Atacama Large Aperture Submillimeter Telescope (AtLAST) science: Probing the transient and time-variable sky.

The study of transient and variable events, including novae, active galactic nuclei, and black hole binaries, has historically been a fruitful path for elucidating the evolutionary mechanisms of our universe. The study of such events in the millimeter and submillimeter is, however, still in its infancy. Submillimeter observations probe a variety of materials, such as optically thick dust, which are hard to study in other wavelengths.

Atacama Large Aperture Submillimeter Telescope (AtLAST) science: The hidden circumgalactic medium.

Our knowledge of galaxy formation and evolution has incredibly progressed through multi-wavelength observational constraints of the interstellar medium (ISM) of galaxies at all cosmic epochs. However, little is known about the physical properties of the more diffuse and lower surface brightness reservoir of gas and dust that extends beyond ISM scales and fills dark matter haloes of galaxies up to their virial radii, the circumgalactic medium (CGM). New theoretical studies increasingly stress the relevance of the latter for understanding the feedback and feeding mechanisms that shape galaxies across cosmic times, whose cumulative effects leave clear imprints into the CGM.

Atacama Large Aperture Submillimeter Telescope (AtLAST) science: Surveying the distant Universe.

During the most active period of star formation in galaxies, which occurs in the redshift range 1 3, strong bursts of star formation result in significant quantities of dust, which obscures new stars being formed as their UV/optical light is absorbed and then re-emitted in the infrared, which redshifts into the mm/sub-mm bands for these early times. To get a complete picture of the high- galaxy population, we need to survey a large patch of the sky in the sub-mm with sufficient angular resolution to resolve all galaxies, but we also need the depth to fully sample their cosmic evolution, and therefore obtain their redshifts using direct mm spectroscopy with a very wide frequency coverage. This requires a large single-dish sub-mm telescope with fast mapping speeds at high sensitivity and angular resolution, a large bandwidth with good spectral resolution and multiplex spectroscopic capabilities.

Science development study for the Atacama Large Aperture Submillimeter Telescope (AtLAST): Solar and stellar observations.

Observations at (sub-)millimeter wavelengths offer a complementary perspective on our Sun and other stars, offering significant insights into both the thermal and magnetic composition of their chromospheres. Despite the fundamental progress in (sub-)millimeter observations of the Sun, some important aspects require diagnostic capabilities that are not offered by existing observatories. In particular, simultaneously observations of the radiation continuum across an extended frequency range would facilitate the mapping of different layers and thus ultimately the 3D structure of the solar atmosphere.

Representation of older patients in the safety analysis of protein kinase inhibitor registration studies.

Introduction: Older patients (≥65 years old) make up the majority of the cancer population. Older patients seem to experience more adverse events (AEs) from protein kinase inhibitors (PKIs) in clinical practice. Yet they are underrepresented in clinical trials.

The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines.

This work gives a brief overview of carrier materials currently used in pharmaceutical studies on the three-dimensional (3D) semi-solid extrusion (SSE) printing of medicines for pediatrics. The suitability of using these carrier materials in pediatric formulations, concerning safety and toxicity, was reviewed by consulting the 'Safety & Toxicity of Excipients for Pediatrics' (STEP) database and the Food and Drug Administration (FDA) regulations. In the second part of this work, carrier materials were tested on their ability to form a semi-solid mixture with lactose by dual asymmetric centrifugation (DAC) and printing by SSE.

3D printed, personalized sustained release cortisol for patients with adrenal insufficiency.

The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluctuations associated with negative health outcomes. Furthermore, there is a high inter-individual variability in cortisol need, necessitating a personalized approach.

Safe-by-Design in Engineering: An Overview and Comparative Analysis of Engineering Disciplines.

In this paper, we provide an overview of how Safe-by-Design is conceived and applied in practice in a large number of engineering disciplines. We discuss the differences, commonalities, and possibilities for mutual learning found in those practices and identify several ways of putting those disciplinary outlooks in perspective. The considered engineering disciplines in the order of historically grown technologies are construction engineering, chemical engineering, aerospace engineering, urban engineering, software engineering, bio-engineering, nano-engineering, and finally cyber space engineering.

Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery.

Skin is an attractive but also very challenging immunisation site for particulate subunit vaccines. The aim of this study was to develop hyaluronan (HA)-based dissolving microneedles (MNs) loaded with PLGA nanoparticles (NPs) co-encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunisation. The NP:HA ratio used for the preparation of dissolving MNs appeared to be critical for the quality of MNs and their dissolution in ex vivo human skin.

Design of Hollow Hyaluronic Acid Cylinders for Sustained Intravitreal Protein Delivery.

A hollow cylinder intravitreal implant was developed to achieve sustained release of protein to the retina for the treatment of retinal diseases. Hollow cylinders were fabricated by molding and cross-linking hyaluronic acid, the major component of the vitreous humor. Hollow cylinders were filled with a concentrated protein solution, and the properties of the cylinder walls were tested.

Superior calvarial bone regeneration using pentenoate-functionalized hyaluronic acid hydrogels with devitalized tendon particles.

Unlabelled: Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation. Severe TBI is commonly treated by a two-stage surgical intervention, where decompressive craniectomy is first conducted to remove a large portion of calvarial bone and allow unimpeded brain swelling. In the second surgery, spaced weeks to months after the first, cranioplasty is performed to restore the cranial bone.

Safe Exploration Algorithms for Reinforcement Learning Controllers.

Self-learning approaches, such as reinforcement learning, offer new possibilities for autonomous control of uncertain or time-varying systems. However, exploring an unknown environment under limited prediction capabilities is a challenge for a learning agent. If the environment is dangerous, free exploration can result in physical damage or in an otherwise unacceptable behavior.

Hematopoietic arginase 1 deficiency results in decreased leukocytosis and increased foam cell formation but does not affect atherosclerosis.

Background And Aims: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages.

Orp8 deficiency in bone marrow-derived cells reduces atherosclerotic lesion progression in LDL receptor knockout mice.

Introduction: Oxysterol binding protein Related Proteins (ORPs) mediate intracellular lipid transport and homeostatic regulation. ORP8 downregulates ABCA1 expression in macrophages and cellular cholesterol efflux to apolipoprotein A-I. In line, ORP8 knockout mice display increased amounts of HDL cholesterol in blood.

Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis.

Alterations in DNA methylation patterns in peripheral blood leukocytes precede atherosclerotic lesion development in mouse models of atherosclerosis and have been linked to cardiovascular death in patients. The aim of this study is to investigate the long-term changes induced by WTD feeding on BM cells and the consequences for atherosclerosis susceptibility. Hereto, WTD BM or Chow BM was transplanted into LDLR KO mice on chow.

Risk and protective factors associated with symptoms of post-traumatic stress, depression, and alcohol misuse in OEF/OIF veterans.

Military personnel returning from the conflicts in Iraq and Afghanistan commonly experience mental health problems and efforts are underway to determine risk and protective factors associated with postdeployment mental health concerns. This study examined the contribution of trait neuroticism, predeployment life events, combat experience, perceptions of threat, and postdeployment social support on mental health symptoms at 6 months, 12 months, and 24 months postdeployment. Two hundred seventy-one veterans completed self-report measures.

Neural network modulation by trauma as a marker of resilience: differences between veterans with posttraumatic stress disorder and resilient controls.

Importance: Posttraumatic stress disorder (PTSD) and resilience reflect 2 distinct outcomes after exposure to potentially traumatic events. The neural mechanisms underlying these different outcomes are not well understood.

Objective: To examine the effect of trauma on synchronous neural interactions for veterans with PTSD and resilient controls using magnetoencephalography.

Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

Aims: Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function.

Methods And Results: Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression.

Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behavior.

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.

Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression.

Activation of transcription factors by receptor mediated signaling is an essential step for T lymphocyte effector function. Following antigenic stimulation of T cells the two central cytokines IL-2 and TNFalpha are co-expressed and co-regulated. Two important transcription factors, i.

Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H.

Factor H (FH) is a potent suppressor of the alternative pathway of C in plasma and when bound to sialic acid- or glycosaminoglycan-rich surfaces. Of the three interaction sites on FH for C3b, one interacts with the C3d part of C3b. In this study, we generated recombinant constructs of FH and FH-related proteins (FHR) to define the sites required for binding to C3d.