Reconnecting the Sciences

During the last three years at the Illinois Mathematics and Science Academy, we have been working on a partial reconstruction of Whitehead\u27s one subject matter, a course reconnecting biology, chemistry, earth and space sciences, and physics into an Integrated Science program

Two-step polarization reversal in biased ferroelectrics

Polarization reversal in polycrystalline ferroelectrics is shown to occur via two distinct and sequential domain reorientation steps. This reorientation sequence, which cannot be readily discriminated in the overall sample polarization, is made apparent using time-resolved high-energy x-ray diffraction. Upon application of electric fields opposite to the initial poling direction, two unique and significantly different time constants are observed. The first (faster time constant) is shown to be derived by the release of a residual stress due to initial electrical biasing and the second (slower time constant) due to the redevelopment of residual stress during further domain wall motion. A modified domain reorientation model is given that accurately describes the domain volume fraction evolution during the reversal process.open1

The 2-loop MSSM finite temperature effective potential with stop condensation

We calculate the finite temperature 2-loop effective potential in the MSSM with stop condensation, using a 3-dimensional effective theory. We find that in a part of the parameter space, a two-stage electroweak phase transition appears possible. The first stage would be the formation of a stop condensate, and the second stage is the transition to the standard electroweak minimum. The two-stage transition could significantly relax the baryon erasure bounds, but the parameter space allowing it (m_H \lsim 100 GeV, m_tR \sim 155-160 GeV) is not very large. We estimate the reliability of our results using renormalization scale and gauge dependence. Finally we discuss some real-time aspects relevant for the viability of the two-stage scenario.Comment: 30 pages, 7 figure

Increased T Cell Proliferative Responses to Islet Antigens Identify Clinical Responders to Anti-CD20 Monoclonal Antibody (Rituximab) Therapy in Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte antibody can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease- associated target antigens, and C-peptide levels of participants that did (responders) or did not (non-responders) show signs of β-cell preservation one year after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after 4 weekly doses of mAb. T cell proliferative responses to diabetes –associated antigens were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 months (58%), the proliferative responses to diabetes associated total (p=0.032), islet-specific (p=0.048), and neuronal auto-antigens (p=0.005) increased over the 12 month observation period. This relationship was not seen in placebo treated patients. We conclude that in patients with T1DM, anti-B cell mAb causes increased proliferative responses to diabetes antigens and attenuated β cell loss. The way in which these responses affect the disease course remains unknown

Time-lapse microscopic observation of non-dividing cells in cultured human osteosarcoma MG-63 cell line

<p>Cancer stem cells resemble normal tissue-specific stem cells in many aspects, such as self-renewal and plasticity. Like their non-malignant counterparts, cancer stem cells are suggested to exhibit a relative quiescence. The established cancer cell lines reportedly harbor slow-proliferating cells that are positive for some cancer stem cells markers. However, the fate of these cells and their progeny remains unknown. We used time-lapse microscopy and the contrast-based segmentation algorithm to identify and monitor actively dividing and non-dividing cells in human osteosarcoma MG-63 cell line. Within the monitored field of view the non-dividing cells were represented by three cells that never divided, and one cell that attempted to divide, but failed cytokinesis, and later, after significantly prolonged division, produced the progeny with enlarged segmented nuclei, thus pointing to a possible mitotic catastrophe. Together, these cells initially constituted about 6.2% of the total number of seeded cells, yet only 0.02% of all cells at the end of the observation period when cells became confluent. Non-dividing cells were characterized by rounded shape, dark nuclei, random cytoplasmic streaming and subtle oscillatory movement, however, they did not migrate and rarely formed cell-cell contacts as compared to actively dividing cells. Our data indicate that the observed non-dividing MG-63 cells do not have a growth advantage over other cells and, therefore, they do not contribute to the cancer stem cells pool.</p

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in Type 1 diabetes

Type 1 diabetes mellitus (T1DM) is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte antibody can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease- associated target antigens, and C-peptide levels of participants that did (responders) or did not (non-responders) show signs of β-cell preservation one year after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after 4 weekly doses of mAb. T cell proliferative responses to diabetes –associated antigens were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 months (58%), the proliferative responses to diabetes associated total (p=0.032), islet-specific (p=0.048), and neuronal auto-antigens (p=0.005) increased over the 12 month observation period. This relationship was not seen in placebo treated patients. We conclude that in patients with T1DM, anti-B cell mAb causes increased proliferative responses to diabetes antigens and attenuated β cell loss. The way in which these responses affect the disease course remains unknown

Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology.

A significant obstacle to the study of human cancer biology and the testing of human specific immunotherapeutics is the paucity of translational models that recapitulate both the growth of human tumors and the functionality of human immune systems. Humanized mice engrafted with human hematopoietic stem cells (HSC) and patient-derived xenografts (PDX) enable preclinical investigation of the interactions between the human immune system and human cancer. We use immunodeficient non-obese diabetic (NOD, scid, gamma) NSG™ or NSG™-SGM3 mice as hosts for establishment of human immunity following HSC injection and for engraftment of human tumors. Here we describe a refined protocol for the subcutaneous implant of solid PDX tumors into humanized mice. Protocols to recover infiltrating immune cells from growing tumors and to evaluate the immune cell subsets by flow cytometry are also described