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This conversation was held on June 17, 2020, and the resulting transcript reflects the events that were current as of the time of the original discussion. Changes to policies, events, and data may have changed between the time of the discussion and its publication.

Two leading physicians' prescription for solving our health care problems: organizing the fragmented system that delivers care.

The serine/threonine kinase RIPK1 is recruited to TNFR1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. A RIPK1 deficiency results in perinatal lethality, impaired NF kappa B and MAPK signaling, and sensitivity to TNF-induced apoptosis. Chemical inhibitor and in vitro-reconstitution studies suggested that RIPK1 displays distinct kinase activity-dependent and -independent functions. To determine the contribution of RIPK1 kinase to inflammation in vivo, we generated knock-in mice endogenously expressing catalytically inactive RIPK1 D138N. Unlike Ripk1(-/-) mice, which die shortly after birth, Ripk1(D138N/D138N) mice are viable. Cells expressing RIPK1 D138N are resistant to TNF- and polyinosinic-polycytidylic acid-induced necroptosis in vitro, and Ripk1(D138N/D138N) mice are protected from TNF-induced shock in vivo. Moreover, Ripk1(D138N/D138N) mice fail to control vaccinia virus replication in vivo. This study provides genetic evidence that the kinase activity of RIPK1 is not required for survival but is essential for TNF-, TRIF-, and viral-initiated necroptosis.

Two leading physicians' prescription for solving our health care problems: organizing the fragmented system that delivers care.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1990., Includes bibliographical references (leaves 134-143)., Thomas H. Lee., Sc.D.

ObjectiveTo determine whether preoperative characteristics influence quality of life outcomes 1, 6, and 12 months after joint replacement surgery.MethodsPatients (n = 222) with osteoarthritis undergoing primary joint replacement surgery at a university hospital between November 1990 and March 1993 were prospectively studied. Bodily pain and physical function were assessed preoperatively and at the 3 postoperative time points using the Medical Outcomes Study 36 Item Short Form Health Survey.ResultsBodily pain and physical function improved after joint replacement. At 1 month after surgery, despite improvements in bodily pain, physical function deteriorated. Preoperative bodily pain and physical function, demographic characteristics, and social support were significant correlates of improvement in bodily pain and physical function.ConclusionsPatients experienced dramatic improvements in bodily pain and physical function after joint replacement. However, decline in physical function at 1 month implies significant need for prolonged informal or formal patient assistance with basic physical function after surgery. Greater preoperative social support was associated with improved bodily pain and physical function outcomes.

The norm of sovereign equality in international law is so resolutely canonical that its precise meaning, origins, and justifications are rarely examined. Whatever the general merits of the norm, its retention seems fairly open to question when one sovereign state appears supremely unequal among 191 states in terms of military power.

Cover title., Includes bibliographical references (p. 6)., Stefane Bressan & Thomas Lee.

Linear time-invariant (LTI) phase noise theories provide important qualitative design insights but are limited in their quantitative predictive power. Part of the difficulty is that device noise undergoes multiple frequency translations to become oscillator phase noise. A quantitative understanding of this process requires abandoning the principle of time invariance assumed in most older theories of phase noise. Fortunately, the noise-to-phase transfer function of oscillators is still linear, despite the existence of the nonlinearities necessary for amplitude stabilization. In addition to providing a quantitative reconciliation between theory and measurement, the time-varying phase noise model presented in this tutorial identifies the importance of symmetry in suppressing the upconversion of 1/f noise into close-in phase noise, and provides an explicit appreciation of cyclostationary effects and AM-PM conversion. These insights allow a reinterpretation of why the Colpitts oscillator exhibits good performance, and suggest new oscillator topologies. Tuned LC and ring oscillator circuit examples are presented to reinforce the theoretical considerations developed. Simulation issues and the accommodation of amplitude noise are considered in appendixes.

This paper presents an ultra-low resistance, high wiring density, through-wafer via (TWV) technology that is compatible with standard silicon wafer processing. Vias as small as 30 µm by 30 µm are fabricated through a 525 µm thick wafer. This results in an aspect ratio for the via that is greater than 17:1. Furthermore, the dc resistance of a single via is less than 50 mΩ. Key fabrication steps, including the silicon dry etch, copper metallization, and photoresist electroplating, are described in detail. As a demonstration of the potential applications of the TWV technology, a novel three dimensional inductor is designed and fabricated. For a 0.9-nH inductor, a quality factor of 18.5 is measured at 800 MHz.

An analysis of phase noise in differential cross-coupled inductance-capacitance (LC) oscillators is presented. The effect of tail current and tank power dissipation on the voltage amplitude is shown. Various noise sources in the complementary cross-coupled pair are identified, and their effect on phase noise is analyzed. The predictions are in good agreement with measurements over a large range of tail currents and supply voltages. A 1.8 GHz LC oscillator with a phase noise of -121 dBc/Hz at 600 kHz is demonstrated, dissipating 6 mW of power using on-chip spiral inductors.

