Purpose - The purpose of this paper is first, to summarize the findings from the book The New Supply Chain Agenda (Slone, Dittmann, and Mentzer 2010). Second, it reviews associated academic research, ...identifies critical knowledge gaps, and suggests areas for future academic research that will aid scholars and managers in improving supply chain management (SCM) performance.Design methodology approach - The paper summarizes and extends The New Supply Chain Agenda and juxtaposes the major elements of that book with a content review of existing literature in logistics and SCM to align gaps in knowledge with a call for future research.Findings - The findings deepen understanding of the complexities and interrelationships prevalent among the five pillars and help identify new ways to improve the performance impact of SCM initiatives.Research limitations implications - Major areas for future research within the broad topics of talent management, technology, internal integration, external collaboration, and change management are identified. Academic research related to each area or pillar is summarized, gaps are identified, and future research directions are suggested to provide avenues in which theoretical grounding and scientific rigor may be applied to each pillar of The New Supply Chain Agenda.Practical implications - Many of the proposed solutions to the challenges faced by supply chain professionals have not been subjected to the scholarly scrutiny that would determine their validity. This paper presents areas for meaningful academic research to help supply chain practitioners separate truth from hype.Originality value - The paper seeks to stimulate thinking and suggest new areas in which to do research related to the book's key premises.
Staphylococcus aureus has evolved into diverse lineages, known as clonal complexes (CCs), which exhibit differences in the coding sequences of core virulence factors. Whether these alterations affect ...functionality is poorly understood. Here, we studied the highly polymorphic pore-forming toxin LukAB. We discovered that the LukAB toxin variants produced by S. aureus CC30 and CC45 kill human phagocytes regardless of whether CD11b, the previously established LukAB receptor, is present, and instead target the human hydrogen voltage-gated channel 1 (HVCN1). Biochemical studies identified the domain within human HVCN1 that drives LukAB species specificity, enabling the generation of humanized HVCN1 mice with enhanced susceptibility to CC30 LukAB and to bloodstream infection caused by CC30 S. aureus strains. Together, this work advances our understanding of an important S. aureus toxin and underscores the importance of considering genetic variation in characterizing virulence factors and understanding the tug of war between pathogens and the host.
Abstract We report a revised analysis for the radius, mass, and hot surface regions of the massive millisecond pulsar PSR J0740+6620, studied previously with joint fits to NICER and XMM-Newton data ...by Riley et al. (2021) and Miller et al. (2021). We perform a similar Bayesian estimation for the pulse-profile model parameters, except that instead of fitting simultaneously the XMM-Newton data, we use the best available NICER background estimates to constrain the number of photons detected from the source. This approach eliminates any potential issues in the cross-calibration between these two instruments, providing thus an independent check of the robustness of the analysis. The obtained neutron star parameter constraints are compatible with the already published results, with a slight dependence on how conservative the imposed background limits are. A tighter lower limit causes the inferred radius to increase, and a tighter upper limit causes it to decrease. We also extend the study of the inferred emission geometry to examine the degree of deviation from antipodality of the hot regions. We show that there is a significant offset to an antipodal spot configuration, mainly due to the non-half-cycle azimuthal separation of the two emitting spots. The offset angle from the antipode is inferred to be above 25° with 84% probability. This seems to exclude a centered-dipolar magnetic field in PSR J0740+6620.
We perform a study of stellar flares for the 24,809 stars observed with 2 minute cadence during the first two months of the TESS mission. Flares may erode exoplanets' atmospheres and impact their ...habitability, but might also trigger the genesis of life around small stars. TESS provides a new sample of bright dwarf stars in our galactic neighborhood, collecting data for thousands of M dwarfs that might host habitable exoplanets. Here, we use an automated search for flares accompanied by visual inspection. Then, our public allesfitter code robustly selects the appropriate model for potentially complex flares via Bayesian evidence. We identify 1228 flaring stars, 673 of which are M dwarfs. Among 8695 flares in total, the largest superflare increased the stellar brightness by a factor of 16.1. Bolometric flare energies range from 1031.0 to 1036.9 erg, with a median of 1033.1 erg. Furthermore, we study the flare rate and energy as a function of stellar type and rotation period. We solidify past findings that fast rotating M dwarfs are the most likely to flare and that their flare amplitude is independent of the rotation period. Finally, we link our results to criteria for prebiotic chemistry, atmospheric loss through coronal mass ejections, and ozone sterilization. Four of our flaring M dwarfs host exoplanet candidates alerted on by TESS, for which we discuss how these effects can impact life. With upcoming TESS data releases, our flare analysis can be expanded to almost all bright small stars, aiding in defining criteria for exoplanet habitability.
