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Expansive soils increase their volume upon wetting, but under high vertical stresses may exhibit collapse, with the latter aspect being rather overlooked in foundation engineering. Oedometer swelling/collapse tests on expansive Pliocene marls of various calcium carbonate content and plasticity index sampled from Nicosia, Cyprus, indicate that, unlike the free swelling strain, the swelling pressure is rather insensitive to the initial degree of saturation. Consequently, significant collapse strains upon wetting are not unlikely to occur in practical situations. The paper discusses the implications of this behavior in the case of shallow foundations and proposes methods of analysis. Under certain conditions, foundation design based on settlement calculations that use as input the fully saturated soil properties may be unconservative and supported structures may be exposed to severe risk of damage. For the design of mat foundations, stepwise distributions of the equivalent modulus of subgrade reaction across the mat as a function of the average bearing pressure are proposed based on the results of coupled finite element simulations. These distributions allow prediction of the peak bending moments produced at the end of the wet and dry seasons due to ground swelling and shrinkage, respectively, for the climatic conditions of Cyprus.

Highly plastic clays are generally regarded as very impermeable materials. However, it is well known that desiccation cracks, as well as inherent fissuring, increase the in-situ apparent permeability inside the active zone. The paper presents long-term measurements of matric suction and moisture sensors installed under a mat foundation, on the shaft of bored piles, and at the free field in expansive marls in area of Nicosia, Cyprus. The data reveal the ease with which rainwater percolates in the ground due to the presence of shrinkage cracks, especially adjacent to foundation elements. Several episodes of full saturation conditions are recorded under the mat close to its perimeter during the course of a hydrological year after significant rainfall events, even during the dry season. Moreover, rapid migration of rainwater along the gap forming between the soil and pile shaft during the dry season can lead to brief full saturation incidents down to at least 1.5m depth. Back-analysis of field wetting experiments using the finite element method indicates that the equivalent in-situ saturated hydraulic conductivity of highly expansive marl near the ground surface is 3 to 4 orders of magnitude larger than the one measured on intact marl samples in the laboratory.

The city of Nicosia in the island of Cyprus is situated on a sedimentary basin, the surface layers of which are dominated by an expansive clayey soil called Nicosia marl. The high potential for volume change of this soil due to the seasonal changes of water content is the leading cause of foundation related damage to the buildings and infrastructure of the city. This paper presents preliminary results of a study focusing on the investigation of the Nicosia marl mechanical characteristics pertaining to moisture changes. Samples of Nicosia marl were collected from a borehole and a trial pit in the University of Cyprus campus. The pit which was subsequently used for installing an in-situ array of sensors monitoring suction and volumetric water content at depths inside the active zone. The Soil-Water Characteristic Curve (SWCC) was measured in the laboratory for the entire range of degree of saturation. The potential of swelling/collapse at various values of vertical stress was studied through a series of oedometer tests.

Drug development in oncology commonly exploits the tools of molecular biology to gain therapeutic benefit through reprograming of cellular responses. In immuno‐oncology (IO) the aim is to direct the patient's own immune system to fight cancer. After remarkable successes of antibodies targeting PD1/PD‐L1 and CTLA4 receptors in targeted patient populations, the focus of further development has shifted toward combination therapies. However, the current drug‐development approach of exploiting a vast number of possible combination targets and dosing regimens has proven to be challenging and is arguably inefficient. In particular, the unprecedented number of clinical trials testing different combinations may no longer be sustainable by the population of available patients. Further development in IO requires a step change in selection and validation of candidate therapies to decrease development attrition rate and limit the number of clinical trials. Quantitative systems pharmacology (QSP) proposes to tackle this challenge through mechanistic modeling and simulation. Compounds' pharmacokinetics, target binding, and mechanisms of action as well as existing knowledge on the underlying tumor and immune system biology are described by quantitative, dynamic models aiming to predict clinical results for novel combinations. Here, we review the current QSP approaches, the legacy of mathematical models available to quantitative clinical pharmacologists describing interaction between tumor and immune system, and the recent development of IO QSP platform models. We argue that QSP and virtual patients can be integrated as a new tool in existing IO drug development approaches to increase the efficiency and effectiveness of the search for novel combination therapies. [ABSTRACT FROM AUTHOR]