A companion analysis of clock jitter and phase noise of single-ended and differential ring oscillators is presented. The impulse sensitivity functions are used to derive expressions for the jitter and phase noise of ring oscillators. The effect of the number of stages, power dissipation, frequency of oscillation, and short-channel effects on the jitter and phase noise of ring oscillators is analyzed. Jitter and phase noise due to substrate and supply noise is discussed, and the effect of symmetry on the upconversion of 1/f noise is demonstrated. Several new design insights are given for low jitter/phase-noise design. Good agreement between theory and measurements is observed.

We present a method for optimizing and automating component and transistor sizing for CMOS LC oscillators. We observe that the performance measures can be formulated as posynomial functions of the design variables. As a result, the LC oscillator design problems can be posed as a geometric program, a special type of optimization problem for which very efficient global optimization methods have recently been developed. The synthesis method is therefore fast, and determines the globally optimal design; in particular the final solution is completely independent of the starting point (which can even be infeasible), and infeasible specifications are unambiguously detected. We can rapidly compute globally optimal trade-off curves between competing objectives such as phase noise and power.

CMOS RF ICs continue their transition from academic curiosities to practical devices. Recent milestones at the device- and building block-level include: Noise figures for single-ended LNAs of ~ldB in the low-GHz range; fully integrated oscillators with phase noise compliant with GSM specifications at under 10mW power con-sumption; 5GHz injection-locked frequency dividers with sub-mW power consumption and large (-30%) tun-ing range; MOSFET ring mixers with over 10dBm IIP3 and "zero" power consumption; shielded spiral and heli-cal inductors with improved Q; accumulation-mode MOS varactors with Q-frequency products in excess of 100-200GHz and tuning ratios approaching 2:1; fixed lateral flux capacitors with still higher Q-f products; coplanar transmission lines with <0.3dB/mm attenuation at 50GHz; microwave-compatible ESD structures; and constant-gm biasing for process independence. These advances have combined to enable a single-chip GPS receiver in 0.5um to exhibit 2.8dB overall NF, 57dB SFDR at 115mW, and a 5GHz HIPERLAN receiver to exhibit 5dB NF at <45mW using a 0.25um technology. Scaling forces that are already firmly in place will con-tinue to drive still greater improvements in performance.

We present a scalable analytical model for on-chip transformers that is suitable for design optimization and circuit simulation. We also provide simple and accurate expressions for evaluating the self inductance and the mutual coupling coefficient (k). The model agrees very well with measurements for a variety of transformer configurations.

This paper presents a novel RF IC varactor implemented in standard CMOS process. This device has shown a remarkable tuning range of 150%, sensitivity of 300%/V, and quality factor of 23 at 1 GHz. A physical model of the varactor is presented and confirmed with measured data. Using the model derived, optimization has shown that a Q as high as 200 can be achieved.

A general model is introduced which is capable of making accurate, quantitative predictions about the phase noise of different types of electrical oscillators by acknowledging the true periodically time-varying nature of all oscillators. This new approach also elucidates several previously unknown design criteria for reducing close-in phase noise by identifying the mechanisms by which intrinsic device noise and external noise sources contribute to the total phase noise. In particular, it explains the details of how 1/f noise in a device upconverts into close-in phase noise and identifies methods to suppress this upconversion. The theory also naturally accommodates cyclostationary noise sources, leading to additional important design insights. The model reduces to previously available phase noise models as special cases. Excellent agreement among theory, simulations, and measurements is observed.

An analysis of phase noise in differential cross-coupled tuned tank voltage controlled oscillators is presented. The effect of active device noise sources as well as the noise due to the passive elements are taken into account. The predictions are in good agreement with the measurements for different tail currents and supply voltages. The effect of the complementary cross-coupled pair is analyzed and verified experimentally. A 1.8 GHz LC oscillator with a phase noise of -121 dBc/Hz at 600 kHz is demonstrated, dissipating 6 mW of power using spiral inductors.

An analysis of the phase noise in differential and single-ended ring oscillators using a time-variant model is presented. An expression for the RMS value of the impulse sensitivity function (ISF) is derived. A closed-form equation for phase noise of ring oscillators is calculated and a lower limit on the phase noise of ring oscillators is shown. Phase noise measurements of oscillators running up to 5.5 GHz are in good agreement with the theory.

This paper presents a physical model for planar spiral inductors on silicon. The model has been confirmed with measured and published data of inductors having different geometric and process parameters. This model is scalable with inductor geometry, allowing designers to predict and optimize the quality factor.