Term limits alone do not cause legislators to shirk their duties—the actual results are far more complicated

A number of U.S. states currently impose some form of legislative term limits in order to ensure competition and accountability among elected officials. However, some argue that term limits actually make legislators less responsible to their constituents, causing them to abstain from more votes and shirk their duties. Jennifer Hayes Clark and R. Lucas Williams argue that the willingness to shirk depends more on future career goals and the type of vote rather than term limits alone

Laser Guide Star for Large Segmented-Aperture Space Telescopes, Part I: Implications for Terrestrial Exoplanet Detection and Observatory Stability

Precision wavefront control on future segmented-aperture space telescopes presents significant challenges, particularly in the context of high-contrast exoplanet direct imaging. We present a new wavefront control architecture that translates the ground-based artificial guide star concept to space with a laser source aboard a second spacecraft, formation flying within the telescope field-of-view. We describe the motivating problem of mirror segment motion and develop wavefront sensing requirements as a function of guide star magnitude and segment motion power spectrum. Several sample cases with different values for transmitter power, pointing jitter, and wavelength are presented to illustrate the advantages and challenges of having a non-stellar-magnitude noise limited wavefront sensor for space telescopes. These notional designs allow increased control authority, potentially relaxing spacecraft stability requirements by two orders of magnitude, and increasing terrestrial exoplanet discovery space by allowing high-contrast observations of stars of arbitrary brightness.Comment: Submitted to A

Linear Self-Motion Cues Support the Spatial Distribution and Stability of Hippocampal Place Cells

The vestibular system provides a crucial component of place-cell and head-direction cell activity [1-7]. Otolith signals are necessary for head-direction signal stability and associated behavior [8, 9], and the head-direction signal's contribution to parahippocampal spatial representations [10-14] suggests that place cells may also require otolithic information. Here, we demonstrate that self-movement information from the otolith organs is necessary for the development of stable place fields within and across sessions. Place cells in otoconia-deficient tilted mice showed reduced spatial coherence and formed place fields that were located closer to environmental boundaries, relative to those of control mice. These differences reveal an important otolithic contribution to place-cell functioning and provide insight into the cognitive deficits associated with otolith dysfunction

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

The POKEMON Speckle Survey of Nearby M dwarfs. I. New Discoveries

M dwarfs are favorable targets for exoplanet detection with current instrumentation, but stellar companions can induce false positives and inhibit planet characterization. Knowledge of stellar companions is also critical to our understanding of how binary stars form and evolve. We have therefore conducted a survey of stellar companions around nearby M dwarfs, and here we present our new discoveries. Using the DSSI speckle imager at the 4.3-meter Lowell Discovery Telescope, and the similar NESSI instrument at the 3.5-meter WIYN telescope, we carried out a volume-limited survey of M-dwarf multiplicity to 15 parsecs, with a special emphasis on including the later M dwarfs that were overlooked in previous surveys. Additional brighter targets at larger distances were included for a total sample size of 1070 M dwarfs. Observations of these 1070 targets revealed 26 new companions; 22 of these systems were previously thought to be single. If all new discoveries are confirmed, then the number of known multiples in the sample will increase by 7.6%. Using our observed properties, as well as the parallaxes and 2MASS K magnitudes for these objects, we calculate the projected separation, and estimate the mass ratio and component spectral types, for these systems. We report the discovery of a new M-dwarf companion to the white dwarf Wolf 672 A, which hosts a known M-dwarf companion as well, making the system trinary. We also examine the possibility that the new companion to 2MASS J13092185-2330350 is a brown dwarf. Finally, we discuss initial insights from the POKEMON survey.Comment: 23 pages, 6 figures, 5 table

Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC)

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). High IRS-2 expression was significantly associated with decreased overall survival in adenocarcinoma (ADC) patients, whereas low IRS-1 cytoplasmic expression showed a trend toward association with decreased overall survival in squamous cell carcinoma (SCC) patients. Tumors with low IRS-1 and high IRS-2 expression were found to be associated with poor outcomes in ADC and SCC, indicating a potential role for IRS-2 in the aggressive behavior of NSCLC. Our results suggest distinct contributions of IRS-1 and IRS-2 to the biology of ADC and SCC that impact disease progression

Differential effect of lactate on synovial fibroblast and macrophage effector functions

Introduction: The synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation. We investigated how lactate regulates fibroblast and macrophage movement, IL-6 secretion and metabolism via specific lactate transporters. Methods: Synovial tissues were taken from patients undergoing joint replacement surgery and fulfilling the 2010 ACR/EULAR RA criteria. Patients with no evidence of degenerative or inflammatory disease were used as control. Expression of the lactate transporters SLC16A1 and SLC16A3 on fibroblasts and macrophages was assessed by immunofluorescence staining and confocal microscopy. To test the effect of lactate in vitro we used RA synovial fibroblasts and monocyte-derived macrophages. Migration was assessed via scratch test assays or using trans-well inserts. Metabolic pathways were analysed by Seahorse analyser. IL-6 secretion was determined by ELISA. Bioinformatic analysis was performed on publicly available single cell and bulk RNA sequencing datasets. Results: We show that: i) SLC16A1 and SLC16A3 which regulate lactate intake and export respectively, are both expressed in RA synovial tissue and are upregulated upon inflammation. SLC16A3 is more highly expressed by macrophages, while SLC16A1 was expressed by both cell types. ii) This expression is maintained in distinct synovial compartments at mRNA and protein level. iii) Lactate, at the concentration found in RA joints (10 mM), has opposite effects on the effector functions of these two cell types. In fibroblasts, lactate promotes cell migration, IL-6 production and increases glycolysis. In contrast macrophages respond to increases in lactate by reducing glycolysis, migration, and IL-6 secretion. Discussion: In this study, we provide the first evidence of distinct functions of fibroblasts and macrophages in presence of high lactate levels, opening new insights in understanding the pathogenesis of RA and offering novel potential therapeutic targets