bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Conscious Thoughts Cause Behavior?
Authors: Baumeister Roy F. , Masicampo E. J. , Vohs Kathleen D.
Published: December 2010

Everyday intuitions suggest full conscious control of behavior, but evidence of unconscious causation and automaticity has sustained the contrary view that conscious thought has little or no impact on behavior. We review studies with random assignment to experimental manipulations of conscious thought and behavioral dependent measures. Topics include mental practice and simulation, anticipation, planning, reflection and rehearsal, reasoning, counterproductive effects, perspective taking, self-affirmation, framing, communication, and overriding automatic responses. The evidence for conscious causation of behavior is profound, extensive, adaptive, multifaceted, and empirically strong. However, conscious causation is often indirect and delayed, and it depends on interplay with unconscious processes. Consciousness seems especially useful for enabling behavior to be shaped by nonpresent factors and by social and cultural information, as well as for dealing with multiple competing options or impulses. It is plausible that almost every human behavior comes from a mixture of conscious and unconscious processing.
Neuroscience of Self and Self-Regulation
Authors: Heatherton Todd F.
Published: December 2010

As a social species, humans have a fundamental need to belong that encourages behaviors consistent with being a good group member. Being a good group member requires the capacity for self-regulation, which allows people to alter or inhibit behaviors that would place them at risk for group exclusion. Self-regulation requires four psychological components. First, people need to be aware of their behavior so as to gauge it against societal norms. Second, people need to understand how others are reacting to their behavior so as to predict how others will respond to them. This necessitates a third mechanism, which detects threat, especially in complex social situations. Finally, there needs to be a mechanism for resolving discrepancies between self-knowledge and social expectations or norms, thereby motivating behavior to resolve any conflict that exists. This article reviews recent social neuroscience research on the psychological components that support the human capacity for self-regulation.
Development in the Early Years: Socialization, Motor Development, and Consciousness
Authors: Kopp Claire B.
Published: December 2010

Patterns of socialization have changed in recent decades. Very young children now have fewer constraints on physical activities and greater freedom to assert themselves. This parenting style, I suggest, has implications for developmental processes related to upright locomotion, the use of hands as tools, and an embodied consciousness. This review explores four issues. First, I summarize historical trends in patterns of child-rearing and possible developmental consequences. Then I explore evolutionary patterns as a means to further developmental understanding of the initial phases of motor development. The third section reviews research on young humans' developmental paths toward locomotion and hand skills, examining early and current findings. Finally, I raise the issue of a body-action consciousness that emerges during infancy and the toddler years, suggest its developmental relevance, situate the theme in current developmental models, and explore applied implications.
Causal Learning and Inference as a Rational Process: The New Synthesis
Authors: Holyoak Keith J. , Cheng Patricia W.
Published: December 2010

Over the past decade, an active line of research within the field of human causal learning and inference has converged on a general representational framework: causal models integrated with Bayesian probabilistic inference. We describe this new synthesis, which views causal learning and inference as a fundamentally rational process, and review a sample of the empirical findings that support the causal framework over associative alternatives. Causal events, like all events in the distal world as opposed to our proximal perceptual input, are inherently unobservable. A central assumption of the causal approach is that humans (and potentially nonhuman animals) have been designed in such a way as to infer the most invariant causal relations for achieving their goals based on observed events. In contrast, the associative approach assumes that learners only acquire associations among important observed events, omitting the representation of the distal relations. By incorporating Bayesian inference over distributions of causal strength and causal structures, along with noisy-logical (i.e., causal) functions for integrating the influences of multiple causes on a single effect, human judgments about causal strength and structure can be predicted accurately for relatively simple causal structures. Dynamic models of learning based on the causal framework can explain patterns of acquisition observed with serial presentation of contingency data and are consistent with available neuroimaging data. The approach has been extended to a diverse range of inductive tasks, including category-based and analogical inferences.
Socialization Processes in the Family: Social and Emotional Development
Authors: Grusec Joan E.
Published: December 2010

Children learn moral values and social conventions through a process of socialization, much of which involves parenting. The process is bidirectional and involves a complex interplay between evolutionary predispositions and genetic and socio-cultural factors. Children's perception of, or assignment of meaning to, parenting interventions is central. Socialization occurs in different domains marked by different aspects of the parent-child relationship and different underlying mechanisms. Each domain requires different parenting actions that must be matched to the domain in which the child is operating and that result in different outcomes for the child. The domains include protection, mutual reciprocity, control, guided learning, and group participation, and are assumed to be operative in all cultures. The review concludes that children need to experience their parents as supportive and understanding, that they need structure, and that they need to feel they have some degree of control over their own actions.
Chronically elevated glucose compromises myocardial mitochondrial DNA integrity by alteration of mitochondrial topoisomerase function
Authors: Medikayala S. , Piteo B. , Zhao X. , Edwards J. G.
Published: December 2010

