Detection of Lyman-alpha Emitting Galaxies at Redshift z=4.55

Studies of the formation and early history of galaxies have been hampered by the difficulties inherent in detecting faint galaxy populations at high redshift. As a consequence, observations at the highest redshifts (3.5 < z < 5) have been restricted to objects that are intrinsically bright. These include quasars, radio galaxies, and some Ly alpha-emitting objects that are very close to (within ~10 kpc) -- and appear to be physically associated with -- quasars. But the extremely energetic processes which make these objects easy to detect also make them unrepresentative of normal (field) galaxies. Here we report the discovery using Keck spectroscopic observations of two Ly alpha-emitting galaxies at redshift z = 4.55, which are sufficiently far from the nearest quasar (~700 kpc) that radiation from the quasar is unlikely to provide the excitation source of the Ly alpha emission. Instead, these galaxies appear to be undergoing their first burst of star formation, at a time when the Universe was less than one billion years old.Comment: 8 pages, 1 landscape table, and 3 PostScript figures. Uses aaspp4.sty, flushrt.sty, aj_pt4.sty, overcite.sty (style macros available from xxx.lanl.gov) Figure 1 is bitmapped to 100 dpi. The original PostScript version of Fig. 1 is available via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints To appear in Natur

Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update

Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the ≥3rd-line setting. The primary analysis (median follow-up: 17 months) of the Phase II ELARA trial (ClinicalTrials.gov identifier: NCT03568461) reported high response rates and excellent safety profile in extensively pretreated patients with r/r FL. Here we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after a median follow-up of 29 months. As of March 29, 2022, 97 patients with r/r FL (grades 1-3A) after ≥2 lines of therapy or who relapsed after autologous stem cell transplant received tisagenlecleucel infusion (0.6-6×108 CAR+ viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment (TME), blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached after 29 months median follow-up (IQR, 22.2-37.7). Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% CI, 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2). Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T-cells and higher baseline levels of naïve CD8+ T-cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA

A life cycle stakeholder management framework for enhanced collaboration between stakeholders with competing interests

This is a postprint version of the Book Chapter. Information regarding the official publication is available from the link below - Copyright @ 2011 SpringerImplementation of a Life Cycle Sustainability Management (LCSM) strategy can involve significant challenges because of competing or conflicting objectives between stakeholders. These differences may, if not identified and managed, hinder successful adoption of sustainability initiatives. This article proposes a conceptual framework for stakeholder management in a LCSM context. The framework identifies the key sustainability stakeholder groups and suggests strategic ambiguity as a management tool to harness dysfunctional conflict into constructive collaboration. The framework is of practical value as it can be used as a guideline by managers who wish to improve collaboration with stakeholders along the supply chain. The article also fills a gap in the academic literature where there is only limited research on sustainability stakeholder management through strategic ambiguity

Coordination of opposing sex-specific and core muscle groups regulates male tail posture during Caenorhabditis elegans male mating behavior

Background To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating. Results Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture. Conclusion Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior

Prior Mating Experience Modulates the Dispersal of Drosophila in Males More Than in Females

Cues from both an animal’s internal physiological state and its local environment may influence its decision to disperse. However, identifying and quantifying the causative factors underlying the initiation of dispersal is difficult in uncontrolled natural settings. In this study, we automatically monitored the movement of fruit flies and examined the influence of food availability, sex, and reproductive status on their dispersal between laboratory environments. In general, flies with mating experience behave as if they are hungrier than virgin flies, leaving at a greater rate when food is unavailable and staying longer when it is available. Males dispersed at a higher rate and were more active than females when food was unavailable, but tended to stay longer in environments containing food than did females. We found no significant relationship between weight and activity, suggesting the behavioral differences between males and females are caused by an intrinsic factor relating to the sex of a fly and not simply its body size. Finally, we observed a significant difference between the dispersal of the natural isolate used throughout this study and the widely-used laboratory strain, Canton-S, and show that the difference cannot be explained by allelic differences in the foraging gene

Knowledge brokering: Exploring the process of transferring knowledge into action

There are many theories about knowledge transfer but there are few clear descriptions of knowledge transfer interventions or the processes they involve. This failure to characterise structure and process in proposed KT interventions is a major barrier to the design and implementation of evaluations of particular KT strategies. This study is designed to provide a detailed description of the processes involved in a knowledge transfer intervention and to develop and refine a useful model of the knowledge transfer process

Effects of Sample Size on Estimates of Population Growth Rates Calculated with Matrix Models

BACKGROUND: Matrix models are widely used to study the dynamics and demography of populations. An important but overlooked issue is how the number of individuals sampled influences estimates of the population growth rate (lambda) calculated with matrix models. Even unbiased estimates of vital rates do not ensure unbiased estimates of lambda-Jensen's Inequality implies that even when the estimates of the vital rates are accurate, small sample sizes lead to biased estimates of lambda due to increased sampling variance. We investigated if sampling variability and the distribution of sampling effort among size classes lead to biases in estimates of lambda. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a long-term field study of plant demography, we simulated the effects of sampling variance by drawing vital rates and calculating lambda for increasingly larger populations drawn from a total population of 3842 plants. We then compared these estimates of lambda with those based on the entire population and calculated the resulting bias. Finally, we conducted a review of the literature to determine the sample sizes typically used when parameterizing matrix models used to study plant demography. CONCLUSIONS/SIGNIFICANCE: We found significant bias at small sample sizes when survival was low (survival = 0.5), and that sampling with a more-realistic inverse J-shaped population structure exacerbated this bias. However our simulations also demonstrate that these biases rapidly become negligible with increasing sample sizes or as survival increases. For many of the sample sizes used in demographic studies, matrix models are probably robust to the biases resulting from sampling variance of vital rates. However, this conclusion may depend on the structure of populations or the distribution of sampling effort in ways that are unexplored. We suggest more intensive sampling of populations when individual survival is low and greater sampling of stages with high elasticities

Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations

Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease

BACKGROUND: One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear. METHODS: Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD. RESULTS: Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I–II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051). CONCLUSION: The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente