Development of nanofluidic/microfluidic interfaces as analyte concentrators for proteomic samples

We have developed a nanofluidic microfluidic analyte concentrator for application to proteomic samples. This dissertation includes a study investigating the current rectification behavior of the device including a temporal characterization of the ON state to OFF state transition and the OFF state to ON state transition as a function of device design. An analyte concentrator compatible with proteomic samples is presented and the current rectifying phenomenon is utilized to ensure adequate analyte delivery for the enrichment process. Finally, characterization of a coating technique to alter the surface charge of the nanofluidic element from anionic to cationic is presented

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© 2016 American Pharmacists Association®.Benzoic acid is a model compound for drug substances in pharmaceutical research. Process design requires information about thermodynamic phase behavior of benzoic acid and its mixtures with water and organic solvents. This work addresses phase equilibria that determine stability and solubility. In this work, Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to model the phase behavior of aqueous and organic solutions containing benzoic acid and chlorobenzoic acids. Absolute vapor pressures of benzoic acid and 2-, 3-, and 4-chlorobenzoic acid from literature and from our own measurements were used to determine pure-component PC-SAFT parameters. Two binary interaction parameters between water and/or benzoic acid were used to model vapor-liquid and liquid-liquid equilibria of water and/or benzoic acid between 280 and 413 K. The PC-SAFT parameters and 1 binary interaction parameter were used to model aqueous solubility of the chlorobenzoic acids. Additionally, solubility of benzoic acid in organic solvents was predicted without using binary parameters. All results showed that pure-component parameters for benzoic acid and for the chlorobenzoic acids allowed for satisfying modeling phase equilibria. The modeling approach established in this work is a further step to screen solubility and to predict the whole phase region of mixtures containing pharmaceuticals

Benzoic Acid and Chlorobenzoic Acids: Thermodynamic Study of the Pure Compounds and Binary Mixtures with Water

© 2016 American Pharmacists Association®.Benzoic acid is a model compound for drug substances in pharmaceutical research. Process design requires information about thermodynamic phase behavior of benzoic acid and its mixtures with water and organic solvents. This work addresses phase equilibria that determine stability and solubility. In this work, Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to model the phase behavior of aqueous and organic solutions containing benzoic acid and chlorobenzoic acids. Absolute vapor pressures of benzoic acid and 2-, 3-, and 4-chlorobenzoic acid from literature and from our own measurements were used to determine pure-component PC-SAFT parameters. Two binary interaction parameters between water and/or benzoic acid were used to model vapor-liquid and liquid-liquid equilibria of water and/or benzoic acid between 280 and 413 K. The PC-SAFT parameters and 1 binary interaction parameter were used to model aqueous solubility of the chlorobenzoic acids. Additionally, solubility of benzoic acid in organic solvents was predicted without using binary parameters. All results showed that pure-component parameters for benzoic acid and for the chlorobenzoic acids allowed for satisfying modeling phase equilibria. The modeling approach established in this work is a further step to screen solubility and to predict the whole phase region of mixtures containing pharmaceuticals

Cybersickness Following Repeated Exposure to DOME and HMD Virtual Environments

Virtual environments (VE) offer unique training opportunities, including training astronauts to preadapt them to the novel sensory conditions of microgravity. However, one unresolved issue with VE use is the occurrence of cybersickness during and following exposure to VE systems. Most individuals adapt and become less ill with repeated interaction with VEs. The goal of this investigation was to compare motion sickness symptoms (MSS) produced by dome and head-mounted (HMD) displays and to examine the effects of repeated exposures on MSS. Sixty-one subjects participated in the study. Three experimental sessions were performed each separated by one day. The subjects performed a navigation and pick and place task in either a dome or HMD VE. MSS were measured using a Simulator Sickness Questionnaire before, immediately after, and at 1, 2, 4 and 6 hours following exposure to the VEs. MSS data were normalized by calculating the natural log of each score and an analysis of variance was performed. We observed significant main effects for day and time and a significant day by time interaction for total sickness and for each of the subscales, nausea, oculomotor and disorientation. However, there was no significant main effect for device. In conclusion, subjects reported a large increase in MSS immediately following exposure to both the HMD and dome, followed by a rapid recovery across time. Sickness severity also decreased over days, which suggests that subjects become dual-adapted over time making VE training a viable pre-flight countermeasure for space motion sickness

Understanding the Effects of Spaceflight on Head-trunk Coordination during Walking and Obstacle Avoidance

Prolonged exposure to spaceflight conditions results in a battery of physiological changes, some of which contribute to sensorimotor and neurovestibular deficits. Upon return to Earth, functional performance changes are tested using the Functional Task Test (FTT), which includes an obstacle course to observe postflight balance and postural stability, specifically during turning. The goal of this study was to quantify changes in movement strategies during turning events by observing the latency between headandtrunk coordinated movements. It was hypothesized that subjects experiencing neurovestibular adaptations would exhibit headtotrunk locking ('en bloc' movement) during turning, exhibited by a decrease in latency between head and trunk movement. FTT data samples were collected from ISS missions. Samples were analyzed three times preexposure, immediately postexposure (1 day post) and 2to3 times during recovery from the microgravity environment. Two 3D inertial measurements units (XSens MTx) were attached to subjects, one on the head and one on the upper back. This study focused primarily on the yaw movements about the subject's center of rotation. Time differences (latency) between head and trunk movement were calculated at two points on the obstacle course: the first turn to enter the obstacle course (approximately 90 turn) and averaged across a slalom obstacle portion, consisting of three turns (approximately three 90 turns). Preliminary analysis of the data shows a trend toward decreasing headtotrunk movement latency during postflight ambulation in slalom turning after reintroduction to Earth gravity in ISS astronauts. It is clear that changes in movement strategies are adopted during exposure to the microgravity environment and upon reintroduction to a gravity environment. Most ISS subjects exhibit symptoms of neurovestibular changes ('en bloc head and trunk movement) which may impact their ability to perform postflight functional tasks

The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma—two sides of the same coin?

