HST Grism Observations of a Gravitationally Lensed Redshift 10 Galaxy

We present deep spectroscopic observations of a Lyman-break galaxy candidate (hereafter MACS1149-JD) at $z\sim9.5$ with the $\textit{Hubble}$ Space Telescope ($\textit{HST}$) WFC3/IR grisms. The grism observations were taken at 4 distinct position angles, totaling 34 orbits with the G141 grism, although only 19 of the orbits are relatively uncontaminated along the trace of MACS1149-JD. We fit a 3-parameter ($z$, F160W mag, and Ly$\alpha$ equivalent width) Lyman-break galaxy template to the three least contaminated grism position angles using an MCMC approach. The grism data alone are best fit with a redshift of $z_{\mathrm{grism}}=9.53^{+0.39}_{-0.60}$ ($68\%$ confidence), in good agreement with our photometric estimate of $z_{\mathrm{phot}}=9.51^{+0.06}_{-0.12}$ ($68\%$ confidence). Our analysis rules out Lyman-alpha emission from MACS1149-JD above a $3\sigma$ equivalent width of 21 \AA{}, consistent with a highly neutral IGM. We explore a scenario where the red $\textit{Spitzer}$/IRAC $[3.6] - [4.5]$ color of the galaxy previously pointed out in the literature is due to strong rest-frame optical emission lines from a very young stellar population rather than a 4000 \AA{} break. We find that while this can provide an explanation for the observed IRAC color, it requires a lower redshift ($z\lesssim9.1$), which is less preferred by the $\textit{HST}$ imaging data. The grism data are consistent with both scenarios, indicating that the red IRAC color can still be explained by a 4000 \AA{} break, characteristic of a relatively evolved stellar population. In this interpretation, the photometry indicate that a $340^{+29}_{-35}$ Myr stellar population is already present in this galaxy only $\sim500~\mathrm{Myr}$ after the Big Bang.Comment: Accepted to ApJ. This is the accepted versio

Detection of Lyman-Alpha Emission From a Triple Imaged z=6.85 Galaxy Behind MACS J2129.4-0741

We report the detection of Ly$\alpha$ emission at $\sim9538$\AA{} in the Keck/DEIMOS and \HST WFC3 G102 grism data from a triply-imaged galaxy at $z=6.846\pm0.001$ behind galaxy cluster MACS J2129.4$-$0741. Combining the emission line wavelength with broadband photometry, line ratio upper limits, and lens modeling, we rule out the scenario that this emission line is \oii at $z=1.57$. After accounting for magnification, we calculate the weighted average of the intrinsic Ly$\alpha$ luminosity to be $\sim1.3\times10^{42}~\mathrm{erg}~\mathrm{s}^{-1}$ and Ly$\alpha$ equivalent width to be $74\pm15$\AA{}. Its intrinsic UV absolute magnitude at 1600\AA{} is $-18.6\pm0.2$ mag and stellar mass $(1.5\pm0.3)\times10^{7}~M_{\odot}$, making it one of the faintest (intrinsic $L_{UV}\sim0.14~L_{UV}^*$) galaxies with Ly$\alpha$ detection at $z\sim7$ to date. Its stellar mass is in the typical range for the galaxies thought to dominate the reionization photon budget at $z\gtrsim7$; the inferred Ly$\alpha$ escape fraction is high ($\gtrsim 10$\%), which could be common for sub-$L^*$ $z\gtrsim7$ galaxies with Ly$\alpha$ emission. This galaxy offers a glimpse of the galaxy population that is thought to drive reionization, and it shows that gravitational lensing is an important avenue to probe the sub-$L^*$ galaxy population.Comment: Accepted by ApJ Letter

Overview of SAND-E: Semi-Autonomous Navigation for Detrital Environments

Rovers are the state of the art for the exploration and detection of past habitability and life on other worlds. One of the most basic functions of a rover is terrain navigation. Information collected by the rover is used autonomously to mitigate terrain hazards such large rocks, while humans qualitatively assess hazardous geologic terrain such as soil type and degree of rock cover. Planetary scientists use the same information to select targets such as drill sites, and for basic scientific analysis such as characterization of rock outcrops. Although the data is complementary, data from terrain analysis for navigation and terrain analysis for scientific investigations are poorly integrated. The lack of integration creates science and operation inefficiencies that limit exploration of habitable environments. As new modes of exploration come online, such as unmanned aerial systems (UAS) (e.g., the Mars Helicopter Scout and Titan Dragonfly), a need exists to integrate terrain data and science analysis to improve operational and scientific outcomes during exploration. We present an overview of a project aimed at evaluating the effectiveness and capability rover and UAS-based semi-automated terrain analysis using the Automated Soil Assessment Systems (ASAS) developed by Mission Control Space Services for navigating, selecting targets for sampling, and characterizing mafic detrital sediments along glacio-fluvial-aeolian sand transport pathways in Iceland. We describe recent advances in automated terrain analysis in sandy environments and scientific uses of terrain assessment from sandy environments. We assess fluvial and aeolian terrains in Iceland and show how terrain analysis data can inform scientific characterization of these environments

Aspiration therapy for the treatment of obesity: 4-year results of a multicenter randomized controlled trial.

