bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of an Intermediate Inclusion in Soil on a Buried Lined Tunnel Due to a Nearby Explosion
Authors: Feldgun V.R. , Karinski Y.S. , Yankelevsky D.Z.
Published: March 2013

The paper presents the analysis of a buried explosion in the proximity of a tunnel in a soil medium. The soil is modeled as an elastic plastic material with irreversible bulk and deviatoric strains. The tunnel lining is modeled as an elastic plastic Timoshenko shell. An inclusion is placed in soil between the explosion source and the tunnel and its effect on the tunnel response is investigated. A coupled approach is proposed to allow to perform stable calculations of that complex problem and to follow the development of the large deformations and distortions of the tunnel lining's shape, as well as the large deformations of the explosive cavity. The effect of the rigid single inclusion or of the set of rigid inclusions located between the charge and the lined tunnel on the tunnel lining's response has been studied. When the inclusion is relatively distant from the lining, even a small inclusion improves the state of displacement and pressure of the lining, while when the inclusion is placed close to the lining, the lining's displacements increase. When the inclusion is small, its size slightly affects the lining shape while for middle sized inclusion the permanent displacement sharply decreases. Compared to the case of a single inclusion, a set of intermediate inclusions of the same size slightly decrease the peak stress at the front point and more significantly protects the periphery zone. The usage of larger inclusions yields better protection of the lining front part.
Simulation of Retrofitted Unreinforced Concrete Masonry Unit Walls under Blast Loading
Authors: Aghdamy Sanam , Wu Chengqing , Griffith Michael
Published: March 2013

This paper describes an investigation into the effectiveness of using spray-on nano-particle reinforced polymer and aluminium foam as new types of retrofit material to prevent the breaching and collapse of unreinforced concrete masonry walls subjected to blast over a whole range of dynamic and impulsive regimes. Material models from the LS-DYNA material library were used to model the behaviors of each of the materials and its interface for retrofitted and unretrofitted masonry walls. Available test data were used to validate the numerical models. Using the validated LS-DYNA numerical models, the pressure-impulse diagrams for retrofitted concrete masonry walls were constructed. The efficiency of using these retrofits to strengthen the unreinforced concrete masonry unit (CMU) walls under various pressures and impulses was investigated using pressure-impulse diagrams. Comparisons were made to find the most efficient retrofits for masonry walls against blasts.
Hfq restructures RNA-IN and RNA-OUT and facilitates antisense pairing in the Tn10/IS10 system
Authors: Ross Joseph A. , Ellis Michael J. , Hossain Shahan , Haniford David B.
Published: March 2013

Hfq functions in post-transcriptional gene regulation in a wide range of bacteria, usually by promoting base-pairing of mRNAs and trans-encoded sRNAs that share partial sequence complementarity. It is less clear if Hfq is required for pairing of cis-encoded RNAs (i.e., antisense RNAs) with their target mRNAs. In the current work, we have characterized the interactions between Escherichia coli Hfq and the components of the Tn10/IS10 antisense system, RNA-IN and RNA-OUT. We show that Hfq interacts with RNA-OUT through its proximal RNA-binding surface, as is typical for Hfq and trans-encoded sRNAs. In contrast, RNA-IN binds both proximal and distal RNA-binding surfaces in Hfq with a higher affinity for the latter, as is typical for mRNA interactions in canonical sRNA-mRNA pairs. Importantly, an amino acid substitution in Hfq that interferes with RNA binding to the proximal site negatively impacts RNA-IN:OUT pairing in vitro and suppresses the ability of Hfq to negatively regulate IS10 transposition in vivo. We also show that Hfq binding to RNA-IN and RNA-OUT alters secondary structure elements in both of these RNAs and speculate that this could be important in how Hfq facilitates RNA-IN:OUT pairing. Based on the results presented here, we suggest that Hfq could be involved in regulating RNA pairing in other antisense systems, including systems encoded by other transposable elements.
Mining Coal or Finding Terrorists: The Expanding Search Paradigm
Authors: Alpern Steve , Lidbetter Thomas
Published: March 2013

We show how to optimize the search for a hidden object, terrorist, or simply Hider, located at a point H according to a known or unknown distribution ν on a rooted network Q. We modify the traditional “pathwise search” approach to a more general notion of “expanding search.” When the Hider is restricted to the nodes of Q, an expanding search S consists of an ordering [Formula: see text] of the arcs of a spanning subtree such that the root node is in a1 and every arc ai is adjacent to a previous arc aj, j < i. If ak contains H, the search time T is [Formula: see text], where λ is length measure on Q. For more general distributions ν, an expanding search S is described by the nested family of connected sets S(t) that specify the area of Q that has been covered by time t. S(0) is the root, [Formula: see text]. For a known Hider distribution ν on a tree Q, the expected time minimizing strategy [Formula: see text] begins with the rooted subtree Q′ maximizing the “density” ν(Q′)/λ(Q′). (For arbitrary networks, we use this criterion on all spanning subtrees.) The search [Formula: see text] can be interpreted as the optimal method of mining known coal seams, when the time to move miners or machines is negligible compared to digging time. When the Hider distribution is unknown, we consider the zero-sum search game where the Hider picks H, the Searcher S, and the payoff is T. For trees Q, the value is V = (λ(Q) + D)/2, where D is a mean distance from root to leaf nodes. If Q is 2-arc connected, V = λ(Q)/2. Applications and interpretations of the expanding search paradigm are given, particularly to multiple agent search.
On a Level-Set Characterization of the Value Function of an Integer Program and Its Application to Stochastic Programming
Authors: Trapp Andrew C. , Prokopyev Oleg A. , Schaefer Andrew J.
Published: March 2013

We propose a level-set approach to characterize the value function of a pure linear integer program with inequality constraints. We study theoretical properties of our characterization and show how they can be exploited to optimize a class of stochastic integer programs through a value function reformulation. Specifically, we develop algorithmic approaches that solve two-stage multidimensional knapsack problems with random budgets, yielding encouraging computational results.
Intraoperative Vancomycin Pharmacokinetics in Cardiac Surgery With or Without Cardiopulmonary Bypass
Authors: Cotogni Paolo , Passera Roberto , Barbero Cristina , Gariboldi Angela , Moscato Donatella , Izzo Gennaro , Rinaldi Mauro
Published: March 2013

BACKGROUND

Vancomycin is administered as antimicrobial prophylaxis to patients undergoing cardiac surgery, an intervention that usually requires cardiopulmonary bypass (CPB). Previous studies reported that CPB modifies vancomycin pharmacokinetic parameters.

OBJECTIVE

To investigate intraoperative vancomycin pharmacokinetic changes in a large population of patients undergoing cardiac surgery with CPB (on-pump) and without CPB (off-pump).

METHODS

In this prospective study, patients undergoing cardiac surgery received a single dose of vancomycin 1000 mg in a 60-minute intravenous infusion, with skin incision performed between 16 and 120 minutes after the end of the infusion. For the on-pump group, arterial samples were drawn before CPB (end of infusion, skin incision), during CPB (5, 30, and 60 minutes, and then every 60 minutes until CPB end), and after CPB (wound closure). For the off-pump group, arterial samples were drawn time-matched to the CPB period of the on-pump group.

RESULTS

Two hundred thirty-six consecutive patients were enrolled: 215 in the on-pump group and 21 in the off-pump group. A total of 1682 serum vancomycin concentrations (median 7/patient) were measured. Vancomycin maximum concentration ([Cmax] on-pump, 45.6 mg/L; off-pump, 47.3 mg/L); area under the concentration-time curve, zero to 8 hours ([AUC0–8] on-pump, 104.6 mg*h/L; off-pump, 96.1 mg*h/L); volume of distribution ([Vd] on-pump, 31 L; off-pump, 28.2 L); and total body clearance ([Cl] on-pump, 6.23 L/h; off-pump, 7.05 L/h) were similar. Moreover, Cmax and AUC0-∞ (AUC, zero to infinity) showed values comparable to those found in previous studies performed on noncardiac surgery patients.

CONCLUSIONS

In our study there were no significant differences in vancomycin Cmax, AUC0–8, Vd, and Cl between the on-pump and off-pump groups. CPB does not seem to significantly modify intraoperative vancomycin pharmaco ki netics in patients undergoing cardiac surgery. The results of this study may contribute to increased knowledge of vancomycin pharmacokinetics.
Severe Cardiotoxicity Associated with Ixabepilone use in Metastatic Breast Cancer
Authors: Santiago Michael J , Hayes Bryan D , Butler Kenneth H
Published: March 2013

OBJECTIVE

To report a case of cardiogenic shock and fulminant heart failure associated with a single dose of ixabepilone.

CASE SUMMARY

A 32-year-old woman presented to the emergency department (ED) with abdominal pain and difficulty breathing within 1 hour after receiving a partial dose of ixabepilone (26 mg/m 2 ) at an oncologist's office. She had breast cancer, with metastases to the bone and liver and evidence of early liver failure. While in the ED, she developed acute respiratory failure requiring intubation. Bedside ultrasound imaging showed free abdominal fluid. Computed tomography (CT) scans showed evidence of right-sided heart failure and abdominal fluid consistent with ascites but no evidence of pulmonary embolism. After the CT scan, the patient experienced pulseless electrical activity cardiac arrest. All attempts at resuscitation were unsuccessful.

DISCUSSION

Ixabepilone is a novel drug for treatment of advanced breast cancer. The most commonly reported adverse effects are peripheral neuropathies and hematologic issues such as neutropenia. To our knowledge, this is the first detailed report of a severe adverse cardiac event associated with ixabepilone use. Many other chemotherapeutic agents have cardiotoxic effects. An objective causality assessment, using the Naranjo probability scale, revealed that an adverse drug event was probable.

