A document by Anurag Varshney. Click on the document to view its contents.

This paper studies the commutativity and stability for the Heun’s linear time-varying system (LTVS) with both zero and non-zero initial conditions(ICs). Given a LTVS A of order 2 , we find it’s commutative pair, that is a new LTVS B of order m ≤ n . Explicit commutative theories and conditions for second-order LTVSs are derived and solved to simplify and guarantee the equivalency between the connected input-output of systems A B and B A . The explicit results obtained are juxtaposed by simulation in order to investigate the commutativity of Heun’s differential system, sensitivity of Heun’s system, effects due to disturbance on Heun’s system, robustness on Heun’s system and problems regarding the stability of Heun’s system. This findings will help to fill the gap on stability problem, system behaviors, commutativity theory, and general theory for solutions of differential equations, which has significant contribution to science and unlimited application in engineering, our results are verify using Heun’s differential system as well as authenticated by Wolfrom Mathematica 1 1 and Matlab.

The targeted next-generation sequencing (NGS) was employed in detecting the pathogenic mutations in inherited heart disease patients in the present study. Two main methods, the NGS and the classic Sanger sequencing, were used in this study. And, the whole-exome sequencing (WES) was specifically used in this study.

The well-known clinical axiom stating that “common things are common” attests to the pivotal role of probability in diagnosis. Despite the popularity of this and related axioms, there is no operationalized definition of a common disease, and no practicable way of incorporating actual disease frequencies into differential diagnosis. In this expository essay, we aim to reduce the ambiguity surrounding the definition of a common (or rare) disease and show that incidence – not prevalence – is the proper metric of disease frequency for diagnosis. We explore how a numerical estimates of disease frequencies based on incidence can be incorporated into differential diagnosis as well as the inherent limitations of this method. These concepts have important implications for diagnostic decision making and medical education, and hold promise as a method to improve diagnostic accuracy.

The comprehensive fire and explosion risk assessment has been studied for Coal Reclaim Tunnel (CRT) facility by applying the Monte Carlo simulation method. In this research, the fire and explosion risk of two existing CRT, namely model A and model B, have been assessed. A set of 30 data for each factor has been used to define the statistical distribution model, sourced from historical data, field measurement, and laboratory experiments. Based on the simulation, CRT model A has a 100% extreme risk group, while model B has two risk groups, high risk=81.73% and moderate risk=18.27%, classified as a not acceptable risk. Several preventive actions were set to reduce the probability and severity level as low as reasonably possible, especially for the controllable factors. Furthermore, the probability and severity levels were re-adjusted by the Monte Carlo simulation. The result shows that both the CRT model have been grouped into a 100% moderate-risk group. For optimal prevention against explosion risk, a sensitivity analysis has been carried out to find the most influential factors for the fire and explosion risk in CRT. Through this research, a method for risk matrix assessment related to the fire and explosion in the CRT facility has been developed.

Background: Newborn screening (NBS) has been shown to improve CF disease course and has been widely implemented worldwide. This monocentric study compared children diagnosed by NBS vs. a cohort preceding the implementation of NBS in Germany in 2016 to evaluate ascribed benefits of NBS. Methods: We compared all children with confirmed CF diagnosis (n=19, “NBS group”) out of all children presenting with positive NBS at our center after implementation of NBS (n=100) to children diagnosed with CF at our center within 4 years before NBS implementation (n=29, “pre-NBS group”) for outcomes of anthropometry, gastrointestinal and pulmonary disease manifestations and respiratory microbiology. Results: Children diagnosed by NBS had a lower incidence of initial feeding problems (15% vs. 41%), had a higher BMI z-score at diagnosis and higher mean z-scores for BMI, weight and length during the study period. Children in the pre-NBS group displayed higher proportions of oxygen-dependent pulmonary exacerbations (10% vs. 0%), a significantly lower amount of normal bacterial flora (p=0.005) along with a significantly higher number of throat swab cultures positive for Pseudomonas aeruginosa (p=0.0154) in the first year of life. Yet, pulmonary imaging did not reveal less pulmonary morbidity in the NBS compared to the pre-NBS group. Conclusions: Our results confirm that NBS for CF leads to earlier diagnosis and improves nutritional outcomes in early childhood. Although trajectories of structural lung damage at early age were unaffected by NBS, NBS positive CF patients at preschool age displayed less severe pulmonary exacerbations and pathological bacteria in throat swabs.

Spodoptera frugiperda (Lepidoptera: Noctuidae) is an invasive pest that ravaging crops in many provinces of China. In order to specifically control this invasive pest, understanding of the relationship between the insect and the host is necessary. In this study, we have compared the biological and nutritional indexes of S. frugiperda by feeding it with five different host-plants (Zea mays, Triticum aestivum, Digitaria sanguinalis, Glycine max and Eleusine indica). The biological and nutritional indexes of Z. mays feeding S. frugiperda were the best. However, the pupa weight and fecundity of S. frugiperda fed with G. max and E. indica were significantly lower than those fed with other hosts, efficiency of conversion of digested food (ECD) and efficiency of conversion of ingested food (ECI) were also lower than others. The total phenol content was negatively correlated with the biological and nutritional indexes of S. frugiperda, while the C/N content was positively correlated. When fed on different host plants, the biological and nutritional indexes of S. frugiperda were different, but all of them could complete the life cycle. Therefore, in the absence of Z. mays, the S. frugiperda may also harm other host plants, and host plants with high C/N content can also with the risk of being infected.

Miracles, like London buses, just seem to come along. The truth is, there are no miracles, just lots of hard work behind the scenes, minds open to opportunity, serendipity and possibly a little luck. In my time as a paediatric respiratory physician, I have born witness to remarkable advances in treatment that have changed patients' fortunes overnight. Examples of these include artificial surfactant replacement for premature newborns, conjugate haemophilus influenzae type b vaccination, propranolol for infants with subglottic haemangiomas, mandibular distraction for babies with micrognathia, cystic fibrosis transmembrane conductance regulator modulators therapy for patients with cystic fibrosis and antisense oligonucleotide therapy for infants with spinal muscular atrophy. There are lessons to be learned from reflection upon these life transforming treatments, and perhaps it is a good time just to pause and wonder.

A document by Peiyu Wang. Click on the document to view its contents.

A document by Yecenia Adelita Hijar Sifuentes. Click on the document to view its contents.

We present a case of successful revascularization for spontaneous coronary artery dissection (SCAD) using coronary artery fenestration followed by the subintimal transcatheter withdrawal (STRAW) technique. The combination of the STRAW technique and coronary artery fenestration with cutting balloon angioplasty could be a new treatment option for SCAD patients requiring revascularization.

The flagellin epitope flg22, a pathogen-associated molecular pattern (PAMP), binds to the receptor-like kinase FLAGELLIN SENSING2 (FLS2), and triggers Ca2+ influx across the plasma membrane (PM). The flg22-induced increases in cytosolic Ca2+ concentration ([Ca2+]i) (FICA) play a crucial role in plant innate immunity. It’s well established that the receptor FLS2 and the key downstream component, reactive oxygen species (ROS) burst, undergoes sensitivity adaptation after flg22 stimulation, referred to as desensitization and resensitization, to prevent over responses to pathogens. However, whether FICA also mount adaptation mechanisms to ensure appropriate and efficient responses against pathogens remains poorly understood. Here, we carried out detailed analyses of [Ca2+]i increases upon two successive flg22 treatments, recorded and characterized, for the first time, rapid desensitization but slow resensitization of FICA in Arabidopsis thaliana. Pharmacological analyses showed that the rapid desensitization might be synergistically regulated by ligand-induced FLS2 endocytosis as well as the PM depolarization. The recovery of desensitized FICA might require to de novo FLS2 protein synthesis. FICA resensitization appeared significantly slower than FLS2 protein recovery, suggesting additional regulatory mechanisms of other components, such as flg22-related Ca2+ permeable channels. Taken together, we have carefully defined the FICA sensitivity adaptation, which will facilitate further molecular and genetic dissection of the Ca2+-mediated adaptive mechanisms in PAMP-triggered immunity.

Convolutional neural networks (CNNs), inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to greatly reduce the network parametric complexity and enhance the predicting accuracy. They are of significant interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis [1-7]. Optical neural networks offer the promise of dramatically accelerating computing speed to overcome the inherent bandwidth bottleneck of electronics. Here, we demonstrate a universal optical vector convolutional accelerator operating beyond 10 Tera-OPS (TOPS-operations per second), generating convolutions of images of 250,000 pixels with 8-bit resolution for 10 kernels simultaneously-enough for facial image recognition. We then use the same hardware to sequentially form a deep optical CNN with ten output neurons, achieving successful recognition of full 10 digits with 900 pixel handwritten digit images with 88% accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as unmanned vehicle and real-time video recognition.

