Integrating automation and LC/MS for drug discovery bioanalysis

A novel, integrated approach for automated sample handling in drug discovery bioanalysis is described. The process includes aspects of animal study design, biological sample collection, sample processing and high-throughput APILC/MS operating in under multiple reaction monitoring (MRM). A semi-automated 96-well liquid—liquid extraction technique for biological fluid sample preparation was developed and used in conjunction with the integrated sample-handling approach. One plate of samples could be prepared within 1.5 h compared with 4 h for a manual approach, and the resulting 96-well plate of extracts was directly compatible with the LC/MS. Feasibility studies for the development of the process included sample collection map generation and information management, sample collection formatting, evaluation of alternative dilution schemes for high-concentration samples, choice of biological fluid, and evaluating the capabilities of the two liquid-handling workstations. Numerous comparisons between the new approach and conventional sample-handling approaches gave equivalent drug-quantitation results for several example compounds. This new sampling process has approximately doubled the efficiency (as measured by studies assayed per month) of drug discovery bioanalysis in our laboratory. The approach was also used in conjunction with time-of-flight mass spectrometry instrumentation (LC/TOF/MS) to quantify and characterize the disposition of simultaneously dosed example drug compounds in the rat. Likely strategies for future automated sample preparation workstations are described

Optimized Compilation of Aggregated Instructions for Realistic Quantum Computers

Recent developments in engineering and algorithms have made real-world applications in quantum computing possible in the near future. Existing quantum programming languages and compilers use a quantum assembly language composed of 1- and 2-qubit (quantum bit) gates. Quantum compiler frameworks translate this quantum assembly to electric signals (called control pulses) that implement the specified computation on specific physical devices. However, there is a mismatch between the operations defined by the 1- and 2-qubit logical ISA and their underlying physical implementation, so the current practice of directly translating logical instructions into control pulses results in inefficient, high-latency programs. To address this inefficiency, we propose a universal quantum compilation methodology that aggregates multiple logical operations into larger units that manipulate up to 10 qubits at a time. Our methodology then optimizes these aggregates by (1) finding commutative intermediate operations that result in more efficient schedules and (2) creating custom control pulses optimized for the aggregate (instead of individual 1- and 2-qubit operations). Compared to the standard gate-based compilation, the proposed approach realizes a deeper vertical integration of high-level quantum software and low-level, physical quantum hardware. We evaluate our approach on important near-term quantum applications on simulations of superconducting quantum architectures. Our proposed approach provides a mean speedup of $5\times$, with a maximum of $10\times$. Because latency directly affects the feasibility of quantum computation, our results not only improve performance but also have the potential to enable quantum computation sooner than otherwise possible.Comment: 13 pages, to apper in ASPLO

Beyond Sodium, Phosphate and Potassium: Potential Dietary Interventions in Kidney Disease

People with kidney disease are advised to restrict individual nutrients, such as sodium, potassium, and phosphate, in line with current best practice guidelines. However, there is limited evidence to support the efficacy of single nutrient strategies, and compliance remains a challenge for clinicians to overcome. Many factors contribute to poor compliance with dietary prescriptions, including conflicting priorities for single nutrient restriction, the arduous self-monitoring required, and the health-related knock-on effects resulting from targeting these nutrients in isolation. This paper reviews the evidence base for the overall pattern of eating as a potential tool to deliver a diet intervention in which all the nutrients and foods work cumulatively and synergistically to improve clinical outcomes. These interventions may assist in kidney disease management and overcome these innate challenges that single nutrient interventions possess. Healthy dietary patterns are typically plant-based and lower in sodium and animal proteins. These patterns may have numerous mechanistic benefits for cardiovascular health in kidney disease, most notably through the increase in fruit, vegetables, and plant-based protein, as well as improved gut health through the increase in dietary fiber. The evidence to date on optimal dietary patterns points toward use of a predominantly plant-based diet, and suggests its adoption may improve clinical outcomes in dialysis patients. However, clinical trials are needed to determine whether these diet interventions are feasible, safe, and effective in this patient population

