Browsing by Subject "Science & Technology - Other Topics"

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    A Brain to Spine Interface for Transferring Artificial Sensory Information.
    (Scientific reports, 2020-01-21) Yadav, Amol P; Li, Daniel; Nicolelis, Miguel AL
    Lack of sensory feedback is a major obstacle in the rapid absorption of prosthetic devices by the brain. While electrical stimulation of cortical and subcortical structures provides unique means to deliver sensory information to higher brain structures, these approaches require highly invasive surgery and are dependent on accurate targeting of brain structures. Here, we propose a semi-invasive method, Dorsal Column Stimulation (DCS) as a tool for transferring sensory information to the brain. Using this new approach, we show that rats can learn to discriminate artificial sensations generated by DCS and that DCS-induced learning results in corticostriatal plasticity. We also demonstrate a proof of concept brain-to-spine interface (BTSI), whereby tactile and artificial sensory information are decoded from the brain of an "encoder" rat, transformed into DCS pulses, and delivered to the spinal cord of a second "decoder" rat while the latter performs an analog-to-digital conversion during a sensory discrimination task. These results suggest that DCS can be used as an effective sensory channel to transmit prosthetic information to the brain or between brains, and could be developed as a novel platform for delivering tactile and proprioceptive feedback in clinical applications of brain-machine interfaces.
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    A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer.
    (PloS one, 2018-01) Ashton, Jeffrey R; Gottlin, Elizabeth B; Patz, Edward F; West, Jennifer L; Badea, Cristian T
    Computed tomography (CT) is the standard imaging test used for the screening and assessment of suspected lung cancer, but distinguishing malignant from benign nodules by CT is an ongoing challenge. Consequently, a large number of avoidable invasive procedures are performed on patients with benign nodules in order to exclude malignancy. Improving cancer discrimination by non-invasive imaging could reduce the need for invasive diagnostics. In this work we focus on developing a gold nanoparticle contrast agent that targets the epidermal growth factor receptor (EGFR), which is expressed on the cell surface of most lung adenocarcinomas. Three different contrast agents were compared for their tumor targeting effectiveness: non-targeted nanoparticles, nanoparticles conjugated with full-sized anti-EGFR antibodies (cetuximab), and nanoparticles conjugated with a single-domain llama-derived anti-EGFR antibody, which is smaller than the cetuximab, but has a lower binding affinity. Nanoparticle targeting effectiveness was evaluated in vitro by EGFR-binding assays and in cell culture with A431 cells, which highly express EGFR. In vivo CT imaging performance was evaluated in both C57BL/6 mice and in nude mice with A431 subcutaneous tumors. The cetuximab nanoparticles had a significantly shorter blood residence time than either the non-targeted or the single-domain antibody nanoparticles. All of the nanoparticle contrast agents demonstrated tumor accumulation; however, the cetuximab-targeted group had significantly higher tumor gold accumulation than the other two groups, which were statistically indistinguishable from one another. In this study we found that the relative binding affinity of the targeting ligands had more of an effect on tumor accumulation than the circulation half life of the nanoparticles. This study provides useful insight into targeted nanoparticle design and demonstrates that nanoparticle contrast agents can be used to detect tumor receptor overexpression. Combining receptor status data with traditional imaging characteristics has the potential for better differentiation of malignant lung tumors from benign lesions.
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    A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study.
    (PloS one, 2018-01) Evon, Donna M; Stewart, Paul W; Amador, Jipcy; Serper, Marina; Lok, Anna S; Sterling, Richard K; Sarkar, Souvik; Golin, Carol E; Reeve, Bryce B; Nelson, David R; Reau, Nancy; Lim, Joseph K; Reddy, K Rajender; Di Bisceglie, Adrian M; Fried, Michael W
    Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables.PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not.This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication.(Clinicaltrial.gov: NCT02601820).
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    A host gene expression approach for identifying triggers of asthma exacerbations.
