Entanglement of nanophotonic quantum memory nodes in a telecom network.

A key challenge in realizing practical quantum networks for long-distance quantum communication involves robust entanglement between quantum memory nodes connected by fibre optical infrastructure1-3. Here we demonstrate a two-node quantum network composed of multi-qubit registers based on silicon-vacancy (SiV) centres in nanophotonic diamond cavities integrated with a telecommunication fibre network. Remote entanglement is generated by the cavity-enhanced interactions between the electron spin qubits of the SiVs and optical photons. Serial, heralded spin-photon entangling gate operations with time-bin qubits are used for robust entanglement of separated nodes. Long-lived nuclear spin qubits are used to provide second-long entanglement storage and integrated error detection. By integrating efficient bidirectional quantum frequency conversion of photonic communication qubits to telecommunication frequencies (1,350 nm), we demonstrate the entanglement of two nuclear spin memories through 40 km spools of low-loss fibre and a 35-km long fibre loop deployed in the Boston area urban environment, representing an enabling step towards practical quantum repeaters and large-scale quantum networks.

Robust multi-qubit quantum network node with integrated error detection.

Long-distance quantum communication and networking require quantum memory nodes with efficient optical interfaces and long memory times. We report the realization of an integrated two-qubit network node based on silicon-vacancy centers (SiVs) in diamond nanophotonic cavities. Our qubit register consists of the SiV electron spin acting as a communication qubit and the strongly coupled silicon-29 nuclear spin acting as a memory qubit with a quantum memory time exceeding 2 seconds. By using a highly strained SiV, we realize electron-photon entangling gates at temperatures up to 1.5 kelvin and nucleus-photon entangling gates up to 4.3 kelvin. We also demonstrate efficient error detection in nuclear spin-photon gates by using the electron spin as a flag qubit, making this platform a promising candidate for scalable quantum repeaters.

Efficient Source of Shaped Single Photons Based on an Integrated Diamond Nanophotonic System.

An efficient, scalable source of shaped single photons that can be directly integrated with optical fiber networks and quantum memories is at the heart of many protocols in quantum information science. We demonstrate a deterministic source of arbitrarily temporally shaped single-photon pulses with high efficiency [detection efficiency=14.9%] and purity [g^{(2)}(0)=0.0168] and streams of up to 11 consecutively detected single photons using a silicon-vacancy center in a highly directional fiber-integrated diamond nanophotonic cavity. Combined with previously demonstrated spin-photon entangling gates, this system enables on-demand generation of streams of correlated photons such as cluster states and could be used as a resource for robust transmission and processing of quantum information.

Taking immunogenicity assessment of therapeutic proteins to the next level.

Therapeutic proteins provide innovative and effective therapies for numerous diseases. However, some of these products are associated with unwanted immunogenicity that may lead to clinical consequences such as reduced or loss of efficacy, altered pharmacokinetics (PK), general immune and hypersensitivity reactions, and neutralisation of the natural counterpart (e.g. the physiological hormone). Regulatory guidance on immunogenicity assessment needs to take into consideration a great diversity of products, indications and patient populations as well as constantly advancing manufacturing technologies. Such guidance needs to be sufficiently specific while, at the same time, allowing interactive discussion and adjusted benefit-risk weighing of each product on a case-by-case basis, e.g. for a unique treatment of a life threatening disease acceptable treatment risks may differ considerably from the ones in case of less serious disease. This theme was the focus of the international conference "Taking immunogenicity assessment of therapeutic proteins to the next level", held at the Paul-Ehrlich-Institut in Langen, Germany, on the 10-11. June 2010. The objectives of the conference were to highlight how the field could move from that of a mere description of risk factors to a system of risk assessment and mitigation, as well as an understanding of the impact of unwanted immunogenicity on the overall benefit/risk consideration for a medicinal product. More than 150 experts from industry, academia and regulatory authorities worldwide discussed the phenomenon of undesired immunogenicity from different perspectives. The conference focussed on issues relevant to three areas: (1) new European guidelines that are currently the subject of discussion; (2) testing strategies for immunogenicity assessment; and (3) scientific progress on the product-related factors that may contribute to the development of pathogenesis of immunogenicity, in particular in the field of protein aggregation and post-translational modifications. This report provides an overview of issues, insights, and conclusions that were discussed and achieved during the meeting.

Cardiac compression by a thymic cyst.

A patient with a giant thymic cyst, causing cardiac compression, is presented. Thymic cysts are uncommon and often asymptomatic.

Miliary tuberculosis following infliximab therapy for Crohn disease: A case report and review of the literature.

We present a case of miliary tuberculosis diagnosed 15 months after infliximab treatment despite negative screening for previous exposure to Mycobacteria on skin PPD and chest X-ray. This case shows that--although screening for TB with a skin PPD and a chest X-ray should be performed in all patients--this is not 100% effective and may be a problem in patients on concomitant immunosuppression. The clinical course of this patient further shows that in a patient treated with anti-TNF antibodies who's condition does not improve one should always be aware of the possibility of a tuberculosis infection. Even though tuberculosis is usually not rapidly fatal, the disease may show a fulminant course in immunocompromised patients.

Radiation-induced impairment of bone healing in the rat femur: effects of radiation dose, sequence and interval between surgery and irradiation.

BACKGROUND AND PURPOSE: Impairment of osseous healing in treatment combining surgery and radiotherapy is a frequent complication. Its dependence on sequence and interval was studied in a defined experimental model. MATERIALS AND METHODS: The effect of pre- and postoperative irradiation by single doses of X-rays on osseous closure of a 1.2 mm drill hole in the rat femur was measured 6 or 7 weeks after surgery in histological sections using morphometrical methods. RESULTS: Irradiation delivered between 1 day and 6 months before surgery resulted in a reduction of bone healing following very similar dose response relationships; there was no evidence of any slow repair of latent radiation damage. Radiosensitivity of bone healing during the first 3 days after surgery was not different from preoperative irradiation; however, irradiation 4 days or later after surgery failed to reduce osseous healing even after very high radiation doses. CONCLUSION: Tolerance increases enormously if radiotherapy is given later than 4 days after surgery. This has great implications for combined radiotherapy and surgery schedules involving bone reconstruction, but may be even more important for radiotherapy applied to prevent heterotopic ossification after total hip arthroplasty. Biologically, target cell regeneration alone is insufficient to account for the drastic rise in radiotolerance; it must be accompanied by an increase in cellular resistance due to differentiation.

Conserved waters in legume lectin crystal structures. The importance of bound water for the sequence-structure relationship within the legume lectin family.

An analysis of the water structure in the crystals of different legume lectins has been carried out. Protein hydration is found to be mainly dependent on the detailed local surface characteristics of the protein and will adapt upon the limited conformational changes that are the resultant of crystal packing forces and point mutations. Yet a significant portion of the water positions determined by x-ray crystallography appears to be conserved in all independent crystal structures of a given protein. Some of these waters are specific to this one specific protein, while others are conserved in crystal structures of homologous proteins as well. For those conserved waters, a clear structural role is often evident. Seven water sites were found to be completely conserved in all legume lectin crystal structures, independent of their degree of sequence homology or carbohydrate specificity. Of these, four waters are ligands to the manganese and calcium ions, and one water is located in the saccharide binding site interacting with a conserved Asp and Asn residue. Of the remaining two conserved waters, one of them stabilizes a beta-hairpin, while the other interacts with a beta-bulge structure of the back sheet.

The activation of Escherichia coli aspartate transcarbamylase by ATP. Specific involvement of helix H2' at the hydrophobic interface between the two domains of the regulatory chains.

The regulatory chain of E. coli aspartate transcarbamylase (E.C. 2.1.3.2) is folded into two domains. The allosteric domain harbours the regulatory site where the activator ATP and the inhibitors CTP and UTP bind competitively. The zinc domain ensures the contact with the catalytic chains. The interface between these two domains is hydrophobic, and involves the carboxy-terminal part of the helix H2' of the allosteric domain and several residues of the zinc domain. This structural feature mediates the transmission of the ATP regulatory signal. In the present work, site-directed mutagenesis and molecular modelling were used to investigate the role of specific amino acid residues in this process. The modifications of the hydrophobic core which are expected to alter the position of helix H2' reduce or abolish the sensitivity of the enzyme to ATP. The properties of the mutants and the results of modelling are fully consistent and suggest that a movement of helix H2' is part of the mechanism of activation by ATP. A model is proposed to account for the transmission of the ATP signal from the regulatory site to the interface between the regulatory and catalytic chains.

Biological effectiveness of neutrons and pi-mesons in gut, bone, and transplantable tumours.

At the Munich RENT-facility a screening project was performed to define the biological characteristics of a fission neutron beam envisaged for radiotherapy. The quantitative endpoints used were jejunal crypt survival, late rectal stenosis in rats, osseous healing in traumatized rat femur and regrowth delay of murine transplantable tumours. The results obtained in normal tissues (with the possible exception of bone) demonstrate a high RBE, in accordance with the well documented dependence of RBE on neutron energy. The RBE-values measured in tumours after single dose treatment endorsed the high effectiveness, although--as has been the case with other beams--they gave no conclusive evidence of a therapeutic advantage. Nevertheless, the specific beam characteristics, i.e. a high RBE at the surface and a fast decline of the biologically effective depth dose suggest possible advantages of the RENT beam when applied in the treatment of selected superficial tumours.