Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes

Peptide-based delivery systems that deliver target molecules into cells have been gaining traction. These systems need cell-penetrating peptides (CPPs), which have the remarkable ability to penetrate into biological membranes and help internalize different cargoes into cells through the cell membranes. The molecular internalization mechanism and structure–function relationships of CPPs are not clear, although the incorporation of nonproteinogenic amino acids such as α-aminoisobutyric acid (Aib) has been reported to increase their helicity, biostability and penetration efficiencies. Here, we used molecular dynamics to study two Aib-containing CPPs, poly(LysAibAla)3 (KAibA) and poly(LysAibGly)₃ (KAibG), that previously showed high cell internalization efficiency. KAibA and KAibG displayed the lowest internalization energies among the studied CPPs, showing distinct internalization mechanisms depending on the lipid composition of the model membranes. The presence of Aib residues allows these CPPs to adopt amphipathic folding to efficiently penetrate through the membranes. Elucidating how Aib incorporation affects CPP–membrane binding and interactions is beneficial for the design of CPPs for efficient intracellular delivery

Molecular dynamics simulation of complexation between plasmid DNA and cationic peptides

The elucidation of the process by which cationic peptides condense plasmid DNA (pDNA) is important for unraveling the mechanism of peptide/pDNA complex formation, which plays a vital role in gene delivery for the genetic transformation of living cells. We performed atomic MD simulations of the complexation of pDNA in the presence of two cationic peptides, KH9 (with an alternating sequence of lysine and histidine) and Cytcox (functioning as a mitochondria-targeting signal), to investigate the mechanism of pDNA condensation. The simulations revealed that the cationic peptides bound to the pDNA and that defects in pDNA formed in response to the densely packed cationic peptides, presumably initiating the folding of the double-stranded pDNA into a globule morphology. The decrease in the radius of gyration and the number of hydrogen bonds and the increase in the writhe structure, with a slightly higher tendency for the Cytcox/pDNA system, strongly support the formation of pDNA defects leading to the bending of the double helix. The results provided insight into the mechanism of pDNA complexation with cationic peptides, which should contribute to the future design of highly efficient gene delivery systems using peptide-mediated nanocarriers.This work was financially supported by Japan Science and Technology Agency Exploratory Research for Advanced Technology (JST ERATO; Grant No. JPMJER1602). We acknowledge the RIKEN Advanced Center for Computing and Communication (ACCC) for providing access to HOKUSAI BigWaterfall Supercomputer resources.Peer ReviewedPostprint (published version

Computational study of the interaction between natural rubber α-terminal groups and l-quebrachitol, one of the major components of natural rubber

Natural rubber is a biomaterial with unique physical and chemical features that are indispensable for many industrial applications. It is widely accepted that the α-terminal groups of its biopolymer molecules play a critical role in its exceptional characteristics. Herein, we used molecular dynamics to model recently structurally defined α-terminal groups and their interaction with L-quebrachitol, which is the second most common compound found in natural rubber particles

Semianalytical Approach to the PDF of SINR in HPHT and LPLT Single-Frequency Networks

(c) 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this[EN] Single-frequency networks (SFN) are widely adopted in terrestrial broadcast networks based on high-power high-tower (HPHT) deployments. The mobile broadcasting standard Evolved Multimedia Broadcast Multicast Service (eMBMS) has been enhanced in Release 14 to enable SFN operation with larger CP duration which may allow for the deployment of large area SFNs and even the combined operation between HPHT and low-power low-tower (LPLT) cellular stations. The knowledge of the signal-to-interference-plus-noise ratio (SINR) distribution over an SFN area may facilitate the selection of transmission parameters according to the network topology. This paper presents a semianalytical method for the calculation of the SINR distribution in SFNs with low computational complexity compared to Monte Carlo simulations. The method, which builds on previous work developed for cellular communications, is applied to HPHT+LPLT SFNs and evaluated against different transmission and network parameters.This work was supported in part by the Ministerio de Educacion y Ciencia, Spain, under Grant TEC2014-56483-R, in part by European FEDER funds.Gimenez Gandia, JJ.; Sung, KW.; Gomez-Barquero, D. (2018). Semianalytical Approach to the PDF of SINR in HPHT and LPLT Single-Frequency Networks. IEEE Transactions on Vehicular Technology. 67(5):4173-4181. https://doi.org/10.1109/TVT.2018.2791347S4173418167

Scattered Pilot Performance and Optimization for ATSC 3.0

[EN] The next-generation U.S. digital terrestrial television (DTT) standard ATSC 3.0 is the most flexible DTT standard ever developed, outperforming the state-of-the-art digital video broadcasting-terrestrial 2nd generation (DVB-T2) standard. This higher flexibility allows broadcasters to select the configuration that better suits the coverage and capacity requirements per service. Regarding the selection of pilot patterns, whereas DVB-T2 provides eight different patterns with a unique pilot amplitude, ATSC 3.0 expands up to 16, with five different amplitudes per pattern. This paper focuses on the pilot pattern and amplitude performance and optimization for time and power multiplexing modes, time division multiplexing and layered division multiplexing (LDM), respectively, of ATSC 3.0. The selection of the optimum pilot configuration is not straightforward. On the one hand, the pilots must be sufficiently dense to follow channel fluctuations. On the other hand, as long as pilot density is increased, more data overhead is introduced. Moreover, this selection is particularly essential in LDM mode, because the LDM implementation in ATSC 3.0 requires that both layers share all the waveform parameters, including pilot pattern configuration. In addition, there is an error proportional to the channel estimate of the top layer that affects to the lower layer performance.This work was supported in part by the Institute for Information and Communications Technology (IITP) by the Korea Government (MSIP) (Development of Service and Transmission Technology for Convergent Realistic Broadcast) under Grant R0101-15-294, and in part by the Ministerio de Educación y Ciencia, Spain, by European FEDER Funds under Grant TEC2014-56483-R.Garro, E.; Gimenez, JJ.; Park, SI.; Gomez-Barquero, D. (2017). Scattered Pilot Performance and Optimization for ATSC 3.0. IEEE Transactions on Broadcasting. 63(1):282-292. https://doi.org/10.1109/TBC.2016.2630304S28229263

Information-Theoretic Analysis and Performance Evaluation of Optimal Demappers for Multi-Layer Broadcast Systems

(c) 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this[EN] Multi-layer broadcast systems distribute services across time and frequency domain by means of power-division multiplexing. Successive interference cancelation is required, in general, in order to extract the content of all services. For a low-complexity implementation, the receiver can obtain the strongest (top-layer) signal assuming underlying signals to behave like thermal noise. The thermal noise assumption may not be valid under certain conditions and a more accurate characterization of the interference could bring improved performance. This paper analyzes the validity of the noise-like assumption considering the power ratio between signals and the required carrier-to-noise ratio for error-free reception. The main contribution of the paper is the proposal of a demapping algorithm that exploits the knowledge of the constellation of underlying signals. Generalized mutual information, performance evaluation, and complexity analysis are provided with the additive white Gaussian noise-like assumptions and with the proposed alternative in order to assess the potential performance improvements that can be achieved.This work was supported by in part by the Ministerio de Educacion y Ciencia, Spain under Grant TEC2014-56483-R, and in part by the European FEDER Funds.Garro, E.; Gimenez Gandia, JJ.; Klenner, P.; Gomez-Barquero, D. (2018). Information-Theoretic Analysis and Performance Evaluation of Optimal Demappers for Multi-Layer Broadcast Systems. IEEE Transactions on Broadcasting. 64(4):781-790. https://doi.org/10.1109/TBC.2018.2799300S78179064

Wideband Broadcasting: A Power-Efficient Approach to 5G Broadcasting

(c) 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this[EN] Efficient and flexible use of spectrum will be inherent characteristics of fifth-generation (5G) communication technologies with native support of wideband operation with frequency reuse 1, i.e. all transmit sites use all available frequency resources. Although not from the very first 5G release of 3GPP (Third Generation Partnership Project), it is expected that broadcast/multicast technology components will later be added and fully integrated in the 5G system. The combination of both wideband and frequency reuse 1 may provide significant gains for broadcast transmissions in terms of energy efficiency, since it is more efficient to increase capacity by extending the bandwidth rather than increasing the transmit power over a given bandwidth. This breaks with the traditional concept of terrestrial broadcast frequency planning, and paves the way to new potential uses of UHF (Ultra High Frequency) spectrum bands for 5G broadcasting. This paper provides an insight into the fundamental advantages in terms of capacity, coverage as well as power saving of wideband broadcast operation. The role of the network deployment, linked to frequency reuse in the UHF band, and its influence in the performance of a Wideband Broadcasting system are discussed. The technical requirements and features that would enable such power-efficient solution are also addressed.This work was supported in part by the European Commission under the 5G-PPP project 5G-Xcast (H2020-ICT-2016-2 call, grant number 761498). The views expressed in this contribution are those of the authors and do not necessarily represent the project. This work was also partially supported by the Ministerio de Educacion y Ciencia, Spain (TEC2014-56483-R), co-funded by European FEDER funds.Gimenez Gandia, JJ.; Gomez-Barquero, D.; Mogarde, J.; Stare, E. (2018). Wideband Broadcasting: A Power-Efficient Approach to 5G Broadcasting. IEEE Communications Magazine. 56(3):119-125. https://doi.org/10.1109/MCOM.2018.170067511912556

