328 research outputs found

    Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task

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    To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context

    Analysis of Multiple Sarcoma Expression Datasets: Implications for Classification, Oncogenic Pathway Activation and Chemotherapy Resistance

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    Background: Diagnosis of soft tissue sarcomas (STS) is challenging. Many remain unclassified (not-otherwise-specified, NOS) or grouped in controversial categories such as malignant fibrous histiocytoma (MFH), with unclear therapeutic value. We analyzed several independent microarray datasets, to identify a predictor, use it to classify unclassifiable sarcomas, and assess oncogenic pathway activation and chemotherapy response. Methodology/Principal Findings: We analyzed 5 independent datasets (325 tumor arrays). We developed and validated a predictor, which was used to reclassify MFH and NOS sarcomas. The molecular “match” between MFH and their predicted subtypes was assessed using genome-wide hierarchical clustering and Subclass-Mapping. Findings were validated in 15 paraffin samples profiled on the DASL platform. Bayesian models of oncogenic pathway activation and chemotherapy response were applied to individual STS samples. A 170-gene predictor was developed and independently validated (80-85% accuracy in all datasets). Most MFH and NOS tumors were reclassified as leiomyosarcomas, liposarcomas and fibrosarcomas. “Molecular match” between MFH and their predicted STS subtypes was confirmed both within and across datasets. This classification revealed previously unrecognized tissue differentiation lines (adipocyte, fibroblastic, smooth-muscle) and was reproduced in paraffin specimens. Different sarcoma subtypes demonstrated distinct oncogenic pathway activation patterns, and reclassified MFH tumors shared oncogenic pathway activation patterns with their predicted subtypes. These patterns were associated with predicted resistance to chemotherapeutic agents commonly used in sarcomas. Conclusions/Significance: STS profiling can aid in diagnosis through a predictor tracking distinct tissue differentiation in unclassified tumors, and in therapeutic management via oncogenic pathway activation and chemotherapy response assessment

    Raman scattering reveals strong LO-phonon-hole-plasmon coupling in nominally undoped GaAsBi: optical determination of carrier concentration

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    We report room-temperature Raman scattering studies of nominally undoped (100) GaAs1−xBix epitaxial layers exhibiting Biinduced (p-type) longitudinal-optical-plasmon coupled (LOPC) modes for 0.018≤x≤0.048. Redshifts in the GaAs-like optical modes due to alloying are evaluated and are paralleled by strong damping of the LOPC. The relative integrated Raman intensities of LO(Γ) and LOPC ALO/ALOPC are characteristic of heavily doped p-GaAs, with a remarkable near total screening of the LO(Γ) phonon (ALO/ALOPC →0) for larger Bi concentrations. A method of spectral analysis is set out which yields estimates of hole concentrations in excess of 5 × 1017 cm−3 and correlates with the Bi molar fraction. These findings are in general agreement with recent electrical transport measurements performed on the alloy, and while the absolute size of the hole concentrations differ, likely origins for the discrepancy are discussed. We conclude that the damped LO-phonon-hole-plasmon coupling phenomena plays a dominant role in Raman scattering from unpassivated nominally undoped GaAsBi

    Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis

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    The dynamic nature of gene regulatory networks allows cells to rapidly respond to environmental change. However, the underlying temporal connections are missed, even in kinetic studies, as transcription factor (TF) binding within at least one time point is required to identify primary targets. The TF-regulated but unbound genes are dismissed as secondary targets. Instead, we report that these genes comprise transient TF-target interactions most relevant to rapid signal transduction. We temporally perturbed a master TF (Basic Leucine Zipper 1, bZIP1) and the nitrogen (N) signal it transduces and integrated TF regulation and binding data from the same cell samples. Our enabling approach could identify primary TF targets based solely on gene regulation, in the absence of TF binding. We uncovered three classes of primary TF targets: (i) poised (TF-bound but not TF-regulated), (ii) stable (TF-bound and TF-regulated), and (iii) transient (TF-regulated but not TF-bound), the largest class. Unexpectedly, the transient bZIP1 targets are uniquely relevant to rapid N signaling in planta, enriched in dynamic N-responsive genes, and regulated by TF and N signal interactions. These transient targets include early N responders nitrate transporter 2.1 and NIN-like protein 3, bound by bZIP1 at 1-5 min, but not at later time points following TF perturbation. Moreover, promoters of these transient targets are uniquely enriched with cis-regulatory motifs coinherited with bZIP1 binding sites, suggesting a recruitment role for bZIP1. This transient mode of TF action supports a classic, but forgotten, "hit-and-run" transcription model, which enables a "catalyst TF" to activate a large set of targets within minutes of signal perturbation

    MBE grown GaAsBi/GaAs multiple quantum well structures: Structural and optical characterization

