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In everyday social environments, demands on attentional resources dynamically shift to balance our attention to targets of interest while alerting us to important objects in our surrounds. The current study uses electroencephalography to explore how the push-pull interaction between top-down and bottom-up attention manifests itself in dynamic auditory scenes. Using natural soundscapes as distractors while subjects attend to a controlled rhythmic sound sequence, we find that salient events in background scenes significantly suppress phase-locking and gamma responses to the attended sequence, countering enhancement effects observed for attended targets. In line with a hypothesis of limited attentional resources, the modulation of neural activity by bottom-up attention is graded by degree of salience of ambient events. The study also provides insights into the interplay between endogenous and exogenous attention during natural soundscapes, with both forms of attention engaging a common fronto-parietal network at different time lags. When walking into a busy restaurant or café, our sense of hearing is bombarded with different sounds that our brain has to sort through to make sense of our surroundings. Our brain has to balance the desire to focus our attention on sounds we choose to listen to (such as the friend we are having a conversation with) and sounds that attract our attention (such as the sound of someone else’s phone ringing). Without the ability to be distracted, we might miss a noise that may or may not be crucial to our survival, like the engine roar of an approaching vehicle or a ping notifying us of an incoming email. However, it remains unclear what happens in our brains that enables us to shift our attention to background sounds. To investigate this further, Huang and Elhilali asked 81 participants to focus their attention on a repeating sound while being exposed to background noises from everyday life, such as sounds from a busy café. The experiment showed that when a more noticeable sound happened in the background, such as a loud voice, the participants were more likely to lose attention on their task and miss changes in the tone of the repeating sound. Huang and Elhilali then measured the brain activity of 12 participants as they counted the number of altered tones in a sequence of sounds, again with noise in the background. This revealed that brain waves synchronized with tones that the participants were concentrating on. However, once there was a noticeable event in the background, this tone synchronization was reduced and the brain waves aligned with the background noise. Huang and Elhilali found that distracting noises in the background activate the same region of the brain as sounds we choose to listen to. This demonstrates how background sounds are able to re-direct our attention. These results are consistent with the idea that we have a limited capacity for attention, and that new sensory information can divert brain activity. Having a better understanding of how these processes work could help develop better communication aids for people with impaired hearing, and improve software for interpreting sounds with a noisy background.

Deep neural networks have been recently shown to capture intricate information transformation of signals from the sensory profiles to semantic representations that facilitate recognition or discrimination of complex stimuli. In this vein, convolutional neural networks (CNNs) have been used very successfully in image and audio classification. Designed to imitate the hierarchical structure of the nervous system, CNNs reflect activation with increasing degrees of complexity that transform the incoming signal onto object-level representations. In this work, we employ a CNN trained for large-scale audio object classification to gain insights about the contribution of various audio representations that guide sound perception. The analysis contrasts activation of different layers of a CNN with acoustic features extracted directly from the scenes, perceptual salience obtained from behavioral responses of human listeners, as well as neural oscillations recorded by electroencephalography (EEG) in response to the same natural scenes. All three measures are tightly linked quantities believed to guide percepts of salience and object formation when listening to complex scenes. The results paint a picture of the intricate interplay between low-level and object-level representations in guiding auditory salience that is very much dependent on context and sound category.

The protein tyrosine phosphatases (PTPs) TCPTP, PTPN22, and SHP1 are critical regulators of the activating phosphotyrosine (pY) site on the initiating T cell kinase, Lck Y394 . Still, the broader implications of these phosphatases in T cell receptor (TCR) signalling and T cell biology remain unclear. By combining CRISPR/Cas9 gene editing and mass spectrometry, we evaluate the protein- and pY-level effects of TCPTP, PTPN22, and SHP1 in the Jurkat T cell model system. We find that deletion of each phosphatase corresponds to unique changes in the proteome of T cells, with few large-scale changes to TCR signalling proteins. Notably, PTPN22 and SHP1 deletions have opposing effects on pY abundance globally, while TCPTP deletion modestly elevates pY levels. Finally, we show that TCPTP is indirectly involved in Erk1/2 positive feedback to the TCR. Overall, our work provides evidence for alternative functions of three T cell phosphatases long thought to be redundant.

Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT) or glutamic acid decarboxylase (GAD) mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85%) between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future studies to manipulate CRH-BP in a cell type-specific manner to better understand its role in stress-related psychiatric disorders, including anxiety, depression and addiction.

Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects. We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes, providing a potential peripheral therapeutic hCB1R target. It is unknown whether there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively) isoforms. In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons. Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or the liver. Rat rCB1R isoforms are differentially expressed in primary cultured neurons, astrocytes, and microglia. We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037, a peripherally restricted CB1R inverse agonist, using the published crystal structure of hCB1R. The results provide models for future CB1R peripheral targeting.

SPT-3G, the third generation camera on the South Pole Telescope (SPT), was deployed in the 2016-2017 Austral summer season. The SPT is a 10-meter telescope located at the geographic South Pole and designed for observations in the millimeter-wave and submillimeter-wave regions of the electromagnetic spectrum. The SPT is primarily used to study the cosmic microwave background (CMB). The upgraded camera produces an order of magnitude more data than the previous generations of SPT cameras. The telescope is expected to collect a petabyte (PB) of data over course of five years, which is a significantly larger data volume than any other CMB telescope in operation. The increase in data rate required radical changes to the SPT computing model both at the South Pole and University of Chicago. This paper will describe the overall integration of distributed storage and compute resources into a common interface, deployment of on-site data reduction and storage infrastructure, and the usage of the Open Science Grid (OSG) by the SPT collaboration.

Observations of the sky at millimeter wavelengths are of critical importance to modern cosmology. Measurements of the primary cosmic microwave background (CMB) anisotropies, its secondary anisotropies, and foreground objects all contribute to our understanding the universe. As the oldest light in the universe, the CMB contains imprints from much of cosmic history. Measurements of these secondary anisotropies provides a window into the evolution of the universe, including the growth of the largest structures in the universe, and the process of reionization by early stars and galaxies.These measurements are only possible with a high-resolution telescope and extremely precise calibration. This dissertation is primarily concerned with the design and calibration of the SPT-3G camera on the South Pole Telescope. In particular, the calibration of the raw detector data, and the measurement of the telescope beams are described in detail. These pieces are essential for making a precise measurement of the mm-wave sky, and properly accounting for the effects of the telescope optics. In the last chapter, we show how all of this comes together to produce a catalog of galaxy clusters discovered through the thermal Sunyaev Zel’dovich effect. We report 89 candidates, with 81 confirmed by optical and infrared follow-up observations. 29 are reported for the first time. This provides a mass-limited catalog of galaxy clusters over 100 square degrees.

The South Pole Telescope SPT-3G camera utilizes Ti/Au transition edge sensors (TESs). A key requirement for these sensors is reproducibility and long-term stability of the superconducting (SC) transitions. Here, we discuss the impact of electrical contacts design and materials on the shape of the SC transitions. Using scanning electron microscope, atomic force microscope, and optical differential interference contrast microscopy, we observed the presence of unexpected defects of morphological nature on the titanium surface and their evolution in time in proximity to Nb contacts. We found direct correlation between the variations of the morphology and the SC transition shape. Experiments with different diffusion barriers between TES and Nb leads were performed to clarify the origin of this problem. We have demonstrated that the reproducibility of superconducting transitions can be significantly improved by preventing diffusion processes in the TES–leads contact areas.

We explore the relationship between the thermal Sunyaev-Zel'dovich (tSZ) power spectrum amplitude and the halo mass and redshift of galaxy clusters in South Pole Telescope (SPT) data, in comparison with three \\(N\\)-body simulations combined with semi-analytical gas models of the intra-cluster medium. Specifically, we calculate both the raw and fractional power contribution to the full tSZ power spectrum amplitude at \\(\\ell = 3000\\) from clusters as a function of halo mass and redshift. We use nine mass bins in the range \\(1 \\times 10^{14}\\ M_\\odot\\ h^{-1} < M_{500} < 2 \\times 10^{15}\\ M_\\odot\\ h^{-1}\\), and two redshift bins defined by \\(0.25 < z < 0.59\\) and \\(0.59 < z < 1.5\\). We additionally divide the raw power contribution in each mass bin by the number of clusters in that bin, as a metric for comparison of different gas models. At lower masses, the SPT data prefers a model that includes a mass-dependent bound gas fraction component and relatively high levels of AGN feedback, whereas at higher masses there is a preference for a model with a lower amount of feedback and a complete lack of non-thermal pressure support. The former provides the best fit to the data overall, in regards to all metrics for comparison. Still, discrepancies exist and the data notably exhibits a steep mass-dependence which all of the simulations fail to reproduce. This suggests the need for additional mass- and redshift-dependent adjustments to the gas models of each simulation, or the potential presence of contamination in the data at halo masses below the detection threshold of SPT-SZ. Furthermore, the data does not demonstrate significant redshift evolution in the per-cluster tSZ power spectrum contribution, in contrast to self-similar model predictions.

The protein tyrosine phosphatases (PTPs) TCPTP, PTPN22, and SHP1 are critical regulators of the activating phosphotyrosine (pY) site on the initiating T cell kinase, Lck the broader implications of these phosphatases in T cell receptor (TCR) signalling and T cell biology remain unclear. By combining CRISPR/Cas9 gene editing and mass spectrometry, we evaluate the protein- and pY-level effects of TCPTP, PTPN22, and SHP1 in the Jurkat T cell model system. We find that deletion of each phosphatase corresponds to unique changes in the proteome of T cells, with few large-scale changes to TCR signalling proteins. Notably, PTPN22 and SHP1 deletions have opposing effects on pY abundance globally, while TCPTP deletion modestly elevates pY levels. Finally, we show that TCPTP is indirectly involved in Erk1/2 positive feedback to the TCR. Overall, our work provides evidence for alternative functions of three T cell phosphatases long thought to be redundant.