THE SAME ASSETS, BUT NEW IMPACTS: IT-ENABLED COORDINATION AND ENVIRONMENTAL PERFORMANCE

In this paper we analyze the effect of information technologies (IT) on the environmental performance of firms. In particular, we study the moderating effect of IT on the relationship between a firm\u27s environmental practices and its environmental performance. The paper considers two moderating effects namely, IT-enabled coordination and IT-enabled control. IT-enabled coordination refers to the integration of processes and the sharing of information between a firm and its suppliers in design and manufacturing. IT-enabled control refers to the use of IT to monitor the environmental practices that a firm implements in production and logistics. The data used were obtained from the fifth (2009) round of the International Manufacturing Strategy Survey (IMSS) which includes responses from manufacturing plants within the assembly industry. Our findings suggest that IT-enabled coordination strengthens the impact of the implementation of environmental practices on the environmental performance of firms. A relevant contribution for practice is derived from this study: firms can use the same technologies (ERP, shared databases) that they once implemented to improve their operational performance to improve the environmental performance

A regenerative active clamp circuit for DC/AC converters with high-frequency isolation in photovoltaic systems

DC/AC converters with high-frequency isolation and bidirectional power flow are extensively used in photovoltaic power systems and small isolated power converters at low and medium power ranges. The main disadvantages of these circuits are: high freewheeling loss of the primary leakage current, limited ZVS range for the lagging leg switches, the effects of the parasitic elements of the systems and others. To avoid these losses an energy recovery circuit based on an active voltage clamper is presented. The control circuit is designed having a number of soft switching transitions. The system has been verified by simulation and a prototype is being tested. In this paper we present an energy recovery system and a modulation sequence for the cycloconverter. The energy recovery system is based on an active voltage clamper; the voltage peaks energy is returned to the source. Furthermore, the presented modulation sequence is designed to have a maximum number of soft-switching transitions independent of the electric variables; which means minimum losses and independence on measurement systems limitations for modulation.Peer ReviewedPostprint (published version

Papain-Catalyzed, Sequence-Dependent Polymerization Yields Polypeptides Containing Periodic Histidine Residues

His-containing polypeptides, including polyHis, are attractive materials due to the unique characteristics of the imidazole ring of the His residue. In particular, His-containing polypeptides with repetitive sequences have a variety of distinctive features based on their periodic structure. In this study, chemoenzymatic polymerization of ethyl ester monomers with sequences His, GlyHis, HisGly, and GlyHisGly with hydrophobic side chains on the imidazole ring was performed using papain as a catalyst. Sequence dependence in chemoenzymatic polymerization was observed for GlyHis- and HisGly-based monomers: GlyHis-based monomers did not undergo polymerization, whereas polymerization of HisGly-based monomers afforded polypeptides with a degree of polymerization from 6 to 38 and from 5 to 31 and a number-average degree of polymerization of 16.4 and 12.4 for poly(HisGly) and poly[His(Bu)Gly], respectively. The difference in polymerizability of these dipeptide monomers was supported by a docking simulation between these monomers and papain, where the ester group of the HisGly-based monomer was closer to the catalytic center of papain than that of the GlyHis-based monomer. Infrared spectroscopy and synchrotron wide-angle X-ray diffraction measurements indicated that poly(HisGly) formed a β-sheet structure whose crystallinity was 41.6%, whereas the other tripeptide-based polypeptides were more amorphous showing 19.6–30.7% of crystallinity. Poly(HisGly) exhibited the highest thermal stability among all of the polypeptides in the thermogravimetric analysis, reflecting the difference in the secondary structures