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    A series of GaAsBi/GaAs multiple quantum well p–i–n diodes were grown by molecular beam epitaxy. Nomarski images showed evidence of sub-surface damage in each diode, with an increase in the cross-hatching associated with strain relaxation for the diodes containing more than 40 quantum wells. X-ray diffraction ω–2θ scans of the (004) reflections showed that multiple quantum well regions with clearly defined well periodicities were grown. The superlattice peaks of the diodes containing more than 40 wells were much broader than those of the other diodes. The photoluminescence spectra showed a redshift of 56 meV and an attenuation of nearly two orders of magnitude for the 54 and 63 well diodes. Calculations of the quantum confinement and strain induced band gap modifications suggest that the wells in all diodes are thinner than their intended widths and that both loss of quantum confinement and strain probably contributed to the observed redshift and attenuation in the 54 and 63 well diodes. Comparison of this data with that gathered for InGaAs/GaAs multiple quantum wells, suggests that the onset of relaxation occurs at a similar average strain–thickness product for both systems. Given the rapid band gap reduction of GaAsBi with Bi incorporation, this data suggests that GaAsBi is a promising photovoltaic material candidate

    Modeling the System Parameters of 2M1533+3759: A New Longer-Period Low-Mass Eclipsing sdB+dM Binary

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    We present new photometric and spectroscopic observations for 2M 1533+3759 (= NSVS 07826147). It has an orbital period of 0.16177042 day, significantly longer than the 2.3--3.0 hour periods of the other known eclipsing sdB+dM systems. Spectroscopic analysis of the hot primary yields Teff = 29230 +/- 125 K, log g = 5.58 +/- 0.03 and log N(He)/N(H) = -2.37 +/- 0.05. The sdB velocity amplitude is K1 = 71.1 +/- 1.0 km/s. The only detectable light contribution from the secondary is due to the surprisingly strong reflection effect. Light curve modeling produced several solutions corresponding to different values of the system mass ratio, q(M2/M1), but only one is consistent with a core helium burning star, q=0.301. The orbital inclination is 86.6 degree. The sdB primary mass is M1 = 0.376 +/- 0.055 Msun and its radius is R1 = 0.166 +/- 0.007 Rsun. 2M1533+3759 joins PG0911+456 (and possibly also HS2333+3927) in having an unusually low mass for an sdB star. SdB stars with masses significantly lower than the canonical value of 0.48 Msun, down to as low as 0.30 Msun, were theoretically predicted by Han et al. (2002, 2003), but observational evidence has only recently begun to confirm the existence of such stars. The existence of core helium burning stars with masses lower than 0.40--0.43 Msun implies that at least some sdB progenitors have initial main sequence masses of 1.8--2.0 Msun or more, i.e. they are at least main sequence A stars. The secondary is a main sequence M5 star.Comment: 47 pages, 7 figure

    MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32

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    Background: Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. Methods: We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. Results: Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. Conclusions: Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis supports a possible role of the 14q32 locus in osteosarcoma progression and outcome. Our study creates a paradigm for formalin-fixed, paraffin-embedded-based miRNA biomarker studies in cancer

    Appointing Women to Boards: Is There a Cultural Bias?

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    Companies that are serious about corporate governance and business ethics are turning their attention to gender diversity at the most senior levels of business (Institute of Business Ethics, Business Ethics Briefing 21:1, 2011). Board gender diversity has been the subject of several studies carried out by international organizations such as Catalyst (Increasing gender diversity on boards: Current index of formal approaches, 2012), the World Economic Forum (Hausmann et al., The global gender gap report, 2010), and the European Board Diversity Analysis (Is it getting easier to find women on European boards? 2010). They all lead to reports confirming the overall relatively low proportion of women on boards and the slow pace at which more women are being appointed. Furthermore, the proportion of women on corporate boards varies much across countries. Based on institutional theory, this study hypothesizes and tests whether this variation can be attributed to differences in cultural settings across countries. Our analysis of the representation of women on boards for 32 countries during 2010 reveals that two cultural characteristics are indeed associated with the observed differences. We use the cultural dimensions proposed by Hofstede (Culture’s consequences: International differences in work-related values, 1980) to measure this construct. Results show that countries which have the greatest tolerance for inequalities in the distribution of power and those that tend to value the role of men generally exhibit lower representations of women on boards

    Phonon engineering in isotopically disordered silicon nanowires

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    The introduction of stable isotopes in the fabrication of semiconductor nanowires provides an additional degree of freedom to manipulate their basic properties, design an entirely new class of devices, and highlight subtle but important nanoscale and quantum phenomena. With this perspective, we report on phonon engineering in metal-catalyzed silicon nanowires with tailor-made isotopic compositions grown using isotopically enriched silane precursors ²⁸SiH, ²⁹SiH, and ³⁰SiH with purity better than 99.9%. More specifically, isotopically mixed nanowires ²⁸Si ³⁰Si with a composition close to the highest mass disorder (x ∼ 0.5) were investigated. The effect of mass disorder on the phonon behavior was elucidated and compared to that in isotopically pure Si nanowires having a similar reduced mass. We found that the disorder-induced enhancement in phonon scattering in isotopically mixed nanowires is unexpectedly much more significant than in bulk crystals of close isotopic compositions. This effect is explained by a nonuniform distribution of ²⁸Si and ³⁰Si isotopes in the grown isotopically mixed nanowires with local compositions ranging from x = ∼0.25 to 0.70. Moreover, we also observed that upon heating, phonons in ²⁸Si ³⁰Si nanowires behave remarkably differently from those in ²⁹Si nanowires suggesting a reduced thermal conductivity induced by mass disorder. Using Raman nanothermometry, we found that the thermal conductivity of isotopically mixed ²⁸Si Si nanowires is ∼30% lower than that of isotopically pure ²⁹Si nanowires in agreement with theoretical predictions. (Figure Presented)
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