The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Wall roughness induces asymptotic ultimate turbulence

Turbulence is omnipresent in Nature and technology, governing the transport of heat, mass, and momentum on multiple scales. For real-world applications of wall-bounded turbulence, the underlying surfaces are virtually always rough; yet characterizing and understanding the effects of wall roughness for turbulence remains a challenge, especially for rotating and thermally driven turbulence. By combining extensive experiments and numerical simulations, here, taking as example the paradigmatic Taylor-Couette system (the closed flow between two independently rotating coaxial cylinders), we show how wall roughness greatly enhances the overall transport properties and the corresponding scaling exponents. If only one of the walls is rough, we reveal that the bulk velocity is slaved to the rough side, due to the much stronger coupling to that wall by the detaching flow structures. If both walls are rough, the viscosity dependence is thoroughly eliminated in the boundary layers and we thus achieve asymptotic ultimate turbulence, i.e. the upper limit of transport, whose existence had been predicted by Robert Kraichnan in 1962 (Phys. Fluids {\bf 5}, 1374 (1962)) and in which the scalings laws can be extrapolated to arbitrarily large Reynolds numbers

A flexible sequential learning deficit in patients with Parkinson’s disease: a 2 × 8 button-press task

A 2 × 8 button-press task is a sequential hand movement task in which subjects are required to press eight pairs of buttons as accurately and quickly as possible. The 2 × 8 task allows us to examine flexible sequential learning, more aptly called sequence-unselective learning. Sequence-unselective learning is observed after repeated experiences with the task, when subjects have shown good progress in learning, with new sequences as well as previously learned ones. Although cognitive inflexibility has been reported in patients with Parkinson’s disease (PD), there have been few studies investigating their flexibility in sequential learning. We examined PD patients’ ability for sequence-unselective learning through the use of a 2 × 8 button-press task. In the first session, PD patients and subjects from the control group performed a sequential 2 × 8 task until the learning criterion was fulfilled (Session 1). After 1 month, they participated in other sessions: one involving the learned sequence (Session 2) and another involving the new sequence (Session 3). We found that PD patients made more errors than the normal control subjects only when learning the new sequence (Session 3) (P < 0.01). In Session 3, control subjects reached the learning target with fewer errors than in the Session 1 (normal sequence-unselective learning), whereas the PD patients did not exhibit such an improvement. Our results revealed a sequence-unselective deficit in PD patients. The deficit may help to emphasize the cognitive and physical inflexibility of PD

[Plasma 2020 Decadal] Disentangling the Spatiotemporal Structure of Turbulence Using Multi-Spacecraft Data

This white paper submitted for 2020 Decadal Assessment of Plasma Science concerns the importance of multi-spacecraft missions to address fundamental questions concerning plasma turbulence. Plasma turbulence is ubiquitous in the universe, and it is responsible for the transport of mass, momentum, and energy in such diverse systems as the solar corona and wind, accretion discs, planet formation, and laboratory fusion devices. Turbulence is an inherently multi-scale and multi-process phenomenon, coupling the largest scales of a system to sub-electron scales via a cascade of energy, while simultaneously generating reconnecting current layers, shocks, and a myriad of instabilities and waves. The solar wind is humankind's best resource for studying the naturally occurring turbulent plasmas that permeate the universe. Since launching our first major scientific spacecraft mission, Explorer 1, in 1958, we have made significant progress characterizing solar wind turbulence. Yet, due to the severe limitations imposed by single point measurements, we are unable to characterize sufficiently the spatial and temporal properties of the solar wind, leaving many fundamental questions about plasma turbulence unanswered. Therefore, the time has now come wherein making significant additional progress to determine the dynamical nature of solar wind turbulence requires multi-spacecraft missions spanning a wide range of scales simultaneously. A dedicated multi-spacecraft mission concurrently covering a wide range of scales in the solar wind would not only allow us to directly determine the spatial and temporal structure of plasma turbulence, but it would also mitigate the limitations that current multi-spacecraft missions face, such as non-ideal orbits for observing solar wind turbulence. Some of the fundamentally important questions that can only be addressed by in situ multipoint measurements are discussed

High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach

Parker solar probe: four years of discoveries at solar cycle minimum

Launched on 12 Aug. 2018, NASA’s Parker Solar Probe had completed 13 of its scheduled 24 orbits around the Sun by Nov. 2022. The mission’s primary science goal is to determine the structure and dynamics of the Sun’s coronal magnetic field, understand how the solar corona and wind are heated and accelerated, and determine what processes accelerate energetic particles. Parker Solar Probe returned a treasure trove of science data that far exceeded quality, significance, and quantity expectations, leading to a significant number of discoveries reported in nearly 700 peer-reviewed publications. The first four years of the 7-year primary mission duration have been mostly during solar minimum conditions with few major solar events. Starting with orbit 8 (i.e., 28 Apr. 2021), Parker flew through the magnetically dominated corona, i.e., sub-Alfvénic solar wind, which is one of the mission’s primary objectives. In this paper, we present an overview of the scientific advances made mainly during the first four years of the Parker Solar Probe mission, which go well beyond the three science objectives that are: (1) Trace the flow of energy that heats and accelerates the solar corona and solar wind; (2) Determine the structure and dynamics of the plasma and magnetic fields at the sources of the solar wind; and (3) Explore mechanisms that accelerate and transport energetic particles

U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line

U87MG is a commonly studied grade IV glioma cell line that has been analyzed in at least 1,700 publications over four decades. In order to comprehensively characterize the genome of this cell line and to serve as a model of broad cancer genome sequencing, we have generated greater than 30× genomic sequence coverage using a novel 50-base mate paired strategy with a 1.4kb mean insert library. A total of 1,014,984,286 mate-end and 120,691,623 single-end two-base encoded reads were generated from five slides. All data were aligned using a custom designed tool called BFAST, allowing optimal color space read alignment and accurate identification of DNA variants. The aligned sequence reads and mate-pair information identified 35 interchromosomal translocation events, 1,315 structural variations (>100 bp), 191,743 small (<21 bp) insertions and deletions (indels), and 2,384,470 single nucleotide variations (SNVs). Among these observations, the known homozygous mutation in PTEN was robustly identified, and genes involved in cell adhesion were overrepresented in the mutated gene list. Data were compared to 219,187 heterozygous single nucleotide polymorphisms assayed by Illumina 1M Duo genotyping array to assess accuracy: 93.83% of all SNPs were reliably detected at filtering thresholds that yield greater than 99.99% sequence accuracy. Protein coding sequences were disrupted predominantly in this cancer cell line due to small indels, large deletions, and translocations. In total, 512 genes were homozygously mutated, including 154 by SNVs, 178 by small indels, 145 by large microdeletions, and 35 by interchromosomal translocations to reveal a highly mutated cell line genome. Of the small homozygously mutated variants, 8 SNVs and 99 indels were novel events not present in dbSNP. These data demonstrate that routine generation of broad cancer genome sequence is possible outside of genome centers. The sequence analysis of U87MG provides an unparalleled level of mutational resolution compared to any cell line to date

Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

<p>Abstract</p> <p>Background</p> <p>The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state <it>in vivo </it>a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed <it>in vivo </it>the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site.</p> <p>Methods</p> <p>Generation 5 (G5) through generation 8 (G8) polyamidoamine dendrimers were labeled with gadolinium (Gd)-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized <it>in vitro </it>by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5) the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized <it>in vivo </it>over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps.</p> <p>Results</p> <p>The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8 dendrimers were 13 ± 1 nm. The BTB of ectopic RG-2 gliomas was more permeable than the BTB of orthotopic RG-2 gliomas to all Gd-dendrimer generations except for Gd-G8. The BTB of both ectopic RG-2 gliomas and orthotopic RG-2 gliomas was not permeable to Gd-G8 dendrimers.</p> <p>Conclusion</p> <p>The physiologic upper limit of pore size in the BTB of malignant solid tumor microvasculature is approximately 12 nanometers. In the physiologic state <it>in vivo </it>the luminal fibrous glycocalyx of the BTB of malignant brain tumor and peripheral tumors is the primary impediment to the effective transvascular transport of particles across the BTB of malignant solid tumor microvasculature independent of tumor host site. The higher permeability of malignant peripheral tumor microvasculature to macromolecules smaller than approximately 12 nm in diameter is attributable to the presence of a greater number of pores underlying the glycocalyx of the BTB of malignant peripheral tumor microvasculature.</p

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice

Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-β-amyloid antibody. Our data suggest a biomarker strategy for the early detection of β-amyloid-related abnormalities

Bringing the real world into the fMRI scanner: Repetition effects for pictures versus real objects

Our understanding of the neural underpinnings of perception is largely built upon studies employing 2-dimensional (2D) planar images. Here we used slow event-related functional imaging in humans to examine whether neural populations show a characteristic repetition-related change in haemodynamic response for real-world 3-dimensional (3D) objects, an effect commonly observed using 2D images. As expected, trials involving 2D pictures of objects produced robust repetition effects within classic object-selective cortical regions along the ventral and dorsal visual processing streams. Surprisingly, however, repetition effects were weak, if not absent on trials involving the 3D objects. These results suggest that the neural mechanisms involved in processing real objects may therefore be distinct from those that arise when we encounter a 2D representation of the same items. These preliminary results suggest the need for further research with ecologically valid stimuli in other imaging designs to broaden our understanding of the neural mechanisms underlying human vision