CONCLUSIONS

Clinicians should maintain broad differential diagnoses that include adverse reactions to drugs relatively new to the market. Ixabepilone may have cardiotoxic effects that necessitate further study, particularly when the drug is administered after cardiotoxic chemotherapy.
Kantian Dilemmas? Moral Conflict in Kant’s Ethical Theory
Authors: Timmermann Jens
Published: March 2013

Abstract: This paper explores the possibility of moral conflict in Kant’s ethics. An analysis of the only explicit discussion of the topic in his published writings confirms that there is no room for genuine moral dilemmas. Conflict is limited to nonconclusive ‘grounds’ of obligation. They arise only in the sphere of ethical duty and, though defeasible, ought to be construed as the result of valid arguments an agent correctly judges to apply in the situation at hand. While it is difficult to determine in theory what makes some of them stronger than others, these ‘grounds’ can account for practical residue in conflict cases and for a plausible form of agent regret. The principle that ‘ought implies can’ survives intact.
The Effect of Comprehensive Smoking Bans in European Workplaces
Authors: Origo Federica , Lucifora Claudio
Published: March 2013

Many European countries have recently implemented comprehensive smoking bans to reduce exposure to tobacco smoke in public places and all indoor workplaces. We use a difference-in-differences approach and comparable microdata for a number of European countries to evaluate the impact of national comprehensive smoking bans on workers’ perceived health. Results show that the introduction of comprehensive smoking bans has a significant effect on the probability of both exposure to smoke and work-related respiratory problems. We also highlight unintended effects in terms of mental distress. The impact across countries is shown to vary with the degree of strictness of the bans.
Should Global Health be Tailored Toward the Rich? Altruism and Efficient R&D for Neglected Diseases
Authors: Jena Anupam B. , Mechoulan Stéphane , Philipson Tomas J.
Published: March 2013

We analyze the problem of incentivizing research and development (R&D) into developing world disease from an economic efficiency perspective. We view the problem as how to best promote R&D into goods with positive external effects in the sense that medicines that directly affect the health of the poor also indirectly affect the utility of the altruistic “rich.” We demonstrate why existing policy proposals – such as price concessions by manufacturers – adversely impact the poor by placing the burden of R&D only on innovators rather than all altruists in the rich world. We offer policy solutions that are based on economic efficiency and therefore rely on a broad sense of how the world values the treatment of developing world disease. We estimate that global altruism toward those with malaria is, at a minimum, valued between $835 million and $2.4 billion annually and for HIV/AIDS, between $9.1 billion and $26.6 billion annually. We argue that future policies toward neglected diseases need to better incorporate how efficient R&D meets the need of this global altruism.
Fire resistance of wood treated with various ionic liquids (ILs)
Authors: Miyafuji Hisashi , Fujiwara Yoshiyuki
Published: March 2013

Ionic liquids (ILs) have been investigated for their potential as reagents for enhancing the fire resistance of wood. The following ILs were in focus: 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium tetrafluoroborate, and 1-ethyl-3-methylimidazolium hexafluorophosphate ([C2mim][PF6]). Supposedly, these ILs do not dissolve or degrade wood components to a large extent. No morphologic changes were observed in any IL-treated wood samples, but they showed an enhanced fire resistance compared with that of untreated wood. Scanning electron microscopy and energy-dispersive X-ray analysis demonstrated that the ILs are penetrated into the cell walls. The wood treated with [C2mim][PF6] exhibited the highest fire resistance based on thermogravimetric and differential thermal analyzer studies: it was more resistant against flaming at approximately 350°C and the subsequent glowing at higher temperatures. This enhanced fire resistance was interpreted by dehydration in the presence of the ILs under observation. In general, ILs are promising reagents for improving the thermal properties of wood.
Effect of maternal body mass index on oxytocin treatment for arrest of dilatation1)
Authors: Soni Shelly , Chivan Niraj , Cohen Wayne R.
Published: March 2013

To determine whether the effectiveness of oxytocin treatment of arrest of dilatation differed in obese compared to lean women, we did a retrospective analysis of 118 subjects in spontaneous labor whose arrest of dilatation was treated with oxytocin. Cases were stratified by maternal body mass index (BMI): Group A, <25 kg/m2; Group B, 25.0–29.9 kg/m2; Group C, 30.0–34.9 kg/m2; and Group D, ≥35 kg/m2. Groups were comparable in maternal age, parity, gestational age, birth weight, and the frequency of infection. Full dilatation was reached in about 90% of Group A and B, 72% of Group C, and 39% of Group D, the most obese women (P<0.001). The cesarean rate was directly related to maternal BMI, 11.4%, 22.9%, 34.3%, and 69.6% in Groups A through D, respectively (P<0.001). Significantly more oxytocin was used in group D than in the other groups during the first 3h of infusion in attempting to overcome the arrest (P=0.003). We conclude that oxytocin treatment of arrest of dilatation was less effective in obese than in lean women. This effect was most prominent in women with a BMI >35 kg/m2, who were, despite having received more oxytocin than those in the leaner groups, less than half as likely to attain full dilatation and more than twice as likely to deliver by cesarean.
Kausalität und Freiheit
Authors: Strohmeyer Ingeborg
Published: March 2013

