Sesame eliciting and safe doses in a large sesame allergic population

Background: Sesame is a significant food allergen causing severe and even fatal reactions. Given its increasing prevalence in western diet, sesame is listed as an allergenic food requiring labeling in the United States and EU. However, data on the population reaction doses to sesame are limited. Methods: All sesame oral food challenges (OFCs), performed either for diagnosis or for threshold identification before the beginning of sesame oral immunotherapy (OIT) between November 2011 and July 2021 in Shamir medical center were analyzed for reaction threshold distribution. Safe-dose challenges with 90–120 min intervals were also analyzed. Results: Two hundred and fifty patients underwent 338 positive OFCs, and additional 158 safe-dose OFCs were performed. The discrete and cumulative protein amounts estimated to elicit an objective reaction in 1% (ED01) of the entire cohort (n = 250) were 0.8 mg (range 0.3–6.3) and 0.7 mg (range 0.1–7.1), respectively, and those for 5% of the population (ED05) were 3.4 mg (range 1.2–20.6) and 4.5 mg (range 1.2–28.8), respectively. Safe-dose OFCs showed similar values of ED01 (0.8, 0.4–7.5 mg) and ED05 (3.4, 1.2–22.9 mg). While doses of ≤1 mg sesame protein elicited oral pruritus in 11.6% of the patients, no objective reaction was documented to this amount in any of the challenges, including safe-dose OFCs. Conclusions: This study provides data on sesame reaction threshold distribution in the largest population of allergic patients studied, with no right or left censored data, and with validation using a safe-dose OFC. It further supports the current methods for ED determination as appropriate for establishing safety precautions for the food industry

Improving Multiple-CMP Systems Using Token Coherence

Improvements in semiconductor technology now enable Chip Multiprocessors (CMPs). As many future computer systems will use one or more CMPs and support shared memory, such systems will have caches that must be kept coherent. Coherence is a particular challenge for Multiple-CMP (M-CMP) systems. One approach is to use a hierarchical protocol that explicitly separates the intra-CMP coherence protocol from the inter-CMP protocol, but couples them hierarchically to maintain coherence. However, hierarchical protocols are complex, leading to subtle, difficult-to-verify race conditions. Furthermore, most previous hierarchical protocols use directories at one or both levels, incurring indirections—and thus extra latency—for sharing misses, which are common in commercial workloads. In contrast, this paper exploits the separation of correctness substrate and performance policy in the recently-proposed token coherence protocol to develop the first M-CMP coherence protocol that is flat for correctness, but hierarchical for performance. Via model checking studies, we show that flat correctness eases verification. Via simulation with micro-benchmarks, we make new protocol variants more robust under contention. Finally, via simulation with commercial workloads on a commercial operating system, we show that new protocol variants can be 10-50% faster than a hierarchical directory protocol

Rhizosphere Microbiomes in a Historical Maize-Soybean Rotation System Respond to Host Species and Nitrogen Fertilization at the Genus and Subgenus Levels

Root-associated microbes are key players in plant health, disease resistance, and nitrogen (N) use efficiency. It remains largely unclear how the interplay of biological and environmental factors affects rhizobiome dynamics in agricultural systems. In this study, we quantified the composition of rhizosphere and bulk soil microbial communities associated with maize (Zea mays L.) and soybean (Glycine max L.) in a long-term crop rotation study under conventional fertilization and low-N regimes. Over two growing seasons, we evaluated the effects of environmental conditions and several treatment factors on the abundance of rhizosphere- and soil-colonizing microbial taxa. Time of sampling, host plant species, and N fertilization had major effects on microbiomes, while no effect of crop rotation was observed. Using variance partitioning as well as 16S sequence information, we further defined a set of 82 microbial genera and functional taxonomic groups at the subgenus level that show distinct responses to treatment factors. We identified taxa that are highly specific to either maize or soybean rhizospheres, as well as taxa that are sensitive to N fertilization in plant rhizospheres and bulk soil. This study provides insights to harness the full potential of soil microbes in maize and soybean agricultural systems through plant breeding and field management

Bioconversion of Pelletized Big Bluestem, Switchgrass, and Low-Diversity Grass Mixtures Into Sugars and Bioethanol

Three crops of warm-season grasses are being developed for biomass production on northern rain-fed marginal farmland: big bluestem (BBS), switchgrass (SG), and a low diversity mixture of grasses (LDM). In this study, biomass harvested from established fields were compared for pelletization and subsequent conversion to sugars and ethanol. Each biomass was successfully pelletized to similar bulk densities without adding a binder at a commercial feed operation. Pelletizing increased the bulk density by 407% on average and was equally effective on all three biomass samples (528–554 kg/m3). Chemical analysis of the samples indicated that glucan and xylan contents were slightly reduced during pelletizing (by 23 and 16 g/kg, respectively), as well as theoretical ethanol yields, which are based upon total carbohydrate contents. Pellets and milled straws were pre-treated with either liquid hot-water or low-moisture ammonium hydroxide (LMA) and subsequently hydrolyzed with cellulases. Glucose and total sugar yields were similar for non-pellets and pellets using either pre-treatment; carbohydrates present in pellets were more efficiently recovered compared to non-pellets. LMA pretreated samples were separately hydrolyzed and fermented to ethanol using Scheffersomyces stipitis yeast. Hydrolysis recovered 69.7–76.8% of the glucose and 66.5–73.3% of the xylose across all samples. Glucose yields were 251–279 g/kg, db and were significantly lower for SG as compared to the other biomass samples. Recovered sugars were fermented to ethanol at 77.7–86.7% of theoretical yield. Final ethanol yields (245.9–275.5 L/Mg, db) were similar for all of the grasses and estimated to equate to production levels for BBS, LDM, and SG of 1,952, 2,586, and 2,636 l of ethanol per ha, respectively

Bioconversion of Pelletized Big Bluestem, Switchgrass, and Low-Diversity Grass Mixtures Into Sugars and Bioethanol

Three crops of warm-season grasses are being developed for biomass production on northern rain-fed marginal farmland: big bluestem (BBS), switchgrass (SG), and a low diversity mixture of grasses (LDM). In this study, biomass harvested from established fields were compared for pelletization and subsequent conversion to sugars and ethanol. Each biomass was successfully pelletized to similar bulk densities without adding a binder at a commercial feed operation. Pelletizing increased the bulk density by 407% on average and was equally effective on all three biomass samples (528–554 kg/m3). Chemical analysis of the samples indicated that glucan and xylan contents were slightly reduced during pelletizing (by 23 and 16 g/kg, respectively), as well as theoretical ethanol yields, which are based upon total carbohydrate contents. Pellets and milled straws were pre-treated with either liquid hot-water or low-moisture ammonium hydroxide (LMA) and subsequently hydrolyzed with cellulases. Glucose and total sugar yields were similar for non-pellets and pellets using either pre-treatment; carbohydrates present in pellets were more efficiently recovered compared to non-pellets. LMA pretreated samples were separately hydrolyzed and fermented to ethanol using Scheffersomyces stipitis yeast. Hydrolysis recovered 69.7–76.8% of the glucose and 66.5–73.3% of the xylose across all samples. Glucose yields were 251–279 g/kg, db and were significantly lower for SG as compared to the other biomass samples. Recovered sugars were fermented to ethanol at 77.7–86.7% of theoretical yield. Final ethanol yields (245.9–275.5 L/Mg, db) were similar for all of the grasses and estimated to equate to production levels for BBS, LDM, and SG of 1,952, 2,586, and 2,636 l of ethanol per ha, respectively

T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17

Experimental autoimmune myocarditis (EAM) appears after infectious heart disease, the most common cause of dilated cardiomyopathy in humans. Here we report that mice lacking T-bet, a T-box transcription factor required for T helper (Th)1 cell differentiation and interferon (IFN)-γ production, develop severe autoimmune heart disease compared to T-bet−/− control mice. Experiments in T-bet−/− IL-4−/− and T-bet−/− IL-4Rα−/− mice, as well as transfer of heart-specific Th1 and Th2 cell lines, showed that autoimmune heart disease develops independently of Th1 or Th2 polarization. Analysis of T-bet−/− IL-12Rβ1−/− and T-bet−/− IL-12p35−/− mice then identified interleukin (IL)-23 as critical for EAM pathogenesis. In addition, T-bet−/− mice showed a marked increase in production of the IL-23–dependent cytokine IL-17 by heart-infiltrating lymphocytes, and in vivo IL-17 depletion markedly reduced EAM severity in T-bet−/− mice. Heart-infiltrating T-bet−/− CD8+ but not CD8− T cells secrete IFN-γ, which inhibits IL-17 production and protects against severe EAM. In contrast, T-bet−/− CD8+ lymphocytes completely lost their capacity to release IFN-γ within the heart. Collectively, these data show that severe IL-17–mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ

Virtual Machine Support for Many-Core Architectures: Decoupling Abstract from Concrete Concurrency Models

The upcoming many-core architectures require software developers to exploit concurrency to utilize available computational power. Today's high-level language virtual machines (VMs), which are a cornerstone of software development, do not provide sufficient abstraction for concurrency concepts. We analyze concrete and abstract concurrency models and identify the challenges they impose for VMs. To provide sufficient concurrency support in VMs, we propose to integrate concurrency operations into VM instruction sets. Since there will always be VMs optimized for special purposes, our goal is to develop a methodology to design instruction sets with concurrency support. Therefore, we also propose a list of trade-offs that have to be investigated to advise the design of such instruction sets. As a first experiment, we implemented one instruction set extension for shared memory and one for non-shared memory concurrency. From our experimental results, we derived a list of requirements for a full-grown experimental environment for further research

DAS181 treatment of severe lower respiratory tract parainfluenza virus infection in immunocompromised patients: A phase 2 randomized, placebo-controlled study

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877

Heavy Ion Testing at the Galactic Cosmic Ray Energy Peak

A 1 GeV/u Fe-56 ion beam allows for true 90deg tilt irradiations of various microelectronic components and reveals relevant upset trends for an abundant element at the GCR flux energy peak