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"Baker, Daniel"
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Dashing: fast and accurate genomic distances with HyperLogLog
Dashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for set unions and intersections. Dashing summarizes genomes more rapidly than previous MinHash-based methods while providing greater accuracy across a wide range of input sizes and sketch sizes. It can sketch and calculate pairwise distances for over 87K genomes in 6 minutes. Dashing is open source and available at
https://github.com/dnbaker/dashing
.
Journal Article
Neural correlates of the deployment of spatial attention, and their modulation by repetitive movements
The deployment of spatial attention generates distinct neural signatures that can be detected at the scalp. Here, we use multivariate pattern analysis of EEG data to decode the deployment of spatial attention, and ask if this is modulated by repetitive movements. ‘Stimming’ movements (also known as repetitive stereotypies), are widely reported in autism, but also present in some neurotypical individuals. Stimming has historically been viewed as a problematic behaviour, but many individuals claim that stimming benefits attention. We first validated our paradigm (a Posner-style cueing design), demonstrating above-chance classification of cue direction from around 300 ms post-cue onset. We then investigated whether stimming modulates decoding accuracy and task performance. Our results, consisting of data primarily from neurotypical participants, do not suggest that stimming has a negative impact on an individual’s ability to attend, unless the individual does not typically engage in stimming behaviours. This suggests interventions aiming to reduce stimming behaviours are not necessarily warranted and highlights the need for further research into the potential benefits of stimming specifically within the autistic population. Future research might also consider the potential overlap between autistic stimming and the fidgeting behaviours which are characteristic of ADHD, to help understand the significant overlaps between the characteristics of the two conditions.
Journal Article
Wave–particle interaction effects in the Van Allen belts
Discovering such structures as the third radiation belt (or “storage ring”) has been a major observational achievement of the NASA Radiation Belt Storm Probes program (renamed the “Van Allen Probes” mission in November 2012). A goal of that program was to understand more thoroughly how high-energy electrons are accelerated deep inside the radiation belts—and ultimately lost—due to various wave–particle interactions. Van Allen Probes studies have demonstrated that electrons ranging up to 10 megaelectron volts (MeV) or more can be produced over broad regions of the outer Van Allen zone on timescales as short as a few minutes. The key to such rapid acceleration is the interaction of “seed” populations of ~ 10–200 keV electrons (and subsequently higher energies) with electromagnetic waves in the lower band (whistler-mode) chorus frequency range. Van Allen Probes data show that “source” electrons (in a typical energy range of one to a few tens of keV energy) produced by magnetospheric substorms play a crucial role in feeding free energy into the chorus waves in the outer zone. These chorus waves then, in turn, rapidly heat and accelerate the tens to hundreds of keV seed electrons injected by substorms to much higher energies. Hence, we often see that geomagnetic activity driven by strong solar storms (coronal mass ejections, or CMEs) commonly leads to ultra-relativistic electron production through the intermediary step of waves produced during intense magnetospheric substorms. More generally, wave–particle interactions are of fundamental importance over a broad range of energies and in virtually all regions of the magnetosphere. We provide a summary of many of the wave modes and particle interactions that have been studied in recent times.
Journal Article
CAR T therapy beyond cancer: the evolution of a living drug
Engineering a patient’s own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.
The rationale behind chimaeric antigen receptor T cell therapy is reviewed, and current challenges in oncology, preliminary reports in noncancerous diseases and relevant emerging technologies are discussed.
Journal Article
Fragment Length of Circulating Tumor DNA
Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.
Journal Article
Signal combination in flutter vibration perception
While the brain's integration of auditory and visual inputs has been extensively investigated, the mechanisms underlying somatosensory signal combination remain less explored. Here, we combine psychophysical thresholds with steady-state somatosensory evoked potentials (SSSEPs) to investigate how vibrotactile inputs are combined across fingers. We find that doubling the number of stimulated digits leads to a weak improvement in detection threshold, consistent with probability summation, whereas introducing a masking stimulus to interleaved digits induces inter-digit suppression. Correspondingly, EEG recordings reveal a ~ 1.4-fold increase in SSSEP amplitude when doubling the number of digits stimulated at the same frequency, reflecting a summation effect. In contrast, SSSEP amplitudes decrease when digits are vibrated at two different frequencies, further supporting the presence of suppression. These results are consistent with a model featuring inhibition between digits and reveal that the weight of suppression is intermediate between that observed in binocular vision and binaural hearing.
Journal Article
Neural correlates of the uncanny valley effect for robots and hyper-realistic masks
Viewing artificial objects and images that are designed to appear human can elicit a sense of unease, referred to as the ‘uncanny valley’ effect. Here we investigate neural correlates of the uncanny valley, using still images of androids (robots designed to look human), and humans wearing hyper-realistic silicone masks, as well as still images of real humans, in two experiments. In both experiments, human-like stimuli were harder to distinguish from real human faces than stimuli that were clearly not designed to mimic humans but contain facial features (mechanical robots and Halloween masks). Stimulus evoked potentials (electromagnetic brain responses) did not show convincing differences between faces and either androids or realistic masks when using traditional univariate statistical tests. However, a more sensitive multivariate analysis identified two regions of above-chance decoding, indicating neural differences in the response between human faces and androids/realistic masks. The first time window was around 100–200 ms post stimulus onset, and most likely corresponds to low-level image differences between conditions. The second time window was around 600 ms post stimulus onset, and may reflect top-down processing, and may correspond to the subjective sense of unease characteristic of the uncanny valley effect. Objective neural components might be used in future to rapidly train generative artificial intelligence systems to produce more realistic images that are perceived as natural by human observers.
Journal Article