•Dynamic mode decomposition (DMD) extracts dynamically coherent patterns from large-scale neuronal recordings.•Multiple, distinct sleep spindle networks are identified by DMD as measured in subdural ...array recordings.•Sleep spindle networks are characterized by different cortical distribution patterns, carrying frequencies and durations.
There is a broad need in neuroscience to understand and visualize large-scale recordings of neural activity, big data acquired by tens or hundreds of electrodes recording dynamic brain activity over minutes to hours. Such datasets are characterized by coherent patterns across both space and time, yet existing computational methods are typically restricted to analysis either in space or in time separately.
Here we report the adaptation of dynamic mode decomposition (DMD), an algorithm originally developed for studying fluid physics, to large-scale neural recordings. DMD is a modal decomposition algorithm that describes high-dimensional dynamic data using coupled spatial–temporal modes. The algorithm is robust to variations in noise and subsampling rate; it scales easily to very large numbers of simultaneously acquired measurements.
We first validate the DMD approach on sub-dural electrode array recordings from human subjects performing a known motor task. Next, we combine DMD with unsupervised clustering, developing a novel method to extract spindle networks during sleep. We uncovered several distinct sleep spindle networks identifiable by their stereotypical cortical distribution patterns, frequency, and duration.
DMD is closely related to principal components analysis (PCA) and discrete Fourier transform (DFT). We may think of DMD as a rotation of the low-dimensional PCA space such that each basis vector has coherent dynamics.
The resulting analysis combines key features of performing PCA in space and power spectral analysis in time, making it particularly suitable for analyzing large-scale neural recordings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Lignin is an energy-dense, heterogeneous polymer comprised of phenylpropanoid monomers used by plants for structure, water transport, and defense, and it is the second most abundant biopolymer on ...Earth after cellulose. In production of fuels and chemicals from biomass, lignin is typically underused as a feedstock and burned for process heat because its inherent heterogeneity and recalcitrance make it difficult to selectively valorize. In nature, however, some organisms have evolved metabolic pathways that enable the utilization of lignin-derived aromatic molecules as carbon sources. Aromatic catabolism typically occurs via upper pathways that act as a “biological funnel” to convert heterogeneous substrates to central intermediates, such as protocatechuate or catechol. These intermediates undergo ring cleavage and are further converted via the β-ketoadipate pathway to central carbon metabolism. Here, we use a natural aromatic-catabolizing organism, Pseudomonas putida KT2440, to demonstrate that these aromatic metabolic pathways can be used to convert both aromatic model compounds and heterogeneous, lignin-enriched streams derived from pilot-scale biomass pretreatment into medium chain-length polyhydroxyalkanoates (mcl -PHAs). mcl -PHAs were then isolated from the cells and demonstrated to be similar in physicochemical properties to conventional carbohydrate-derived mcl -PHAs, which have applications as bioplastics. In a further demonstration of their utility, mcl -PHAs were catalytically converted to both chemical precursors and fuel-range hydrocarbons. Overall, this work demonstrates that the use of aromatic catabolic pathways enables an approach to valorize lignin by overcoming its inherent heterogeneity to produce fuels, chemicals, and materials.
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Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such ...individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction.
A total of 291 bereaved respondents were interviewed three times, grouped as 0-6, 6-12, and 12-24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment.
The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Formation of the Orientale lunar multiring basin Johnson, Brandon C.; Blair, David M.; Collins, Gareth S. ...
Science (American Association for the Advancement of Science),
10/2016, Volume:
354, Issue:
6311
Journal Article
Peer reviewed
Open access
Multiring basins, large impact craters characterized by multiple concentric topographic rings, dominate the stratigraphy, tectonics, and crustal structure of the Moon. Using a hydrocode, we simulated ...the formation of the Orientale multiring basin, producing a subsurface structure consistent with high-resolution gravity data from the Gravity Recovery and Interior Laboratory (GRAIL) spacecraft. The simulated impact produced a transient crater, ~390 kilometers in diameter, that was not maintained because of subsequent gravitational collapse. Our simulations indicate that the flow of warm weak material at depth was crucial to the formation of the basin's outer rings, which are large normal faults that formed at different times during the collapse stage. The key parameters controlling ring location and spacing are impactor diameter and lunar thermal gradients.
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Adipic acid production from lignin Vardon, Derek R; Franden, Mary Ann; Johnson, Christopher W ...
