Dynamic optimization of metabolic networks coupled with gene expression

The regulation of metabolic activity by tuning enzyme expression levels is crucial to sustain cellular growth in changing environments. Metabolic networks are often studied at steady state using constraint-based models and optimization techniques. However, metabolic adaptations driven by changes in gene expression cannot be analyzed by steady state models, as these do not account for temporal changes in biomass composition. Here we present a dynamic optimization framework that integrates the metabolic network with the dynamics of biomass production and composition, explicitly taking into account enzyme production costs and enzymatic capacity. In contrast to the established dynamic flux balance analysis, our approach allows predicting dynamic changes in both the metabolic fluxes and the biomass composition during metabolic adaptations. We applied our algorithm in two case studies: a minimal nutrient uptake network, and an abstraction of core metabolic processes in bacteria. In the minimal model, we show that the optimized uptake rates reproduce the empirical Monod growth for bacterial cultures. For the network of core metabolic processes, the dynamic optimization algorithm predicted commonly observed metabolic adaptations, such as a diauxic switch with a preference ranking for different nutrients, re-utilization of waste products after depletion of the original substrate, and metabolic adaptation to an impending nutrient depletion. These examples illustrate how dynamic adaptations of enzyme expression can be predicted solely from an optimization principle

Dark states of single NV centers in diamond unraveled by single shot NMR

The nitrogen-vacancy (NV) center in diamond is supposed to be a building block for quantum computing and nanometer scale metrology at ambient conditions. Therefore, precise knowledge of its quantum states is crucial. Here, we experimentally show that under usual operating conditions the NV exists in an equilibrium of two charge states (70% in the expected negative (NV-) and 30% in the neutral one (NV0)). Projective quantum non-demolition measurement of the nitrogen nuclear spin enables the detection even of the additional, optically inactive state. The nuclear spin can be coherently driven also in NV0 (T1 ~ 90 ms and T2 ~ 6 micro-s).Comment: 4 pages, 3 figure

The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: A clinical phase II study

Purpose: The aim of this phase II study was to evaluate the tumour response of neuroendocrine tumours to targeted irradiation with the radiolabelled somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90-Y-DO-TATOC treatment on the malignant carcinoid syndrome and tumour-associated pain was investigated. Patients and methods: Forty-one patients (mean age 53 years) with neuroendocrine gastroenteropancreatic and bronchial tumours were included. Eighty-two percent of the patients had therapy resistant and progressive disease. The treatment con sisted of four intravenous injections ofa total of 6000 MBq/m2 90Y-DOTATOC, administered at intervals of six weeks. Results:The overall response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of 41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of4l) and progressive disease (PD) in 15% (6 of4l). The median follow up was 15 months (range 1 month to 36 months). The median duration of response has not been reached at 26 months. The two-year survival time was 76 ± 16%. Eighty-three percent of the patients suffering from the malignant carcinoid syndrome achieved a significant reduction of symptoms. The treatment was well tolerated. A reduction of pain score was observed in all patients (5 of 41) with morphine dependent tumour-associated pain. Side effects included grade LU (NCIGC) pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III—IV renal toxicity was observed. Conclusion: Targeted radiotherapy with 90Y-DOTATOC is a novel, well-tolerated treatment for neuroendocrine turnours with a remarkable objective response rate, survival time, and symptomatic respons

Photo induced ionization dynamics of the nitrogen vacancy defect in diamond investigated by single shot charge state detection

The nitrogen-vacancy centre (NV) has drawn much attention for over a decade, yet detailed knowledge of the photophysics needs to be established. Under typical conditions, the NV can have two stable charge states, negative (NV-) or neutral (NV0), with photo induced interconversion of these two states. Here, we present detailed studies of the ionization dynamics of single NV centres in bulk diamond at room temperature during illumination in dependence of the excitation wavelength and power. We apply a recent method which allows us to directly measure the charge state of a single NV centre, and observe its temporal evolution. Results of this work are the steady state NV- population, which was found to be always < 75% for 450 to 610 nm excitation wavelength, the relative absorption cross-section of NV- for 540 to 610 nm, and the energy of the NV- ground state of 2.6 eV below the conduction band. These results will help to further understand the photo-physics of the NV centre.Comment: 9 pages, 7 figure

Opening up the Quantum Three-Box Problem with Undetectable Measurements

One of the most striking features of quantum mechanics is the profound effect exerted by measurements alone. Sophisticated quantum control is now available in several experimental systems, exposing discrepancies between quantum and classical mechanics whenever measurement induces disturbance of the interrogated system. In practice, such discrepancies may frequently be explained as the back-action required by quantum mechanics adding quantum noise to a classical signal. Here we implement the 'three-box' quantum game of Aharonov and Vaidman in which quantum measurements add no detectable noise to a classical signal, by utilising state-of-the-art control and measurement of the nitrogen vacancy centre in diamond. Quantum and classical mechanics then make contradictory predictions for the same experimental procedure, however classical observers cannot invoke measurement-induced disturbance to explain this discrepancy. We quantify the residual disturbance of our measurements and obtain data that rule out any classical model by > 7.8 standard deviations, allowing us for the first time to exclude the property of macroscopic state-definiteness from our system. Our experiment is then equivalent to a Kochen-Spekker test of quantum non-contextuality that successfully addresses the measurement detectability loophole

Composite-pulse magnetometry with a solid-state quantum sensor

The sensitivity of quantum magnetometers is challenged by control errors and, especially in the solid-state, by their short coherence times. Refocusing techniques can overcome these limitations and improve the sensitivity to periodic fields, but they come at the cost of reduced bandwidth and cannot be applied to sense static (DC) or aperiodic fields. Here we experimentally demonstrate that continuous driving of the sensor spin by a composite pulse known as rotary-echo (RE) yields a flexible magnetometry scheme, mitigating both driving power imperfections and decoherence. A suitable choice of RE parameters compensates for different scenarios of noise strength and origin. The method can be applied to nanoscale sensing in variable environments or to realize noise spectroscopy. In a room-temperature implementation based on a single electronic spin in diamond, composite-pulse magnetometry provides a tunable trade-off between sensitivities in the microT/sqrt(Hz) range, comparable to those obtained with Ramsey spectroscopy, and coherence times approaching T1

Demonstration of entanglement-by-measurement of solid state qubits

Projective measurements are a powerful tool for manipulating quantum states. In particular, a set of qubits can be entangled by measurement of a joint property such as qubit parity. These joint measurements do not require a direct interaction between qubits and therefore provide a unique resource for quantum information processing with well-isolated qubits. Numerous schemes for entanglement-by-measurement of solid-state qubits have been proposed, but the demanding experimental requirements have so far hindered implementations. Here we realize a two-qubit parity measurement on nuclear spins in diamond by exploiting the electron spin of a nitrogen-vacancy center as readout ancilla. The measurement enables us to project the initially uncorrelated nuclear spins into maximally entangled states. By combining this entanglement with high-fidelity single-shot readout we demonstrate the first violation of Bells inequality with solid-state spins. These results open the door to a new class of experiments in which projective measurements are used to create, protect and manipulate entanglement between solid-state qubits.Comment: 6 pages, 4 figure