Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.

Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has expanded tremendously over the past years, the choice of E3 ligases remains limited, with an almost exclusive focus on CRBN and VHL. Here, we report the discovery of novel ligands to the PRY-SPRY domain of TRIM58, a RING ligase that is specifically expressed in erythroid precursor cells.

The viable bioengineered allogeneic cellularized construct StrataGraft® synthesizes, deposits, and organizes human extracellular matrix proteins into tissue type-specific structures and secretes soluble factors associated with wound healing.

Background: StrataGraft® (allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen-dsat) is an FDA-approved viable bioengineered allogeneic cellularized construct for adult patients with deep partial-thickness burns requiring surgery. We characterized the structural and functional properties of StrataGraft to improve product understanding by evaluating extracellular matrix (ECM) molecule distribution and secreted protein factor expression in vitro.

Methods: ECM protein expression was determined using indirect immunofluorescence on construct cross sections using commercial antibodies against collagen III, IV, VI, laminin-332, and decorin.

Strategies for implementing the Appointment-Based Model at a rural independent chain of community pharmacies.

Background: The Appointment-Based Model (ABM) is a care model that helps community pharmacists streamline their medication dispensing workflow while simultaneously integrating patient care into the medication preparation process through medication synchronization. Implementation of the ABM has varied across community pharmacies. Further studies that identify tailored implementation approaches are needed to support broad adoption of the ABM in practice.

A systematic review of community pharmacy initiatives to improve treatment of depression and pain: Focus on types of programs and patient-reported outcomes.

Introduction: Depression and pain are common, disabling, mutually exacerbating conditions. Many patients living with these conditions present to community pharmacies on a regular schedule to purchase both prescribed and over-the-counter medications. Community-pharmacy based programs have been developed to improve depression and pain outcomes.

On the bandwidth dependent performance of split transmitter-receiver optical fiber nonlinearity compensation.

The Gaussian noise model is used to estimate the performance of three digital nonlinearity compensation (NLC) algorithms in C-band, long-haul, optical fiber transmission, when the span length and NLC bandwidth are independently varied. The algorithms are receiver-side digital backpropagation (DBP), transmitter-side DBP (digital precompensation), and Split NLC (an equal division of DBP between transmitter and receiver). For transmission over 100×100 km spans, the model predicts a 0.

Reduction Dynamics of Doped Ceria, Nickel Oxide, and Cermet Composites Probed Using In Situ Raman Spectroscopy.

The redox properties of gadolinium doped ceria (CGO) and nickel oxide (NiO) composite cermets underpin the operation of solid oxide electrochemical cells. Although these systems have been widely studied, a full comprehension of the reaction dynamics at the interface of these materials is lacking. Here, in situ Raman spectroscopic monitoring of the redox cycle is used to investigate the interplay between the dynamic and competing processes of hydrogen spillover and water dissociation on the doped ceria surface.

Increasing the information rates of optical communications via coded modulation: a study of transceiver performance.

Optical fibre underpins the global communications infrastructure and has experienced an astonishing evolution over the past four decades, with current commercial systems transmitting data rates in excess of 10 Tb/s over a single fibre core. The continuation of this dramatic growth in throughput has become constrained due to a power dependent nonlinear distortion arising from a phenomenon known as the Kerr effect. The mitigation of fibre nonlinearities is an area of intense research.

Maximizing the optical network capacity.

Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available.

High spectral density transmission emulation using amplified spontaneous emission noise.

We demonstrate the use of spectrally shaped amplified spontaneous emission (SS-ASE) noise for wideband channel loading in the investigation of nonlinear transmission limits in wavelength-division multiplexing transmission experiments using Nyquist-spaced channels. The validity of this approach is explored through statistical analysis and experimental transmission of Nyquist-spaced 10 GBaud polarization-division multiplexing (PDM) quadrature phase-shift keying and PDM-16-ary quadrature amplitude modulation (QAM) channels, co-propagated with SS-ASE over single mode fiber. It is shown that this technique, which is simpler to implement than a fully modulated comb of channels, is valid for distances exceeding 240 km for PDM-16QAM with dispersion of 16 ps/nm/km, yields a good agreement with theory, and provides a conservative measure of system performance.

Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses.

Purpose: The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management.

Experimental Design: As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy.

Unrepeatered Nyquist PDM-16QAM transmission over 364 km using Raman amplification and multi-channel digital back-propagation.

Transmission of a net 467-Gb/s PDM-16QAM Nyquist-spaced superchannel is reported with an intra-superchannel net spectral efficiency (SE) of 6.6 (b/s)/Hz, over 364-km SMF-28 ULL ultra-low loss optical fiber, enabled by bi-directional second-order Raman amplification and digital nonlinearity compensation. Multi-channel digital back-propagation (MC-DBP) was applied to compensate for nonlinear interference; an improvement of 2 dB in Q(2) factor was achieved when 70-GHz DBP bandwidth was applied, allowing an increase in span length of 37 km.

Spectrally shaped DP-16QAM super-channel transmission with multi-channel digital back-propagation.

The achievable transmission capacity of conventional optical fibre communication systems is limited by nonlinear distortions due to the Kerr effect and the difficulty in modulating the optical field to effectively use the available fibre bandwidth. In order to achieve a high information spectral density (ISD), while simultaneously maintaining transmission reach, multi-channel fibre nonlinearity compensation and spectrally efficient data encoding must be utilised. In this work, we use a single coherent super-receiver to simultaneously receive a DP-16QAM super-channel, consisting of seven spectrally shaped 10GBd sub-carriers spaced at the Nyquist frequency.

Printing in three dimensions with graphene.

Responsive graphene oxide sheets form non-covalent networks with optimum rheological properties for 3D printing. These networks have shear thinning behavior and sufficiently high elastic shear modulus (G') to build self-supporting 3D structures by direct write assembly. Drying and thermal reduction leads to ultra-light graphene-only structures with restored conductivity and elastomeric behavior.

The Drosophila Huntington's disease gene ortholog dhtt influences chromatin regulation during development.

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by a CAG expansion mutation in HTT, the gene encoding huntingtin. Evidence from both human genotype-phenotype relationships and mouse model systems suggests that the mutation acts by dysregulating some normal activity of huntingtin. Recent work in the mouse has revealed a role for huntingtin in epigenetic regulation during development.

Mesoscale assembly of chemically modified graphene into complex cellular networks.

The widespread technological introduction of graphene beyond electronics rests on our ability to assemble this two-dimensional building block into three-dimensional structures for practical devices. To achieve this goal we need fabrication approaches that are able to provide an accurate control of chemistry and architecture from nano to macroscopic levels. Here, we describe a versatile technique to build ultralight (density ≥1 mg cm(-3)) cellular networks based on the use of soft templates and the controlled segregation of chemically modified graphene to liquid interfaces.

Gain-switched multicarrier transmitter in a long-reach UDWDM PON with a digital coherent receiver.

The authors report on the downlink performance of a 10 Gb/s long-reach and ultra-dense wavelength-division multiplexed passive optical network, based on a multicarrier transmitter realized by using an externally injected gain-switched distributed-feedback laser diode. Each of the comb channels, spaced by 10 GHz, is modulated with a 3 Gbaud dual polarization quadrature phase shift keying signal that included a 20% overhead for forward error correction. Frequency selectivity and enhanced receiver sensitivity is achieved by employing a digital coherent receiver to receive the signal.

Genetic and functional studies implicate synaptic overgrowth and ring gland cAMP/PKA signaling defects in the Drosophila melanogaster neurofibromatosis-1 growth deficiency.

Neurofibromatosis type 1 (NF1), a genetic disease that affects 1 in 3,000, is caused by loss of a large evolutionary conserved protein that serves as a GTPase Activating Protein (GAP) for Ras. Among Drosophila melanogaster Nf1 (dNf1) null mutant phenotypes, learning/memory deficits and reduced overall growth resemble human NF1 symptoms. These and other dNf1 defects are relatively insensitive to manipulations that reduce Ras signaling strength but are suppressed by increasing signaling through the 3'-5' cyclic adenosine monophosphate (cAMP) dependent Protein Kinase A (PKA) pathway, or phenocopied by inhibiting this pathway.

Clinical consequences of polypharmacy in elderly.

Introduction: Polypharmacy, defined as the use of multiple drugs or more than are medically necessary, is a growing concern for older adults. MEDLINE and EMBASE databases were searched from January 1, 1986 to June 30, 2013) to identify relevant articles in people aged > 65 years.

Areas Covered: We present information about: i) prevalence of polypharmacy and unnecessary medication use; ii) negative consequences of polypharmacy; and iii) interventions to improve polypharmacy.

Burst Mode Receiver for 112 Gb/s DP-QPSK with parallel DSP.

A burst mode 112 Gb/s DP-QPSK digital coherent optical receiver with parallel DSP suitable for implementation in a CMOS ASIC with a 218.75 MHz clock speed is presented. The receiver performance is validated in a five channel 50 GHz grid WDM burst switching experiment using a commercially available wavelength tunable laser as the local oscillator.

Estimating OSNR of equalised QPSK signals.

We propose and demonstrate a technique to estimate the OSNR of an equalised QPSK signal based on the radial moments of the complex signal constellation. The technique is compared through simulation with maximum likelihood estimation and the effect of the block size used in the estimation is also assessed. The technique is verified experimentally and when combined with a single point calibration the OSNR of the input signal was estimated to within 0.

Dynamic linewidth measurement technique using digital intradyne coherent receivers.

The phase noise characteristics and laser stabilization time of a tunable laser under both static and fast switching operation is characterized using a dynamic linewidth measurement technique which employs a digital intradyne coherent receiver. The measurement technique utilizes a time domain frequency estimator to characterize the laser phase noise and also analyses the separate noise contributions to the overall laser linewidth. The performance of the measurement technique is validated using a phase noise emulator and a low linewidth (10 kHz) external cavity laser.