Hyperpolarisation-activated inward current in isolated sheep mesenteric lymphatic smooth muscle.

1. Freshly isolated sheep lymphatic smooth muscle cells were studied using the perforated patch-clamp technique. Hyperpolarisation with constant-current pulses caused a time-dependent rectification evident as a depolarising 'sag' followed by an anode-break overshoot at the end of the pulse. Both sag and overshoot were blocked with 1 mM Cs+. 2. Cells were voltage clamped at -30 mV and stepped to -120 mV in 10 mV steps of 2 s duration. Steps negative to -60 mV evoked a slowly activating, non-inactivating inward current which increased in size and rate of activation with increasing hyperpolarisation. 3. The slowly activating current was reduced in Na+-free bathing solution but enhanced when the extracellular K+ concentration was increased to 60 mM. The current was significantly reduced by 1 mM Cs+ and 1 microM ZD7288 but not by 1.8 mM Ba2+. 4. The steady-state activation curve of the underlying conductance showed a threshold at -50 mV and half-maximal activation at -81 mV. Neither threshold nor half-maximal activation was significantly affected by increasing the external K+ concentration to 60 mM. 5. The frequency of spontaneous contractions and fluid propulsion in isolated cannulated segments of sheep mesenteric lymphatics were decreased by 1 mM Cs+ and by 1 microM ZD7288. 6. We conclude that sheep lymphatics have a hyperpolarisation-activated inward current similar to the If seen in sinoatrial node cells of the heart. Blockade of this current slows spontaneous pumping in intact lymphatic vessels suggesting that it is important in normal pacemaking.

Revised response criteria for polycythemia vera and essential thrombocythemia:an ELN and IWG-MRT consensus project

Standardized response criteria to interpret and compare clinical trials are needed for approval of new therapeutic agents by regulatory agencies. The European LeukemiaNet (ELN) response criteria for essential thrombocythemia (ET) and polycythemia vera (PV) issued in 2009 have been widely adopted as end points in a number of recent clinical trials. However, evidence exists that they do not predict response or provide clinically relevant measures of benefit for the patients. This article presents revised recommendations for assessing response in ET and PV provided by a working group established by ELN and International Working Group-Myeloproliferative Neoplasms Research and Treatment. New definitions of complete and partial remission incorporate clinical, hematological, and histological response assessments that include a standardized symptom assessment form and consider absence of disease progression and vascular events. We anticipate that these criteria will be adopted widely to facilitate the development of new and more effective therapies for ET and PV.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

Multipair massive MIMO full-duplex relaying with MRC/MRT processing

We consider a multipair relay channel, where multiple sources communicate with multiple destinations with the help of a full-duplex (FD) relay station (RS). All sources and destinations have a single antenna, while the RS is equipped with massive arrays. We assume that the RS estimates the channels by using training sequences transmitted from sources and destinations. Then, it uses maximum-ratio combining/maximum-ratio transmission (MRC/MRT) to process the signals. To significantly reduce the loop interference (LI) effect, we propose two massive MIMO processing techniques: i) using a massive receive antenna array; or ii) using a massive transmit antenna array together with very low transmit power at the RS. We derive an exact achievable rate in closed-form and evaluate the system spectral efficiency. We show that, by doubling the number of antennas at the RS, the transmit power of each source and of the RS can be reduced by 1.5 dB if the pilot power is equal to the signal power and by 3 dB if the pilot power is kept fixed, while maintaining a given quality-of-service. Furthermore, we compare FD and half-duplex (HD) modes and show that FD improves significantly the performance when the LI level is low.

Multipair Full-Duplex Relaying with Massive Arrays and Linear Processing

We consider a multipair decode-and-forward relay channel, where multiple sources transmit simultaneously their signals to multiple destinations with the help of a full-duplex relay station. We assume that the relay station is equipped with massive arrays, while all sources and destinations have a single antenna. The relay station uses channel estimates obtained from received pilots and zero-forcing (ZF) or maximum-ratio combining/maximum-ratio transmission (MRC/MRT) to process the signals. To reduce significantly the loop interference effect, we propose two techniques: i) using a massive receive antenna array; or ii) using a massive transmit antenna array together with very low transmit power at the relay station. We derive an exact achievable rate in closed-form for MRC/MRT processing and an analytical approximation of the achievable rate for ZF processing. This approximation is very tight, especially for large number of relay station antennas. These closed-form expressions enable us to determine the regions where the full-duplex mode outperforms the half-duplex mode, as well as, to design an optimal power allocation scheme. This optimal power allocation scheme aims to maximize the energy efficiency for a given sum spectral efficiency and under peak power constraints at the relay station and sources. Numerical results verify the effectiveness of the optimal power allocation scheme. Furthermore, we show that, by doubling the number of transmit/receive antennas at the relay station, the transmit power of each source and of the relay station can be reduced by 1.5dB if the pilot power is equal to the signal power, and by 3dB if the pilot power is kept fixed, while maintaining a given quality-of-service.

Secure Transmission in Cooperative Relaying Networks with Multiple Antennas

We investigate the secrecy performance of dualhop amplify-and-forward (AF) multi-antenna relaying systems over Rayleigh fading channels, by taking into account the direct link between the source and destination. In order to exploit the available direct link and the multiple antennas for secrecy improvement, different linear processing schemes at the relay and different diversity combining techniques at the destination are proposed, namely, 1) Zero-forcing/Maximal ratio combining (ZF/MRC), 2) ZF/Selection combining (ZF/SC), 3) Maximal ratio transmission/MRC (MRT/MRC) and 4) MRT/Selection combining (MRT/SC). For all these schemes, we present new closed-form approximations for the secrecy outage probability. Moreover, we investigate a benchmark scheme, i.e., cooperative jamming/ZF (CJ/ZF), where the secrecy outage probability is obtained in exact closed-form. In addition, we present asymptotic secrecy outage expressions for all the proposed schemes in the high signal-to-noise ratio (SNR) regime, in order to characterize key design parameters, such as secrecy diversity order and secrecy array gain. The outcomes of this paper can be summarized as follows: a) MRT/MRC and MRT/SC achieve a full diversity order of M + 1, ZF/MRC and ZF/SC achieve a diversity order of M, while CJ/ZF only achieves unit diversity order, where M is the number of antennas at the relay. b) ZF/MRC (ZF/SC) outperforms the corresponding MRT/MRC (MRT/SC) in the low SNR regime, while becomes inferior to the corresponding MRT/MRC (MRT/SC) in the high SNR. c) All of the proposed schemes tend to outperform the CJ/ZF with moderate number of antennas, and linear processing schemes with MRC attain better performance than those with SC.

Secrecy Performance of Wirelessly Powered Wiretap Channels

This paper considers a wirelessly powered wiretap channel, where an energy constrained multi-antenna information source, powered by a dedicated power beacon, communicates with a legitimate user in the presence of a passive eavesdropper. Based on a simple time-switching protocol where power transfer and information transmission are separated in time, we investigate two popular multi-antenna transmission schemes at the information source, namely maximum ratio transmission (MRT) and transmit antenna selection (TAS). Closed-form expressions are derived for the achievable secrecy outage probability and average secrecy rate for both schemes. In addition, simple approximations are obtained at the high signal-to-noise ratio (SNR) regime. Our results demonstrate that by exploiting the full knowledge of channel state information (CSI), we can achieve a better secrecy performance, e.g., with full CSI of the main channel, the system can achieve substantial secrecy diversity gain. On the other hand, without the CSI of the main channel, no diversity gain can be attained. Moreover, we show that the additional level of randomness induced by wireless power transfer does not affect the secrecy performance in the high SNR regime. Finally, our theoretical claims are validated by the numerical results.