Analytical Gradients for Projection-Based Wavefunction-in-DFT Embedding

Projection-based embedding provides a simple, robust, and accurate approach for describing a small part of a chemical system at the level of a correlated wavefunction method while the remainder of the system is described at the level of density functional theory. Here, we present the derivation, implementation, and numerical demonstration of analytical nuclear gradients for projection-based wavefunction-in-density functional theory (WF-in-DFT) embedding. The gradients are formulated in the Lagrangian framework to enforce orthogonality, localization, and Brillouin constraints on the molecular orbitals. An important aspect of the gradient theory is that WF contributions to the total WF-in-DFT gradient can be simply evaluated using existing WF gradient implementations without modification. Another simplifying aspect is that Kohn-Sham (KS) DFT contributions to the projection-based embedding gradient do not require knowledge of the WF calculation beyond the relaxed WF density. Projection-based WF-in-DFT embedding gradients are thus easily generalized to any combination of WF and KS-DFT methods. We provide numerical demonstration of the method for several applications, including calculation of a minimum energy pathway for a hydride transfer in a cobalt-based molecular catalyst using the nudged-elastic-band method at the CCSD-in-DFT level of theory, which reveals large differences from the transition state geometry predicted using DFT.Comment: 15 pages, 4 figure

Analytical Gradients for Molecular-Orbital-Based Machine Learning

Molecular-orbital-based machine learning (MOB-ML) enables the prediction of accurate correlation energies at the cost of obtaining molecular orbitals. Here, we present the derivation, implementation, and numerical demonstration of MOB-ML analytical nuclear gradients which are formulated in a general Lagrangian framework to enforce orthogonality, localization, and Brillouin constraints on the molecular orbitals. The MOB-ML gradient framework is general with respect to the regression technique (e.g., Gaussian process regression or neural networks) and the MOB feature design. We show that MOB-ML gradients are highly accurate compared to other ML methods on the ISO17 data set while only being trained on energies for hundreds of molecules compared to energies and gradients for hundreds of thousands of molecules for the other ML methods. The MOB-ML gradients are also shown to yield accurate optimized structures, at a computational cost for the gradient evaluation that is comparable to Hartree-Fock theory or hybrid DFT

A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis:a sub‐study from the DISCUSS project

Aim: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC.Method: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs.Results: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0–100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery.Conclusion: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC

Temporal Expression of Bacterial Proteins Instructs Host CD4 T Cell Expansion and Th17 Development

Pathogens can substantially alter gene expression within an infected host depending on metabolic or virulence requirements in different tissues, however, the effect of these alterations on host immunity are unclear. Here we visualized multiple CD4 T cell responses to temporally expressed proteins in Salmonella-infected mice. Flagellin-specific CD4 T cells expanded and contracted early, differentiated into Th1 and Th17 lineages, and were enriched in mucosal tissues after oral infection. In contrast, CD4 T cells responding to Salmonella Type-III Secretion System (TTSS) effectors steadily accumulated until bacterial clearance was achieved, primarily differentiated into Th1 cells, and were predominantly detected in systemic tissues. Thus, pathogen regulation of antigen expression plays a major role in orchestrating the expansion, differentiation, and location of antigen-specific CD4 T cells in vivo

CT densitometry as a predictor of pulmonary function in lung cancer patients.

