ZHONG HUI
Published: April 2013

In this paper we investigate the constant- and variable-coefficient Zakharov–Kuznetsov (ZK) equations respectively for the electrostatic solitons and two-dimensional ion-acoustic waves obliquely propagating in the inhomogeneous magnetized two-ion-temperature dusty plasmas. By virtue of the symbolic computation and Hirota method, new bilinear forms and N-soliton solutions are both derived. Asymptotic analysis on two-soliton solutions indicates that the soliton interaction is elastic. Propagation characteristics and interaction behavior of the solitons are discussed via graphical analysis. Effects of the dispersive and disturbed coefficients are analyzed. For the constant-coefficient ZK equation, amplitude of the one soliton becomes larger when the absolute value of dispersive coefficient B increases, while interaction between the two solitons varies with the product of B and disturbed coefficient C: when BC>0, two solitons are always parallel, or they interact with each other that way. For the variable-coefficient ZK equation, periodical soliton arises when the disturbed coefficient γ(t) is a periodical function, and periods of the solitons are inversely correlated to the period of γ(t).
DIVERSE STRUCTURE SYNCHRONIZATION OF FRACTIONAL ORDER HYPER-CHAOTIC SYSTEMS
Authors: WANG XING-YUAN , ZHAO GUO-BIN , YANG YU-HONG
Published: April 2013

This paper studied the dynamic behavior of the fractional order hyper-chaotic Lorenz system and the fractional order hyper-chaotic Rössler system, then numerical analysis of the different fractional orders hyper-chaotic systems are carried out under the predictor–corrector method. We proved the two systems are in hyper-chaos when the maximum and the second largest Lyapunov exponential are calculated. Also the smallest orders of the systems are proved when they are in hyper-chaos. The diverse structure synchronization of the fractional order hyper-chaotic Lorenz system and the fractional order hyper-chaotic Rössler system is realized using active control method. Numerical simulations indicated that the scheme was always effective and efficient.
SEARCH FOR THE STANDARD MODEL HIGGS BOSON WITH THE ATLAS DETECTOR
Authors:   on behalf of the ATLAS Collaboration, ORESTANO DOMIZIA
Published: April 2013

This document presents a brief overview of some of the experimental techniques employed by the ATLAS experiment at the CERN Large Hadron Collider (LHC) in the search for the Higgs boson predicted by the standard model (SM) of particle physics. The data and the statistical analyses that allowed in July 2012, only few days before this presentation at the Marcel Grossman Meeting, to firmly establish the observation of a new particle are described. The additional studies needed to check the consistency between the newly discovered particle and the Higgs boson are also discussed.
MAGNETO-PLASMA PROCESSES IN RELATIVISTIC ASTROPHYSICS: MODERN DEVELOPMENTS
Authors: TSUPKO OLEG YU.
Published: April 2013

This contribution is a review of some talks presented at the session "Magneto-Plasma Processes in Relativistic Astrophysics" of the Thirteenth Marcel Grossmann Meeting MG13. We discuss the modern developments of relativistic astrophysics, connected with presence of plasma and magnetic fields. The influence of magneto-plasma processes on the structure of the compact objects and accretion processes is considered. We also discuss a crucial role of magnetic field for the mechanism of core-collapse supernova explosions. Gravitational lensing in plasma is also considered.
AMPEROMETRIC DETECTION OF PYOCYANIN IN NANOFLUIDIC CHANNELS
Authors: WEBSTER THADDAEUS A. , SISMAET HUNTER J. , GOLUCH EDGAR D.
Published: April 2013

Microfabricated nanofluidic electrode assemblies (NEAs) with integrated palladium references were used to amperometrically monitor changes in pyocyanin concentration. Pyocyanin is an electroactive molecule that is produced by the opportunistic pathogen Pseudomonas aeruginosa and is directly linked to cellular processes that increase both robustness and virulence in this bacterium. This is the first time that pyocyanin has been measured in real time using microfabricated sensors. A linear response in faradaic current (R2= 0.96) was observed over a biomedically relevant range of pyocyanin concentrations (0–100 μM) while continuously measuring the current for 2 h. Measurement of the current that results from the repeated oxidation and reduction of pyocyanin at two closely spaced electrodes inside the device nanochannel yielded a 1.07 μM limit of detection without electrical isolation of the electrochemical cell. Since a reference electrode is integrated inside the nanofluidic channel of these sensors, they can potentially be employed to detect pyocyanin and other redox-active molecules in wide range of medical and environmental settings where space is limited. NEAs were also used with an external Ag/AgCl reference electrode to determine the concentration of pyocyanin in trypticase soy broth samples. This type of analysis is completed in less than 2 min and the detection limit was determined to be 441 nM.
Next-Generation Sequencing Platforms
Authors: Mardis Elaine R.
Published: April 2013

