Processing irrelevant location information: practice and transfer effects in a Simon task.

How humans produce cognitively driven fine motor movements is a question of fundamental importance in how we interact with the world around us. For example, we are exposed to a constant stream of information and we must select the information that is most relevant by which to guide our actions. In the present study, we employed a well-known behavioral assay called the Simon task to better understand how humans are able to learn to filter out irrelevant information. We trained subjects for four days with a visual stimulus presented, alternately, in central and lateral locations. Subjects responded with one hand moving a joystick in either the left or right direction. They were instructed to ignore the irrelevant location information and respond based on color (e.g. red to the right and green to the left). On the fifth day, an additional testing session was conducted where the task changed and the subjects had to respond by shape (e.g. triangle to the right and rectangle to the left). They were instructed to ignore the color and location, and respond based solely on the task relevant shape. We found that the magnitude of the Simon effect decreases with training, however it returns in the first few trials after a break. Furthermore, task-defined associations between response direction and color did not significantly affect the Simon effect based on shape, and no significant associative learning from the specific stimulus-response features was found for the centrally located stimuli. We discuss how these results are consistent with a model involving route suppression/gating of the irrelevant location information. Much of the learning seems to be driven by subjects learning to suppress irrelevant location information, however, this seems to be an active inhibition process that requires a few trials of experience to engage

Reaching for the stars – JWST/NIRSpec spectroscopy of a lensed star candidate at z = 4.76

We present JWST/NIRSpec observations of a highly magnified star candidate at a photometric redshift of zphot ≃ 4.8, previously detected in JWST/NIRCam imaging of the strong lensing (SL) cluster MACS J0647+7015 (z = 0.591). The spectroscopic observation allows us to precisely measure the redshift of the host arc at zspec = 4.758 ± 0.004, and the star’s spectrum displays clear Lyman- and Balmer-breaks commensurate with this redshift. A fit to the spectrum suggests a B-type super-giant star of surface temperature  K with either a redder F-type companion (⁠ K) or significant dust attenuation (AV ≃ 0.82) along the line of sight. We also investigate the possibility that this object is a magnified young globular cluster rather than a single star. We show that the spectrum is in principle consistent with a star cluster, which could also accommodate the lack of flux variability between the two epochs. However, the lack of a counter image and the strong upper limit on the size of the object from lensing symmetry, r ≲ 0.5 pc, could indicate that this scenario is somewhat less likely – albeit not completely ruled out by the current data. The presented spectrum seen at a time when the Universe was only ∼1.2 Gyr old showcases the ability of JWST to study early stars through extreme lensing

Reaching for the stars -- JWST/NIRSpec spectroscopy of a lensed star candidate at z=4.76z=4.76

We present JWST/NIRSpec observations of a highly magnified star candidate at a photometric redshift of $z_{\mathrm{phot}}\simeq4.8$, previously detected in JWST/NIRCam imaging of the strong lensing (SL) cluster MACS J0647+7015 ($z=0.591$). The spectroscopic observation allows us to precisely measure the redshift of the host arc at $z_{\mathrm{spec}}=4.758\pm0.004$, and the star's spectrum displays clear Lyman- and Balmer-breaks commensurate with this redshift. A fit to the spectrum suggests a B-type super-giant star of surface temperature $T_{\mathrm{eff,B}}\simeq15000$ K with either a redder F-type companion ($T_{\mathrm{eff,F}}\simeq6250$K) or significant dust attenuation ($A_V\simeq0.82$) along the line of sight. We also investigate the possibility that this object is a magnified young globular cluster rather than a single star. We show that the spectrum is in principle consistent with a star cluster, which could also accommodate the lack of flux variability between the two epochs. However, the lack of a counter image and the strong upper limit on the size of the object from lensing symmetry, $r\lesssim0.5$ pc, could indicate that this scenario is somewhat less likely -- albeit not completely ruled out by the current data. The presented spectrum seen at a time when the Universe was only $\sim1.2$ Gyr old showcases the ability of JWST to study early stars through extreme lensing.Comment: Accepted for publication in MNRAS letters. v2 updated to match the published versio

An Evolutionary Framework for Association Testing in Resequencing Studies

Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing), generates a single test per gene (substantially reducing multiple testing concerns), facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4

JWST reveals a possible z∼11z \sim 11 galaxy merger in triply-lensed MACS0647−-JD

MACS0647$-$JD is a triply-lensed $z\sim11$ galaxy originally discovered with the Hubble Space Telescope. Here we report new JWST imaging, which clearly resolves MACS0647$-$JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. Both are very small, with stellar masses $\sim10^8\,M_\odot$ and radii $r<100\,\rm pc$. The brighter larger component "A" is intrinsically very blue ($\beta\sim-2.6$), likely due to very recent star formation and no dust, and is spatially extended with an effective radius $\sim70\,\rm pc$. The smaller component "B" appears redder ($\beta\sim-2$), likely because it is older ($100-200\,\rm Myr$) with mild dust extinction ($A_V\sim0.1\,\rm mag$), and a smaller radius $\sim20\,\rm pc$. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be out of phase. With an estimated stellar mass ratio of roughly 2:1 and physical projected separation $\sim400\,\rm pc$, we may be witnessing a galaxy merger 400 million years after the Big Bang. We also identify a candidate companion galaxy C $\sim3\,{\rm kpc}$ away, likely destined to merge with galaxies A and B. The combined light from galaxies A+B is magnified by factors of $\sim$8, 5, and 2 in three lensed images JD1, 2, and 3 with F356W fluxes $\sim322$, $203$, $86\,\rm nJy$ (AB mag 25.1, 25.6, 26.6). MACS0647$-$JD is significantly brighter than other galaxies recently discovered at similar redshifts with JWST. Without magnification, it would have AB mag 27.3 ($M_{UV}=-20.4$). With a high confidence level, we obtain a photometric redshift of $z=10.6\pm0.3$ based on photometry measured in 6 NIRCam filters spanning $1-5\rm\mu m$, out to $4300\,\r{A}$ rest-frame. JWST NIRSpec observations planned for January 2023 will deliver a spectroscopic redshift and a more detailed study of the physical properties of MACS0647$-$JD.Comment: 27 pages, 14 figures, submitted to Natur

Once bitten, not necessarily shy? Determinants of foreign market re-entry commitment strategies

We investigate foreign market re-entry commitment strategies, namely the changes in the modes of operation (commitment) undertaken by multinational enterprises (MNEs) as they return to foreign markets from which they had previously exited. We combine organisational learning theory with the institutional change literature to examine the antecedents of re-entry commitment strategies. From an analysis of 1,020 re-entry events between 1980 and 2016, we find that operation mode prior to exit is a strong predictor of subsequent re-entry mode. Contrary to the predictions of learning theory, we did not find support for the effect of experience accumulated during the initial market endeavour on the re-entry commitment strategies of MNEs. In turn, exit motives significantly impact on the re-entrants' decision to re-enter via a different mode of operation, by either increasing or decreasing their commitment to the market. We show that re-entrants do not replicate unsuccessful operation mode strategies if they had previously underperformed in the market. When favourable host institutional changes occur during the time-out period re-entrants tend to increase commitment in the host market irrespective of the degree of prior experience accumulated in the market

Maize Inbreds Exhibit High Levels of Copy Number Variation (CNV) and Presence/Absence Variation (PAV) in Genome Content

Following the domestication of maize over the past ∼10,000 years, breeders have exploited the extensive genetic diversity of this species to mold its phenotype to meet human needs. The extent of structural variation, including copy number variation (CNV) and presence/absence variation (PAV), which are thought to contribute to the extraordinary phenotypic diversity and plasticity of this important crop, have not been elucidated. Whole-genome, array-based, comparative genomic hybridization (CGH) revealed a level of structural diversity between the inbred lines B73 and Mo17 that is unprecedented among higher eukaryotes. A detailed analysis of altered segments of DNA conservatively estimates that there are several hundred CNV sequences among the two genotypes, as well as several thousand PAV sequences that are present in B73 but not Mo17. Haplotype-specific PAVs contain hundreds of single-copy, expressed genes that may contribute to heterosis and to the extraordinary phenotypic diversity of this important crop

CTSA Consortium Consensus Scientific Review Committee (SRC) Working Group Report on the SRC Processes

Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate