89 research outputs found
Transitions in genetic toggle switches driven by dynamic disorder in rate coefficients
In biochemical systems, intrinsic noise may drive the system switch from one stable state to another. We investigate how kinetic switching between stable states in a bistable network is influenced by dynamic disorder, i.e., fluctuations in the rate coefficients. Using the geometric minimum action method, we first investigate the optimal transition paths and the corresponding minimum actions based on a genetic toggle switch model in which reaction coefficients draw from a discrete probability distribution. For the continuous probability distribution of the rate coefficient, we then consider two models of dynamic disorder in which reaction coefficients undergo different stochastic processes with the same stationary distribution. In one, the kinetic parameters follow a discrete Markov process and in the other they follow continuous Langevin dynamics. We find that regulation of the parameters modulating the dynamic disorder, as has been demonstrated to occur through allosteric control in bistable networks in the immune system, can be crucial in shaping the statistics of optimal transition paths, transition probabilities, and the stationary probability distribution of the network.National Institutes of Health (U.S.) (Grant P01-AI09158)Singapore-MIT Alliance for Research and Technology (SMART
Chaos in a Two-Dimensional Ising Spin Glass
We study chaos in a two dimensional Ising spin glass by finite temperature
Monte Carlo simulations. We are able to detect chaos with respect to
temperature changes as well as chaos with respect to changing the bonds, and
find that the chaos exponents for these two cases are equal. Our value for the
exponent appears to be consistent with that obtained in studies at zero
temperature.Comment: 4 pages, LaTeX, 4 postscript figures included. The analysis of the
data is now done somewhat differently. The results are consistent with the
chaos exponent found at zero temperature. Additional papers of PY can be
obtained on-line at http://schubert.ucsc.edu/pete
Incidental and Non-Incidental Processing of Biological Motion: Orientation, Attention and Life Detection
Abstract Based on the unique traits of biological motion perception, the existence of a "life detector", a special sensitivity to perceiving motion patterns typical for animals, seems to be plausibl
Highlights from the Annual Meeting of the American Society of Clinical Oncology 2014 in Chicago - Expert Opinions Revisited
Update breast cancer 2020 part 5: moving therapies from advanced to early breast cancer patients
Systemic therapy of premenopausal patients with early stage hormone receptor-positive, HER2-negative breast cancer: controversies and standards in healthcare
Infant Botulism
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66984/2/10.1177_000992289303201105.pd
Update breast cancer 2021 part 5 – advanced breast cancer
Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials
Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019)
A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynakologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was Estimating the magnitude of clinical benefit. The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient
Update breast cancer 2021 part 4 – prevention and early stages
This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this yearʼ s most important study outcomes
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