Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing.

Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries expressed gene programs for vascular development. HEV-expressed genes showed enrichment for genes encoding molecules involved in immunological defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated recruitment of lymphocytes, including a lymph node HEV-selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate-recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs.

Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice.

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(-) DCs were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported the induction of regulatory T cells. Both CD103(+) DC subsets induced the TH17 subset of helper T cells, while CD103(-)Sirpα(+) DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103(+) DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.

Design of Dielectric Resonator Antenna Using Dielectric Paste.

In this publication, the use of a dielectric paste for dielectric resonator antenna (DRA) design is investigated. The dielectric paste can serve as an alternative approach of manufacturing a dielectric resonator antenna by subsequently filling a mold with the dielectric paste. The dielectric paste is obtained by mixing nanoparticle sized barium strontium titanate (BST) powder with a silicone rubber. The dielectric constant of the paste can be adjusted by varying the BST powder content with respect to the silicone rubber content. The tuning range of the dielectric constant of the paste was found to be from 3.67 to 18.45 with the loss tangent of the mixture being smaller than 0.044. To demonstrate the idea of the dielectric paste approach, a circularly polarized DRA with wide bandwidth, which is based on a fractal geometry, is designed. The antenna is realized by filling a 3D-printed mold with the dielectric paste material, and the prototype was found to have an axial ratio bandwidth of 16.7% with an impedance bandwidth of 21.6% with stable broadside radiation.

Public Intoxication: Sobering Centers as an Alternative to Incarceration, Houston, 2010-2017.

In 2010, the Houston police department admitted 20 508 publicly intoxicated individuals into its jail. To address jail overcrowding, the city created a jail diversion policy that allowed law enforcement to admit publicly intoxicated individuals into a new sobering center. By 2017, public intoxication jail admissions had decreased by 95%, freeing valuable resources. A promising public health intervention, sobering centers offer an alternative to incarceration and relieve overuse of emergency services while assisting individuals with substance use issues.

Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo.

UNLABELLED: Circulating factor VIII (FVIII) is derived from liver and from extrahepatic sources probably of endothelial origin, but the vascular sites of FVIII production remain unclear. Among organs profiled, only liver and lymph nodes (LNs) show abundant expression of F8 messenger RNA (mRNA). Transcriptomic profiling of subsets of stromal cells, including endothelial cells (ECs) from mouse LNs and other tissues, showed that F8 mRNA is expressed by lymphatic ECs (LECs) but not by capillary ECs (capECs), fibroblastic reticular cells, or hematopoietic cells. Among blood ECs profiled, F8 expression was seen only in fenestrated ECs (liver sinusoidal and renal glomerular ECs) and some high endothelial venules. In contrast, von Willebrand factor mRNA was expressed in capECs but not in LECs; it was coexpressed with F8 mRNA in postcapillary high endothelial venules. Purified LECs and liver sinusoidal ECs but not capECs from LNs secrete active FVIII in culture, and human and mouse lymph contained substantial FVIII: C activity. Our results revealed localized vascular expression of FVIII and von Willebrand factor and identified LECs as a major cellular source of FVIII in extrahepatic tissues.

Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in Peyer's patches.

Although the homing of lymphocytes to GALT has been extensively studied, little is known about how high endothelial venules (HEVs) within Peyer's patches (PPs) are patterned to display dominantly mucosal addressin cell adhesion molecule 1 (MAdCAM-1). In this study, we report that Nkx2-3-deficient mice show gradual loss of MAdCAM-1 in PPs postnatally and increased levels of mRNA for peripheral lymph node addressin (PNAd) backbone proteins as well as enhanced expression of MECA79 sulfated glycoepitope at the luminal aspect of HEVs, thus replacing MAdCAM-1 with PNAd. Induction of PNAd in mutant PPs requires lymphotoxin ß receptor activity, and its upregulation needs the presence of mature T and B cells. Furthermore, treatment with MECA-79 anti-PNAd mAb in vivo effectively blocks lymphocyte homing to mutant PPs. Despite the replacement of MAdCAM-1 by PNAd in HEV endothelia, lymphocytes could efficiently home to PPs in mutant mice. We conclude that although Nkx2-3 activity controls the addressin balance of HEVs in GALT, the general HEV functionality is preserved independently from Nkx2-3, indicating a substantial plasticity in the specification of GALT HEV endothelium.

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system.

Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a "neurolymphocrine" system.

The role of surface and deep-level defects on the emission of tin oxide quantum dots.

This paper reports on the role of surface and deep-level defects on the blue emission of tin oxide quantum dots (SnO2 QDs) synthesized by the solution-combustion method at different combustion temperatures. X-ray diffraction studies showed the formation of a single rutile SnO2 phase with a tetragonal lattice structure. High resolution transmission electron microscopy studies revealed an increase in the average dot size from 2.2 to 3.6 nm with an increase of the combustion temperature from 350 to 550 °C. A decrease in the band gap value from 3.37 to 2.76 eV was observed with the increase in dot size due to the quantum confinement effect. The photoluminescence emission was measured for excitation at 325 nm and it showed a broad blue emission band for all the combustion temperatures studied. This was due to the creation of various oxygen and tin vacancies/defects as confirmed by x-ray photoelectron spectroscopy data. The origin of the blue emission in the SnO2 QDs is discussed with the help of an energy band diagram.

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

Humoral immune response of the small-spotted catshark, Scyliorhinus canicula.

Cartilaginous fishes are the oldest group in which an adaptive immune system based on immunoglobulin-superfamily members is found. This manuscript compares humoral immune function in small-spotted catshark (Scyliorhinus canicula) with that described for spiny dogfish (Squalus acanthias), another member of the Squalomorphi superorder, and nurse shark, the model for humoral immunity in elasmobranchs and a member of the Galeomorphi superorder. Although small-spotted catshark and nurse shark are separated by over 200 million years we found that immunoglobulin isoforms are well conserved between the two species. However, the plasma protein profile of small-spotted catshark was most similar to that of spiny dogfish, with low levels of pentameric IgM, and IgNAR present as a multimer in plasma rather than a monomer. We show that an antigen-specific monomeric IgM response, with a profile similar to that described previously for nurse sharks, can be raised in small-spotted catshark. Lacking polyclonal or monoclonal antibody reagents for detecting catshark IgNAR we investigated phage-display and recombinant Fc-fusion protein expression as alternative methods to look for an antigen-specific response for this isotype. However, we could find no evidence of an antigen-specific IgNAR in the animals tested using either of these techniques. Thus, unlike nurse sharks where antigen-specific monomeric IgM and IgNAR appear together, it seems there may be a temporal or complete 'uncoupling' of these isotypes during a humoral response in the small-spotted catshark.

Systems thinking and efficiency under emissions constraints: Addressing rebound effects in digital innovation and policy.

Innovations and efficiencies in digital technology have lately been depicted as paramount in the green transition to enable the reduction of greenhouse gas emissions, both in the information and communication technology (ICT) sector and the wider economy. This, however, fails to adequately account for rebound effects that can offset emission savings and, in the worst case, increase emissions. In this perspective, we draw on a transdisciplinary workshop with 19 experts from carbon accounting, digital sustainability research, ethics, sociology, public policy, and sustainable business to expose the challenges of addressing rebound effects in digital innovation processes and associated policy. We utilize a responsible innovation approach to uncover potential ways forward for incorporating rebound effects in these domains, concluding that addressing ICT-related rebound effects ultimately requires a shift from an ICT efficiency-centered perspective to a "systems thinking" model, which aims to understand efficiency as one solution among others that requires constraints on emissions for ICT environmental savings to be realized.

Bronchial artery embolization for hemoptysis in a postpartum patient via cesarean section with COVID-19 while on extracorporeal membrane oxygenation.

Although COVID-19 coagulopathy typically manifests with thrombotic complications, hemorrhagic complications also occur and must be considered when making decisions about anticoagulation in these patients. Here, we report a case of massive hemoptysis occurring in a recently post-partum woman via Cesarean section with COVID-19 who was managed via bronchial artery embolization while on extracorporeal membrane oxygenation.

Correlations of Radiographic and Endoscopic Observations in Subglottic Stenosis.