Mitochondrial dysfunction has a significant role in the development and complications of diabetic cardiomyopathy. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) mutations are also associated with different types of cancer and neurodegenerative diseases. The goal of this study was to determine if chronically elevated glucose increase in mtDNA damage contributed to mitochondrial dysfunction and identify the underlying basis for mtDNA damage. H9c2 myotubes (a cardiac-derived cell line) were studied in the presence of 5.5, 16.5, or 33.0 mM glucose for up to 13 days. Tests of mitochondria function (Complex I and IV activity and ATP generation) were all significantly depressed by elevated media glucose. Intramitochondrial superoxide and intracellular superoxide levels were transiently increased during the experimental period. AnnexinV binding (a marker of apoptosis) was significantly increased after 7 and 13 days of high glucose. Thirteen days of elevated glucose significantly increased mtDNA damage globally and across the region encoding for the three subunits of cytochrome oxidase. Using mitochondria isolated from cells chronically exposed to elevated glucose, we observed significant increases in topoisomerase-linked DNA cleavage. Mitochondria-dependent DNA cleavage was significantly exacerbated by H2O2 and that immunoprecipitation of mitochondrial extracts with a mtTOP1 antibody significantly decreased DNA cleavage, indicating that at least part of this activity could be attributed to mtTOP1. We conclude that even mild increases in glucose presentation compromised mitochondrial function as a result of a decline in mtDNA integrity. Separate from a direct impact of oxidative stress on mtDNA, ROS-induced alteration of mitochondrial topoisomerase activity exacerbated and propagated increases in mtDNA damage. These findings are significant in that the activation/inhibition state of the mitochondrial topoisomerases will have important consequences for mitochondrial DNA integrity and the well being of the myocardium.
Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis
Authors: Basuroy Shyamali , Tcheranova Dilyara , Bhattacharya Sujoy , Leffler Charles W. , Parfenova Helena
Published: December 2010

We investigated the role of reactive oxygen species (ROS) in promoting cell survival during oxidative stress induced by the inflammatory mediator tumor necrosis factor-α (TNF-α) in cerebral microvascular endothelial cells (CMVEC) from newborn piglets. Nox4 is the major isoform of NADPH oxidase responsible for TNF-α-induced oxidative stress and apoptosis in CMVEC. We present novel data that Nox4 NADPH oxidase-derived ROS also initiate a cell survival mechanism by increasing production of a gaseous antioxidant mediator carbon monoxide (CO) by constitutive heme oxygenase-2 (HO-2). TNF-α rapidly enhanced endogenous CO production in a superoxide- and NADPH oxidase-dependent manner in CMVEC with innate, but not with small interfering RNA (siRNA)-downregulated Nox4 activity. CORM-A1, a CO-releasing compound, inhibited Nox4-mediated ROS production and enhanced cell survival in TNF-α-challenged CMVEC. The ROS-induced CO-mediated survival mechanism requires functional interactions between the protein kinase B/Akt and extracellular signal-related kinase (ERK)/p38 MAPK signaling pathways activated by TNF-α. In Akt siRNA-transfected CMVEC and in cells with pharmacologically inhibited Akt, Erk1/2, and p38 mitogen-activated protein kinase (MAPK) activities, CORM-A1 was no longer capable of blocking Nox4 activation and apoptosis caused by TNF-α. Overall, Nox4 NADPH oxidase-derived ROS initiate both death and survival pathways in TNF-α-challenged CMVEC. The ROS-dependent cell survival pathway is mediated by an endogenous antioxidant CO, which inhibits Nox4 activation via a mechanism that includes Akt, ERK1/2, and p38 MAPK signaling pathways. The ability of CO to inhibit TNF-α-induced ERK1/2 and p38 MAPK activities in an Akt-dependent manner appears to be the key element in ROS-dependent survival of endothelial cells during TNF-α-mediated brain inflammatory disease.
Sca-1 influences the innate immune response during skeletal muscle regeneration
Authors: Long Kimberly K. , Pavlath Grace K. , Montano Monty
Published: December 2010

Efficient muscle regeneration requires the clearance of dead and dying tissue via phagocytosis before remodeling. We have previously shown that mice lacking stem cell antigen-1 (Sca-1) display a defect in skeletal muscle regeneration characterized by increased fibrosis and decreased turnover of the extracellular matrix. In the present study we demonstrate that Sca-1−/− mice have a defect in their capacity to recruit soluble IgM, and subsequently C3 complement, to damaged muscle. We hypothesize that this defect in recruitment delays or decreases phagocytosis by macrophages, contributing to the previously observed fibrotic phenotype of these mice. As the primary source of soluble IgM is peritoneal B-1a cells, which are a subset of self-renewing B cells, we analyzed this cell population and observed a significant reduction in B-1a cells in Sca-1−/− animals. Interestingly, these mice are protected from ischemia-reperfusion injury, an acute inflammatory reaction also mediated by IgM and C3 complement that has been linked to a deficit in B-1a cells in previous studies. Collectively, these data reveal a novel role for Sca-1 in innate immunity during muscle regeneration and indicate that further elucidation of immuno-myogenic processes will help to better understand and promote muscle regeneration.
Hypoxia. 2. Hypoxia regulates cellular metabolism
Authors: Wheaton William W. , Chandel Navdeep S.
Published: December 2010

