PESPIP: Software to fit complex molecular and many-body potential energy surfaces with permutationally invariant polynomials.

We wish to describe a potential energy surface by using a basis of permutationally invariant polynomials whose coefficients will be determined by numerical regression so as to smoothly fit a dataset of electronic energies as well as, perhaps, gradients. The polynomials will be powers of transformed internuclear distances, usually either Morse variables, exp(-ri,j/λ), where λ is a constant range hyperparameter, or reciprocals of the distances, 1/ri,j. The question we address is how to create the most efficient basis, including (a) which polynomials to keep or discard, (b) how many polynomials will be needed, (c) how to make sure the polynomials correctly reproduce the zero interaction at a large distance, (d) how to ensure special symmetries, and (e) how to calculate gradients efficiently. This article discusses how these questions can be answered by using a set of programs to choose and manipulate the polynomials as well as to write efficient Fortran programs for the calculation of energies and gradients. A user-friendly interface for access to monomial symmetrization approach results is also described. The software for these programs is now publicly available.

Cabozantinib-induced osteoblast secretome promotes survival and migration of metastatic prostate cancer cells in bone.

Therapies that target cancer cells may have unexpected effects on the tumor microenvironment that affects therapy outcomes or render therapy resistance. Prostate cancer (PCa) bone metastasis is uniquely associated with osteoblastic bone lesions and treatment with cabozantinib, a VEGFR-2 and MET inhibitor, leads to a reduction in number and/or intensity of lesions on bone scans. However, resistance to cabozantinib therapy inevitably occurs. We examined the effect of cabozantinib on osteoblast differentiation and secretion in the context of therapy resistance. We showed that primary mouse osteoblasts express VEGFR2 and MET and cabozantinib treatment decreased osteoblast proliferation but enhanced their differentiation. A genome-wide analysis of transcriptional responses of osteoblasts to cabozantinib identified a set of genes accounting for inhibition of proliferation and stimulation of differentiation, and a spectrum of secreted proteins induced by cabozantinib, including pappalysin, IGFBP2, WNT 16, and DKK1. We determined that these proteins were upregulated in the conditioned medium of cabozantinib-treated osteoblasts (CBZ-CM) compared to control CM. Treatment of C4-2B4 or PC3-mm2 PCa cells with CBZ-CM increased the anchorage-independent growth and migration of these PCa cells compared to cells treated with control CM. These results suggest that the effect of cabozantinib on the tumor microenvironment may increase tumor cell survival and cause therapy resistance.

Survey on imaging management and handling of breast surgical specimens by radiologists.

PURPOSE: Imaging management of surgically removed breast biopsy specimens is a common, perhaps daily, procedure for radiologists and breast imagers. At many institutions throughout the United States, excised specimens are radiographically analyzed for verification of lesion removal. However, the exact process by which this is performed differs substantially among institutions, with wide variability of practice and lack of a uniform protocol. METHODS: An anonymous survey consisting of 13 multiple-choice questions was sent to 2,428 members of the Society of Breast Imaging. Results were subsequently categorized and tabulated in the Henry Ford Hospital Department of Biostatistics. RESULTS: There was a total of 354 responses to the survey, for a response rate of 14.6% (354 of 2,428). A clear majority of respondents (85%) reported the presence of department-wide standards for excisional (surgical) biopsy specimen processing. In 31% of cases, specimens were transferred two or more times between separate containers. This resulted in an increased concern for spills and leakage of biohazardous materials for 17% of the surveyed population. In addition, increased concern for sharps, or "needlestick" injuries, was also reported. CONCLUSIONS: There exist within many breast imaging departments standardized methods for processing breast biopsy specimens arriving from the operating room. However, the protocols and methods of analysis differ substantially from institution to institution. These survey results demonstrate a clear desire among radiologists for a more widespread, uniform standard, taking into account the accuracy of the procedure, cost, and the health and safety of staff members within the department.