OBJECTIVE(S): Subglottic stenosis (SGS) represents a constellation of diverse pathologic processes that ultimately lead to narrowing of the subglottic region and can produce significant morbidity. Existing endoscopic and radiographic assessments may not be consistent in practice. METHODS: Severity of stenosis was evaluated and reported using the Cotton-Myer classification system from 33 endoscopic procedures from 32 unique subjects. Radiographic imaging within the preceding 3 month period was subsequently reviewed and narrowing was measured by a blinded radiologist. Degree of stenosis was reported as a percentage in 30 out of 33 endoscopic evaluations and subsequently compared to radiographically determined percentage of stenosis. Statistical analyzes were conducted to evaluate concordance between endoscopic and radiographic assessments. RESULTS: About 45.5% (15/33) of the evaluations were in agreement using Cotton-Myer scoring, while 27.3% (9/33) were discrepant by 1 grade and 27.3% (9/33) by 2 grades. Correlation of degree of stenosis as a percentage using Spearman (coefficient: 0.233, P-value: .214) and Pearson (coefficient: 0.138, P-value: .466) methods demonstrated very weak relationships. Radiographic scoring did not predict endoscopic classification to a significant degree using mixed effects regression. CONCLUSIONS: Radiographic and endoscopic grading of subglottic stenosis may not be reliably concordant in practice.

Erratum: The real climate and transformative impact of ICT: A critique of estimates, trends, and regulations.

[This corrects the article DOI: 10.1016/j.patter.2021.100340.].

Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease.

Immunotherapy targeting of amyloid beta (Abeta) peptide in transgenic mouse models of Alzheimer disease (AD) has been widely demonstrated to resolve amyloid deposition as well as associated neuronal, glial, and inflammatory pathologies. These successes have provided the basis for ongoing clinical trials of immunotherapy for treatment of AD in humans. Acute as well as chronic Abeta-targeted immunotherapy has also been demonstrated to reverse Abeta-related behavioral deficits assessing memory in AD transgenic mouse models. We observe that three antibodies targeting the same linear epitope of Abeta, Abeta(3-7), differ in their ability to reverse contextual fear deficits in Tg2576 mice in an acute testing paradigm. Reversal of contextual fear deficit by the antibodies does not correlate with in vitro recognition of Abeta in a consistent or correlative manner. To better define differences in antigen recognition at the atomic level, we determined crystal structures of Fab fragments in complex with Abeta. The conformation of the Abeta peptide recognized by all three antibodies was highly related and is also remarkably similar to that observed in independently reported Abeta:antibody crystal structures. Sequence and structural differences between the antibodies, particularly in CDR3 of the heavy chain variable region, are proposed to account for differing in vivo properties of the antibodies under study. These findings provide a structural basis for immunotherapeutic strategies targeting Abeta species postulated to underlie cognitive deficits in AD.

The Impact of a Virtual Radiology Medical Student Rotation: Maintaining Engagement During COVID-19 Mitigation.

INTRODUCTION: The purpose of this study is to introduce a virtual radiology rotation curriculum that is being used to safely maintain medical student and intern education and engagement with the Department of Radiology at Walter Reed National Military Medical Center during coronavirus disease 2019 (COVID-19) mitigation. MATERIALS AND METHODS: The curriculum is designed as a 4-week block with each week representing one of the four highest yield radiology subspecialties for medical students; neuroradiology, thoracic radiology, body radiology, and musculoskeletal radiology. A subspecialist radiologist from each section was identified as a primary mentor and tasked with designing a daily schedule for medical students and interns. The first 2 months of virtual rotators were surveyed to assess the effectiveness of the course. RESULTS: Thirty-five of 41 rotators responded to the survey, a response rate of 85%. Thirty-one of 35 (89%) of the rotators gave this virtual elective rotation a positive rating, with 16 trainees scoring the course as 4 out of 5 and 15 trainees selecting 5 out of 5. Four respondents selected 3 out of 5. Five out of 5 respondents who had experienced an in-person radiology elective rotation before this virtual rotation rated the virtual elective as more educational than the in-person rotation. We found the 4-week subspecialist mentor-based structure to be highly versatile, allowing us to simultaneously accommodate multiple groups of full or partial block rotators throughout COVID-19 mitigation. CONCLUSION: A virtual rotation curriculum is a viable method of maintaining medical student and intern education and engagement with the department of radiology during COVID-19 mitigation.

The real climate and transformative impact of ICT: A critique of estimates, trends, and regulations.