Purpose: Preoperative pulmonary assessment is undertaken in patients with resectable lung cancer to identify those at increased risk of perioperative complications. Guidelines from the American College of Chest Physicians indicate that if the FEV1 and DLCO are ≥60% of predicted, patients are suitable for resection without further evaluation. The aim of our study is to determine if quantitative measures of lung volume and density obtained from pre-operative CT scans correlate with pulmonary function tests. This may allow us to predict pulmonary function in patients with lung cancer and identify patients who would tolerate surgical resection. Materials and Methods: Patients were identified retrospectively from the lung cancer database of a tertiary hospital. Image segmentation software was utilized to estimate total lung volume, normal lung volume (values -500 HU to -910 HU), emphysematous volume (values less than -910 HU), and mean lung density from pre-operative CT studies for each patient and these values were compared to contemporaneous pulmonary function tests. Results: A total of 77 patients were enrolled. FEV1 was found to correlate significantly with the mean lung density (r=.762, p<.001) and the volume of emphysema (r= -.678, p<.001). DLCO correlated significantly with the mean lung density (r =.648, p<.001) and the volume of emphysematous lung (r= -.535, p<.001). Conclusion: The results of this study suggest that both FEV1 and DLCO correlate significantly with volume of emphysema and mean lung density. We now plan to prospectively compare these CT parameters with measures of good and poor outcome postoperatively to identify CT measures that may predict surgical outcome preoperatively

Bringing "The Moth" to Light: A Planet-Sculpting Scenario for the HD 61005 Debris Disk

The HD 61005 debris disk ("The Moth") stands out from the growing collection of spatially resolved circumstellar disks by virtue of its unusual swept-back morphology, brightness asymmetries, and dust ring offset. Despite several suggestions for the physical mechanisms creating these features, no definitive answer has been found. In this work, we demonstrate the plausibility of a scenario in which the disk material is shaped dynamically by an eccentric, inclined planet. We present new Keck NIRC2 scattered-light angular differential imaging of the disk at 1.2-2.3 microns that further constrains its outer morphology (projected separations of 27-135 AU). We also present complementary Gemini Planet Imager 1.6 micron total intensity and polarized light detections that probe down to projected separations less than 10 AU. To test our planet-sculpting hypothesis, we employed secular perturbation theory to construct parent body and dust distributions that informed scattered-light models. We found that this method produced models with morphological and photometric features similar to those seen in the data, supporting the premise of a planet-perturbed disk. Briefly, our results indicate a disk parent body population with a semimajor axis of 40-52 AU and an interior planet with an eccentricity of at least 0.2. Many permutations of planet mass and semimajor axis are allowed, ranging from an Earth mass at 35 AU to a Jupiter mass at 5 AU.Comment: Accepted to AJ; added Figure 5 and minor text edit

Biodegradation of the herbicide mecoprop-p with soil depth and its relationship with class III tfdA genes

Mecoprop-p [(R)-2-(4-chloro-2-methylphenoxy) propanoic acid) is widely used 37 in agriculture and poses an environmental concern because of its susceptibility to leach 38 from soil to water. We investigated the effect of soil depth on mecoprop-p 39 biodegradation and its relationship with the number and diversity of tfdA related genes, 40 which are the most widely known genes involved in degradation of the 41 phenoxyalkanoic acid group of herbicides by bacteria. Mecoprop-p half-life (DT50) was 42 approximately 12 days in soil sampled from <30 cm depth, and increased progressively 43 with soil depth, reaching over 84 days at 70-80 cm. In sub-soil there was a lag period of 44 between 23 and 34 days prior to a phase of rapid degradation. No lag phase occurred in 45 top-soil samples prior to the onset of degradation. The maximum degradation rate was 46 the same in top-soil and sub-soil samples. Although diverse tfdAα and tfdA genes were 47 present prior to mecoprop-p degradation, real time PCR revealed that degradation was 48 associated with proliferation of tfdA genes. The number of tfdA genes and the most 49 probable number of mecoprop-p degrading organisms in soil prior to mecoprop-p 50 addition were below the limit of quantification and detection respectively. Melting 51 curves from the real time PCR analysis showed that prior to mecoprop-p degradation 52 both class I and class III tfdA genes were present in top- and sub-soil samples. However 53 at all soil depths only tfdA class III genes proliferated during degradation. Denaturing 54 gradient gel electrophoresis confirmed that class III tfdA genes were associated with 55 mecoprop-p degradation. Degradation was not associated with the induction of novel 56 tfdA genes in top- or sub-soil samples, and there were no apparent differences in tfdA 57 gene diversity with soil depth prior to or following degradation