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BACKGROUND: The aim of this case study was to investigate the safety and efficacy of the SONG Laser Protocol in the context of dementia. Our hypothesis is that the SONG Laser Protocol, when administered intravenously, may have a beneficial effect on the alpha waves [as assessed by electroencephalography (EEG)] in a patient suffering from dementia. CASE REPORT: This was a case study focusing on a single patient suffering from dementia. The SONG Laser Protocol was delivered in a clinical setting, and the primary outcome measures were the amplitude of alpha waves as seen in EEG, the target frequency of the alpha waves, and the power spectrum density. The pre- and post-SONG Laser Protocol EEGs were compared. A clear increase in alpha wave activity on Day 3 post-SONG Laser Protocol was detected. The alpha wave target frequency increased to 8.0 (normal range 8.0-12.0), and the power spectrum density (PSD) increased by 65%. The patient also expressed feelings of improved well-being following the SONG Laser Protocol. CONCLUSIONS: The SONG Laser Protocol may have a beneficial effect on alpha wave activity in a patient suffering from dementia. Clinical trials are needed to confirm safety and efficacy.

A global in situ data set for validation of ocean colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI) is presented. This version of the compilation, starting in 1997, now extends to 2021, which is important for the validation of the most recent satellite optical sensors such as Sentinel 3B OLCI and NOAA-20 VIIRS. The data set comprises in situ observations of the following variables: spectral remote-sensing reflectance, concentration of chlorophyll-a, spectral inherent optical properties, spectral diffuse attenuation coefficient, and total suspended matter. Data were obtained from multi-project archives acquired via open internet services or from individual projects acquired directly from data providers. Methodologies were implemented for homogenization, quality control, and merging of all data. Minimal changes were made on the original data, other than conversion to a standard format, elimination of some points, after quality control and averaging of observations that were close in time and space. The result is a merged table available in text format. Overall, the size of the data set grew with 148 432 rows, with each row representing a unique station in space and time (cf. 136 250 rows in previous version; Valente et al., 2019). Observations of remote-sensing reflectance increased to 68 641 (cf. 59 781 in previous version; Valente et al., 2019). There was also a near tenfold increase in chlorophyll data since 2016. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) are included in the final table. By making the metadata available, provenance is better documented and it is also possible to analyse each set of data separately. The compiled data are available at https://doi.org/10.1594/PANGAEA.941318 (Valente et al., 2022).

Since the mid-1990s, Australia's Commonwealth Science Industry and Research Organisation (CSIRO) has been developing a biogeochemical (BGC) model for coupling with a hydrodynamic and sediment model for application in estuaries, coastal waters and shelf seas. The suite of coupled models is referred to as the CSIRO Environmental Modelling Suite (EMS) and has been applied at tens of locations around the Australian continent. At a mature point in the BGC model's development, this paper presents a full mathematical description, as well as links to the freely available code and user guide. The mathematical description is structured into processes so that the details of new parameterisations can be easily identified, along with their derivation. In EMS, the underwater light field is simulated by a spectrally resolved optical model that calculates vertical light attenuation from the scattering and absorption of 20+ optically active constituents. The BGC model itself cycles carbon, nitrogen, phosphorous and oxygen through multiple phytoplankton, zooplankton, detritus and dissolved organic and inorganic forms in multiple water column and sediment layers. The water column is dynamically coupled to the sediment to resolve deposition, resuspension and benthic–pelagic biogeochemical fluxes. With a focus on shallow waters, the model also includes detailed representations of benthic plants such as seagrass, macroalgae and coral polyps. A second focus has been on, where possible, the use of geometric derivations of physical limits to constrain ecological rates. This geometric approach generally requires population-based rates to be derived from initially considering the size and shape of individuals. For example, zooplankton grazing considers encounter rates of one predator on a prey field based on summing relative motion of the predator with the prey individuals and the search area; chlorophyll synthesis includes a geometrically derived self-shading term; and the bottom coverage of benthic plants is calculated from their biomass using an exponential form derived from geometric arguments. This geometric approach has led to a more algebraically complicated set of equations when compared to empirical biogeochemical model formulations based on populations. But while being algebraically complicated, the model has fewer unconstrained parameters and is therefore simpler to move between applications than it would otherwise be. The version of EMS described here is implemented in the eReefs project that delivers a near-real-time coupled hydrodynamic, sediment and biogeochemical simulation of the Great Barrier Reef, northeast Australia, and its formulation provides an example of the application of geometric reasoning in the formulation of aquatic ecological processes.

A global compilation of in situ data is useful to evaluate the quality of ocean-colour satellite data records. Here we describe the data compiled for the validation of the ocean-colour products from the ESA Ocean Colour Climate Change Initiative (OC-CCI). The data were acquired from several sources (including, inter alia, MOBY, BOUSSOLE, AERONET-OC, SeaBASS, NOMAD, MERMAID, AMT, ICES, HOT and GeP&CO) and span the period from 1997 to 2018. Observations of the following variables were compiled: spectral remote-sensing reflectances, concentrations of chlorophyll a, spectral inherent optical properties, spectral diffuse attenuation coefficients and total suspended matter. The data were from multi-project archives acquired via open internet services or from individual projects, acquired directly from data providers. Methodologies were implemented for homogenization, quality control and merging of all data. No changes were made to the original data, other than averaging of observations that were close in time and space, elimination of some points after quality control and conversion to a standard format. The final result is a merged table designed for validation of satellite-derived ocean-colour products and available in text format. Metadata of each in situ measurement (original source, cruise or experiment, principal investigator) was propagated throughout the work and made available in the final table. By making the metadata available, provenance is better documented, and it is also possible to analyse each set of data separately. This paper also describes the changes that were made to the compilation in relation to the previous version (Valente et al., 2016). The compiled data are available at https://doi.org/10.1594/PANGAEA.898188 (Valente et al., 2019).

Biotechnology students entering the workforce often struggle in their application of textbook knowledge to build the solutions that we see in science and health fields today. Some students may be naive to what a job in the biotechnology industry can encompass. Students should graduate having a firm grasp of the prospects of their field and have the confidence to begin contributing to the growth of the industry. For this, it is necessary for students to be able to start practising applications in their coursework before they graduate. A competition titled "Biotech BioBrawl" was incorporated in the University of Central Florida's Methods in Biotechnology (MCB4721C/MCB5722C) course agenda during the semester of Fall 2021. This competition challenged students to harness innovation and applied science in a group setting that led to the development and pitch of an original idea to a panel of judges with various biotechnology industry experiences.

Skillful marine biogeochemical (BGC) models are required to understand a range of coastal and global phenomena such as changes in nitrogen and carbon cycles. The refinement of BGC models through the assimilation of variables calculated from observed in-water inherent optical properties (IOPs), such as phytoplankton absorption, is problematic. Empirically derived relationships between IOPs and variables such as chlorophyll-a concentration (Chl a), total suspended solids (TSS) and coloured dissolved organic matter (CDOM) have been shown to have errors that can exceed 100 % of the observed quantity. These errors are greatest in shallow coastal regions, such as the Great Barrier Reef (GBR), due to the additional signal from bottom reflectance. Rather than assimilate quantities calculated using IOP algorithms, this study demonstrates the advantages of assimilating quantities calculated directly from the less error-prone satellite remote-sensing reflectance (RSR). To assimilate the observed RSR, we use an in-water optical model to produce an equivalent simulated RSR and calculate the mismatch between the observed and simulated quantities to constrain the BGC model with a deterministic ensemble Kalman filter (DEnKF). The traditional assumption that simulated surface Chl a is equivalent to the remotely sensed OC3M estimate of Chl a resulted in a forecast error of approximately 75 %. We show this error can be halved by instead using simulated RSR to constrain the model via the assimilation system. When the analysis and forecast fields from the RSR-based assimilation system are compared with the non-assimilating model, a comparison against independent in situ observations of Chl a, TSS and dissolved inorganic nutrients (NO3, NH4 and DIP) showed that errors are reduced by up to 90 %. In all cases, the assimilation system improves the simulation compared to the non-assimilating model. Our approach allows for the incorporation of vast quantities of remote-sensing observations that have in the past been discarded due to shallow water and/or artefacts introduced by terrestrially derived TSS and CDOM or the lack of a calibrated regional IOP algorithm.

The use of in situ measurements is essential in the validation and evaluation of the algorithms that provide coastal water quality data products from ocean colour satellite remote sensing. Over the past decade, various types of ocean colour algorithms have been developed to deal with the optical complexity of coastal waters. Yet there is a lack of a comprehensive intercomparison due to the availability of quality checked in situ databases. The CoastColour Round Robin (CCRR) project, funded by the European Space Agency (ESA), was designed to bring together three reference data sets using these to test algorithms and to assess their accuracy for retrieving water quality parameters. This paper provides a detailed description of these reference data sets, which include the Medium Resolution Imaging Spectrometer (MERIS) level 2 match-ups, in situ reflectance measurements, and synthetic data generated by a radiative transfer model (HydroLight). These data sets, representing mainly coastal waters, are available from doi:10.1594/PANGAEA.841950. The data sets mainly consist of 6484 marine reflectance (either multispectral or hyperspectral) associated with various geometrical (sensor viewing and solar angles) and sky conditions and water constituents: total suspended matter (TSM) and chlorophyll a (CHL) concentrations, and the absorption of coloured dissolved organic matter (CDOM). Inherent optical properties are also provided in the simulated data sets (5000 simulations) and from 3054 match-up locations. The distributions of reflectance at selected MERIS bands and band ratios, CHL and TSM as a function of reflectance, from the three data sets are compared. Match-up and in situ sites where deviations occur are identified. The distributions of the three reflectance data sets are also compared to the simulated and in situ reflectances used previously by the International Ocean Colour Coordinating Group (IOCCG, 2006) for algorithm testing, showing a clear extension of the CCRR data which covers more turbid waters.

COVID-19 posed new challenges to undergraduate medical biochemistry instructors, providing an opportunity of exploring novel approaches online through methods such as case-based learning curriculum. In this study, an entire curriculum was created for medical biochemistry teaching online using case-based learning including the standards, time for lessons, cases, and methods behind teaching in an online format. To evaluate the effectiveness of the curriculum, student case study question results, grades on exams, and perception were analyzed. The results show that 40 students enrolled in the case-based learning curriculum had an average final exam score of 10.33% (95% CI [3.539,17.112], p = 0.004) higher compared to the traditional curriculum students (d = 0.861, 95% CI [0.269, 1.444]).No significant difference was found between exam scores on any other exam in the course. Due to the final exam being a cumulative exam, the results suggest that the case-based learning curriculum improved student retention of information long-term but had no discernible effect on individual exams. This study provides all the tools necessary for instructors to immediately use a medical biochemistry case-based learning curriculum supported by research without the necessary time investment of creating their own cases from scratch.

We report the observation of field emission (FE) from InP nanocrystals (NCs) epitaxially grown on an array of p-Si nanotips. We prove that FE can be enhanced by covering the InP NCs with graphene. The measurements are performed inside a scanning electron microscope chamber with a nano-controlled W-thread used as an anode. We analyze the FE by Fowler–Nordheim theory and find that the field enhancement factor increases monotonically with the spacing between the anode and the cathode. We also show that InP/p-Si junction has a rectifying behavior, while graphene on InP creates an ohmic contact. Understanding the fundamentals of such nanojunctions is key for applications in nanoelectronics. [ABSTRACT FROM AUTHOR]

Unveiling the physical nature of the oxygen-deficient conductive filaments (CFs) that are responsible for the resistive switching of the HfO2-based resistive random access memory (RRAM) devices represents a challenging task due to the oxygen vacancy related defect nature and nanometer size of the CFs. As a first important step to this goal, we demonstrate in this work direct visualization and a study of physico–chemical properties of oxygen-deficient amorphous HfO2−x by carrying out transmission electron microscopy electron holography as well as energy dispersive x-ray spectroscopy on HfO2/HfO2−x bilayer heterostructures, which are realized by reactive molecular beam epitaxy. Furthermore, compared to single layer devices, Pt/HfO2/HfO2−x/TiN bilayer devices show enhanced resistive switching characteristics with multilevel behavior, indicating their potential as electronic synapses in future neuromorphic computing applications. [ABSTRACT FROM AUTHOR]

The formation of new ternary NiGeSn and quaternary NiSiGeSn alloys has been investigated to fabricate metallic contacts on high Sn content, potentially direct bandgap group IV semiconductors. (Si)GeSn layers were pseudomorphically grown on Ge buffered Si(001) by reduced pressure chemical vapor deposition. Ni, i.e. the metal of choice for source/drain metallization in Si nanoelectronics, is employed for the stano-(silicon)-germanidation of highly strained (Si)GeSn alloys. We show that NiGeSn on GeSn layers change phase from well-oriented Ni5(GeSn)3 to poly-crystalline Ni1(GeSn)1 at very low annealing temperatures. A large range of GeSn compositions with Sn concentrations up to 12 at.%, and SiGeSn ternaries with large Si and Sn compositions from 18%/3% to 4%/11% are investigated. In addition, the sheet resistance, of importance for electronic or optoelectronic device contacts, is quantified. The incorporation of Si extends the thermal stability of the resulting low resistive quaternary phase compared to their NiGeSn counterparts. [ABSTRACT FROM AUTHOR]

The reactive growth of cobalt germanide on Ge(001) was investigated by means of in situ x-ray absorption spectroscopy photoemission electron microscopy (XAS-PEEM), micro-illumination low-energy electron diffraction (μ-LEED), and ex situ atomic force microscopy (AFM). At a Co deposition temperature of 670 °C, a rich morphology with different island shapes and dimensions is observed, and a correlation between island morphology and stoichiometry is found. By combining XAS-PEEM and μ-LEED, we were able to identify a large part of the islands to consist of CoGe2, with many of them having an unusual epitaxial relationship: CoGe2 Ge . Side facets with (112) and (113) orientation have been found for such islands. However, two additional phases were observed, most likely Co5Ge7 and CoGe. Comparing growth on Ge(001) single crystals and on Ge(001)/Si(001) epilayer substrates, the occurrence of these intermediate phases seems to be promoted by defects or residual strain. [ABSTRACT FROM AUTHOR]

