Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

In a recent study, visual signals were recorded for the first time in starburst amacrine cells of the macaque retina, and, as for mouse and rabbit, a directional bias observed in calcium signals was recorded from near the dendritic tips. Stimulus motion from the soma toward the tip generated a larger calcium signal than motion from the tip toward the soma. Two mechanisms affecting the spatiotemporal summation of excitatory postsynaptic currents have been proposed to contribute to directional signaling at the dendritic tips of starbursts: (1) a “morphological” mechanism in which electrotonic propagation of excitatory synaptic currents along a dendrite sums bipolar cell inputs at the dendritic tip preferentially for stimulus motion in the centrifugal direction; (2) a “space–time” mechanism that relies on differences in the time-courses of proximal and distal bipolar cell inputs to favor centrifugal stimulus motion. To explore the contributions of these two mechanisms in the primate, we developed a realistic computational model based on connectomic reconstruction of a macaque starburst cell and the distribution of its synaptic inputs from sustained and transient bipolar cell types. Our model suggests that both mechanisms can initiate direction selectivity in starburst dendrites, but their contributions differ depending on the spatiotemporal properties of the stimulus. Specifically, the morphological mechanism dominates when small visual objects are moving at high velocities, and the space–time mechanism contributes most for large visual objects moving at low velocities.

An emergent volume electron microscopy technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualization and analysis of the data is possible. SEM images are affected by noise, drift, and charging effects, that can make precise 3D reconstruction of biological features difficult. This article presents Okapi-EM, an open-source napari plugin developed to process and analyze cryogenic serial pFIB/SEM images. Okapi-EM enables automated image registration of slices, evaluation of image quality metrics specific to pFIB-SEM imaging, and mitigation of charging artifacts. Implementation of Okapi-EM within the napari framework ensures that the tools are both user- and developer-friendly, through provision of a graphical user interface and access to Python programming.

The shape of emission lines in the optical spectra of star-forming galaxies reveals the kinematics of the diffuse gaseous component. We analyse the shape of prominent emission lines in a sample of $\sim$ 53000 star-forming galaxies from the Sloan Digital Sky Survey, focusing on departures from gaussianity. Departures from a single gaussian profile allow us to probe the motion of gas and to assess the role of outflows. The sample is divided into groups according to their stellar velocity dispersion and star formation rate (SFR). The spectra within each group are stacked to improve the signal-to-noise ratio of the emission lines, to remove individual signatures, and to enhance the effect of SFR on the shapes of the emission lines. The moments of the emission lines, including kurtosis and skewness, are determined. We find that most of the emission lines in strong star-forming systems unequivocally feature negative kurtosis. This signature is present in $\mathrm{H}\unicode{x03B2}$ , $\mathrm{H}\unicode{x03B1}$ , [N ii], and [S ii] in massive galaxies with high SFRs. We attribute it as evidence of radial outflows of ionised gas driven by the star formation of the galaxies. Also, most of the emission lines in low-mass systems with high SFRs feature negative skewness, and we interpret it as evidence of dust obscuration in the galactic disk. These signatures are however absent in the [O iii] line, which is believed to trace a different gas component. The observed trend is significantly stronger in face-on galaxies, indicating that star formation drives the outflows along the galactic rotation axis, presumably the path of least resistance. The data suggest that outflows driven by star formation exert accumulated impacts on the interstellar medium, and the outflow signature is more evident in older galaxies as they have experienced a longer total duration of star formation.

We find that organization capital is negatively related to the cost of bank loans. This finding is robust to additional analyses including those that address omitted variable bias and reverse causality. In addition, we find that organization capital reduces all-in-spread-undrawn. When we decompose the bank loan cost, we find that organization capital increases facility fees due to its risk-engendering characteristics. Finally, we find that organization capital is positively associated with a high likelihood of the presence of inventors and innovation output, consistent with the argument that organization capital is embedded in the key talent within a firm.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

Ice breaking has become one of the main problems faced by ships and other equipment operating in an ice-covered water region. New methods are always being pursued and studied to improve ice-breaking capabilities and efficiencies. Based on the strong damage capability, a high-speed water jet impact is proposed to be used to break an ice plate in contact with water. A series of experiments of water jet impacting ice were performed in a transparent water tank, where the water jets at tens of metres per second were generated by a home-made device and circular ice plates of various thicknesses and scales were produced in a cold room. The entire evolution of the water jet and ice was recorded by two high-speed cameras from the top and front views simultaneously. The focus was the responses of the ice plate, such as crack development and breakup, under the high-speed water jet loads, which involved compressible pressure ${P_1}$ and incompressible pressure ${P_2}$. According to the main cause and crack development sequence, it was found that the damage of the ice could be roughly divided into five patterns. On this basis, the effects of water jet strength, ice thickness, ice plate size and boundary conditions were also investigated. Experiments validated the ice-breaking capability of the high-speed water jet, which could be a new auxiliary ice-breaking method in the future.

Background: Duchenne muscular dystrophy (DMD) is a severe progressive neuromuscular disease. This study aimed to estimate the prevalence, healthcare resource utilization (HRU), and medical costs of DMD in Alberta. Methods: This retrospective study linked provincial healthcare administrative data to identify patients with DMD utilizing a modified diagnostic code algorithm, including males <30 years of age. Five-year (April 2012 to March 2017) prevalence estimates were calculated and all-cause direct HRU and costs were examined in the first-year post-diagnosis. Results: Overall, 111 patients (median age: 12.0 years (IQR 4.7-18.3)) with DMD were identified. The estimated five-year period prevalence was 35.72 (95% CI 31.88-39.91) per 100,000 persons. All-cause HRU in the first-year post-diagnosis included a mean (SD) of 0.48 (1.19) hospitalizations (length of stay: 9.37 days (36.47)), 3.96 (6.16) general practitioner visits, 28.52 (62.98) specialist visits, and 20.14 (16.49) ambulatory care visits. Mean (SD) all-cause direct costs were $18,868 ($29,206) CAD in the first-year post-diagnosis. Conclusions: Patients with DMD had multiple interactions with the healthcare system in the year following diagnosis, resulting in substantial direct medical costs. More effective treatment strategies are needed to improve health outcomes and reduce the burden of DMD.

We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.

The GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) is a radio continuum survey at 76–227 MHz of the entire southern sky (Declination $<\!{+}30^{\circ}$ ) with an angular resolution of ${\approx}2$ arcmin. In this paper, we combine GLEAM data with optical spectroscopy from the 6dF Galaxy Survey to construct a sample of 1 590 local (median $z \approx 0.064$ ) radio sources with $S_{200\,\mathrm{MHz}} > 55$ mJy across an area of ${\approx}16\,700\,\mathrm{deg}^{2}$ . From the optical spectra, we identify the dominant physical process responsible for the radio emission from each galaxy: 73% are fuelled by an active galactic nucleus (AGN) and 27% by star formation. We present the local radio luminosity function for AGN and star-forming (SF) galaxies at 200 MHz and characterise the typical radio spectra of these two populations between 76 MHz and ${\sim}1$ GHz. For the AGN, the median spectral index between 200 MHz and ${\sim}1$ GHz, $\alpha_{\mathrm{high}}$ , is $-0.600 \pm 0.010$ (where $S \propto \nu^{\alpha}$ ) and the median spectral index within the GLEAM band, $\alpha_{\mathrm{low}}$ , is $-0.704 \pm 0.011$ . For the SF galaxies, the median value of $\alpha_{\mathrm{high}}$ is $-0.650 \pm 0.010$ and the median value of $\alpha_{\mathrm{low}}$ is $-0.596 \pm 0.015$ . Among the AGN population, flat-spectrum sources are more common at lower radio luminosity, suggesting the existence of a significant population of weak radio AGN that remain core-dominated even at low frequencies. However, around 4% of local radio AGN have ultra-steep radio spectra at low frequencies ( $\alpha_{\mathrm{low}} < -1.2$ ). These ultra-steep-spectrum sources span a wide range in radio luminosity, and further work is needed to clarify their nature.