Automated DNA sequencing instruments embody an elegant interplay among chemistry, engineering, software, and molecular biology and have built upon Sanger's founding discovery of dideoxynucleotide sequencing to perform once-unfathomable tasks. Combined with innovative physical mapping approaches that helped to establish long-range relationships between cloned stretches of genomic DNA, fluorescent DNA sequencers produced reference genome sequences for model organisms and for the reference human genome. New types of sequencing instruments that permit amazing acceleration of data-collection rates for DNA sequencing have been developed. The ability to generate genome-scale data sets is now transforming the nature of biological inquiry. Here, I provide an historical perspective of the field, focusing on the fundamental developments that predated the advent of next-generation sequencing instruments and providing information about how these instruments work, their application to biological research, and the newest types of sequencers that can extract data from single DNA molecules.
Price Rigidity: Microeconomic Evidence and Macroeconomic Implications
Authors: Nakamura Emi , Steinsson Jón
Published: April 2013

We review recent evidence on price rigidity from the macroeconomics literature and discuss how this evidence is used to inform macroeconomic modeling. Sluggish price adjustment is a leading explanation for the large effects of demand shocks on output and, in particular, the effects of monetary policy on output. A recent influx of data on individual prices has greatly deepened macroeconomists’ understanding of individual price dynamics. However, the analysis of these new data raises a host of new empirical issues that have not traditionally been confronted by parsimonious macroeconomic models of price setting. Simple statistics such as the frequency of price change may be misleading guides to the flexibility of the aggregate price level in a setting in which temporary sales, product churning, cross-sectional heterogeneity, and large idiosyncratic price movements play an important role. We discuss empirical evidence on these and other important features of micro price adjustment and ask how they affect the sluggishness of aggregate price adjustment and the economy’s response to demand shocks.
Deterrence: A Review of the Evidence by a Criminologist for Economists
Authors: Nagin Daniel S.
Published: April 2013

This article reviews the evidence on the deterrent effect of police, imprisonment, and capital punishment and additionally summarizes knowledge of sanction risk perceptions. Studies of changes in police presence, whether achieved by changes in police numbers or in their strategic deployment, consistently find evidence of deterrent effects. Studies of the deterrent effect of increases in already long prison sentences find at most a modest deterrent effect. Studies of the deterrent effect of capital punishment provide no useful information on the topic. Four high-priority areas for future research are identified: developing and testing an integrated model of the effects of the threat and experience of punishment, measuring perceptions of sanction regimes, developing and testing a theory of criminal opportunities, and estimating the deterrent effect of shorter prison sentences and identifying high-deterrence policies.
Vesicle Photonics
Authors: Vasdekis A.E. , Scott E.A. , Roke S. , Hubbell J.A. , Psaltis D.
Published: April 2013

Amphiphiles, under appropriate conditions, can self-assemble into nanoscale thin membrane vessels (vesicles) that encapsulate and hence protect and transport molecular payloads. Vesicles assemble naturally within cells but can also be artificially synthesized. In this article, we review the mechanisms and applications of light-field interactions with vesicles. By being associated with light-emitting entities (e.g., dyes, fluorescent proteins, or quantum dots), vesicles can act as imaging agents in addition to cargo carriers. Vesicles can also be optically probed on the basis of their nonlinear response, typically from the vesicle membrane. Light fields can be employed to transport vesicles by using optical tweezers (photon momentum) or can directly perturb the stability of vesicles and hence trigger the delivery of the encapsulated payload (photon energy). We conclude with emerging vesicle applications in biology and photochemical microreactors.
Accurate First Principles Model Potentials for Intermolecular Interactions
Authors: Gordon Mark S. , Smith Quentin A. , Xu Peng , Slipchenko Lyudmila V.
Published: April 2013

The general effective fragment potential (EFP) method provides model potentials for any molecule that is derived from first principles, with no empirically fitted parameters. The EFP method has been interfaced with most currently used ab initio single-reference and multireference quantum mechanics (QM) methods, ranging from Hartree-Fock and coupled cluster theory to multireference perturbation theory. The most recent innovations in the EFP model have been to make the computationally expensive charge transfer term much more efficient and to interface the general EFP dispersion and exchange repulsion interactions with QM methods. Following a summary of the method and its implementation in generally available computer programs, these most recent new developments are discussed.
Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice
Authors: Cattaruzza Fiore , Johnson Cali , Leggit Alan , Grady Eileen , Schenk A. Katrin , Cevikbas Ferda , Cedron Wendy , Bondada Sandhya , Kirkwood Rebekah , Malone Brian , Steinhoff Martin , Bunnett Nigel , Kirkwood Kimberly S.
Published: April 2013

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1+/+and trpa1-/-mice. Chronic inflammatory changes and pain behaviors were assessed after 2–3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1-/-mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.
Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase
Authors: Namachivayam Kopperuncholan , Blanco Cynthia L. , Frost Brandy L. , Reeves Aaron A. , Jagadeeswaran Ramasamy , MohanKumar Krishnan , Safarulla Azif , Mandal Partha , Garzon Steven A. , Raj J. Usha , Maheshwari Akhil
Published: April 2013

Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.
Time- and age-dependent effects of serotonin on gasping and autoresuscitation in neonatal mice
Authors: Chen Jianping , Magnusson Jennifer , Karsenty Gerard , Cummings Kevin J.
Published: April 2013

The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would compromise gasping and autoresuscitation mainly in the second postnatal week and that acute restoration of 5-HT would reverse the defects. We exposed postnatal day (P)4–5, P8–9, and P11–12 tryptophan-hydroxylase-2 knockout ( TPH2−/−) and wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring survival, gasp latency, gasp frequency ( fB), and the time required to restore eupnea and heart rate. We also tested P8–9 TPH2−/− mice after restoring 5-HT with a single injection of 5-hydroxytryptophan (5-HTP) 1–2 h before testing or with multiple injections beginning 24 h before testing. At P4–5 and P8–9, but not at P11–12, gasp latency and the recovery of eupnea were delayed ∼2- to 3-fold in TPH2−/− pups compared with WT ( P < 0.001). At all ages, TPH2−/− pups displayed reduced gasp fB (∼20–30%; P < 0.001) and delayed heart rate recovery (∼60%; P = 0.002) compared with WT littermates. TPH2−/− survival was reduced compared with WT ( P < 0.001), especially at P8–9 and P11–12 ( P = 0.004). Whereas 1–2 h of 5-HTP treatment improved the gasp latency and fB of P8–9 TPH2−/− pups, improved cardiorespiratory recovery and survival required 24 h of treatment. Our data suggest that 5-HT operates over a long time span (∼24 h) to improve survival during episodic severe hypoxia. Early in development (P4–9), 5-HT is critical for both respiratory and cardiovascular components of autoresuscitation; later (P11–12), it is critical mainly for cardiovascular components. Nevertheless, the effect of 5-HT deficiency on survival is most striking from P8 to P12.
Elastase-coupled beads as a tool for characterizing localized alveolar tissue destruction associated with the onset of emphysema
Authors: Craig J. M. , Scott A. L. , Mitzner W.
Published: April 2013

Intratracheal elastase challenge of laboratory animals has long been established as a model for observing the physiological and morphological changes that result from alveolar destruction, the hallmark of emphysema. However, instillation of elastase suspended in buffer results in widespread inflammation and variable emphysematous lesions, which has made the identification of specific cellular and molecular events associated with the onset of emphysema difficult to define. Here we establish a bead-based elastase delivery system that induces localized tissue destruction, a key event in the initiation of emphysema. Elastase was coupled to bisacrylamide beads, which were shown to retain enzymatic activity prior to intratracheal administration in mice. C57BL/6 mice were given a single dose of 40,000 beads, which became distributed throughout the small airways and parenchyma of the lung. Elastase-coupled beads resulted in a quantifiable loss of alveolar tissue immediately surrounding the beads, an effect that was not observed with beads that lacked protein altogether or with beads containing elastase inactivated by an irreversible inhibitor. Furthermore, beads bound with active elastase elicited local recruitment of mononuclear cells, including macrophages, and polymorphonuclear neutrophils to the site of bead deposition, a feature consistent with the cellular infiltration observed following conventional solubilized elastase challenges. This work identifies a novel bead-based enzyme delivery system that also extends the elastase model of emphysema to permit the characterization of mechanisms that drive alveolar surface area loss following elastin degradation in focal emphysematous lesions.
Acute superoxide scavenging reduces sympathetic vasoconstrictor responsiveness in short-term exercise-trained rats
Authors: Jendzjowsky Nicholas G. , DeLorey Darren S.
Published: April 2013

We hypothesized that acute superoxide (O2−) scavenging would attenuate sympathetic vasoconstrictor responsiveness by augmenting nitric oxide (NO)-mediated inhibition of sympathetic vasoconstriction in exercise-trained rats. Sprague-Dawley rats were randomly assigned to sedentary time control (S; n = 7) or mild- (M: 20 m/min, 5° grade; n = 7) or heavy-intensity (H: 40 m/min, 5° grade; n = 7) exercise training (ET) groups and trained 5 days/wk for 4 wk with matched training volume. Following ET, rats were anesthetized and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance. In resting skeletal muscle, the percentage change of femoral vascular conductance in response to continuous (2 Hz) and patterned (20 and 40 Hz) sympathetic stimulation was determined during control conditions, O2− scavenging (TIRON, 1 g·kg−1·h−1 iv) and combined O2− scavenging + nitric oxide synthase blockade ( Nω-nitro-l-arginine methyl ester, 5 mg/kg iv). ET augmented the vasoconstrictor response to sympathetic stimulation in a training intensity-dependent manner ( P < 0.05) (S: 2 Hz: −26 ± 7.1%; 20 Hz: −26.9 ± 7.3%; 40 Hz: −27.7 ± 7.0%; M: 2 Hz: −37.4 ± 8.3%; 20 Hz: −35.9 ± 7.4%; 40 Hz: −38.2 ± 9.4%; H: 2 Hz: −46.9 ± 7.8%; 20 Hz: −48.5 ± 7.2%; 40 Hz: −51.2 ± 7.3%). O2− scavenging did not alter ( P > 0.05) the vasoconstrictor response in S rats (S: 2 Hz: −23.9 ± 7.6%; 20 Hz: −26.1 ± 9.1%; 40 Hz: −27.5 ± 7.2%), whereas the response in ET rats was diminished (M: 2 Hz: −26.3 ± 5.1%; 20 Hz: −28.7 ± 5.3%; 40 Hz: −28.5 ± 5.6%; H: 2 Hz: −35.5 ± 10.3%; 20 Hz: −38.6 ± 6.8%; 40 Hz: −43.9 ± 5.9%, P < 0.05). TIRON + Nω-nitro-l-arginine methyl ester increased vasoconstrictor responsiveness ( P < 0.05) in ET rats (M: 2 Hz: −47.7 ± 9.8%; 20 Hz: −41.2 ± 7.2%; 40 Hz: −50.5 ± 7.9%; H: 2 Hz: −55.8 ± 7.6%; 20 Hz: −55.7 ± 7.8%; 40 Hz: −58.7 ± 6.2%), whereas, in S rats, the response was unchanged (2 Hz: −29.4 ± 8.7%; 20 Hz: −30.0 ± 7.4%; 40 Hz: −35.2 ± 10.3%; P > 0.05). These data indicate that the augmented sympathetic vasoconstrictor responsiveness in ET rats was related to increased oxidative stress and altered nitric oxide-mediated inhibition of vasoconstriction.
Historical Perspective: Harvey's epoch-making discovery of the Circulation, its historical antecedents, and some initial consequences on medical practice
Authors: Pasipoularides Ares
Published: April 2013

