305 research outputs found

    Characteristics of Contemporary Artificial Intelligence Technologies and Implications for IS Research

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    Artificial Intelligence (AI) is often presented as a new phenomenon that is primarily driven by advances in contemporary machine learning technologies. Despite the steep rise, conceptualizations of contemporary AI technologies tend to be vague in many studies. This is problematic not only for positioning and focusing such research, but also for theorizing on the pervasive AI phenomenon. This paper presents a systematic literature review to understand and synthesize distinctive characteristics of contemporary AI technologies. In the course of our ongoing research, the preliminary findings encompass the changing role of data, feature extraction, adaptivity, transparency, and biases. With our future research, we seek to provide guidance on the conceptualizations of AI in IS research and to facilitate a more nuanced and focused theorization of AI in future IS studies

    The Structure of Nuclear Star Clusters in Nearby Late-type Spiral Galaxies from Hubble Space Telescope Wide Field Camera 3 Imaging

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    We obtained Hubble Space Telescope/Wide Field Camera 3 imaging of a sample of ten of the nearest and brightest nuclear clusters residing in late-type spiral galaxies, in seven bands that span the near-ultraviolet to the near-infrared. Structural properties of the clusters were measured by fitting two-dimensional surface brightness profiles to the images using GALFIT. The clusters exhibit a wide range of structural properties. For six of the ten clusters in our sample, we find changes in the effective radius with wavelength, suggesting radially varying stellar populations. In four of the objects, the effective radius increases with wavelength, indicating the presence of a younger population which is more concentrated than the bulk of the stars in the cluster. However, we find a general decrease in effective radius with wavelength in two of the objects in our sample, which may indicate extended, circumnuclear star formation. We also find a general trend of increasing roundness of the clusters at longer wavelengths, as well as a correlation between the axis ratios of the NCs and their host galaxies. These observations indicate that blue disks aligned with the host galaxy plane are a common feature of nuclear clusters in late-type galaxies, but are difficult to detect in galaxies that are close to face-on. In color-color diagrams spanning the near-UV through the near-IR, most of the clusters lie far from single-burst evolutionary tracks, showing evidence for multi-age populations. Most of the clusters have integrated colors consistent with a mix of an old population (> 1 Gyr) and a young population (~100-300 Myr). The wide wavelength coverage of our data provides a sensitivity to populations with a mix of ages that would not be possible to achieve with imaging in optical bands only.Comment: Corrected a typo in author name and affiliation for MC and corrected a typo in the conclusio

    Discrepancies from registered protocols and spin occurred frequently in randomized psychotherapy trials:A meta-epidemiologic study

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    Objectives: This study aimed to investigate the relationship between trial registration, trial discrepancy from registered protocol, and spin in nonpharmacological trials. Study Design and Setting: Recent psychotherapy trials on depression (2015-2018) were analyzed regarding their registration status and its relationship to discrepancies between registered and published primary outcomes and to spin (discrepancy between the nonsignificant finding in a study and an overly beneficial interpretation of the effect of the treatment). Results: A total of 196 trials were identified, of which 78 (40%) had been registered prospectively and 56 (29%) had been registered retrospectively. In 102 (76%) of 134 registered trials, discrepancies between trial and protocol were present. Of 72 trials with a nonsignif-icant difference between treatments for the primary outcome, 68 trials (94%) showed spin. Discrepancies from protocol were less frequent in prospectively than in retrospectively registered trials (odds ratio5 0.19; 95% confidence interval [CI]: 0.07-0.52), but regarding the amount of spin, there was no difference between prospectively and retrospectively registered trials (rb=0.12; 95% CI: -0.41 to 0.19) or between registered and unregistered trials (rb=0.22, 95% CI -0.49 to 0.08). Conclusion: Protocol discrepancies and spin have a high prevalence in psychotherapy outcome research. The results show no relation between registration and spin, but prospective registration may prevent discrepancies from protocol

    A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes

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    A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality is the extracellular spacer module. However, several studies have elucidated that membrane proximal epitopes are best targeted through CARs comprising long spacers, while short spacer CARs exhibit highest activity on distal epitopes. This finding can be explained by the requirement to have an optimal distance between the effector T cell and target cell. Commonly used long spacer domains are the CH2-CH3 domains of IgG molecules. However, CARs containing these spacers generally show inferior in vivo efficacy in mouse models compared to their observed in vitro activity, which is linked to unspecific Fcγ-Receptor binding and can be abolished by mutating the respective regions. Here, we first assessed a CAR therapy targeting membrane proximal CD20 using such a modified long IgG1 spacer. However, despite these mutations, this construct failed to unfold its observed in vitro cytotoxic potential in an in vivo model, while a shorter but less structured CD8α spacer CAR showed complete tumor clearance. Given the shortage of well-described long spacer domains with a favorable functionality profile, we designed a novel class of CAR spacers with similar attributes to IgG spacers but without unspecific off-target binding, derived from the Sialic acid-binding immunoglobulin-type lectins (Siglecs). Of five constructs tested, a Siglec-4 derived spacer showed highest cytotoxic potential and similar performance to a CD8α spacer in a CD20 specific CAR setting. In a pancreatic ductal adenocarcinoma model, a Siglec-4 spacer CAR targeting a membrane proximal (TSPAN8) epitope was efficiently engaged in vitro, while a membrane distal (CD66c) epitope did not activate the T cell. Transfer of the TSPAN8 specific Siglec-4 spacer CAR to an in vivo setting maintained the excellent tumor killing characteristics being indistinguishable from a TSPAN8 CD8α spacer CAR while outperforming an IgG4 long spacer CAR and, at the same time, showing an advantageous central memory CAR T cell phenotype with lower release of inflammatory cytokines. In summary, we developed a novel spacer that combines cytotoxic potential with an advantageous T cell and cytokine release phenotype, which make this an interesting candidate for future clinical applications

    Measuring the mass of the central black hole in the bulgeless galaxy ngc 4395 from gas dynamical modeling

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    NGC 4395 is a bulgeless spiral galaxy, harboring one of the nearest known type 1 Seyfert nuclei. Although there is no consensus on the mass of its central engine, several estimates suggest it is one of the lightest massive black holes (MBHs) known. We present the first direct dynamical measurement of the mass of this MBH from a combination of two-dimensional gas kinematic data, obtained with the adaptive optics assisted near-infrared integral field spectrograph Gemini/NIFS and high-resolution multiband photometric data from Hubble Space Telescope's Wide Field Camera 3. We use the photometric data to model the shape and stellar mass-to-light ratio of the nuclear star cluster (NSC). From the Gemini/NIFS observations, we derive the kinematics of warm molecular hydrogen gas as traced by emission through the H2 1–0 S(1) transition. These kinematics show a clear rotational signal, with a position angle orthogonal to NGC 4395's radio jet. Our best-fitting tilted ring models of the kinematics of the molecular hydrogen gas contain a black hole with mass M={4}-3+8× {10}5 M⊙ (3σ uncertainties) embedded in an NSC of mass M=2× {10}6 M⊙. Our black hole mass measurement is in excellent agreement with the reverberation mapping mass estimate of Peterson et al. but shows some tension with other mass measurement methods based on accretion signals

    Dispatch from the field II: the mystery of the red and blue Opadometa male (Araneae, Tetragnathidae, Opadometa sarawakensis)

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    Background Males of Opadometa are difficult to associate with conspecific females, and sex-matching errors may persist in the taxonomic literature. Recommended best practices for definitive sex matching in this genus suggest finding a male in the web of a female, or better yet, mating pairs. New information A male Opadometa was observed hanging on a frame line of the web of a female Opadometa sarawakensis, a species for which the male was previously undescribed. This occurred during a tropical ecology field course held at the Danau Girang Field Centre in Sabah, Malaysia. A taxonomic description was completed as a course activity

    Revealing the intermediate-mass black hole at the heart of the dwarf galaxy NGC404 with sub-parsec resolution ALMA observations

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    We estimate the mass of the intermediate-mass black hole at the heart of the dwarf elliptical galaxy NGC 404 using Atacama Large Millimeter/submillimeter Array( ALMA) observations of the molecular interstellar medium at an unprecedented linear resolution of ≈0.5pc, in combination with existing stellar kinematic information. These ALMA observations reveal a central disc/torus of molecular gas clearly rotating around the black hole. This disc is surrounded by a morphologically and kinematically complex flocculent distribution of molecular clouds, that we resolve in detail. Continuum emission is detected from the central parts of NGC404, likely arising from the Rayleigh–Jeans tail of emission from dust around the nucleus, and potentially from dusty massive star-forming clumps at discrete locations in the disc. Several dynamical measurements of the black hole mass in this system have been made in the past, but they do not agree. We show here that both the observed molecular gas and stellar kinematics independently require a ≈5×105M black hole once we include the contribution of the molecular gas to the potential. Our best estimate comes from the high-resolution molecular gas kinematics, suggesting the black hole mass of this system is 5.5+4.1 −3.8×105 M (at the 99% confidence level), in good agreement with our revised stellar kinematic measurement and broadly consistent with extrapolations from the black hole mass–velocity dispersion and black hole mass – bulge mass relations. This highlights the need to accurately determine the mass and distribution of each dynamically important component around intermediate-mass black holes when attempting to estimate their masses

    Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect

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    Anoctamins are a family of Ca2+^{2+}-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy. In silico modeling of the ANO4 structure predicted that all identified variants lead to destabilization of the ANO4 structure. Four variants are localized close to the Ca2+^{2+} binding sites of ANO4, suggesting impaired protein function. Variant mapping to the protein topology suggests a preliminary genotype-phenotype correlation. Moreover, the observation of a heterozygous ANO4 deletion in a healthy individual suggests a dysfunctional protein as disease mechanism rather than haploinsufficiency. To test this hypothesis, we examined mutant ANO4 functional properties in a heterologous expression system by patchclamp recordings, immunocytochemistry, and surface expression of annexin A5 as a measure of phosphatidylserine scramblase activity. All ANO4 variants showed severe loss of ion channel function and DEE/EE associated variants presented mild loss of surface expression due to impaired plasma membrane trafficking. Increased levels of Ca2+^{2+}-independent annexin A5 at the cell surface suggested an increased apoptosis rate in DEE-mutant expressing cells, but no changes in Ca2+^{2+}-dependent scramblase activity were observed. Co-transfection with ANO4 wild-type suggested a dominant-negative effect. In summary, we expand the genetic base for both encephalopathic sporadic and inherited fever-sensitive epilepsies and link germline variants in ANO4 to a hereditary disease
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