Coal Quality Management Model For Dome Storage (DS-CQMM)

Coal quality (ash, sulphur, moisture, and heating value) is one of the fundamental concerns for both coal mines and power plants. In order to deliver uniform coal quality to the power plant, there is a need for realtime monitoring of coal quality from the mine to the coal stockpiles. The specific problem represents the process of stacking the coal inside an enclosed facility such as a dome. The objective of this research was to develop a custom-made and integrated coal quality management model for dome storage (DS-CQMM). The DS-CQMM merges existing technology in surface mines, such as coal analysers, together with automation technologies, information technologies (IT), and mathematical models. The DS-CQMM is organized into four major sections: Delay Time application, Stacker application, Reclaimer application, and Live Stockpile application. A sub-process called Volume Calculation is embedded in Stacker application, while an additional feature called Forecast tool is included in the Reclaimer application. The DS-CQMM model was developed for a surface coal mine in the southern USA

Chiral particle separation by a non-chiral micro-lattice

We conceived a model experiment for a continuous separation strategy of chiral molecules (enantiomers) without the need of any chiral selector structure or derivatization agents: Micro-particles that only differ by their chirality are shown to migrate along different directions when driven by a steady fluid flow through a square lattice of cylindrical posts. In accordance with our numerical predictions, the transport directions of the enantiomers depend very sensitively on the orientation of the lattice relatively to the fluid flow

Wave Influenced Wind and the Effect on Offshore Wind Turbine Performance

In this paper the effect of wave influenced wind on offshore wind turbines is studied numerically. The wave is seen as a dynamical roughness that influences the wind flow and hence the wind turbine performance. An actuator line representation of the NREL's 5 MW offshore baseline wind turbine is placed in a simulation domain with a moving mesh that resolves the ocean waves. These wave influenced wind turbine simulations, WIWiTS, show that the wave will influence the wind field at the turbine rotor height. Both the produced power and the tangential forces on the rotor blades will vary according to the three different cases studied: wind aligned with a swell, wind opposing the swell and wind over a surface with low roughness (no waves).publishedVersio

Outcome of all-inside second-generation meniscal repair: Minimum five-year follow-up

BACKGROUND: Meniscal repair and preservation are the goal, when possible, of the treatment of meniscal injury. Current research on second-generation all-inside repair systems has been limited to a maximum of three years of follow-up. The purpose of this study was to evaluate the mid-term clinical success (at more than five years) of meniscal repair performed with a second-generation all-inside repair device, both as an isolated procedure and with a concomitant anterior cruciate ligament (ACL) reconstruction. METHODS: This is a retrospective review of patients who underwent meniscal repair with use of the all-inside FAST-FIX Meniscal Repair System (Smith & Nephew Arthroscopy, Andover, Massachusetts) from December 1999 to January 2007. Eighty-three meniscal repairs (in eighty-one patients) were identified, and follow-up data were obtained for seventy-five (90%). Twenty-six (35%) of the meniscal repairs were performed as isolated procedures. Clinical failure was defined as repeat surgical intervention involving resection or revision repair. Clinical outcomes were also assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and the Marx activity score. RESULTS: The minimum duration of follow-up was five years (average, seven years). Twelve patients (16%) had failure of the meniscal repair, at an average of forty-seven months (range, fifteen to ninety-five months). The data did not offer enough statistical evidence, at alpha = 0.05, to establish a difference in average patient age, patient sex, or number of sutures utilized between successful repairs and failures. There was no difference in the failure rate between isolated repairs (12%; 95% confidence interval [CI]: −0.76% to 23.76%) and those performed with concurrent ACL reconstruction (18%; 95% CI: 7.47% to 29.13%), and the average time to failure was similar between these two groups (48.1 months versus 46.6 months, p = 0.939). Postoperative KOOS and IKDC outcome scores were also similar between the groups. CONCLUSIONS: This report of mid-term follow-up results of primary second-generation all-inside meniscal repair demonstrates its effectiveness both as an isolated procedure and when it is performed with concurrent ACL reconstruction. After a minimum of five years of follow-up, 84% of the patients continued to demonstrate successful repair. Treatment success was further supported by favorable results on patient-based outcome measures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

ISG15 protects human Tregs from interferon alpha-induced contraction in a cell-intrinsic fashion

Objectives: Type I interferons (IFNs) inhibit regulatory T-cell (Treg) expansion and activation, making them beneficial in antiviral responses, but detrimental in autoimmune diseases. Herein, we investigate the role of ISG15 in human Tregs in the context of refractoriness to type I IFN stimulation. Methods: ISG15 expression and Treg dynamics were analysed in vitro and ex vivo from patients with chronic hepatitis C, with lupus and ISG15 deficiency. Results: ISG15 is expressed at high levels in human Tregs, renders them refractory to the IFN-STAT1 signal, and protects them from IFN-driven contraction. In vitro, Tregs from healthy controls upregulate ISG15 upon activation to higher levels than conventional CD4 T cells, and ISG15-silenced Tregs are more susceptible to IFNα-induced contraction. In human ISG15 deficiency, patient Tregs display an elevated IFN signature relative to Tregs from healthy control. In vivo, in patients with chronic hepatitis C, 2 days after starting pegIFN/ribavirin therapy, a stronger ISG15 inducibility correlates with a milder Treg depletion. Ex vivo, in systemic lupus erythematosus patients, higher levels of ISG15 are associated to reduced STAT1 phosphorylation in response to IFNα, and also to increased frequencies of Tregs, characterising active disease. Conclusion: Our results reveal a Treg-intrinsic role of ISG15 in dictating their refractoriness to the IFN signal, thus preserving the Treg population under inflammatory conditions

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease

Clinical relevance of Neutral Endopeptidase (NEP/CD10) in melanoma

BACKGROUND: Overexpression of Neutral Endopeptidase (NEP) has been reported in metastatic carcinomas, implicating NEP in tumor progression and suggesting a role for NEP inhibitors in its treatment. We investigated the role of NEP expression in the clinical progression of cutaneous melanoma. METHODS: We screened 7 melanoma cell lines for NEP protein expression. NEP-specific siRNA was transfected into the lines to examine the role of gene transcription in NEP expression. Immunohistochemistry was done for 93 specimens and correlated with clinicopathologic parameters. Thirty-seven metastatic melanoma specimens were examined for NEP transcript expression using Affymetrix GeneChips. In a subset of 25 specimens for which both transcript and protein expression was available, expression ratios were used to identify genes that co-express with NEP in GeneChip analysis. RESULTS: NEP was overexpressed in 4/7 human melanoma cell lines, and siRNA knock-down of NEP transcripts led to downregulation of its protein expression. NEP protein overexpression was significantly more common in metastatic versus primary tumors (P = 0.002). Twelve of 37 (32%) metastatic tumors had increased NEP transcript expression, and an association was observed between NEP transcript upregulation and protein overexpression (P < 0.0001). Thirty-eight genes were found to significantly co-express with NEP (p < 0.005). Thirty-three genes positively correlated with NEP, including genes involved in the MAP kinase pathway, antigen processing and presentation, apoptosis, and WNT signaling pathway, and 5 genes negatively correlated with NEP, including genes of focal adhesion and the notch signaling pathways. CONCLUSION: NEP overexpression, which seems to be largely driven by increased transcription, is rare in primary melanoma and occurs late in melanoma progression. Functional studies are needed to better understand the mechanisms of NEP regulation in melanoma

Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma

Background Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism. Case presentation A 65-year-old patient with metastatic melanoma who progressed through two immunotherapy strategies with immune checkpoint inhibitor antibodies was enrolled in a phase I study (NCT02285101) and treated with 2 mg/kg intravenously, weekly pegylated recombinant arginase (BCT-100). The patient experienced no toxicities > grade 2 and entered a complete remission which is sustained for over 30 months. RNA-sequencing identified a number of transcriptomic pathway alterations compared to control samples. The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples. Conclusions Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy