The effects of osmotic stress on the structure and function of the cell nucleus.

Osmotic stress is a potent regulator of the normal function of cells that are exposed to osmotically active environments under physiologic or pathologic conditions. The ability of cells to alter gene expression and metabolic activity in response to changes in the osmotic environment provides an additional regulatory mechanism for a diverse array of tissues and organs in the human body. In addition to the activation of various osmotically- or volume-activated ion channels, osmotic stress may also act on the genome via a direct biophysical pathway. Changes in extracellular osmolality alter cell volume, and therefore, the concentration of intracellular macromolecules. In turn, intracellular macromolecule concentration is a key physical parameter affecting the spatial organization and pressurization of the nucleus. Hyper-osmotic stress shrinks the nucleus and causes it to assume a convoluted shape, whereas hypo-osmotic stress swells the nucleus to a size that is limited by stretch of the nuclear lamina and induces a smooth, round shape of the nucleus. These behaviors are consistent with a model of the nucleus as a charged core/shell structure pressurized by uneven partition of macromolecules between the nucleoplasm and the cytoplasm. These osmotically-induced alterations in the internal structure and arrangement of chromatin, as well as potential changes in the nuclear membrane and pores are hypothesized to influence gene transcription and/or nucleocytoplasmic transport. A further understanding of the biophysical and biochemical mechanisms involved in these processes would have important ramifications for a range of fields including differentiation, migration, mechanotransduction, DNA repair, and tumorigenesis.

Cost Heterogeneity and the Potential Savings from Market-Based Policies

Policy makers and analysts are often faced with situations where it is unclear whether market-based instruments hold real promise of reducing costs, relative to conventional uniform standards. We develop analytic expressions that can be employed with modest amounts of information to estimate the potential cost savings associated with market-based policies, with an application to the environmental policy realm. These simple formulae can identify instruments that merit more detailed investigation. We illustrate the use of these results with an application to nitrogen oxides control by electric utilities in the United States.

Evaluation of the Does Reduction Potential Using a Breast Positioning Technique for Organ-based Tube Current Modulated CT Examinations

Purpose: The purpose of this work was to investigate the breast dose saving potential of a breast positioning technique (BP) for thoracic CT examinations with organ-based tube current modulation (OTCM).

Methods: The study included 13 female patient models (XCAT, age range: 27-65 y.o., weight range: 52 to 105.8 kg). Each model was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were further deformed, emulating a BP that would constrain the breasts within 120° anterior tube current (mA) reduction zone. The tube current value of the CT examination was modeled using an attenuation-based program, which reduces the radiation dose to 20% in the anterior region with a corresponding increase to the posterior region. A validated Monte Carlo program was used to estimate organ doses with a typical clinical system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDIvol were compared between attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCMBP).

Results: On average, compared to ATCM, OTCM reduced the breast dose by 19.3±4.5%, whereas OTCMBP reduced breast dose by 36.6±6.9% (an additional 21.3±7.3%). The dose saving of OTCMBP was more significant for larger breasts (on average 32, 38, and 44% reduction for 0.5, 1.5, and 2.5 kg breasts, respectively). Compared to ATCM, OTCMBP also reduced thymus and heart dose by 12.1 ± 6.3% and 13.1 ± 5.4%, respectively.

Conclusions: In thoracic CT examinations, OTCM with a breast positioning technique can markedly reduce unnecessary exposure to the radiosensitive organs in the anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts.