COURSE-KEEPING CONTROL FOR DIRECTIONALLY UNSTABLE LARGE TANKERS USING THE MIRROR-MAPPING TECHNIQUE

This study examines the course-keeping control of directionally unstable large oil tankers involving a pole in the right half plane. Treated as an unstable plant in control engineering, tankers are theoretically and experimentally investigated during the controller design process. First, the unstable plant is mirror-mapped to its corresponding stable minimum phase plant using the mirror-mapping technique, which enables an easy controller design. Then, a linear proportional-differential and a first-order filter controller is designed based on the closed-loop gain shaping algorithm, which requires only one controller parameter to be properly selected based on the system’s characteristics. Numerical simulation results confirmed that the designed controller can successfully stabilise an unstable plant subjected to external wind and wave disturbances. The controller designed with the proposed method is suitable for course-keeping control of directionally unstable large tankers. The controller design method is simple with an uncomplicated structure that can easily be implemented in engineering endeavours. Moreover, the rudder motion is small and soft

Materijal od mješavine kenafa i poliestera za unutrašnje uređenje automobila sa svojstvom otpuštanja aniona

Danas, količina automobila u svijetu konstantno raste i ljudi provode više vremena u njima nego prije stoga su mnogi znanstvenici sve više zabrinuti za kvalitetu zraka u unutrašnjosti automobila. Onečišćenje zraka u automobilu uglavnom uzrokuju polimerni materijali koji se koriste za unutrašnje uređenje, odnosno materijali koji se koriste za izradu vrata, ukrasnih tkanina, podnih tepiha i navlaka za sjedala. Ovi su materijali uglavnom proizvedeni od kemijskih vlakana koja otpuštaju štetne plinove kao formaldehid, aceton, dimetilbenzen, i utječu na kvalitetu zraka u ograničenom prostoru automobila. U svrhu rješavanja tog problema i poboljšanja kvalitete zraka u vozilima razvijen je novi materijal za unutrašnje uređenje automobila sa svojstvom otpuštanja aniona od mješabine kenafovih i poliesterskih vlakna niskog tališta s dodatkom anionskog turmalinskog sredstva. Ortogonalna metoda primijenjena je za optimizaciju parametara aniona: materijal se uranja u turmalinsko sredstvo koncentracije 500 g/L dva puta po 20 min. Za analizu količine otpuštanja aniona pod utjecajem različitih faktora korišten je SPSS program te je dobivena sljedeća shema optimiziranog procesa: vruće prešanje na temperaturi od 189,9 oC i pritisak od 5,5 MPa u vremenu od 5,3 min. Ovako proizveden materijal može postići maksimalnu količinu oslobađanja aniona od 14801690 ion/cm-3. Anioni mogu adsorbirati, vezivati i deponirati lebdeće čestice iz zraka, a zbog piezoelektriciteta i piroelektriciteta turmalinskog praha anioni se mogu reciklirati i kontinuirano otpuštati u svrhu poboljšanja kvalitete zraka u unutrašnjosti automobila

FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies

Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domain-containing-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed

Pan-Genomic Study of Mycobacterium tuberculosis Reflecting the Primary/Secondary Genes, Generality/Individuality, and the Interconversion Through Copy Number Variations

Tuberculosis (TB) has surpassed HIV as the leading infectious disease killer worldwide since 2014. The main pathogen, Mycobacterium tuberculosis (Mtb), contains ~4,000 genes that account for ~90% of the genome. However, it is still unclear which of these genes are primary/secondary, which are responsible for generality/individuality, and which interconvert during evolution. Here we utilized a pan-genomic analysis of 36 Mtb genomes to address these questions. We identified 3,679 Mtb core (i.e., primary) genes, determining their phenotypic generality (e.g., virulence, slow growth, dormancy). We also observed 1,122 dispensable and 964 strain-specific secondary genes, reflecting partially shared and lineage-/strain-specific individualities. Among which, five L2 lineage-specific genes might be related to the increased virulence of the L2 lineage. Notably, we discovered 28 Mtb “Super Core Genes” (SCGs: more than a copy in at least 90% strains), which might be of increased importance, and reflected the “super phenotype generality.” Most SCGs encode PE/PPE, virulence factors, antigens, and transposases, and have been verified as playing crucial roles in Mtb pathogenicity. Further investigation of the 28 SCGs demonstrated the interconversion among SCGs, single-copy core, dispensable, and strain-specific genes through copy number variations (CNVs) during evolution; different mutations on different copies highlight the delicate adaptive-evolution regulation amongst Mtb lineages. This reflects that the importance of genes varied through CNVs, which might be driven by selective pressure from environment/host-adaptation. In addition, compared with Mycobacterium bovis (Mbo), Mtb possesses 48 specific single core genes that partially reflect the differences between Mtb and Mbo individuality

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data