Mastering the Master Field

The basic concepts of non-commutative probability theory are reviewed and applied to the large $N$ limit of matrix models. We argue that this is the appropriate framework for constructing the master field in terms of which large $N$ theories can be written. We explicitly construct the master field in a number of cases including QCD$_2$. There we both give an explicit construction of the master gauge field and construct master loop operators as well. Most important we extend these techniques to deal with the general matrix model, in which the matrices do not have independent distributions and are coupled. We can thus construct the master field for any matrix model, in a well defined Hilbert space, generated by a collection of creation and annihilation operators---one for each matrix variable---satisfying the Cuntz algebra. We also discuss the equations of motion obeyed by the master field.Comment: 46 pages plus 11 uuencoded eps figure

Ryegrass Seeding Rate Alters Plant Morphology and Size--Possible Implications for Pasture Persistence

Poor persistence of perennial ryegrass (Lolium perenne L.) is a major dairy industry issue in New Zealand and Australia. New ryegrass seed is often drilled at 18-30 kg/ha, although previous research indicated that pastures drilled at 10-12 kg/ha can be just as productive (Frame and Boyd 1986; Praat et al. 1996). High seeding rates increase competition between developing seedlings for light, water and nutrients, reduce plant size (Harris 1990) and potentially survival. The experiment reported here investigated the effect of plant density (created by differences in seeding rate) on plant morphology and survival. The hypothesis was that plants established from high seeding rates will be smaller and, therefore, less likely to survive the first summer; a period of substantial environmental stress (e.g., high temperatures, low soil moisture, insect attack)

Turbulence and transport suppression scaling with flow shear on the Large Plasma Device

Continuous control over azimuthal flow and shear in the edge of the Large Plasma Device (LAPD) [W. Gekelman et al., Rev. Sci. Instr. 62, 2875 (1991)] has been achieved using a biasable limiter. This flow control has allowed a careful study of the effect of flow shear on pressure-gradient-driven turbulence and particle transport in LAPD. The combination of externally controllable shear in a turbulent plasma along with the detailed spatial diagnostic capabilities on LAPD makes the experiment a useful testbed for validation of shear suppression models. Motivated by these models, power-law fits are made to the density and radial velocity fluctuation amplitudes, particle flux, density-potential crossphase, and radial correlation length. The data show a break in the trend of these quantities when the shearing rate ( γs=∂Vθ/∂r ) is comparable to the turbulent decorrelation rate ( 1/τac ). No one model captures the trends in the all turbulent quantities for all values of the shearing rate, but some models successfully match the trend in either the weak ( γsτac\u3c1 ) or strong ( γsτac\u3e1 ) shear limits

Optical signature of erythrocytes by light scattering in microfluidic flows

A camera-based light scattering approach coupled with a viscoelasticity-induced cell migration technique has been used to characterize the morphological properties of erythrocytes in microfluidic flows. We have obtained the light scattering profiles (LSPs) of individual living cells in microfluidic flows over a wide angular range and matched them with scattering simulations to characterize their morphological properties. The viscoelasticity-induced 3D cell alignment in microfluidic flows has been investigated by bright-field and holographic microscopy tracking, where the latter technique has been used to obtain precise cell alignment profiles in-flow. Such information allows variable cell probability control in microfluidic flows at very low viscoelastic polymer concentrations, obtaining cell measurements that are almost physiological. Our results confirm the possibility of precise, label-free analysis of individual living erythrocytes in microfluidic flows

Соматоформная вегетативная дисфункция у лиц молодого возраста в свете современньїх представлений об этиопатогенезе, диагностике и методах восстановительного лечения

Guiding the self-assembly of materials by controlling the shape of the individual particle constituents is a powerful approach to material design. We show that colloidal silica superballs crystallize into canted phases in the presence of depletants. Some of these phases are consistent with the so-called "Λ1" lattice that was recently predicted as the densest packing of superdisks. As the size of the depletant is reduced, however, we observe a transition to a square phase. The differences in these entropically stabilized phases result from an interplay between the size of the depletants and the fine structure of the superball shape. We find qualitative agreement of our experimental results both with a phase diagram computed on the basis of the volume accessible to the depletants and with simulations. By using a mixture of depletants, one of which is thermosensitive, we induce solid-to-solid phase transitions between square and canted structures. The use of depletant size to leverage fine features of the shape of particles in driving their self-assembly demonstrates a general and powerful mechanism for engineering novel materials