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Nitrogen-polar III-nitride heterostructures offer advantages over metal-polar structures in high frequency and high power applications. However, polarity control in III-nitrides is difficult to achieve as a result of unintentional polarity inversion domains (IDs). Herein, we present a comprehensive structural investigation with both atomic detail and thermodynamic analysis of the polarity evolution in low- and high-temperature AlN layers on on-axis and 4$^{\circ}$ off-axis Carbon-face 4H-SiC (000$\bar{1}$) grown by hot-wall metal organic chemical vapor deposition. A polarity control strategy has been developed by variation of thermodynamic Al supersaturation and substrate misorientation angle in order to achieve desired growth mode and polarity. We demonstrate that IDs are totally suppressed for high-temperature AlN nucleation layers when step-flow growth mode is achieved at the off-axis. We employ this approach to demonstrate high quality N-polar epitaxial AlGaN/GaN/AlN heterostructures., Comment: 9 pages, 6 figures

Owing to their very large piezoelectric coefficients and spontaneous polarizations, (Sc,Y)xAl1−xN alloys have emerged as a new class of III-nitride semiconductor materials with great potential for high-frequency electronic and acoustic devices. The thermal conductivity of constituent materials is a key parameter for design, optimization, and thermal management of such devices. In this study, transient thermoreflectance technique is applied to measure the thermal conductivity of ScxAl1−xN and YxAl1−xN (0 ≤x ≤0.22) layers grown by magnetron sputter epitaxy in the temperature range of 100–400 K. The room-temperature thermal conductivity of both alloys is found to decrease significantly with increasing Sc(Y) composition compared to that of AlN. We also found that the thermal conductivity of YxAl1−xN is lower than that of ScxAl1−xN for all studied compositions. In both alloys, the thermal conductivity increases with the temperature up to 250 K and then saturates. The experimental data are analyzed using a model based on the solution of the phonon Boltzmann transport equation within the relaxation time approximation. The contributions of different phonon-scattering mechanisms to the lattice thermal conductivity of (Sc,Y)xAl1−xN alloys are identified and discussed.

Primary immunodeficiency diseases (PIDs) caused by a single-gene defect generally are referred to as monogenic autoimmune disorders. For example, mutations in the transcription factor autoimmune regulator (AIRE) result in a condition called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; while mutations in forkhead box P3 lead to regulatory T cell (Treg)-deficiency-induced multiorgan inflammation, which in humans is called "immune dysregulation, polyendocrinopathy, enteropathy with X-linked inheritance" (or IPEX syndrome). Previous studies concluded that monogenic diseases are insensitive to commensal microbial regulation because they develop even in germ-free (GF) animals, a conclusion that has limited the number of studies determining the role of microbiota in monogenic PIDs. However, emerging evidence shows that although the onset of the disease is independent of the microbiota, several monogenic PIDs vary in severity in association with the microbiome. In this review, we focus on monogenic PIDs associated with Treg deficiency/dysfunction, summarizing the gut microbial dysbiosis that has been shown to be linked to these diseases. From limited studies, we have gleaned several mechanistic insights that may prove to be of therapeutic importance in the early stages of life. IMPACT: This review paper serves to refute the concept that monogenic PIDs are not linked to the microbiome. The onset of monogenic PIDs is independent of microbiota; single-gene mutations such as AIRE or Foxp3 that affect central or peripheral immune tolerance produce monogenic diseases even in a GF environment. However, the severity and outcome of PIDs are markedly impacted by the microbial composition. We suggest that future research for these conditions may focus on targeting the microbiome.

Dried vegetables are considered convenient for storage, transportation and preservation. The different drying techniques could influence the quality of resulting products. This study aimed to evaluate the effects of three distinguish drying methods as hot-air drying, foam-mat drying and microwave drying on the color retention and chlorophyll of green vegetables powder. Fresh spinach(Spinacia oleraceaL.), celery (Apium graveolensL.), Malabar spinach (Basella albaL.) were dried by different methods: hot air at 60oC, foam-mat at 60oC and microwave at 270 W until the samples reached approximately 9% of moisture content (wb). The drying time of the dried samples by microwave, foam-mat and hot-air method were 60, 210 and 240 min, respectively. Foam-mat dried vegetables were found to have the best quality in terms of color and the residual chlorophyll content. The findings suggest that foam-mat drying is promising in dried vegetable processing

Economic analysis of managed aquifer recharge (MAR) typically focuses on identifying the quantity of water to add cost-effectively to natural rates of recharge. However, to the extent that MAR is successful, higher groundwater levels or at least slower depletion are likely to influence crop choice and groundwater pumping dynamics. Using a landscape-level model, we maximize farm net returns taking into account MAR and on-farm surface reservoir storage, crop choice, and the impacts of drought on groundwater use in Eastern Arkansas, USA, over 120 years. We find that drought frequency (risk) has a stronger influence on groundwater pumping and MAR use compared with drought severity. There is evidence of a substantial slippage, the percentage of the increase in groundwater use with versus without MAR divided by the MAR use, under a range of MAR cost and drought scenarios. Total slippage ranges from about 32 to 75% of total MAR water, indicating that only 68-25% of the MAR water raises groundwater levels. Even if the costs of MAR are relatively high and slippage is present, the total net returns to farms in this region are higher, and the variability in those returns are less with MAR.

In this study, new donor–acceptor (D–A) conjugated polymers based on 4-(4-((2-ethylhexyl)oxy)phenyl)-4H-dithieno[3,2-b:2′,3′-d]pyrrole (EPDP) and 3,6-bis(5-bromothiophen-2-yl)-2,5-bis(2-ethylhexyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (BTBP) or 4,7-bis(5-bromothiophen-2-yl)benzo[c][1,2,5]thiadiazole (BT) have been synthesized successfully via direct (hetero)arylation polymerization using Pd(OAc)2 and PCy3·HBF4 as a catalyst system. The obtained D–A conjugated polymers have been characterized via1H NMR, GPC, FTIR, DSC, XRD, PL and UV-Vis methods. Afterward, the D–A conjugated polymers have been applied for the fabrication of organic solar cells based on bulk-heterojunction (BHJ) structures.

Severe illness caused by coronavirus disease 2019 (COVID-19) is characterized by an overexuberant inflammatory response resulting in acute respiratory distress syndrome (ARDS) and progressive respiratory failure (A. Gupta, M. V. Madhavan, K. Sehgal, N. Nair, et al., Nat Med 26:1017-1032, 2020, https://doi.org/10.1038/s41591-020-0968-3). Rhesus theta (θ) defensin-1 (RTD-1) is a macrocyclic host defense peptide exhibiting antimicrobial and immunomodulatory activities. RTD-1 treatment significantly improved survival in murine models of a severe acute respiratory syndrome (SARS-CoV-1) and endotoxin-induced acute lung injury (ALI) (C. L. Wohlford-Lenane, D. K. Meyerholz, S. Perlman, H. Zhou, et al., J Virol 83:11385-11390, 2009, https://doi.org/10.1128/JVI.01363-09; J. G. Jayne, T. J. Bensman, J. B. Schaal, A. Y. J. Park, et al., Am J Respir Cell Mol Biol 58:310-319, 2018, https://doi.org/10.1165/rcmb.2016-0428OC). This investigation aimed to characterize the preclinical pharmacokinetics (PK) and safety of intravenous (i.v.) RTD-1. Based on the lack of adverse findings, the no observed adverse effect level (NOAEL) was established at 10 mg/kg/day in rats and 15 mg/kg/day in monkeys. Analysis of single ascending dose studies in both species revealed greater-than-dose-proportional increases in the area under the curve extrapolated to infinity (AUC

We report on the free charge carrier properties of a two-dimensional electron gas (2DEG) in an AlN/AlxGa1-xN high electron mobility transistor structure with a high aluminum content (x = 0.78). The 2DEG sheet density N s = ( 7.3 +/- 0.7 ) x 10 12 cm(-2), sheet mobility mu s = ( 270 +/- 40 ) cm(2)/(Vs), sheet resistance R- s = ( 3200 +/- 500 ) omega/ ?, and effective mass m( eff) = ( 0.63 +/- 0.04 ) m( 0) at low temperatures ( T = 5 K ) are determined by terahertz (THz) optical Hall effect measurements. The experimental 2DEG mobility in the channel is found within the expected range, and the sheet carrier density is in good agreement with self-consistent Poisson-Schrodinger calculations. However, a significant increase in the effective mass of 2DEG electrons at low temperatures is found in comparison with the respective value in bulk Al0.78Ga22N ( m( eff) = 0.334 m( 0)). Possible mechanisms for the enhanced 2DEG effective mass parameter are discussed and quantified using self-consistent Poisson-Schrodinger calculations .Published under an exclusive license by AIP Publishing. Funding Agencies|Swedish Governmental Agency for Innovation Systems (VINNOVA) under the Competence Center Program [2016-05190]; Chalmers University of technology; Ericsson; United Monolithic Semiconductors (UMS); Volvo Cars; Swedish Research Council Vetenskapsradet (VR) [2016-00889]; Swedish Foundation for Strategic Research [RIF14-055, EM16-0024]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoeping University, Faculty Grant Stark forskningsmiljoe (SFO) Mat LiU [2009-00971]; National Science Foundation [DMR 1808715, OIA-2044049]; Air Force Office of Scientific Research [FA9550-18-1-0360, FA9550-19-S-0003, FA9550-21-1-0259]

Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.

Adoptive transfer of regulatory T cells (FOXP3+ Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion. Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP). The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer. The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay. Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively. Results: LAP+ repurification results in >90% LAP+FOXP3+ Tregs, leaving behind FOXP3- and FOXP3+ nonTregs within the LAP- population. After 4-week expansion, the LAP+ Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity. In the xGVHD model, exogenous CD25-PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP+ Tregs increased median survival to 47 days, while the LAP parent (CD25+) and LAP- nonTregs had median survival of 39 and 31 days, respectively. Conclusions: These preclinical data together provide evidence that LAP+ Tregs are highly purified with fully suppressive function for cell therapy. This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP+ Tregs to prevent or treat GVHD and other autoimmune diseases.

The Endoscopy Computer Vision Challenge (EndoCV) is a crowd-sourcing initiative to address eminent problems in developing reliable computer aided detection and diagnosis endoscopy systems and suggest a pathway for clinical translation of technologies. Whilst endoscopy is a widely used diagnostic and treatment tool for hollow-organs, there are several core challenges often faced by endoscopists, mainly: 1) presence of multi-class artefacts that hinder their visual interpretation, and 2) difficulty in identifying subtle precancerous precursors and cancer abnormalities. Artefacts often affect the robustness of deep learning methods applied to the gastrointestinal tract organs as they can be confused with tissue of interest. EndoCV2020 challenges are designed to address research questions in these remits. In this paper, we present a summary of methods developed by the top 17 teams and provide an objective comparison of state-of-the-art methods and methods designed by the participants for two sub-challenges: i) artefact detection and segmentation (EAD2020), and ii) disease detection and segmentation (EDD2020). Multi-center, multi-organ, multi-class, and multi-modal clinical endoscopy datasets were compiled for both EAD2020 and EDD2020 sub-challenges. The out-of-sample generalization ability of detection algorithms was also evaluated. Whilst most teams focused on accuracy improvements, only a few methods hold credibility for clinical usability. The best performing teams provided solutions to tackle class imbalance, and variabilities in size, origin, modality and occurrences by exploring data augmentation, data fusion, and optimal class thresholding techniques., 32 pages

Mid-infrared (IR) laser spectroscopy is broadly used to study trace gas species in medical diagnostics, atmospheric monitoring, remote sensing, and industrial applications. Its capability to measure fundamental rovibrational bands due to the chemical functional groups in the most relevant gas molecules allows for high instrumental sensitivity. In this work, we used a target mid-IR wavelength laser diode to measure the concentration of CO2 gas. In addition, detecting the weak mid-IR molecular absorption bands of gases like CO2 at low concentrations requires increasing optical path lengths to be used. There are a number of methods that can potentially be used to lengthen the beam path in a spectroscopic system; the most obvious being to use a longer linear gas cell, which in some situations may suffice; however, space and volume requirements need to be considered. In this work, we used a circular multi-reflection (CMR) cell, which reflects the radiation back and forth through the sample medium multiple times greatly reducing the footprint size compared to a linear cell of equivalent path length. A CMR cell is designed and constructed so that it allows multi-reflections within the cell. The optical alignment of the cell and the convenience of changing the optical path length by adjusting its position with respect to the entering light beam are key advantages. This work will be used as the groundwork for designing an instrument for high-resolution measurement of gas abundances in planetary atmospheres.

With the rapid advancement of imaging technology, space-based remote sensing instruments are becoming more sophisticated and are producing substantially more amounts of data for downloading. Data alteration is very likely to occur during the transmission over the long distances from probes to carrier spacecraft and subsequently back to Earth,. Cyclic Redundancy Check (CRC) is the most well-known data package error check technique which has been used in many applications. Unfortunately, due to its serial computation process, it could be a bottleneck for critical applications that require rapid processing. To overcome such issue, we present here a parallel CRC computational method based on an FPGA with simulation and testing to validate the methodology.

In this research, a novel organic photocatalyst of 10-(Perylene-3-yl-10H-Phenoxazine (PHP) has been synthesized successfully from perylene and phenoxazine via Buchwald-Hartwig C-N coupling. The chemical structure of catalyst was determined via proton nuclear magnetic resonance (1H-NMR) spectrum and optical properties were investigated through UV-Vis spectroscopy. The PHP has been used as the reducing photoredox catalyst for organocatalyzed atom transfer radical polymerization (ATRP) under UV irradiation. The well controlled molecular weight of polymers based on methyl methacrylate monomers have been obtained with monomer conversion up to 77.61% and low polydispersity index under 1.5.

Chest radiography is one of the most common types of diagnostic radiology exams, which is critical for screening and diagnosis of many different thoracic diseases. Specialized algorithms have been developed to detect several specific pathologies such as lung nodule or lung cancer. However, accurately detecting the presence of multiple diseases from chest X-rays (CXRs) is still a challenging task. This paper presents a supervised multi-label classification framework based on deep convolutional neural networks (CNNs) for predicting the risk of 14 common thoracic diseases. We tackle this problem by training state-of-the-art CNNs that exploit dependencies among abnormality labels. We also propose to use the label smoothing technique for a better handling of uncertain samples, which occupy a significant portion of almost every CXR dataset. Our model is trained on over 200,000 CXRs of the recently released CheXpert dataset and achieves a mean area under the curve (AUC) of 0.940 in predicting 5 selected pathologies from the validation set. This is the highest AUC score yet reported to date. The proposed method is also evaluated on the independent test set of the CheXpert competition, which is composed of 500 CXR studies annotated by a panel of 5 experienced radiologists. The performance is on average better than 2.6 out of 3 other individual radiologists with a mean AUC of 0.930, which ranks first on the CheXpert leaderboard at the time of writing this paper., Comment: This is a pre-print of our paper that was accepted by Neurocomputing - Its shorter version has been accepted by Medical Imaging with Deep Learning conference (MIDL 2020)

NASA Goddard Space Flight Center (GSFC) has successfully developed and tested a custom-designed low-noise multi-channel digitizer (MCD) application specific integrated circuit (ASIC) for operation in harsh radiation environments. The MCD-ASIC is optimized for low-frequency and low-voltage signal measurements from sensors and transducers. It has 20 input channels where each channel is comprised of auto-zeroed chopper variable-gain amplifier, post amplifier, and a second order ΣΔ modulator. ΣΔ analog-to-digital converter (ADC) relies on oversampling and noise shaping to achieve high-resolution conversion. However, the MCD-ASIC requires digital filtering and decimation to convert the output single bit streams from the ADC to useful data words. A parallel digital platform such as a field-programmable-gate-array (FPGA) is highly suitable to fully leverage the capabilities of the MCD-ASIC. The FPGA controls the MCD-ASIC via serial peripheral interface (SPI) protocol and acquires data from it. A Python-script communicates with the FPGA board through a USB interface on a cross operating platform. Using this architecture, the system is capable of monitoring up to 20 voltage readout channels simultaneously in a real-time manner. Each channel’s parameters can be programmed independently allowing maximum user versatility. In this paper, we present analysis of the analog front-end, the implementation of the digital processing unit on the FPGA, and provide noise performance results from the MCD-ASIC readout.

The design of an advanced Net Flux Radiometer (NFR), for inclusion as a payload on a future Ice Giants probe mission, is given. The Ice Giants NFR (IG-NFR) will measure the upward and downward radiation flux (hence net radiation flux), in seven spectral bands, spanning the range from solar to far infra-red wavelengths, each with a 5° Field-Of-View (FOV) and in five sequential view angles (±80°, ±45°, and 0°) as a function of altitude. IG-NFR measurements within either Uranus or Neptune’s atmospheres, using dedicated spectral filter bands will help derive radiative heating and cooling profiles, and will significantly contribute to our understanding of the planet’s atmospheric heat balance and structure, tropospheric 3-D flow, and compositions and opacities of the cloud layers. The IG-NFR uses an array of non-imaging Winston cones integrated to a matched thermopile detector Focal Plane Assembly (FPA), with individual bandpass filters, housed in a diamond windowed vacuum micro-vessel. The FPA thermopile detector signals are read out in parallel mode, amplified and processed by a multi-channel digitizer application specific integrated circuit (MCD ASIC) under field programmable gate array (FPGA) control. The vacuum micro-vessel rotates providing chopping between FOV’s of upward and downward radiation fluxes. This unique design allows for small net flux measurements in the presence of large ambient fluxes and rapidly changing ambient temperatures during the probe descent to ≥10 bar pressure.

We propose a novel method that combines a convolutional neural network (CNN) with a long short-term memory (LSTM) mechanism for accurate prediction of intracranial hemorrhage on computed tomography (CT) scans. The CNN plays the role of a slice-wise feature extractor while the LSTM is responsible for linking the features across slices. The whole architecture is trained end-to-end with input being an RGB-like image formed by stacking 3 different viewing windows of a single slice. We validate the method on the recent RSNA Intracranial Hemorrhage Detection challenge and on the CQ500 dataset. For the RSNA challenge, our best single model achieves a weighted log loss of 0.0522 on the leaderboard, which is comparable to the top 3% performances, almost all of which make use of ensemble learning. Importantly, our method generalizes very well: the model trained on the RSNA dataset significantly outperforms the 2D model, which does not take into account the relationship between slices, on CQ500. Our codes and models is publicly avaiable at https://github.com/VinBDI-MedicalImagingTeam/midl2020-cnnlstm-ich.

Transient thermoreflectance (TTR) technique is employed to study the thermal conductivity of beta-Ga2O3 and high Al-content AlxGa1-xN semiconductors, which are very promising materials for high-power device applications. The experimental data are analyzed with the Callaways model taking into account all relevant phonon scattering processes. Our results show that out-of-plane thermal conductivity of high Al-content AlxGa1-xN and (-201) beta-Ga2O3 is of the same order of magnitude and approximately one order lower than that of GaN or AlN. The low thermal conductivity is attributed to the dominant phonon-alloy scattering in AlxGa1-xN and to the strong Umklapp phonon-phonon scattering in beta-Ga2O3. It is also found that the phonon-boundary scattering is essential in thin beta-Ga2O3 and AlxGa1-xN layers even at high temperatures and the thermal conductivity strongly deviates from the common 1/T temperature dependence. Funding Agencies|Swedish Governmental Agency for Innovation Systems (VINNOVA) under the Competence Center Program [2016-05190]; Swedish Research Council VRSwedish Research Council [2016-00889, 2017-03714]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [FL12-0181, RIF14-055, EM16-0024]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University, Faculty Grant SFO Mat LiU [2009-00971]; NSFNational Science Foundation (NSF) [CBET-1336464, DMR-1506159]

Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic-associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single-species probiotics.

Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by Toll-like receptor 2 (TLR2), which is known to mediate proinflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2−/− or wild-type (WT) mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress. Treatment groups were administered formula supplemented with LR 17938 or placebo (deMan-Rogosa-Sharpe media). We observed that LR 17938 significantly reduced the incidence of NEC and reduced the percentage of activated effector CD4+T cells, while increasing Foxp3+ regulatory T cells in the intestinal mucosa of WT mice with NEC, but not in TLR2−/− mice. Dendritic cell (DC) activation by LR 17938 was mediated by TLR2. The percentage of tolerogenic DC in the intestine of WT mice was increased by LR 17938 treatment during NEC, a finding not observed in TLR2−/− mice. Furthermore, gut levels of proinflammatory cytokines IL-1β and IFN-γ were decreased after treatment with LR 17938 in WT mice but not in TLR2−/− mice. In conclusion, the combined in vivo and in vitro findings suggest that TLR2 receptors are involved in DC recognition and DC-priming of T cells to protect against NEC after oral administration of LR 17938. Our studies further clarify a major mechanism of probiotic LR 17938 action in preventing NEC by showing that neonatal immune modulation of LR 17938 is mediated by a mechanism requiring TLR2. NEW & NOTEWORTHY Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to protect against necrotizing enterocolitis (NEC) in neonates and in neonatal animal models. The role of Toll-like receptor 2 (TLR2) as a sensor for gram-positive probiotics, activating downstream anti-inflammatory responses is unclear. Our current studies examined TLR2 −/− mice subjected to experimental NEC and demonstrated that the anti-inflammatory effects of LR 17938 are mediated via a mechanism requiring TLR2.

We report on crystallographic behaviors of inclined GaAs nanowires (NWs) self-crystallized on GaAs (001) substrate. The NWs were grown on hydrogen-silsesquioxane (HSQ) covered substrates using molecular beam epitaxy (MBE). Commonly, the epitaxial growth of GaAs " is="true"> 111 B (B-polar) NWs is prominently observed on GaAs (001); however, we yielded a remarkable number of epitaxially grown GaAs " is="true"> 111 A (A-polar) NWs in addition to the majorly obtained B-polar NWs. Such NW orientations are always accompanied by a typical inclined angle of 35° from (001) plane. NWs with another inclined angle of 74° were additionally observed and attributed to be " is="true"> 111 -oriented, not in direct epitaxial relation with the substrate. Such 74° NWs' existence is related to first-order three-dimensional (3D) lattice rotation taking place at the very beginning of the growth. It turns out that spatially 60° lattice rotation around " is="true"> 111 directions at GaAs seeds is essentially in charge of A- and B-polar 74° NWs. Transmission electron microscope observations reveal a high density of twinning in the B-polar NWs and twin-free characteristic in the A-polar NWs.

Theta-defensins (θ-defensins) are macrocyclic peptides expressed exclusively in granulocytes and selected epithelia of Old World monkeys. They contribute to anti-pathogen host defense responses by directly killing a diverse range of microbes. Of note, θ-defensins also modulate microbe-induced inflammation by affecting the production of soluble tumor necrosis factor (sTNF) and other proinflammatory cytokines. Here, we report that natural rhesus macaque θ-defensin (RTD) isoforms regulate sTNF cellular release by inhibiting TNF-α–converting enzyme (TACE; also known as a disintegrin and metalloprotease 17; ADAM17), the primary pro-TNF sheddase. Dose-dependent inhibition of cellular TACE activity by RTDs occurred when leukocytes were stimulated with live Escherichia coli cells as well as numerous Toll-like receptor agonists. Moreover, the relative inhibitory potencies of the RTD isoforms strongly correlated with their suppression of TNF release by stimulated blood leukocytes and THP-1 monocytes. RTD isoforms also inhibited ADAM10, a sheddase closely related to TACE. TACE inhibition was abrogated by introducing a single opening in the RTD-1 backbone, demonstrating that the intact macrocycle is required for enzyme inhibition. Enzymologic analyses showed that RTD-1 is a fast binding, reversible, non-competitive inhibitor of TACE. We conclude that θ-defensin–mediated inhibition of pro-TNF proteolysis by TACE represents a rapid mechanism for the regulation of sTNF and TNF-dependent inflammatory pathways. Molecules with structural and functional features mimicking those of θ-defensins may have clinical utility as TACE inhibitors for managing TNF-driven diseases.

Research on nanowire (NW) growth of III-V semiconductors including GaAs and InAs demonstrated the ability to grow in both wurtzite (WZ) and zincblende (ZB) polymorphs. However, the control of crystal phase in self-catalyzed NW growth is still a remaining challenge. In this study we report a controlled growth of GaAs/InAs core/shell nanowires in WZ phase using self-catalyzed molecular beam epitaxy (MBE). The GaAs NWs having pure WZ crystal were achieved and attributed to the effect of small wetting angle, which is realized by supplying high V/III ratio. Furthermore, the WZ formation is shown to be uninfluenced by NW diameter. For the wetting angle larger than 90°, mixed phase starts to be observed. The InAs shell is planarly grown on six m-plane facets of the GaAs core NWs leading to the same strain states along a and c axes of growth plane, in which tensile and compressive strains are observed for GaAs core and InAs shell, respectively. High-resolution transmission electron microscopy (HR-TEM) reveals a few misfit dislocations (~0.03 nm−1) at GaAs/InAs interface indicating insignificant strain relief via creating misfit dislocation. Electrical characterization of the hetero-wires shows that the InAs shell exhibits n-type conduction. A room-temperature sheet carrier concentration at zero gate-bias of 2.5 × 1012 cm−2 and the corresponding carrier mobility of ~ 900 cm2 V−1 s−1 are demonstrated.

Understanding and documenting historical agricultural land use and farming practices is important for assessment of environmental benefits of no-till (NT). To address the need for quantitative estimates of time patterns of tillage practices, this study proposes modeling the time patterns using the Markov chains framework and estimating the probabilities of transition from one tillage-crop combination to another tillage-crop combination from time-ordered spatially aggregated data. We developed a first-order, four-state Markov chain model of tillage-crop dynamics in corn (Zea mays L.)–soybean (Glycine max L.) production systems and estimated the transition probabilities for the state of Iowa using the 1992 to 1997 data collected by the Conservation Technology Information Center. The transition probabilities strongly suggest that the majority of NT acreage is not in continuous but rather in rotational NT, i.e., NT crop production in rotation with conventional or other tillage systems. We find that the probability of two-year continuous NT is 8%, and that 70% of Iowa cropland has never used NT over two consecutive years. When three-year tillage history is considered on corn acreage, 3% is in continuous NT, 62% has never used NT, and the rest of the acreage is in rotational NT. When three-year tillage history is considered on soybean acreage, 4% is in continuous NT, 56% has never used NT, and the rest of the acreage is in rotational NT. The methodology presented is applicable to corn–soybean production systems in other regions and is generalizable to other cropping systems. Regional estimates of the use of rotational and continuous NT are likely to benefit simulation modeling for the assessment of the environmental effects of alternative tillage practices.

He et al. show that T reg deficiency markedly induces autoimmunity and shifts gut microbiota. Remodeling microbiota by Lactobacillus reuteri was found to inhibit autoimmunity via the metabolite inosine, which interacts with the adenosine A2A receptor. This finding establishes a link between the gut microbiota, A2A receptors, and autoimmunity induced by T reg cell deficiency., Regulatory T (T reg) cell deficiency causes lethal, CD4+ T cell–driven autoimmune diseases. Stem cell transplantation is used to treat these diseases, but this procedure is limited by the availability of a suitable donor. The intestinal microbiota drives host immune homeostasis by regulating the differentiation and expansion of T reg, Th1, and Th2 cells. It is currently unclear if T reg cell deficiency–mediated autoimmune disorders can be treated by targeting the enteric microbiota. Here, we demonstrate that Foxp3+ T reg cell deficiency results in gut microbial dysbiosis and autoimmunity over the lifespan of scurfy (SF) mouse. Remodeling microbiota with Lactobacillus reuteri prolonged survival and reduced multiorgan inflammation in SF mice. L. reuteri changed the metabolomic profile disrupted by T reg cell deficiency, and a major effect was to restore levels of the purine metabolite inosine. Feeding inosine itself prolonged life and inhibited multiorgan inflammation by reducing Th1/Th2 cells and their associated cytokines. Mechanistically, the inhibition of inosine on the differentiation of Th1 and Th2 cells in vitro depended on adenosine A2A receptors, which were also required for the efficacy of inosine and of L. reuteri in vivo. These results reveal that the microbiota–inosine–A2A receptor axis might represent a potential avenue for combatting autoimmune diseases mediated by T reg cell dysfunction.

The galvanic-cell-based synthesis is considered as an effective method for the seed-layer free preparation of ZnO nanorods. However, the nucleation stage of the growth which decides the final structures of ZnO nanorods is still not well-understood. Here we show that the nucleation is almost completed after two minutes of growth and the galvanic-cell-based method results in a condensed ZnO layer beneath of the ZnO nanorods. Beyond this finding, we propose a hybrid approach that combines the galvanic and hydrothermal growth to fabricate the condensed-layer free, well-separated ZnO nanorods that might be compatible for the ZnO-based devices.

Chest radiography is one of the most common types of diagnostic radiology exams, which is critical for screening and diagnosis of many different thoracic diseases. Specialized algorithms have been developed to detect several specific pathologies such as lung nodule or lung cancer. However, accurately detecting the presence of multiple diseases from chest X-rays (CXRs) is still a challenging task. This paper presents a supervised multi-label classification framework based on deep convolutional neural networks (CNNs) for predicting the risk of 14 common thoracic diseases. We tackle this problem by training state-of-the-art CNNs that exploit dependencies among abnormality labels. We also propose to use the label smoothing technique for a better handling of uncertain samples, which occupy a significant portion of almost every CXR dataset. Our model is trained on over 200,000 CXRs of the recently released CheXpert dataset and achieves a mean area under the curve (AUC) of 0.940 in predicting 5 selected pathologies from the validation set. This is the highest AUC score yet reported to date. The proposed method is also evaluated on the independent test set of the CheXpert competition, which is composed of 500 CXR studies annotated by a panel of 5 experienced radiologists. The performance is on average better than 2.6 out of 3 other individual radiologists with a mean AUC of 0.930, which ranks first on the CheXpert leaderboard at the time of writing this paper.

Rhesus theta defensin-1 (RTD-1), a macrocyclic immunomodulatory host defense peptide from Old World monkeys, is therapeutic in pristane-induced arthritis (PIA) in rats, a model of rheumatoid arthritis (RA). RNA-sequence (RNA-Seq) analysis was used to interrogate the changes in gene expression in PIA rats, which identified 617 differentially expressed genes (DEGs) in PIA synovial tissue of diseased rats. Upstream regulator analysis showed upregulation of gene expression pathways regulated by TNF, IL1B, IL6, proinflammatory cytokines, and matrix metalloproteases (MMPs) involved in RA. In contrast, ligand-dependent nuclear receptors like the liver X-receptors NR1H2 and NR1H3 and peroxisome proliferator-activated receptor gamma (PPARG) were downregulated in arthritic synovia. Daily RTD-1 treatment of PIA rats for 1–5 days following disease presentation modulated 340 of the 617 disease genes, and synovial gene expression in PIA rats treated 5 days with RTD-1 closely resembled the gene signature of naive synovium. Systemic RTD-1 inhibited proinflammatory upstream regulators such as TNF, IL1, and IL6 and activated antiarthritic ligand-dependent nuclear receptor pathways, including PPARG, NR1H2, and NR1H3, that were suppressed in untreated PIA rats. RTD-1 also inhibited proinflammatory responses in IL-1β-stimulated human RA fibroblast-like synoviocytes (FLS) in vitro and diminished expression of human orthologs of disease genes that are induced in rat PIA synovium. Thus, the antiarthritic mechanisms of systemic RTD-1 include homeostatic regulation of arthritogenic gene networks in a manner that correlates temporally with clinical resolution of rat PIA.

Background and objective: Breast milk has many growth-promoting and immune-active components, including transforming growth factor-β, lactoferrin, lysozyme, immunoglobulin A, and prebiotics such as the human milk oligosaccharides. Treatment with Lactobacillus reuteri DSM 17938 (LR), a probiotic with immunomodulatory functions, significantly increases regulatory T cells (Tregs) in the intestinal mucosa of newborn suckling rats. In humans, treatment with LR of infants with colic reduces crying optimally if the infants are breast-fed. Therefore, we examined the effects of human breast milk (HBM) on LR-associated immune modulation. Methods: Newborn rats were divided into 8 feeding groups, including dam-fed ± LR (106 CFU/kg bw/day, daily), formula-fed ± LR, formula with 20% (v/v) HBM-fed ± LR, and HBM-fed ± LR. Pups were fed by gavage from d1 to d3 of age. Subsequently, we measured intestinal immune cell profiles, including Tregs and tolerogenic dendritic cells (tDCs) by flow cytometry. We also measured inflammatory cytokine and chemokine levels of interleukin (IL)-1β and cytokine-induced neutrophil chemoattratant (CINC)-1 in intestinal tissue lysates by ELISA. Results and Conclusion: (1) Formula feeding increased intestinal CD3+ T cells, CD4+ helper T (TH) cells and CD11c+ DCs, pro-inflammatory effects which were reversed by HBM. (2) When comparing HBM-fed with formula-fed newborns, HBM supplementation produced a lower percentage of CD4+ TH cells and a higher percentage of CD8+ (cytotoxic) T cells, while reducing protein levels of IL-1β and CINC-1 in the intestine. (3) Probiotic LR feeding maximally stimulated the percentage of intestinal Tregs and tDCs when the pups were fed HBM. In conclusion, HBM reduced formula-induced intestinal gut immune activation, and the addition of LR further promoted immune tolerance.

Early administration of Lactobacillus reuteri DSM 17938 (LR) prevents necrotizing enterocolitis and inhibits regulatory T-cell (Treg)-deficiency-associated autoimmunity in mice. In humans, LR reduces crying time in breastfed infants with colic, modifies severity in infants with acute diarrheal illnesses, and improves pain in children with functional bowel disorders. In healthy breastfed newborns with evolving microbial colonization, it is unclear if early administration of LR can modulate gut microbiota and their metabolites in such a way as to promote homeostasis. We gavaged LR (107colony-forming units/day, daily) to C57BL/6J mice at age of day 8 for 2 wk. Both male and female mice were investigated in these experiments. We found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+regulatory T cells (Tregs) in the intestine. LR also increased bacterial diversity and the relative abundance of p_Firmicutes, f_Lachnospiraceae, f_Ruminococcaceae, and genera Clostridium and Candidatus arthromitus, while decreasing the relative abundance of p_Bacteriodetes, f_Bacteroidaceae, f_Verrucomicrobiaceae, and genera Bacteroides, Ruminococcus, Akkermansia, and Sutterella. Finally, LR exerted a major impact on the plasma metabolome, upregulating amino acid metabolites formed via the urea, tricarboxylic acid, and methionine cycles and increasing tryptophan metabolism. In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health.NEW & NOTEWORTHY Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulates plasma metabolites that are involved in the urea cycle, the TCA cycle, methionine methylation, and the polyamine pathway. Herein, we show that LR given to newborn mice specifically increases levels of tryptophan metabolites and the purine nucleoside adenosine that are known to enhance tolerance to inflammatory stimuli.

Human breast milk (HBM) may have beneficial effects on Lactobacillus reuteri DSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of L. reuteri.