From Cold to Hot: Changing Perceptions and Future Opportunities for Quantitative Systems Pharmacology Modeling in Cancer Immunotherapy.

Immuno-oncology (IO) is a fast-expanding field due to recent success using IO therapies in treating cancer. As IO therapies do not directly kill tumor cells but rather act upon the patients' own immune cells either systemically or in the tumor microenvironment, new and innovative approaches are required to inform IO therapy research and development. Quantitative systems pharmacology (QSP) modeling describes the biological mechanisms of disease and the mode of action of drugs with mathematical equations, which has significant potential to address the big challenges in the IO field, from identifying patient populations that respond to different therapies to guiding the selection, dosing, and scheduling of combination therapy.

Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations.

The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety.

Structure-Dependent Chiroptical Properties of Twisted Multilayered Silver Nanowire Assemblies.

The optical properties of chiral plasmonic metasurfaces depend strongly on their architecture, in particular the orientation and spacing between the individual building blocks assembled into large arrays. However, methods to obtain chiral metamaterials with fully tunable chiroptical properties in the UV, visible, and near-infrared range are scarce. Here, we show that the chiroptical properties of silver nanowires assembled in helical nanostructures by grazing incidence spraying and Layer-by-Layer assembly can be finely tuned over a broad wavelength range using simple design principles.

Nanoscale Bouligand Multilayers: Giant Circular Dichroism of Helical Assemblies of Plasmonic 1D Nano-Objects.

Chirality is found at all length scales in nature, and chiral metasurfaces have recently attracted attention due to their exceptional optical properties and their potential applications. Most of these metasurfaces are fabricated by top-down methods or bottom-up approaches that cannot be tuned in terms of structure and composition. By combining grazing incidence spraying of plasmonic nanowires and nanorods and Layer-by-Layer assembly, we show that nonchiral 1D nano-objects can be assembled into scalable chiral Bouligand nanostructures whose mesoscale anisotropy is controlled with simple macroscopic tools.

Tuning the Chiroptical Properties of Elongated Nano-objects Hierarchical Organization.

Chiral materials appear as excellent candidates to control and manipulate the polarization of light in optical devices. In nanophotonics, the self-assembly of colloidal plasmonic nanoparticles gives rise to strong resonances in the visible range, and when such organizations are chiral, a strong chiroplasmonic effect can be observed. In the present work, we describe the optical properties of chiral artificial nanophotonic materials, , which are hierarchically organized by grazing incidence spraying.

Dynamics of Bone Cell Interactions and Differential Responses to PTH and Antibody-Based Therapies.

We propose a mathematical model describing the dynamics of osteoblasts and osteoclasts in bone remodeling. The goal of this work is to develop an integrated modeling framework for bone remodeling and bone cell signaling dynamics that could be used to explore qualitatively combination treatments for osteoporosis in humans. The model has been calibrated using 57 checks from the literature.

Analysis of the IJCNN 2011 UTL challenge.

We organized a challenge in "Unsupervised and Transfer Learning": the UTL challenge (http://clopinet.com/ul). We made available large datasets from various application domains: handwriting recognition, image recognition, video processing, text processing, and ecology.

Free flaps for pressure sore coverage.

Management of pressure sores still represents a major challenge in plastic surgery practice due to recurrence. The surgeon may have to face multiple or recurrent pressure ulcerations without any local flap left. In this very limited indication, free flap surgery appears to be a useful adjunct in the surgical treatment.

Sequential recruitment and combinatorial assembling of multiprotein complexes in transcriptional activation.

In human cells, estrogenic signals induce cyclical association and dissociation of specific proteins with the DNA in order to activate transcription of estrogen-responsive genes. These oscillations can be modeled by assuming a large number of sequential reactions represented by linear kinetics with random kinetic rates. Application of the model to experimental data predicts robust binding sequences in which proteins associate with the DNA at several different phases of the oscillation.

Modeling the interactions between osteoblast and osteoclast activities in bone remodeling.

We propose a mathematical model explaining the interactions between osteoblasts and osteoclasts, two cell types specialized in the maintenance of the bone integrity. Bone is a dynamic, living tissue whose structure and shape continuously evolves during life. It has the ability to change architecture by removal of old bone and replacement with newly formed bone in a localized process called remodeling.

New approach to vascular injection in fresh cadaver dissection.

Vascular injection techniques for anatomic studies are often complementary. Use of colored gelatinous mixtures with methylene blue provides precious data about descriptive anatomy by the contrast that it produces in the tissues. The introduction of radiopaque medium, such as lead oxide, into the gelatinous mixture can be used as a complement by means of x-ray examination, in order to facilitate and to reduce the time of investigation.

Spatial effects in modeling pharmacokinetics of rapid action drugs.

We develop a model to describe the time course of plasma concentration of neuromuscular blocking agents used as anesthetics during surgery. This model, which overcomes the limitations of the classical compartment models routinely used in pharmacokinetics, incorporates spatial effects due to heterogeneity in the circulation: it takes the form of a dispersion equation on a circular domain, with a time-dependent leakage term. This term is fitted to the functional form desired once first-stage transients have died out.