Software defined networking (SDN) over space division multiplexing (SDM) optical networks: features, benefits and experimental demonstration.

We present results from the first demonstration of a fully integrated SDN-controlled bandwidth-flexible and programmable SDM optical network utilizing sliceable self-homodyne spatial superchannels to support dynamic bandwidth and QoT provisioning, infrastructure slicing and isolation. Results show that SDN is a suitable control plane solution for the high-capacity flexible SDM network. It is able to provision end-to-end bandwidth and QoT requests according to user requirements, considering the unique characteristics of the underlying SDM infrastructure.

Fully-elastic multi-granular network with space/frequency/time switching using multi-core fibres and programmable optical nodes.

We present the first elastic, space division multiplexing, and multi-granular network based on two 7-core MCF links and four programmable optical nodes able to switch traffic utilising the space, frequency and time dimensions with over 6000-fold bandwidth granularity. Results show good end-to-end performance on all channels with power penalties between 0.75 dB and 3.7 dB.

Experimental demonstration of an OpenFlow based software-defined optical network employing packet, fixed and flexible DWDM grid technologies on an international multi-domain testbed.

Software defined networking (SDN) and flexible grid optical transport technology are two key technologies that allow network operators to customize their infrastructure based on application requirements and therefore minimizing the extra capital and operational costs required for hosting new applications. In this paper, for the first time we report on design, implementation & demonstration of a novel OpenFlow based SDN unified control plane allowing seamless operation across heterogeneous state-of-the-art optical and packet transport domains. We verify and experimentally evaluate OpenFlow protocol extensions for flexible DWDM grid transport technology along with its integration with fixed DWDM grid and layer-2 packet switching.

Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) represents a highly prevalent and deadly malignancy worldwide. The prognosis for locoregionally advanced HNSCC has not appreciably improved over the past 30 years despite advances in surgical, radiation, and targeted therapies and less than 20% of HNSCC patients respond to recently approved immune checkpoint inhibitors. The Hippo signaling pathway, originally discovered as a mechanism regulating tissue growth and organ size, transduces intracellular and extracellular signals to regulate the transcriptional co-activators YAP and TAZ. Alterations in the Hippo pathway resulting in persistent YAP and TAZ activation have emerged as major oncogenic drivers. Our analysis of the human HNSCC oncogenome revealed multiple genomic alterations impairing Hippo signaling and activating YAP and TAZ, which in turn contribute to HNSCC development. This includes mutations and deletions of the FAT1 gene (29%) and amplification of the WWTR1 (encoding TAZ, 14%) and YAP1 genes (8%), together representing one of the most genetically altered signaling mechanisms in this malignancy. Here, we discuss key elements of the mammalian Hippo pathway, detail mechanisms by which perturbations in Hippo signaling promote HNSCC initiation and progression and outline emerging strategies to target Hippo signaling vulnerabilities as part of novel multimodal precision therapies for HNSCC.

Experimental demonstration of gridless spectrum and time optical switching.

An experimental demonstration of gridless spectrum and time switching is presented. We propose and demonstrate a bit-rate and modulation-format independent optical cross-connect architecture, based on gridless spectrum selective switch, 20-ms 3D-MEMS and 10-ns PLZT optical switches, that supports arbitrary spectrum allocation and transparent time multiplexing. The architecture is implemented in a four-node field-fiber-linked testbed to transport continuous RZ and NRZ data channels at 12.5, 42.7 and 170.8 Gb/s, and selectively groom sub-wavelength RZ channels at 42.7 Gb/s. We also showed that the architecture is dynamic and can be reconfigured to meet the routing requirements of the network traffic. Results show error-free operation with an end-to-end power penalty between 0.8 dB and 5 dB for all continuous and sub-wavelength channels.

Field trial of a 1.5 Tb/s adaptive and gridless OXC supporting elastic 1000-fold all-optical bandwidth granularity.

An adaptive gridless OXC is implemented using a 3D-MEMS optical backplane plus optical modules (sub-systems) that provide elastic spectrum and time switching functionality. The OXC adapts its architecture on demand to fulfill the switching requirements of incoming traffic. The system is implemented in a seven-node network linked by installed fiber and is shown to provide suitable architectures on demand for three scenarios with increasing traffic and switching complexity. In the most complex scenario, signals of mixed bit-rates and modulation formats are successfully switched with flexible per-channel allocation of spectrum, time and space, achieving over 1000-fold bandwidth granularity and 1.5 Tb/s throughput with good end-to-end performance.

Gridless optical networking field trial: flexible spectrum switching, defragmentation and transport of 10G/40G/100G/555G over 620-km field fiber.

We present results from the first gridless networking field trial with flexible spectrum switching nodes and 620 km of installed fibre links. Signals at 10G, 12.25G, 42.7G, DP-QPSK 40G, DP-QPSK 100G and 555G are generated, successfully transported and switched using flexible, custom spectrum allocation per channel. Spectrum defragmentation is demonstrated using integrated SOA-MZI wavelength converters. Results show error-free end-to-end performance (BER<1e-9) for the OOK channels and good pre-FEC BER performance with sufficient margin to FEC limit for the 40G and 100G coherent channels as well as for the 555G super-channel.

Successful salvage treatment with irinotecan (CPT-11) of recurrent malignant lymphoma in an aged patient; and CPT-11 pharmacokinetics.

A 72-year-old patient with relapsed non-Hodgkin's lymphoma (diffuse large B-cell type) in the tongue was treated with irinotecan (CPT-11) as the 4th salvage therapy. A two-thirds reduced dose of 40 mg/m2 of CPT-11 was administered, as were granulocyte-colony stimulating factor and antidiarrheal agents. Complete remission was achieved. Although grade 3 leukopenia and grade 1 diarrhea were observed, these adverse reactions did not interrupt the treatment schedule and CPT-11 was administered without interruption for a total of 12 weeks. Despite the dose reduction, the area under the concentration-time curve of SN-38, the active metabolite of CPT-11, was nearly equal to the values reported in phase I and II studies of CPT-11. The patient's ratio of SN-38 to the SN-38 glucuronide (SN-38G) was low, suggesting a low risk of diarrhea. The optimal dose modification provided a sufficient amount of the active metabolite. Supportive therapy managed therapy-related toxicities and resulted in a stable treatment schedule. This is a rare case of a patient successfully treated with CPT-11 after a 4th relapse, in which the agent was administered at the total dose of 960 mg/m2, despite the patient's advanced age.

Degradation of myelin basic protein by calcium-activated neutral protease (CANP) in human brain and inhibition by E-64 analogue.

A calcium-activated neutral protease (CANP) was extracted from human brain and partially purified. The activity was measured using alkali-denatured casein (Hammersten) as a substrate. The optimum pH was around 7.0. The activity required the presence of calcium ions, maximum activity was obtained with over 5 mM calcium ions. The Km for the casein concentration was about 1.62 mg/ml. The activity of CANP was inhibited by one of the thiol protease inhibitors, E-64 analogue (E-64-a). The rate of inhibition was about 50% at an E-64-a concentration of 10(-5)M. This CANP degraded selectively basic protein in myelin proteins and the degradation was inhibited by E-64-a or EGTA. The role of the brain CANP in the process of demyelination was suggested by this study.