Convolutional neural networks (CNNs), inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to greatly reduce the network parametric complexity and enhance the predicting accuracy. They are of significant interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis [1-7]. Optical neural networks offer the promise of dramatically accelerating computing speed to overcome the inherent bandwidth bottleneck of electronics. Here, we demonstrate a universal optical vector convolutional accelerator operating beyond 10 Tera-OPS (TOPS-operations per second), generating convolutions of images of 250,000 pixels with 8-bit resolution for 10 kernels simultaneously-enough for facial image recognition. We then use the same hardware to sequentially form a deep optical CNN with ten output neurons, achieving successful recognition of full 10 digits with 900 pixel handwritten digit images with 88% accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as unmanned vehicle and real-time video recognition.

A document by Mark Rubin. Click on the document to view its contents.

A document by Natasha Correa. Click on the document to view its contents.

This non-randomized controlled study aimed to assess the efficacy of tofacitinib in reducing the risk of invasive mechanical ventilation or death in patients with COVID-19. Patients with COVID-19 associated with reduced oxygen saturation, increased C-reactive protein (≥50 mg/L), and/or persisting fever were recruited. Tofacitinib was administered in addition to standard of care therapy. Study outcomes were evaluated separately in the groups of patients with oxygen saturation at rest ≤93% and >93%. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analysis adjusted for inverse propensity score weighting. Overall, 384 patients with COVID-19 (212 males; median age 60 years) were included in our study and were treated with tofactinib (n=131) or standard of care alone (n=253). The percentages of patients who started mechanical ventilation or died during hospitalization in the tofacitinib and control groups were 12.5% (9/72) vs. 14.1% (26/185) among patients who required respiratory support (HR 0.92, 95% CI 0.33-2.56), and 1.7% (1/59) vs. 4.4% (3/68) in those with normal oxygen saturation (HR 0.83; 95 CI 0.07-9.44). Tofacitinib did not reduce the risk of invasive mechanical ventilation or death in patients with COVID-19, although the analysis of these outcomes favored tofacitinib.

Carotenoids and tocopherols are health-promoting metabolites in livestock and human diets. Some important crops have been genetically modified to increase their content. Although the usefulness of transgenic plants to alleviate nutritional deficiencies is obvious, their social acceptance has been controversial. Here, we demonstrate an alternative biotechnological strategy for carotenoid and tocopherol fortification of edible fruits in which no transgenic DNA is involved. A viral RNA vector derived from Zucchini yellow mosaic virus (ZYMV) was modified to express a bacterial phytoene synthase (crtB), and inoculated in zucchini (Cucurbita pepo L.) leaves nurturing pollinated flowers. After the viral vector moved to the developing fruit and expressed crtB, the rind and flesh of the fruits developed yellow-orange rather than green color. Metabolite analyses showed a substantial enrichment in health-promoting carotenoids, such as α- and β-carotene (pro-vitamin A), lutein and phytoene, in both rind and flesh. Considerably higher accumulation of α- and γ-tocopherol was also detected, particularly in fruit rind. Although this strategy is perhaps not free from controversy due to the use of genetically modified viral RNA, our work does demonstrate the possibility of metabolically fortifying edible fruits using an approach in which no transgenes are involved.

Environmental (e)DNA methods have enabled rapid, sensitive, and specific inferences of taxa presence throughout diverse fields of ecological study. However, use of eDNA results for decision-making has been impeded by uncertainties associated with false positive tests putatively caused by contamination. Sporadic contamination is a process that is inconsistent across samples and systemic contamination occurs consistently over a group of samples. Here, we used empirical data and lab experiments to (1) estimate the sporadic contamination rate for each stage of a common, targeted eDNA workflow employing best practice quality control measures under simulated conditions of rare and common target DNA presence, (2) determine the rate at which negative controls (i.e., “blanks”) detect varying concentrations of systemic contamination, (3) estimate the effort that would be required to consistently detect sporadic and systemic contamination. Sporadic contamination rates were very low across all eDNA workflow steps, and, therefore, an intractably high number of negative controls (>100) would be required to determine occurrence of sporadic contamination with any certainty. Contrarily, detection of intentionally introduced systemic contamination was more consistent; therefore, very few negative controls (<5) would be needed to consistently alert to systemic contamination. These results have considerable implications to eDNA study design when resources for sample analyses are constrained.

