Perturbed Field Ionization for Improved State Selectivity

Selective field ionization (SFI) is used to determine the state or distribution of states to which a Rydberg atom is excited. By evolving a small perturbation to the ramped electric field using a genetic algorithm, the shape of the time-resolved ionization signal can be controlled. This allows for the separation of signals from pairs of states that would be indistinguishable with unperturbed SFI. Measurements and calculations are presented that demonstrate this technique and shed light on how the perturbation directs the pathway of the electron to ionization. Pseudocode for the genetic algorithm is provided. Using the improved resolution afforded by this technique, quantitative measurements of the 36p3/2 + 36p3/2 --\u3e 36s1/2 + 37s1/2 dipole–dipole interaction are made

Extremely obscured galaxy nuclei — hidden AGNs and extreme starbursts

Galaxie

Internal medicine residency training for unhealthy alcohol and other drug use: recommendations for curriculum design

<p>Abstract</p> <p>Background</p> <p>Unhealthy substance use is the spectrum from use that risks harm, to use associated with problems, to the diagnosable conditions of substance abuse and dependence, often referred to as substance abuse disorders. Despite the prevalence and impact of unhealthy substance use, medical education in this area remains lacking, not providing physicians with the necessary expertise to effectively address one of the most common and costly health conditions. Medical educators have begun to address the need for physician training in unhealthy substance use, and formal curricula have been developed and evaluated, though broad integration into busy residency curricula remains a challenge.</p> <p>Discussion</p> <p>We review the development of unhealthy substance use related competencies, and describe a curriculum in unhealthy substance use that integrates these competencies into internal medicine resident physician training. We outline strategies to facilitate adoption of such curricula by the residency programs. This paper provides an outline for the actual implementation of the curriculum within the structure of a training program, with examples using common teaching venues. We describe and link the content to the core competencies mandated by the Accreditation Council for Graduate Medical Education, the formal accrediting body for residency training programs in the United States. Specific topics are recommended, with suggestions on how to integrate such teaching into existing internal medicine residency training program curricula.</p> <p>Summary</p> <p>Given the burden of disease and effective interventions available that can be delivered by internal medicine physicians, teaching about unhealthy substance use must be incorporated into internal medicine residency training, and can be done within existing teaching venues.</p

Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels

The ubiquitous Ca2+\ua0release-activated Ca2+\ua0(CRAC) channel is crucial to many physiological functions. Both gain and loss of CRAC function is linked to disease. While ORAI1 is a crucial subunit of CRAC channels, recent evidence suggests that ORAI2 and ORAI3 heteromerize with ORAI1 to form native CRAC channels. Furthermore, ORAI2 and ORAI3 can form CRAC channels independently of ORAI1, suggesting diverse native CRAC stoichiometries. Yet, most available CRAC modifiers are presumed to target ORAI1 with little knowledge of their effects on ORAI2/3 or heteromers of ORAIs. Here, we used ORAI1/2/3 triple-null cells to express individual ORAI1, ORAI2, ORAI3 or ORAI1/2/3 concatemers. We reveal that GSK-7975A and BTP2 essentially abrogate ORAI1 and ORAI2 activity while causing only a partial inhibition of ORAI3. Interestingly, Synta66 abrogated ORAI1 channel function, while potentiating ORAI2 with no effect on ORAI3. CRAC channel activities mediated by concatenated ORAI1-1, ORAI1-2 and ORAI1-3 dimers were inhibited by Synta66, while ORAI2-3 dimers were unaffected. The CRAC enhancer IA65 significantly potentiated ORAI1 and ORAI1-1 activity with marginal effects on other ORAIs. Further, we characterized the profiles of individual ORAI isoforms in the presence of Gd3+\ua0(5μM), 2-APB (5 μM and 50 μM), as well as changes in intracellular and extracellular pH. Our data reveal unique pharmacological features of ORAI isoforms expressed in an ORAI-null background and provide new insights into ORAI isoform selectivity of widely used CRAC pharmacological compounds