Unique Response Research Articles

Homopolymer-block-Alternating Copolymers Composed of Acrylamide Units: Design of Transformable Divinyl Monomers and Sequence-Specific Thermoresponsive Properties.

In this work, we synthesized an acrylamide-based terpolymer that is a block copolymer composed of an AB alternating copolymer and a C homopolymer. The key to the unprecedented achievement is rational design of an acrylate-acrylamide divinyl monomer carrying CF3-substituted salicylic acid ester bonds (AAm-CF3) to realize the efficient and selective cyclopolymerization as well as the quantitative transformation of the resultant cyclorepeating units. The selectivity in the cyclopolymerization and the pendant transformation ability were evaluated through reactivity ratios of the corresponding model monomers and quantitative aminolysis reactions of the model compound. The cyclopolymerization via the photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) process with a macrochain-transfer agent and subsequent aminolysis reaction afforded the homopolymer-block-alternating copolymer. The sequence-controlled terpolymer exhibited a very unique thermal response behavior in water that was strikingly different from the corresponding sequence-uncontrolled terpolymers, such as homopolymer-block-statistical copolymers and all statistical terpolymers, despite the fact that the structure cannot be distinguished by 1H NMR.

Unique Isospora-associated histologic lesions in white-rumped shama (Copsychus malabaricus).

Twenty-one white-rumped shamas (19 necropsied, 2 biopsied) (Copsychus malabaricus) housed at the San Diego Zoo between 1992 and 2020 were diagnosed with Isospora infection based on evaluation of histologic sections. Review of these cases revealed a consistent histologic lesion characterized by nodular aggregates of atypical epithelioid macrophages containing few intracytoplasmic protozoa, with or without lymphocytic infiltrates. Of the 19 necropsied cases, 16 (84%) had systemic lesions variably affecting the liver, spleen, gastrointestinal tract, lung, pancreas, connective tissues, or bone marrow, while all 21 diagnosed cases had skin involvement. The findings suggest that white-rumped shamas have a unique inflammatory response to isosporosis with a predilection for the skin. Skin may be a diagnostically sensitive sampling site for histologic diagnosis of Isospora in this species.

Flexible-reliable operation of green microgrids including sources and energy storage-based active loads considering ANFIS-based data forecasting method

This paper presents the flexible-reliable operation (FRO) of microgrids (MGs) constrained to supplying clean energy. The scheme minimizes the total expected costs of the MG and sources operation, MG reliability, and MG flexibility and is subject to power flow equations, operation, environmental, and reliability constraints, and formulation of sources and energy storage-based active loads. The problem is mixed-integer nonlinear programming (MINLP). To achieve an optimal reliable solution with unique response conditions, a combination of an artificial bee colony (ABC) and sine-cosine algorithm (SCA) is utilized in this study. In the given scheme, stochastic programming is employed to model the uncertainties of load, energy price, renewable power, and availability of MG equipment. Furthermore, mean and standard deviation values of the above-mentioned first three uncertainty parameters are obtained using the data forecasting method based on the hybrid ABC+SCA method, adaptive network-based fuzzy inference system (ANFIS), and wavelet transform (WT). Finally, by implementing the proposed strategy on a standard MG, the capabilities of the proposed scheme in improving economic, environmental, operation, reliability, and flexibility conditions of the network are validated.

Spirooxazine-Based Dual-Sensing Probe for Colorimetric Detection of Cu2+ and Fe3+ and Its Application in Drinking Water and Rice Quality Monitoring.

A spirooxazine derivative, PheSPO (3,3-dimethyl-1-phenethylspiro[indoline-2,3′-naphtho[2,1-b][1,4]oxazine]), as a dual-sensing probe for Cu2+ and Fe3+ was synthesized, and its structure was confirmed by 1H NMR, 13C NMR, HRMS, and single-crystal X-ray diffraction. The results reveal that the PheSPO probe is selective to both Cu2+ and Fe3+ through distinct colorimetric responses in acetonitrile. The sensing performance of PheSPO toward Cu2+ was investigated, and upon addition of Cu2+, an instant change in color from colorless to bright yellow with a strong absorption band at 467 nm was observed. Due to a dual-sensing behavior, PheSPO also exhibits a unique response toward Fe3+ that can be discovered from a color change from colorless to red at an absorption wavelength of 514 nm. Based on spectroscopic analyses and density functional theory calculations, the 1:1 stoichiometric complexation of PheSPO with the targeted metal ions was proposed and the binding constants of 1.95 × 103 M–1 for Cu2+ and 1.29 × 103 M–1 for Fe3+ were obtained. In addition, the detection limits of PheSPO for Cu2+ and Fe3+ were 0.94 and 2.01 μM, respectively. To verify its applicability in real samples, PheSPO was further explored for quantitative determination of both Cu2+ and Fe3+ in spiked drinking water. The results showed that the recoveries of Cu2+ and Fe3+ examined using the PheSPO probe were found comparable to those obtained from atomic absorption spectroscopy. Moreover, the PheSPO strip test was developed, and its utilization for qualitative detection of Fe3+ in real rice samples was demonstrated.

Human M1 macrophages express unique innate immune response genes after mycobacterial infection to defend against tuberculosis

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced Inregs expression. M1-MΦs and M2-MΦs express pro- and anti-inflammatory cytokine-chemokines, respectively, and M1-MΦs show nitric oxide and autophagy-dependent degradation of Mtb, leading to increased antigen presentation to T cells through an ATG-RAB7-cathepsin pathway. Despite Mtb infection, M1-MΦs show increased histone acetylation at the ATG5 promoter and pro-autophagy phenotypes, while increased histone deacetylases lead to decreased autophagy in M2-MΦs. Finally, Mtb-infected neonatal macaques express human Inregs in their lymph nodes and macrophages, suggesting that M1 and M2 phenotypes can mediate immunity to TB in both humans and macaques. We conclude that human MФ subsets show unique patterns of gene expression that enable differential control of TB after infection. These genes could serve as targets for diagnosis and immunotherapy of TB.

Board gender diversity and responsible banking during the COVID-19 pandemic

This study investigates whether board gender diversity matters in banks' initial responses to the COVID-19 pandemic in supporting their customers, communities and governments. We construct a unique and comprehensive COVID-19 Bank Response Measure (C19BRM) by compiling a novel hand-collected dataset on supportive measures announced by US and European banks during the first wave of the pandemic. We find that banks with higher board representation of women directors supported their customers and communities more. Our findings also reveal that banks with more women on the boards increased their charity and donations. Our results are robust to the potential self-selection bias of women choosing to join boards of more responsible banks, the omitted variables bias, and alternative measures of gender diversity.

Glacial Warming in the Eastern Pacific Warm Pool

The Eastern Pacific Warm Pool (EPWP) modulates global climate through its connection with tropical Pacific circulation, but sparse paleoceanographic data from this region limits our understanding of its role in past climate variability. We present a 144 kyr alkenone-sea surface temperature (SST) reconstruction from core NH22P, located in the northern EPWP, that shows local warming occurred during periods of global cooling. Climate model simulations of the Last Glacial Maximum indicate that both ice sheet and greenhouse gas forcing slowed wind speeds over the EPWP, which attenuated glacial cooling of local SST via the wind-evaporation-SST feedback. Spectral analysis further suggests precessional pacing of the warming spikes. Vernal equinox insolation could explain this pacing as direct shortwave heating during boreal spring would have contributed to the early seasonal intensification of the EPWP. This work provides crucial constraints on tropical Pacific glacial climate variability and highlights the unique response of the EPWP to global climate forcings.

A colorimetric electronic tongue for point-of-care detection of COVID-19 using salivary metabolites

The monitoring of profile concentrations of chemical markers in saliva samples can be used to diagnose COVID-19 patients, and differentiate them from healthy individuals. Here, this purpose is achieved by designing a paper-based colorimetric sensor with an origami structure, containing general receptors such as pH-sensitive organic dyes, Lewis donors or acceptors, functionalized nanoparticles, and ion metal complexes. The color changes taking place in the receptors in the presence of chemical markers are visually observed and recorded with a digital instrument. Different types and amounts of the chemical markers provide the sensor with a unique response for patients (60 samples) or healthy (55 samples) individuals. These two categories can be discriminated with 84.3% accuracy. This study evidences that the saliva composition of cured and healthy participants is different from each other with accuracy of 85.7%. Moreover, viral load values obtained from the rRT-PCR method can be estimated by the designed sensor. Besides COVID-19, it may possible to simultaneously identify smokers and people with kidney disease and diabetes using the specified electronic tongue. Due to its high efficiency, the prepared paper device can be employed as a rapid detection kit to detect COVID-19.

