LC

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory requirement for the carriage of bulk liquid chemicals transported by sea in tank ships, thereby creating the need for inhalation data on many hundreds of chemicals in bulk maritime transport. Taking note of previously published proposals for estimating acute inhalation toxicity hazards for chemicals, and the paucity of measured experimental data, an extrapolation method has been developed by the Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) to partly fulfil this need. This method should be seen as a pragmatic approach to the challenge of missing measured experimental test data, with the added benefit of reducing tests in experimental animals. The metho...

This policy brief is based on an extensive body of research across Europe and elsewhere conducted by leading researchers in the field across more than 30 countries. We have studied the use of digital technologies by children under 8 years old in a variety of settings using an extensive range of research methods.

To obtain a more comprehensive profile of bile acids (BAs) in blood, we developed an ultrahigh performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC-MRM-MS) method for the separation and detection of 50 known BAs. This method utilizes phospholipid-depletion solid-phase extraction as a new high-efficiency sample preparation procedure for BA assay. UPLC/scheduled MRM-MS with negative ion electrospray ionization enabled targeted quantitation of 43 and 44 BAs, respectively, in serum samples from seven individuals with and without fasting, as well as in plasma samples from six cholestatic gene knockout mice and six age- and gender-matched wild-type (FVB/NJ) animals. Many minor BAs were identified and quantitated in the blood for the first time. Method validation indicated good quantitation precision with intraday and interday relative standard deviations of ≤9.3% and ≤10.8%, respectively. Using a pooled human serum sample and a pooled mouse plasma sample ...

Time Response enhancement utilizing photovoltaic based cascaded Landsman Converter (LC) structure is one of the soft strategies in the recent scenario. The prime function of a DC-DC Landsman converter is to optimize the output power of the photovoltaic array and reduce the output voltage ripples. This paper reveals the demonstration and simulation of the Cascaded Landsman Converter Inverter System (CLCIS) with a PV source. MATLAB Simulink-model for CLCIS has been created utilizing the components of Simulink and closed-loop examinations are performed with PI and Fractional-Order-PID (FOPID) Controllers. The present work deal with the comparison of transient and steady-state time responses of CLCIS with PI and FOPID controllers. The outcomes demonstrate that dynamic reaction is enhanced by utilizing FOPID controller.

Alterations in the autophagic pathway are associated with the onset and progression of various diseases. However, despite the therapeutic potential for pharmacological modulators of autophagic flux, few such compounds have been characterised. Here we show that clomipramine, an FDA-approved drug long used for the treatment of psychiatric disorders, and its active metabolite desmethylclomipramine (DCMI) interfere with autophagic flux. Treating cells with DCMI caused a significant and specific increase in autophagosomal markers and a concomitant blockage of the degradation of autophagic cargo. This observation might be relevant in therapy in which malignant cells exploit autophagy to survive stress conditions, rendering them more susceptible to the action of cytotoxic agents. In accordance, DCMI-mediated obstruction of autophagic flux increased the cytotoxic effect of chemotherapeutic agents. Collectively, our studies describe a new function of DCMI that can be exploited for the treatm...

The 96-h LC 50 value of cadmium chloride (CdCl 2 · H 2 O), a metal salt widely used in industry, was determined in the water frog (Rana ridibunda Pallas, 1771). The experiments were conducted in two series and a total of 140 frogs were used to determine acute toxicity. In ...

The hallmark of granular corneal dystrophy type 2 (GCD2) is the deposit of mutant transforming growth factor-β (TGF-β)-induced protein (TGFBIp) in the cornea. We have recently shown that there is a delay in autophagic degradation of mutant-TGFBIp via impaired autophagic flux in GCD2 corneal fibroblasts. We hypothesized that melatonin can specifically induce autophagy and consequently eliminate mutant-TGFBIp in GCD corneal fibroblasts. Our results show that melatonin activates autophagy in both wild-type (WT) and GCD2-homozygous (HO) corneal fibroblast cell lines via the mammalian target of rapamycin (mTOR)-dependent pathway. Melatonin treatment also led to increased levels of beclin 1, which is involved in autophagosome formation and maturation. Furthermore, melatonin significantly reduced the amounts of mutant- and WT-TGFBIp. Treatment with melatonin counteracted the autophagy-inhibitory effects of bafilomycin A1, a potent inhibitor of autophagic flux, demonstrating that melatonin enhances activation of autophagy and increases degradation of TGFBIp. Cotreatment with melatonin and rapamycin, an autophagy inducer, had an additive effect on mutant-TGFBIp clearance compared to treatment with either drug alone. Treatment with the selective melatonin receptor antagonist luzindole did not block melatonin-induced autophagy. Given its ability to activate autophagy, melatonin is a potential therapeutic agent for GCD2.