Abstract: According to Kant, all events in nature are subject to the principle of causality. Nevertheless, free actions are possible, because freedom and the universal law of causality are compatible without contradiction. Quantum mechanics is indeterministic, i.e. it implies a violation of causality. It is shown that: 1) this indeterminism can be understood by means of a continuation of Kant’s transcendental philosophy, as it is, like determinism, just a special type of universal causality, occurring when objects are not completely determined, 2) quantum mechanical indeterminacy must not be identified with freedom, because it occurs only within the realm of sensible appearances existing in space and time, whereas freedom belongs to an intelligible substratum that is not part of the sensuous world.
Trophic interactions between puma and endemic culpeo fox after livestock removal in the high mountains of central Argentina
Authors: Pia Mónica V.
Published: March 2013

This study presents the first data on the diet of the puma (Puma concolor) and an endemic culpeo fox (Pseudalopex culpaeus smithersi) in the high mountains of central Argentina, based on scat analysis. Trophic interactions of both carnivores were examined from 2003 to 2008 inside a protected area after livestock removal. A total of 604 scats were analyzed. Native species (small cavids and cricetine rodents) were most frequently consumed (58%–100%) by both carnivores. Exotic prey were consumed more in 2003 than in other years by both carnivores. Culpeo foxes consumed a higher number of prey items and a lower mean weight of mammalian prey than pumas. Niche breadth was high for pumas in 2003 and for culpeo foxes in 2004, decreasing in subsequent years with the same tendency in both carnivores. Diet overlap was high in all years. Pumas seemed to prey on available prey items, suggesting a trend toward diet specialization in small prey in both carnivores. Native prey are the most important food items for both carnivores inside the park; these results are encouraging in terms of the resilience of at least some components of the predator-prey assemblage in the high mountains of central Argentina.
Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes
Authors: Jovičić Ana , Roshan Reema , Moisoi Nicoleta , Pradervand Sylvain , Moser Roger , Pillai Beena , Luthi-Carter Ruth
Published: March 2013

MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions. However, a systematic analysis of brain miRNA functions has been hindered by a lack of comprehensive information regarding the distribution of miRNAs in neuronal versus glial cells. To address this issue, we performed microarray analyses of miRNA expression in the four principal cell types of the CNS (neurons, astrocytes, oligodendrocytes, and microglia) using primary cultures from postnatal d 1 rat cortex. These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types. We also demonstrate that individual neuron-enriched or neuron-diminished RNAs had a significant impact on the specification of neuronal phenotype: overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons, whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32. In addition, glia-enriched miRNAs were shown to inhibit aberrant glial expression of neuronal proteins and phenotypes, as exemplified by miR-146a, which inhibited neuroligin 1-dependent synaptogenesis. This study identifies new nervous system functions of specific miRNAs, reveals the global extent to which the brain may use differential miRNA expression to regulate neural cell-type-specific phenotypes, and provides an important data resource that defines the compartmentalization of brain miRNAs across different cell types.
Automatic Phoneme Category Selectivity in the Dorsal Auditory Stream
Authors: Chevillet Mark A. , Jiang Xiong , Rauschecker Josef P. , Riesenhuber Maximilian
Published: March 2013

Debates about motor theories of speech perception have recently been reignited by a burst of reports implicating premotor cortex (PMC) in speech perception. Often, however, these debates conflate perceptual and decision processes. Evidence that PMC activity correlates with task difficulty and subject performance suggests that PMC might be recruited, in certain cases, to facilitate category judgments about speech sounds (rather than speech perception, which involves decoding of sounds). However, it remains unclear whether PMC does, indeed, exhibit neural selectivity that is relevant for speech decisions. Further, it is unknown whether PMC activity in such cases reflects input via the dorsal or ventral auditory pathway, and whether PMC processing of speech is automatic or task-dependent. In a novel modified categorization paradigm, we presented human subjects with paired speech sounds from a phonetic continuum but diverted their attention from phoneme category using a challenging dichotic listening task. Using fMRI rapid adaptation to probe neural selectivity, we observed acoustic-phonetic selectivity in left anterior and left posterior auditory cortical regions. Conversely, we observed phoneme-category selectivity in left PMC that correlated with explicit phoneme-categorization performance measured after scanning, suggesting that PMC recruitment can account for performance on phoneme-categorization tasks. Structural equation modeling revealed connectivity from posterior, but not anterior, auditory cortex to PMC, suggesting a dorsal route for auditory input to PMC. Our results provide evidence for an account of speech processing in which the dorsal stream mediates automatic sensorimotor integration of speech and may be recruited to support speech decision tasks.
Short Neuropeptide F Acts as a Functional Neuromodulator for Olfactory Memory in Kenyon Cells ofDrosophilaMushroom Bodies
Authors: Knapek Stephan , Kahsai Lily , Winther Åsa M. E. , Tanimoto Hiromu , Nässel Dick R.
Published: March 2013

