Charge Gain Research Articles

Increased sensitivity to broadly neutralizing antibodies of end-stage disease R5 HIV-1 correlates with evolution in Env glycosylation and charge.

BackgroundInduction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is the objective of most antibody-based HIV-1 vaccine undertakings. However, despite the relative conserved nature of epitopes targeted by these antibodies, mechanisms underlying the sensitivity of circulating HIV-1 variants to broadly neutralizing antibodies are not fully understood. Here we have studied sensitivity to broadly neutralizing antibodies of HIV-1 variants that emerge during disease progression in relation to molecular alterations in the viral envelope glycoproteins (Env), using a panel of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset.Principal FindingsHIV-1 R5 isolates obtained at end-stage disease, after AIDS onset, were found to be more sensitive to neutralization by TriMab, an equimolar mix of the IgGb12, 2F5 and 2G12 antibodies, than R5 isolates from the chronic phase. The increased sensitivity correlated with low CD4+ T cell count at time of virus isolation and augmented viral infectivity. Subsequent sequence analysis of multiple env clones derived from the R5 HIV-1 isolates revealed that, concomitant with increased TriMab neutralization sensitivity, end-stage R5 variants displayed envelope glycoproteins (Envs) with reduced numbers of potential N-linked glycosylation sites (PNGS), in addition to increased positive surface charge. These molecular changes in Env also correlated to sensitivity to neutralization by the individual 2G12 monoclonal antibody (mAb). Furthermore, results from molecular modeling suggested that the PNGS lost at end-stage disease locate in the proximity to the 2G12 epitope.ConclusionsOur study suggests that R5 HIV-1 variants with increased sensitivity to broadly neutralizing antibodies, including the 2G12 mAb, may emerge in an opportunistic manner during severe immunodeficiency as a consequence of adaptive molecular Env changes, including loss of glycosylation and gain of positive charge.

Photorefractive space charge electric field in GaAs:Cr with external electric and magnetic fields

Using band charge transport model, the effect of external dc electric (E0) and magnetic fields (B0) on photorefractive parameters, viz, space charge electric field (ESC) and gain coefficient in steady state regime is investigated for Cr doped GaAs. In particular, space charge electric field of ∼105 V/cm is obtained for E0=5.0×102 V/cm and B0=0.064 T. ESC obtained is nearly 103 times higher than, in absence of either E0 or B0. The gain coefficient exhibits considerable enhancement at above values of E0 and B0.

The Cardiac Conduction System

The human heart beats 2.5 billion times during a normal lifespan, a feat accomplished by cells of the cardiac conduction system (CCS). The functional components of the CCS can be broadly divided into the impulse-generating nodes and the impulse-propagating His-Purkinje system. Human diseases of the conduction system have been identified that alter impulse generation, impulse propagation, or both. CCS dysfunction is primarily due to acquired conditions such as myocardial ischemia/infarct, age-related degeneration, procedural complications, and drug toxicity. Inherited forms of CCS disease are rare, but each new mutation provides invaluable insight into the molecular mechanisms governing CCS development and function. Applying a multidisciplinary approach, which includes human genetic screening, biophysical analysis, and transgenic mouse technology, has yielded a broad array of gene families involved in maintaining normal CCS physiology (Figure 1). In this review, we discuss gene families that have been implicated in human CCS diseases of rhythm, conduction block, accessory conduction, and development (Table). We also investigate evolving therapeutic strategies that may serve as adjuvant or replacement therapy to current implantable pacemakers. Figure 1. Cardiac conduction system cell. Genes identified in human cardiac conduction system disease are highlighted. View this table: Table. Genetic Basis of Conduction System Disease The human sinoatrial node (SAN) is a crescent-shaped, intramural structure with its head located subepicardially at the junction of the right atrium and the superior vena cava and its tail extending 10 to 20 mm along the crista terminalis.26 The SAN has complex 3-dimensional tissue architecture with central and peripheral components made up of distinct ion channel and gap junction expression profiles.27 Central and peripheral cells have different action potential characteristics and conduction properties (Figure 2).27 Experimental and computational models have demonstrated that SAN heterogeneity is necessary to maintain normal automaticity and impulse conduction.28,–,30 Figure 2. Electrophysiological heterogeneity of the …

The ASPP interaction network: electrostatic differentiation between pro‐ and anti‐apoptotic proteins

