Precision oncology for patients with advanced cancer: the challenges of malignant snowflakes.

Precision oncology implies customizing treatment to the unique molecular and biologic characteristics of each individual and their cancer. Its implementation is being facilitated by remarkable technological advances in genomic sequencing, as well as the increasing availability of targeted and immunotherapeutic drugs. Yet, next generation sequencing may be a disruptive technology in that its results suggest that classic paradigms for clinical research and practice are a poor fit with the complex reality encountered in metastatic malignancies. Indeed, it is evident that advanced tumors have heterogeneous molecular landscapes that mostly differ between patients. Traditional modes of clinical research/practice are drug centered, with a strategy of finding commonalities between patients so that they can be grouped together and treated similarly. However, if each patient with metastatic cancer has a unique molecular portfolio, a new patient-centered, N-of-one approach that utilizes individually tailored treatment is needed

Electromagnetic atmosphere-plasma coupling: the global atmospheric electric circuit

A description is given of the global atmospheric electric circuit operating between the Earth’s surface and the ionosphere. Attention is drawn to the huge range of horizontal and vertical spatial scales, ranging from 10−9 m to 1012 m, concerned with the many important processes at work. A similarly enormous range of time scales is involved from 10−6 s to 109 s, in the physical effects and different phenomena that need to be considered. The current flowing in the global circuit is generated by disturbed weather such as thunderstorms and electrified rain/shower clouds, mostly occurring over the Earth’s land surface. The profile of electrical conductivity up through the atmosphere, determined mainly by galactic cosmic ray ionization, is a crucial parameter of the circuit. Model simulation results on the variation of the ionospheric potential, ∼250 kV positive with respect to the Earth’s potential, following lightning discharges and sprites are summarized. Experimental results comparing global circuit variations with the neutron rate recorded at Climax, Colorado, are then discussed. Within the return (load) part of the circuit in the fair weather regions remote from the generators, charge layers exist on the upper and lower edges of extensive layer clouds; new experimental evidence for these charge layers is also reviewed. Finally, some directions for future research in the subject are suggested

Analysis of hypersonic pressure and heat transfer tests on a flat plate with a flap and a delta wing with body, elevons, fins, and rudders Final report

Hypersonic boundary layer separation and flow field interference analysis during Dyna-Soar space glider testin

The optical counterpart of SAX J1808.4-3658, the transient bursting millisecond X-ray pulsar

A set of CCD images have been obtained during the decline of the X-ray transient SAX J1808.4-3658 during April-June 1998. The optical counterpart has been confirmed by several pieces of evidence. The optical flux shows a modulation on several nights which is consistent with the established X-ray binary orbit period of 2 hours. This optical variability is roughly in antiphase with the weak X-ray modulation. The source mean magnitude of V=16.7 on April 18 declined rapidly after April 22. From May 2 onwards the magnitude was more constant at around V=18.45 but by June 27 was below our sensitivity limit. The optical decline precedes the rapid second phase of the X-ray decrease by 3 +/- 1 days. The source has been identified on a 1974 UK Schmidt plate at an estimated magnitude of ~20. The nature of the optical companion is discussed.Comment: 5 pages, 3 figures; published in MNRAS, March 15th 199

Implementation of structural response sensitivity calculations in a large-scale finite-element analysis system

The implementation includes a generalized method for specifying element cross-sectional dimensions as design variables that can be used in analytically calculating derivatives of output quantities from static stress, vibration, and buckling analyses for both membrane and bending elements. Limited sample results for static displacements and stresses are presented to indicate the advantages of analytically calclating response derivatives compared to finite difference methods. Continuing developments to implement these procedures into an enhanced version of the system are also discussed