Influence of pH and temperature on alunite dissolution: Rates, products and insights on mechanisms from atomistic simulation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe processes, rates, controlling factors and products of alunite (KAl3(SO4)2(OH)6) dissolution were assessed using batch dissolution experiments at pHs of c. 3, 4, 4.6, 7 and 8, and temperatures of c. 280, 293 and 313K. Alunite dissolution is roughly congruent at pH3, while at pH≥3.9 the process is incongruent, giving a lower Al/K ratio in solution than in the pristine alunite sample. The decrease in the Al/K ratio appears to be caused by precipitation of secondary aluminium sulfate/hydroxysulfate minerals coating the surface of the dissolving alunite, as inferred from SEM images and XPS determinations, but these minerals do not passivate the alunite surface for the time frame of the experiments (up to 400h). The lowest dissolution rates are obtained for pH4.6 and 280K. Both the temperature increase and any pH variation from that point lead to faster dissolution rates. Based on the potassium release to solution, the influence of pH and temperature on the alunite dissolution rate for pH of 4.8 and below can be expressed as;. rateK= 104.4 ± 0.5aH+0.10 ± 0.02e32±3/RTwhere rateKis the alunite dissolution rate (in mol·m-2·s-1); aH+is the activity of hydrogen ions in solution; R is the Universal gas constant (in kJ·mol-1·K-1) and T is temperature (in K).For pH of 4.6 and above, the alunite dissolution rate can instead be expressed as;. rateK= 102.5±0.8aOH0.14±0.02e-39±4/RTwhere aOH-is the activity of hydroxyl ions in solution. In light of the calculated values for the activation energy under the two sets of pH conditions (32 ± 3 and 39 ± 4 kJ·mol-1), alunite dissolution appears to be surface-controlled. Examination of the most stable solvated alunite surfaces obtained by atomistic computer simulations suggests that the least energetically favourable steps during alunite dissolution are the detachment of either Al atoms or SO4tetrahedra from exposed surfaces. Thus, these processes are most probably the rate-determining steps in alunite dissolution.This work has been funded by the EC Marie Curie Intra-European Fellowship program (Project entitled ‘Reactivity of Aluminium Sulfate Minerals in Mine Wastes’; RASMIM) through a fellowship to P.A. The authors acknowledge also the NERC (National Environmental Research Council, United Kingdom) for partially funding the characterisation of mineral samples through the project ‘Characterisation of nanometre-sized aluminium sulphates: implications for mobility of aluminium from mine wastes’ (FENAC/2013/11/001)

A new class of self-assembled monolayers on gold using an alkynyl group as a linker

The geometry and energetics for adsorption of ethynylbenzene on Au(111) have been studied using Density Functional Theory. The alkynyl group, following removal of the terminal H atom, adsorbs covalently to the surface in the fcc hollow site with a bond energy of about 70 kcal.mol-1. Intermediate adsorption states are also possible via a hydrogen 1,2 shift to form a surface-bound vinylidene, or through the opening of the C-C triple bond without removing the hydrogen atom. © 2006 IEEE

Encouraging Rural Health Clinics to Provide Mental Health Services: What are the options?

Key Findings: Approximately 6% of independent and 2% of provider-based RHCs offer mental health services. 38% of study RHCs reported their mental health services were not profitable but continued to provide them in response to community and patient needs. An important factor in the development of RHC mental health services is the presence of a local champion who spearheads the development effort

The Provision of Mental Health Services by Rural Health Clinics

The number of Rural Health Clinics (RHCs) providing specialty mental health services remains limited. This study examined changes in the delivery of mental health services by RHCs, their operational characteristics, barriers to the development of services, and policy options to encourage more RHCs to deliver mental health services. Key Findings: Approximately 6% of independent and 2% of provider-based RHCs offer mental health services by doctoral-level psychologists and/or clinical social workers. Models used to provide mental health services include contracted and/or employed clinicians housed in the same facility as primary care providers. A key element in the development of mental health services is the presence of an internal champion (typically clinicians or senior administrators) who identify the need for and undertake implementation of services, help overcome internal barriers, and direct resources to the development of services