In this paper, we critique ICT's current and projected climate impacts. Peer-reviewed studies estimate ICT's current share of global greenhouse gas (GHG) emissions at 1.8%-2.8% of global GHG emissions; adjusting for truncation of supply chain pathways, we find that this share could actually be between 2.1% and 3.9%. For ICT's future emissions, we explore assumptions underlying analysts' projections to understand the reasons for their variability. All analysts agree that ICT emissions will not reduce without major concerted efforts involving broad political and industrial action. We provide three reasons to believe ICT emissions are going to increase barring intervention and find that not all carbon pledges in the ICT sector are ambitious enough to meet climate targets. We explore the underdevelopment of policy mechanisms for enforcing sector-wide compliance, and contend that, without a global carbon constraint, a new regulatory framework is required to keep the ICT sector's footprint aligned with the Paris Agreement.

Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis.

Centrosomes act as sites of microtubule growth, but little is known about how the number and stability of microtubules emanating from a centrosome are controlled during the cell cycle. We studied the role of the TACC3-XMAP215 complex in this process by using purified proteins and Xenopus laevis egg extracts. We show that TACC3 forms a one-to-one complex with and enhances the microtubule-stabilizing activity of XMAP215 in vitro. TACC3 enhances the number of microtubules emanating from mitotic centrosomes, and its targeting to centrosomes is regulated by Aurora A-dependent phosphorylation. We propose that Aurora A regulation of TACC3 activity defines a centrosome-specific mechanism for regulation of microtubule polymerization in mitosis.

Forecasting Air Quality in Taiwan by Using Machine Learning.

This study proposes a gradient-boosting-based machine learning approach for predicting the PM2.5 concentration in Taiwan. The proposed mechanism is evaluated on a large-scale database built by the Environmental Protection Administration, and Central Weather Bureau, Taiwan, which includes data from 77 air monitoring stations and 580 weather stations performing hourly measurements over 1 year. By learning from past records of PM2.5 and neighboring weather stations' climatic information, the forecasting model works well for 24-h prediction at most air stations. This study also investigates the geographical and meteorological divergence for the forecasting results of seven regional monitoring areas. We also compare the prediction performance between Taiwan, Taipei, and London; analyze the impact of industrial pollution; and propose an enhanced version of the prediction model to improve the prediction accuracy. The results indicate that Taipei and London have similar prediction results because these two cities have similar topography (basin) and are financial centers without domestic pollution sources. The results also suggest that after considering industrial impacts by incorporating additional features from the Taichung and Thong-Siau power plants, the proposed method achieves significant improvement in the coefficient of determination (R2) from 0.58 to 0.71. Moreover, for Taichung City the root-mean-square error decreases from 8.56 for the conventional approach to 7.06 for the proposed method.

P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion.

P2Y5 is a G protein-coupled receptor that binds and is activated by lysophosphatidic acid (LPA). We determined that P2Y5 transcript is expressed along the intestinal mucosa and investigated the intracellular pathways induced by P2Y5 activation, which could contribute to LPA effects on intestinal cell adhesion. P2Y5 heterologously expressed in CHO and small intestinal hBRIE 380i cells was activated by LPA resulting in an increase in intracellular calcium ([Ca(2+)](i)) when the cells concurrently expressed G(alpha)(Delta6qi5myr). P2Y5 activation also increased the phosphorylation of ERK1/2 that was sensitive to pertussis toxin. Together these indicate that P2Y5 activation by LPA induces an increase in [Ca(2+)](i) and ERK1/2 phosphorylation through G(alpha)(i). We discovered that P2Y5 was activated by farnesyl pyrophosphate (FPP) without a detectable change in [Ca(2+)](i). The activation of P2Y5 by LPA or FPP induced the activity of a serum response element (SRE)-linked luciferase reporter that was inhibited by the RGS domain of p115RhoGEF, C3 exotoxin, and Y-27632, suggesting the involvement of G(alpha)(12/13), Rho GTPase, and ROCK, respectively. However, only LPA-mediated induction of SRE reporter activity was sensitive to inhibitors targeting p38 MAPK, PI3K, PLC, and PKC. In addition, only LPA transactivated the epidermal growth factor receptor, leading to an induction of ERK1/2 phosphorylation. These observations correlate with our subsequent finding that P2Y5 activation by LPA, and not FPP, reduced intestinal cell adhesion. This study elucidates a mechanism whereby LPA can act as a luminal and/or serosal cue to alter mucosal integrity.