The ASPP proteins are apoptosis regulators: ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis. The mechanism by which these different outcomes are achieved is still unknown. The C-terminal ankyrin repeats and SH3 domain (ANK-SH3) mediate the interactions of the ASPP proteins with major apoptosis regulators such as p53, Bcl-2, and NFκB. The structure of the complex between ASPP2(ANK-SH3) and the core domain of p53 (p53CD) was previously determined. We have recently characterized the individual interactions of ASPP2(ANK-SH3) with Bcl-2 and NFκB, as well as a regulatory intramolecular interaction with the proline rich domain of ASPP2. Here we compared the ASPP interactions at two levels: ASPP2(ANK-SH3) with different proteins, and different ASPP family members with each protein partner. We found that the binding sites of ASPP2 to p53CD, Bcl-2, and NFκB are different, yet lie on the same face of ASPP2(ANK-SH3) . The intramolecular binding site to the proline rich domain overlaps the three intermolecular binding sites. To reveal the basis of functional diversity in the ASPP family, we compared their protein-binding domains. A subset of surface-exposed residues differentiates ASPP1 and ASPP2 from iASPP: ASPP1/2 are more negatively charged in specific residues that contact positively charged residues of p53CD, Bcl-2, and NFκB. We also found a gain of positive charge at the non-protein binding face of ASPP1/2, suggesting a role in electrostatic direction towards the negatively charged protein binding face. The electrostatic differences in binding interfaces between the ASPP proteins may be one of the causes for their different function.

Characterization of Co-doped birnessites and application for removal of lead and arsenite

Nanostructured Co-doped birnessites were successfully synthesized, and their application for the removal of Pb 2+ and As(III) from aquatic systems was investigated. Powder X-ray diffraction, chemical analysis, nitrogen physical adsorption, field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS) were used to characterize the crystal structure, chemical composition, micromorphologies and surface properties of the birnessites. Doping cobalt into the layer of birnessite had little effect on its crystal structure and micromorphology. Both chemical and XPS analyses showed that the manganese average oxidation state (Mn AOS) decreased after cobalt doping. The Co dopant existed mainly in the form of Co(III)OOH in the birnessite structure. Part of the doped Co 3+ substituted for Mn 4+, resulting in the gain of negative charge of the layer and an increase in the content of the hydroxyl group, which accounted for the improved Pb 2+ adsorption capacity. The maximum capacity of Pb 2+ adsorption on HB, CoB5, CoB10 and CoB20 was 2538 mmol kg −1, 2798 mmol kg −1, 2932 mmol kg −1 and 3146 mmol kg −1, respectively. The total As(III) removal from solution was 94.30% for CoB5 and 100% for both CoB10 and CoB20, compared to 92.03% for undoped HB, by oxidation, adsorption and fixation, simultaneously.

Micromegas operation in high pressure xenon: charge and scintillation readout

The operational characteristics of a Micromegas operating in pure xenon at the pressure range of 1 to 10 bar are investigated. The maximum charge gain achieved in each pressure is approximately constant, around 4 × 102, for xenon pressures up to 5 bar and decreasing slowly above this pressure down to values somewhat above 102 at 10 bar. The MM presents the highest gains for xenon pressures above 4 bar, when compared to other micropattern gaseous multipliers. The lowest energy resolution obtained for X-rays of 22.1 keV exhibits a steady increase with pressure, from 13% at 1 bar to about 32% at 10 bar. The effective scintillation yield, defined as the number of photons exiting through the MM mesh holes per primary electron produced in the conversion region was calculated. This yield is about 2 × 102 photons per primary electron at 1 bar, increasing to about 6 × 102 at 5 bar and, then, decreasing again to 2 × 102 at 10 bar. The readout of this scintillation by a suitable photosensor will result in higher gains but with increased statistical fluctuations.

A FIRST-PRINCIPLE INVESTIGATION OF BORON- AND NITROGEN-DOPED HETEROFULLERENES

A systematic study of structural, electronic and vibrational properties of boron- and nitrogen-doped heterofullerenes has been performed. N and B doping lead to the structural deformation, and the dopant has a tendency to occupy a single position in a pentagon and two positions in a hexagon which are not adjacent. B -substitution produces clusters of greater thermodynamic stability than N substitution. The C–N and C–B bond lengths lie in the range of 1.40–1.44 Å and 1.53–1.57 Å for hexagon–hexagon (6, 6) and 1.39–1.46 Å and 1.55–1.60 Å at pentagon–hexagon (5, 6) interfaces, respectively. The Mulliken charge analysis shows a charge transfer of -0.30 to -0.45 electrons from N to C atoms; B atom act as electron acceptors with charge gain ranging between -0.59 to -0.70 electrons. N - and B -doping in fullerene molecules present an interesting way to alter electronic and chemical properties of the C 60 molecule for useful device applications.

Underneath the fascinations of carbon nanotubes and graphene nanoribbons

As a new class of materials, carbon nanotubes (CNTs) and graphene nanoribbons (GNRs) have been continuing fascinating the community with properties that can be seen from neither bulk graphite nor diamond. Although the physics and chemistry of these carbon allotropes have been intensively investigated from various perspectives, the laws governing the fascinations and their interdependence remain as yet undetermined. From the perspectives of bond and nonbond formation, dissociation, relaxation, vibration, and the associated energetics and dynamics of charge repopulation, polarization, densification, and localization, this article aims to show that the broken-bond-induced local bond contraction and bond strength gain, quantum entrapment and densification of charge and energy, polarization of the unpaired edge dangling σ-bond electrons, and the formation of the pseudo-π-bond between the dangling σ-bond electrons along the edges are responsible for the anomalies. Theoretical reproduction of the experimentally observed elastic modulus enhancement, melting point depression, layer-number, strain, pressure and temperature induced Raman shift, C 1s core-level positive shift, work function reduction, band gap expansion, edge and defect selective generation of the Dirac-Fermi polarons and the associated magnetism consistently confirmed that the shorter and stronger bonds between undercoordinated carbon atoms modulate locally the atomic cohesive energy, the Hamiltonian, and hence the detectable bulk properties. The polarization of the unpaired dangling σ-bond electrons by the densely, deeply, and locally entrapped core and bonding electrons generates the massless, magnetic and mobile Dirac-Fermi polarons at sites surrounding vacancies and zigzag-GNR edges. The pseudo-π-bond formation between the nearest dangling σ-bond electrons along the armchair-GNR and the reconstructed zigzag-GNR edges discriminates them from the zigzag-GNR edges or vacancies in the electronic and magnetic properties. Consistency between predictions and observations confirmed that the C–C bond contracts by up to 30% with a 152% bond strength gain at the edges with respect to those in the bulk diamond.

Ion Back-Flow Suppression in GEM-MIGAS

The Gas Electron Multiplier with a MIcromegas Gap Amplifying Structure (GEM-MIGAS) is obtained by the coupling of a GEM to a short induction gap, typically 50 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm m}$</tex> </formula> , where additional charge multiplication occurs. In this work, the GEM-MIGAS gain and ion back-flow are investigated, for induction regions in the range of 50–300 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm m}$</tex></formula> . The studies were carried out with a GEM-MIGAS coupled to a semitransparent CsI-photocathode operated in <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">${\rm Ar}/5\%{\rm CH}_{4}$</tex></formula> gas mixture at atmospheric pressure. The increase of the induction gap thickness from 50 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm m}$</tex></formula> to 300 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm m}$</tex></formula> leads to an increase of the maximum achievable charge gain by a factor of 100, from <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim 2\times 10^{3}$</tex></formula> to <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim 2\times 10^{5}$</tex></formula> . Moreover, the high field ratio between amplification and conversion regions, which prevents ions to drift towards the conversion region, allows a strong reduction, by a factor <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim$</tex> </formula> 20, of the ion back-flow ratio to the drift region, when compared with the operation in GEM-mode (i.e. at low induction field). For typical drift fields of 0.1 and 0.5 kV/cm, an ion back-flow fraction <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">$\sim$</tex></formula> 1% and <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex Notation="TeX">$\sim$</tex></formula> 4%, respectively, was obtained for the corresponding charge gains of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim 5\times 10^{4}$</tex></formula> and <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim 2\times 10^{5}$</tex></formula> , respectively.

Linking Surface Potential and Deprotonation in Nanoporous Silica: Second Harmonic Generation and Acid/Base Titration

The adsorption of ions at the oxide/water interface is important for a variety of technological and environmental applications. Understanding ion adsorption is complicated, even for smooth planar surfaces, because it is the result of both chemical and electrostatic effects. Adsorption on rough or porous phases further requires description of the influence of pore geometry. In this work we systematically study ion adsorption and charge development in nanoporous silica. We do so using conventional titration techniques and a noninvasive, all optical method of measuring particle surface potential: second harmonic generation. We find that at pH greater than ≈6.5 surface proton loss is completely compensated by counterion adsorption, leading to little detectable gain in surface charge, and that surface deprotonation above this threshold pH is dominated by internal surface sites. Such a threshold pH, above which acid/base or ion titration curves of porous mineral phases are dominated by adsorption to internal surfaces and surface charge is relatively constant, is expected to be a general feature of the porous oxide/water interface and its explicit consideration important in describing the adsorption of large ions on porous mineral phases and the stability of aqueous suspensions of porous mineral particles. Our results also suggest that the surface of nanoporous silica, synthesized using the method of Stöber, does not polymerize in aqueous solution.

Multiscale three-dimensional simulations of charge gain and transport in diamond

A promising new concept of a diamond-amplified photocathode for generation of high-current, high-brightness, and low thermal emittance electron beams was recently proposed and is currently under active development. Detailed understanding of physical processes with multiple energy and time scales is required to design reliable and efficient diamond-amplifier cathodes. We have implemented models, within the VORPAL computational framework, to simulate secondary electron generation and charge transport in diamond in order to facilitate the investigation of the relevant effects involved. The models include inelastic scattering of electrons and holes for generation of electron-hole pairs, elastic, phonon, and charge impurity scattering. We describe the integrated modeling capabilities we developed and present results on charge gain and collection efficiency as a function of primary electron energy and applied electric field. We compare simulation results with available experimental data. The simulations show an overall qualitative agreement with the observed charge gain from transmission mode experiments and have enabled better understanding of the collection efficiency measurements.

Charge Gain, NBTI, and Random Telegraph Noise in EEPROM Flash Memory Devices

Different charge-gain (CG) processes are reported in EEPROM nonvolatile Flash memory devices. The process originally characterized in nitride-trapping devices is reexamined. Its mechanism is reinterpreted in terms of the recovery of negative-bias temperature instability (NBTI). We show that this CG process is controlled by nonequilibrium random-telegraph-noise-like mechanism, similar to NBTI recovery in MOS devices.

Dependence of space charge field and gain coefficient on the applied electric field in photorefractive materials

Intensity dependent space charge field and gain coefficient in the photorefractive medium due to the two interfering beams have been calculated by solving the material rate equations in presence of externally applied dc electric field. The gain coefficient has been studied with respect to variations in the input intensity, modulation depth, concentration ratio and normalized diffusion field in the absence and presence of the externally applied dc electric field. Space charge field has also been computed by varying the intensity ratio in the presence and absence of the externally applied dc electric field. It has been found that the rate of change of the space charge field with the normalized dc field decreases with the increasing intensity ratio for different values of the normalized diffusion field. It has also been found that the externally applied dc electric field has appreciable effect only when it is larger than the diffusion field.

Local Electrophilicity Predicts the Toxicity-Relevant Reactivity of Michael Acceptors

Electrophilic substances can form covalent bonds to proteins and DNA, resulting in reactive toxicity and according diseases such as dermal or respiratory sensitization and mutagenicity. Employing site-specific quantum chemical parameters for quantifying the energy change associated with the gain or loss of electronic charge, two new local electrophilicity parameters are derived. Application to a set of 31 α,β-unsaturated carbonyl compounds and their experimental rates of reaction toward glutathione as a model nucleophile yields r2 values up to 0.95, outperforming both the global electrophilicity and its earlier introduced local variant based on the condensed-to-atom Fukui function. A second data set demonstrates the suitability of the new reactivity parameters to also model Mayr’s electrophilicity parameter, again superior to existing approaches. The results indicate the suitability of the new parameters to screen, without experimental investigation, organic compounds for their electrophilic reactivity in...

Gain limits of a Thick GEM in high-purity Ne, Ar and Xe

The dependence of the avalanche charge gain in Thick Gas Electron Multipliers (THGEM) on the purity of Ne, Ar and Xe filling gases was investigated. The gain, measured with alpha-particles in standard conditions (atmospheric pressure, room temperature), was found to considerably drop in gases purified by non-evaporable getters. On the other hand, small N2 admixtures to noble gases resulted in high reachable gains. The results are of general relevance in the operation of gas-avalanche detectors in noble gases, particularly that of two-phase cryogenic detectors for rare events.

GEM-MIGAS: Charge gain characteristics for the induction gap in the 50–300 μm range

A conventional gas electron multiplier with its induction gap set around 50μm results in a two stage electron amplification device called the gas electron multiplier with micro-induction gap amplifying structure (GEM-MIGAS). We present results on the charge gain characteristics of GEM-MIGAS induction gap as a function of induction gap thickness, using the single electron response method. In the present study, the induction gap was varied between 50 and 300μm and the GEM-MIGAS was operated in gas flow mode using He/iso-C4H10 (85/15%). The charge gain response agreed well with the classical parallel plate gain formula. From the experimental data, it was possible to derive the approximate values of the ionisation potential threshold and the ionisation mean free path, which exhibits an approximately linear dependence on the induction gap thickness. The optimum gap thickness region, where the charge gain was at a maximum for a given induction voltage and where it was least sensitive to variations in the gap thickness, was found to be in the 50–70μm range. Nevertheless, the highest charge gains, achieved before the onset of detector instabilities, were obtained with the gap thickness set between 150 and 300μm with values reaching the 106 region, owing to the higher voltages that can be applied to the device.

Investigation of avalanche silicon detectors for low energy single ion implantation applications

Avalanche silicon photodiodes have potential applications to detect low energy single ions for counting single ion impacts in shallow implant depths for the deterministic doping of nanoscale electronic devices. This paper reports the investigation of avalanche photodiode detectors in the linear operation mode for detection of 0.5–2 MeV helium ions. The measured charge gain was found to be up to 100 depending on bias voltage. The charge gain was found to saturate at a level that correlated with the ion stopping depth in silicon. The measured charge gain for energetic ions, which have a well-defined depth in a silicon substrate for the deposition of ionization energy, is compared with that of X-rays and photons, which deposit the ionization energy over a wider range of depth. This allowed the identification of a suitable structure for an avalanche photodiode optimised for the detection of sub-10 keV heavy ions with an internal charge gain above 10 achievable. This offers significant advantages over conventional PIN devices where the signals from such ions would be lost in the noise.

Guard-Ring Structures for Silicon Photomultipliers

Si photomultipliers with three different guard-ring structures are fabricated, and a detailed comparative study on their device performances is performed. The virtual guard-ring structure shows a high-resolution full width at half maximum in the gamma spectrum and a high breakdown voltage of ~ 66 V but the lowest fill factor of 46.6%-59.8% among the examined structures. The best charge conversion performance, gain, and fill factor (67.1%) are achieved with the trench guard-ring structure. However, this structure shows a low energy resolution, which is supposed to be due to the trench-associated defects. The performance of the N-implantation guard-ring structure is intermediate in most aspects of the device performance compared to the other structures.

LiMSO4F (M = Fe, Co and Ni): promising new positive electrode materials through the DFT microscope

A theoretical study of the lithium intercalated LiMSO(4)F and deintercalated MSO(4)F systems, where M = Fe, Co and Ni has been performed within the framework of density functional theory. Beyond predictions of structural evolution and average voltages versus a lithium electrode, we have applied partial density of states and Bader's topological analysis of the electron density to the study of lithium deintercalation. Upon lithium extraction, charge rearrangement occurs for nickel between different d-orbitals, but with little net positive charge gain, while cobalt and iron atoms end up with a clear oxidized state. The participation of oxygen ions in accepting the electron of the lithium is thus enhanced for LiNiSO(4)F. However, this effect does not affect the long-range electrostatic interactions a lot in the lithiated phase, since the valence of all transition metals is very close due to initial lower oxidized state for the Ni atom in the host. It is found that this is not essentially a long-range electrostatic interaction within the lithiated phase but within the host which explains, at least partly, the increase in voltage by passing from Fe to Ni. Our results also shed light upon the possibility of getting an approximate evaluation of the local strain associated with delithiation from the atomic volume evolutions, which are also likely to affect the electrochemical potential.

GEM-MIGAS Electron Multiplier Operation in Argon-Methane Mixtures

A Gas Electron Multiplier with a Micro-Induction Gap Amplifying Structure (GEM-MIGAS) is formed when a conventional GEM is operated with a short induction gap, typically 50 mum. A three-dimensional electric field simulation of a GEM-MIGAS detector was performed in order to evaluate the electric field profile in the different regions of the structure. Different electrostatic conditions were undertaken to forecast the detector performance in gas medium. An experimental study of GEM-MIGAS operating in an Ar/CH4 (90/10%) gas mixture, in pure CH4 and in pure Ar was carried out. Performance characteristics including charge gain and energy resolution for 5.9 keV X-rays are presented.