N,N′-Bis(pyridin-2-yl)benzene-1,4-dicarboxamide

Mol­ecules of the title compound, C18H14N4O2, are located around an inversion center and connected into chains in the crystal via inter­molecular N—H⋯N hydrogen bonds generating an R 2 2(8) motif

A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

<p>Abstract</p> <p>Background</p> <p>In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.</p> <p>Methods</p> <p>Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.</p> <p>Results</p> <p>Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (<it>p </it>< 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.</p> <p>Conclusions</p> <p>HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.</p

Treatment efficacy and acceptability of pharmacotherapies for dementia with lewy bodies: a systematic review and network meta-analysis

Introduction We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms (NPS), cognitive function, motor symptoms, and acceptability. Methods Electronic databases were searched from inception through June 5, 2019, for randomized controlled trials (RCTs) and open-label trials (OLTs) in patients with DLB. We performed a pairwise conventional meta-analysis (PWMA) and network meta-analysis (NMA) within a frequentist framework. The main outcomes were mean change scores in NPS, general cognition, motor symptoms and acceptability. The effect sizes and odds ratios with 95% confidence intervals (CIs) were calculated. This study was registered with PROSPERO (CRD42018096996). Results In total, we included 29 studies (9 RCTs and 20 OLTs). In the NMA with 9 RCTs, both high- (mean difference [MD] 2.00, 95% CIs, 0.69 to 3.31) and low-dose (1.86, 0.58 to 3.15) donepezil were associated with a greater cognitive improvement than placebo. High-dose zonisamide was associated with greater motor symptom improvement ( -4.10, -7.03 to -1.17]). No medications reached statistical significance regarding improving neuropsychiatric symptoms or developing intolerable adverse effects as compared to placebo. In the second NMA, with 29 studies as an exploratory analysis, aripiprazole and yokukansan may be effective for neuropsychiatric symptoms, while levodopa may be associated with cognitive impairment. Conclusions We report the most comprehensive evidence for the selection of pharmacotherapy for treating different clusters of DLB-related symptoms. Due to the limited availability of RCTs on DLB, more well-conducted RCTs are needed for MMA to warrant clinical efficacy in the future

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Lens Design Method Prediction of Local Optimization Algorithm by Using Deep Learning

A design rule prediction is proposed to assist a lens design in this paper. Deep learning was applied in order to predict a lens design rule that is based on a local optimization algorithm. Three separate lens design rules related to the aperture stop and FOV variation were made for the optimization in the two-lens element optical systems whose structural parameters were created randomly. These random lens structures were optimized by using three separate lens design rules that were developed by Zemax OpticStudio API to create a big optimization dataset. All of the optimization results were collected by means of a further deep learning process to determine which optimization rule would be the better choice for lens optimization when given the lens parameters. The model developed via deep learning shows that the prediction has a 78.89% accuracy in determining an appropriate optimization rule for an assistant lens design

Lens Design Method Prediction of Local Optimization Algorithm by Using Deep Learning

A design rule prediction is proposed to assist a lens design in this paper. Deep learning was applied in order to predict a lens design rule that is based on a local optimization algorithm. Three separate lens design rules related to the aperture stop and FOV variation were made for the optimization in the two-lens element optical systems whose structural parameters were created randomly. These random lens structures were optimized by using three separate lens design rules that were developed by Zemax OpticStudio API to create a big optimization dataset. All of the optimization results were collected by means of a further deep learning process to determine which optimization rule would be the better choice for lens optimization when given the lens parameters. The model developed via deep learning shows that the prediction has a 78.89% accuracy in determining an appropriate optimization rule for an assistant lens design

Performance Evaluation of Major Asian Airline Companies Using DEA Window Model and Grey Theory

Being an essential part of the global transport system, airline transportation is capable of delivering fast service for passengers and commodities. In the past decade, the Asia aviation industry has experienced a high growth rate of transport due to higher economic development in this area, and this trend is expected to continue in the next two decades. However, competition in the Asia aviation industry will increase dramatically. To survive in the Asia aviation industry, the Asia airline companies should understand their current and future performance. A methodology for this purpose is required. This paper proposes a hybrid approach, combining Grey model GM(1,1) and Data Envelopment Analysis (DEA) Window model, to satisfy this need. The hybrid approach proposed in this research has been used to evaluate the current and future performance of 16 major Asia airline companies. The DEA Window analysis showed that airline companies Emirates, Cebu Pacific, and Sri Lankan were leading companies in the time period of 2012 to 2016, while Singapore Airlines, Japan Airlines, and All Nippon Airways followed behind. We found that Chinese airline corporations are rising in the Asia aviation industry. All 16 Asia airline companies studied in the research were found to improve their productivity in the time period of 2017 to 2021 as their Malmquist productivity indexes (MPIs) are greater than 1