In Harvey's Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus of 1628, we see the mechanisms of the Circulation worked out more or less in full from the results of experimental demonstration, virtually complete but for the direct visual evidence of a link between the minute final terminations and initial branches of the arterial and venous systems, respectively. This would become available only when the capillaries could be seen under the microscope, by Malpighi. Harvey's amazingly modern order of magnitude analysis of volumetric circulatory flow and appreciation of the principle of continuity (mass conservation), his adroit investigational uses of ligatures of varying tightness in elegant flow experiments, and his insightful deductions truly explain the movement of the blood in animals. His end was accomplished. So radical was his discovery that early in the 18th century, the illustrious Hermann Boerhaave, professor of medicine at Leyden, declared that nothing that had been written before Harvey was worthy of consideration any more. The conclusions of De Motu Cordis are unassailable and beautiful in their simplicity. Harvey's genius and tireless determination have served physiology and medicine well.
TNF signals via neuronal-type nitric oxide synthase and reactive oxygen species to depress specific force of skeletal muscle
Authors: Stasko Shawn A. , Hardin Brian J. , Smith Jeffrey D. , Moylan Jennifer S. , Reid Michael B.
Published: April 2013

TNF promotes skeletal muscle weakness, in part, by depressing specific force of muscle fibers. This is a rapid, receptor-mediated response, in which TNF stimulates cellular oxidant production, causing myofilament dysfunction. The oxidants appear to include nitric oxide (NO); otherwise, the redox mechanisms that underlie this response remain undefined. The current study tested the hypotheses that 1) TNF signals via neuronal-type NO synthase (nNOS) to depress specific force, and 2) muscle-derived reactive oxygen species (ROS) are essential co-mediators of this response. Mouse diaphragm fiber bundles were studied using live cell assays. TNF exposure increased general oxidant activity ( P < 0.05; 2′,7′-dichlorodihydrofluorescein diacetate assay) and NO activity ( P < 0.05; 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate assay) and depressed specific force across the full range of stimulus frequencies (1-300 Hz; P < 0.05). These responses were abolished by pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME; a nonspecific inhibitor of NOS activity), confirming NO involvement. Genetic nNOS deficiency replicated L-NAME effects on TNF-treated muscle, diminishing NO activity (−80%; P < 0.05) and preventing the decrement in specific force ( P < 0.05). Comparable protection was achieved by selective depletion of muscle-derived ROS. Pretreatment with either SOD (degrades superoxide anion) or catalase (degrades hydrogen peroxide) depressed oxidant activity in TNF-treated muscle and abolished the decrement in specific force. These findings indicate that TNF signals via nNOS to depress contractile function, a response that requires ROS and NO as obligate co-mediators.
Reference values for vastus lateralis fiber size and type in healthy subjects over 40 years old: a systematic review and metaanalysis
Authors: Gouzi Fares , Maury Jonathan , Molinari Nicolas , Pomiès Pascal , Mercier Jacques , Préfaut Christian , Hayot Maurice
Published: April 2013

Skeletal muscle atrophy is a major systemic impairment in chronic diseases. Yet its determinants have been hard to identify because a clear research definition has not been agreed upon. The reduction in muscle fiber cross-sectional area (CSA) is a widely acknowledged marker of muscle atrophy, but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published. Thus, we aimed to systematically review the studies providing data on fiber CSA and fiber type proportion in the vastus lateralis of the quadriceps of healthy subjects (age >40 yr) and then to pool and analyze the data from the selected studies to determine reference values for fiber CSA. We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and identified 19 studies, including 423 subjects that matched the inclusion criteria. On the basis of fiber type and gender, the mean fiber CSA and the lower limits of normal (LLNs) were (%type I*60) + 1,743 μm2 and (%type I*60) − 718 μm2, respectively, for men; and (%type I*70) + 139 μm2 and (%type I*70) − 1,485 μm2, respectively, for women. There was no significant heterogeneity among subgroups of fiber type and gender. The pooled type I fiber proportion was 50.3% (LLN = 32.9%). In multivariate analysis, fiber CSA was significantly correlated with V̇o2 peak ( r = 190.92; P = 0.03), and type I fiber proportion was correlated with age ( r = −0.024; P = 0.005), body mass index ( r = 0.096; P = 0.005), and V̇o2 peak ( r = −0.053; P = 0.005). Our metaanalysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender. This analysis will be improved by prospective assessment in well-characterized healthy subjects.
Diacylglycerol Kinase α Is a Critical Signaling Node and Novel Therapeutic Target in Glioblastoma and Other Cancers
Authors: Dominguez Charli L. , Floyd Desiree H. , Xiao Aizhen , Mullins Garrett R. , Kefas Benjamin A. , Xin Wenjun , Yacur Melissa N. , Abounader Roger , Lee Jae K. , Wilson Gabriela Mustata , Harris Thurl E. , Purow Benjamin W.
Published: April 2013

Although diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible factor-1α (HIF-1α) are key targets of DGKα inhibition, in addition to its regulation of other oncogenes. DGKα regulates mTOR transcription via a unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKα inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and melanoma xenograft treatment models, with growth delay and decreased vascularity. This study establishes DGKα as a central signaling hub and a promising therapeutic target in the treatment of cancer.

Significance: DGKα, which converts diacylglycerol to phosphatidic acid, regulates critical oncogenic pathways, notably HIF-1α and mTOR. DGKα knockdown and small-molecule inhibition are selectively toxic to human cancer cells but not normal human cells, and DGKα inhibition slows tumor growth, decreases angiogenesis, and increases mouse survival in xenograft models. Cancer Discov; 3(7); 782–97. ©2013 AACR.

See related commentary by Bhat and Aldape, p. 726

This article is highlighted in the In This Issue feature, p. 705
A Weight Loss Diet Intervention Has a Similar Beneficial Effect on Both Metabolically Abnormal Obese and Metabolically Healthy but Obese Premenopausal Women
Authors: Ruiz Jonatan R. , Ortega Francisco B. , Labayen Idoia
Published: April 2013

Background/Aims: We studied the effect of a 12-week energy-restricted diet intervention on cardiometabolic risk in two groups of nonmorbid obese premenopausal Caucasian women, i.e. a metabolically abnormal obese (MAO) and a metabolically healthy but obese (MHO) group. Methods: The participants were 53 MAO and 25 MHO women (age range 19-49 years; body mass index inclusion criterion: 30-39.9). We assessed changes in body weight and composition, blood lipids, insulin resistance, hepatic enzymes, inflammatory markers and adipocytokines. Results: Overall, many of the study outcomes improved with the intervention in both MAO and MHO participants, but there was no difference in the magnitude of change between the groups. Body weight, waist circumference and total fat mass decreased significantly in response to the intervention in both MAO and MHO women (all p < 0.001). Fasting insulin, insulin resistance (homeostasis model assessment), hepatic enzymes (alanine aminotransferase and γ-glutamyltransferase), fatty liver index and leptin levels also decreased in both groups after the intervention (all p < 0.001), whereas total cholesterol, triglycerides and C-reactive protein decreased significantly only in MAO women (all p < 0.001). Conclusion: These findings reinforce the idea that MHO women would also benefit from a lifestyle weight reduction intervention.
Impaired Visual Recognition Memory Predicts Alzheimer's Disease in Amnestic Mild Cognitive Impairment
Authors: Didic Mira , Felician Olivier , Barbeau Emmanuel J. , Mancini Julien , Latger-Florence Caroline , Tramoni Eve , Ceccaldi Mathieu
Published: April 2013

Background: In the common form of Alzheimer's disease (AD), neurofibrillary tangles, which are associated with cognitive dysfunction, initially develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before reaching the hippocampus. This area plays a key role in visual recognition memory (VRM). Impaired VRM could therefore be an early marker of AD. Methods: An extensive neuropsychological assessment including VRM tasks was performed in 26 patients with single-domain amnestic mild cognitive impairment at baseline. We evaluated the diagnostic accuracy of neuropsychological tests using ROC curve analyses in a prospective longitudinal study until conversion to probable AD or with a follow-up of at least 6 years. Results: VRM performance predicted conversion to AD with a sensitivity of 80% and a specificity of 90.9%. Combining the assessment of VRM with a verbal memory task increased diagnostic accuracy. Conclusions: Cognitive ‘biomarkers' evaluating the function of brain areas that are the target of degenerative change should be considered for the early diagnosis of AD.
The Complexity of Arterial Classical Monocyte Recruitment
Authors: Drechsler Maik , Soehnlein Oliver
Published: April 2013

Accumulation of classical monocytes is imperative for the progression of atherosclerosis. Hence, therapeutic interference with mechanisms of lesional monocyte recruitment, the primary mechanism controlling macrophage accumulation, may allow for targeting atheroprogression and its clinical complications. Here, we review the important role of classical monocytes in atheroprogression as well as their routes of arterial recruitment. We specifically highlight the role of cell adhesion molecules as well as of platelet-derived chemokines and neutrophil-borne alarmins.
Integrative Schmerztherapie bei chronischem Rückenschmerz
Authors: Unger Andreas
Published: April 2013

Jedes schulmedizinische sowie komplementärmedizinische Verfahren, wie z.B. Neuraltherapie, Akupunktur/TCM oder Manuelle Therapie/Osteopathie, stösst bei noch so gekonnter Durchführung an Grenzen. Gezielte Kombinationen von Therapien auf struktureller, biomechanischer, myofaszialer und bioenergetischer Ebene, begleitender Psychotherapie, Berücksichtigung von Umweltbelastungen sowie Substitution von Vitaminen und Spurenelementen führen häufig weiter. Die Notwendigkeit von Integrativer Schmerztherapie ergibt sich nicht nur aus dem Wunsch des Patienten nach einer nebenwirkungsarmen Therapie, sondern auch aufgrund der Grenzen klassischer schulmedizinischer Verfahren.
Agraphia Caused by Left Thalamic Hemorrhage
Authors: Osawa Aiko , Maeshima Shinichiro , Yamane Fumitaka , Uemiya Nahoko , Ochiai Ikuo , Yoshihara Tomoyuki , Ishihara Shoichiro , Tanahashi Norio
Published: April 2013

A 71-year-old right-handed man was admitted to our hospital with right hemiparesis and sensory impairment associated with mild aphasia. Although aphasia gradually resolved within 2 weeks after stroke onset, his writing ability remained disturbed. A computed tomography (CT) scan at stroke onset revealed a hematoma in the left thalamus, but no cortical lesions were observed. Further, a single-photon emission CT (SPECT) scan showed decreased blood flow in the left thalamus, in the cortical region extending from the left superior temporal gyrus to the parietal lobe, and in the frontal lobe. It is possible that agraphia may have directly resulted from the thalamic lesion, but SPECT findings strongly suggested that a general decrease in left cortical function concomitant with a disruption of the thalamocortical and cortico-thalamocortical projection fibers produced these cognitive deficits.
Posterior Hyaloidotomy by Nd:YAG Laser Application in a Patient with Postpartum Depression Caused by Valsalva Retinopathy
Authors: Dağlıoğlu Mutlu Cihan , Coşkun Mesut , İlhan Nilüfer , Tuzcu Esra Ayhan , Arı Mustafa , Ayıntap Emre , İlhan Özgür
Published: April 2013

Purpose: The aim of this report is to present a case of premacular hemorrhage in a 37-week pregnant woman with concurrent presence of postpartum depression secondary to her ocular disease. Methods: A 27-year-old woman in her 37th week of pregnancy presented with Valsalva retinopathy, which occurred in her left eye secondary to severe coughing. Her visual acuity was reduced to perception of hand motions, and she was agitated because of the loss of vision. The patient, who gave birth by cesarean section, was admitted for control examination 2 weeks after birth. No change was observed in premacular hemorrhage in control examination. However, the patient's relatives stated that the patient was very agitated and disinterested in her baby. For this reason, the patient was referred to the psychiatry clinic, and she was diagnosed with postpartum depression. The anatomical location of the premacular hemorrhage was determined by spectral domain optical coherence tomography. Results: Neodymium yttrium aluminum garnet (Nd:YAG) laser hyaloidotomy was performed to her left eye on the same day. Rapid release of premacular hemorrhage into the vitreous cavity was observed immediately after Nd:YAG laser application. Two days after the application, the patient's visual acuity had improved to 20/20. The clinical improvement positively impacted on the patient's mood. Conclusion: In pregnant patients suffering from Valsalva retinopathy during the postpartum period, posterior hyaloidotomy by Nd:YAG laser can be implemented in terms of the patients' own and their babies' physical and mental health.
Anti-Inflammatory and Antiatherogenic Role of BMP Receptor II in Endothelial Cells
Authors: Kim Chan Woo , Song Hannah , Kumar Sandeep , Nam Douglas , Kwon Hyuk Sang , Chang Kyung Hwa , Son Dong Ju , Kang Dong-Won , Brodie Seth A. , Weiss Daiana , Vega J. David , Alberts-Grill Noah , Griendling Kathy , Taylor W. Robert , Jo Hanjoong
Published: April 2013

Objective—

Atherosclerosis is an inflammatory disease with multiple underlying metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression is increased in endothelium in atherosclerosis-prone regions and is known to induce endothelial inflammation, endothelial dysfunction, and hypertension. BMP actions are mediated by 2 different types of BMP receptors (BMPRI and BMPRII). Here, we show a surprising finding that loss of BMPRII expression causes endothelial inflammation and atherosclerosis.

Approach and Results—

Using BMPRII siRNA and BMPRII
+/−
mice, we found that specific knockdown of BMPRII, but not other BMP receptors (Alk1, Alk2, Alk3, Alk6, ActRIIa, and ActRIIb), induced endothelial inflammation in a ligand-independent manner by mechanisms mediated by reactive oxygen species, nuclear factor-KappaB, and reduced nicotinamide adenine dinucleotide phosphate oxidases. Further, BMPRII
+/−
ApoE
−/−
mice developed accelerated atherosclerosis compared with BMPRII
+/+
ApoE
−/−
mice. Interestingly, we found that multiple proatherogenic stimuli, such as hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, and the proinflammatory cytokine (tumor necrosis factor-α), downregulated BMPRII expression in endothelium, whereas antiatherogenic stimuli, such as stable flow and statin treatment, upregulated its expression in vivo and in vitro. Moreover, BMPRII expression was significantly diminished in human coronary advanced atherosclerotic lesions. Also, we were able to rescue the endothelial inflammation induced by BMPRII knockdown by overexpressing the BMPRII wild type, but not by the BMPRII short form lacking the carboxyl-terminal tail region.