We conducted the first detailed mineral magnetic investigation of more than nine loess–paleosol couplets of the composite Titel-Stari Slankamen loess section in Serbia, which provides one of the longest and most complete terrestrial record of paleoclimatic changes in Europe since ~1.0 Ma. The results show that the ferrimagnetic mineral assemblage of the loess units is dominated by partially oxidized multidomain (MD) and pseudo-single domain (PSD) magnetite; however, with an increasing degree of pedogenesis, the eolian contribution is gradually masked by pedogenic superparamagnetic(SP) and single-domain (SD) ferrimagnets (mainly maghemite). The overall consistency of ferrimagnetic grain-size parameters indicates an absence of dissolution of the fine-grained ferrimagnetic fraction despite changes in climate regime over the past 1.0 Ma. The variations of normalized dJ/dT@120K and normalized χheating@530°C reflect a long-term stepwise increase in aridity during glacials with a major step at ~0.6–0.5 Ma, over the last 1.0 Ma. Overall, the results provide an improved basis for the future use of the magnetic properties of Serbian loess deposits for paleoclimatic reconstruction.

The aeolian loess-paleosol sequences in the Chinese Loess Plateau (CLP) are an excellent archive of variations in atmospheric circulation in the geological past. However, there is no consensus regarding the roles of the East Asian winter monsoon and westerly winds in transporting the dust responsible for loess deposition during glacial and interstadial periods. We conducted detailed measurements of the anisotropy of magnetic susceptibility (AMS) on two parallel loess profiles covering the most recent 130 ka in the western CLP to determine paleowind directions. Results show that the magnetic lineations of the loess and paleosol units in both sections are significantly clustered along the northwest to southeast direction. These observations demonstrate that the prevailing wind system responsible for dust transport in the western CLP was the northwesterly winter monsoon, rather than the westerly winds. The AMS-derived dust-bearing wind direction was relatively stable during the last glacial and interglacial cycle in the western CLP, consistent with sedimentary and AMS evidence from the eastern CLP. Accordingly, it is reasonable to conclude that large areas of deserts and Gobi deserts areas located in the upwind direction were the dominant sources for the aeolian deposits of the Loess Plateau.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

To evaluate the dynamic properties of a coupled structure based on the dynamic properties of its substructures, this paper investigates the dynamic substructuring issue from the perspective of response prediction. The main idea is that the connecting forces at the interface of substructures can be expressed by the unknown coupled structural responses, and the responses can be solved rather easily. Not only rigidly coupled structures but also resiliently coupled structures are investigated. In order to further comprehend and visualize the nature of coupling problems, the Neumann series expansion for a matrix describing the relation between the coupled and uncoupled substructures is also introduced in this paper. Compared with existing response prediction methods, the proposed method does not have to measure any forces, which makes it easier to apply than the others. Clearly, the frequency response function matrix of coupled structures can be derived directly based on the response prediction method. Compared with existing frequency response function synthesis methods, it is more straightforward and comprehensible. Through demonstration of two examples, it is concluded that the proposed method can deal with structural coupling problems very well.

Coronavirus disease (COVID-19) is a “disaster of uncertainty” with ambiguity about its nature and trajectory. These features amplify its psychological toxicity and increase the number of psychological casualties it inflicts. Uncertainty was fueled by lack of knowledge about the lethality of a disaster, its duration, and ambiguity in messaging from leaders and health care authorities. Human resilience can have a buffering effect on the psychological impact. Experts have advocated “flattening the curve” to slow the spread of the infection. Our strategy for crisis leadership is focused on flattening the rise in psychological casualties by increasing resilience among health care workers. This paper describes an approach employed at Johns Hopkins to promote and enhance crisis leadership. The approach is based on 4 factors: vision for the future, decisiveness, effective communication, and following a moral compass. We make specific actionable recommendations for implementing these factors that are being disseminated to frontline leaders and managers. The COVID-19 pandemic is destined to have a strong psychological impact that extends far beyond the end of quarantine. Following these guidelines has the potential to build resilience and thus reduce the number of psychological casualties and speed the return to normal – or at least the new normal in the post-COVID world.

