Horizon effects with surface waves on moving water

Surface waves on a stationary flow of water are considered, in a linear model that includes the surface tension of the fluid. The resulting gravity-capillary waves experience a rich array of horizon effects when propagating against the flow. In some cases three horizons (points where the group velocity of the wave reverses) exist for waves with a single laboratory frequency. Some of these effects are familiar in fluid mechanics under the name of wave blocking, but other aspects, in particular waves with negative co-moving frequency and the Hawking effect, were overlooked until surface waves were investigated as examples of analogue gravity [Sch\"utzhold R and Unruh W G 2002 Phys. Rev. D 66 044019]. A comprehensive presentation of the various horizon effects for gravity-capillary waves is given, with emphasis on the deep water/short wavelength case kh>>1 where many analytical results can be derived. A similarity of the state space of the waves to that of a thermodynamic system is pointed out.Comment: 30 pages, 15 figures. Minor change

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r’s ≥ 0.35; P’s < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself

3D characterization of CdSe nanoparticles attached to carbon nanotubes

The crystallographic structure of CdSe nanoparticles attached to carbon nanotubes has been elucidated by means of high resolution transmission electron microscopy and high angle annular dark field scanning transmission electron microscopy tomography. CdSe rod-like nanoparticles, grown in solution together with carbon nanotubes, undergo a morphological transformation and become attached to the carbon surface. Electron tomography reveals that the nanoparticles are hexagonal-based with the (001) planes epitaxially matched to the outer graphene layer.Comment: 7 pages, 8 figure

Artifacts In Magnetic Resonance Imaging and Computed Tomography Caused By Dental Materials

BACKGROUND: Artifacts caused by dental restorations, such as dental crowns, dental fillings and orthodontic appliances, are a common problem in MRI and CT scans of the head and neck. The aim of this in-vitro study was to identify and evaluate the artifacts produced by different dental restoration materials in CT and MRI images. METHODS: Test samples of 44 materials (Metal and Non-Metal) commonly used in dental restorations were fabricated and embedded with reference specimens in gelatin moulds. MRI imaging of 1.5T and CT scan were performed on the samples and evaluated in two dimensions. Artifact size and distortions were measured using a digital image analysis software. RESULTS: In MRI, 13 out of 44 materials produced artifacts, while in CT 41 out of 44 materials showed artifacts. Artifacts produced in both MRI and CT images were categorized according to the size of the artifact. SIGNIFICANCE: Metal based restoration materials had strong influence on CT and less artifacts in MRI images. Rare earth elements such as Ytterbium trifluoride found in composites caused artifacts in both MRI and CT. Recognizing these findings would help dental materials manufacturers and developers to produce materials which can cause less artifacts in MRI and CT images

A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales

Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket was accessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates. The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1

Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer

Background A contemporary view of the cancer genome reveals extensive rearrangement compared to normal cells. Yet how these genetic alterations translate into specific proteomic changes that underpin acquiring the hallmarks of cancer remains unresolved. The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer. Results A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. We observed protein ubiquitination and apoptosis signaling pathways were both enriched in the two breast cancer models while IGF signaling and cell motility pathways were enriched in BT474 and amino acid metabolism were enriched in the SKBR3 cell line. Conclusion While protein ubiquitination and apoptosis signaling pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared to 184A1

The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis.

The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis. Accordingly, we detected elevated levels of 25-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol in mice with acute colonic inflammation. Knockout of EBI2 or CH25H did not affect severity of DSS colitis; however, inflammation was decreased in male EBI2 &lt;sup&gt;-/-&lt;/sup&gt; mice in the IL-10 colitis model. The colonic immune system comprises mucosal lymphoid structures, which accumulate upon chronic inflammation in IL-10-deficient mice and in chronic DSS colitis. However, EBI2 &lt;sup&gt;-/-&lt;/sup&gt; mice formed significantly less colonic lymphoid structures at baseline and showed defects in inflammation-induced accumulation of lymphoid structures. In summary, we report induction of the EBI2-7α,25-dihydroxycholesterol axis in colitis and a role of EBI2 for the accumulation of lymphoid tissue during homeostasis and inflammation. These data implicate the EBI2-7α,25-dihydroxycholesterol axis in IBD pathogenesis

Facile Hydrogen Evolution Reaction on WO3Nanorods

Tungsten trioxide nanorods have been generated by the thermal decomposition (450 °C) of tetrabutylammonium decatungstate. The synthesized tungsten trioxide (WO3) nanorods have been characterized by XRD, Raman, SEM, TEM, HRTEM and cyclic voltammetry. High resolution transmission electron microscopy and X-ray diffraction analysis showed that the synthesized WO3nanorods are crystalline in nature with monoclinic structure. The electrochemical experiments showed that they constitute a better electrocatalytic system for hydrogen evolution reaction in acid medium compared to their bulk counterpart