    (PloS one, 2019-01) Lydon, Emily C; Bullard, Charles; Aydin, Mert; Better, Olga M; Mazur, Anna; Nicholson, Bradly P; Ko, Emily R; McClain, Micah T; Ginsburg, Geoffrey S; Woods, Chris W; Burke, Thomas W; Henao, Ricardo; Tsalik, Ephraim L
    RATIONALE:Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES:To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. METHODS:Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. RESULTS:Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. CONCLUSIONS:Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.
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    Adaptive Transcriptome Profiling of Subterranean Zokor, Myospalax baileyi, to High- Altitude Stresses in Tibet.
    (Scientific reports, 2018-03-16) Cai, Zhenyuan; Wang, Liuyang; Song, Xiaoying; Tagore, Somnath; Li, Xiangfeng; Wang, Huihua; Chen, Jiarui; Li, Kexin; Frenkel, Zeev; Gao, Dahai; Frenkel-Morgenstern, Milana; Zhang, Tongzuo; Nevo, Eviatar
    Animals living at high altitudes have evolved distinct phenotypic and genotypic adaptations against stressful environments. We studied the adaptive patterns of altitudinal stresses on transcriptome turnover in subterranean plateau zokors (Myospalax baileyi) in the high-altitude Qinghai-Tibetan Plateau. Transcriptomes of zokors from three populations with distinct altitudes and ecologies (Low: 2846 m, Middle: 3282 m, High: 3,714 m) were sequenced and compared. Phylogenetic and principal component analyses classified them into three divergent altitudinal population clusters. Genetic polymorphisms showed that the population at H, approaching the uppermost species boundary, harbors the highest genetic polymorphism. Moreover, 1056 highly up-regulated UniGenes were identified from M to H. Gene ontologies reveal genes like EPAS1 and COX1 were overexpressed under hypoxia conditions. EPAS1, EGLN1, and COX1 were convergent in high-altitude adaptation against stresses in other species. The fixation indices (F ST and G ST )-based outlier analysis identified 191 and 211 genes, highly differentiated among L, M, and H. We observed adaptive transcriptome changes in Myospalax baileyi, across a few hundred meters, near the uppermost species boundary, regardless of their relatively stable underground burrows' microclimate. The highly variant genes identified in Myospalax were involved in hypoxia tolerance, hypercapnia tolerance, ATP-pathway energetics, and temperature changes.
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    Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions.
    (Science advances, 2019-11-27) Blus, Bartlomiej Jan; Koh, Junseock; Krolak, Aleksandra; Seo, Hyuk-Soo; Coutavas, Elias; Blobel, Günter
    Intrinsically disordered regions (IDRs) of proteins are implicated in key macromolecular interactions. However, the molecular forces underlying IDR function within multicomponent assemblies remain elusive. By combining thermodynamic and structural data, we have discovered an allostery-based mechanism regulating the soluble core region of the nuclear pore complex (NPC) composed of nucleoporins Nup53, Nic96, and Nup157. We have identified distinct IDRs in Nup53 that are functionally coupled when binding to partner nucleoporins and karyopherins (Kaps) involved in NPC assembly and nucleocytoplasmic transport. We show that the Nup53·Kap121 complex forms an ensemble of structures that destabilize Nup53 hub interactions. Our study provides a molecular framework for understanding how disordered and folded domains communicate within macromolecular complexes.
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    Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.