Nickel germanide is deemed an excellent material system for low resistance contact formation for future Ge device modules integrated into mainstream, Si-based integrated circuit technologies. In this study, we present a multi-technique experimental study on the formation processes of nickel germanides on Ge(001). We demonstrate that room temperature deposition of ∼1 nm of Ni on Ge(001) is realized in the Volmer–Weber growth mode. Subsequent thermal annealing results first in the formation of a continuous NixGey wetting layer featuring well-defined terrace morphology. Upon increasing the annealing temperature to 300 °C, we observed the onset of a de-wetting process, characterized by the appearance of voids on the NixGey terraces. Annealing above 300 °C enhances this de-wetting process and the surface evolves gradually towards the formation of well-ordered, rectangular NixGey 3D nanostructures. Annealing up to 500 °C induces an Ostwald ripening phenomenon, with smaller nanoislands disappearing and larger ones increasing their size. Subsequent annealing to higher temperatures drives the Ni-germanide diffusion into the bulk and the consequent formation of highly ordered, {111} faceted Ni-Ge nanocrystals featuring an epitaxial relationship with the substrate Ni-Ge (101); (010) || Ge(001); (110). [ABSTRACT FROM AUTHOR]

We investigate the structural properties and strain state of Ge nano-structures selectively grown on Si pillars of about 60 nm diameter with different SiGe buffer layers. A matrix of TEOS SiO2 surrounding the Si nano-pillars causes a tensile strain in the top part at the growth temperature of the buffer that reduces the misfit and supports defect-free initial growth. Elastic relaxation plays the dominant role in the further increase of the buffer thickness and subsequent Ge deposition. This method leads to Ge nanostructures on Si that are free from misfit dislocations and other structural defects, which is not the case for direct Ge deposition on these pillar structures. The Ge content of the SiGe buffer is thereby not a critical parameter; it may vary over a relatively wide range. [ABSTRACT FROM AUTHOR]

The formation of new ternary NiGeSn and quaternary NiSiGeSn alloys has been investigated to fabricate metallic contacts on high Sn content, potentially direct bandgap group IV semiconductors. (Si)GeSn layers were pseudomorphically grown on Ge buffered Si(001) by reduced pressure chemical vapor deposition. Ni, i.e. the metal of choice for source/drain metallization in Si nanoelectronics, is employed for the stano-(silicon)-germanidation of highly strained (Si)GeSn alloys. We show that NiGeSn on GeSn layers change phase from well-oriented Ni5(GeSn)3 to poly-crystalline Ni1(GeSn)1 at very low annealing temperatures. A large range of GeSn compositions with Sn concentrations up to 12 at.%, and SiGeSn ternaries with large Si and Sn compositions from 18%/3% to 4%/11% are investigated. In addition, the sheet resistance, of importance for electronic or optoelectronic device contacts, is quantified. The incorporation of Si extends the thermal stability of the resulting low resistive quaternary phase compared to their NiGeSn counterparts. [ABSTRACT FROM AUTHOR]

We use controlled annealing to tune the interfacial properties of a sub-monolayer and monolayer coverages of Ba atoms deposited on Ge(001), enabling the generation of either of two fundamentally distinct interfacial phases, as revealed by scanning tunneling microscopy. Firstly we identify the two key structural phases associated with this adsorption system, namely on-top adsorption and surface alloy formation, by performing a deposition and annealing experiment at a coverage low enough (∼0.15 ML) that isolated Ba-related features can be individually resolved. Subsequently we investigate the monolayer coverage case, of interest for passivation schemes of future Ge based devices, for which we find that the thermal evaporation of Ba onto a Ge(001) surface at room temperature results in on-top adsorption. This separation (lack of intermixing) between Ba and Ge layers is retained through successive annealing steps to temperatures of 470, 570, 670 and 770 K although a gradual ordering of the Ba layer is observed at 570 K and above, accompanied by a decrease in Ba layer density. Annealing above 770 K produces the 2D surface alloy phase accompanied by strain relief through monolayer height trench formation. An annealing temperature of 1070 K sees a further change in surface morphology but retention of the 2D surface alloy characteristic. These results are discussed in view of their possible implications for future semiconductor integrated circuit technology. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a dramatic sex bias, affecting 9 times more women than men. Activation of Toll-like receptor 7 (TLR7) by self-RNA is a central pathogenic process leading to aberrant production of type I interferon (IFN) in SLE, but the specific RNA molecules that serve as TLR7 ligands have not been defined. By leveraging gene expression data and the known sequence specificity of TLR7, we identified the female-specific X-inactive specific transcript (XIST) long noncoding RNA as a uniquely rich source of TLR7 ligands in SLE. XIST RNA stimulated IFN-α production by plasmacytoid DCs in a TLR7-dependent manner, and deletion of XIST diminished the ability of whole cellular RNA to activate TLR7. XIST levels were elevated in blood leukocytes from women with SLE compared with controls, correlated positively with disease activity and the IFN signature, and were enriched in extracellular vesicles released from dying cells in vitro. Importantly, XIST was not IFN inducible, suggesting that XIST is a driver, rather than a consequence, of IFN in SLE. Overall, our work elucidated a role for XIST RNA as a female sex–specific danger signal underlying the sex bias in SLE.

Background: The linkage of HLA-DQB1*0301 to autoimmune disorders is becoming more common in literature. Despite bullous pemphigoid (BP) and pemphigus vulgaris (PV) both having similar symptoms, such as blistering skin conditions, research has shown different relationships with HLAs. Methods: In this systematic review, HLA-DQB1*0301 and the odds of developing BP and PV were explored. Google Scholar and Pubmed were consulted, and articles were included if living subjects were used, odds ratio was available or could be ascertained from the study, and if it was not a meta-analysis of other researcher’s works. MetaXL software was used to generate data for analysis and a forest plot was generated for each. Nine studies conducted between 1996 and 2021 met study selection criteria for the BP HLA-DQB1*0301 meta-analysis (1,340 patients and 6,673 controls) and five studies (247 patients and 2,435 controls) for PV. Results: HLA-DQB1*0301 increased the odds of developing BP (OR= 1.64, 95% CI [1.44, 1.87], I2= 0%) yet decreased odds of PV (OR= 0.60, 95% CI [0.40, 0.89], I2= 34%). Conclusion: Results suggest HLA-DQB1*0301 may serve opposite roles in BP and PV despite similarity in symptoms, finding higher odds for developing BP versus lower odds for developing PV. Understanding this HLA’s function in each requires further exploration. Limitations of the analysis included minor asymmetry in the PV Doi plot, suggesting publication bias. No funding was used; study protocol was not registered.

Basophils bind IgE via FcεRI-αβγ2, which they uniquely share only with mast cells. In doing so, they can rapidly release mediators that are hallmark of allergic disease. This fundamental similarity, along with some morphological features shared by the two cell types, has long brought into question the biological significance that basophils mediate beyond that of mast cells. Unlike mast cells, which mature and reside in tissues, basophils are released into circulation from the bone marrow (constituting 1% of leukocytes), only to infiltrate tissues under specific inflammatory conditions. Evidence is emerging that basophils mediate non-redundant roles in allergic disease and, unsuspectingly, are implicated in a variety of other pathologies [e.g., myocardial infarction, autoimmunity, chronic obstructive pulmonary disease, fibrosis, cancer, etc.]. Recent findings strengthen the notion that these cells mediate protection from parasitic infections, whereas related studies implicate basophils promoting wound healing. Central to these functions is the substantial evidence that human and mouse basophils are increasingly implicated as important sources of IL-4 and IL-13. Nonetheless, much remains unclear regarding the role of basophils in pathology vs. homeostasis. In this review, we discuss the dichotomous (protective and/or harmful) roles of basophils in a wide spectrum of non-allergic disorders.

Human basophils, first identified over 140 years ago, account for just 0.5-1% of circulating leukocytes. While this scarcity long hampered basophil studies, innovations during the past 30 years, beginning with their isolation and more recently in the development of mouse models, have markedly advanced our understanding of these cells. Although dissimilarities between human and mouse basophils persist, the overall findings highlight the growing importance of these cells in health and disease. Indeed, studies continue to support basophils as key participants in IgE-mediated reactions, where they infiltrate inflammatory lesions, release pro-inflammatory mediators (histamine, leukotriene C4: LTC4) and regulatory cytokines (IL-4, IL-13) central to the pathogenesis of allergic diseases. Studies now report basophils infiltrating various human cancers where they play diverse roles, either promoting or hampering tumorigenesis. Likewise, this activity bears remarkable similarity to the mounting evidence that basophils facilitate wound healing. In fact, both activities appear linked to the capacity of basophils to secrete IL-4/IL-13, with these cytokines polarizing macrophages toward the M2 phenotype. Basophils also secrete several angiogenic factors (vascular endothelial growth factor: VEGF-A, amphiregulin) consistent with these activities. In this review, we feature these newfound properties with the goal of unraveling the increasing importance of basophils in these diverse pathobiological processes.

BackgroundAllergic drug reaction or drug allergy is an immunologically mediated drug hypersensitivity reaction (DHR). G-protein coupled receptors (GPCRs) are common drug targets and communicate extracellular signals that initiate cellular responses. Recent evidence shows that GPCR MRGPRX2 is of major importance in IgE-independent pseudo-allergic DHRs based on the suspected interactions between many FDA-approved peptidergic compounds and MRGPRX2.ObjectiveOur aim was to uncover novel MRGPRX2-selective and -potent agonists as drug candidates responsible for clinical features of pseudo-allergic DHRs.MethodsWe conducted a primary high-throughput screening (HTS), coupled with mutagenesis targeting the MRGPRX2 N62S mutation, on a panel of 3,456 library compounds. We discovered pharmacologically active hit compounds as agonists of the MRGPRX2 protein according to high degrees of potency evaluated by the calcium response and validated by the degranulation assay. Using the molecular tool Forge, we also characterized the structure-activity relationship shared by identified hit compounds.ResultsThe alternative allele of single nucleotide polymorphism rs10833049 (N62S) in MRGPRX2 demonstrated loss-of-function property in response to substance P and antineoplastic agent daunorubicin hydrochloride. We applied a unique assay system targeting the N62S mutation to the HTS and identified 84 MRGPRX2-selective active hit compounds representing diverse classes according to primary drug indications. The top five highly represented groups included fluoroquinolone and non-fluoroquinolone antibiotics; antidepressive/antipsychotic; antihistaminic and antineoplastic agents. We classified hit compounds into 14 clusters representing a variety of chemical and drug classes beyond those reported, such as opioids, neuromuscular blocking agents, and fluoroquinolones. We further demonstrated MRGPRX2-dependent degranulation in the human mast cell line LAD2 cells induced by three novel agonists representing the non-fluoroquinolone antibiotics (bacitracin A), anti-allergic agents (brompheniramine maleate) and tyrosine-kinase inhibitors (imatinib mesylate).ConclusionOur findings could facilitate the development of interventions for personalized prevention and treatment of DHRs, as well as future pharmacogenetic investigations of MRGPRX2 in relevant disease cohorts.

While research in the learning sciences has spurred advancements in educational technology, the implementation of those learning resources in natural learning contexts advances teaching and learning. In this paper, two faculty members at the University of Central Florida used courseware generated with artificial intelligence as the primary learning resource for their students. The selection and enhancement of this courseware is contextualized for each course. Instructor implementation practices over multiple semesters are described and related to resulting student engagement and exam scores. Finally, benefits of the adaptive courseware are discussed not only for student outcomes, but the qualitative changes faculty identified and the impact that iterative changes in teaching practice had on instructors as well as students.

Abstract During locomotion, humans sometimes entrain (i.e. synchronize) their steps to external oscillations: e.g. swaying bridges, tandem walking, bouncy harnesses, vibrating treadmills, exoskeletons. Previous studies have discussed the role of nonlinear oscillators (e.g. central pattern generators) in facilitating entrainment. However, the energetics of such interactions are unknown. Given substantial evidence that humans prioritize economy during locomotion, we tested whether reduced metabolic expenditure is associated with human entrainment to vertical force oscillations, where frequency and amplitude were prescribed via a custom mechatronics system during walking. Although metabolic cost was not significantly reduced during entrainment, individuals expended less energy when the oscillation forces did net positive work on the body and roughly selected phase relationships that maximize positive work. It is possible that individuals use mechanical cues to infer energy cost and inform effective gait strategies. If so, an accurate prediction may rely on the relative stability of interactions with the environment. Our results suggest that entrainment occurs over a wide range of oscillation parameters, though not as a direct priority for minimizing metabolic cost. Instead, entrainment may act to stabilize interactions with the environment, thus increasing predictability for the effective implementation of internal models that guide energy minimization.

Epithelial-derived alarmins (IL-33, TSLP, and IL-25) play an upstream role in the pathogenesis of asthma. Basophil-derived cytokines are a pivotal component of allergic inflammation. We evaluated the in vitro effects of IL-33, TSLP, and IL-25, alone and in combination with IL-3 on purified peripheral blood human basophils (hBaso) and bone marrow-derived mouse basophils (mBaso) in modulating the production of IL-4, IL-13, CXCL8 or the mouse CXCL8 equivalents CXCL1 and CXCL2. IL-3 and IL-33, but not TSLP and IL-25, concentration-dependently induced IL-4, IL-13, and CXCL8 release from hBaso. IL-3 synergistically potentiated the release of cytokines induced by IL-33 from hBaso. In mBaso, IL-3 and IL-33 rapidly induced IL-4 and IL-13 mRNA expression and protein release. IL-33, but not IL-3, induced CXCL2 and CXCL1 from mBaso. Differently from hBaso, TSLP induced IL-4, IL-13, CXCL1 and CXCL2 mRNA expression and protein release from mBaso. IL-25 had no effect on IL-4, IL-13, and CXCL1/CXCL2 mRNA expression and protein release even in the presence of IL-3. No synergism was observed between IL-3 and either IL-25 or TSLP. IL-3 inhibited both TSLP- and IL-33-induced CXCL1 and CXCL2 release from mBaso. Our results highlight some similarities and marked differences between the effects of IL-3 and alarmins on the release of cytokines from human and mouse basophils.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly evolved into a pandemic –the likes of which has not been experienced in 100 years. While novel vaccines show great efficacy, and therapeutics continue to be developed, the persistence of disease, with the concomitant threat of emergent variants, continues to impose massive health and socioeconomic issues worldwide. Studies show that in susceptible individuals, SARS-CoV-2 infection can rapidly progress toward lung injury and acute respiratory distress syndrome (ARDS), with evidence for an underlying dysregulated innate immune response or cytokine release syndrome (CRS). The mechanisms responsible for this CRS remain poorly understood, yet hyper-inflammatory features were also evident with predecessor viruses within the β-coronaviridae family, namely SARS-CoV-1 and the Middle East Respiratory Syndrome (MERS)-CoV. It is further known that the spike protein (S) of SARS-CoV-2 (as first reported for other β-coronaviruses) possesses a so-called galectin-fold within the N-terminal domain of the S1 subunit (S1-NTD). This fold (or pocket) shows structural homology nearly identical to that of human galectin-3 (Gal-3). In this respect, we have recently shown that Gal-3, when associated with epithelial cells or anchored to a solid phase matrix, facilitates the activation of innate immune cells, including basophils, DC, and monocytes. A synthesis of these findings prompted us to test whether segments of the SARS-CoV-2 spike protein might also activate innate immune cells in a manner similar to that observed in our Gal-3 studies. Indeed, by immobilizing S components onto microtiter wells, we show that only the S1 subunit (with the NTD) activates human monocytes to produce a near identical pattern of cytokines as those reported in COVID-19-related CRS. In contrast, both the S1-CTD/RBD, which binds ACE2, and the S2 subunit (stalk), failed to mediate the same effect. Overall, these findings provide evidence that the SARS-CoV-2 spike protein can activate monocytes for cytokines central to COVID-19, thus providing insight into the innate immune mechanisms underlying the CRS and the potential for therapeutic interventions.

The energetic economy of running benefits from tendon and other tissues that store and return elastic energy, thus saving muscles from costly mechanical work. The classic "Spring-mass" computational model successfully explains the forces, displacements and mechanical power of running, as the outcome of dynamical interactions between the body center of mass and a purely elastic spring for the leg. However, the Spring-mass model does not include active muscles and cannot explain the metabolic energy cost of running, whether on level ground or on a slope. Here we add explicit actuation and dissipation to the Spring-mass model, and show how they explain substantial active (and thus costly) work during human running, and much of the associated energetic cost. Dissipation is modeled as modest energy losses (5% of total mechanical energy for running at 3 m s-1) from hysteresis and foot-ground collisions, that must be restored by active work each step. Even with substantial elastic energy return (59% of positive work, comparable to empirical observations), the active work could account for most of the metabolic cost of human running (about 68%, assuming human-like muscle efficiency). We also introduce a previously unappreciated energetic cost for rapid production of force, that helps explain the relatively smooth ground reaction forces of running, and why muscles might also actively perform negative work. With both work and rapid force costs, the model reproduces the energetics of human running at a range of speeds on level ground and on slopes. Although elastic return is key to energy savings, there are still losses that require restorative muscle work, which can cost substantial energy during running.

There is mounting evidence that galectin-3 is a prognostic and diagnostic biomarker associated with diverse diseases and conditions, including cancer, cardiovascular disease, autoimmunity, wound healing, allergic disease, and chronic inflammation in general. Yet, whether and exactly how galectin-3 may participate in the pathogenesis of these diseases remains poorly understood. Recently, we have linked the expression of galectin-3 on the A549 epithelial cell line –an adenocarcinoma, to the activation of human basophils for the release of histamine and secretion of IL-4 and IL-13. These responses proved dependent on cell-to-cell contact, basophil expression of IgE, were inhibited by n-acetyllactosamine, and were ablated when basophils were co-cultured with A549 clones lacking galectin-3 expression. While recombinant galectin-3 failed to activate basophils when in solution, microspheres expressing this lectin did so by mimicking the responses seen when using A549 cells. Given the IgE dependency of the basophil responses, and the fact that galectin-3 is long known to bind this immunoglobulin, we hypothesize that a similar mode of activation extends to other IgE-bearing cells. To investigate this possibility, we tested epithelial cell-associated galectin-3 for its capacity to activate human dendritic cells, including the plasmacytoid and myeloid subtypes as well as monocytes, all of which bind IgE. Indeed, results indicate that epithelial cell-associated galectin-3 activated these cells for robust production of TNF-α and IL-6 and up-regulated the expression of activation markers found on dendritic cells. Moreover, many of the same parameters previously observed for basophils applied to the findings herein, including evidence that matrix-bound galectin-3 (whether on epithelial cells or microspheres) facilitates this mode of activation. In contrast, IgE expression was dispensable for these galectin-3-dependent cytokine responses, implying that this lectin activates dendritic cells (and monocytes) by binding to a glycoprotein other than this immunoglobulin. Overall, these findings further demonstrate how galectin-3 mediates immune cell activation, providing novel insight into how this lectin may promote chronic inflammation underlying the pathogenesis of many diseases.

Scholarship on underresourced languages bring with them a variety of challenges which make access to the full spectrum of source materials and their evaluation difficult. For Coptic in particular, large scale analyses and any kind of quantitative work become difficult due to the fragmentation of manuscripts, the highly fusional nature of an incorporational morphology, and the complications of dealing with influences from Hellenistic era Greek, among other concerns. Many of these challenges, however, can be addressed using Digital Humanities tools and standards. In this paper, we outline some of the latest developments in Coptic Scriptorium, a DH project dedicated to bringing Coptic resources online in uniform, machine readable, and openly available formats. Collaborative web-based tools create online 'virtual departments' in which scholars dispersed sparsely across the globe can collaborate, and natural language processing tools counterbalance the scarcity of trained editors by enabling machine processing of Coptic text to produce searchable, annotated corpora.

Basophils were identified in human peripheral blood by Paul Ehrlich over 140 years ago. Human basophils represent

Features of gait are determined at multiple levels, from the selection of the gait itself (e.g., walk or run) through the specific parameters utilized (stride length, frequency, etc.) to the pattern of muscular excitation. The ultimate choices are determined neurally, but what is involved with deciding on the appropriate strategy? Human locomotion appears stereotyped not so much because the pattern is predetermined, but because these movement patterns are good solutions for providing movement utilizing the machinery available to the individual (the legs and their requisite components). Under different circumstances the appropriate solution may differ broadly (different gait) or subtly (different parameters). Interpretation of the neural decision making process would benefit from understanding the influences that are utilized in the selection of the appropriate solution in any set of circumstances, including normal conditions. In this review we survey an array of studies that point to energetic cost as a key input to the gait coordination system, and not just an outcome of the gait pattern implemented. We then use that information to rigorously define the construct proposed by Sparrow and Newell (1998) where the effects of environment, organism, and task act as constraints determining the solution set available, and the coordination pattern is then implemented under pressure for energetic economy. The fit between the environment and the organism define affordances that can be actualized. We rely on a novel conceptualization of task that recognizes that the task goal needs to be separated from the mechanisms that achieve it so that the selection of a particular implementation strategy can be exposed and understood. This reformulation of the Sparrow and Newell construct is then linked to the proposed pressure for economy by considering it as an optimization problem, where the most readily selected gait strategy will be the one that achieves the task goal at (or near) the energetic minimum.

Terrestrial organisms adept at locomotion employ strut-like legs for economical and robust movement across the substrate. Although it is relatively easy to observe and analyze details of the solutions these organic systems have arrived at, it is not as easy to identify the problems these movement strategies have solved. As such, it is useful to investigate fundamental challenges that effective legged locomotion overcomes in order to understand why the mechanisms employed by biological systems provide viable solutions to these challenges. Such insight can inform the design and development of legged robots that may eventually match or exceed animal performance. In the context of human walking, we apply control optimization as a design strategy for simple bipedal walking machines with minimal actuation. This approach is used to discuss key facilitators of energetically efficient locomotion in simple bipedal walkers. Furthermore, we extrapolate the approach to a novel application—a theoretical exoskeleton attached to the trunk of a human walker—to demonstrate how coordinated efforts between bipedal actuation and a machine oscillator can potentially alleviate a meaningful portion of energetic exertion associated with leg function during human walking.

Compliant bamboo poles have long been used for load carriage in Asian cultures. Although this custom differs from Western conventions of rigid body attachments (e.g. backpack), potential benefits include reduced peak shoulder forces as well as metabolic transport cost savings. Evidence that carrying a flexible pole benefits locomotion remains mixed, perhaps in part because the properties of pole design (e.g. bamboo material, structural geometry, etc.) have largely been neglected. These properties influence vibrational forces and consequently, the energy required by the user to manage the oscillations. We collected authentic bamboo poles from northern Vietnam and characterized their design parameters. Four poles were extensively studied in the lab (load-deflection testing, resonance testing, and computed tomography scans of three-dimensional geometry), and 10 others were tested at a rural Vietnamese farm site (basic measures of form and resonance). A mass-spring-damper model was used to characterize a relationship between resonant frequency (which affects the energetics of the pole-carrier system) and pole properties concerning stiffness, damping, etc. Model predictions of resonant frequencies agreed well with empirical data. Although measured properties suggest the poles are not optimally designed to reduce peak oscillation forces, resonant frequencies are within range of a typical human walking cadence, and this is likely to have a consequence on locomotion energetics.

Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10), respectively (PCS peptides), and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

Coptic SCRIPTORIUM is a platform for interdisciplinary and computational research in Coptic texts and linguistics. The purpose of this project was to research and implement a system of stable identification for the texts and linguistic data objects in Coptic SCRIPTORIUM to facilitate their citation and reuse. We began the project with a preferred solution, the Canonical Text Services URN model, which we validated for suitability for the corpus and compared it to other approaches, including HTTP URLs and Handles. The process of applying the CTS model to Coptic SCRIPTORIUM required an in-depth analysis that took into account the domain-specific scholarly research and citation practices, the structure of the textual data, and the data management workflow.

Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology.