ELUCIDATING THE ROLE OF ALPHA1-CONTAINING GABA(A) RECEPTORS IN ETHANOL ACTION

Alcohol (ethanol) has a prominent role in society and is one of the most frequently used and abused drugs. Despite the pervasive use and abuse of ethanol, the molecular mechanisms of ethanol action remain unclear. What is well known is that ethanol intoxication elicits a range of behavioral effects. These effects most likely occur through the direct action of ethanol on targets in the central nervous system. By studying behavioral effects, the role of individual targets can be determined. The function of γ-amino butyric acid type A (GABAA) receptors is altered by ethanol, but due to multiple receptor subunits the exact role of individual GABAA receptor subunits in ethanol action is not known. This dissertation focused on the role of α1-containing GABAA receptors in ethanol action using gene knockin mice with ethanol insensitive α1 GABAA receptors. In the second chapter, knockin mice were molecularly characterized and ethanol-induced behavioral effects were assessed. α1 was found to mediate acute tolerance to the motor ataxic effects of ethanol. In the third chapter, α1 involvement in ethanol induction of neuronal activity was assessed in discrete neuroanatomic regions using the immediate early gene c-fos. Specifically, c-fos immunohistochemistry was characterized after acute ethanol exposure, after chronic ethanol exposure, and finally during the ethanol withdrawal phase. α1 was found to be involved in ethanol-mediated effects in the dentate gyrus. In the fourth chapter, α1 involvement in chronic tolerance to ethanol as well as physical dependence on ethanol was characterized. Results demonstrated that α1-GABAA-Rs play a role in the development of tolerance to chronic ethanol in motor ataxia. Intriguingly, α1 was implicated in dependence as assessed with ethanol withdrawal-related hyperexcitability. Knockin mice were more sensitive to ethanol's withdrawal-related hyperexcitability effects. In summary, this dissertation further supports α1 GABAA-Rs in the mechanism of ethanol action. By chiseling away at the various components of ethanol action we are beginning to elucidate the mechanism of ethanol action. Further elucidation of the mechanism of action of α1 GABAA-Rs in tolerance and dependence could deepen our understanding of the molecular mechanisms behind alcohol abuse and alcoholism. By understanding the molecular mechanisms of ethanol, alcohol abuse may be lessened and alcoholism could potentially be cured

Measurement Uncertainty for Finite Quantum Observables

Measurement uncertainty relations are lower bounds on the errors of any approximate joint measurement of two or more quantum observables. The aim of this paper is to provide methods to compute optimal bounds of this type. The basic method is semidefinite programming, which we apply to arbitrary finite collections of projective observables on a finite dimensional Hilbert space. The quantification of errors is based on an arbitrary cost function, which assigns a penalty to getting result x rather than y, for any pair (x,y) . This induces a notion of optimal transport cost for a pair of probability distributions, and we include an Appendix with a short summary of optimal transport theory as needed in our context. There are then different ways to form an overall figure of merit from the comparison of distributions. We consider three, which are related to different physical testing scenarios. The most thorough test compares the transport distances between the marginals of a joint measurement and the reference observables for every input state. Less demanding is a test just on the states for which a “true value” is known in the sense that the reference observable yields a definite outcome. Finally, we can measure a deviation as a single expectation value by comparing the two observables on the two parts of a maximally-entangled state. All three error quantities have the property that they vanish if and only if the tested observable is equal to the reference. The theory is illustrated with some characteristic examples.BMBF/Q.com-QDFG/WE1240/20DQSIMSIQ

Bell inequalities stronger than the CHSH inequality for 3-level isotropic states

We show that some two-party Bell inequalities with two-valued observables are stronger than the CHSH inequality for 3 \otimes 3 isotropic states in the sense that they are violated by some isotropic states in the 3 \otimes 3 system that do not violate the CHSH inequality. These Bell inequalities are obtained by applying triangular elimination to the list of known facet inequalities of the cut polytope on nine points. This gives a partial solution to an open problem posed by Collins and Gisin. The results of numerical optimization suggest that they are candidates for being stronger than the I_3322 Bell inequality for 3 \otimes 3 isotropic states. On the other hand, we found no Bell inequalities stronger than the CHSH inequality for 2 \otimes 2 isotropic states. In addition, we illustrate an inclusion relation among some Bell inequalities derived by triangular elimination.Comment: 9 pages, 1 figure. v2: organization improved; less references to the cut polytope to make the main results clear; references added; typos corrected; typesetting style change

Interactions between extracorporeal support and the cardiopulmonary system.

This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies

Using MOST to reveal the secrets of the mischievous Wolf-Rayet binary CV Ser

The WR binary CV Serpentis (= WR113, WC8d + O8-9IV) has been a source of mystery since it was shown that its atmospheric eclipses change with time over decades, in addition to its sporadic dust production. The first high-precision time-dependent photometric observations obtained with the MOST space telescope in 2009 show two consecutive eclipses over the 29d orbit, with varying depths. A subsequent MOST run in 2010 showed a seemingly asymmetric eclipse profile. In order to help make sense of these observations, parallel optical spectroscopy was obtained from the Mont Megantic Observatory (2009, 2010) and from the Dominion Astrophysical Observatory (2009). Assuming these depth variations are entirely due to electron scattering in a beta-law wind, an unprecedented 62% increase in mass-loss rate is observed over one orbital period. Alternatively, no change in mass-loss rate would be required if a relatively small fraction of the carbon ions in the wind globally recombined and coaggulated to form carbon dust grains. However, it remains a mystery as to how this could occur. There also seems to be evidence for the presence of corotating interaction regions (CIR) in the WR wind: a CIR-like signature is found in the light curves, implying a potential rotation period for the WR star of 1.6 d. Finally, a new circular orbit is derived, along with constraints for the wind collision.Comment: 11 pages, 11 figures, 5 table

Peritoneal dialysis in children after cardiopulmonary bypass

AbstractObjective: We reviewed 5 years' experience with peritoneal dialysis in children with acute renal failure after cardiac operations. We hypothesized that peritoneal dialysis is safe and effective in children with low-output cardiac failure after cardiac operations. Results: Mortality in these patients with renal failure (n = 32) was 46.9%. Fluid removed by peritoneal dialysis was 48 ± 28 ml/kg per 24 hours. Most complications of peritoneal dialysis were minor, hyperglycemia being the most frequent (53.1%). Peritoneal infection was suspected in 25%. Bowel perforation developed in two patients. None of the complications required early termination of dialysis. Hemodynamics and pulmonary function improved continuously during the study period. Conclusion: The early institution of peritoneal dialysis in acute renal failure and low cardiac output after cardiac operations not only removes fluid, thus easing fluid restriction, but may also improve cardiopulmonary function(J Thorac Cardiovasc Surg 1997;113:64-70

A stable quasi-periodic 4.18 d oscillation and mysterious occultations in the 2011 MOST light curve of TWHya

We present an analysis of the 2011 photometric observations of TW Hya by the MOST satellite; this is the fourth continuous series of this type. The large-scale light variations are dominated by a strong, quasi-periodic 4.18 d oscillation with superimposed, apparently chaotic flaring activity; the former is most likely produced by stellar rotation with one large hot spot created by a stable accretion funnel in the stable regime of accretion while the latter may be produced by small hot spots, created at moderate latitudes by unstable accretion tongues. A new, previously unnoticed feature is a series of semi-periodic, well defined brightness dips of unknown nature of which 19 were observed during 43 days of our nearly-continuous observations. Re-analysis of the 2009 MOST light curve revealed the presence of 3 similar dips. On the basis of recent theoretical results, we tentatively conclude that the dips may represent occultations of the small hot spots created by unstable accretion tongues by hypothetical optically thick clumps.Comment: Printed in MNRA

Accelerated return to sport after osteochondral autograft plug transfer

Background:Previous studies have reported varying return-to-sport protocols after knee cartilage restoration procedures.Purpose:To (1) evaluate the time for return to sport in athletes with an isolated chondral injury who underwent an accelerated return-to-sport protocol after osteochondral autograft plug transfer (OAT) and (2) evaluate clinical outcomes to assess for any consequences from the accelerated return to sport.Study Design:Case series; Level of evidence, 4.Methods:An institutional cohort of 152 OAT procedures was reviewed, of which 20 competitive athletes met inclusion and exclusion criteria. All patients underwent a physician-directed accelerated rehabilitation program after their procedure. Return to sport was determined for all athletes. Clinical outcomes were assessed using International Knee Documentation Committee (IKDC) and Tegner scores as well as assessment of level of participation on return to sport.Results:Return-to-sport data were available for all 20 athletes; 13 of 20 athletes (65%) were available for clinical evaluation at a mean 4.4-year follow-up. The mean time for return to sport for all 20 athletes was 82.9 ± 25 days (range, 38-134 days). All athletes were able to return to sport at their previous level and reported that they were satisfied or very satisfied with their surgical outcome and ability to return to sport. The mean postoperative IKDC score was 84.5 ± 9.5. The mean Tegner score prior to injury was 8.9 ± 1.7; it was 7.7 ± 1.9 at final follow-up.Conclusion:Competitive athletes with traumatic chondral defects treated with OAT managed using this protocol had reduced time to preinjury activity levels compared with what is currently reported, with excellent clinical outcomes and no serious long-term sequelae.</jats:sec