3,947 research outputs found
Generic compression and recall of signals with application to dolphin whistles
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1993.Includes bibliographical references (leaves 215-219).by Kevin G. Christian.Ph.D
Blood Pressure in Seizures and Epilepsy
In this narrative review, we summarize the current knowledge of neurally mediated blood pressure (BP) control and discuss how recently described epilepsy- and seizure-related BP alterations may contribute to premature mortality and sudden unexpected death in epilepsy (SUDEP). Although people with epilepsy display disturbed interictal autonomic function with a shift toward predominant sympathetic activity, prevalence of arterial hypertension is similar in people with and without epilepsy. BP is transiently increased in association with most types of epileptic seizures but may also decrease in some, illustrating that seizure activity can cause both a decrease and increase of BP, probably because of stimulation or inhibition of distinct central autonomic function by epileptic activity that propagates into different neuronal networks of the central autonomic nervous system. The principal regulatory neural loop for short-term BP control is termed baroreflex, mainly involving peripheral sensors and brain stem nuclei. The baroreflex sensitivity (BRS, expressed as change of interbeat interval per change in BP) is intact after focal seizures, whereas BRS is markedly impaired in the early postictal period following generalized convulsive seizures (GCS), possibly due to metabolically mediated muscular hyperemia in skeletal muscles, a massive release of catecholamines and compromised brain stem function. Whilst most SUDEP cases are probably caused by a cardiorespiratory failure during the early postictal period following GCS, a profoundly disturbed BRS may allow a life-threatening drop of systemic BP in the aftermath of GCS, as recently reported in a patient as a plausible cause of SUDEP in a few patients
Co-infections of Adenovirus Species in Previously Vaccinated Patients
Adenoviral infections associated with respiratory illness in military trainees involve multiple co-infecting species and serotypes
Roles of distal aspartate and arginine of B-class dye-decolorizing peroxidase in heterolytic hydrogen peroxide cleavage
Dye-decolorizing peroxidases (DyPs) represent the most recently classified hydrogen peroxide dependent heme peroxidase family. Although widely distributed with more than 5000 annotated genes and hailed for their biotechnological potential detailed biochemical characterization of their reaction mechanism remains limited. Here, we present the high resolution crystal structures of wild-type B-class DyP from the pathogenic bacterium Klebsiella pneumoniae (KpDyP) (1.6 \uc5) and the variants D143A (1.3 \uc5), R232A (1.9 \uc5), and D143A/R232A (1.1 \uc5). We demonstrate the impact of elimination of the DyP-typical, distal residues Asp 143 and Arg 232 on (i) the spectral and redox properties, (ii) the kinetics of heterolytic cleavage of hydrogen peroxide, (iii) the formation of the low-spin (LS) cyanide complex as well as on (iv) the stability and reactivity of an oxoiron(IV)porphyrin \u3c0-cation radical (Compound I). Structural and functional studies reveal that the distal aspartate is responsible for deprotonation of H2O2 and for the poor oxidation capacity of Compound I. Elimination of the distal arginine promotes a collapse of the distal heme cavity including blocking of one access channel and a conformational change of the catalytic aspartate. We also provide evidence of formation of an oxoiron(IV)-type Compound II in KpDyP with absorbance maxima at 418, 527 and 553 nm. In summary, a reaction mechanism of the peroxidase cycle of B-class DyPs is proposed. Our observations challenge the idea that peroxidase activity toward conventional aromatic substrates is related to the physiological roles of B-class DyPs
An unmanned aerial vehicle sampling platform for atmospheric water vapor isotopes in polar environments
Above polar ice sheets, atmospheric water vapor exchange occurs across the planetary boundary layer (PBL) and is an important mechanism in a number of processes that affect the surface mass balance of the ice sheets. Yet, this exchange is not well understood and has substantial implications for modeling and remote sensing of the polar hydrologic cycle. Efforts to characterize the exchange face substantial logistical challenges including the remoteness of ice sheet field camps, extreme weather conditions, low humidity and temperature that limit the effectiveness of instruments, and dangers associated with flying manned aircraft at low altitudes. Here, we present an unmanned aerial vehicle (UAV) sampling platform for operation in extreme polar environments that is capable of sampling atmospheric water vapor for subsequent measurement of water isotopes. This system was deployed to the East Greenland Ice-core Project (EastGRIP) camp in northeast Greenland during summer 2019. Four sampling flight missions were completed. With a suite of atmospheric measurements aboard the UAV (temperature, humidity, pressure, GPS) we determine the height of the PBL using online algorithms, allowing for strategic decision-making by the pilot to sample water isotopes above and below the PBL. Water isotope data were measured by a Picarro L2130-i instrument using flasks of atmospheric air collected within the nose cone of the UAV. The internal repeatability for δD and δ18O was 2.8 ‰ and 0.45 ‰, respectively, which we also compared to independent EastGRIP tower-isotope data. Based on these results, we demonstrate the efficacy of this new UAV-isotope platform and present improvements to be utilized in future polar field campaigns. The system is also designed to be readily adaptable to other fields of study, such as measurement of carbon cycle gases or remote sensing of ground conditions.publishedVersio
Emergence of low-symmetry foldamers from single monomers
Self-assembly is a powerful method to obtain large discrete functional molecular architectures. When using a single building block, self-assembly generally yields symmetrical objects in which all the subunits relate similarly to their neighbours. Here we report the discovery of a family of self-constructing cyclic macromolecules with stable folded conformations of low symmetry, which include some with a prime number (13, 17 and 23) of units, despite being formed from a single component. The formation of these objects amounts to the production of polymers with a perfectly uniform length. Design rules for the spontaneous emergence of such macromolecules include endowing monomers with a strong potential for non-covalent interactions that remain frustrated in competing entropically favoured yet conformationally restrained smaller cycles. The process can also be templated by a guest molecule that itself has an asymmetrical structure, which paves the way to molecular imprinting techniques at the level of single polymer chains
University of Michigan Undergraduate Research Journal, Issue 9, Winter 2012
Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97010/1/UMURJ-Issue09_2012.pd
Erysense, a Lab-on-a-Chip-Based Point-of-Care Device to Evaluate Red Blood Cell Flow Properties With Multiple Clinical Applications
In many medical disciplines, red blood cells are discovered to be biomarkers since they “experience” various conditions in basically all organs of the body. Classical examples are diabetes and hypercholesterolemia. However, recently the red blood cell distribution width (RDW), is often referred to, as an unspecific parameter/marker (e.g., for cardiac events or in oncological studies). The measurement of RDW requires venous blood samples to perform the complete blood cell count (CBC). Here, we introduce Erysense, a lab-on-a-chip-based point-of-care device, to evaluate red blood cell flow properties. The capillary chip technology in combination with algorithms based on artificial neural networks allows the detection of very subtle changes in the red blood cell morphology. This flow-based method closely resembles in vivo conditions and blood sample volumes in the sub-microliter range are sufficient. We provide clinical examples for potential applications of Erysense as a diagnostic tool [here: neuroacanthocytosis syndromes (NAS)] and as cellular quality control for red blood cells [here: hemodiafiltration (HDF) and erythrocyte concentrate (EC) storage]. Due to the wide range of the applicable flow velocities (0.1–10 mm/s) different mechanical properties of the red blood cells can be addressed with Erysense providing the opportunity for differential diagnosis/judgments. Due to these versatile properties, we anticipate the value of Erysense for further diagnostic, prognostic, and theragnostic applications including but not limited to diabetes, iron deficiency, COVID-19, rheumatism, various red blood cell disorders and anemia, as well as inflammation-based diseases including sepsis
Discovery of a small molecule probe that post-translationally stabilizes the survival motor neuron protein for the treatment of spinal muscular atrophy.
Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing. Initially, we identified analog 4m that had good in vitro properties but low plasma and brain exposure in a mouse PK experiment due to short plasma stability; this was overcome by reversing the amide bond and changing the heterocycle. Thiazole 27 showed excellent in vitro properties and a promising mouse PK profile, making it suitable for in vivo testing. This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA
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