Data on the prevalence of extrapulmonary tuberculosis (EPTB) patients are limited in many African countries including Malawi. We conducted a retrospective review of all histology reports for cancer suspected patients at Mzuzu Central Hospital (MZCH) between 2013 and 2018 to determine the proportion of EPTB cases among cancer suspected patients and characterised them epidemiologically. All reports with inconclusive findings were excluded. In total, 2214 reports were included in the review, 47 of which reported EPTB, representing 2.1% (95% CI 1.6−2.8). The incidence of EPTB was significantly associated with sex, age and HIV status. Men were more than twice (OR 2.1; 95% CI 1.2–3.9) as likely to have EPTB as women while those with HIV were more than six times (OR 6.4; 95% CI 1.7–24.8) as likely to have EPTB compared to those who were HIV-negative. EPTB demonstrated an inverse relationship with age. The highest proportion of EPTB was found from neck lymph nodes (10.3% (5.4–17.2)). A reasonable number of EPTB cases are diagnosed late or missed in Malawi's hospitals. There is a need for concerted efforts to increase EPTB awareness and likely come up with a policy to consider EPTB as a differential diagnosis in cancer suspected patients.

Residual deformation and failure are two critical issues in powder bed fusion (PBF) additive manufacturing (AM) of metal products. Residual deformation caused by the non-uniform residual stress distribution dramatically affects the quality of AM product and can result in catastrophic failure in operation. Therefore, the development of an effective numerical approach to predict residual deformation and failure characteristics of AM product is always a major concern in industrial applications.

In this paper, a numerical approach in predicting residual distortion, stress and failure in AM products is presented. The conventional inherent strain method used in welding process is modified to consider the specific characteristic of AM process, such as the influences of reheating and scanning pattern. This approach consists of three simulation steps including a detailed process simulation in small-scale, a onetime static mechanical finite element analysis in part-scale, and a material failure analysis. First, the inherent strains are calculated from a thermo-mechanical process simulation in small-scale, which considers AM process parameters, such as laser power, scanning speed and path. The physical state in deposited materials including powder, liquid and solid states are taken into account in the simulation by specifying the solidus and liquidus temperature and corresponding material properties. Then the inherent strains are applied layer by layer to the part-scale simulation, where the residual distortion and stress can be predicted efficiently. Finally, a Lagrange particle method is utilized to study the failure characteristics of AM products. Numerical examples are studied to investigate the effectiveness and applicability of present approach.

We investigate the impact on the boundary-layer stability of spanwise-periodic, streamwise-elongated surface roughness elements. Our interest is in their effects on the so-called lower-branch Tollmien–Schlichting modes, and so the spanwise spacing of the elements is taken to be comparable with the spanwise wavelength of the latter, which is of $O(R^{-3/8} L)$, where $L$ is the dimensional length from the leading edge of the flat plate to the surface roughness, and $R$ is the Reynolds number based on $L$. The streamwise length is much longer, consistent with experimental set-ups. The roughness height is chosen such that the wall shear is altered by $O(1)$. From the generic triple-deck theory for three-dimensional roughness elements with both the streamwise and spanwise length scales being of $O(R^{-3/8 }L)$, we derived the relevant governing equations by appropriate rescaling. The resulting equations are nonlinear but parabolic because the pressure gradient in the streamwise direction is negligible while in the spanwise direction it is completely determined by the roughness shape. Appropriate upstream, boundary and matching conditions are derived for the problem. Owing to the parabolicity, the equations are solved efficiently using a marching method to obtain the streaky flow. The instability of the streaky flow is shown to be controlled by the spanwise-dependent (periodic) wall shear. Two- and weakly three-dimensional lower-frequency modes are found to be stabilised by the streaks, confirming previous experimental findings, while stronger three-dimensional and higher-frequency modes are destabilised. Among the three roughness shapes considered, the roughness elements in the form of hemispherical caps are found to be most effective for a given height. A resonant subharmonic interaction was found to occur for modes with spanwise wavelength twice that of the roughness elements.