High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Measuring Invisible Particle Masses Using a Single Short Decay Chain

We consider the mass measurement at hadron colliders for a decay chain of two steps, which ends with a missing particle. Such a topology appears as a subprocess of signal events of many new physics models which contain a dark matter candidate. From the two visible particles coming from the decay chain, only one invariant mass combination can be formed and hence it is na\"ively expected that the masses of the three invisible particles in the decay chain cannot be determined from a single end point of the invariant mass distribution. We show that the event distribution in the $\log(E_{1T}/E_{2T})$ vs. invariant mass-squared plane, where $E_{1T}$, $E_{2T}$ are the transverse energies of the two visible particles, contains the information of all three invisible particle masses and allows them to be extracted individually. The experimental smearing and combinatorial issues pose challenges to the mass measurements. However, in many cases the three invisible particle masses in the decay chain can be determined with reasonable accuracies.Comment: 45 pages, 32 figure

Indirect measurement of pinch and pull forces at the shaft of laparoscopic graspers

The grasping instruments used in minimally invasive surgery reduce the ability of the surgeon to feel the forces applied on the tissue, thereby complicating the handling of the tissue and increasing the risk of tissue damage. Force sensors implemented in the forceps of the instruments enable accurate measurements of applied forces, but also complicate the design of the instrument. Alternatively, indirect estimations of tissue interaction forces from measurements of the forces applied on the handle are prone to errors due to friction in the linkages. Further, the force transmission from handle to forceps exhibits large nonlinearities, so that extensive calibration procedures are needed. The kinematic analysis of the grasping mechanism and experimental results presented in this paper show that an intermediate solution, force measurements at the shaft and rod of the grasper, enables accurate measurements of the pinch and pull forces on tissue with only a limited number of calibration measurements. We further show that the force propagation from the shaft and rod to the forceps can be approximated by a linear two-dimensional function of the opening angle of the grasper and the force on the rod

The statistics of natural hand movements.

Humans constantly use their hands to interact with the environment and they engage spontaneously in a wide variety of manual activities during everyday life. In contrast, laboratory-based studies of hand function have used a limited range of predefined tasks. The natural movements made by the hand during everyday life have thus received little attention. Here, we developed a portable recording device that can be worn by subjects to track movements of their right hand as they go about their daily routine outside of a laboratory setting. We analyse the kinematic data using various statistical methods. Principal component analysis of the joint angular velocities showed that the first two components were highly conserved across subjects, explained 60% of the variance and were qualitatively similar to those reported in previous studies of reach-to-grasp movements. To examine the independence of the digits, we developed a measure based on the degree to which the movements of each digit could be linearly predicted from the movements of the other four digits. Our independence measure was highly correlated with results from previous studies of the hand, including the estimated size of the digit representations in primary motor cortex and other laboratory measures of digit individuation. Specifically, the thumb was found to be the most independent of the digits and the index finger was the most independent of the fingers. These results support and extend laboratory-based studies of the human hand

Geometry and BMS Lie algebras of spatially isotropic homogeneous spacetimes

Simply-connected homogeneous spacetimes for kinematical and aristotelian Lie algebras (with space isotropy) have recently been classified in all dimensions. In this paper, we continue the study of these "maximally symmetric" spacetimes by investigating their local geometry. For each such spacetime and relative to exponential coordinates, we calculate the (infinitesimal) action of the kinematical symmetries, paying particular attention to the action of the boosts, showing in almost all cases that they act with generic non-compact orbits. We also calculate the soldering form, the associated vielbein and any invariant aristotelian, galilean or carrollian structures. The (conformal) symmetries of the galilean and carrollian structures we determine are typically infinite-dimensional and reminiscent of BMS Lie algebras. We also determine the space of invariant affine connections on each homogeneous spacetime and work out their torsion and curvature.Comment: 62 pages, 3 figures, 4 tables, v2: Matches published version, mistake corrected in Section 4.1.3., 10.2, 10.3, other minor improvements, added reference

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

The mental status of 1090 heroin addicts at entry into treatment: should depression be considered a 'dual diagnosis'?

<p>Abstract</p> <p>Background</p> <p>Mental symptoms are common in heroin addiction and may arise from issues of addiction and withdrawal, raising doubts about the patients truly having co-morbid psychiatric diagnoses.</p> <p>Methods</p> <p>We studied the mental status of 1090 heroin addicts (831 males and 259 females aged between 16 and 51 years) at the beginning of treatment, and its relationship to relevant demographic and clinical data through the use of standardised instruments.</p> <p>Results</p> <p>A total of 506 (46.42%) heroin addicts showed depressive-anxious symptomatology, 421 (38.62%) had psychomotor excitement and 163 (14.95%) demonstrated a psychotic state. Patients with depressive-anxious symptomatology on the whole had a less severe addictive illness compared to those demonstrating excited and psychotic symptoms. The presence of depressive-anxious features was felt to not necessarily be indicative of the presence of a dual diagnosis.</p> <p>Conclusion</p> <p>The presence of depressive-anxious symptomatology in the clinical presentation in heroin addicts appears to be unrelated to 'dual diagnosis'.</p

New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range

We survey the phenomenological constraints on abelian gauge bosons having masses in the MeV to multi-GeV mass range (using precision electroweak measurements, neutrino-electron and neutrino-nucleon scattering, electron and muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic parity violation, low-energy neutron scattering and primordial nucleosynthesis). We compute their implications for the three parameters that in general describe the low-energy properties of such bosons: their mass and their two possible types of dimensionless couplings (direct couplings to ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue that gauge bosons with very small couplings to ordinary fermions in this mass range are natural in string compactifications and are likely to be generic in theories for which the gravity scale is systematically smaller than the Planck mass - such as in extra-dimensional models - because of the necessity to suppress proton decay. Furthermore, because its couplings are weak, in the low-energy theory relevant to experiments at and below TeV scales the charge gauged by the new boson can appear to be broken, both by classical effects and by anomalies. In particular, if the new gauge charge appears to be anomalous, anomaly cancellation does not also require the introduction of new light fermions in the low-energy theory. Furthermore, the charge can appear to be conserved in the low-energy theory, despite the corresponding gauge boson having a mass. Our results reduce to those of other authors in the special cases where there is no kinetic mixing or there is no direct coupling to ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which appears in JHE