Considerations for the Development and Implementation of Structures for Lossless Ion Manipulations (SLIM) Platforms

Owing to its unique geometry, traveling wave structures for lossless ion manipulations (TW-SLIM) is able to maneuver ions at elevated pressures (2-4 Torr) without incurring significant ion loss. Building upon this unique capability, TW-SLIM has shown promise as a technique which can redefine the limits of ion mobility separations and potentially serve as a platform for gas-phase ion experiments. While the ultimate fate of the technique remains unknown at the time of this work, the greatest obstacle at present is clear: limited access to the technique. Motivated by a desire to expand both access to TW-SLIM and the scope of its capabilities, the work outlined herein outlines numerous approaches that simplify TW-SLIM implementation, optimize TW-SLIM analyses, and showcase the technique’s ability to aid in experiments outside of traditional separations. Regarding implementation, technologies that reduce the cost of TW-SLIM experiments were evaluated, and tools that enable individuals with limited skill sets to develop TW-SLIM platforms were disseminated. Concerning experimentation, observations that pertain to the concurrent analysis of disparate species as well as the transmission of dynamic biomolecules are explored and used to inform strategies to optimize TW-SLIM methodologies. Lastly, utilization of TW-SLIM as a platform for gas-phase ion chemistry showcases the ability of TW-SLIM to address complex chemical phenomena

Применение метода "Detensor" у больных, длительно страдающих обструктивными заболеваниями легких

Detensor elastic therapeutic mats provide mild vertebral traction as patients lie relaxed, without strapping, to unload the kinematic system of the spinal column with optimum lines of traction force.The present study demonstrates Detensor effects on the functional state of respiratory muscles of chronic obstructive pulmonary patients. The characteristics dependent on efforts during treatment (VC, PIF, PEF, FIF1 and MW) reveal a major increase after ten sessions in the experimental group, while staying unchanged in the control group.Detensor treatment as part of all-round rehabilitation of COP patients spectacularly increases respiratory muscular strength and endurance.Simplicity of this treatment makes it applicable not only in hospital but in outpatient clinics and at home.Метод “Детензор” предназначен для щадящего вытяжения позвоночного столба при помощи специального эластичного устройства терапевтического мата "Детензор” . При укладывании пациента (свободно, без привязывания) на “Детензор” в условиях релаксации формируются оптимально направленные силы вытяжения, что приводит к разгрузке кинематической системы позвоночника.Проведенное исследование показывает эффективность воздействия метода “Детензор” на функциональное состояние дыхательных мышц у больных ХОЗЛ. Параметры, зависимые от усилий во время выполнения маневра (VC, PIF, PEF, FIF|, M W ) достоверно возрастают после 10 сеансов в основной группе, без изменений — в контрольной группе. Повышается и уровень M W у больных в основной группе.Таким образом, включение метода в комплексную реабилитацию больных ХОЗЛ улучшает показатели ФВД, отражающие деятельность респираторных мышц (их силу и выносливость).Простота метода позволяет применять его не только при стационарном лечении, но и в амбулаторной практике и на дому

Breed and adaptive response modulate bovine peripheral blood cells’ transcriptome

Background: Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins (APPs) are reactants synthesized against environmental stimuli like stress, infection, inflammation. Methods: To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein (IH) and Italian Simmental (IS) breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals (five APP+ and APP- variants) from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed (DE) genes were analyzed using dynamic impact approach (DIA) and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP+ and APP- gene expression patterns with variations in milk parameters. Results: The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP+ vs. all APP- variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism. Conclusions: Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP+ and APP- variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP+ and APP- gene expression patterns

Impacts of disrupted stress responses on brain and behavior

Stress is a term used in everyday life to describe everything from feelings of anxiety and grief, to shock and fear. However, at their most basic level, these psychological expressions of stress are all driven by similar underlying biological processes acting on neural circuits in the brain. These biological processes are evolutionarily ancient and serve the primary function of improving the odds of survival in dangerous or threatening circumstances. However, in modern society, these biological stress-response systems are frequently and persistently engaged in situations that do not pose a significant real threat to life and limb. This incessant and insidious activation results in a gradual breakdown in normal regulation of physiology in the brain and body and leads to negative outcomes for physical and mental health. One of the primary systems which mediates the effects of stress on physiology is the hypothalamic-pituitary-adrenal (HPA) axis, which exerts its effects on the brain and body through the secretion of the “stress hormones” known as glucocorticoids. Dysregulation of this system is strongly linked to the development of stress-related metabolic and psychiatric diseases, however the biological substrates through which improper HPA axis function causes these problems is unclear. The chapters comprising this dissertation describe how dysfunction of the HPA axis alters the normal patterns of neural adaptation in the brain and show that these changes are related to the way in which an organism responds behaviorally when faced with stress. Together, the findings presented support the idea that appropriate function of the neuroendocrine stress response is crucial for responding and adapting to stress

SLIM Tricks: Tools, Concepts, and Strategies for the Development of Planar Ion Guides

Traveling wave ion mobility experiments using planar electrode structures (e.g., structures for lossless ion manipulation, TW-SLIM) leverage the mature manufacturing capabilities of printed circuit boards (PCBs). With routine levels of mechanical precision below 150 μm, the conceptual flexibility afforded by PCBs for use as planar ion guides is expansive. To date, the design and construction of TW-SLIM platforms require considerable legacy expertise, especially with respect to simulation and circuit layout strategies. To lower the barrier of TW-SLIM implementation, we introduce Python-based interactive tools that assist in graphical layout of the core electrode footprints for planar ion guides with minimal user inputs. These scripts also export the exact component locations and assignments for direct integration into KiCad and SIMION for PCB finalization and ion flight simulations. The design concepts embodied in the set of scripts comprising SLIM Pickins (PCB CAD generation) and pigsim (SIMION workspace generation) build upon the lessons learned in the independent development of the research-grade TW-SLIM platforms in operation at WSU. Due to the inherent flexibility of the PCB manufacturing process and the time devoted to board layouts prior to manufacturing, both scripts serve to enable rapid, iterative design considerations. Because only a few predefined parameters are necessary (i.e., the TW-SLIM monomer width, x position following a TW Turn, and y position following a TW Turn) it is possible to design the exact component layouts and accompanying simulation space in a manner of minutes. There is no known limitation to the board layout capacities of the scripts, and the size of a designed layout is ultimately constrained by the abilities of the final PCB design and simulation tools, KiCad and SIMION, to accommodate the thousands of electrodes comprising the final design (i.e., RAM and software overhead). Toward removing the barriers to exploring new SLIM tracks and the likelihood of layout errors that require considerable revision and engineering time, the SLIM Pickins and pigsim tools (included as Supporting Information) allow the user to quickly design a length of planar ion guide, simulate its abilities to confine and transmit ions, compare hypothetical board outlines to given vacuum chamber dimensions, and generate a near-production ready PCB CAD file. In addition to these tools, this report outlines a series of cost-saving strategies with respect to vacuum feedthroughs and vacuum chamber design for TW ion mobility experiments using planar ion guides

Chronic hypothalamic-pituitary-adrenal axis disruption alters glutamate homeostasis and neural responses to stress in male C57Bl6/N mice

It is now well-established that stress elicits brain- and body-wide changes in physiology and has significant impacts on many aspects of health. The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine system mediating the integrated response to stress. Appropriate engagement and termination of HPA activity enhances survival and optimizes physiological and behavioral responses to stress, while dysfunction of this system is linked to negative health outcomes such as depression, anxiety, and post-traumatic stress disorder. Glutamate signaling plays a large role in the transmission of stress-related information throughout the brain. Furthermore, aberrant glutamate signaling has negative consequences for neural plasticity and synaptic function and is linked to stress-related pathology. However, the connection between HPA dysfunction and glutamate signaling is not fully understood. We tested how HPA axis dysfunction (using low dose chronic corticosterone in the drinking water) affects glutamate homeostasis and neural responses under baseline and acute stress in male C57BL/6N mice. Using laser microdissection and transcriptomic analyses, we show that chronic disruption of the HPA axis alters the expression of genes related to glutamate signaling in the medial prefrontal cortex (mPFC), hippocampus, and amygdala. While neural responses to stress (as measured by FOS) in the hippocampus and amygdala were not affected in our model of HPA dysfunction, we observed an exaggerated response to stress in the mPFC. To further probe this we undertook in vivo biosensor measurements of the dynamics of extracellular glutamate responses to stress in the mPFC in real-time, and found glutamate dynamics in the mPFC were significantly altered by chronic HPA dysfunction. Together, these findings support the hypothesis that chronic HPA axis dysfunction alters glutamatergic signaling in regions known to regulate emotional behavior, providing more evidence linking HPA dysfunction and stress vulnerability