Conclusions—

These results suggest that BMPRII is a critical, anti-inflammatory, and antiatherogenic protein that is commonly targeted by multiple pro- and antiatherogenic factors. BMPRII may be used as a novel diagnostic and therapeutic target in atherosclerosis.
Walking Versus Running for Hypertension, Cholesterol, and Diabetes Mellitus Risk Reduction
Authors: Williams Paul T. , Thompson Paul D.
Published: April 2013

Objective—

To test whether equivalent energy expenditure by moderate-intensity (eg, walking) and vigorous-intensity exercise (eg, running) provides equivalent health benefits.

Approach and Results—

We used the National Runners’ (n=33 060) and Walkers’ (n=15 945) Health Study cohorts to examine the effect of differences in exercise mode and thereby exercise intensity on coronary heart disease (CHD) risk factors. Baseline expenditure (metabolic equivant hours per day [METh/d]) was compared with self-reported, physician-diagnosed incident hypertension, hypercholesterolemia, diabetes mellitus, and CHD during 6.2 years follow-up. Running significantly decreased the risks for incident hypertension by 4.2% (
P
<10
−7
), hypercholesterolemia by 4.3% (
P
<10
−14
), diabetes mellitus by 12.1% (
P
<10
−5
), and CHD by 4.5% per METh/d (
P
=0.05). The corresponding reductions for walking were 7.2% (
P
<10
−6
), 7.0% (
P
<10
−8
), 12.3% (
P
<10
−4
), and 9.3% (
P
=0.01). Relative to <1.8 METh/d, the risk reductions for 1.8 to 3.6, 3.6 to 5.4, 5.4 to 7.2, and ≥7.2 METh/d were as follows: (1) 10.1%, 17.7%, 25.1%, and 34.9% from running and 14.0%, 23.8%, 21.8%, and 38.3% from walking for hypercholesterolemia; (2) 19.7%, 19.4%, 26.8%, and 39.8% from running and 14.7%, 19.1%, 23.6%, and 13.3% from walking for hypertension; and (3) 43.5%, 44.1%, 47.7%, and 68.2% from running, and 34.1%, 44.2% and 23.6% from walking for diabetes mellitus (walking >5.4 METh/d excluded for too few cases). The risk reductions were not significantly different for running than walking for diabetes mellitus (
P
=0.94), hypertension (
P
=0.06), or CHD (
P
=0.26), and only marginally greater for walking than running for hypercholesterolemia (
P
=0.04).

Conclusions—

Equivalent energy expenditures by moderate (walking) and vigorous (running) exercise produced similar risk reductions for hypertension, hypercholesterolemia, diabetes mellitus, and possibly CHD.
Targeting Platelet GPIbβ Reduces Platelet Adhesion, GPIb Signaling and Thrombin Generation and Prevents Arterial Thrombosis
Authors: Maurer Eric , Tang Chaojun , Schaff Mathieu , Bourdon Catherine , Receveur Nicolas , Ravanat Catherine , Eckly Anita , Hechler Béatrice , Gachet Christian , Lanza Francois , Mangin Pierre H.
Published: April 2013

Objective—

The glycoprotein (GP) Ib-V-IX complex regulates the adhesion, activation, and procoagulant activity of platelets. We previously reported that RAM.1, a rat monoclonal antibody directed against the extracellular domain of mouse GPIbβ, diminished adhesion of platelets and chinese hamster ovary cells transfected with the human GPIb-IX complex to von Willebrand factor under flow conditions. Here, we further evaluated the functional importance of GPIbβ by studying the impact of RAM.1 on GPIb-mediated platelet responses and in vitro and in vivo thrombus formation.

Approach and Results—

We show that RAM.1 dramatically reduced GPIb-mediated filopodia extension of chinese hamster ovary GPIb-IX cells after adhesion to von Willebrand factor. RAM.1 also reduced filopodia extension and GPIb-mediated Ca
2+
signaling after adhesion of mouse platelets to von Willebrand factor. RAM.1 inhibited thrombin generation in platelet-rich plasma without impairing phosphatidylserine exposure. In addition, RAM.1 reduced thrombus formation after perfusion of mouse whole blood over collagen in a shear-dependent manner. This effect was confirmed in vivo, because injection of F(ab)′2 fragments of RAM.1 diminished thrombus formation induced by laser beam injury of mesenteric arterioles and forceps injury of the abdominal aorta. In contrast, RAM.1 F(ab)′2 did not prolong the tail-bleeding time or increase the volume of blood lost.

Conclusions—

These findings are the first evidence that targeting a subunit other than GPIbα can lead to an antithrombotic effect via the GPIb-V-IX complex. This could represent an alternative way to reduce thrombus formation with a minor impact on hemostasis.
Chemerin Connects Fat to Arterial Contraction
Authors: Watts Stephanie W. , Dorrance Anne M. , Penfold Mark E. , Rourke Jillian L. , Sinal Christopher J. , Seitz Bridget , Sullivan Timothy J. , Charvat Trevor T. , Thompson Janice M. , Burnett Robert , Fink Gregory D.
Published: April 2013

Objective—

Obesity and hypertension are comorbid in epidemic proportion, yet their biological connection is largely a mystery. The peptide chemerin is a candidate for connecting fat deposits around the blood vessel (perivascular adipose tissue) to arterial contraction. We presently tested the hypothesis that chemerin is expressed in perivascular adipose tissue and is vasoactive, supporting the existence of a chemerin axis in the vasculature.