BackgroundThe AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity.ObjectivesWe earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes.SettingUnited States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization).MethodsAT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis.ResultsOf the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m2. At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders.ConclusionsThe results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior

Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery.

BACKGROUND: The nematode worm C. elegans is a model organism widely used for studies of genetics and of human disease. The health and fitness of the worms can be quantified in different ways, such as by measuring their bending frequency, speed or lifespan. Manual assays, however, are time consuming and limited in their scope providing a strong motivation for automation. NEW METHOD: We describe the development and application of an advanced machine vision system for characterising the behaviour of C. elegans, the Wide Field-of-View Nematode Tracking Platform (WF-NTP), which enables massively parallel data acquisition and automated multi-parameter behavioural profiling of thousands of worms simultaneously. RESULTS: We screened more than a million worms from several established models of neurodegenerative disorders and characterised the effects of potential therapeutic molecules for Alzheimer's and Parkinson's diseases. By using very large numbers of animals we show that the sensitivity and reproducibility of behavioural assays is very greatly increased. The results reveal the ability of this platform to detect even subtle phenotypes. COMPARISON WITH EXISTING METHODS: The WF-NTP method has substantially greater capacity compared to current automated platforms that typically either focus on characterising single worms at high resolution or tracking the properties of populations of less than 50 animals. CONCLUSIONS: The WF-NTP extends significantly the power of existing automated platforms by combining enhanced optical imaging techniques with an advanced software platform. We anticipate that this approach will further extend the scope and utility of C. elegans as a model organism

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine

12 pags, 3 figs. -- The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acschembio.8b00466.The aggregation of α-synuclein, an intrinsically disordered protein that is highly abundant in neurons, is closely associated with the onset and progression of Parkinson's disease. We have shown previously that the aminosterol squalamine can inhibit the lipid induced initiation process in the aggregation of α-synuclein, and we report here that the related compound trodusquemine is capable of inhibiting not only this process but also the fibril-dependent secondary pathways in the aggregation reaction. We further demonstrate that trodusquemine can effectively suppress the toxicity of α-synuclein oligomers in neuronal cells, and that its administration, even after the initial growth phase, leads to a dramatic reduction in the number of α-synuclein inclusions in a Caenorhabditis elegans model of Parkinson's disease, eliminates the related muscle paralysis, and increases lifespan. On the basis of these findings, we show that trodusquemine is able to inhibit multiple events in the aggregation process of α-synuclein and hence to provide important information about the link between such events and neurodegeneration, as it is initiated and progresses. Particularly in the light of the previously reported ability of trodusquemine to cross the blood-brain barrier and to promote tissue regeneration, the present results suggest that this compound has the potential to be an important therapeutic candidate for Parkinson's disease and related disorders.This work was supported by the Boehringer Ingelheim Fonds (P.F.), the Studienstiftung des Deutschen Volkes (P.F.), Gates Cambridge Scholarships (R.L. and G.T.H) and a St. John’s College Benefactors’ Scholarship (R.L.), the UK Biotechnology and Biochemical Sciences Research Council (M.V. and C.M.D.), a Senior Research Fellowship award from the Alzheimer’s Society, UK, grant number (317, AS-SF-16-003) (F.A.A.), the Wellcome Trust (C.M.D., M.V., and T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.), the Regione Toscana—FAS Salute—Supremal project (R.C., C.C., and F.C.), a Marie Skłodowska-Curie Actions—Individual Fellowship (C.G.), Sidney Sussex College Cambridge (G.M.), the Spanish Government—MINECO (N.C.), and by the Cambridge Centre for Misfolding Diseases (M.P., P.F., R.L., F.A.A., C.G., G.T.H., S.W.C., J.R.K., T.P.J.K., M.V., and C.M.D)

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

The aggregation of α-synuclein, an intrinsically disordered protein that is highly abundant in neurons, is closely associated with the onset and progression of Parkinson's disease. We have shown previously that the aminosterol squalamine can inhibit the lipid induced initiation process in the aggregation of α-synuclein, and we report here that the related compound trodusquemine is capable of inhibiting not only this process but also the fibril-dependent secondary pathways in the aggregation reaction. We further demonstrate that trodusquemine can effectively suppress the toxicity of α-synuclein oligomers in neuronal cells, and that its administration, even after the initial growth phase, leads to a dramatic reduction in the number of α-synuclein inclusions in a Caenorhabditis elegans model of Parkinson's disease, eliminates the related muscle paralysis, and increases lifespan. On the basis of these findings, we show that trodusquemine is able to inhibit multiple events in the aggregation process of α-synuclein and hence to provide important information about the link between such events and neurodegeneration, as it is initiated and progresses. Particularly in the light of the previously reported ability of trodusquemine to cross the blood-brain barrier and to promote tissue regeneration, the present results suggest that this compound has the potential to be an important therapeutic candidate for Parkinson's disease and related disorders

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents