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In this paper, we analyze experimental data from state-of-the-art vertical InAs/InGaAsSb/GaSb nanowire tunneling field-effect transistors (TFETs) to study the influence of source doping on their performance. Overall, the doping level impacts both the off-state and on-state performance of these devices. Separation of the doping from the heterostructure improved the subthreshold swing of the devices. The best devices reached a point subthreshold swing of 30 mV/dec at 100 x higher currents than previous Si-based TFETs. However, separation of doping from the heterostructure had a significant impact on the on-state performance of these devices due to effects related to source depletion. An increase in the doping level helped to improve the on-state performance, which also increased the subthreshold swing. Thus, further optimization of doping incorporation with the heterostructure will help to improve vertical InAs/InGaAsSb/GaSb nanowire TFETs. [ABSTRACT FROM AUTHOR]

The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10)-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure) and the first intermediate state towards channel closing (C1), modeled from experimental constraints. We show that conformations within 3 Å of the X-ray structure are obtained in simulations starting from the C1 model, and directly observe the previously suggested sliding 3(10)-helix region in S4. Through systematic free energy calculations, we show that the C1 state is a stable intermediate conformation and determine free energy profiles for moving between the states without constraints. Mutations indicate several residues in a narrow hydrophobic band in the voltage sensor contribute to the barrier between the open and C1 states, with F233 in the S2 helix having the largest influence. Substitution for smaller amino acids reduces the transition cost, while introduction of a larger ring increases it, largely confirming experimental activation shift results. There is a systematic correlation between the local aromatic ring rotation, the arginine barrier crossing, and the corresponding relative free energy. In particular, it appears to be more advantageous for the F233 side chain to rotate towards the extracellular side when arginines cross the hydrophobic region.

Cys-loop receptors constitute a superfamily of pentameric ligand-gated ion channels (pLGICs), including receptors for acetylcholine, serotonin, glycine and γ-aminobutyric acid. Several bacterial homologues have been identified that are excellent models for understanding allosteric binding of alcohols and anesthetics in human Cys-loop receptors. Recently, we showed that a single point mutation on a prokaryotic homologue (GLIC) could transform it from a channel weakly potentiated by ethanol into a highly ethanol-sensitive channel. Here, we have employed molecular simulations to study ethanol binding to GLIC, and to elucidate the role of the ethanol-enhancing mutation in GLIC modulation. By performing 1-µs simulations with and without ethanol on wild-type and mutated GLIC, we observed spontaneous binding in both intra-subunit and inter-subunit transmembrane cavities. In contrast to the glycine receptor GlyR, in which we previously observed ethanol binding primarily in an inter-subunit cavity, ethanol primarily occupied an intra-subunit cavity in wild-type GLIC. However, the highly ethanol-sensitive GLIC mutation significantly enhanced ethanol binding in the inter-subunit cavity. These results demonstrate dramatic effects of the F(14')A mutation on the distribution of ligands, and are consistent with a two-site model of pLGIC inhibition and potentiation.

Membrane fusion is essential to both cellular vesicle trafficking and infection by enveloped viruses. While the fusion protein assemblies that catalyze fusion are readily identifiable, the specific activities of the proteins involved and nature of the membrane changes they induce remain unknown. Here, we use many atomic-resolution simulations of vesicle fusion to examine the molecular mechanisms for fusion in detail. We employ committor analysis for these million-atom vesicle fusion simulations to identify a transition state for fusion stalk formation. In our simulations, this transition state occurs when the bulk properties of each lipid bilayer remain in a lamellar state but a few hydrophobic tails bulge into the hydrophilic interface layer and make contact to nucleate a stalk. Additional simulations of influenza fusion peptides in lipid bilayers show that the peptides promote similar local protrusion of lipid tails. Comparing these two sets of simulations, we obtain a common set of structural changes between the transition state for stalk formation and the local environment of peptides known to catalyze fusion. Our results thus suggest that the specific molecular properties of individual lipids are highly important to vesicle fusion and yield an explicit structural model that could help explain the mechanism of catalysis by fusion proteins.

Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees ) of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10) helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.

The incidence of West Nile virus (WNv) has remained high in the northern Great Plains compared to the rest of the United States. However, the reasons for the sustained high risk of WNv transmission in this region have not been determined. To assess the environmental drivers of WNv in the northern Great Plains, we analyzed the county-level spatial pattern of human cases during the 2003 epidemic across a seven-state region.County-level data on WNv cases were examined using spatial cluster analysis, and were used to fit statistical models with weather, climate, and land use variables as predictors. In 2003 there was a single large cluster of elevated WNv risk encompassing North Dakota, South Dakota, and Nebraska along with portions of eastern Montana and Wyoming. The relative risk of WNv remained high within the boundaries of this cluster from 2004-2007. WNv incidence during the 2003 epidemic was found to have a stronger relationship with long-term climate patterns than with annual weather in either 2002 or 2003. WNv incidence increased with mean May-July temperature and had a unimodal relationship with total May-July precipitation. WNv incidence also increased with the percentage of irrigated cropland and with the percentage of the human population living in rural areas.The spatial pattern of WNv cases during the 2003 epidemic in the northern Great Plains was associated with both climatic gradients and land use patterns. These results were interpreted as evidence that environmental conditions across much of the northern Great Plains create a favorable ecological niche for Culex tarsalis, a particularly efficient vector of WNv. Further research is needed to determine the proximal causes of sustained WNv transmission and to enhance strategies for disease prevention.

We demonstrate and characterize junctionless tri-gate InGaAs MOSFETs, fabricated using a simplified process with gate lengths down to Lg = 25 nm at a nanowire dimension of 7 × 16 nm2. These devices use a single 7-nm-thick In0.80Ga0.20As (ND = 1 × 1019 cm−3) layer as both channel and contacts. The devices show SSsat = 76 mV/dec, peak gm = 1.6 mS/µm and ION = 160 µA/µm (at IOFF = 100 nA/µm and VDD = 0.5 V), the latter which is the highest reported value for a junctionless FET. We also show that device performance is mainly limited by high parasitic access resistance due to the narrow and thin contact layer. [ABSTRACT FROM AUTHOR]

III–V nanowire transistors are promising candidates for very high frequency electronics applications. The improved electrostatics originating from the gate-all-around geometry allow for more aggressive scaling as compared with planar field-effect transistors, and this can lead to device operation at very high frequencies. The very high mobility possible with In-rich devices can allow very high device performance at low operating voltages. GaN nanowires can take advantage of the large band gap for high voltage operation. In this paper, we review the basic physics and device performance of nanowire field- effect transistors relevant for high frequency performance. First, the geometry of lateral and vertical nanowire field-effect transistors is introduced, with special emphasis on the parasitic capacitances important for nanowire geometries. The basic important high frequency transistor metrics are introduced. Secondly, the scaling properties of gate-all-around nanowire transistors are introduced, based on geometric length scales, demonstrating the scaling possibilities of nanowire transistors. Thirdly, to model nanowire transistor performance, a two-band non-parabolic ballistic transistor model is used to efficiently calculate the current and transconductance as a function of band gap and nanowire size. The intrinsic RF metrics are also estimated. Finally, experimental state-of-the-art nanowire field-effect transistors are reviewed and benchmarked, lateral and vertical transistor geometries are explored, and different fabrication routes are highlighted. Lateral devices have demonstrated operation up to 350 GHz, and vertical devices up to 155 GHz. [ABSTRACT FROM AUTHOR]

Integration of III–V semiconductors on Si substrates allows for the realization of high-performance, low power III–V electronics on the Si-platform. In this work, we demonstrate the implementation of single balanced down-conversion mixer circuits, fabricated using vertically aligned InAs nanowire devices on Si. A thin, highly doped InAs buffer layer has been introduced to reduce the access resistance and serve as a bottom electrode. Low-frequency voltage conversion gain is measured up to 7 dB for a supply voltage of 1.5V. Operation of these mixers extends into the GHz regime with a cut-off frequency of 2 GHz, limited by the optical lithography system used. The circuit dc power consumption is measured at 3.9 mW. [ABSTRACT FROM AUTHOR]

Introduction The prudent use of antibiotics in veterinary medicine necessitates the selection of antibiotic compounds with narrow-spectrums targeted against the specific pathogens involved. The same pathotype of enterotoxigenic E. coli (ETEC) was recently found both in diarrhoeic pigs and in samples from the pen floor where the pigs were housed. The first objective of this study was to compare resistance profiles from ETEC isolates and Non-ETEC isolates. The second objective was to evaluate the agreement between resistance profiles of ETEC isolated from pen floor samples and from individual rectal samples from pigs. Across three Danish pig herds, faecal samples were collected from the floors of 31 pens that had a within-pen diarrhoea prevalence of >25%, and from rectal samples of 93 diarrhoeic nursery pigs from the same pens. A total of 380 E. coli isolates were analysed by PCR and classified as ETEC when genes for adhesin factors and enterotoxins were detected. Minimum inhibitory concentrations of 13 antimicrobial agents were determined by the broth micro dilution method. Isolates were classified as resistant based on clinical breakpoints. Results Based on logistic regression models, the odds of Non-ETEC isolates (n = 291) being pan-susceptible were significantly higher compared to ETEC isolates (n = 89), (P < 0.001, OR = 20.22, CI95% = 6.35-64.35). The odds of ETEC isolates having multidrug resistance were significantly higher compared to Non-ETEC isolates (p < 0.001, OR: 7.21, CI95%: 2.87-18.10). The odds of an isolate being resistant were significantly higher in ETEC isolates compared to Non-ETEC isolates for ampicillin (p < 0.001), apramycin (p = 0.003), sulphamethoxazole (p < 0.001) and trimethoprim (p<0.001). No overlap of resistance patterns between the three study herds was observed in the sampled ETEC isolates. In addition, there was generally good or excellent agreement when comparing resistance profiles from isolates from the same pen (pen floor and pig samples), and perfect agreement (Kappa = 1.000, SE = 0.316) was observed for ampicillin, apramycin, gentamycin, sulphamethoxazole, tetracycline and trimethoprim. Conclusions We found that ETEC isolates were more resistant than Non-ETEC isolates. Furthermore, this study indicates that resistance testing of ETEC isolates from pen floor samples can be used as a convenient sampling method for resistance testing and in the selection of clinically relevant antimicrobial agents in the treatment of diarrhoeic pigs. The herd-level variation of resistance in ETEC isolates emphasises the importance of performing antimicrobial susceptibility testing at farm level when selecting antimicrobial agents for the treatment of E. coli -related diarrhoea. [ABSTRACT FROM AUTHOR]

This study presents a novel approach for indirect integration of InAs nanowires on 2'' Si substrates. We have investigated and developed epitaxial growth of InAs nanowires on 2'' Si substrates via the introduction of a thin yet high-quality InAs epitaxial layer grown by metalorganic vapor phase epitaxy. We demonstrate well-aligned nanowire growth including precise position and diameter control across the full wafer using very thin epitaxial layers (<300 nm). Statistical analysis results performed on the grown nanowires across the 2'' wafer size verifies our full control on the grown nanowire with 100% growth yield. From the crystallographic viewpoint, these InAs nanowires are predominantly of wurtzite structure. Furthermore, we show one possible device application of the aforementioned structure in vertical wrap-gated field-effect transistor geometry. The vertically aligned InAs nanowires are utilized as transistor channels and the InAs epitaxial layer is employed as the source contact. A high uniformity of the device characteristics for numerous transistors is further presented and RF characterization of these devices demonstrates an ft of 9.8 GHz. [ABSTRACT FROM AUTHOR]