4,406 research outputs found

    A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice.

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    A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing

    Mammalian body size evolution was shaped by habitat transitions as an indirect effect of climate change

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    Aim: Body size evolution has long been hypothesized to have been driven by factors linked to climate change, but the specific mechanisms are difficult to disentangle due to the wide range of functional traits that covary with body size. In this study, we investigated the impact of regional habitat changes as a potential indirect effect of climate change on body size evolution. Location: Europe and North America. Time period: The Neogene (similar to 23-2 million years ago). Major taxa: Five orders of terrestrial mammals: Artiodactyla, Carnivora, Perissodactyla, Proboscidea and Primates. Methods: We compared the two continental faunas, which have exceptional fossil records of terrestrial mammals and underwent different processes of habitat transition during the Neogene. Using Bayesian multilevel regression models, we assessed the variation in the temporal dynamics of body size diversity among ecographic groups, defined by their continent of occurrence and dietary preference. Results: Model comparisons unanimously supported a combined effect of diet and continent on all metrics of body size frequency distributions, rejecting the shared energetic advantage of larger bodies in colder climates as a dominant mechanism of body size evolution. Rather, the diet-specific dynamics on each continent pinpointed an indirect effect of climate change - change in habitat availability, and thus the resource landscape as a key driver of mammalian evolution. Main conclusions: Our study highlights dietary preference as a mechanistic link between mammalian evolution and habitat transition mediating an indirect climate-change effect and demonstrates the complexity of climatic influence on biodiversity. Our findings suggest that the intensified habitat modification today likely poses a bigger threat than climate change in itself to living mammals, and perhaps all endotherms.Peer reviewe

    High intensity exercise as a dishabituating stimulus restores counterregulatory responses in recurrently hypoglycemic rodents

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    Hypoglycemia is a major adverse effect of insulin therapy for people with type 1 diabetes (T1D). Profound defects in the normal counterregulatory response to hypoglycemia explain the frequency of hypoglycemia occurrence in T1D. Defective counterregulation results to a large extent from prior exposure to hypoglycemia per se, leading to a condition called impaired awareness of hypoglycemia (IAH), the cause of which is unknown. In the current study, we investigate the hypothesis that IAH develops through a special type of adaptive memory referred to as habituation. To test this hypothesis, we used a novel intense stimulus (high-intensity exercise) to demonstrate two classic features of a habituated response, namely dishabituation and response recovery. We demonstrate that after recurrent hypoglycemia the introduction of a novel dishabituating stimulus (a single burst of high-intensity exercise) in male Sprague-Dawley rats restores the defective hypoglycemia counterregulatory response. In addition, the rats showed an enhanced response to the novel stimulus (response recovery). We make the further observation using proteomic analysis of hypothalamic extracts that high-intensity exercise in recurrently hypoglycemic rats increases levels of a number of proteins linked with brain-derived neurotrophic factor signaling. These findings may lead to novel therapeutic approaches for individuals with T1D and IAH.</jats:p

    HIV infection is an independent risk factor for decreased 6-minute walk test distance.

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    BackgroundAmbulatory function predicts morbidity and mortality and may be influenced by cardiopulmonary dysfunction. Persons living with HIV (PLWH) suffer from a high prevalence of cardiac and pulmonary comorbidities that may contribute to higher risk of ambulatory dysfunction as measured by 6-minute walk test distance (6-MWD). We investigated the effect of HIV on 6-MWD.MethodsPLWH and HIV-uninfected individuals were enrolled from 2 clinical centers and completed a 6-MWD, spirometry, diffusing capacity for carbon monoxide (DLCO) and St. George's Respiratory Questionnaire (SGRQ). Results of 6-MWD were compared between PLWH and uninfected individuals after adjusting for confounders. Multivariable linear regression analysis was used to determine predictors of 6-MWD.ResultsMean 6-MWD in PLWH was 431 meters versus 462 in 130 HIV-uninfected individuals (p = 0.0001). Older age, lower forced expiratory volume (FEV1)% or lower forced vital capacity (FVC)%, and smoking were significant predictors of decreased 6-MWD in PLWH, but not HIV-uninfected individuals. Lower DLCO% and higher SGRQ were associated with lower 6-MWD in both groups. In a combined model, HIV status remained an independent predictor of decreased 6-MWD (Mean difference = -19.9 meters, p = 0.005).ConclusionsHIV infection was associated with decreased ambulatory function. Airflow limitation and impaired diffusion capacity can partially explain this effect. Subjective assessments of respiratory symptoms may identify individuals at risk for impaired physical function who may benefit from early intervention

    AEGIS: Enhancement of Dust-enshrouded Star Formation in Close Galaxy Pairs and Merging Galaxies up to z ~ 1

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    Using data from the DEEP2 Galaxy Redshift Survey and HST/ACS imaging in the Extended Groth Strip, we select nearly 100 interacting galaxy systems including kinematic close pairs and morphologically identified merging galaxies. Spitzer MIPS 24 micron fluxes of these systems reflect the current dusty star formation activity, and at a fixed stellar mass (M_{*}) the median infrared luminosity (L_{IR}) among merging galaxies and close pairs of blue galaxies is twice (1.9 +/- 0.4) that of control pairs drawn from isolated blue galaxies. Enhancement declines with galaxy separation, being strongest in close pairs and mergers and weaker in wide pairs compared to the control sample. At z ~ 0.9, 7.1% +/- 4.3% of massive interacting galaxies (M_{*} > 2*10^{10} M_{solar}) are found to be ULIRGs, compared to 2.6% +/- 0.7% in the control sample. The large spread of IR luminosity to stellar mass ratio among interacting galaxies suggests that this enhancement may depend on the merger stage as well as other as yet unidentified factors (e.g., galaxy structure, mass ratio, orbital characteristics, presence of AGN or bar). The contribution of interacting systems to the total IR luminosity density is moderate (<= 36 %).Comment: 12 pages, 2 figures, 1 table, minor changes to match the proof version, accepted for publication in the ApJL AEGIS Special Issu

    Prospective serum metabolomic profiling of lethal prostate cancer

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/1/ijc32218.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/2/ijc32218_am.pd
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