Adaptation to lowering oxygen levels (hypoxia) requires coordinated downregulation of metabolic demand and supply to prevent a mismatch in ATP utilization and production that might culminate in a bioenergetic collapse. Hypoxia diminishes ATP utilization by downregulating protein translation and the activity of the Na-K-ATPase. Hypoxia diminishes ATP production in part by lowering the activity of the electron transport chain through activation of the transcription factor hypoxia-inducible factor-1. The decrease in electron transport limits the overproduction of reactove oxygen species during hypoxia and slows the rate of oxygen depletion to prevent anoxia. In this review, we discuss these mechanisms that diminish metabolic supply and demand for adaptation to hypoxia.
Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans
Authors: Matsukawa Toshiyoshi , Miyamoto Takenori
Published: December 2010

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg−1·min−1) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg−1·min−1) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg−1·min−1) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.
Evidence for basolateral Cl−channels as modulators of apical Cl−secretion in pulmonary epithelia of Xenopus laevis
Authors: Berger Jens , Richter Katrin , Clauss Wolfgang G. , Fronius Martin
Published: December 2010

Pulmonary epithelia of air-breathing vertebrates are covered by a thin, fluid layer that is essential for immune defense and gas diffusion. The composition of this layer is maintained by ion transport mechanisms, including Cl−transport. The present study focuses on the function of basolateral Cl−channels in Xenopus pulmonary epithelia, since knowledge concerning this issue is limited. Therefore, Ussing chamber measurements were performed, and transepithelial short-circuit currents ( ISC) were monitored. Basolateral application of the Cl−channel inhibitor N-phenylanthranilic acid (DPC) resulted in an increase of the ISC, indicating a DPC-sensitive Cl−conductance. This observation was confirmed in experiments using an apical-to-basolateral Cl−gradient, with and without nystatin (apical side) to permeabilize the epithelia as well as by establishing an iodide gradient. The DPC-sensitive Cl−conductance was influenced by procedures interfering with apical Cl−secretion. For example, the effect of forskolin was increased when basolateral Cl−channels were blocked by the simultaneous application of DPC. Activation of apical Cl−secretion by forskolin/IBMX and subsequent DPC application resulted in a significantly reduced DPC effect. Accordingly, DPC led to an increased apical Cl−secretion estimated by an increased 5-nitro-2-(3-phenylpropylamino)benzoic acid-sensitive ISC. Furthermore, inhibition of basolateral anion exchangers responsible for Cl−uptake resulted in a decreased DPC-sensitive current. Taken together, we have evidence concerning the function of basolateral Cl−channels in Xenopus pulmonary epithelium and that these channels play a significant role in mediating apical Cl−secretion involving a novel Cl−recycling mechanism across the basolateral membrane.
Characteristics of myogenic reactivity in isolated rat mesenteric veins
Authors: Enouri Saad , Monteith Gabrielle , Johnson Ron
Published: December 2010

Mechanisms of mechanically induced venous tone and its interaction with the endothelium and key vasoactive neurohormones are not well established. We investigated the contribution of the endothelium, l-type voltage-operated calcium channels (l-VOCCs), and PKC and Rho kinase to myogenic reactivity in mesenteric vessels exposed to increasing transmural pressure. The interaction of myogenic reactivity with norepinephrine (NE) and endothelin-1 (ET-1) was also investigated. Pressure myography was used to study isolated, cannulated, third-order rat mesenteric small veins and arteries. NE and ET-1 concentration response curves were constructed at low, intermediate, and high transmural pressures. Myogenic reactivity was not altered by nitric oxide synthase inhibition with Nω-nitro-l-arginine (l-NNA; 100 μM) or endothelium removal in both vessels. l-VOCCs blockade (nifedipine, 1 μM) completely abolished arterial tone, while only partially reducing venous tone. PKC (chelerythrine, 2.5 μM) and Rho kinase (Y27632, 3 μM) inhibitors largely abolished venous and arterial myogenic reactivity. There was no significant difference in the sensitivity of NE or ET-1-induced contractions within vessels. However, veins were more sensitive to NE and ET-1 when compared with corresponding arteries at low, intermediate, and high transmural pressures, respectively. These results suggest that 1) myogenic factors are important contributors to net venous tone in mesenteric veins; 2) PKC and Rho activation are important in myogenic reactivity in both vessels, while l-VOCCs play a limited role in the veins vs. the arteries, and the endothelium does not appear to modulate myogenic reactivity in either vessel type; and 3) mesenteric veins maintain an enhanced sensitivity to NE and ET-1 compared with the arteries when studied under conditions of changing transmural distending pressure.
Lengthening-contractions in isolated myocardium impact force development and worsen cardiac contractile function in the mdx mouse model of muscular dystrophy
Authors: Xu Ying , Delfín Dawn A. , Rafael-Fortney Jill A. , Janssen Paul M. L.
Published: December 2010

