Endoplasmic reticulum (ER) proteins are degraded by proteasomes in the cytosol through ER-associated degradation (ERAD). This process involves the retrotranslocation of substrates across the ER membrane, their ubiquitination, and membrane extraction by the Cdc48/Npl4/Ufd1 ATPase complex prior to delivery to proteasomes for degradation. How the presence of a folded luminal domain affects substrate retrotranslocation and this event is coordinated with subsequent ERAD steps remains unknown. Here, using a model substrate with a folded luminal domain, we showed that Cdc48 ATPase activity is sufficient to drive substrate retrotranslocation independently of ERAD membrane components. However, the complete degradation of the folded luminal domain required substrate-tight coupling of retrotranslocation and proteasomal degradation, which was ensured by the derlin Dfm1. Mutations in Dfm1 intramembrane rhomboid-like or cytosolic Cdc48-binding regions resulted in partial degradation of the substrate with accumulation of its folded domain. Our study revealed Dfm1 as a critical regulator of Cdc48-driven retrotranslocation and highlights the importance of coordinating substrate retrotranslocation and degradation during ERAD.

Endoplasmic reticulum (ER) proteins are degraded by proteasomes in the cytosol through ER-associated degradation (ERAD). This process involves retrotranslocation of substrates across the ER membrane, their ubiquitination and subsequent membrane extraction by the Cdc48/Npl4/Ufd1 ATPase complex prior delivery to proteasomes for degradation. Recently a mechanism for the retrotranslocation of misfolded substrates by the Hrd1 ubiquitin ligase complex was described. However, how substrates with folded luminal domains are retrotranslocated remains unknown. Here, we identify Dfm1 as an essential membrane component for the retrotranslocation of proteins with folded luminal domains. Both Dfm1 intramembrane rhomboid-like and the cytosolic Cdc48-binding domains are essential for substrate retrotranslocation. Substrate processing by Dfm1 and Cdc48 complex requires the ubiquitin shuttle factors Rad23/Dsk2 and the multi-ubiquitination enzyme Ufd2. Our findings suggest a pathway in which a series of ubiquitin modifying factors recruit Dfm1 to resolve a stalled retrotranslocation intermediate due to the presence of a folded luminal domain.

Disposal of membrane proteins in the late secretory pathway is thought to be exclusively facilitated by ESCRT‐dependent lysosomal degradation. In this issue of The EMBO Journal, Schmidt et al define a previously uncharacterized endosome and Golgi‐associated degradation (EGAD) pathway. This pathway, which has remarkable similarities to ERAD in the endoplasmic reticulum, operates in post‐ER organelles via the proteasome and contributes to lipid homeostasis in eukaryotic cells. Identification of an ERAD‐like mechanism in Golgi and endosomes shows that membrane protein degradation in the late secretory pathway is not exclusively facilitated by ESCRT‐dependent lysosomal targeting.

We demonstrated a 400Gb/s Ethernet end-to-end circuit, inclusive of 400GbE client card with CPF8 interface and dual-carrier 16QAM line-side, on a production 100G core network segment between New York City and Washington DC. During the field trial, we demonstrated the feasibility of SDN-enabled creation, deletion, and re-routing of the 400G service.

Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases. Human fibrinogen, an extracellular chaperone, was reported to specifically interact with a wide spectrum of stressed proteins and suppress their aggregation, being an interacting protein with TTR. Fibrinogen is differentially glycated in ATTR, leading to its chaperone activity loss. Here we show the existence of a proteostasis imbalance in ATTR linked to fibrinogen glycation by methylglyoxal.

The impact of site-dependent pumping (SDP) on the performance of erbium-doped fiber amplifiers (EDFAs) pumped at wavelengths around 1480 nm is investigated, both experimentally and numerically. An improved numerical model incorporating the SDP effect for two-level EDFAs is derived and experimentally validated. We confirm by comparing with experimental data that the proposed model accurately describes the dependence of the amplifier gain spectrum on the pump wavelength and pump power. We conclude that SDP has a significant impact on the dynamic response of an EDFA due to input spectral variations and should be considered when simulating high performance links.

In this paper, we investigate the impact of inter-modal four-wave mixing on mode- and wavelength-division-multiplexing systems. A set of coupled nonlinear Schrödinger equations, including linear mode coupling, is derived allowing to isolate the inter-modal four-wave mixing terms. The efficiency of inter-modal four-wave mixing between degenerate LP modes is found to be significantly higher than the intra-modal four-wave mixing efficiency. However, it is shown that the inter-modal four-wave mixing efficiency between degenerate modes is significantly reduced by the linear mode coupling.

The transmission improvement obtained through the usage of pre-emphasis (PE) of single-band and multi-band orthogonal frequency division multiplexing (OFDM) ultra-wideband (UWB) signals using directly modulated lasers (DML) along long-reach passive optical networks is experimentally evaluated. Additionally, OFDM-UWB sub-bands with central frequencies above the cut-off frequency of the DML are experimentally considered in order to evaluate extending the transmission capacity through the usage of PE. In case of single-band transmission, PE improves the bit error ratio (BER) of several OFDM-UWB sub-bands by more than two orders of magnitude in back-to-back conditions as well as after transmission along 100km of standard single-mode fiber transmission (SSMF). Such improvement is limited by the reduced intensity modulation response variation of the DML within the passband of each OFDM-UWB sub-band, as fixed modulation index is considered in all tested cases. Considering multi-band transmission along 100km of SSMF, PE allows doubling the number of transmitted sub-bands before a BER exceeding is achieved for any of the sub-bands and an optical signal-to-noise ratio of 25dB0.1nm. Such improvement is obtained as PE changes the effective modulation depth of each transmitted OFDM-UWB sub-band, so that equalized signal power after detection and almost identical BER in all OFDM-UWB sub-bands occur.

In this paper, we investigate the design of few-mode fibers (FMFs) guiding 4 to 12 non-degenerate linearly polarized (LP) modes with low differential mode delay (DMD) over the C-band, suitable for long-haul transmission. The refractive index profile considered is composed by a graded-core with a cladding trench (GCCT). The optimization of the profile parameters aims the lowest possible DMD and macro-bend losses (MBL) lower than the ITU-T standard recommendation. The optimization results show that the optimum DMD and the MBL scale with the number of modes. Additionally, it is shown that the refractive-index relative difference at the core center is one of the most preponderant parameters, allowing to reduce the DMD at the expense of increasing MBL. Finally, the optimum DMD obtained for 12 LP modes is lower than 3 ps/km.

Flexgrid technology has recently been presented as the most promising option for upgrading the currently operating fixed grid optical networks and extending their capacity to be able to deal with the massive traffic volumes forecast for the next decade. Although the current traffic is successfully supported on fixed grid networks, flexgrid technology brings features that are not offered by the fixed grid networks, such as transporting optical connections with a capacity beyond 100 Gb/s and elasticity against time-varying traffic. In light of this, a gradual fixed grid to flexgrid migration is generally accepted in order to add these useful features to the network. In this article, we study the migration process where flexgrid is deployed in the network progressively, and review the main drivers and open issues induced by its deployment.

This paper presents the design of few-mode fibers (FMFs) with low differential mode delay (DMD) over the C-band, considering a refractive index profile with a graded core and a cladding trench. By optimizing the core grading exponent and the dimensioning of the trench, the lowest DMD achievable is obtained for different numbers of linearly polarized (LP) modes. Additionally, considering the concatenation of two FMFs with profiles of the same type but with different parameters values, both profiles are optimized in order to minimize the residual DMD. For both cases, the accumulated DMD increase rate with the number of LP modes is presented, as well as the maximum distance reach for mode-division multiplexing transmission.

This letter proposes the use of a refractive index profile with a graded core and a cladding trench for the design of few-mode fibers, aiming an arbitrary differential mode delay (DMD) flattened over the C+L band. By optimizing the core grading exponent and the dimensioning of the trench, a deviation lower than 0.01 ps/km from a target DMD is observed over the investigated wavelength range. Additionally, it is found that the dimensioning of the trench is almost independent of the target DMD, thereby enabling the use of a simple design rule that guarantees a maximum DMD deviation of 1.8 ps/km for a DMD target between -200 and 200 ps/km.

This letter proposes the introduction of discrete modal crosstalk (XT) through fiber splices for the improvement of the distance reach (DR) of mode division multiplexed (MDM) transmission systems over few mode fibers (FMFs). The proposed method increases the DR, reducing the time spread of the FMFs' impulse response. The effectiveness of this method is assessed through simulation considering 3 × 136-Gbit/s MDM-coherently-detected polarization-multiplexed quadrature-phase-shift-keying ultralong haul transmission systems employing inherently low differential mode delay (DMD) FMFs or DMD compensated FMFs. A maximum DR increase factor of 1.9 is obtained for the optimum number of splices per span and optimum splice XT level.

In the above-named article [ibid., vol. 25, no. 5, pp. 438-441, Mar. 1, 2013], the authors' affiliations were listed incorrectly. The correct affiliations are provided here.

This paper investigates the most favorable conditions for a full defragmentation procedure when evolving from a fixed to a flexible-grid scenario. Results show that migrating legacy channels to flexible-grid formats can yield up to 50% more capacity for future traffic, provided these legacy channels are also spectrally re-planned.

In the above-named article [ibid., vol. 25, no. 5, pp. 438-441, Mar. 1, 2013], the authors' affiliations were listed incorrectly. The correct affiliations are provided here.

The influence of the spectral allocation of input channels on the dynamic response of three-level erbium-doped fiber amplifiers (EDFAs) governed by spectral hold burning (SHB) and site dependent pumping (SDP) is investigated, both, experimentally and theoretically. Using an experimental setup specifically designed to isolate and assess the SHB and SDP behavior we are able to validate, with a good accuracy, a mathematical model derived from the fundamental equations of the three-level amplifier. We conclude that by selecting a pump wavelength centered at 974 nm instead of 980 nm, we can reduce the power excursions by 23 %, and that by increasing the channel spacing from 100 GHz to 150 GHz the power excursions decrease by more than 20 %. Further simulations are done to investigate the behavior of SHB and SDP in an EDFA with ideal gain control. We verify that in a subband switch, changing from the red subband to the blue subband causes higher deviations than when changing from the blue subband to the red subband of the c-band. Also, in a drop scenario, the overshoots and undershoots of the surviving channel depend on the input channels spectral allocation and on the gain of the amplifier.

This paper discusses the technical feasibility and network-level potential of defragmentation as a means of extending the capacity of optical transport networks. An experimental setup successfully demonstrates the possibility of rearranging connections spectrally in order to compact spectrum and harvest the benefits from more efficient flexible-grid channel formats. Furthermore, network simulations for fixed and flexible-grid formats highlight that the most promising cases for a full re-planning based defragmentation arise when the spectral mismatch between the different channel widths is more evident and when there are noticeable differences between the traffic patterns at different periods of the network life cycle.

A general memory polynomial (GMP) for transmission impairments mitigation in optical coherent detection systems is proposed. An error vector magnitude improvement of 9 dB, resulting mainly from the regenerator characteristic of the GMP, is shown.