Histological sub‐classification of cirrhosis using collagen proportionate area in patients with chronic hepatitis C

Collagen proportionate area (CPA, %) is used to quantify liver fibrosis. Here we assessed CPA performance to subclassify cirrhosis. CPA was measured in explanted livers from consecutively transplanted patients for hepatitis C virus‐related cirrhosis. MELD, Child‐Pugh score and decompensating events (ascites, variceal bleeding, non‐obstructive jaundice and encephalopathy) were recorded at the time of liver transplant. Of the 154 patients, 24%, 12%, 35%, 24% and 5% had 0, 1, 2, 3 and 4 previous decompensating events. Patients with decompensation had significantly higher CPA than those without (25.1±8.4 vs. 15.8±5.5, P<0.001). Decompensation was independently associated with CPA, bilirubin and albumin or with CPA and MELD score. CPA did not differ between patients with 1, 2, 3 or 4 decompensating events (22.2±6.3 vs. 26.6±8.9 vs. 24.5±7.7 vs. 24.4±10.9, P=0.242). Overall, CPA correlates with the clinical severity of cirrhosis until the advent of decompensation but not with subsequent decompensating events

Thermodynamics of mixing in diopside-jadeite, CaMgSi2O6-NaAlSi2O6, solid solution from staticlattice energy calculations

Static lattice energy calculations (SLEC), based on empirical interatomic potentials, have beenperformed for a set of 800 different structures in a 2 2 4 supercell of C2/c diopside with compositionsbetween diopside and jadeite, and with different states of order of the exchangeable Na/Ca and Mg/Al cations. Excess static energies of these structures have been cluster expanded in a basis set of 37 pair-interaction parameters. These parameters have been used to constrain Monte Carlo simulations of temperature-dependent properties in the range of 273?2,023 K and to calculate a temperature?composition phase diagram. The simulations predict the order?disorder transition in omphacite at1,150 20C in good agreement with the experimental data of Carpenter (Mineral Petrol 78:433?440, 1981). The stronger ordering of Mg/Al within the M1 site than of Ca/Na in the M2 site is attributed to the shorter M1?M1 nearest-neighbor distance, and, consequently, the stronger ordering force. The comparison of the simulated relationship between the order parameters corresponding to M1 and M2 sites with the X-ray refinement data on natural omphacites (Boffa Ballaran et al. in Am Mineral83:419?433, 1998) suggests that the cation ordering becomes kinetically ineffective at about 600C

Interaction of silicon dangling bonds with insulating surfaces

We use first principles density functional theory calculations to study the interaction of a model dangling bond silicon tip with the surfaces of CaF2, Al2O3, TiO2, and MgO. In each case the strongest interaction is with the highest anions in the surface. We show that this is due to the onset of chemical bonding with the surface anions, which can be controlled by an electric field across the system. Combining our results and previous studies on semiconductor surfaces suggests that using dangling bond Si tips can provide immediate identification of surface species in atomically resolved noncontact atomic force microscopy and facilitate selective measurements of short-range interactions with surface sites

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

Exploratory Analysis of TP53\textit{TP53} Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

$\textbf{Background:}$ Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic $\textit{TP53}$ mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). $\textbf{Methods and Findings:}$ We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific $\textit{TP53}$ assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The $\textit{TP53}$ mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson $r$ = 0.59, $p$ 32 cm$^3$, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, $p$ = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. $\textbf{Conclusions:}$ In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.This work was supported by Cancer Research UK Grant numbers: A15601 (JDB), A11906 (NR), A20240 (NR), A18072 (JDB). JDB was supported by the National Institute for Health Research Cambridge Biomedical Research Centre. CAP was supported in part by the Academy of Medical Sciences, the Wellcome Trust, British Heart Foundation and Arthritis Research UK