Tissue-resident memory T cells (TRM cells) have become an interesting subject of study for antitumor immunity in melanoma and other solid tumors. In the initial phases of antitumor immunity, they maintain an immune equilibrium and protect against challenges with tumor cells and the formation of primary melanomas. In metastatic settings, they are a prime target cell population for immune checkpoint inhibition (ICI) because they highly express inhibitory checkpoint molecules such as PD-1, CTLA-4, or LAG-3. Once melanoma patients are treated with ICI, TRM cells residing in the tumor are reactivated and expand. Tumor killing is achieved by secreting effector molecules such as IFN-γ. However, off-target effects are also observed. Immune-related adverse events, such as those affecting barrier organs like the skin, can be mediated by ICI-induced TRM cells. Therefore, a detailed understanding of this memory T-cell type is obligatory to better guide and improve immunotherapy regimens

Model for initiation of quality factor degradation at high accelerating fields in superconducting radio-frequency cavities

A model for the onset of the reduction in SRF cavity quality factor, the so-called Q-drop, at high accelerating electric fields is presented. Breakdown of the surface barrier against magnetic flux penetration at the cavity equator is considered to be the critical event that determines the onset of Q-drop. The worst case of triangular grooves with low field of first flux penetration Hp, as analyzed previously by Buzdin and Daumens, [1998 Physica C 294: 257], was adapted. This approach incorporates both the geometry of the groove and local contamination via the Ginzburg-Landau parameter kappa, so the proposed model allows new comparisons of one effect in relation to the other. The model predicts equivalent reduction of Hp when either roughness or contamination were varied alone, so smooth but dirty surfaces limit cavity performance about as much as rough but clean surfaces do. When in combination, contamination exacerbates the negative effects of roughness and vice-versa. To test the model with actual data, coupons were prepared by buffered chemical polishing and electropolishing, and stylus profilometry was used to obtain distributions of angles. From these data, curves for surface resistance generated by simple flux flow as a function of magnetic field were generated by integrating over the distribution of angles for reasonable values of kappa. This showed that combined effects of roughness and contamination indeed reduce the Q-drop onset field by ~30%, and that that contamination contributes to Q-drop as much as roughness. The latter point may be overlooked by SRF cavity research, since access to the cavity interior by spectroscopy tools is very difficult, whereas optical images have become commonplace. The model was extended to fit cavity test data, which indicated that reduction of the superconducting gap by contaminants may also play a role in Q-drop.Comment: 15 pages with 7 figure

Jump-Down Performance Alterations after Space Flight

INTRODUCTION: Successful jump performance requires functional coordination of visual, vestibular, and somatosensory systems, which are affected by prolonged exposure to microgravity. Astronauts returning from space flight exhibit impaired ability to coordinate effective landing strategies when jumping from a platform to the ground. This study compares jump strategies used by astronauts before and after flight, changes to those strategies within a test session, and recoveries in jump-down performance parameters across several postflight test sessions. These data were obtained as part of an ongoing interdisciplinary study (Functional Task Test, FTT) designed to evaluate both astronaut postflight functional performance and related physiological changes. METHODS: Seven astronauts from short-duration (Shuttle) and three from long-duration (International Space Station) flights performed 3 two-footed jumps from a platform 30 cm high onto a force plate that measured the ground reaction forces and center-of-pressure displacement from the landings. Neuromuscular activation data were collected from the medial gastrocnemius and anterior tibialis of both legs using surface electromyography electrodes. Two load cells in the platform measured the load exerted by each foot during the takeoff phase of the jump. Data were collected in 2 preflight sessions, on landing day (Shuttle only), and 1, 6, and 30 days after flight. RESULTS: Postural settling time was significantly increased on the first postflight test session and many of the astronauts tested were unable to maintain balance on their first jump landing but recovered by the third jump, showing a learning progression in which performance improvements could be attributed to adjustments in takeoff or landing strategy. Jump strategy changes were evident in reduced air time (time between takeoff and landing) and also in increased asymmetry in foot latencies on takeoff. CONCLUSIONS: The test results revealed significant decrements in astronauts abilities to maintain balance and achieve a postural stability upon landing from a jump early after flight. However, the jump landing adaptation process often begins after the first jump with full recovery of most performance parameters within days after space flight. As expected, performance of ISS astronauts on the first day after flight was similar to that of Shuttle crewmembers on landing day

Impact of Virtual Environments on Sensorimotor Coordination and User Safety

One critical unresolved issue related to the safe use of virtual environments (VEs) is maladaptive sensorimotor coordination following exposure to VEs. Moving visual displays used in VEs, especially in the absence of concordant vestibular signals leads to adaptive responses during VE exposure, but maladaptive responses following return to the normal environment. In the current set of investigations, we examined the effect of HMD and dome VE displays on eye-head-hand coordination, gaze holding and postural equilibrium. Subjects (61) performed a navigation and a pick and place task. Further, we compared 30 min and 60 min exposures across 3 days (each separated by 1 day). A subset of these results will be presented. In general, we found significant decrements in all three measures following exposure to the VEs. In addition, we found that these disturbances generally recovered within 1-2 hrs and decreased across days. These findings suggest the need for post-VE monitoring of sensorimotor coordination and for developing a set of recommendations for users concerning activities that are safe to engage in following use of a VE