Approach and Results—

Real-time polymerase chain reaction, immunohistochemistry, and Western analyses supported the synthesis and expression of chemerin in perivascular adipose tissue, whereas the primary chemerin receptor ChemR23 was expressed both in the tunica media and endothelial layer. The ChemR23 agonist chemerin-9 caused receptor, concentration-dependent contraction in the isolated rat thoracic aorta, superior mesenteric artery, and mesenteric resistance artery, and contraction was significantly amplified (more than 100%) when nitric oxide synthase was inhibited and the endothelial cell mechanically removed or tone was placed on the arteries. The novel ChemR23 antagonist CCX832 inhibited phenylephrine-induced and prostaglandin F2α-induced contraction (+perivascular adipose tissue), suggesting that endogenous chemerin contributes to contraction. Arteries from animals with dysfunctional endothelium (obese or hypertensive) demonstrated a pronounced contraction to chemerin-9. Finally, mesenteric arteries from obese humans demonstrate amplified contraction to chemerin-9.

Conclusions—

These data support a new role for chemerin as an endogenous vasoconstrictor that operates through a receptor typically attributed to function only in immune cells.
Capturing the Voices of Pseudepigraphic Personae: On the Form and Function of Incipits in the Aramaic Dead Sea Scrolls
Authors: Perrin Andrew B.
Published: April 2013

Abstract

It is widely recognized that the authors of the Aramaic Dead Sea Scrolls often shrouded their tales in first person voices and exhibited a perennial interest in the production and transmission of ancestral booklore. The present study explores the literary convention of the incipit in light of these interrelated methods of pseudepigraphy. Throughout the Aramaic Scrolls incipits introduce entire compositions and putative texts within narratives. Comparative philological analysis reveals that these incipits feature strikingly similar literary-linguistic idioms. However, it is equally apparent that that these common elements were uniquely patterned by individual authors. It is suggested that these commonalities should inform how we conceive of the scribal milieu(s) from which the Aramaic Scrolls emerged and our understanding of pseudepigraphy in early Judaism. The article concludes with a fresh proposal for the function of the title “A Copy of the Writing of the Words of Noah” in 1QapGen 5:29.
Archaeometry of the Dead Sea Scrolls
Authors: Rabin Ira
Published: April 2013

Abstract

For many years after the discovery of the Dead Sea Scrolls, text analysis and fragment attribution were the main concern of the scholars dealing with them. The uncertain archaeological provenance of a large part of the collection added an additional difficulty to the formidable task of sorting thousands of fragments. After sixty years of scholarly research, the questions of origin, archaeological provenance, and correct attribution of the fragments are still debated. In many cases, material characterization of the scroll writing media delivers answers to these questions.

Physical and chemical examination of the skin-based material of the Dead Sea Scrolls started shortly after their discovery. Subsequent studies dedicated to long-term preservation resulted in a respectable body of knowledge about this material, in many ways very different from medieval parchment.

A new multi-instrumental approach, developed for an accurate characterization of the highly inhomogeneous “parchment” of the Dead Sea Scrolls, might lead to a reliable reconstruction of their history. This approach is illustrated by the case studies, in which we discuss the specific questions of origin (1QHa), archaeological provenance (11QTa), and post-discovery interventions (1QapGen ar).
Ntaolaltica and Pseudophygasia, two new flea beetle genera from Madagascar (Coleoptera: Chrysomelidae: Galerucinae: Alticini)
Authors: Biondi Maurizio , D’Alessandro Paola
Published: April 2013

Ntaolaltica antennata gen.n. and sp.n. and Pseudophygasia gen.n. from Madagascar are described. The following new combinations are established: Phygasia ambohitsitondroensis Bechyné, 1952 (= Pseudophygasia ambohitsitondroensis (Bechyné, 1952) comb.n.); Phygasia analis (Harold, 1877) (= Pseudophygasia analis (Harold, 1877) comb.n.); Phygasia apolinaria Bechyné, 1952 (= Pseudophygasia apolinaria (Bechyné, 1952) comb.n.); Phygasia denotata Bechyné, 1952 (= Pseudophygasia denotata (Bechyné, 1952) comb.n.); Phygasia freyi Bechyné, 1964 (= Pseudophygasia freyi (Bechyné, 1964) comb.n.); Phygasia furax Bechyné, 1952 (= Pseudophygasia furax (Bechyné, 1952) comb.n.); Phygasia goudoti (Harold, 1877) (= Pseudophygasia goudoti (Harold, 1877) comb.n.); Phygasia bicolor Weise, 1910 (= Diphaulacosoma bicolor (Weise, 1910) comb.n.); Phygasia scutellaris Weise, 1910 (= Diphaulacosoma scutellare (Weise, 1910) comb.n.). Photomicrographs and scanning electron micrographs of peculiar morphological characters, and distributional data are also provided.