T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.
Solid-state quantum computer architectures with qubits encoded using single atoms are now feasible given recent advances in the atomic doping of semiconductors. Here we present a charge qubit consisting of two dopant atoms in a semiconductor crystal, one of which is singly ionized. Surface electrodes control the qubit and a radio-frequency single-electron transistor provides fast readout. The calculated single gate times, of order 50 ps or less, are much shorter than the expected decoherence time. We propose universal one-and two-qubit gate operations for this system and discuss prospects for fabrication and scale up. DOI: 10.1103/PhysRevB.69.113301 PACS number͑s͒: 03.67.Lx, 73.21.Ϫb, 85.40.Ry In the search for an inherently scalable quantum computer ͑QC͒ technology solid-state systems are of great interest. One of the most advanced proposals is based on superconducting qubits, 1 where coherent control of qubits has been demonstrated and decoherence times measured.2 The Kane scheme, 3 in which qubits are defined by nuclear spin states of buried phosphorus dopants in a silicon crystal, has also attracted considerable attention due to its promise of very long ͑ms or longer͒ decoherence times below 1 K. Recent advances in single-dopant fabrication, 4 -6 together with the demonstration of fast single-electron transistor ͑SET͒ charge detection, 7,8 bring the Kane Si:P architecture closer to reality. These important results notwithstanding, the demonstration of single-spin readout remains a major challenge. Here we consider a Si:P dopant-based qubit in which the logical information is encoded on the charge degrees of freedom. This system, which is complementary to the Kane concept, is not dependent on single-spin readout and, given the present availability of fabrication 4 -6 and readout 7,8 technologies, can now be built. A two-qubit gate based on the charge qubit scheme we describe will enable an experimental determination to be made of the key sources of decoherence and error in a nanoscale silicon QC architecture. Such devices therefore provide an important and necessary pathway towards the longer term goal of real-spin Si:P devices.Semiconductor quantum-dot charge-based qubits were first considered in 1995 by Barenco et al.,9 where quantum information was encoded in excitation levels, and later by Fedichkin et al. 10 for position-based charge qubits in GaAs. Very recently, coherent oscillations have been observed 11 in a GaAs double quantum dot providing realization of a chargebased qubit with coherence times above 1 ns, accessible by existing fast pulse technology. In this paper we assess the potential of Si:P donor-based charge qubits by calculating the energetics and gate operation times for realistic device configurations and gate potentials and find that both one-and two-qubit operations times are well within the relevant decoherence times for the system.The buried donor charge qubit is shown in Fig. 1 for the case of P dopants in Si, although a number of other dopantsubstrate systems could also be consi...
In response to stimulation, B lymphocytes pursue a large number of distinct fates important for immune regulation. Whether each cell's fate is determined by external direction, internal stochastic processes, or directed asymmetric division is unknown. Measurement of times to isotype switch, to develop into a plasmablast, and to divide or to die for thousands of cells indicated that each fate is pursued autonomously and stochastically. As a consequence of competition between these processes, censorship of alternative outcomes predicts intricate correlations that are observed in the data. Stochastic competition can explain how the allocation of a proportion of B cells to each cell fate is achieved. The B cell may exemplify how other complex cell differentiation systems are controlled.
The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.
The Stark shift of the hyperfine coupling constant is investigated for a P donor in Si far below the ionization regime in the presence of interfaces using tight-binding and band minima basis approaches and compared to the recent precision measurements. In contrast with previous effective mass-based results, the quadratic Stark coefficient obtained from both theories agrees closely with the experiments. It is also shown that there is a significant linear Stark effect for an impurity near the interface, whereas, far from the interface, the quadratic Stark effect dominates. This work represents the most sensitive and precise comparison between theory and experiment for single donor spin control. Such precise control of single donor spin states is required particularly in quantum computing applications of single donor electronics, which forms the driving motivation of this work.
Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G 1 phase, and many mathematical models assume a constant time for traversing the S/G 2 /M phases. By direct observation of transgenic fluorescent fusion proteins that report the onset of S phase, we establish that dividing B and T lymphocytes spend a near-fixed proportion of total division time in S/G 2 /M phases, and this proportion is correlated between sibling cells. This result is inconsistent with models that assume independent times for consecutive phases. Instead, we propose a stretching model for dividing lymphocytes where all parts of the cell cycle are proportional to total division time. Data fitting based on a stretched cell cycle model can significantly improve estimates of cell cycle parameters drawn from DNA labeling data used to monitor immune cell dynamics.he kinetic relationship between phases of the cell cycle first came to attention with the advent of autoradiographic techniques for detecting DNA synthesis in the 1950s (1, 2). It was realized that such data could be used to resolve the dynamics of the proliferating population if combined with an appropriate cell cycle model. However, direct filming of times to divide revealed remarkable variation, even among cloned, presumed identical, cells (3-6), eliminating simple deterministic models as the basis for cell cycle control. Working toward developing a general model, Smith and Martin made the striking observation that plotting the proportion of undivided cells versus time (so-called "alpha plots"), gave curves suggestive of two distinct phases, one relatively constant and another stochastic (7). They proposed that the two phases mapped to discrete states of the cell cycle. A resting "A state," they suggested, was contained within the G 1 phase from which cells could exit with constant probability per unit time (analogous to radioactive decay). The cells then entered the "B phase," which includes that part of G 1 not included in A state, as well as the entirety of S/G 2 /M. In B phase, cells' activities were first described to be "deterministic, and directed towards replication," implying a constant B phase. However, in the same paper, this assumption was relaxed and the duration of B phase was described with a relatively constant random variable (7).Although details of the quantitative relationship and biological interpretation have been debated (7-12), the rule that the bulk of kinetic variation is in G 1 phase, and that time in S/G 2 /M is relatively fixed, is widely accepted. Furthermore, mathematical models adopting this mechanical description (so-called "transition probability" or "compartment" models) remain popular and form the basis of many studies of lymphocyte and cancer kinetics in vitro and in vivo today (13-21).More recently, a molecular description of cell cycle regulation, including the discovery of key regulatory proteins such as cyclins a...
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