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The exploration of the fundamental nature of matter is the central quest of high-energy physics. In particular, collisions of particles at energies above [10.sup.11] eV are required to test some [...], Plasmas are an attractive medium for the next generation of particle accelerators because they can support electric fields greater than several hundred gigavolts per meter. These accelerating fields are generated by relativistic plasma waves--space-charge oscillations--that can be excited when a high-intensity laser propagates through a plasma. Large currents of background electrons can then be trapped and subsequently accelerated by these relativistic waves. In the forced laser wake field regime, where the laser pulse length is of the order of the plasma wavelength, we show that a gain in maximum electron energy of up to 200 megaelectronvolts can be achieved, along with an improvement in the quality of the ultrashort electron beam.

Using significant technological breakthroughs and unconventional approaches, the goal of the in situ probing of glacier ice for a better understanding of the orbital response of climate (SUBGLACIOR) project is to advance ice core research by inventing, constructing and testing an in situ probe to evaluate if a target site is suitable for recovering ice as old as 1.5 million years. Embedding a laser spectrometer, the probe is intended to make its own way down into the ice and to measure, in real time and down to the bedrock, the depth profiles of the ice dD water isotopes as well as the trapped CH4 gas concentration and dust concentration. The probe descent is achieved through electromechanical drilling combined with continuous meltwater sample production using a central melting finger in the drill head. A key aspect of the project lies in the design and implementation of an efficient method to continuously transfer to the surface the ice chips being produced by the drill head and from the refreezed water expulsed downstream from the melting finger, into the borehole. This paper presents a detailed calculation and analysis of the flow rates and pressure conditions required to overcome friction losses of the drilling fluid and to effectively transport ice chips to the surface. [ABSTRACT FROM AUTHOR]

The article discusses a research note discussing one aspect of an ongoing investigation into the symbolic interpretation of the sanctuary of Our Lady of Aparecida in southeastern Brazil, which is considered the largest Marian pilgrimage site in the world. Information about the statue of Our Lady of Immaculate Conception of Aparecida as well as the construction of a Baroque church in 1834 at the end of the colonial period is presented.

In Brazil, religion influences many aspects of the everyday life of most citizens. But despite this ubiquity, Brazil has favored a strong separation between church and state. Whilst these two realities are by no means incompatible, I ask the question: in a society where religion is ubiquitous, how does state secularism function? As I attempt an answer, I discuss some of the meanings associated with the term "secularism," whilst critically engaging with the idea underpinning much of our sociological understanding of secularism, namely Max Weber's differentiation of "value spheres." I ground the more theoretical part of the argument on the much-publicized "shift" from Catholicism to Protestantism that has occurred in Brazil in the past three decades. I argue that this shift is forcing a more fluid relationship between Brazil's secular and religious spheres. As a result, the institutional and constitutional boundaries between these spheres could be considered porous. This insight reveals a Brazilian-style state secularism that is more inclined toward accommodation than conflict. [ABSTRACT FROM AUTHOR]

In response to the 'oldest ice' challenge initiated by the International Partnerships in Ice Core Sciences (IPICS), new rapid-access drilling technologies through glacier ice need to be developed. These will provide the information needed to qualify potential sites on the Antarctic ice sheet where the deepest section could include ice that is >1 Ma old and still in good stratigraphic order. Identifying a suitable site will be a prerequisite for deploying a multi-year deep ice-core drilling operation to elucidate the cause and mechanisms of the mid-Pleistocene transition from 40 ka glacial-interglacial cycles to 100 ka cycles. As part of the ICE&LASERS/SUBGLACIOR projects, we have designed an innovative probe, SUBGLACIOR, with the aim of perforating the ice sheet down to the bedrock in a single season and continuously measuring in situ the isotopic composition of the melted water and the methane concentration in trapped gases. Here we present the general concept of the probe, as well as the various technological solutions that we have favored so far to reach this goal. [ABSTRACT FROM AUTHOR]

This paper describes a versatile, light weight, and portable chamber dedicated to the transfer of electrodes from ultra-high vacuum (UHV) to atmospheric pressure and the liquid phase. This chamber can be connected to a liquid-phase reaction cell to perform electrochemical measurements and transfer back the electrode to the UHV environment. The experimental set-up can also be turned in order to make the electrode the bottom of the electrochemical cell. The validity and the efficiency of the experimental set-up were tested with a Pt(111) surface that provides unique electrochemical features in acidic sulphate-containing solution. This transfer chamber concept provides the surface science community with a new and versatile tool, complementary to existing systems, which allows fast electrolyte purging or electrochemical measurements under well-controlled mass transport conditions. [ABSTRACT FROM AUTHOR]