The Santa Barbara Binary−disk Code Comparison Duffell, Paul C.; Dittmann, Alexander J.; D’Orazio, Daniel J. ...
The Astrophysical journal,
08/2024, Letnik:
970, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract We have performed numerical calculations of a binary interacting with a gas disk, using 11 different numerical methods and a standard binary−disk setup. The goal of this study is to ...determine whether all codes agree on a numerically converged solution and to determine the necessary resolution for convergence and the number of binary orbits that must be computed to reach an agreed-upon relaxed state of the binary−disk system. We find that all codes can agree on a converged solution (depending on the diagnostic being measured). The zone spacing required for most codes to reach a converged measurement of the torques applied to the binary by the disk is roughly 1% of the binary separation in the vicinity of the binary components. For our disk model to reach a relaxed state, codes must be run for at least 200 binary orbits, corresponding to about a viscous time for our parameters, 0.2( a 2 Ω B / ν ) binary orbits, where ν is the kinematic viscosity. The largest discrepancies between codes resulted from the dimensionality of the setup (3D vs. 2D disks). We find good agreement in the total torque on the binary between codes, although the partition of this torque between the gravitational torque, orbital accretion torque, and spin accretion torque depends sensitively on the sink prescriptions employed. In agreement with previous studies, we find a modest difference in torques and accretion variability between 2D and 3D disk models. We find cavity precession rates to be appreciably faster in 3D than in 2D.
Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain “reader” modules. Inhibitors of the ...bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition.
Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, ...but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.
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•SERPINE1/PAI-1 was identified as an unconventional ISG that acts extracellularly•PAI-1 inhibits influenza A virus (IAV) spread by inhibiting glycoprotein cleavage•Endogenous PAI-1 blocks IAV spread in human and murine cells, ex vivo and in vivo•PAI-1 potentially inhibits other viruses requiring extracellular maturation
Plasminogen activator inhibitor (PAI-1) blocks surface glycoprotein maturation of influenza A virus, thus reducing virus spread in the airways and revealing that the innate immune system, driven by type I IFN, uses modulation of the extracellular environment to inhibit viruses.
We describe the X-ray pulse profile models we use and how we use them to analyze Neutron Star Interior Composition Explorer(NICER)observations of rotation-powered millisecond pulsars to obtain ...information about the mass–radius relation of neutron stars and the equation of state of the dense matter in their cores. Here we detail our modeling of the observed profile of PSR J0030+0451 that we analyzed in Miller et al. and Riley et al. and describe a cross-verification of computations of the pulse profiles of a star with R/M 3, in case stars this compact need to be considered in future analyses. We also present our early cross-verification efforts of the parameter estimation procedures used by Miller et al. and Riley et al. by analyzing two distinct synthetic data sets. Both codes yielded credible regions in the mass–radius plane that are statistically consistent with one another, and both gave posterior distributions for model parameter values consistent with the values that were used to generate the data. We also summarize the additional tests of the parameter estimation procedure of Miller et al. that used synthetic pulse profiles and the NICER pulse profile of PSR J0030+0451. We then illustrate how the precision of mass and radius estimates depends on the pulsar’s spin rate and the size of its hot spot by analyzing four different synthetic pulse profiles. Finally, we assess possible sources of systematic error in the estimates made using this technique, some of which may warrant further investigation.
Abstract
We report the detection of X-ray pulsations from the rotation-powered millisecond-period pulsars PSR J0740+6620 and PSR J1614−2230, two of the most massive neutron stars known, using ...observations with the Neutron Star Interior Composition Explorer (NICER). We also analyze X-ray Multi-Mirror Mission (XMM-Newton) data for both pulsars to obtain their time-averaged fluxes and study their respective X-ray fields. PSR J0740+6620 exhibits a broad double-peaked profile with a separation of ∼0.4 in phase. PSR J1614−2230, on the other hand, has a broad single-peak profile. We show the NICER detections of X-ray pulsations for both pulsars and also discuss the phase relationship to their radio pulsations. The XMM-Newton X-ray spectra of both pulsars shows they are thermally dominated but in the case of PSR J1614−2230 a weak nonthermal high energy tail appears to be present in the spectrum. The thermally dominated spectra along with broad modulations for both pulsars are indicative of thermal radiation from one or more small regions of the stellar surface. For PSR J0740+6620, this paper documents the data reduction performed to obtain the pulsation detection and prepare for pulse light curve modeling analysis.
The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the ...public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.
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