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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

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.

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.

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.

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.

With the rapid advancement of radiation hard imaging technology, space-based remote sensing instruments are becoming not only more sophisticated but are also generating substantially more amounts of data for rapid processing. For applications that rely on data transmitted from a planetary probe to a relay spacecraft to Earth, alteration or discontinuity in data over a long transmission distance is likely to happen. Cyclic Redundancy Check (CRC) is one of the most well-known package error check techniques in sensor networks for critical applications. However, serial CRC computation could be a bottleneck of the throughput in such systems. In this work, we design, implement, and validate an efficient hybrid look-up-table and matrix transformation algorithm for high throughput parallel computational unit to speed-up the process of CRC computation using both CPU and Field Programmable Gate Array (FPGA) with comparison of both methods.

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.

Background Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. Methods In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. Results Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. Conclusions CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Beware of T cells that don't know how to stop During an infection, T cells divide extensively and secrete proteins that can severely damage tissues. But T cells know when to stop—they express proteins on their surface such as CTLA4, which put on the brakes. Kuehn et al. now report genetic evidence of the importance of CTLA4 in humans (see the Perspective by Rieux-Laucat and Casanova). They identified six patients with mutations in one copy of CTLA4 . Patients presented with symptoms of an overzealous immune response, with immune cells infiltrating their organs. The findings support the idea that CTLA4 tells the immune system when enough is enough. Science , this issue p. 1623 ; see also p. 1560

Will soil organic carbon (SOC) and yields increase for conservation management systems in tropical zones in response to the next 100 years? To answer the question, the Environmental Policy Integrated Climate (EPIC) model was used to study the effects of climate change, cropping systems, conservation agriculture (CA) and conservation tillage management practices on SOC and crop productivity in Kampong Cham, Cambodia. The EPIC model was successfully calibrated and validated for crop yields, biomass, SOC and nitrogen based on field data from a five-year field experiment. Historical weather (1994&ndash, 2013) was used for baseline assessment versus mid-century (2046&ndash, 2064) and late-century (2081&ndash, 2100) climate projections generated by the Geophysical Fluids Dynamics Laboratory (GFDL) CM2.1 global climate model. The simulated results showed that upland rice yield would increase the most under the B1 scenario in mid-century for all treatments, followed by soybean and maize. Cassava yield only increased under CA treatment when cultivated as a continuous primary crop. Carbon sequestration was more sensitive to cropping systems and crop rotation than climate change. The results indicated that the rotated CA primary crop (maize) systems should be prioritized for SOC sequestration as well as for increasing crop productivity. In addition, rice systems may increase SOC compared to soybean and cassava.

FOXP3 + regulatory T cells, a unique subset of T cells, are critical for orchestrating an immune response and preventing self-reactivity. With the increasing prevalence and unsatisfactory treatment of autoimmunity, allergic diseases, cancer and chronic infections, much attention has been focused on understanding their mechanisms of action in order to manipulate their function. One goal is to develop drugs or biologics that can enhance or abrogate their functions. Another approach is to utilize Tregs in adoptive cell-based therapy to treat autoimmune diseases or transplant-related complications. This review will focus on their therapeutic potential and mechanisms of action, particularly their interaction with dendritic cells.

CD4(+)FoxP3(+) regulatory T (T reg) cells comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. The molecular mechanism(s) by which T reg cells mediate their suppressive effects remains poorly understood. One molecule that has been extensively studied in T reg cell suppression is transforming growth factor (TGF)-beta, but its importance remains controversial. We found that TGF-beta complexed to latency-associated peptide (LAP) is expressed on the cell surface of activated but not resting T reg cells. T reg cell LAP-TGF-beta plays an important role in the suppression of the proliferation of activated T cells, but it is not required for the suppression of naive T cell activation. More importantly, T reg cell-derived TGF-beta could generate de novo CD4(+)FoxP3(+) T cells in vitro from naive precursors in a cell contact-dependent, antigen-presenting cell-independent and alpha(V) integrin-independent manner. The newly induced CD4(+)FoxP3(+) T cells are suppressive both in vitro and in vivo. Transfer of activated antigen-specific T reg cells with naive antigen-specific responder T cells to normal recipients, followed by immunization, also results in induction of FoxP3 expression in the responder cells. T reg cell-mediated generation of functional CD4(+)FoxP3(+) cells via this TGF-beta-dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities.

While traditional transport of intensity equation (TIE) based phase retrieval of a phase object is performed through axial translation of the CCD, in this work a tunable lens TIE is employed in both transmission and reflection configurations. These configurations are extended to a 360° tomographic 3D reconstruction through multiple illuminations from different angles by a custom fabricated rotating assembly of the phase object. Synchronization circuitry is developed to control the CCD camera and the Arduino board, which in its turn controls the tunable lens and the stepper motor to automate the tomographic reconstruction process. Finally, a MATLAB based user friendly graphical user interface is developed to control the whole system and perform tomographic reconstruction using both multiplicative and inverse radon based techniques.

Background Mutations in signal transducer and activator of transcription (STAT) 1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles) to mild disseminated mycobacterial disease (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity, and squamous cell cancers. Objective We sought to investigate the role of STAT1 gain-of-function mutations in phenotypes other than CMC. Methods We initially screened patients with CMC and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T (Treg) cells. After our initial case identifications, we explored 2 large cohorts of patients with wild-type forkhead box protein 3 and an immune dysregulation–polyendocrinopathy–enteropathy–X-linked (IPEX)–like phenotype for STAT1 mutations. Results We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety of mucosal and disseminated fungal infections. All patients lacked forkhead box protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1 phosphorylation in response to IFN-γ, IL-6, and IL-21 was increased and prolonged. CD4 + IL-17–producing T-cell numbers were diminished. All patients had normal Treg cell percentages in the CD4 + T-cell compartment, and their function was intact in the 2 patients tested. Patients with cells available for study had normal levels of IL-2–induced STAT5 phosphorylation. Conclusions Gain-of-function mutations in STAT1 can cause an IPEX-like phenotype with normal frequency and function of Treg cells.

Herein, the potential of reformed GaN nanowires (NWs) fabricated by metalorganic chemical vapor deposition (MOCVD) for device-quality low-defect density templates and low-cost alternative to bulk GaN substrates is demonstrated. The effects of epilayer thickness and NW reformation conditions on the crystalline quality and thermal conductivity of the subsequent GaN epilayers are investigated. Smooth surfaces with atomically step-like morphologies with no spirals are achieved for GaN epilayers on the reformed NW templates, indicating step-flow growth mode. It is further found that annealing of the NWs at a temperature of 1030 °C in the presence of NH3 and H2, followed by a coalescence done at the same temperature under planar growth conditions, leads to the most efficient screw dislocation density reduction by nearly an order of magnitude. At these optimized conditions, the growth takes place in a layer-by-layer fashion, producing a smooth surface with a root mean square (RMS) roughness of 0.12 nm. The highest thermal conductivity of k = 206 W m−1 K−1, approaching the respective value of bulk GaN, is obtained for the optimized 2 μm-thick GaN layer. The thermal conductivity results are further discussed in terms of the phonon-dislocation and the phonon-boundary scattering. (Less)