Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE

Large Eccentricity, Low Mutual Inclination: The Three-dimensional Architecture of a Hierarchical System of Giant Planets

We establish the three-dimensional architecture of the Kepler-419 (previously KOI-1474) system to be eccentric yet with a low mutual inclination. Kepler-419b is a warm Jupiter at semi-major axis ɑ = 0.370^(+0.007)_(-0.006) AU with a large eccentricity (e = 0.85^(+0.08)_(-0.07)) measured via the "photoeccentric effect." It exhibits transit timing variations (TTVs) induced by the non-transiting Kepler-419c, which we uniquely constrain to be a moderately eccentric (e = 0.184 ± 0.002), hierarchically separated (a = 1.68 ± 0.03 AU) giant planet (7.3 ± 0.4 M J_(up)). We combine 16 quarters of Kepler photometry, radial-velocity (RV) measurements from the HIgh Resolution Echelle Spectrometer on Keck, and improved stellar parameters that we derive from spectroscopy and asteroseismology. From the RVs, we measure the mass of the inner planet to be 2.5 ± 0.3 M J_(up) and confirm its photometrically measured eccentricity, refining the value to e = 0.83 ± 0.01. The RV acceleration is consistent with the properties of the outer planet derived from TTVs. We find that despite their sizable eccentricities, the planets are coplanar to within 9^(+8)_(-6) degrees, and therefore the inner planet's large eccentricity and close-in orbit are unlikely to be the result of Kozai migration. Moreover, even over many secular cycles, the inner planet's periapse is most likely never small enough for tidal circularization. Finally, we present and measure a transit time and impact parameter from four simultaneous ground-based light curves from 1 m class telescopes, demonstrating the feasibility of ground-based follow-up of Kepler giant planets exhibiting large TTVs

PTF11eon/SN2011dh: Discovery of a Type IIb Supernova From a Compact Progenitor in the Nearby Galaxy M51

On May 31, 2011 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras, as well as by the Palomar Transient Factory (PTF) survey, and rapidly confirmed it to be a Type II supernova. Our early light curve and spectroscopy indicates that PTF11eon resulted from the explosion of a relatively compact progenitor star as evidenced by the rapid shock-breakout cooling seen in the light curve, the relatively low temperature in early-time spectra and the prompt appearance of low-ionization spectral features. The spectra of PTF11eon are dominated by H lines out to day 10 after explosion, but initial signs of He appear to be present. Assuming that He lines continue to develop in the near future, this SN is likely a member of the cIIb (compact IIb; Chevalier and Soderberg 2010) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~10^13 cm) would be highly inconsistent with constraints from our post-explosion photometric and spectroscopic data

Thinking outside the gundeck: maritime history, the royal navy, and the outbreak of British civil war, 1625-1642

This is the peer reviewed version of the following article: Thinking outside the gundeck: maritime history, the royal navy and the outbreak of British civil war, 1625–1642, Historical Research, vol. 87 no. 236 (2014), pp. 251-274, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/1468-2281.12049/full. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.Maritime history seems to be suffering an identity crisis, rising in popularity but unsure of its place within historical scholarship and divided in approach. Seafarers, as a consequence, have remained marginal within mainstream history. This article argues that only by integrating the study of maritime topics into wider historical debates can maritime history overcome these doubts, taking as a case study the role of seafarers and the navy in British politics during 1625−42. First examining previous interpretations offered by scholars, largely based on a conception of seafarers as politically and socially isolated from developments ashore, the article then reassesses the available evidence for popular political activity within the maritime community. It argues that seafarers were deeply involved in the political and religious divisions that drove Britain into civil war in 1642; and, more broadly, that scholars should recognize the importance of both local and global approaches to maritime history – that they should think outside the gundeck.Arts and Humanities Research Council (AHRC

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Quantifying Earth system interactions for sustainable food production via expert elicitation

Several safe boundaries of critical Earth system processes have already been crossed due to human perturbations; not accounting for their interactions may further narrow the safe operating space for humanity. Using expert knowledge elicitation, we explored interactions among seven variables representing Earth system processes relevant to food production, identifying many interactions little explored in Earth system literature. We found that green water and land system change affect other Earth system processes strongly, while land, freshwater and ocean components of biosphere integrity are the most impacted by other Earth system processes, most notably blue water and biogeochemical flows. We also mapped a complex network of mechanisms mediating these interactions and created a future research prioritization scheme based on interaction strengths and existing knowledge gaps. Our study improves the understanding of Earth system interactions, with sustainability implications including improved Earth system modelling and more explicit biophysical limits for future food production

DIY Methods 2022 Conference Proceedings

As the past years have proven, the methods for conducting and distributing research that we’ve inherited from our disciplinary traditions can be remarkably brittle in the face of rapidly changing social and mobility norms. The ways we work and the ways we meet are questions newly opened for practical and theoretical inquiry; we both need to solve real problems in our daily lives and account for the constitutive effects of these solutions on the character of the knowledge we produce. Methods are not neutral tools, and nor are they fixed ones. As such, the work of inventing, repairing, and hacking methods is a necessary, if often underexplored, part of the wider research process. This conference aims to better interrogate and celebrate such experiments with method. Borrowing from the spirit and circuits of exchange in earlier DIY cultures, it takes the form of a zine ring distributed via postal mail. Participants will craft zines describing methodological experiments and/or how-to guides, which the conference organisers will subsequently mail out to all participants. Feedback on conference proceedings will also proceed through the mail, as well as via an optional Twitter hashtag. The conference itself is thus an experiment with different temporalities and medialities of research exchange. As a practical benefit, this format guarantees that the experience will be free of Zoom fatigue, timezone difficulties, travel expenses, and visa headaches. More generatively, it may also afford slower thinking, richer aesthetic possibilities, more diverse forms of circulation, and perhaps even some amount of delight. The conference format itself is part of the DIY experiment

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival