BackgroundEfforts to modulate the function of tumor-associated myeloid cell are underway to overcome the challenges in immunotherapy and find a cure. One potential therapeutic target is integrin ...CD11b, which can be used to modulate the myeloid-derived cells and induce tumor-reactive T-cell responses. However, CD11b can bind to multiple different ligands, leading to various myeloid cell functions such as adhesion, migration, phagocytosis, and proliferation. This has created a major challenge in understanding how CD11b converts the differences in the receptor-ligand binding into subsequent signaling responses and using this information for therapeutic development.MethodsThis study aimed to investigate the antitumor effect of a carbohydrate ligand, named BG34-200, which modulates the CD11b+ cells. We have applied peptide microarrays, multiparameter FACS (fluorescence-activated cell analysis) analysis, cellular/molecular immunological technology, advanced microscopic imaging, and transgenic mouse models of solid cancers, to study the interaction between BG34-200 carbohydrate ligand and CD11b protein and the resulting immunological changes in the context of solid cancers, including osteosarcoma, advanced melanoma, and pancreatic ductal adenocarcinoma (PDAC).ResultsOur results show that BG34-200 can bind directly to the activated CD11b on its I (or A) domain, at previously unreported peptide residues, in a multisite and multivalent manner. This engagement significantly impacts the biological function of tumor-associated inflammatory monocytes (TAIMs) in osteosarcoma, advanced melanoma, and PDAC backgrounds. Importantly, we observed that the BG34-200-CD11b engagement triggered endocytosis of the binding complexes in TAIMs, which induced intracellular F-actin cytoskeletal rearrangement, effective phagocytosis, and intrinsic ICAM-1 (intercellular adhesion molecule I) clustering. These structural biological changes resulted in the differentiation in TAIMs into monocyte-derived dendritic cells, which play a crucial role in T-cell activation in the tumor microenvironment.ConclusionsOur research has advanced the current understanding of the molecular basis of CD11b activation in solid cancers, revealing how it converts the differences in BG34 carbohydrate ligands into immune signaling responses. These findings could pave the way for the development of safe and novel BG34-200-based therapies that modulate myeloid-derived cell functions, thereby enhancing immunotherapy for solid cancers.
The Total Carbon Column Observing Network (TCCON) measures column-average mole fractions of several greenhouse gases (GHGs), beginning in 2004, from over 30 current or past measurement sites around ...the world using solar absorption spectroscopy in the near-infrared (near-IR) region. TCCON GHG data have been used extensively for multiple purposes, including in studies of the carbon cycle and anthropogenic emissions, as well as to validate and improve observations from space-based sensors. Here, we describe an update to the retrieval algorithm used to process the TCCON near-IR solar spectra and to generate the associated data products. This version, called GGG2020, was initially released in April 2022. It includes updates and improvements to all steps of the retrieval, including but not limited to the conversion of the original interferograms into spectra, the spectroscopic information used in the column retrieval, post hoc air mass dependence correction, and scaling to align with the calibration scales of in situ GHG measurements.
El presente estudio se ha ocupado de examinar los conocimientos (aciertos), concepciones erróneas (fallos) y lagunas (no sé) sobre el Trastorno por Déficit de Atención e Hiperactividad (TDAH) en base ...a tres áreas de contenido específicas: información general, sintomatología y tratamiento. Para ello, se ha empleado el cuestionario del KADDS (Knowledge of Attention Deficit Hyperactivity Disorder), cumplimentado por un total de 58 maestros/as españoles y boloñeses y 53 estudiantes. Los resultados del KADDS respecto a los docentes muestran un porcentaje de aciertos del 47,3%, 39,2% en fallos y 13,2% en lagunas. En estudiantes el porcentaje es del 56,6%, 26,6% y 16,8% respectivamente. Se observan diferencias entre el profesorado español e italiano. Respecto al porcentaje de aciertos, los docentes españoles puntúan menos en las tres áreas respecto a los docentes italianos: información general (54,5% vs. 78,4%), sintomatología (63,2% vs. 77%) y tratamiento (50,1% vs. 72,7%). Además, se observa que los docentes con estudios específicos en educación especial puntúan mejor en las tres áreas. Debido a la alta prevalencia del TDAH y el posible desconocimiento para su diagnóstico, manejo y tratamiento, sería recomendable una mayor formación a los docentes.
Bacterial spot of tomato is among the most economically relevant diseases affecting tomato plants globally. In previous studies, non-formulated magnesium oxide nanoparticles (nano-MgOs) significantly ...reduced the disease severity in greenhouse and field conditions. However, the aggregation of nano-MgO in liquid suspension makes it challenging to use in field applications. Therefore, we formulated two novel MgO nanomaterials (SgMg #3 and SgMg #2.5) and one MgOH
nanomaterial (SgMc) and evaluated their physical characteristics, antibacterial properties, and disease reduction abilities. Among the three Mg nanomaterials, SgMc showed the highest efficacy against copper-tolerant strains of
in vitro, and provided disease reduction in the greenhouse experiments compared with commercial Cu bactericide and an untreated control. However, SgMc was not consistently effective in field conditions. To determine the cause of its inconsistent efficacy in different environments, we monitored particle size, zeta potential, morphology, and crystallinity for all three formulated materials and nano-MgOs. The MgO particle size was determined by the scanning electron microscopy (SEM) and dynamic light scattering (DLS) techniques. An X-ray diffraction (XRD) study confirmed a change in the crystallinity of MgO from a periclase to an Mg(OH)
brucite crystal structure. As a result, the bactericidal activity correlated with the high crystallinity present in nano-MgOs and SgMc, while the inconsistent antimicrobial potency of SgMg #3 and SgMg #2.5 might have been related to loss of crystallinity. Future studies are needed to determine which specific variables impair the performance of these nanomaterials in the field compared to under greenhouse conditions. Although SgMc did not lead to significant disease severity reduction in the field, it still has the potential to act as an alternative to Cu against bacterial spot disease in tomato transplant production.
Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile ...Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models.
This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months.
MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes (
<0.01). MIST and mothership had similar median door-to-recanalization times of 192 minutes and 179 minutes, respectively (
=0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%;
<0.01). MIST had 52.8% of patients with modified Rankin Scale of ≤2 at 3 months compared with 38.9% in DS (
=0.10).
MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03048292.
Precalving feeding level affects dry matter intake, postcalving energy balance, the risk of hepatic lipidosis and metabolic disease, and gene expression in liver and adipose tissue. These coincide ...with a higher risk of disease postpartum and, very likely, a failure to reach optimum production as well as reproductive targets. Current interpretation of the available evidence suggest that metabolic stressors affect the immune system of transition dairy cows and lead to reduced immunocompetence. The objective of the current study was to investigate the effect of precalving body condition score (BCS) and level of feeding on immunocompetence during the peripartum period. Twenty-three weeks before calving, 78 cows were allocated randomly to 1 of 6 treatment groups (n=13) in a 2×3 factorial arrangement: 2 precalving BCS categories (4.0 and 5.0, based on a 10-point scale) and 3 levels of energy intake during the 3 wk preceding calving (75, 100, and 125% of estimated requirements). Blood was sampled precalving and at 1, 2 and 4 wk after calving. Cells were analyzed by flow cytometry and quantitative real-time PCR. The numbers of T helper lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), natural killer cells (CD335+), and γδ T lymphocytes (WC1+) as well as their activation status IL-2 receptor (CD25)+ cells were highly variable between animals, but there was no evident effect of BCS, feeding level, or time. All groups presented with an increase in expression of cytokines in unstimulated blood cells in the week after calving, although this was significant only for IFNG in the BCS 4.0 group. Analysis of in vitro-stimulated cells allowed 2 general observations: (1) cows with high energy intake precalving (125%) had increased cytokine expression precalving, and (2) all cows had increased cytokine expression in the week after calving. The present study provides evidence that prepartum feed management can affect immunocompetence during the transition period. Considering the current results, optimally conditioned animals might benefit from a restricted precalving diet, whereas underconditioned cows can be fed to requirements.
Level0 to Level1B processor for MethaneAIR Conway, Eamon K; Souri, Amir H; Benmergui, Joshua ...
Atmospheric measurement techniques,
02/2024, Letnik:
17, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This work presents the development of the MethaneAIR Level0–Level1B processor, which converts raw L0 data to calibrated and georeferenced L1B data. MethaneAIR is the airborne simulator for ...MethaneSAT, a new satellite under development by MethaneSAT LLC, a subsidiary of the Environmental Defense Fund (EDF). MethaneSAT's goals are to precisely map over 80 % of the production sources of methane from oil and gas fields across the globe to an accuracy of 2–4 ppb on a 2 km2 scale. Efficient algorithms have been developed to perform dark corrections, estimate the noise, radiometrically calibrate data, and correct stray light. A forward model integrated into the L0–L1B processor is demonstrated to retrieve wavelength shifts during flight accurately. It is also shown to characterize the instrument spectral response function (ISRF) changes occurring at each sampled spatial footprint. We demonstrate fast and accurate orthorectification of MethaneAIR data in a three-step process: (i) initial orthorectification of all observations using aircraft avionics, a simple camera model, and a medium-resolution digital elevation map; (ii) registration of oxygen (O2) channel grayscale images to reference Multispectral Instrument (MSI) band 11 imagery via Accelerated-KAZE (A-KAZE) feature extraction and linear transformation, with similar co-registration of methane (CH4) channel grayscale images to the registered O2 channel images; and finally (iii) optimization of the aircraft position and attitude to the registered imagery and calculation of viewing geometry. This co-registration technique accurately orthorectifies each channel to the referenced MSI imagery. However, in the pixel domain, radiance data for each channel are offset by almost 150–200 across-track pixels (rows) and need to be aligned for the full-physics or proxy retrievals where both channels are simultaneously used. We leveraged our orthorectification tool to identify tie points with similar geographic locations in both CH4 and O2 images in order to produce shift parameters in the across-track and along-track dimensions. These algorithms described in this article will be implemented into the MethaneSAT L0–L1B processor.
We evaluate vertical profile retrievals of CO.sub.2 from 0.02 cm.sup.-1 resolution ground-based near-infrared solar absorption spectra with the GFIT2 algorithm, using improved spectroscopic line ...lists and line shapes. With these improvements, CO.sub.2 profiles were obtained from sequential retrievals in five spectral windows with different vertical sensitivities using synthetic and real spectra. A sensitivity study using synthetic spectra shows that the leading source of uncertainty in the retrieved CO.sub.2 profiles is the error in the a priori temperature profile, even with 3-hourly reanalysis a priori profiles. A 2 .sup." C error in the temperature profile in the lower troposphere between 0.6 and 0.85 atm causes deviations in the retrieved CO.sub.2 profiles that are larger than the typical vertical variations of CO.sub.2 . To distinguish the effect of errors in the a priori meteorology and trace gas concentration profiles from those in the instrument alignment and spectroscopic parameters, we retrieve CO.sub.2 profiles from atmospheric spectra while using an a priori profile built from coincident AirCore, radiosonde, and surface in situ measurements at the Lamont, Oklahoma (USA), Total Carbon Column Observing Network station. In those cases, the deviations in retrieved CO.sub.2 profiles are also larger than typical vertical variations of CO.sub.2, suggesting that remaining errors in the forward model limit the accuracy of the retrieved profiles. Implementing a temperature retrieval or correction and quantifying and modeling an imperfect instrument alignment are critical to improve CO.sub.2 profile retrievals. Without significant advances in modeling imperfect instrument alignment, and improvements in the accuracy of the temperature profile, the CO.sub.2 profile retrieval with GFIT2 presents no clear advantage over scaling retrievals for the purpose of ascertaining the total column.
OBJECTIVES/GOALS: Assistive technology (AT) can improve older adults’ function in daily activities. However, Latinos are among the least likely to use AT. Given that primary health care physicians ...(PCPs) have low awareness about AT, this study aims to evaluate the usability and acceptability of an AT WebAPP among PCPs to increase older Latinos’ access to AT. METHODS/STUDY POPULATION: A team of an established researcher, a sub-graduate faculty and student, and a graduate student will recruit ten PCPs in Puerto Rico and will interview them to explore their current practice in addressing the functional needs of older Spanish-speaking Latinos. The researchers will then train PCPs in the use of a Spanish evidence-based AT WebAPP developed in one of our earlier studies. PCP participants will use the APP with their older patients for 30 days. At the end of the usage period, the analysis will include a mixed method design, consisting of the simultaneous collection of quantitative data using a validated scale followed by qualitative data through individual interviews. Quantitative data will be analyzed with descriptive statistics and qualitative data with thematic content analysis. RESULTS/ANTICIPATED RESULTS: We expect that the AT WebAPP will be rated as particularly useful and acceptable by the PCPs to increase older Latinos’ access to information about AT that could compensate for their physical function disabilities. We also expect that PCPs will offer recommendations for enhancing the design and usability of the AT WebAPP. DISCUSSION/SIGNIFICANCE: Studying the usability and acceptability of this AT WebAPP among PCPs will advance our understanding of its feasibility in enhancing PCPs AT knowledge and recommendations of AT devices for older adults with disabilities in Puerto Rico and in Latino communities in the continental United States.
Intoxication often prevents clinical clearance of the cervical spine (Csp) after trauma leading to prolonged immobilization even with a normal computed tomography (CT) scan. We evaluated the accuracy ...of CT at detecting clinically significant Csp injury, and surveyed participants on related opinions and practice.
A prospective multicenter study (2013-2015) at 17 centers. All adult blunt trauma patients underwent structured clinical examination and imaging including a Csp CT, with follow-up thru discharge. alcohol- and drug-intoxicated patients (TOX+) were identified by serum and/or urine testing. Primary outcomes included the incidence and type of Csp injuries, the accuracy of CT scan, and the impact of TOX+ on the time to Csp clearance. A 36-item survey querying local protocols, practices, and opinions in the TOX+ population was administered.
Ten thousand one hundred ninety-one patients were prospectively enrolled and underwent CT Csp during the initial trauma evaluation. The majority were men (67%), had vehicular trauma or falls (83%), with mean age of 48 years, and mean Injury Severity Score (ISS) of 11. The overall incidence of Csp injury was 10.6%. TOX+ comprised 30% of the cohort (19% EtOH only, 6% drug only, and 5% both). TOX+ were significantly younger (41 years vs. 51 years; p < 0.01) but with similar mean Injury Severity Score (11) and Glasgow Coma Scale score (13). The TOX+ cohort had a lower incidence of Csp injury versus nonintoxicated (8.4% vs. 11.5%; p < 0.01). In the TOX+ group, CT had a sensitivity of 94%, specificity of 99.5%, and negative predictive value (NPV) of 99.5% for all Csp injuries. For clinically significant injuries, the NPV was 99.9%, and there were no unstable Csp injuries missed by CT (NPV, 100%). When CT Csp was negative, TOX+ led to longer immobilization versus sober patients (mean, 8 hours vs. 2 hours; p < 0.01), and prolonged immobilization (>12 hrs) in 25%. The survey showed marked variations in protocols, definitions, and Csp clearance practices among participating centers, although 100% indicated willingness to change practice based on these data.
For intoxicated patients undergoing Csp imaging, CT scan was highly accurate and reliable for identifying clinically significant spine injuries, and had a 100% NPV for identifying unstable injuries. CT-based clearance in TOX+ patients appears safe and may avoid unnecessary prolonged immobilization. There was wide disparity in practices, definitions, and opinions among the participating centers.
Diagnostic tests or criteria, level II.
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