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We examined the ability of each method to estimate the mixture's overall effect and to identify important chemicals. The results showed that as the number of BDL values increased, the accuracy, precision, model fit, and power declined for all imputation approaches. When chemical values were missing at 10%, 33%, or 50%, the MI approaches generally performed better than single imputation and BDLQ1. In the extreme case of 80% of all the chemical values were missing, the BDLQ1 approach was superior in some examined metrics. For the past decades, forensic chemists have made considerable efforts to develop methods capable of dating ballpoint pen ink by monitoring the loss of volatile solvents over time; however, few studies have been reported on carbon-based black gel inks. In China, carbon-based black gel pens are typically used for formal writing and signatures, such as contracts, loan receipts, testaments, and paper tests. Thus, it is imperative to analyze the age of carbon-based black gel inks for questioned document examiners in forensic casework. In this study, by employing the combination of gas chromatography with mass spectrometry (GC-MS) and GC with a flame ionization detector, a useful method for ink dating was proposed according to the dissipation of triethylene glycol from three novel carbon-based black gel inks. The ink aging curves suggested that this approach can distinguish questioned ink samples that are less than or greater than 9 months. This result could help to identify some questioned documents actually written within a month but are passed off as documents written years ago. Induced-charge electrokinetics (ICEK) remains a hot topic due to its promising applications in micro- and nano-fluidics. Over the past decade, researchers have made a great advancement in both fundamental studies and application developments. They captured (I) a flow reversal in induced-charge electroosmosis (ICEO) and attributed it to the phase delay effect of ions, (II) a chaotic ICEO and attributed it to the concentration polarization in the bulk solution, (III) a non-quadratic correlation for ICEO of non-Newtonian fluids and attributed it to the power-law viscosity, (IV) an induced-charge electrophoretic (ICEP) rotation of Janus doublets, etc. Furthermore, various ICEK-based micro- and nano-fluidic devices have been developed, namely, micropumps, particle focusers, trappers, sorters, and nanopore ion diodes. The present article provides a comprehensive review on the recent advancement of ICEK. Firstly, the fundamental studies of ICEK are introduced; then the micro- and nano-fluidic applications based on ICEK are presented; lastly, promising future directions for both fundamental and applications are discussed. This review presents the basic framework of ICEK, and can facilitate the development of ICEK-based applications. Semiconductor photocatalysis is regarded as most privileged solution for energy conversion and environmental application. Recently, photocatalysis methods using bismuth-based photocatalysts, such as BiPO4, have been extensively investigated owing to their superior efficacy regarding organic pollutant degradation and their further mineralization into CO2 and H2O. It is well known that BiPO4 monoclinic phase exhibited better photocatalytic performance compared to Degussa (Evonik) P25 TiO2 in term of ultraviolet light driven organic pollutants degradation. However, its wide band gap, poor adsorptive performance and large size make BiPO4 less active under visible light irradiation. However, extensive research works have been conducted in the past with the aim of improving visible light driven BiPO4 activity by constructing a series of heterostructures, mainly coupled with π-conjugated architecture (e.g., conductive polymer, dye sensitization and carbonaceous materials). However, a critical review of modified BiPO4 systems using π-conjugated materials has not been published to date. Therefore, this current review article was designed with the aim of presenting a brief current state-of-the-art towards synthesis methods of BiPO4 in the first section, with an especial focuses onto its crystal-microstructure, optical and photocatalytic properties. Moreover, the most relevant strategies that have been employed to improve its photocatalytic activities are then addressed as the main part of this review. Finally, the last section presents ongoing challenges and perspectives for modified BiPO4 systems using π-conjugated materials. One of the widely used applications of the popular Cre-loxP method for targeted recombination is the permanent activation of marker genes, such as reporter genes or antibiotic resistance genes, by excision of a preceding transcriptional stop signal. The STOP cassette consists of three identical SV40-derived poly(A) signal repeats and is flanked by two loxP sites. We found that in addition to complete loxP-mediated recombination, limiting levels of the Cre recombinase also cause incomplete recombination of the STOP cassette. Partial recombination leads to the loss of only one or two of the three identical poly(A) repeats with recombination breakpoints always precisely matching the end/start of each poly(A) signal repeat without any relevant similarity to the canonical or known cryptic loxP sequences, suggesting that this type of Cre-mediated recombination is loxP-independent. Incomplete deletion of the STOP cassette results in partial read-through transcription, explaining at least some of the variability often observed in marker gene expression from an otherwise identical locus. The pandemic spread of a novel coronavirus - SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle - the risk of antibody-mediated disease enhancement. The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. We also discuss how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis. BACKGROUND Excessive bleeding, incomplete wound drainage, and subsequent accumulation of blood and clots in the pericardium have been associated with a broad spectrum of bleeding-related complications after cardiac surgery. We developed and studied the continuous postoperative pericardial flushing (CPPF) method to improve wound drainage and reduce blood loss and bleeding-related complications. METHODS We conducted a single-center, open-label, ITT, randomized controlled trial at the Academic Medical Center Amstserdam. Adults undergoing cardiac surgery for non-emergent valvular or congenital heart disease (CHD) were randomly assigned (11) to receive CPPF method or standard care. The primary outcome was actual blood loss after 12-hour stay in the intensive care unit (ICU). Secondary outcomes included bleeding-related complications and clinical outcome after six months follow-up. FINDINGS Between May 2013 and February 2016, 170 patients were randomly allocated to CPPF method (study group; n = 80) or to standard care (control group; n = 90). CPPF significantly reduced blood loss after 12-hour stay in the ICU (-41%) when compared to standard care (median differences -155 ml, 95% confidence interval (CI) -310 to 0; p=≤0·001). Cardiac tamponade and reoperation for bleeding did not occur in the study group versus one and three in the control group, respectively. At discharge from hospital, patients in the study group were less likely to have pleural effusion in a surgically opened pleural cavity (22% vs. 36%; p = 0·043). INTERPRETATION Our study results indicate that CPPF is a safe and effective method to improve chest tube patency and reduce blood loss after cardiac surgery. Larger trials are needed to draw final conclusions concerning the effectiveness of CPPF on clinically relevant outcomes. BACKGROUND Salmonella causes intracellular infections in humans. Besides quinolones, third generation cephalosporins are first line drugs used for salmonellosis therapy. An unresolved anomaly of this practice involves high relapse rates associated to quinolone- or cephalosporin-susceptible Salmonella isolates in patients that are discharged clinically following initial recovery. Reduced drug accessibility to intracellular locations has been hypothesized to impair pathogen eradication although supporting evidence is lacking in vivo. Here, we uncover a novel penicillin-binding protein as the first Salmonella factor likely contributing to relapse following beta-lactam, mainly ceftriaxone, therapy. METHODS We used Salmonella enterica serovar Typhimurium mutants lacking the alternative penicillin-binding proteins PBP2SAL or PBP3SAL. Affinity of PBP2SAL and PBP3SAL for beta-lactam antibiotics was tested. Relapse after ceftriaxone therapy was analysed in the murine typhoid model. FINDINGS S. Typhimurium does not express PBP2SAL or PBP3SAL in the Mueller-Hinton medium used for susceptibility testing. The pathogen produces these PBPs in response to acidic pH and nutrient limitation, conditions found in phagosomes of mammalian cells. PBP3SAL has low affinity for beta-lactams, even at acidic pH. In vitro susceptibility to ceftriaxone at low pH is strongly reduced. S. Typhimurium lacking PBP3SAL was unable to cause relapse in mice following ceftriaxone therapy. INTERPRETATION The reduced capacity of ceftriaxone to clear S. Typhimurium in vivo is favoured by a switch in beta-lactam targets. This switch, involving production of the less-susceptible PBP3SAL, remains invisible for standard procedures used in clinical therapy. We conclude that eradication of salmonellosis will be possible only upon targeting of PBP3SAL with novel drugs. BACKGROUND The bile acid (BA) pathway plays a role in regulation of food intake and glucose metabolism, based mainly on findings in animal models. Our aim was to determine whether the BA pathway is altered and correctable in human obesity and diabetes. METHODS We conducted 3 investigations 1) BA receptor pathways were studied in NCI-H716 enteroendocrine cell (EEC) line, whole human colonic mucosal tissue and in human colonic EEC isolated by Fluorescence-activated Cell Sorting (ex vivo) from endoscopically-obtained biopsies colon mucosa; 2) We characterized the BA pathway in 307 participants by measuring during fasting and postprandial levels of FGF19, 7αC4 and serum BA; 3) In a placebo-controlled, double-blind, randomised, 28-day trial, we studied the effect of ileo-colonic delivery of conjugated BAs (IC-CBAS) on glucose metabolism, incretins, and lipids, in participants with obesity and diabetes. FINDINGS Human colonic GLP-1-producing EECs express TGR5, and upon treatment with bile acids in vitro, human EEC differentially expressed GLP-1 at the protein and mRNA level.

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