Lengthening-contractions exert eccentric stress on myofibers in normal myocardium. In congestive heart failure caused by a variety of diseases, the impact of lengthening-contractions of myocardium likely becomes more prevalent and severe. The present study introduces a method to investigate the role of stretching imposed by repetitive lengthening-contractions in myocardium under near-physiological conditions. By exerting various stretch-release ramps while the muscle is contracting, consecutive lengthening-contractions and their potential detrimental effect on cardiac function can be studied. We tested our model and hypothesis in age-matched (young and adult) mdx and wild-type mouse right ventricular trabeculae. These linear and ultrathin muscles possess all major cardiac cell types, and their contractile behavior very closely mimics that of the whole myocardium. In the first group of experiments, 10 lengthening-contractions at various magnitudes of stretch were performed in trabeculae from 10-wk-old mdx and wild-type mice. In the second group, 100 lengthening-contractions at various magnitudes were conducted in trabeculae from 10- and 20-wk-old mice. The peak isometric active developed tension (Fdev, in mN/mm2) and kinetic parameters time to peak tension (TTP, in ms) and time from peak tension to half-relaxation (RT50, in ms) were measured. Our results indicate lengthening-contractions significantly impact contractile behavior, and that dystrophin-deficient myocardium in mdx mice is significantly more susceptible to these damaging lengthening-contractions. The results indicate that lengthening-contractions in intact myocardium can be used in vitro to study this emerging contributor to cardiomyopathy.
Sensorimotor adaptation error signals are derived from realistic predictions of movement outcomes
Authors: Wong Aaron L. , Shelhamer Mark
Published: December 2010

Neural systems that control movement maintain accuracy by adaptively altering motor commands in response to errors. It is often assumed that the error signal that drives adaptation is equivalent to the sensory error observed at the conclusion of a movement; for saccades, this is typically the visual (retinal) error. However, we instead propose that the adaptation error signal is derived as the difference between the observed visual error and a realistic prediction of movement outcome. Using a modified saccade-adaptation task in human subjects, we precisely controlled the amount of error experienced at the conclusion of a movement by back-stepping the target so that the saccade is hypometric (positive retinal error), but less hypometric than if the target had not moved (smaller retinal error than expected). This separates prediction error from both visual errors and motor corrections. Despite positive visual errors and forward-directed motor corrections, we found an adaptive decrease in saccade amplitudes, a finding that is well-explained by the employment of a prediction-based error signal. Furthermore, adaptive changes in movement size were linearly correlated to the disparity between the predicted and observed movement outcomes, in agreement with the forward-model hypothesis of motor learning, which states that adaptation error signals incorporate predictions of motor outcomes computed using a copy of the motor command (efference copy).
Interregional synaptic competition in neurons with multiple STDP-inducing signals
Authors: Bar Ilan Lital , Gidon Albert , Segev Idan
Published: December 2010

Neocortical layer 5 (L5) pyramidal cells have at least two spike initiation zones: Na+ spikes are generated near the soma, and Ca2+ spikes at the apical dendritic tuft. These spikes interact with each other and serve as signals for synaptic plasticity. The present computational study explores the implications of having two spike-timing-dependent plasticity (STDP) signals in a neuron, each with its respective regional population of synaptic “pupils.” In a detailed model of an L5 pyramidal neuron, competition emerges between synapses belonging to different regions, on top of the competition among synapses within each region, which characterizes the STDP mechanism. Interregional competition results in strengthening of one group of synapses, which ultimately dominates cell firing, at the expense of weakening synapses in other regions. This novel type of competition is inherent to dendrites with multiple regional signals for Hebbian plasticity. Surprisingly, such interregional competition exists even in a simplified model of two identical coupled compartments. We find that in a model of an L5 pyramidal cell, the different synaptic subpopulations “live in peace” when the induction of Ca2+ spikes requires the back-propagating action potential (BPAP). Thus we suggest a new key role for the BPAP, to maintain the balance between synaptic efficacies throughout the dendritic tree, thereby sustaining the functional integrity of the entire neuron.
Corticospinal excitability during preparation for an anticipatory action is modulated by the availability of visual information
Authors: Marinovic Welber , Reid Campbell S. , Plooy Anna M. , Riek Stephan , Tresilian James R.
Published: December 2010