In insects, many complex behaviors, including olfactory memory, are controlled by a paired brain structure, the so-called mushroom bodies (MB). InDrosophila, the development, neuroanatomy, and function of intrinsic neurons of the MB, the Kenyon cells, have been well characterized. Until now, several potential neurotransmitters or neuromodulators of Kenyon cells have been anatomically identified. However, whether these neuroactive substances of the Kenyon cells are functional has not been clarified yet. Here we show that a neuropeptide precursor gene encoding four types of short neuropeptide F (sNPF) is required in the Kenyon cells for appetitive olfactory memory. We found that activation of Kenyon cells by expressing a thermosensitive cation channel (dTrpA1) leads to a decrease in sNPF immunoreactivity in the MB lobes. Targeted expression of RNA interference against the sNPF precursor in Kenyon cells results in a highly significant knockdown of sNPF levels. This knockdown of sNPF in the Kenyon cells impairs sugar-rewarded olfactory memory. This impairment is not due to a defect in the reflexive sugar preference or odor response. Consistently, knockdown of sNPF receptors outside the MB causes deficits in appetitive memory. Altogether, these results suggest that sNPF is a functional neuromodulator released by Kenyon cells.
Behavioral Transition from Attack to Parenting in Male Mice: A Crucial Role of the Vomeronasal System
Authors: Tachikawa Kashiko S. , Yoshihara Yoshihiro , Kuroda Kumi O.
Published: March 2013

Sexually naive male mice show robust aggressive behavior toward pups. However, the proportion of male mice exhibiting pup-directed aggression declines after cohabitation with a pregnant female for 2 weeks after mating. Subsequently, on becoming fathers, they show parental behavior toward pups, similar to maternal behavior by mothers. To elucidate the neural mechanisms underlying this behavioral transition, we examined brain regions differentially activated in sexually naive males and fathers after exposure to pups, using c-Fos expression as a neuronal activation marker. We found that, after pup exposure, subsets of neurons along the vomeronasal neural pathway—including the vomeronasal sensory neurons, the accessory olfactory bulb, the posterior medial amygdala, the medioposterior division of the bed nucleus of stria terminalis, and the anterior hypothalamic area—were more strongly activated in sexually naive males than in fathers. Notably, c-Fos induction was not observed in the vomeronasal sensory neurons of fathers after pup exposure. Surgical ablation of the vomeronasal organ in sexually naive males resulted in the abrogation of pup-directed aggression and simultaneous induction of parental behavior. These results suggest that chemical cues evoking pup-directed aggression are received by the vomeronasal sensory neurons and activate the vomeronasal neural pathway in sexually naive male mice but not in fathers. Thus, the downregulation of pup pheromone-induced activation of the vomeronasal system might be important for the behavioral transition from attack to parenting in male mice.
Training the Emotional Brain: Improving Affective Control through Emotional Working Memory Training
Authors: Schweizer Susanne , Grahn Jessica , Hampshire Adam , Mobbs Dean , Dalgleish Tim
Published: March 2013

Affective cognitive control capacity (e.g., the ability to regulate emotions or manipulate emotional material in the service of task goals) is associated with professional and interpersonal success. Impoverished affective control, by contrast, characterizes many neuropsychiatric disorders. Insights from neuroscience indicate that affective cognitive control relies on the same frontoparietal neural circuitry as working memory (WM) tasks, which suggests that systematic WM training, performed in an emotional context, has the potential to augment affective control. Here we show, using behavioral and fMRI measures, that 20 d of training on a novel emotional WM protocol successfully enhanced the efficiency of this frontoparietal demand network. Critically, compared with placebo training, emotional WM training also accrued transfer benefits to a “gold standard” measure of affective cognitive control–emotion regulation. These emotion regulation gains were associated with greater activity in the targeted frontoparietal demand network along with other brain regions implicated in affective control, notably the subgenual anterior cingulate cortex. The results have important implications for the utility of WM training in clinical, prevention, and occupational settings.
Regional and Hemispheric Variation in Cortical Thickness in Chimpanzees (Pan troglodytes)
Authors: Hopkins William D. , Avants Brian B.
Published: March 2013

Recent advances in structural magnetic resonance imaging technology and analysis now allows for accuratein vivomeasurement of cortical thickness, an important aspect of cortical organization that has historically only been conducted on postmortem brains. In this study, for the first time, we examined regional and lateralized cortical thickness in a sample of 71 chimpanzees for comparison with previously reported findings in humans. We also measured gray and white matter volumes for each subject. The results indicated that chimpanzees showed significant regional variation in cortical thickness with lower values in primary motor and sensory cortex compared with association cortex. Furthermore, chimpanzees showed significant rightward asymmetries in cortical thickness for a number of regions of interest throughout the cortex and leftward asymmetries in white but not gray matter volume. We also found that total and region-specific cortical thickness was significantly negatively correlated with white matter volume. Thus, chimpanzees with greater white matter volumes had thinner cortical thickness. The collective findings are discussed within the context of previous findings in humans and theories on the evolution of cortical organization and lateralization in primates.
Hypocretin/Orexin Neurons Contribute to Hippocampus-Dependent Social Memory and Synaptic Plasticity in Mice
Authors: Yang Liya , Zou Bende , Xiong Xiaoxing , Pascual Conrado , Xie James , Malik Adam , Xie Julian , Sakurai Takeshi , Xie Xinmin (Simon)
Published: March 2013

Hypocretin/orexin (Hcrt)-producing neurons in the lateral hypothalamus project throughout the brain, including to the hippocampus, where Hcrt receptors are widely expressed. Hcrt neurons activate these targets to orchestrate global arousal state, wake-sleep architecture, energy homeostasis, stress adaptation, and reward behaviors. Recently, Hcrt has been implicated in cognitive functions and social interaction. In the present study, we tested the hypothesis that Hcrt neurons are critical to social interaction, particularly social memory, using neurobehavioral assessment and electrophysiological approaches. The validated “two-enclosure homecage test” devices and procedure were used to test sociability, preference for social novelty (social novelty), and recognition memory. A conventional direct contact social test was conducted to corroborate the findings. We found that adult orexin/ataxin-3-transgenic (AT) mice, in which Hcrt neurons degenerate by 3 months of age, displayed normal sociability and social novelty with respect to their wild-type littermates. However, AT mice displayed deficits in long-term social memory. Nasal administration of exogenous Hcrt-1 restored social memory to an extent in AT mice. Hippocampal slices taken from AT mice exhibited decreases in degree of paired-pulse facilitation and magnitude of long-term potentiation, despite displaying normal basal synaptic neurotransmission in the CA1 area compared to wild-type hippocampal slices. AT hippocampi had lower levels of phosphorylated cAMP response element-binding protein (pCREB), an activity-dependent transcription factor important for synaptic plasticity and long-term memory storage. Our studies demonstrate that Hcrt neurons play an important role in the consolidation of social recognition memory, at least in part through enhancements of hippocampal synaptic plasticity and cAMP response element-binding protein phosphorylation.
Sustained Multifocal Attentional Enhancement of Stimulus Processing in Early Visual Areas Predicts Tracking Performance
Authors: Störmer Viola S. , Winther Gesche N. , Li Shu-Chen , Andersen Søren K.
Published: March 2013

Keeping track of multiple moving objects is an essential ability of visual perception. However, the mechanisms underlying this ability are not well understood. We instructed human observers to track five or seven independent randomly moving target objects amid identical nontargets and recorded steady-state visual evoked potentials (SSVEPs) elicited by these stimuli. Visual processing of moving targets, as assessed by SSVEP amplitudes, was continuously facilitated relative to the processing of identical but irrelevant nontargets. The cortical sources of this enhancement were located to areas including early visual cortex V1–V3 and motion-sensitive area MT, suggesting that the sustained multifocal attentional enhancement during multiple object tracking already operates at hierarchically early stages of visual processing. Consistent with this interpretation, the magnitude of attentional facilitation during tracking in a single trial predicted the speed of target identification at the end of the trial. Together, these findings demonstrate that attention can flexibly and dynamically facilitate the processing of multiple independent object locations in early visual areas and thereby allow for tracking of these objects.
Hyperactivation of B-Type Motor Neurons Results in Aberrant Synchrony of theCaenorhabditis elegansMotor Circuit
Authors: Qi Yingchuan B. , Po Michelle D. , Mac Patrick , Kawano Taizo , Jorgensen Erik M. , Zhen Mei , Jin Yishi
Published: March 2013

Excitatory acetylcholine motor neurons driveCaenorhabditis eleganslocomotion. Coordinating the activation states of the backward-driving A and forward-driving B class motor neurons is critical for generating sinusoidal and directional locomotion. Here, we show byin vivocalcium imaging that expression of a hyperactive, somatodendritic ionotropic acetylcholine receptor ACR-2(gf) in A and B class motor neurons induces aberrant synchronous activity in both ventral- and dorsal-innervating B and A class motor neurons. Expression of ACR-2(gf) in either ventral- or dorsal-innervating B neurons is sufficient for triggering the aberrant synchrony that results in arrhythmic convulsions. Silencing of AVB, the premotor interneurons that innervate B motor neurons suppresses ACR-2(gf)-dependent convulsion; activating AVB by channelrhodopsin induces the onset of convulsion. These results support that the activity state of B motor neurons plays an instructive role for the coordination of motor circuit.
Shifting Attentional Priorities: Control of Spatial Attention through Hemispheric Competition
Authors: Szczepanski Sara M. , Kastner Sabine
Published: March 2013

Regions of frontal and posterior parietal cortex are known to control the allocation of spatial attention across the visual field. However, the neural mechanisms underlying attentional control in the intact human brain remain unclear, with some studies supporting a hemispatial theory emphasizing a dominant function of the right hemisphere and others supporting an interhemispheric competition theory. We previously found neural evidence to support the latter account, in which topographically organized frontoparietal areas each generate a spatial bias, or “attentional weight,” toward the contralateral hemifield, with the sum of the weights constituting the overall bias that can be exerted across visual space. Here, we used a multimodal approach consisting of functional magnetic resonance imaging (fMRI) of spatial attention signals, behavioral measures of spatial bias, and fMRI-guided single-pulse transcranial magnetic stimulation (TMS) to causally test this interhemispheric competition account. Across the group of fMRI subjects, we found substantial individual differences in the strengths of the frontoparietal attentional weights in each hemisphere, which predicted subjects' respective behavioral preferences when allocating spatial attention, as measured by a landmark task. Using TMS to interfere with attentional processing within specific topographic frontoparietal areas, we then demonstrated that the attentional weights of individual subjects, and thus their spatial attention behavior, could be predictably shifted toward one visual field or the other, depending on the site of interference. The results of our multimodal approach, combined with an emphasis on neural and behavioral individual differences, provide compelling evidence that spatial attention is controlled through competitive interactions between hemispheres rather than a dominant right hemisphere in the intact human brain.
Spinal Serum-Inducible and Glucocorticoid-Inducible Kinase 1 Mediates Neuropathic Pain via Kalirin and Downstream PSD-95-Dependent NR2B Phosphorylation in Rats
Authors: Peng Hsien-Yu , Chen Gin-Den , Lai Cheng-Yuan , Hsieh Ming-Chun , Lin Tzer-Bin
Published: March 2013

The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergicN-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95–NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1–kalirin–PSD-95–pNR2B coprecipitation in the ipsilateral dorsal horn (L4–L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin–PSD-95 and PSD-95–pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1–kalirin costaining and SGK1–kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95–NR2B coupling-dependent NR2B phosphorylation.
Multiplex Genetic Fate Mapping Reveals a Novel Route of Neocortical Neurogenesis, Which Is Altered in the Ts65Dn Mouse Model of Down Syndrome
Authors: Tyler William A. , Haydar Tarik F.
Published: March 2013

While several major classes of neocortical neural precursor cells have been identified, the lineal relationships and molecular profiles of these cells are still largely unknown. Furthermore, the individual contribution of each cell class to neocortical growth during normal development and in neurodevelopmental disorders has not been determined. Using a novel fate-mapping approach, we demonstrate that precursors in the embryonic ventricular (VZ) and subventricular zones (SVZ), which give rise to excitatory neurons, are divided into distinct subtypes based on lineage profile, morphology, and transcription factor expressionin vivo. Using this technique, we show that short neural precursors are a unique class of VZ intermediate progenitors derived from radial glial cells and are distinct from the multipolar Tbr2(+)intermediate progenitors, which divide in the SVZ. To test whether these multiple groups of intermediate progenitors are redundant or whether they are necessary for proper neocortical growth, we measured precursor cell diversity in the Ts65Dn mouse model of Down syndrome (DS), which exhibits reduced neurogenesis and postnatal microcephaly. We report that SNP generation is markedly reduced in the Ts65Dn VZ during mid-neurogenesis, indicating that faulty specification of this progenitor pool is a central component of the neocortical abnormality in DS. Together, these findings demonstrate that neocortical neurons are produced via multiple indirect routes during embryonic development and that these parallel streams of neurogenesis collectively contribute to the proper growth and development of the neocortex.
Collaborative Writing and Ethical Know-how
Authors: Speedy Jane
Published: March 2013

It may seem incongruous to come across a ‘sole authored’ text amidst a journal special issue on collaborative writing. For my part the contradiction ‘plays’ eloquently with what it might mean to be/come a singular-yet-silted-up-accumulation of a human being. This paper represents not so much an assemblage (although that, too) as a collectively auto/biographical constellation, accumulation, and distillation of the traces that have remained lying around and about after many decades spent engaged with collective, collaborative and participatory writing.

By themselves these sediments and dregs do not amount to much and certainly do not fit together, but as they have accumulated over time they have come to represent something of a body of work. Hence, the conditions of possibility surface for me to give an account of the very particular kinds of ethical know-how that I have witnessed emerging from many groups of people writing together collaboratively within (and to some extent against) the Academy.

This paper draws on feminist sensibilities, narrative and poststructuralist ideas, therapeutic practices, Utopian methodologies and multiple writing accumulations over time to suggest that the continued and explicit practice of collaborative writing amongst social researchers alters the academic spaces they inhabit and the ethical know-how that they come by. In time the (albeit fragile) emergence of this different sense of scholarship and scholarly work and even, perhaps, of what it means to be a human being amidst human beings and other elements can begin to rework and expand the social imagination.
After Writes
Authors:   Bristol Collaborative Writing Group
Published: March 2013

In this paper we write our way into the space generated by the ending/not ending of the Bristol Collaborative Writing Group that we had all engaged with for over seven years. This writing was to have taken the form of a post script or ‘after writes,’ since we ended, or ‘petered out,’ some months before. Rather than ending responsibly, with attention to matters of ‘closure,’ talk of transition and carefully held space for reflective thinking (Birnbaum & Cichetti, 2008), we unravelled somewhat unceremoniously on the way back from lunch at the Pizza Express, perched outside the gents in the downstairs foyer at the university, unable to find an empty room to host our farewells. Yet in a manner completely congruent with our starting out and working together, the task we had set ourselves to end did not materialise as it ‘should.’ This special issue has afforded us the opportunity to attend differently to our endings/beginnings and also to each other “as if for the first time” (Eliot, 1944). And in doing so, we have learnt more about a richness of being together, an invisible dynamic, that has lurked secretly throughout our meanderings, revealing itself only when we abandoned intentfulness and allowed ourselves the indulgence of being, rather than doing.
In the Threshold
Authors: Mazzei Lisa A. , Jackson Alecia Y.
Published: March 2013

In this paper, we describe our encounters in and passes through the figuration of the threshold as producing writing between-the-two: or, loss of the individual subject. We describe how in the threshold, we meet in that in-between space, a space of shared deterritorialization in which we constitute one another. Also, we describe writing between-the-two in the threshold as a site of embodiment, of affect. In thinking of how to articulate our way of thinking and writing together as between-the-two and as different than a collaborative project where two “I”s contribute pieces both with and independent of the other, we take our cue from Ken Gale and Jonathan Wyatt's (2009) Between the Two. In this book, they articulate a way of thinking and writing inspired by Deleuze and Guattari's collaborative work as that which is not a working together, but a working in the gap “between the two” (Deleuze & Parnet, 1987/2002, p. 13). This spark of creativity in the gap is both like and unlike what we will explain in this article. Like Gale and Wyatt, we lean on figurations and concepts in the writings of Deleuze and Guattari as a referent; however, our between-the-two is pursued more deliberately through a materialist knowing in being that produces our becoming with and in a digital threshold.
Diagnostic and prognostic value of immunocytochemistry and BRAF mutation analysis on liquid-based biopsies of thyroid neoplasms suspicious for carcinoma
Authors: Rossi Esther Diana , Martini Maurizio , Capodimonti Sara , Straccia Patrizia , Cenci Tonia , Lombardi Celestino Pio , Pontecorvi Alfredo , Larocca Luigi Maria , Fadda Guido
Published: March 2013

Objective

In the field of fine-needle aspiration cytology, the category of suspicious for malignancy (SM) thyroid lesions, that bears 55–85% risk of malignant histology, is a challenging topic in which morphology alone is not always able to make a correct diagnosis. Recently, immunocytochemistry (ICC) has been referred to as helpful in differentiating low- and high-malignant risk lesions andBRAFactivating mutations have been identified in a significant amount of papillary thyroid carcinomas (PTC). The introduction of the liquid-based cytology (LBC) may simplify the application of these techniques to thyroid cytology.

Design

Our aim is to evaluate the diagnostic and prognostic role of both ICC andBRAFmutation for the SM category on LBC.

Methods

From October 2010 through June 2011, 113 LBC cytological cases (including 37 SM and 76 PTC) underwent surgery. All cases were studied forBRAFmutation and ICC.

Results

ICC resulted positive in 26 (86.6%) histologically malignant SM with 15 of which (40.5%) expressing aBRAFmutation. Overall, 63 cases showed aBRAFmutation resulting in PTC. Concerning the prognostic role ofBRAFmutation for the two categories, we reported a significant correlation with multifocality, nodal involvement and extra-capsular invasion (P<0.0001).

Conclusions

Special techniques such as ICC and molecular markers might be successfully carried out on LBC-processed material. For both categories, ICC is more sensitive whereasBRAFanalysis is an interesting support due to its high specificity adding a prognostic value in both SM and PTCs.
Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism
Authors: D'Amico Eva , Gayral Stéphanie , Massart Claude , Van Sande Jacqueline , Reiter Jeremy F , Dumont Jacques E , Robaye Bernard , Schurmans Stéphane
Published: March 2013

Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminals, to cilia, to nonpolarized cell surfaces or to epithelial cell basolateral membranes, thus taking part in the establishment of cellular polarity. We report here the consequences of kinesin 2 motor inactivation in the thyroid of 3-week-old Kif3aΔ/floxPax8Cre/+mutant mice. Our results indicate first that 3-week-old Pax8Cre/+mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood thyroxine levels in the normal range. Second, Kif3a inactivation in thyrocytes markedly amplified the phenotype observed in Pax8Cre/+mice, resulting in altered TSH signaling upstream of the second messenger cAMP and mild hypothyroidism. Finally, our results in mouse embryonic fibroblasts indicate that Kif3a inactivation in the absence of anyPax8gene alteration leads to altered G protein-coupled receptor plasma membrane expression, as shown for the β2adrenergic receptor, and we suggest that a similar mechanism may explain the altered TSH signaling and mild hypothyroidism detected in Kif3aΔ/floxPax8Cre/+mutant mice.