Dinutuximab, an immune-mediated therapy used in the treatment of high-risk neuroblastoma targets the protein disialoganglioside (GD2) present on neuroblastoma cells, neurons, and peripheral nerve fibers. Off target effects could lead to severe nerve pain. Pain regimens including continuous infusion opioids are required during the first treatment course. Our institution utilizes a combination of intravenous (IV) lidocaine infusions and morphine for the treatment of dinutuximab-associated neuropathic pain. The primary outcome of this study was to compare morphine equivalents for cycle one of dinutuximab at an institution that uses IV lidocaine (primary) versus those that do not (comparison). Secondary outcomes included both dinutuximab infusion time and safety of IV lidocaine. A retrospective, multi-centered, electronic chart review was performed at three tertiary academic medical centers. Patients between 0-18 years of age during their first course of dinutuximab were included to evaluate the primary outcome of adjuvant morphine equivalents needed. Total morphine equivalents at the primary institution were 1.87 mg/kg vs 1.79 mg/kg at the comparison institutions (p=0.413). Dinutuximab infusion time was significantly lower at the primary institution: 610.5 minutes vs 676.23 minutes (p=0.046). Only one patient at the primary institution experienced nausea, vomiting and paresthesias. This study did not find a statistically significant difference in morphine equivalents between patients who received IV lidocaine and those who did not. However, we did find that use of IV lidocaine resulted in a statistically significant lower dinutuximab infusion time and that it is a safe adjuvant medication in the treatment of dinutuximab-associated neuropathic pain.

The integrity of science and engineering research is grounded in assumptions of rigor and transparency on the part of those engaging in such research. HPC community effort to strengthen rigor and transparency take the form of reproducibility efforts. In a recent survey of the SC conference community, we collected information about the SC Reproducibility Initiative activities. We present the survey results in this paper. Results show that the reproducibility initiative activities have contributed to higher levels of awareness on the part of SC conference technical program participants, and hint at contributing to greater scientific impact for the published papers of the SC conference series. Stringent point-of-manuscript-submission verification is problematic for reasons we point out, as are inherent difficulties of computational reproducibility in HPC. Future efforts should better decouple the community educational goals from goals that specifically strengthen a research work's potential for long-term impact through reuse 5-10 years down the road.

How carbohydrate reserves change in conifers during drought and bark beetle attacks are poorly understood. We investigated changes in carbohydrate reserves and carbon-dependent terpene defenses in ponderosa pine trees experimentally subjected to two levels of drought stress (via root trenching) and two types of biotic challenge treatments (pheromone-induced bark beetle attacks or inoculations with crushed beetles that include beetle-associated fungi) for two consecutive years. Our results showed that trenching did not influence carbohydrates whereas both biotic challenges reduced amounts of starch and sugars of trees. However, only the trenched-beetle attacked trees depleted carbohydrates and died within the first year of bark beetle attacks. While live trees contained higher carbohydrates than dying trees, amounts of constitutive and induced terpenes produced did not vary between live and beetle-attacked dying trees, respectively. Based on these results we propose that reallocation of carbohydrates to terpenes during the early stages of beetle attacks is limited in drought-stricken trees, and that the combination of biotic and abiotic stress leads to tree death. The process tree death is subsequently aggravated by beetle girdling of phloem, occlusion of vascular tissue by bark beetle-vectored fungi, and potential exploitation of host carbohydrates by beetle symbionts as nutrients.

NK cells and Lipoxin A4 promote resolution of eosinophilic inflammation after nasal allergen challenge

Density functional theory (DFT) calculations were adopted in this work to investigate the ability of the B12N12 fullerene like nano-cage for sensing juglone (Jug) and one of its derivative (Jug-OH) using DFT based methods in gas phase, pentyl ethanoate (PE) and water. Results showed that B12N12 is able to adsorbed Jug preferentially by binding to one of the O-atom of its carbonyl groups. Based on NBO analysis, a charge transfer from the oxygen atoms of Jug and Jug-OH to the anti-bonding orbital of B was revealed. QTAIM analysis showed that the B12N12-Jug and B12N12-Jug-OH complexes are stabilized by a partially covalent B-O bond in addition to attractive non covalent interactions. The ability of Jug, Jug-OH as well as their complexes A and A-OH to scavenge radicals has been investigated via the usual hydrogen atom transfer (HAT) mechanism in the three media of study previously stated. Theoretical results revealed that in PE and water, the complexes are better antioxidant than Jug and Jug-OH. These results provide fundamental knowledge for the development of new antioxidant delivery careers.