    (Scientific reports, 2019-06-21) Jones, Edward G; Mazaheri, Neda; Maroofian, Reza; Zamani, Mina; Seifi, Tahereh; Sedaghat, Alireza; Shariati, Gholamreza; Jamshidi, Yalda; Allen, Hugh D; Wehrens, Xander HT; Galehdari, Hamid; Landstrom, Andrew P
    Junctophilin-2 (JPH2) is a part of the junctional membrane complex that facilitates calcium-handling in the cardiomyocyte. Previously, missense variants in JPH2 have been linked to hypertrophic cardiomyopathy; however, pathogenic "loss of function" (LOF) variants have not been described. Family-based genetic analysis of GME individuals with cardiomyopathic disease identified an Iranian patient with dilated cardiomyopathy (DCM) as a carrier of a novel, homozygous single nucleotide insertion in JPH2 resulting in a stop codon (JPH2-p.E641*). A second Iranian family with consanguineous parents hosting an identical heterozygous variant had 2 children die in childhood from cardiac failure. To characterize ethnicity-dependent genetic variability in JPH2 and to identify homozygous JPH2 variants associated with cardiac disease, we identified variants in JPH2 in a worldwide control cohort (gnomAD) and 2 similar cohorts from the Greater Middle East (GME Variome, Iranome). These were compared against ethnicity-matched clinical whole exome sequencing (WES) referral tests and a case cohort of individuals with hypertrophic cardiomyopathy (HCM) based on comprehensive review of the literature. Worldwide, 1.45% of healthy individuals hosted a rare JPH2 variant with a significantly higher proportion among GME individuals (4.45%); LOF variants were rare overall (0.04%) yet were most prevalent in GME (0.21%). The increased prevalence of LOF variants in GME individuals was corroborated among region-specific, clinical WES cohorts. In conclusion, we report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk of hosting homozygous LOF variants. This conclusion is supported by the identification of a novel JPH2 LOF variant confirmed by segregation analysis resulting in autosomal recessive pediatric DCM due to presumptive JPH2 truncation.
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    Artificial intelligence for art investigation: Meeting the challenge of separating x-ray images of the Ghent Altarpiece.
    (Science advances, 2019-08-30) Sabetsarvestani, Z; Sober, B; Higgitt, C; Daubechies, I; Rodrigues, MRD
    X-ray images of polyptych wings, or other artworks painted on both sides of their support, contain in one image content from both paintings, making them difficult for experts to "read." To improve the utility of these x-ray images in studying these artworks, it is desirable to separate the content into two images, each pertaining to only one side. This is a difficult task for which previous approaches have been only partially successful. Deep neural network algorithms have recently achieved remarkable progress in a wide range of image analysis and other challenging tasks. We, therefore, propose a new self-supervised approach to this x-ray separation, leveraging an available convolutional neural network architecture; results obtained for details from the Adam and Eve panels of the Ghent Altarpiece spectacularly improve on previous attempts.
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    Associations Between Nutrition, Gut Microbiome, and Health in A Novel Nonhuman Primate Model.
    (Scientific reports, 2018-07-24) Clayton, Jonathan B; Al-Ghalith, Gabriel A; Long, Ha Thang; Tuan, Bui Van; Cabana, Francis; Huang, Hu; Vangay, Pajau; Ward, Tonya; Minh, Vo Van; Tam, Nguyen Ai; Dat, Nguyen Tat; Travis, Dominic A; Murtaugh, Michael P; Covert, Herbert; Glander, Kenneth E; Nadler, Tilo; Toddes, Barbara; Sha, John CM; Singer, Randy; Knights, Dan; Johnson, Timothy J
    Red-shanked doucs (Pygathrix nemaeus) are endangered, foregut-fermenting colobine primates which are difficult to maintain in captivity. There are critical gaps in our understanding of their natural lifestyle, including dietary habits such as consumption of leaves, unripe fruit, flowers, seeds, and other plant parts. There is also a lack of understanding of enteric adaptations, including their unique microflora. To address these knowledge gaps, we used the douc as a model to study relationships between gastrointestinal microbial community structure and lifestyle. We analyzed published fecal samples as well as detailed dietary history from doucs with four distinct lifestyles (wild, semi-wild, semi-captive, and captive) and determined gastrointestinal bacterial microbiome composition using 16S rRNA sequencing. A clear gradient of microbiome composition was revealed along an axis of natural lifestyle disruption, including significant associations with diet, biodiversity, and microbial function. We also identified potential microbial biomarkers of douc dysbiosis, including Bacteroides and Prevotella, which may be related to health. Our results suggest a gradient-like shift in captivity causes an attendant shift to severe gut dysbiosis, thereby resulting in gastrointestinal issues.
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    Author Correction: Quantifying Nearshore Sea Turtle Densities: Applications of Unmanned Aerial Systems for Population Assessments.
    (Scientific reports, 2018-04-19) Sykora-Bodie, Seth T; Bezy, Vanessa; Johnston, David W; Newton, Everette; Lohmann, Kenneth J
    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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    Biological feedbacks in global desertification
    (Science, 1990) Shlesinger; WB; REYNOLDS, JF; Cunningham, GL; Huennecke, LF; Jarrell, WM; Virginia, RA; Whitford, WG
    Studies of ecosystem processes on the Jornada Experimental Range in southern New Mexico suggest that longterm grazing of semiarid grasslands leads to an increase in the spatial and temporal heterogeneity of water, nitrogen, and other soil resources. Heterogeneity of soil resources promotes invasion by desert shrubs, which leads to a further localization of soil resources under shrub canopies. In the barren area between shrubs, soil fertility is lost by erosion and gaseous emissions. This positive feedback leads to the desertification of formerly productive land in southern New Mexico and in other regions, such as the Sahel. Future desertification is likely to be exacerbated by global climate warming and to cause significant changes in global biogeochemical cycles.
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    Classification of crystallization outcomes using deep convolutional neural networks.
    (PloS one, 2018-01) Bruno, Andrew E; Charbonneau, Patrick; Newman, Janet; Snell, Edward H; So, David R; Vanhoucke, Vincent; Watkins, Christopher J; Williams, Shawn; Wilson, Julie
    The Machine Recognition of Crystallization Outcomes (MARCO) initiative has assembled roughly half a million annotated images of macromolecular crystallization experiments from various sources and setups. Here, state-of-the-art machine learning algorithms are trained and tested on different parts of this data set. We find that more than 94% of the test images can be correctly labeled, irrespective of their experimental origin. Because crystal recognition is key to high-density screening and the systematic analysis of crystallization experiments, this approach opens the door to both industrial and fundamental research applications.
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    Clinical Features and Outcomes of Patients with Sarcoidosis-associated Pulmonary Hypertension.
    (Scientific reports, 2019-03-11) Parikh, Kishan S; Dahhan, Talal; Nicholl, Leigh; Ruopp, Nicole; Pomann, Gina-Maria; Fortin, Terry; Tapson, Victor F; Rajagopal, Sudarshan
    The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990-2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (-387.0 (IQR: -1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.
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    Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin.
    (PloS one, 2019-01) Mitchell, James; Balem, Fernanda; Tirupula, Kalyan; Man, David; Dhiman, Harpreet Kaur; Yanamala, Naveena; Ollesch, Julian; Planas-Iglesias, Joan; Jennings, Barbara J; Gerwert, Klaus; Iannaccone, Alessandro; Klein-Seetharaman, Judith
    Mutations in the RHO gene encoding for the visual pigment protein, rhodopsin, are among the most common cause of autosomal dominant retinitis pigmentosa (ADRP). Previous studies of ADRP mutations in different domains of rhodopsin have indicated that changes that lead to more instability in rhodopsin structure are responsible for more severe disease in patients. Here, we further test this hypothesis by comparing side-by-side and therefore quantitatively two RHO mutations, N15S and P23H, both located in the N-terminal intradiscal domain. The in vitro biochemical properties of these two rhodopsin proteins, expressed in stably transfected tetracycline-inducible HEK293S cells, their UV-visible absorption, their Fourier transform infrared, circular dichroism and Metarhodopsin II fluorescence spectroscopy properties were characterized. As compared to the severely impaired P23H molecular function, N15S is only slightly defective in structure and stability. We propose that the molecular basis for these structural differences lies in the greater distance of the N15 residue as compared to P23 with respect to the predicted rhodopsin folding core. As described previously for WT rhodopsin, addition of the cytoplasmic allosteric modulator chlorin e6 stabilizes especially the P23H protein, suggesting that chlorin e6 may be generally beneficial in the rescue of those ADRP rhodopsin proteins whose stability is affected by amino acid replacement.
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    Correction: In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia.
    (PloS one, 2017-01) Minagawa, Kentaro; Jamil, Muhammad O; Al-Obaidi, Mustafa; Pereboeva, Larisa; Salzman, Donna; Erba, Harry P; Lamb, Lawrence S; Bhatia, Ravi; Mineishi, Shin; Di Stasi, Antonio
    [This corrects the article DOI: 10.1371/journal.pone.0166891.].
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    Distributed solar photovoltaic array location and extent dataset for remote sensing object identification.
    (Scientific data, 2016-12) Bradbury, Kyle; Saboo, Raghav; L Johnson, Timothy; Malof, Jordan M; Devarajan, Arjun; Zhang, Wuming; M Collins, Leslie; G Newell, Richard
    Earth-observing remote sensing data, including aerial photography and satellite imagery, offer a snapshot of the world from which we can learn about the state of natural resources and the built environment. The components of energy systems that are visible from above can be automatically assessed with these remote sensing data when processed with machine learning methods. Here, we focus on the information gap in distributed solar photovoltaic (PV) arrays, of which there is limited public data on solar PV deployments at small geographic scales. We created a dataset of solar PV arrays to initiate and develop the process of automatically identifying solar PV locations using remote sensing imagery. This dataset contains the geospatial coordinates and border vertices for over 19,000 solar panels across 601 high-resolution images from four cities in California. Dataset applications include training object detection and other machine learning algorithms that use remote sensing imagery, developing specific algorithms for predictive detection of distributed PV systems, estimating installed PV capacity, and analysis of the socioeconomic correlates of PV deployment.
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    Enhancing activation in the right temporoparietal junction using theta-burst stimulation: Disambiguating between two hypotheses of top-down control of behavioral mimicry.
    (PloS one, 2019-01-25) Duffy, Korrina A; Luber, Bruce; Adcock, R Alison; Chartrand, Tanya L
    Whereas previous research has focused on the role of the rTPJ when consciously inhibiting mimicry, we test the role of the rTPJ on mimicry within a social interaction, during which mimicking occurs nonconsciously. We wanted to determine whether higher rTPJ activation always inhibits the tendency to imitate (regardless of the context) or whether it facilitates mimicry during social interactions (when mimicking is an adaptive response). Participants received either active or sham intermittent theta-burst stimulation (iTBS: a type of stimulation that increases cortical activation) to the rTPJ. Next, we measured how much participants mimicked the hair and face touching of another person. Participants in the active stimulation condition engaged in significantly less mimicry than those in the sham stimulation condition. This finding suggests that even in a context in which mimicking is adaptive, rTPJ inhibits mimicry rather than facilitating it, supporting the hypothesis that rTPJ enhances representations of self over other regardless of the goals within a given context.
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    Extreme events reveal an alimentary limit on sustained maximal human energy expenditure.
    (Science advances, 2019-06-05) Thurber, Caitlin; Dugas, Lara R; Ocobock, Cara; Carlson, Bryce; Speakman, John R; Pontzer, Herman
    The limits on maximum sustained energy expenditure are unclear but are of interest because they constrain reproduction, thermoregulation, and physical activity. Here, we show that sustained expenditure in humans, measured as maximum sustained metabolic scope (SusMS), is a function of event duration. We compiled measurements of total energy expenditure (TEE) and basal metabolic rate (BMR) from human endurance events and added new data from adults running ~250 km/week for 20 weeks in a transcontinental race. For events lasting 0.5 to 250+ days, SusMS decreases curvilinearly with event duration, plateauing below 3× BMR. This relationship differs from that of shorter events (e.g., marathons). Incorporating data from overfeeding studies, we find evidence for an alimentary energy supply limit in humans of ~2.5× BMR; greater expenditure requires drawing down the body's energy stores. Transcontinental race data suggest that humans can partially reduce TEE during long events to extend endurance.