Energy & environmental science,
02/2015, Volume:
8, Issue:
2
Journal Article
Peer reviewed
Lignin is an alkyl-aromatic polymer present in plant cell walls for defense, structure, and water transport. Despite exhibiting a high-energy content, lignin is typically slated for combustion in ...modern biorefineries due to its inherent heterogeneity and recalcitrance, whereas cellulose and hemicellulose are converted to renewable fuels and chemicals. However, it is critical for the viability of third-generation biorefineries to valorize lignin alongside polysaccharides. To that end, we employ metabolic engineering, separations, and catalysis to convert lignin-derived species into cis,cis-muconic acid, for subsequent hydrogenation to adipic acid, the latter being the most widely produced dicarboxylic acid. First, Pseudomonas putidaKT2440 was metabolically engineered to funnel lignin-derived aromatics to cis,cis-muconate, which is an atom-efficient biochemical transformation. This engineered strain was employed in fed-batch biological cultivation to demonstrate a cis,cis-muconate titer of 13.5 g L super(-1) in 78.5 h from a model lignin-derived compound. cis,cis-Muconic acid was recovered in high purity (>97%) and yield (74%) by activated carbon treatment and crystallization (5 degree C, pH 2). Pd/C was identified as a highly active catalyst for cis,cis-muconic acid hydrogenation to adipic acid with high conversion (>97%) and selectivity (>97%). Under surface reaction controlling conditions (24 degree C, 24 bar, ethanol solvent), purified cis,cis-muconic acid exhibits a turnover frequency of 23-30 s super(-1) over Pd/C, with an apparent activation energy of 70 kJ mol super(-1). Lastly, cis,cis-muconate was produced with engineered P. putidagrown on a biomass-derived, lignin-enriched stream, demonstrating an integrated strategy towards lignin valorization to an important commodity chemical.
Previously we proposed that transmission of the hedgehog signal across the plasma membrane by Smoothened is triggered by its interaction with cholesterol (Luchetti et al., 2016). But how is ...cholesterol, an abundant lipid, regulated tightly enough to control a signaling system that can cause birth defects and cancer? Using toxin-based sensors that distinguish between distinct pools of cholesterol, we find that Smoothened activation and Hedgehog signaling are driven by a biochemically-defined, small fraction of membrane cholesterol, termed accessible cholesterol. Increasing cholesterol accessibility by depletion of sphingomyelin, which sequesters cholesterol in complexes, amplifies Hedgehog signaling. Hedgehog ligands increase cholesterol accessibility in the membrane of the primary cilium by inactivating the transporter-like protein Patched 1. Trapping this accessible cholesterol blocks Hedgehog signal transmission across the membrane. Our work shows that the organization of cholesterol in the ciliary membrane can be modified by extracellular ligands to control the activity of cilia-localized signaling proteins.
Alzheimer's disease (AD) is the fifth leading cause of death among adults aged 65 and older, yet the onset and progression of the disease is poorly understood. What is known is that the presence of ...amyloid, particularly polymerized Aβ42, defines when people are on the AD continuum. Interestingly, as AD progresses, less Aβ42 is detectable in the plasma, a phenomenon thought to result from Aβ becoming more aggregated in the brain and less Aβ42 and Aβ40 being transported from the brain to the plasma via the CSF. We propose that extracellular vesicles (EVs) play a role in this transport. EVs are found in bodily fluids such as blood, urine, and cerebrospinal fluid and carry diverse "cargos" of bioactive molecules (e.g., proteins, nucleic acids, lipids, metabolites) that dynamically reflect changes in the cells from which they are secreted. While Aβ42 and Aβ40 have been reported to be present in EVs, it is not known whether this interaction is specific for these peptides and thus whether amyloid-carrying EVs play a role in AD and/or serve as brain-specific biomarkers of the AD process. To determine if there is a specific interaction between Aβ and EVs, we used isothermal titration calorimetry (ITC) and discovered that Aβ42 and Aβ40 bind to EVs in a manner that is sequence specific, saturable, and endothermic. In addition, Aβ incubation with EVs overnight yielded larger amounts of bound Aβ peptide that was fibrillar in structure. These findings point to a specific amyloid-EV interaction, a potential role for EVs in the transport of amyloid from the brain to the blood, and a role for this amyloid pool in the AD process.
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Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed ...B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation.
This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1.
Intergenerational Transmission of Partner Violence Ehrensaft, Miriam K; Cohen, Patricia; Brown, Jocelyn ...
Journal of consulting and clinical psychology,
08/2003, Volume:
71, Issue:
4
Journal Article
Peer reviewed
An unselected sample of 543 children was followed over 20 years to test the independent effects of parenting, exposure to domestic violence between parents (ETDV), maltreatment, adolescent disruptive ...behavior disorders, and emerging adult substance abuse disorders (SUDs) on the risk of violence to and from an adult partner. Conduct disorder (CD) was the strongest risk for perpetrating partner violence for both sexes, followed by ETDV, and power assertive punishment. The effect of child abuse was attributable to these 3 risks. ETDV conferred the greatest risk of receiving partner violence; CD increased the odds of receiving partner violence but did not mediate this effect. Child physical abuse and CD in adolescence were strong independent risks for injury to a partner. SUD mediated the effect of adolescent CD on injury to a partner but not on injury by a partner. Prevention implications are highlighted.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The majority of subjects who attempt to learn control of a brain–computer interface (BCI) can do so with adequate training. Much like when one learns to type or ride a bicycle, BCI users report ...transitioning from a deliberate, cognitively focused mindset to near automatic control as training progresses. What are the neural correlates of this process of BCI skill acquisition? Seven subjects were implanted with electrocorticography (ECoG) electrodes and had multiple opportunities to practice a 1D BCI task. As subjects became proficient, strong initial task-related activation was followed by lessening of activation in prefrontal cortex, premotor cortex, and posterior parietal cortex, areas that have previously been implicated in the cognitive phase of motor sequence learning and abstract task learning. These results demonstrate that, although the use of a BCI only requires modulation of a local population of neurons, a distributed network of cortical areas is involved in the acquisition of BCI proficiency.
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