To intercept rapidly moving objects, people must predict the right time to initiate their actions. The timing of movement initiation in interceptions is thought to be determined when a perceptual variable specifying time to contact reaches a criterion value. If a response needs to be aborted, the performer must make a decision before this moment. It has been recently shown that the minimal time to suppress an anticipatory action takes longer during motion extrapolation than during continuous visual information. In experiment 1, we sought to determine whether or not the availability of visual information would 1) affect the latency to inhibit an anticipatory action, and 2) modulate the level of excitability in the motor cortex (M1). The behavioral results showed that the absence of visual information prolonged the latency to stop the movement as previously reported. The neurophysiological data indicated that corticospinal excitability levels were affected by the availability of visual information. In experiment 2, we sought to verify whether corticospinal excitability levels would also differ between the two visual conditions when the task did not involve response suppression. The results of experiment 2 indicated that excitability levels did not differ between visual conditions. Overall, our findings indicated that the buildup of motor activation can also play a role in determining different latencies to inhibit an anticipatory action. They also suggest that the buildup of motor activation in the corticospinal pathways can be strategically modulated to the requirements of the task during continuous visual information.
A new approach for detecting and analyzing cutaneous reflexes during locomotion
Authors: Bagna Maimouna , Bouyer Laurent J.
Published: December 2010

During human walking, due to their small amplitude, individual cutaneous reflex responses are difficult to detect in surface EMG recordings. In this study, we present a new algorithm to automatically detect individual cutaneous reflex responses and to extract their corresponding onset latency, amplitude, duration, and sign. To discriminate reflex responses from the intrinsic variability of the background EMG, each stimulated cycle is compared with 10 adjacent nonstimulated cycles, looking for consistent differences. In the first 200 ms after stimulation, reflex responses are detected when ≥9/10 of these differences are either positive or negative. This approach does not require amplitude thresholds or fixed time windows for reflex detection. To reduce false detections, a postprocessing step selects 50 nonstimulated cycles randomly, processes them through the algorithm as stimulated cycles, and establishes a minimal reflex duration criterion that it then used to validate the detected responses. Validated responses from an entire test session are then reported on a colormap (reflex activity map) from which specific responses can be identified and quantified. The new method was validated in ten participants, three cutaneous nerves, and two protocols (phase modulation and recruitment curves). Compared with the classical method, the new algorithm showed better performance in terms of detection accuracy, specificity, and reliability. Although tested here to evaluate cutaneous reflexes during human walking, the simplicity of this method is such that it could easily be used with other reflexes, signals, and preparations.
A Holographic View on Physics out of Equilibrium
Authors: Hubeny Veronika E. , Rangamani Mukund
Published: December 2010

We review the recent developments in applying holographic methods to understand
nonequilibrium physics in strongly coupled field theories. The emphasis will be on elucidating the relation between evolution of quantum field theories perturbed away from equilibrium and the dual picture of dynamics of classical fields in black hole
backgrounds. In particular, we discuss the linear response regime, the hydrodynamic regime, and finally the nonlinear regime of interacting quantum systems. We also describe how the duality might be used to learn some salient aspects of black hole
physics in terms of field theory observables.
An Update in Management of Noncutaneous T-Cell Lymphomas
Authors: Hwang Y. Y. , Liang R. H. S.
Published: December 2010

T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive anaplastic large cell lymphoma, T-cell lymphoma responds to conventional chemotherapy unfavourably, and most patients carry poor prognosis. In recent years, efforts have been made to improve the outcome of T-cell lymphoma patients. Novel agents, high-dose therapy, and allogeneic stem cell transplantation are studied, and various results are reported in literature. This paper looks into the prognostication and treatment approach of different entities of noncutaneous T-cell lymphoma and would focus on the latest updates in its management.
Regularity of Weakly Well‐Posed Characteristic Boundary Value Problems
Authors: Morando Alessandro , Secchi Paolo
Published: December 2010

We study the boundary value problem for a linear first‐order partial differential system with characteristic boundary of constant multiplicity. We assume the problem to be “weakly” well posed, in the sense that a unique L2‐solution exists, for sufficiently smooth data, and obeys an a priori
energy estimate with a finite loss of tangential/conormal regularity. This is the case of problems that do not satisfy the uniform Kreiss‐Lopatinskiĭ condition in the hyperbolic region of the frequency domain. Provided that the data are sufficiently smooth, we obtain the regularity of solutions, in the natural framework
of weighted conormal Sobolev spaces.
Simulating Marine New Particle Formation and Growth Using the M7 Modal Aerosol Dynamics Modal
Authors: Monahan Ciaran , Vuollekoski Henri , Kulmala Markku , O′Dowd Colin
Published: December 2010

A modal atmospheric aerosol model (M7) is evaluated in terms of predicting marine new particle formation and growth. Simulations were carried out for three different nucleation schemes involving (1) kinetic self‐nucleation of OIO (2) nucleation via OIO activation by H2SO4 and (3) nucleation via OIO activation by H2SO4 plus condensation of a low‐volatility organic vapour. Peak OIO and H2SO4 vapour concentrations were both limited to 6 × 106 molecules cm-3 at noontime while the peak organic vapour concentration was limited to 12 × 106 molecules cm-3. All simulations produced significant concentrations of new particles in the Aitken mode. From a base case particle concentration of 222 cm-3 at radii >15 nm, increases in concentrations to 366 cm-3 were predicted from the OIO‐OIO case, 722 cm-3 for the OIO‐H2SO4 case, and 1584 cm-3 for the OIO‐H2SO4 case with additional condensing organic vapours. The results indicate that open ocean new particle production is feasible for clean conditions; however, new particle production becomes most significant when an additional condensable organic vapour is available to grow the newly formed particles to larger sizes. Comparison to sectional model for a typical case study demonstrated good agreement and the validity of using the modal model.
Improved Generalized Belief Propagation for Vision Processing
Authors: Chen S. Y. , Tong Hanyang , Wang Zhongjie , Liu Sheng , Li Ming , Zhang Beiwei
Published: December 2010

Generalized belief propagation (GBP) is a region‐based belief propagation algorithm which can get good convergence in Markov random fields. However, the computation time is too heavy to use in practical engineering applications. This paper proposes a method to accelerate the efficiency of GBP. A caching technique and chessboard passing strategy are used to speed up algorithm. Then, the direction set method which is used to reduce the complexity of computing clique messages from quadric to cubic. With such a strategy the processing speed can be greatly increased. Besides, it is the first attempt to apply GBP for solving the stereomatching problem. Experiments show that the proposed algorithm can speed up by 15+ times for typical stereo matching problem and infer a more plausible result.
Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa
Authors: Wallis Carole L. , Mellors John W. , Venter Willem D. F. , Sanne Ian , Stevens Wendy
Published: December 2010

Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n=72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n=29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression.
A SP1/MIZ1/MYCN Repression Complex Recruits HDAC1 at theTRKAandp75NTRPromoters and Affects Neuroblastoma Malignancy by Inhibiting the Cell Response to NGF
Authors: Iraci Nunzio , Diolaiti Daniel , Papa Antonella , Porro Antonio , Valli Emanuele , Gherardi Samuele , Herold Steffi , Eilers Martin , Bernardoni Roberto , Valle Giuliano Della , Perini Giovanni
Published: December 2010

Neuroblastoma is the most common extracranial solid tumor of childhood. One important factor that predicts a favorable prognosis is the robust expression of the TRKA and p75NTR neurotrophin receptor genes. Interestingly, TRKA and p75NTR expression is often attenuated in aggressive MYCN-amplified tumors, suggesting a causal link between elevated MYCN activity and the transcriptional repression of TRKA and p75NTR, but the precise mechanisms involved are unclear. Here, we show that MYCN acts directly to repress TRKA and p75NTR gene transcription. Specifically, we found that MYCN levels were critical for repression and that MYCN targeted proximal/core promoter regions by forming a repression complex with transcription factors SP1 and MIZ1. When bound to the TRKA and p75NTR promoters, MYCN recruited the histone deacetylase HDAC1 to induce a repressed chromatin state. Forced re-expression of endogenous TRKA and p75NTR with exposure to the HDAC inhibitor TSA sensitized neuroblastoma cells to NGF-mediated apoptosis. By directly connecting MYCN to the repression of TRKA and p75NTR, our findings establish a key pathway of clinical pathogenicity and aggressiveness in neuroblastoma. Cancer Res; 71(2); 404–12. ©2010 AACR.
Modulation of Genetic and Epigenetic Biomarkers of Colorectal Cancer in Humans by Black Raspberries: A Phase I Pilot Study
Authors: Wang Li-Shu , Arnold Mark , Huang Yi-Wen , Sardo Christine , Seguin Claire , Martin Edward , Huang Tim H.-M. , Riedl Ken , Schwartz Steven , Frankel Wendy , Pearl Dennis , Xu Yiqing , Winston John , Yang Guang-Yu , Stoner Gary
Published: December 2010

Purpose: This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis, and expression of Wnt pathway genes.

Experimental Design: Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1–9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured.

Results: The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1–9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction.

Conclusions: These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted. Clin Cancer Res; 17(3); 598–610. ©2010 AACR.
Analysis of the Inhibitory Effect of Flavonoids on H-Ras Protein: An Anticancer Drug Target
Authors: Alhamdan Adel A. , Masoodi Tariq Ahmad
Published: December 2010

Background: GTP-bound mutant forms of H-Ras (Harvey-Ras) proteins are found in almost 30% of human tumors. In the present in silico study, the inhibitory effect of different flavonoid compounds on mutant H-Ras protein p21 has been assessed. The inhibitory effect of flavonoids is compared with three known clinical anticancer drugs. Besides, these have been interacted with normal H-Ras and tumor necrosis factor (TNF) proteins for toxicity check. Results: Upon docking, it was found that flavonoids such as naringenin, daidzein, and hesperetin showed highest affinity (most negative ΔG), while rutin showed no affinity towards mutant H-Ras. The three clinical anticancer agents (erlotinib, letrozole and exemestane) showed binding energies in the range of –1.11 to –5.51 kcal/mol which is comparatively lower than the flavonoids indicating efficacy of flavonoids to prevent complex formation with Raf and thereby prevent downstream effects. However, flavonoids showed no interaction with normal H-Ras and TNF indicating little or no cytotoxicity. Conclusion: Our study demonstrates that flavonoids (naringenin, daidzein, and hesperetin) are effective drugs to inhibit complex formation between mutant H-Ras P21 and RBD of Raf.
A Tale of Tailless
Authors: Gui Hongxing , Li Mei-Ling , Tsai Chih-Cheng
Published: December 2010

Drosophila Tailless(Tll) and its vertebrate homologue Tlx are conserved orphan nuclear receptors specifically expressed in the eye and the forebrain. Tll and Tlx act primarily as transcriptional repressors through their interactions with transcriptional corepressors, Atrophin family proteins, and histone-tail/chromatin-modifying factors such as lysine-specific histone demethylase 1 and histone deacetylases. The functional importance of Tll and Tlx is made apparent by the recent discovery that they are expressed in neural stem cells (NSCs) and are required for self-renewal of these cells in both Drosophila and the mouse. This review provides a snapshot of current knowledge about Tll and Tlx and their transcriptional network, which maintains NSCs in developing and adult animals.
Elder Abuse and Mortality: The Role of Psychological and Social Wellbeing
Authors: Dong X.Q. , Simon M.A. , Beck T.T. , Farran C. , McCann J.J. , Mendes de Leon C.F. , Laumann E. , Evans D.A.
Published: December 2010

Background: Elder abuse is a pervasive human right and public health issue. Objectives: We aimed to examine the mortality associated with elder abuse across levels of psychological and social factors. Methods: The Chicago Health and Aging Project (CHAP) is a prospective population-based cohort study that began in 1993. A subset of these participants enrolled between 1993 and 2005 had elder abuse reported to social services agencies (n = 113). Mortality was ascertained during follow-up and with the National Death Index. Psychosocial factors (depression, social network and social engagement) were assessed during the CHAP interview. Cox proportional hazard models were used to assess the mortality of elder abuse across levels of psychosocial factors using time-varying covariate analyses. Results: The median follow-up time for the cohort (n = 7,841) was 7.6 years (interquartile range 3.8–12.4 years). In multivariate analyses, those with highest (hazard ratio (HR) 2.60, 95% CI 1.58–4.28) and middle levels (HR 2.18, 95% CI 1.19–3.99) of depressive symptoms had an increased mortality risk associated with elder abuse. For social network, those with lowest (HR 2.50, 95% CI 1.62–3.87) and middle levels (HR 2.65, 95% CI 1.52–4.60) of social network had increased mortality risk associated with elder abuse. For social engagement, those with lowest (HR 2.32, 95% CI 1.47–3.68) and middle levels (HR 2.59, 95% CI 1.65–5.45) of social engagement had increased mortality risk associated with elder abuse. Among those with lowest levels of depressive symptoms, highest levels of social network and social engagement, there was no significant effect of reported or confirmed elder abuse on mortality risk. Conclusion: Mortality risk associated with elder abuse was most prominent among those with higher levels of depressive symptoms and lower levels of social network and social engagement.
Use and Effect of Vasopressors after Pediatric Traumatic Brain Injury
Authors: Di Gennaro Jane L. , Mack Christopher D. , Malakouti Amin , Zimmerman Jerry J. , Armstead William , Vavilala Monica S.
Published: December 2010

