Understanding the Anomalous Diffusion of Water in Aqueous Electrolytes Using Machine Learned Potentials

The diffusivity of water in aqueous cesium iodide solutions is larger than that in neat liquid water, and vice versa for sodium chloride solutions. Such peculiar ion-specific behavior, called anomalous diffusion, is not reproduced in typical force field-based molecular dynamics (MD) simulations due to inadequate treatment of ion-water interactions. Herein, this hurdle is tackled using machine learned atomic potentials (MLPs) trained on data from density functional theory calculations. MLP-based atomistic MD simulations of aqueous salt solutions reproduce experimentally determined thermodynamic, structural, dynamical, and transport properties, including their varied trends of water diffusivities across salt concentration. This enables an examination of their intermolecular structure to unravel the microscopic underpinnings of the distinction in their transport. While both ions in CsI solutions contribute to faster diffusion of water molecules, the competition between the heavy retardation by Na-ions and slight acceleration by Cl-ions in NaCl solutions reduces their water diffusivity.Comment: 23 pages, 5 figure

Quantitative measurement of blood flow in paediatric brain tumours. A comparative study of dynamic susceptibility contrast and multi-timepoint arterial spin-labelled MRI

OBJECTIVE: Arterial spin-labelling (ASL) MRI uses intrinsic blood water to quantify the cerebral blood flow (CBF), removing the need for the injection of a gadolinium-based contrast agent used for conventional perfusion imaging such as dynamic susceptibility contrast (DSC). Owing to the non-invasive nature of the technique, ASL is an attractive option for use in paediatric patients. This work compared DSC and multi-timepoint ASL measures of CBF in paediatric brain tumours. METHODS: Patients (n = 23; 20 low-grade tumours and 3 high-grade tumours) had DSC and multi-timepoint ASL with and without vascular crushers (VC). VC removes the contribution from larger vessel blood flow. Mean perfusion metrics were extracted from control and T(1)-enhanced tumour regions of interest (ROIs): arterial arrival time (AAT) and CBF from the ASL images with and without VC, relative cerebral blood flow (rCBF), relative cerebral blood volume, delay time (DT) and mean transit time (MTT) from the DSC images. RESULTS: Significant correlations existed for: AAT and DT (r = 0.77, p = 0.0002) and CBF and rCBF (r = 0.56, p = 0.02) in control ROIs for ASL-noVC. No significant correlations existed between DSC and ASL measures in the tumour region. Significant differences between control and tumour ROI were found for MTT (p < 0.001) and rCBF (p < 0.005) measures. CONCLUSION: Significant correlations between ASL-noVC and DSC measures in the normal brain suggest that DSC is most sensitive to macrovascular blood flow. The absence of significant correlations within the tumour ROI suggests that ASL is sensitive to different physiological mechanisms compared with DSC measures. ADVANCES IN KNOWLEDGE: ASL provides information which is comparable with that of DSC in healthy tissues, but appears to reflect a different physiology in tumour tissues

A Web Infrastructure for Certifying Multimedia News Content for Fake News Defense

In dealing with altered visual multimedia content, also referred to as fake news, we present a ready-to-deploy extension of the current public key infrastructure (PKI), to provide an endorsement and integrity check platform for newsworthy visual multimedia content. PKI, which is primarily used for Web domain authentication, can directly be utilized with any visual multimedia file. Unlike many other fake news researches that focus on technical multimedia data processing and verification, we enable various news organizations to use our developed program to certify/endorse a multimedia news content when they believe this news piece is truthiness and newsworthy. Our program digitally signs the multimedia news content with the news organization's private key, and the endorsed news content can be posted not only by the endorser, but also by any other websites. By installing a web browser extension developed by us, an end user can easily verify whether a multimedia news content has been endorsed and by which organization. During verification, our browser extension will present to the end user a floating logo next to the image or video. This logo, in the shape of a shield, will show whether the image has been endorsed, by which news organization, and a few more pieces of essential text information of the news multimedia content. The proposed system can be easily integrated to other closed-web system such as social media networks and easily applied to other non-visual multimedia files.Comment: 7 pages, 6 figure

Pathway-specific inhibition of primaquine metabolism by chloroquine/quinine

BACKGROUND: There has been some evidence to suggest that the addition of chloroquine (CQ) or quinine (QN) to 8-aminoquinoline (8-AQ) treatment regimens may increase the therapeutic efficacy of the 8-AQ and simultaneously mitigate against its haemolytic toxicity. However, both CQ and QN are considered effective, although perhaps moderate inhibitors of CYP2D6, an enzyme now regarded as necessary for primaquine (PQ) pharmacologic activity. An understanding of the influence of CQ and QN on the metabolism of PQ may shed light on the potential mechanisms of the beneficial interaction. METHODS: Differential metabolism of PQ enantiomers by recombinant human CYP2D6, monoamine oxidase A (MAO), and cryopreserved human hepatocytes in the presence/absence of CQ and QN. RESULTS: Both CQ and QN significantly inhibited the activity of CYP2D6. PQ depletion by MAO and human hepatocytes was not affected significantly by the presence of CQ and QN. CYP2D6-mediated hydroxylation was largely suppressed by both CQ and QN. The formation of the primary deaminated metabolites, including carboxyprimaquine (CPQ) and cyclized side chain derivative from the aldehyde (m/z 241), was not sensitive to the presence of CQ and QN. However, the appearance of the glucuronides of CPQ and PQ alcohol were significantly suppressed. CQ and QN also inhibited the appearance of the m/z 257 metabolite with a similar pattern, suggesting that it may be derived from the CPQ conjugate. The apparent quinone-imine of CPQ (m/z 289) was only partially suppressed by both QN and CQ, but with a differential pattern of inhibition for the two drugs. The m/z 274 (quinone-imine of a ring-hydroxylated PQ metabolite) and m/z 422 (an apparent glucose conjugate of PQ) metabolites in hepatocytes were strongly suppressed by both QN and CQ, perhaps a reflection of the 2D6 inhibition by these drugs. The formation of the carbamoyl glucuronide of PQ (m/z 480) was not affected by CQ/QN. CONCLUSION: The metabolite-specific interactions in the current studies seem at variance with earlier reports of the dependence of PQ on CYP2D6 metabolism, and enhanced PQ anti-malarial activity/reduced toxicity in the presence of CQ/QN. These results suggest a complex picture in which CQ/QN may shift metabolite pathway balances towards a profile that retains efficacy, while reducing the formation or availability of toxic metabolites to erythrocytes. Alternatively, these drugs may alter transport or distribution of PQ metabolites in a fashion that reduces toxicity while maintaining efficacy against the parasite

Formation primaquine-5, 6-orthoquinone, the putative active and toxic metabolite of primaquine via direct oxidation in human erythrocytes

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics Short precorneal residence time and poor transocular membrane permeability are the major challenges associated with topical ocular drug delivery. In the present research, the efficiency of the electrolyte-triggered sol-to-gel-forming system of natamycin (NT) transfersomes was investigated for enhanced and prolonged ophthalmic delivery. Transfersomes were optimized by varying the molar ratios of phospholipid, sorbitan monostearate (Span) and tocopheryl polyethylene glycol succinate (TPGS). NT transfersome formulations (FNs) prepared with a 1:1 molar ratio of phospholipid-to-Span and low levels of TPGS showed optimal morphometric properties, and were thus selected to fabricate the in situ gelling system. Gellan gum-based (0.3% w/v) FN-loaded formulations (FNGs) immediately formed an in situ gel in the simulated tear fluid, with considerable viscoelastic characteristics. In vitro cytotoxicity in corneal epithelial cells and corneal histology studies demonstrated the ocular safety and cytocom-patibility of these optimized formulations. Transcorneal permeability of NT from these formulations was significantly higher than in the control suspension. Moreover, the ocular disposition studies of NT, from the FNs and FNGs, in New Zealand male albino rabbits demonstrated the superiority of the electrolyte-sensitive FNGs in terms of NT delivery to the ocular tissues

Gastrointestinal Bleeding in Patients With Acute Respiratory Distress Syndrome: A National Database Analysis.

Background:The goal of our study was to determine the impact of gastrointestinal bleeding (GIB) on in-hospital outcomes among acute respiratory distress syndrome (ARDS) patients, and subsequently determine the potential risk factors for the development of GIB. Methods:ARDS patients with and without GIB were identified using the National Inpatient Sample (2002 - 2012). Linear regression analysis was used to assess impact of GIB on in-hospital mortality, length of stay and total charges. Univariate logistic regression was used to determine associated odds ratios (OR) for causes of ARDS and common comorbid conditions. Results:We identified 149,190 ARDS patients. The incidence of GIB was the highest among patients \u3e 60 years (P \u3c 0.001). GIB was associated with longer hospitalization days (7.3 days versus 11.9 days, P \u3c 0.001), higher mortality (11% versus 27%, P \u3c 0.001) and greater economic burden ($82,812 versus$45,951, P \u3c 0.001). GIB was common in cirrhosis (OR: 8.3), peptic ulcer disease (OR: 3.7), coagulopathy disorders (OR: 3.003), thrombocytopenia (OR: 2.6), anemia (OR: 2.5) and atrial fibrillation (OR: 1.5). ARDS secondary to aspiration pneumonia (OR: 2.0), pancreatitis (OR: 2.0), sepsis (OR: 1.6) and community acquired pneumonia (OR: 0.8) was more likely to have GIB. Conclusion:Our study demonstrates that GIB in ARDS patients is associated with significant increased mortality, hospitalization and health care cost

Magnetic properties of strained multiferroic CoCr2O4\mathrm{CoC}{\mathrm{r}}_{2}{\mathrm{O}}_{4}: A soft x-ray study

Using resonant soft x-ray techniques we follow the magnetic behavior of a strained epitaxial film of CoCr2O4, a type-II multiferroic. The film is [110] oriented, such that both the ferroelectric and ferromagnetic moments can coexist in-plane. X-ray magnetic circular dichroism (XMCD) is used in scattering and in transmission modes to probe the magnetization of Co and Cr separately. The transmission measurements utilized x-ray excited optical luminescence from the substrate. Resonant soft x-ray diffraction (RXD) was used to study the magnetic order of the low temperature phase. The XMCD signals of Co and Cr appear at the same ordering temperature TC≈90K, and are always opposite in sign. The coercive field of the Co and of Cr moments is the same, and is approximately two orders of magnitude higher than in bulk. Through sum rules analysis an enlarged Co2+ orbital moment (mL) is found, which can explain this hardening. The RXD signal of the (q q 0) reflection appears below TS, the same ordering temperature as the conical magnetic structure in bulk, indicating that this phase remains multiferroic under strain. To describe the azimuthal dependence of this reflection, a slight modification is required to the spin model proposed by the conventional Lyons-Kaplan-Dwight-Menyuk theory for magnetic spinels

The Spin-Reorientation Transition in TmFeO3

X-ray magnetic circular and linear dichroism (XMCD and XMLD) have been used to investigate the Fe magnetic response during the spin reorientation transition (SRT) in TmFeO3. These experiments are complemented with resonant magnetic diffraction experiments at the Tm M5 edge to study simultaneously the induced magnetic order in the Tm 4f shell and the behavior of the Tm orbitals through the SRT. Comparing the Fe XMLD results with neutron diffraction and magnetization measurements on the same sample indicate that the SRT has an enhanced temperature range in the near surface region. This view is supported by the resonant soft x-ray diffraction results at the Tm M5 edge. These find an induced magnetic moment on the Tm sites, which is well-described by a dipolar mean field model originating from the Fe moments. Even though such a model can describe the 4f response in the experiments, it is insufficient to describe the SRT even when considering a change in the 4f anisotropy. Moreover, the results of the Fe XMCD are indicative of a decoupling of spin canting and antiferromagnetic spin rotation in the near surface regime close to the SRT, which remains to be understood.Comment: 28 pages, 12 figure

Magnetic properties of strained multiferroic CoCr2O4: a soft X-ray study

Using resonant soft X-ray techniques we follow the magnetic behavior of a strained epitaxial film of CoCr2O4, a type-II multiferroic. The film is [110]-oriented, such that both the ferroelectric and ferromagnetic moments can coexist in plane. X-ray magnetic circular dichroism (XMCD) is used in scattering and in transmission modes to probe the magnetization of Co and Cr separately. The transmission measurements utilized X-ray excited optical luminescence from the substrate. Resonant soft X-ray diffraction (RSXD) was used to study the magnetic order of the low temperature phase. The XMCD signals of Co and Cr appear at the same ordering temperature Tc~90K, and are always opposite in sign. The coercive field of the Co and of Cr moments is the same, and is approximately two orders of magnitude higher than in bulk. Through sum rules analysis an enlarged Co2+ orbital moment (m_L) is found, which can explain this hardening. The RSXD signal of the (q q 0) reflection appears below Ts, the same ordering temperature as the conical magnetic structure in bulk, indicating that this phase remains multiferroic under strain. To describe the azimuthal dependence of this reflection, a slight modification is required to the spin model proposed by the conventional Lyons-Kaplan-Dwight-Menyuk theory for magnetic spinels. Lastly, a slight increase in reflected intensity is observed below Ts=27K when measuring at the Cr edge (but not at the Co edge).Comment: 28 pages, 15 figure