Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy II. Cellular dose enhancement within macroscopic tumor models.

Background: Gold NanoParticle (GNP) dose-enhanced radiation therapy (GNPT) requires consideration of physics across macro- to microscopic length scales, however, this presents computational challenges that have limited previous investigations.

Purpose: To develop and apply multiscale Monte Carlo (MC) simulations to assess variations in nucleus and cytoplasm dose enhancement factors (n,cDEFs) over tumor-scale volumes.

Methods: The intrinsic variation of n,cDEFs (due to fluctuations in local gold concentration and cell/nucleus size variation) are estimated via MC modeling of varied cellular GNP uptake and cell/nucleus sizes.

Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy I: Cellular dose enhancement in microscopic models.

Background: The introduction of Gold NanoParticles (GNPs) in radiotherapy treatments necessitates considerations such as GNP size, location, and quantity, as well as patient geometry and beam quality. Physics considerations span length scales across many orders of magnitude (nanometer-to-centimeter), presenting challenges that often limit the scope of dosimetric studies to either micro- or macroscopic scales.

Purpose: To investigate GNP dose-enhanced radiation Therapy (GNPT) through Monte Carlo (MC) simulations that bridge micro-to-macroscopic scales.

Update of the CLRP Monte Carlo TG-43 parameter database for high-energy brachytherapy sources.

Purpose: To update and extend version 2 of the Carleton Laboratory for Radiotherapy Physics (CLRP) TG-43 dosimetry database (CLRP_TG43v2) for high-energy (HE, ≥50 keV) brachytherapy sources (1 Yb, 23 Ir, 5 Cs, and 4 Co) using egs_brachy, an open-source EGSnrc application. A comprehensive dataset of TG-43 parameters is compiled, including detailed source descriptions, dose-rate constants, radial dose functions, 1D and 2D anisotropy functions, along-away dose-rate tables, Primary and Scatter Separated (PSS) dose tables, and mean photon energies escaping each source. The database also documents the source models which are freely distributed with egs_brachy.

Fast beta-emitter Monte Carlo simulations and full patient dose calculations of targeted radionuclide therapy: introducing egs_mird.

Background: Targeted radionuclide therapy (TRT) is a fast-growing field garnering much interest, with several clinical trials currently underway, that has a steady increase in development of treatment techniques. Unfortunately, within the field and many clinical trials, the dosimetry calculation techniques used remain relatively simple, often using a mix of S-value calculations and kernel convolutions.

Purpose: The common TRT calculation techniques, although very quick, can often ignore important aspects of patient anatomy and radionuclide distribution, as well as the interplay there-in.

First case of ocular dirofilariosis in Bulgaria caused by gravid female Dirofilaria repens.

Dirofilariosis caused by Dirofilaria (Nochtiella) repens is recorded sporadically among people in Europe, Asia and Africa. Still a worldwide controversy exist upon human parasite hosting. Herein, the first case of ocular dirofilariosis in Bulgaria caused by gravid female is presented.

Update of the CLRP TG-43 parameter database for low-energy brachytherapy sources.

Purpose: To update the Carleton Laboratory for Radiotherapy Physics (CLRP) TG-43 dosimetry database for low-energy (≤50 keV) photon-emitting low-dose rate (LDR) brachytherapy sources utilizing the open-source EGSnrc application egs_brachy rather than the BrachyDose application used previously for 27 LDR sources in the 2008 CLRP version (CLRPv1). CLRPv2 covers 40 sources ( Pd, I, and Cs). A comprehensive set of TG-43 parameters is calculated, including dose-rate constants, radial dose functions with functional fitting parameters, 1D and 2D anisotropy functions, along-away dose-rate tables, Primary-Scatter separation dose tables (for some sources), and mean photon energies at the surface of the sources.

Technical Note: Taking EGSnrc to new lows: Development of egs++ lattice geometry and testing with microscopic geometries.

Purpose: This work introduces a new lattice geometry library, egs_lattice, into the EGSnrc Monte Carlo code, which can be used for both modeling very large (previously unfeasible) quantities of geometries (e.g., cells or gold nanoparticles (GNPs)) and establishing recursive boundary conditions.

Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization.

Purpose: To introduce the heterogeneous multiscale (HetMS) model for Monte Carlo simulations of gold nanoparticle dose-enhanced radiation therapy (GNPT), a model characterized by its varying levels of detail on different length scales within a single phantom; to apply the HetMS model in two different scenarios relevant for GNPT and to compare computed results with others published.

Methods: The HetMS model is implemented using an extended version of the EGSnrc user-code egs_chamber; the extended code is tested and verified via comparisons with recently published data from independent GNP simulations. Two distinct scenarios for the HetMS model are then considered: (a) monoenergetic photon beams (20 keV to 1 MeV) incident on a cylinder (1 cm radius, 3 cm length); (b) isotropic point source (brachytherapy source spectra) at the center of a 2.

Discovery of Novel Liver-Stage Antimalarials through Quantum Similarity.

Without quantum theory any understanding of molecular interactions is incomplete. In principal, chemistry, and even biology, can be fully derived from non-relativistic quantum mechanics. In practice, conventional quantum chemical calculations are computationally too intensive and time consuming to be useful for drug discovery on more than a limited basis.

Discovery of potent, novel Nrf2 inducers via quantum modeling, virtual screening, and in vitro experimental validation.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is the master transcription factor of the antioxidant response element pathway, coordinating the induction of detoxifying and antioxidant enzymes. Nrf2 is normally sequestered in the cytoplasm by Kelch-like ECH-associating protein 1 (Keap1). To identify novel small molecules that will disturb Nrf2-Keap1 binding and promote activation of the Nrf2- antioxidant response element pathway, we generated a quantum model based on the structures of known Nrf2- antioxidant response element activators.

Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation.

Background: Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties.

Liquid flow residence time in a fibrous fixed bed reactor with recycle.

Waste removal efficiency of gas-liquid biofilter reactors for waste water treatment depends on its flow regime and residence time distribution (RTD) as key parameters of bio-reactor performance. The present study reports RTD regime in a fibrous fixed bed biofilm reactor related to a fluid velocity range appropriate for biofilm operation. The data from tracer experiments are correlated in terms of the one-parameter "tanks-in-series" model.