Vernacular Music Material Culture in Space and Time

Few musical instruments are more closely tied or hold greater significance to American history than the banjo. From its West African roots, to its birth in the seventeenth century Caribbean, and through its meteoric rise in nineteenth century American popular culture, the banjo is an iconic instrument whose impact is woven into the cultural fabric of the American experience. As scholars, researchers, and enthusiasts continue to discover new information about the early banjo, there is no collective location to maintain, interact with, and collectively analyze this important data. The proposed Banjo Sightings Database Project (BSD) will combine rare and widely-dispersed primary source material (circa 1650-1870) with appropriate and innovative technological applications, resulting in a system that not only catalogs information about the early banjo, but also establishes an interactive, peer-reviewed knowledge management system, allowing users to explore the early banjo

Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

Timed degradation of the cyclin-dependent kinase inhibitor p27^(Kip1) by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leukemia models, with little effect on normal tissues. We also demonstrate a novel feed forward feedback loop by which Notch and IL-7 signaling cooperatively converge on SKP2 induction and cell cycle activation. These studies show that the Notch/SKP2/p27^(Kip1) pathway plays a unique role in T-ALL development and provide a proof-of-concept for the use of SKP2 as a new therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL)

Transcranial direct current stimulation of right dorsolateral prefrontal cortex does not affect model-based or model-free reinforcement learning in humans

There is broad consensus that the prefrontal cortex supports goal-directed, model-based decision-making. Consistent with this, we have recently shown that model-based control can be impaired through transcranial magnetic stimulation of right dorsolateral prefrontal cortex in humans. We hypothesized that an enhancement of model-based control might be achieved by anodal transcranial direct current stimulation of the same region. We tested 22 healthy adult human participants in a within-subject, double-blind design in which participants were given Active or Sham stimulation over two sessions. We show Active stimulation had no effect on model-based control or on model-free ('habitual') control compared to Sham stimulation. These null effects are substantiated by a power analysis, which suggests that our study had at least 60% power to detect a true effect, and by a Bayesian model comparison, which favors a model of the data that assumes stimulation had no effect over models that assume stimulation had an effect on behavioral control. Although we cannot entirely exclude more trivial explanations for our null effect, for example related to (faults in) our experimental setup, these data suggest that anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex does not improve model-based control, despite existing evidence that transcranial magnetic stimulation can disrupt such control in the same brain region

It's not what you say but the way that you say it: an fMRI study of differential lexical and non-lexical prosodic pitch processing

<p>Abstract</p> <p>Background</p> <p>This study aims to identify the neural substrate involved in prosodic pitch processing. Functional magnetic resonance imaging was used to test the premise that prosody pitch processing is primarily subserved by the right cortical hemisphere.</p> <p>Two experimental paradigms were used, firstly pairs of spoken sentences, where the only variation was a single internal phrase pitch change, and secondly, a matched condition utilizing pitch changes within analogous tone-sequence phrases. This removed the potential confounder of lexical evaluation. fMRI images were obtained using these paradigms.</p> <p>Results</p> <p>Activation was significantly greater within the right frontal and temporal cortices during the tone-sequence stimuli relative to the sentence stimuli.</p> <p>Conclusion</p> <p>This study showed that pitch changes, stripped of lexical information, are mainly processed by the right cerebral hemisphere, whilst the processing of analogous, matched, lexical pitch change is preferentially left sided. These findings, showing hemispherical differentiation of processing based on stimulus complexity, are in accord with a 'task dependent' hypothesis of pitch processing.</p

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

The first fossil opilioacariform mite (Acari: Opilioacariformes) and the first Baltic amber camel spider (Solifugae)

The first fossil opilioacariform mite (Acari: Opilioacariformes), Paracarus pristinus sp. n., is described from Baltic amber (Tertiary: Eocene). This well-preserved inclusion has six eyes and, thus, can be excluded from the derived, four-eyed genera. Based on characters such as the extremely long leg 4, it is assigned to the extant central Asian genus Paracarus Chamberlin & Mulaik, 1942. As with many Baltic amber inclusions, we lack an exact provenance for the type specimen, but the Baltic region is further north than the present day range of Recent opilioacariform species and suggests that the range of this group was once more extensive within Eurasia. The first solifuge (Solifugae) from Baltic amber is described as Palaeoblossia groehni gen. et sp. n. Based on its size and general appearance, it can be assigned to Daesiidae, and again represents an arachnid group which previously had a much wider geographical range. If adult, it may represent the smallest solifuge known.Peer Reviewe