Showcase citizens: citizenship in the making along the borders of post-colonial South Asia

ABSTRACT Drawing on newly incorporated citizens’ experiences, interviews with numerous state officials, and field observations in the former border enclaves of India inside Bangladesh after their exchange in 2015, I contend that the state of Bangladesh took extraordinary measures to incorporate its new citizens. Such exceptional measures resulted in a category of citizens that cannot be fully grasped by the existing citizenship vocabulary. In this paper I therefore offer the concept of showcase citizens. Showcase citizens represent an exceptionally treated group of citizens who became subjects to special attention from the state in certain spaces at a specific time. The key to our understanding of such ‘exceptions’ and the unique response from the Bangladesh state, I argue, lies in placing the enclaves within the broader context of post-colonial South Asia, specifically in relation to the imagination of nation and territory, sovereignty, (performative) governance, and state-making. As such, showcase citizens becomes both an analytical tool – which links the imagination of territory, sovereignty, and citizenship in post-colonial South Asia – and a technique of performative governance that combines the formal with the informal.

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy.

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided.

Facile synthesis of dual-ligand terbium-organic gels as ratiometric fluorescence probes for efficient mercury detection

Mercury (Hg) pollution can negatively impact ecosystems, and there is a need for simple Hg2+ monitoring platforms. Here, a dual-ligand fluorescence probe based on terbium-organic gels (Tb-L0.2P0.8 MOGs) was constructed for efficient Hg2+ detection. Tb-L0.2P0.8 MOGs were developed through a facile room-temperature gelation method, showing two emission peaks derived from luminol and Tb3+ at 424 nm and 544 nm, respectively. The aggregation-induced emission (AIE) effect between luminol and Tb3+ led to luminol with blue fluorescence. However, Hg2+ could dramatically quench the fluorescence signal of luminol at 424 nm because of the intense coordination interaction of Hg2+ with luminol and photo-induced electron transfer (PET). The Phen ligand could sensitize the luminescence of Tb3+ and offer a reference fluorescence, thus resulting in a unique ratiometric fluorescence response toward Hg2+. This novel nanoprobe had excellent linearity with Hg2+ concentrations range of 0.1–30 μM; the detection limit was 3.6 nM. The analysis of real samples showed the potential application of MOGs for measuring Hg2+ in porphyra and tap water. Mixed ligands were introduced for high-efficiency strategies to improve the analytical performance by regulating the emission behavior of MOGs.

Movie Events Detecting Reveals Inter-Subject Synchrony Difference of Functional Brain Activity in Autism Spectrum Disorder

Recently, movie-watching fMRI has been recognized as a novel method to explore brain working patterns. Previous researchers correlated natural stimuli with brain responses to explore brain functional specialization by “reverse correlation” methods, which were based on within-group analysis. However, what external stimuli drove significantly different brain responses in two groups of different subjects were still unknown. To address this, sliding time windows technique combined with inter-Subject functional correlation (ISFC) was proposed to detect movie events with significant group differences between autism spectrum disorder (ASD) and typical development (TD) subjects. Then, using inter-Subject correlation (ISC) and ISFC analysis, we found that in three movie events involving character emotions, the ASD group showed significantly lower ISC in the middle temporal gyrus, temporal pole, cerebellum, caudate, precuneus, and showed decreased functional connectivity between large scale networks than that in TD. Under the movie event focusing on objects and scenes shot, the dorsal and ventral attentional networks of ASD had a strong synchronous response. Meanwhile, ASD also displayed increased functional connectivity between the frontoparietal network (FPN) and dorsal attention network (DAN), FPN, and sensorimotor network (SMN) than TD. ASD has its own unique synchronous response rather than being “unresponsive” in natural movie-watching. Our findings provide a new method and valuable insight for exploring the inconsistency of the brain “tick collectively” to same natural stimuli. This analytic approach has the potential to explore pathological mechanisms and promote training methods of ASD.

Pulmonary endothelial cells from different vascular segments exhibit unique recovery from acidification and Na+/H+ exchanger isoform expression.

Sodium-hydrogen exchangers (NHEs) tightly regulate intracellular pH (pHi), proliferation, migration and cell volume. Heterogeneity exists between pulmonary endothelial cells derived from different vascular segments, yet the activity and isoform expression of NHEs between these vascular segments has not been fully examined. Utilizing the ammonium-prepulse and recovery from acidification technique in a buffer lacking bicarbonate, pulmonary microvascular and pulmonary artery endothelial cells exhibited unique recovery rates from the acid load dependent upon the concentration of the sodium transport inhibitor, amiloride; further, pulmonary artery endothelial cells required a higher dose of amiloride to inhibit sodium-dependent acid recovery compared to pulmonary microvascular endothelial cells, suggesting a unique complement of NHEs between the different endothelial cell types. While NHE1 has been described in pulmonary endothelial cells, all NHE isoforms have not been accounted for. To address NHE expression in endothelial cells, qPCR was performed. Using a two-gene normalization approach, Sdha and Ywhag were identified for qPCR normalization and analysis of NHE isoforms between pulmonary microvascular and pulmonary artery endothelial cells. NHE1 and NHE8 mRNA were equally expressed between the two cell types, but NHE5 expression was significantly higher in pulmonary microvascular versus pulmonary artery endothelial cells, which was confirmed at the protein level. Thus, pulmonary microvascular and pulmonary artery endothelial cells exhibit unique NHE isoform expression and have a unique response to acid load revealed through recovery from cellular acidification.

Stimulation of Osteoblastic Bone Metastasis by Canine Prostate Cancer

Prostate cancer metastases primarily localize in the bone where they induce a unique osteoblastic response. The mechanisms are not well understood; however, they depend on a complex interplay between prostate cancer cells and the cellular microenvironment in the bone marrow. We hypothesize that prostate cancer cells secreted biological factors that induce new bone formation and either induce or stimulate osteoclastic bone resorption to permit growth of bone metastasis. Dogs are the only other species that develop spontaneous prostate cancer with bone metastases in addition to men. Previously, our laboratory has developed three canine prostate cancer cell lines that mimic human osteoblastic bone metastases when injected into the left cardiac ventricle of nude mice. This study then investigated the effect of three canine prostate cancer cell lines (Ace‐1, Probasco, and LuMa) on bone formation and resorption. Mouse calvaria were treated with conditioned medium (CM) collected from cell lines. A novel calcein uptake assay was developed to measure bone formation and mineralization in vitro. Ace‐1 CM induced predominantly bone resorption in calvaria, while Probasco CM induced marked bone formation, mineralization, and healing of calvaria defects. The expression of osteoblast‐related genes in calvaria showed that Probasco CM stimulated the maturation and differentiation of osteoblasts and inhibited osteoclastogenesis. Both bone modeling and remodeling were involved in Probasco‐induced bone formation and mineralization by inhibiting remodeling with zoledronic acid. RNAseq results from CM treated osteoblasts indicated that the WNT signaling pathway was activated by Probasco compared to either control or Ace‐1. In addition, Calvaria treated with Probasco+hDKK‐1 CM, Probasco transduced with human DKK‐1 cDNA (a WNT antagonist), showed decreased bone formation. In vivo, Our preliminary data showed that DKK‐1 significantly increased the growth of Probasco tumors after intratibial injection of Probasco+hDKK‐1 cells in nude mice, which suggested the autocrine effect of DKK‐1 on tumor cells. In conclusion, Probasco cells induced bone formation and mineralization in vitro that depended on the WNT signaling pathway. Probasco cells serve as a valuable model for studying the mechanisms of osteoblastic bone metastasis in prostate cancer.

Blockade of dendritic cell glutaminolysis induces allergic asthma desensitization via suppression of Tfh13 polarization

Abstract Allergic asthma is a pulmonary disease characterized by airway hyperresponsiveness (AhR) in response to inhaled allergens. AhR is largely mediated by allergen-specific (Ag-specific) IgE induced mast cell (MC) degranulation which drives inflammation of the airways following allergen exposure. Ag-specific IgE production requires T follicular helper 13 cells (Tfh13s) which must first be polarized by dendritic cells (DCs). The mechanisms by which DCs polarize Tfh13s, however, are unclear. We hypothesized that the Tfh13 inducing allergen Alternaria would induce a unique metabolic response compared to non-Tfh13 inducing stimuli. We found, by untargeted metabolomic analysis, that Alternaria induced accumulation of the glutamine-derived TCA cycle metabolite α-ketoglutarate compared to LPS stimulated or unstimulated DCs. Glutamine is converted to α-ketoglutarate by glutaminase (Gls), so we predicted that inhibition of Gls may suppress Tfh13 polarization by DCs. Indeed, we found that treatment with the Gls inhibitor, CB-839, reduced Tfh13 polarization and increased T follicular regulatory cells following Alternaria exposure. This finding was recapitulated in a DC adoptive transfer model, indicating that this mechanism is DC intrinsic. We next tested if CB-839 causes allergen desensitization in a model of allergic asthma. Mice were intranasally sensitized and challenged with Alternaria and intranasally treated with CB-839 or vehicle control prior to challenge. CB-839 treated mice exhibited reduced AhR, Ag-specific IgE, and airway MC degranulation. These data demonstrate that DC glutaminolysis is required for Tfh13 polarization, and that Gls inhibitors may promote allergen desensitization in allergic asthma. This work was funded by VCU's National Center for Advancing Translational Sciences (UL1TR002649) and NIAID (R56AI139658).

Carbon Nanotubes Film Integrated With Silicon Microfluidic Channel for a Novel Composite THz Metasurface

Owing to the unique electromagnetic response ability, artificial electromagnetic metasurfaces have potential applications in medical, imaging, sensing, and other fields. In this paper, a novel composite THz metasurface integrated by carbon nanotubes (CNTs) resonant metasurface and silicon microfluidic channel has been proposed, which combines the advantages of semiconductor and carbon nanotubes film materials. The absorption characteristics and the refractive index sensing capabilities are investigated comprehensively. Calculation results show that two obvious resonant absorption peaks located at 1.20 THz and 1.85 THz and the absorption is nearly 99.6% and 89.8%, respectively; the device performs a good linear relationship between the position of resonant absorption peaks and the refractive index, and the frequency sensitivity can achieve 492 GHz/RIU. The influence of structural parameters and the offset of the center of the CNTs metasurface on the absorption spectrum demonstrate that the novel composite metasurface has a good reliability and stability and can be used for sensing various materials in other frequency regions range from radio frequency through THz and to the infrared regime. This novel composite metasurface has good biocompatibility and low cost, which widens the application range of terahertz functional devices.

BESPOKE IO protocol: a multicentre, prospective observational study evaluating the utility of ctDNA in guiding immunotherapy in patients with advanced solid tumours

IntroductionImmunotherapy (IO) has transformed the treatment paradigm for a wide variety of solid tumours. However, assessment of response can be challenging with conventional radiological imaging (eg, iRECIST), which do not...

Abstract 503: Multiparameter Mass Cytometry Reveals The Unique Response Of NaïVe B Cell Cd27 - Subset With The Increase Of T-bet And Cd38 Expression After Radiation Therapy In Thoracic Cancer Patients

Cancer Radiation therapy (RT) induces cardiovascular disease (CVD) even when the heart is shealed or not irradiated, but there is a paucity of available preventive measures for RT-induced CVD. Ionizing radiation (IR) induces senescence, which was originally discovered to suppress tumorigenesis by inducing cell cycle blockade and necrosis, and positioned IR as pro-senescence cancer therapy. IR-induced senescence cells secrete cytokines, growth factors, and reactive oxygen species (ROS), becoming so called senescence associated secretory phenotype (SASP), and we hypothesize that SASP induction in immune cells cause CVD after RT. Although the involvement of DNA damage response (DDR), efferocytosis, and clonal hematopoiesis drivers (CHD) to SASP induction has been suggested, the exact mechanisms through which RT induces SASP in a specific cell type remains unclear. We characterize most of the major human immune cell lineages in a single assay using mass cytometery (CyTOF). We generated a CyTOF panel which includes antibodies against various senescence phenotype, DDR, efferocytosis, and CHD. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 month after RT from 16 thoracic cancer patients. First, we found the frequency of only B cell subtype was decreased after RT. Second, we obtained 138 functional profiling subsets by unsupervised clustering with our antibody set, and found that T-bet expression was increased in the largest B cell subset of naïve B Cell (CD27 - ) Ki67 lo CD38 lo DNMT3a hi after RT, which showed the good correlation with p-p90RSK expression in the samples from pre-RT and post-RT. Lastly, the significant increase of CD38 expression in the subsets of naïve B cell (CD27 - ) and CD8 + T cell (EMRA) was detected. These data suggest the unique response of naïve B cell (CD27-) to RT with the increase of CD38 expression, and T-bet in the subset of B Cell (CD27 - ) Ki67 lo CD38 lo DNMT3a hi , and also the potential role of p90RSK activation in IR-induced T-bet expression. T-bet plays a role in developing the age-associated B cell (ABC), and the increase of CD38 expression promotes aging-related events. Therefore, the induction of T-bet and CD38 in naïve B (CD27 - ) cell after RT supports the novel role of naïve B cell in IR-induced SASP and subsequent CVD.

Pulmonary endothelial cells from different vascular compartments exhibit unique recovery from acidification and Na+/H+ exchanger isoform expression

Sodium‐hydrogen exchangers (NHEs) tightly regulate intracellular pH (pHi), proliferation, migration and cell volume. Heterogeneity exists between pulmonary endothelial cells derived from different vascular segments, yet the activity and isoform expression of NHEs between these vascular segments has not been fully examined.Utilizing the ammonium‐prepulse and recovery from acidification technique in a buffer lacking bicarbonate, pulmonary microvascular and pulmonary artery endothelial cells exhibited a similar rate of recovery from the acid load regardless of the concentrations of the sodium transport inhibitor, amiloride; however, pulmonary artery endothelial cells required a higher dose of amiloride to inhibit sodium‐dependent acid recovery compared to pulmonary microvascular endothelial cells, suggesting a unique complement of NHEs between the different endothelial cell types. While NHE1 has been described in pulmonary endothelial cells, all NHE isoforms have not been accounted for. To address NHE expression in endothelial cells, qPCR was performed. Using a two‐gene normalization approach, Sdha and Ywhag were identified for qPCR normalization and analysis of NHE isoforms between pulmonary microvascular and pulmonary artery endothelial cells. NHE1 and NHE8 mRNA were equally expressed between the two cell types, but NHE5 expression was significantly higher in pulmonary microvascular and pulmonary artery endothelial cells.Thus, pulmonary microvascular and pulmonary artery endothelial cells exhibit unique NHE isoform expression and have a unique response to acid load revealed through recovery from cellular acidification.

Hiding in plain sight: What can interpretable unsupervised machine learning and clustering analysis tell us about the fire behavior of reinforced concrete columns?

The role of machine learning (ML) continues to rise in the structural fire engineering area. Noting the widespread of supervised ML approaches, such methods are being heavily utilized nowadays. On the other hand, little interest has been dedicated to unsupervised ML. Unlike supervised learning, unsupervised learning algorithms are trained using data that is neither classified nor labeled, thus, allowing the algorithm, and without guidance, to identify unseen patterns and decode hidden structures of complex phenomena residing in data. In this pursuit, this study presents findings obtained from one of the earliest investigations aimed to explore the potential of unsupervised and interpretable machine learning (ML) clustering analysis to investigate the response of reinforced concrete (RC) columns under fire conditions. We used four algorithms (namely, K-Means, Hierarchical, Fuzzy C-Means, and DBSCAN) to cluster over 140 fire-exposed RC columns. Results from our clustering analysis show that the performance of such columns can be distinctly grouped into unique clusters. Our findings allow structural fire engineers to 1) identify and avoid RC columns with poor fire performance and, when possible, 2) upgrade the features/characteristics of columns of poor fire response to achieve an improved behavior. Overall, our analysis indicates that fire-exposed RC columns naturally fit into four clusters – each with unique properties and response – that are governed by the material, geometric and loading features.