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Abstract As a toy model for the microscopic description of matter in de Sitter space, we consider a Hamiltonian acting on the spin-j representation of SU(2). This is a model with a finite-dimensional Hilbert space, from which quasinormal modes emerge in the large-spin limit. The path integral over coherent spin states can be evaluated at the semiclassical level and from it we find the single-particle de Sitter density of states, including 1/j corrections. Along the way, we discuss the use of quasinormal modes in quantum mechanics, starting from the paradigmatic upside-down harmonic oscillator.

Abstract We consider the superfluid phase of a specific renormalizable relativistic quantum field theory. We prove that, within the regime of validity of perturbation theory and of the superfluid effective theory, there are consistent and regular vortex solutions where the superfluid’s velocity field as traditionally defined smoothly interpolates between zero and arbitrarily large superluminal values. We show that this solution is free of instabilities and of superluminal excitations. We show that, in contrast, a generic vortex solution for an ordinary fluid does develop an instability if the velocity field becomes superluminal. All this questions the characterization of a superfluid velocity field as the actual velocity of “something”.

Prosthetic legs are typically passive systems without active ankle control, restricting mediolateral balancing to a hip strategy. Resulting balance control impairments for persons with a lower extremity amputation may be mitigated by increasing hip strategy effectiveness, in which relatively small hip moments of force are adequate for mediolateral balancing. To increase hip strategy effectiveness we have developed a prosthetic leg prototype based on the Peaucellier mechanism, the Sideways Balance Mechanism (SBM). This polycentric mechanism adds a frontal plane degree of freedom, reducing mediolateral body displacements. Adding a passive joint alone introduces instability, in which mediolateral body rotation leads to CoM height loss, ultimately resulting in a fall. The SBM however provides stability typically absent by lengthening under rotation, thereby compensating for CoM height loss. By allowing for both foot rotation (in-/eversion), and increased mediolateral ground reaction force the SBM increases hip strategy effectiveness. We aimed to provide proof of principle that the SBM can improve active mediolateral balance control in prosthetic walking by increasing hip strategy effectiveness compared to a typical set-up. Comparison between a typical set-up and the SBM showed an increased mediolateral ground reaction force at equal hip moments of force for a 2D forwards dynamics computer simulation, and a reduced hip moment of force at equal mediolateral ground reaction force for a case study. Results validate increased hip strategy effectiveness of the SBM compared to a typical set-up, providing proof of principle that adding an SBM to a prosthetic set-up improves mediolateral balance control in prosthetic walking.

Abstract Gamma‐hydroxy‐butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß‐amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high‐resolution atlas‐based 1H‐magnetic resonance spectroscopic imaging (MRSI) at ultra‐high magnetic field strength of 7 Tesla for gray matter‐specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß‐burden (ß = 0.60, p

IntroductionNecrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development.MethodsIn this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence.ResultsThe study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24–28) weeks, postmenstrual age at diagnosis 28 (26–31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41–50) U/g of protein] compared to controls [115 (76–144), P = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0–0.1)] than in controls [0.3 (0.2–0.5), P = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens.ConclusionThis study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.

Abstract Parallel evolution provides strong evidence of adaptation by natural selection due to local environmental variation. Yet, the chronology, and mode of the process of parallel evolution remains debated. Here, we harness the temporal resolution of paleogenomics to address these long-standing questions, by comparing genomes originating from the mid-Holocene (8610-5626 years before present, BP) to contemporary pairs of coastal-pelagic ecotypes of bottlenose dolphin. We find that the affinity of ancient samples to coastal populations increases as the age of the samples decreases. We assess the youngest genome (5626 years BP) at sites previously inferred to be under parallel selection to coastal habitats and find it contained coastal-associated genotypes. Thus, coastal-associated variants rose to detectable frequencies close to the emergence of coastal habitat. Admixture graph analyses reveal a reticulate evolutionary history between pelagic and coastal populations, sharing standing genetic variation that facilitated rapid adaptation to newly emerged coastal habitats.

Abstract We extend a formula for 1-loop black hole determinants by Denef, Hartnoll, and Sachdev (DHS) to spinning fields on any (d + 1)-dimensional static spherically symmetric black hole. By carefully analyzing the regularity condition imposed on the Euclidean eigenfunctions, we reveal an unambiguous bulk-edge split in the 1-loop Euclidean partition function for tensor fields of arbitrary integer spin: the bulk part captures the “renormalized” thermal canonical partition function recently discussed in [1]; the edge part is related to quasinormal modes (QNMs) that fail to analytically continue to a subset of Euclidean modes with enhanced fall-offs near the origin. Since the edge part takes the form of a path integral on S d−1, this suggests that these are associated with degrees of freedom living on the bifurcation surface in the Lorentzian two-sided black hole geometry. For massive higher spin on static BTZ and massive vector on Nariai black holes, we find that the edge partition function is related to the QNMs with lowest overtone numbers.

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of Pachycetus (Morphotype 1b), a not-elongated vertebra of a large ‘dorudontid’ basilosaurid (Morphotype 2) and ‘shortened’ vertebrae of a new, unnamed taxon (Morphotype 3). This article deals with a still undescribed, smaller vertebra, NMR-16642, from this site. Our first aim was to date it by dinoflagellate cysts in adhering sediments. Yielding an age of about 38 Ma, it is one of the very few remains of basilosaurids from Europe, of which the age could be assessed with reasonable certainty. The vertebra, Morphotype 1a, is assigned to a small species of Pachycetus. High-quality CT scans are used to differentiate between NMR-16642, Morphotype 1a, and the large species of Pachycetus, Morphotype 1b. Another aim of this paper is to investigate the inner structure and vascularity of the study vertebra and that of the other morphotypes (1b, 2, 3) from this area by using high-quality CT scans. Notwithstanding differences in size, shape and compactness, the vertebral inner structure with a multi-layered cortex of periosteal bone, surrounding two cones of endosteal bone appears to be basically similar in all morphotypes. Apparently, this inner structure reflects the ontogenetic vertebral growth. An attempt to reconstruct the vascularity of the vertebrae reveals a remarkable pattern of interconnected vascular systems. From the dorsal and, if present, ventral foramina, vascular canals are running to a central vascular node. From this node a system of vascular canals goes to the epiphyseal ends, giving rise to separate systems for cortex and cones. It is the first time that the vascularity of vertebrae of archaeocetes is investigated.

Insulin-like growth factor I (IGF-I) is a growth-promoting anabolic hormone that fosters cell growth and tissue homeostasis. IGF-I deficiency is associated with several diseases, including growth disorders and neurological and musculoskeletal diseases due to impaired regeneration. Despite the vast regenerative potential of IGF-I, its unfavorable pharmacokinetic profile has prevented it from being used therapeutically. In this study, we resolved these challenges by the local administration of IGF-I mRNA, which ensures desirable homeostatic kinetics and non-systemic, local dose-dependent expression of IGF-I protein. Furthermore, IGF-I mRNA constructs were sequence engineered with heterologous signal peptides, which improved in vitro protein secretion (2- to 6-fold) and accelerated in vivo functional regeneration (16-fold) over endogenous IGF-I mRNA. The regenerative potential of engineered IGF-I mRNA was validated in a mouse myotoxic muscle injury and rabbit spinal disc herniation models. Engineered IGF-I mRNA had a half-life of 17–25 h in muscle tissue and showed dose-dependent expression of IGF-I over 2–3 days. Animal models confirm that locally administered IGF-I mRNA remained at the site of injection, contributing to the safety profile of mRNA-based treatment in regenerative medicine. In summary, we demonstrate that engineered IGF-I mRNA holds therapeutic potential with high clinical translatability in different diseases.

Abstract We derive soft theorems for theories in which time symmetries — symmetries that involve the transformation of time, an example of which are Lorentz boosts — are spontaneously broken. The soft theorems involve unequal-time correlation functions with the insertion of a soft Goldstone in the far past. Explicit checks are provided for several examples, including the effective theory of a relativistic superfluid and the effective field theory of inflation. We discuss how in certain cases these unequal-time identities capture information at the level of observables that cannot be seen purely in terms of equal-time correlators of the field alone. We also discuss when it is possible to phrase these soft theorems as identities involving equal-time correlators.

Abstract When computing the ideal gas thermal canonical partition function for a scalar outside a black hole horizon, one encounters the divergent single-particle density of states (DOS) due to the continuous nature of the normal mode spectrum. Recasting the Lorentzian field equation into an effective 1D scattering problem, we argue that the scattering phases encode non-trivial information about the DOS and can be extracted by “renormalizing” the DOS with respect to a reference. This defines a renormalized free energy up to an arbitrary additive constant. Interestingly, we discover that the 1-loop Euclidean path integral, as computed by the Denef-Hartnoll-Sachdev formula, fixes the reference free energy to be that on a Rindler-like region, and the renormalized DOS captures the quasinormal modes for the scalar. We support these claims with the examples of scalars on static BTZ, Nariai black holes and the de Sitter static patch. For black holes in asymptotically flat space, the renormalized DOS is captured by the phase of the transmission coefficient whose magnitude squared is the greybody factor. We comment on possible connections with recent works from an algebraic point of view.

Abstract We argue that a type IIB Euclidean supergravity solution of the form ℝ × S 1 × 𝕋8 with imaginary self-dual F 1 flux through ℝ × S 1 belongs to the chain of AdS d × S d × 𝕋10−2d vacua with (imaginary) self-dual F d flux, where d ≤ 5. Such vacua come from the near-horizon of D(d − 2)/D(8 − d) branes and are supersymmetric for odd values of d. For d = 1 we speculate that the hallmark of conformal symmetry for the matrix model dual is a vanishing free energy. The matrix dual was recently constructed by [1] by adding matrix interactions coming from strings stretching between the D(−1) and D7 branes to the IKKT matrix model. We find that the corresponding supergravity solution indeed has vanishing on-shell action. Specific F 5 fluxes need to be switched on as a consequence of (a T-dual version of) the Hanany-Witten effect.

Drone-based photogrammetry typically requires the task of georeferencing aerial images by detecting the center of Ground Control Points (GCPs) placed in the field. Since this is a very labor-intensive task, it could benefit greatly from automation. In this study, we explore the extent to which traditional computer vision approaches can be generalized to deal with variability in real-world drone data sets and focus on training different residual neural networks (ResNet) to improve generalization. The models were trained to detect single keypoints of fixed-sized image tiles with a historic collection of drone-based Red–Green–Blue (RGB) images with black and white GCP markers in which the center was manually labeled by experienced photogrammetry operators. Different depths of ResNets and various hyperparameters (learning rate, batch size) were tested. The best results reached sub-pixel accuracy with a mean absolute error of 0.586. The paper demonstrates that this approach to drone-based mapping is a promising and effective way to reduce the human workload required for georeferencing aerial images.

Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8+ T cell response and confers protection in a lethal murine challenge model of infection.

Abstract An integral representation of the 1-loop partition function for charged scalars and spinors, minimally coupled to a uniform U(1) field on S 2, is given in terms of SO(1, 2) Harish-Chandra group characters and evaluated exactly in terms of Hurwitz ζ-functions. Analytically continuing the U(1) field, we interpret the path integrals as quasicanonical partition functions in dS2 with an electric field. The character itself is obtained as a trace over states living at the future boundary of de Sitter and has a quasinormal mode expansion. The imaginary part of the partition function captures Schwinger pair creation in the static patch at finite temperature. The thermal enhancement is most noticeable for scalar masses below Hubble and leads to non-monotonicity of the current as a function of the field. This parameter range, when dimensionally reducing from a charged or rotating Nariai spacetime, is excluded by Swampland-inspired bounds. Around the AdS2 black hole, in contrast to dS2, there is a threshold to pair creation.

In this case report, we describe the diagnosis, treatment, and outcome of two feline cases of vertebral osteosarcoma. Case 1: A 6-year-old female neutered domestic longhaired cat was presented with progressive paraparesis, ataxia, and spinal hyperesthesia. MRI of the thoracolumbar spinal cord and vertebral column revealed a strongly contrast-enhancing mass lesion originating from the dorsal lamina and spinous process of T13. The lesion caused extradural compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation of surgical biopsies was consistent with vertebral osteosarcoma. The cat was paraplegic with intact nociception post-surgery. Subsequently, the cat recovered ambulation while remaining mildly ataxic and paraparetic at long-term follow-up. Post-operative chemotherapy was started with doxorubicin. CT scans at 2, 4, 9, 13, and 20 months post-surgery showed no signs of local recurrence or metastasis. Case 2: A 15.5-year-old male neutered domestic shorthaired cat was presented with progressive paraparesis, tail paresis, and spinal hyperesthesia. Radiographs and CT scan of the lumbar vertebral column showed a large mass originating from the dorsal lamina and spinous process of L6, suggestive of neoplasia, with severe compression of the spinal cord. Surgical debulking was performed, and the histopathological evaluation was consistent with vertebral osteosarcoma. Post-operative chemotherapy was started with doxorubicin. Seven months post-surgery, the patient was neurologically normal with no signs of metastatic disease. This case report highlights the possibility of good outcomes after the surgical treatment of feline vertebral osteosarcoma supplemented with post-surgical chemotherapy.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

We present data collected for the research article “Advances in Spiral fMRI: A High-resolution Study with Single-shot Acquisition” (Kasper et al. 2022). All data was acquired on a 7T ultra-high field MR system (Philips Achieva), equipped with a concurrent magnetic field monitoring setup based on 16 NMR probes. For task-based fMRI, a visual quarterfield stimulation paradigm was employed, alongside physiological monitoring via peripheral recordings.This data collection contains different datasets pertaining to different purposes:(1) Measured magnetic field dynamics (k0, spiral k-space trajectories, 2nd order spherical harmonics, concomitant fields) during ultra-high field fMRI sessions from six subjects, as well as concurrent temperature curves of the gradient coil, to explore MR system and subject-induced variability of field fluctuations and assess the impact of potential correction methods.(2) MR Raw Data, i.e., coil and concurrent encoding magnetic field (trajectory) data, of a single subject, as well as nominal spiral gradient waveforms, precomputed B0 and coil sensitivity maps, to enable testing of alternative image reconstruction approaches for spiral fMRI data.(3) Reconstructed image time series of the same subject alongside behavioral and physiological logfiles, to reproduce the fMRI preprocessing and analysis, as well as figures presented in the research article related to this article, using the published analysis code repository.All data is provided in standardized formats for the respective research area. In particular, ISMRMRD (HDF5) is used to store raw coil data and spiral trajectories, as well as measured field dynamics. Likewise, the NIfTI format is used for all imaging data (anatomical MRI and spiral fMRI, B0 and coil sensitivity maps).

Abstract We demonstrate that all rigidly rotating strings with center of mass at the origin of the dS3 static patch satisfy the Higuchi bound. This extends the observation of Noumi et al. for the open GKP-like string to all solutions of the Larsen-Sanchez class. We argue that strings violating the bound end up expanding towards the horizon and provide a numerical example. Adding point masses to the open string only increases the mass/spin ratio. For segmented strings, we write the conserved quantities, invariant under Gubser’s algebraic evolution equation, in terms of discrete lightcone coordinates describing kink collisions. Randomly generated strings are found to have a tendency to escape through the horizon that is mostly determined by their energy. For rapidly rotating segmented strings with mass/spin < 1, the kink collisions eventually become causally disconnected. Finally we consider the scenario of cosmic strings captured by a black hole in dS and find that horizon friction can make the strings longer.

Spiral fMRI has been put forward as a viable alternative to rectilinear echo-planar imaging, in particular due to its enhanced average k-space speed and thus high acquisition efficiency. This renders spirals attractive for contemporary fMRI applications that require high spatiotemporal resolution, such as laminar or columnar fMRI. However, in practice, spiral fMRI is typically hampered by its reduced robustness and ensuing blurring artifacts, which arise from imperfections in both static and dynamic magnetic fields.Recently, these limitations have been overcome by the concerted application of an expanded signal model that accounts for such field imperfections, and its inversion by iterative image reconstruction. In the challenging ultra-high field environment of 7 Tesla, where field inhomogeneity effects are aggravated, both multi-shot and single-shot 2D spiral imaging at sub-millimeter resolution was demonstrated with high depiction quality and anatomical congruency.In this work, we further these advances towards a time series application of spiral readouts, namely, single-shot spiral BOLD fMRI at 0.8 mm in-plane resolution. We demonstrate that high-resolution spiral fMRI at 7 T is not only feasible, but delivers both excellent image quality, BOLD sensitivity, and spatial specificity of the activation maps, with little artifactual blurring. Furthermore, we show the versatility of the approach with a combined in/out spiral readout at a more typical resolution (1.5 mm), where the high acquisition efficiency allows to acquire two images per shot for improved sensitivity by echo combination.

The bone health guidelines for breast cancer (BC) patients recommend bone mineral density (BMD) testing. Patients with low BMD and elevated serum calcium levels (SCLs) are further evaluated for primary hyperparathyroidism (PHPT). We aimed to determine the prevalence of PHPT in treated BC patients with low BMD and analyze the association of SCLs with histopathologic tumor features and cancer treatment. This retrospective study included postmenopausal BC patients examined at Osteoporosis Clinic between 2013 and 2020. Clinical and BMD data were collected from patient medical records. Patients with biochemical suspicion of PHPT underwent standard parathyroid imaging procedures. Nine out of 137 (6.6%) patients were diagnosed with PHPT; 8/9 patients underwent parathyroidectomy and one patient was advised to follow-up. Among the rest of 128 non-PHPT patients, higher SCLs showed a trend of positive association with higher tumor grade and axillary lymph node involvement, and received immunotherapy, although without statistical significance. We found a higher prevalence of PHPT in treated BC patients compared to the general population. Higher SCLs show a trend of positive correlation with some more aggressive histopathologic tumor features and with immunotherapy. The results of this study suggest that assessment of SCLs should be routinely performed to rule out PHPT in treated BC patients with low BMD.

IntroductionHippocampal atrophy is an established Alzheimer’s Disease (AD) biomarker. Volume loss in specific subregions as measurable with ultra-high field magnetic resonance imaging (MRI) may reflect earliest pathological alterations.MethodsData from positron emission tomography (PET) for estimation of cortical amyloid β (Aβ) and high-resolution 7 Tesla T1 MRI for assessment of hippocampal subfield volumes were analyzed in 61 non-demented elderly individuals who were divided into risk-categories as defined by high levels of cortical Aβ and low performance in standardized episodic memory tasks.ResultsHigh cortical Aβ and low episodic memory interactively predicted subicular volume [F(3,57) = 5.90, p = 0.018]. The combination of high cortical Aβ and low episodic memory was associated with significantly lower subicular volumes, when compared to participants with high episodic memory (p = 0.004).DiscussionOur results suggest that low subicular volume is linked to established indicators of AD risk, such as increased cortical Aβ and low episodic memory. Our data support subicular volume as a marker of dementia-risk susceptibility in old-aged non-demented persons.

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and postharvest regulation), plant responses to environmental signals (endoplasmic-reticulum-associated degradation, chloroplast-associated degradation, drought tolerance, and the growth-defense trade-off), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.

Abstract We establish an attractor mechanism for the horizon metric of asymptotically locally AdS4 supersymmetric black holes. The horizon is a smooth Riemann surface with arbitrary metric at asymptotic infinity which is fixed to the constant curvature metric in the near horizon region. We show how this mechanism is realized for four-dimensional N $$ \mathcal{N} $$ = 2 gauged supergravity coupled to vector multiplets by focusing on the STU model. A similar analysis is performed for gauged supergravity theories in five, six, and seven dimen- sions where we establish the same mechanism by extending previous results on holographic uniformization.

Abstract Background Porcine teschovirus (PTV) circulates among wild and domesticated pig populations without causing clinical disease, however neuroinvasive strains have caused high morbidity and mortality in the past. In recent years, several reports appeared with viral agents as a cause for neurologic signs in weanling and growing pigs among which PTV and new strains of PTV were described. Case presentation On two unrelated pig farms in the Netherlands the weanling pig population showed a staggering gate, which developed progressively to paresis or paralysis of the hind legs with a morbidity up to 5%. After necropsy we diagnosed a non-suppurative encephalomyelitis on both farms, which was most consistent with a viral infection. PTV was detected within the central nervous system by qPCR. From both farms PTV full-length genomes were sequenced, which clustered closely with PTV-3 (98%) or PTV-11 (85%). Other common swine viruses were excluded by qPCR and sequencing of the virus. Conclusion Our results show that new neuroinvasive PTV strains still emerge in pigs in the Netherlands. Further research is needed to investigate the impact of PTV and other viral agents causing encephalomyelitis within wild and domestic pig populations supported by the awareness of veterinarians.

Abstract Objectives High‐magnitude CD8+ T cell responses are associated with mild COVID‐19 disease; however, the underlying characteristics that define CD8+ T cell‐mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope‐specific CD8+ T cells remain largely unexplored and are essential for the development of next‐generation broad‐protective vaccines. This study identified a broad spectrum of conserved SARS‐CoV‐2 CD8+ T cell epitopes and defined their respective immunodominance and phenotypic profiles following SARS‐CoV‐2 infection. Methods CD8+ T cells from 51 convalescent COVID‐19 donors were analysed for their ability to recognise 133 predicted and previously described SARS‐CoV‐2‐derived peptides restricted by 11 common HLA class I allotypes using heterotetramer combinatorial coding, which combined with phenotypic markers allowed in‐depth ex vivo profiling of CD8+ T cell responses at quantitative and phenotypic levels. Results A comprehensive panel of 49 mostly conserved SARS‐CoV‐2‐specific CD8+ T cell epitopes, including five newly identified low‐magnitude epitopes, was established. We confirmed the immunodominance of HLA‐A*01:01/ORF1ab1637–1646 and B*07:02/N105–113 and identified B*35:01/N325–333 as a third epitope with immunodominant features. The magnitude of subdominant epitope responses, including A*03:01/N361–369 and A*02:01/S269–277, depended on the donors' HLA‐I context. All epitopes expressed prevalent memory phenotypes, with the highest memory frequencies in severe COVID‐19 donors. Conclusion SARS‐CoV‐2 infection induces a predominant CD8+ T memory response directed against a broad spectrum of conserved SARS‐CoV‐2 epitopes, which likely contributes to long‐term protection against severe disease. The observed immunodominance hierarchy emphasises the importance of T cell epitopes derived from nonspike proteins to the overall protective and cross‐reactive immune response, which could aid future vaccine strategies.

Spiral imaging is very well suited for functional MRI, however its use has been limited by the fact that artifacts caused by gradient imperfections and B0 inhomogeneity are more difficult to correct compared to EPI. Effective correction requires accurate knowledge of the traversed k-space trajectory. With the goal of making spiral fMRI more accessible, we have evaluated image reconstruction using trajectories predicted by the gradient impulse response function (GIRF), which can be determined in a one-time calibration step.GIRF-predicted reconstruction was tested for high-resolution (0.8 mm) fMRI at 7T. Image quality and functional results of the reconstructions using GIRF-prediction were compared to reconstructions using the nominal trajectory and concurrent field monitoring.The reconstructions using nominal spiral trajectories contain substantial artifacts and the activation maps contain misplaced activation. Image artifacts are substantially reduced when using the GIRF-predicted reconstruction, and the activation maps for the GIRF-predicted and monitored reconstructions largely overlap. The GIRF reconstruction provides a large increase in the spatial specificity of the activation compared to the nominal reconstruction.The GIRF-reconstruction generates image quality and fMRI results similar to using a concurrently monitored trajectory. The presented approach does not prolong or complicate the fMRI acquisition. Using GIRF-predicted trajectories has the potential to enable high-quality spiral fMRI in situations where concurrent trajectory monitoring is not available.

Abstract Detailed knowledge of the intra‐field variability of soil properties and crop characteristics is indispensable for the establishment of sustainable precision agriculture. We present an approach that combines ground‐based agrogeophysical soil and aerial crop data to delineate field‐specific management zones that we interpret with soil attribute measurements of texture, bulk density, and soil moisture, as well as yield and nitrate residue in the soil after potato (Solanum tuberosum L.) cultivation. To delineate the management zones, we use aerial drone‐based normalized difference vegetation index (NDVI), spatial electromagnetic induction (EMI) soil scanning, and the EMI–NDVI data combination as input in a machine learning clustering technique. We tested this approach in three successive years on six agricultural fields (two per year). The field‐scale EMI data included spatial soil information of the upper 0–50 cm, to approximately match the soil depth sampled for attribute measurements. The NDVI measurements over the growing season provide information on crop development. The management zones delineated from EMI data outperformed the management zones derived from NDVI in terms of spatial coherence and showed differences in properties relevant for agricultural management: texture, soil moisture deficit, yield, and nitrate residue. The combined EMI–NDVI analysis provided no extra benefit. This underpins the importance of including spatially distributed soil information in crop data interpretation, while emphasizing that high‐resolution soil information is essential for variable rate applications and agronomic modeling.

Connectomics is essential for understanding large-scale brain networks but requires that individual connection estimates are neurobiologically interpretable. In particular, a principle of brain organization is that reciprocal connections between cortical areas are functionally asymmetric. This is a challenge for fMRI-based connectomics in humans where only undirected functional connectivity estimates are routinely available. By contrast, whole-brain estimates of effective (directed) connectivity are computationally challenging, and emerging methods require empirical validation.Here, using a motor task at 7T, we demonstrate that a novel generative model can infer known connectivity features in a whole-brain network (>200 regions, >40,000 connections) highly efficiently. Furthermore, graph-theoretical analyses of directed connectivity estimates identify functional roles of motor areas more accurately than undirected functional connectivity estimates. These results, which can be achieved in an entirely unsupervised manner, demonstrate the feasibility of inferring directed connections in whole-brain networks and open new avenues for human connectomics.

We present a system of session types based on adjoint logic which generalize standard binary session types. Our system allows us to uniformly capture several new behaviors in the space of asynchronous message-passing communication, including multicast, where a process sends a single message to multiple clients, replicable services, which have multiple clients and replicate themselves on-demand to handle requests from those clients, and cancellation, where a process discards a channel without communicating along it. We provide session fidelity and deadlock-freedom results for this system, from which we then derive a logically justified form of garbage collection.

T2*-weighted gradient-echo sequences count among the most widely used techniques in neuroimaging and offer rich magnitude and phase contrast. The susceptibility effects underlying this contrast scale with B0, making T2*-weighted imaging particularly interesting at high field. High field also benefits baseline sensitivity and thus facilitates high-resolution studies. However, enhanced susceptibility effects and high target resolution come with inherent challenges. Relying on long echo times, T2*-weighted imaging not only benefits from enhanced local susceptibility effects but also suffers from increased field fluctuations due to moving body parts and breathing. High resolution, in turn, renders neuroimaging particularly vulnerable to motion of the head. This work reports the implementation and characterization of a system that aims to jointly address these issues. It is based on the simultaneous operation of two control loops, one for field stabilization and one for motion correction. The key challenge with this approach is that the two loops both operate on the magnetic field in the imaging volume and are thus prone to mutual interference and potential instability. This issue is addressed at the levels of sensing, timing, and control parameters. Performance assessment shows the resulting system to be stable and exhibit adequate loop decoupling, precision, and bandwidth. Simultaneous field and motion control is then demonstrated in examples of T2*-weighted in vivo imaging at 7T.