Background: Vasopressors are commonly used to increase mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP) after traumatic brain injury (TBI), but there are few data comparing vasopressor effectiveness after pediatric TBI. Objective: To determine which vasopressor is most effective at increasing MAP and CPP in children with moderate-to-severe TBI. Methods: After institutional review board approval, we performed a retrospective cohort study of children 0–17 years old admitted to a level 1 trauma center (Harborview Medical Center, Seattle, Wash., USA) between 2002 and 2007 with moderate-to-severe TBI who received a vasopressor to increase blood pressure. Baseline demographic and physiologic characteristics and hourly physiologic monitoring for 3 h after having started a vasopressor were abstracted. We evaluated differences in MAP and CPP at 3 h after initiation of therapy between phenylephrine, dopamine and norepinephrine among patients who did not require a second vasopressor during this time. Multivariate linear regression was used to adjust for age, gender, injury severity score and baseline MAP or CPP and to cluster by subject. Results: Eighty-two patients contributed data to the entire dataset. The most common initial medication was phenylephrine for 47 (57%). Patients receiving phenylephrine and norepinephrine tended to be older than those receiving dopamine and epinephrine. Thirteen (16%) of the patients received a second vasopressor during the first 3 h of treatment and were thus not included in the regression analyses; these patients received more fluid resuscitation and exhibited higher in-hospital mortality (77 vs. 32%; p = 0.004) compared to patients receiving a single vasopressor. The norepinephrine group exhibited a 5 mm Hg higher MAP (95% CI: –4 to 13; p = 0.31) and a 12 mm Hg higher CPP (95% CI: –2 to 26; p = 0.10) than the phenylephrine group, and a 5 mm Hg higher MAP (95% CI: –4 to 15; p = 0.27) and a 10 mm Hg higher CPP (95% CI: –5 to 25; p = 0.18) than the dopamine group. However, in post hoc analysis, after adjusting for time to start of vasopressor, hypertonic saline and pentobarbital, the effect on MAP was lost, but the CPP was 8 mm Hg higher (95% CI: –10 to 25; p = 0.39) than in the phenylephrine group, and 5 mm Hg higher (95% CI: –14 to 24; p = 0.59) than in the dopamine group. Conclusions: Vasopressor use varied by age. While there was no statistically significant difference in MAP or CPP between vasopressor groups, norepinephrine was associated with a clinically relevant higher CPP and lower intracranial pressure at 3 h after start of vasopressor therapy compared to the other vasopressors examined.
The Neural Career of Sensory-motor Metaphors
Authors: Desai Rutvik H. , Binder Jeffrey R. , Conant Lisa L. , Mano Quintino R. , Seidenberg Mark S.
Published: December 2010

The role of sensory-motor systems in conceptual understanding has been controversial. It has been proposed that many abstract concepts are understood metaphorically through concrete sensory-motor domains such as actions. Using fMRI, we compared neural responses with literal action (Lit; The daughter grasped the flowers), metaphoric action (Met; The public grasped the idea), and abstract (Abs; The public understood the idea) sentences of varying familiarity. Both Lit and Met sentences activated the left anterior inferior parietal lobule, an area involved in action planning, with Met sentences also activating a homologous area in the right hemisphere, relative to Abs sentences. Both Met and Abs sentences activated the left superior temporal regions associated with abstract language. Importantly, activation in primary motor and biological motion perception regions was inversely correlated with Lit and Met familiarity. These results support the view that the understanding of metaphoric action retains a link to sensory-motor systems involved in action performance. However, the involvement of sensory-motor systems in metaphor understanding changes through a gradual abstraction process whereby relatively detailed simulations are used for understanding unfamiliar metaphors, and these simulations become less detailed and involve only secondary motor regions as familiarity increases. Consistent with these data, we propose that anterior inferior parietal lobule serves as an interface between sensory-motor and conceptual systems and plays an important role in both domains. The similarity of abstract and metaphoric sentences in the activation of left superior temporal regions suggests that action metaphor understanding is not completely based on sensory-motor simulations but relies also on abstract lexical-semantic codes.
Memory Strength Effects in fMRI Studies: A Matter of Confidence
Authors: de Zubicaray Greig I. , McMahon Katie L. , Dennis Simon , Dunn John C.
Published: December 2010

To investigate potentially dissociable recognition memory responses in the hippocampus and perirhinal cortex, fMRI studies have often used confidence ratings as an index of memory strength. Confidence ratings, although correlated with memory strength, also reflect sources of variability, including task-irrelevant item effects and differences both within and across individuals in terms of applying decision criteria to separate weak from strong memories. We presented words one, two, or four times at study in each of two different conditions, focused and divided attention, and then conducted separate fMRI analyses of correct old responses on the basis of subjective confidence ratings or estimates from single- versus dual-process recognition memory models. Overall, the effect of focussing attention on spaced repetitions at study manifested as enhanced recognition memory performance. Confidence- versus model-based analyses revealed disparate patterns of hippocampal and perirhinal cortex activity at both study and test and both within and across hemispheres. The failure to observe equivalent patterns of activity indicates that fMRI signals associated with subjective confidence ratings reflect additional sources of variability. The results are consistent with predictions of single-process models of recognition memory.