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"Kessler, David"
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Minimal frustration underlies the usefulness of incomplete regulatory network models in biology
Regulatory networks as large and complex as those implicated in cell-fate choice are expected to exhibit intricate, very high-dimensional dynamics. Cell-fate choice, however, is a macroscopically simple process. Additionally, regulatory network models are almost always incomplete and/or inexact, and do not incorporate all the regulators and interactions that may be involved in cell-fate regulation. In spite of these issues, regulatory network models have proven to be incredibly effective tools for understanding cell-fate choice across contexts and for making useful predictions. Here, we show that minimal frustration—a feature of biological networks across contexts but not of random networks—can compel simple, low-dimensional steady-state behavior even in large and complex networks. Moreover, the steady-state behavior of minimally frustrated networks can be recapitulated by simpler networks such as those lacking many of the nodes and edges and those that treat multiple regulators as one. The present study provides a theoretical explanation for the success of network models in biology and for the challenges in network inference.
Journal Article
A Tale of Three Approaches: Dynamical Phase Transitions for Weakly Bound Brownian Particles
We investigate a system of Brownian particles weakly bound by attractive parity-symmetric potentials that grow at large distances as V(x)∼|x|α, with 0<α<1. The probability density function P(x, t) at long times reaches the Boltzmann–Gibbs equilibrium state, with all moments finite. However, the system’s relaxation is not exponential, as is usual for a confining system with a well-defined equilibrium, but instead follows a stretched exponential e-consttν with exponent ν=α/(2+α), as we announced recently in a short letter. In turn, the stretched exponential relaxation is related to large-deviation theory, which is studied from three perspectives. First, we propose a straightforward and general scaling rate-function solution for P(x, t). This rate function displays anomalous time scaling and a dynamical phase transition. Second, through the eigenfunctions of the Fokker–Planck operator, we obtain, using the WKB method, more complete solutions that reproduce the rate function approach and provide important pre-exponential corrections. Finally, we show how the alternative path-integral formalism allows us to recover the same results, with the above rate function being the solution of the classical Hamilton–Jacobi equation describing the most probable path. Properties such as parity, the role of initial conditions, and the dynamical phase transition are thoroughly studied in all three approaches.
Journal Article
Finding meaning : the sixth stage of grief
\"In this groundbreaking new work, David Kessler-an expert on grief and the coauthor with Elisabeth Kèubler-Ross of the iconic On Grief and Grieving-journeys beyond the classic five stages to discover a sixth stage: meaning\"-- Provided by publisher.
Book
Flexible ultrasound transceiver array for non-invasive surface-conformable imaging enabled by geometric phase correction
Ultrasound imaging provides the means for non-invasive real-time diagnostics of the internal structure of soft tissue in living organisms. However, the majority of commercially available ultrasonic transducers have rigid interfaces which cannot conform to highly-curved surfaces. These geometric limitations can introduce a signal-quenching air gap for certain topographies, rendering accurate imaging difficult or impractical. Here, we demonstrate a 256-element flexible two-dimensional (2D) ultrasound piezoelectric transducer array with geometric phase correction. We show surface-conformable real-time B-mode imaging, down to an extreme radius of curvature of 1.5 cm, while maintaining desirable performance metrics such as high signal-to-noise ratio (SNR) and minimal elemental cross-talk at all stages of bending. We benchmark the array capabilities by resolving reflectors buried at known locations in a medical-grade tissue phantom, and demonstrate how phase correction can improve image reconstruction on curved surfaces. With the current array design, we achieve an axial resolution of ≈ 2 mm at clinically-relevant depths in tissue, while operating the array at 1.4 MHz with a bandwidth of ≈ 41%. We use our prototype to image the surface of the human humerus at different positions along the arm, demonstrating proof-of-concept applicability for real-time diagnostics using phase-corrected flexible ultrasound probes.
Journal Article
تستطيع شفاء قلبك
يناقش هذا الكتاب الرائع المشاعر التي تحدث عندما تتركك العلاقة محطمة القلوب، أو ينتهي الزواج بالطلاق، أو يموت أحد أفراد أسرتك. سيعزز أيضا الوعي والرحمة، مما يوفر لك الشجاعة لمواجهة العديد من أنواع الخسائر والتحديات الأخرى، مثل قول وداعا لحيوان أليف محبوب، أو فقدان وظيفتك، أو التعامل مع مرض أو مرض يهدد الحياة، وأكثر بكثير. مع مزيج مثالي من تعاليم لويز والتأكيدات على النمو والتحول الشخصي وسنوات ديفيد العديدة من العمل مع أولئك الذين يعانون من الحزن، فإن هذا الكتاب التمكيني سيلهم طريقة جديدة غير عادية في التفكير، وتجلب الأمل ورؤى جديدة في حياتك وحتى في حياتك الحالية والعلاقات المستقبلية. لن تتعلم فقط كيفية المساعدة في شفاء حزنك، ولكن ستكتشف أيضا أنه، نعم، يمكنك شفاء قلبك.
The process and delivery of CBT for depression in adults: a systematic review and network meta-analysis
Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of −1.11 (95% credible interval −1.62 to −0.60) for face-to-face CBT, −1.06 (−2.05 to −0.08) for hybrid CBT, and −0.59 (−1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.
Journal Article
Vincent van Gogh : his life in art
\"Featuring about 50 works by Vincent van Gogh, from his early drawings to his later iconic paintings, this catalogue traces the artist's life, the development of his art, and his significant legacy\"-- Provided by publisher.
Book
FDA Regulation of Stem-Cell–Based Therapies
The authors review existing regulations regarding cell and tissue products and discuss how they expect the Food and Drug Administration to apply these regulations to scientists' efforts to develop and test stem-cell–based therapies.
The authors review existing regulations regarding cell and tissue products and discuss how they expect the FDA to apply these regulations to scientists' efforts to develop and test stem-cell–based therapies. Figure courtesy of Drs. Susan Fisher, Ana Krtolica, and Olga Genbacev, University of California, San Francisco.
In the interest of public safety, the Food and Drug Administration (FDA) has jurisdiction over the production and marketing of any stem-cell–based therapy involving the transplantation of human cells into patients. The FDA's recently promulgated regulations regarding human cells, tissues, and cellular and tissue-based products
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provide an appropriate regulatory structure for the wide range of stem-cell–based products that may be developed to replace or repair damaged tissue.
Basic and clinical scientists, as well as scientists working in the biotechnology and pharmaceutical industries, need an increased awareness of the questions that must be answered before a stem-cell–based product can be used . . .
Journal Article