Previous reports have indicated the anomalous excitation rate for the 6.2 keV nuclear level of 181Ta in a plasma produced with a femtosecond laser. A detailed characterization of the electrons and x-ray sources produced in such a plasma is required to interpret these results. In a preliminary work, the continuous energy distribution of hard x rays (10–500 keV) produced in the interaction of a kilohertz femtosecond laser beam with a tantalum solid target is investigated in the 3×1015–6×1016 W/cm2 range of intensity. A sodium iodide detector with appropriate shielding is used. Strong collimation and absorption filters are used to avoid the pileup of photons in the detector. The response function of this setup is calculated with the GEANT3 simulation code. We demonstrate the necessity to quantify the Compton scattered events in the raw spectra in order to restore the absolute x-ray energy distribution. [ABSTRACT FROM AUTHOR]

The total excitation probability of the 1 s σ molecular orbital on the way into the nuclear reactionNi+Fe at 238 MeV has been directly measured. The result found is (3.1±0.6) 10. The method is based on the detection at zero degree with respect to the beam direction of the x-rays emitted in the reaction, in coincidence with the gamme rays following the deexcitation of the evaporation residues produced in the nuclear reaction. The difference in the doppler shift of the x-ray energies enables to discriminate between the internal conversion x-rays and the prompt atomic x-rays following the decay of the vacancies made in the approach of the nuclear reaction. The experimental data is compared with numerical evaluations of different mechanisms which can produce a vacancy in the K-shell of the united atom at the end of the collision. The best agreement is found with the value of the direct ionization of the 1 sσ MO evaluated in the framework of the Brigg's model. [ABSTRACT FROM AUTHOR]

The7Be(p,γ)8B cross section has been re-measured using radioactive targets. The zero-energy astrophysical S-factor is found significantly lower than the previously adopted value. [ABSTRACT FROM AUTHOR]

Projectile and target X-ray cross-sections have been measured in collisions of bare and hydrogenlike Silicon ions with argon atoms. Projectile energies are 125 MeV and 153 MeV, i.e. the intermediate velocity region for K-shell capture. Coincidence measurements between X-ray photons and the scattered Si projectiles with charge states n-1, n-2 and n-3 have been made. The relative contribution of charge exchange and direct ionization (or excitation) of the target K-shell has been obtained directly by this new method. Double K-shell electron transfer is demonstrated to be very large in the case of fully stripped Si ions. A thorough theoretical analysis of the data is carried out and multiple capture processes are evaluated using an independent electron model. [ABSTRACT FROM AUTHOR]

We have remeasured the K-shell vacancy production probability P across the 460-keVC( p, p) resonance, previously investigated by Duinker et al. We are unable to confirm the large (∼70 %) variation of P across the resonance, found by Duinker et al. for protons elastically scattered at 125°. Our values for the ratio P(142°)/ P(16°) are independent (within±20%) of the proton bombarding energy over the resonance region, in agreement with theoretical predictions by Blair and Anholt, Feagin and Kocbach, McVoy and Weidenmüller. Our average value for this ratio, equal to 0.88 ±0.06, agrees with the value 0.88 calculated by Amundsen and Aashamar. [ABSTRACT FROM AUTHOR]

The impact parameter dependence of the ionization of Gold L-subshells has been measured and compared to theoretical values calculated in the SCA framework by Aashamar et al. [17]. Special attention has been paid to large scattering angle measurements and results are obtained for 0=30°, 45°, 65°, 90°, 110°, 130°, 153° and 166°. Taking into account the sum of L, L, L, L, L lines we conclude firstly that the experimental ionization probability P(b) is in good agreement with the theoretical values. Secondly, comparing experimental and theoretical intensity of ( L+ L) and ( L+ L) X-ray lines, we show that ionization of L and L subshells is also fairly well described by the SCA model. [ABSTRACT FROM AUTHOR]

The Ca V 3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability of nociceptive neurons; the endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover a novel peptide albumin (1-26) that facilitates channel gating by chelating trace metals that tonically inhibit Ca V 3.2 via H191 residue. Importantly, serum also potently modulated T-currents in human and rodent dorsal root ganglion (DRG) neurons. In vivo pain studies revealed that injections of serum and albumin (1-26) peptide resulted in robust mechanical and heat hypersensitivity. This hypersensitivity was abolished with a T-channel inhibitor, in Ca V 3.2 null mice and in Ca V 3.2 H191Q knock-in mice. The discovery of endogenous chelators of trace metals in the serum deepens our understanding of the role of Ca V 3.2 channels in neuronal hyperexcitability and may facilitate the design of novel analgesics with unique mechanisms of action.

Background and Purpose: Voltage sensitivity is a common feature of many membrane proteins, including some G-protein coupled receptors (GPCRs). However, the functional consequences of voltage sensitivity in GPCRs are not well understood., Experimental Approach: In this study, we investigated the voltage sensitivity of the post-synaptic metabotropic glutamate receptor mGlu 5 and its impact on synaptic transmission. Using biosensors and electrophysiological recordings in non-excitable HEK293T cells or neurons., Key Results: We found that mGlu 5 receptor function is optimal at resting membrane potentials. We observed that membrane depolarization significantly reduced mGlu 5 receptor activation, Gq-PLC/PKC stimulation, Ca 2+ release and mGlu 5 receptor-gated currents through transient receptor potential canonical, TRPC6, channels or glutamate ionotropic NMDA receptors. Notably, we report a previously unknown activity of the NMDA receptor at the resting potential of neurons, enabled by mGlu 5 ., Conclusions and Implications: Our findings suggest that mGlu 5 receptor activity is directly regulated by membrane voltage which may have a significant impact on synaptic processes and pathophysiological functions., (© 2024 British Pharmacological Society.)

Protein film electrochemistry is a technique in which an enzyme is immobilized on an electrode in a configuration that allows following the changes in turnover frequency as a response to changes in the experimental conditions. Insights into the reactivity of the enzyme can be obtained by quantitatively modeling such responses. As a consequence, the more the technique allows flexibility in changing conditions, the more useful it becomes. The most commonly used setup, based on the rotating disc electrode, allows easy stepwise increases in the concentration of nongaseous substrates, or exposure to constant concentration of dissolved gas, but does not permit to easily decrease the concentration of nongaseous substrates, or to change the concentration of dissolved gas in a stepwise fashion. To overcome the limitation by mass transport of the substrate toward the electrode when working with fast enzymes, we have designed another kind of electrochemical cell based on the wall-tube electrode (WTE). We demonstrate here that by using a system combining two syringe pumps, a commercial mixer, and the WTE, it is possible to change the concentration of species in a stepwise fashion in all directions, opening new possibilities to study redox enzymes. As a proof of concept, this device was applied to the study of the electrochemical response of the cytochrome c nitrite reductase of Desulfovibrio desulfuricans .

The recent development of single-cell and single-nucleus RNA sequencing has highlighted the extraordinary diversity of dorsal root ganglia neurons. However, the few available genetic tools limit our understanding of the functional significance of this heterogeneity. We generated a new mouse line expressing the flippase recombinase from the scn10a locus. By crossing Na v 1.8 Ires-FLPo mice with the Advillin Cre and RC::FL-hM3Dq mouse lines in an intersectional genetics approach, we were able to obtain somatodendritic expression of hM3Dq-mCherry selectively in the Na v 1.8 lineage. The bath application of clozapine N-oxide triggered strong calcium responses selectively in mCherry + neurons. The intraplantar injection of CNO caused robust flinching, shaking, and biting responses accompanied by strong cFos activation in the ipsilateral lumbar spinal cord. The Na v 1.8 Ires-FLPo mouse model will be a valuable tool for extending our understanding of the in vivo functional specialization of neuronal subsets of the Na v 1.8 lineage for which inducible Cre lines are available., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that might influence the work reported in this study., (© 2024 The Author(s).)

L-type voltage-gated calcium channels are involved in multiple physiological functions. Currently available antagonists do not discriminate between L-type channel isoforms. Importantly, no selective blocker is available to dissect the role of L-type isoforms Ca v 1.2 and Ca v 1.3 that are concomitantly co-expressed in the heart, neuroendocrine and neuronal cells. Here we show that calciseptine, a snake toxin purified from mamba venom, selectively blocks Ca v 1.2 -mediated L-type calcium currents (I CaL ) at concentrations leaving Ca v 1.3-mediated I CaL unaffected in both native cardiac myocytes and HEK-293T cells expressing recombinant Ca v 1.2 and Ca v 1.3 channels. Functionally, calciseptine potently inhibits cardiac contraction without altering the pacemaker activity in sino-atrial node cells, underscoring differential roles of Ca v 1.2- and Ca v 1.3 in cardiac contractility and automaticity. In summary, calciseptine is a selective L-type Ca v 1.2 Ca 2+ channel blocker and should be a valuable tool to dissect the role of these L-channel isoforms., (© 2024. The Author(s).)

We set up an in silico experiment and designed a chimeric compound integrating molecular features from different efficient ROS (Reactive Oxygen Species) scavengers, with the purpose of investigating potential relationships between molecular structure and antioxidant activity. Furthermore, a selenium centre was inserted due to its known capacity to reduce hydroperoxides, acting as a molecular mimic of glutathione peroxidase; finally, since this organoselenide is a precursor of a N-heterocyclic carbene ligand, its Au(I) carbene complex was designed and examined. A validated protocol based on DFT (Density Functional Theory) was employed to investigate the radical scavenging activity of available sites on the organoselenide precursor ((SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)), as well as on the organometallic complex ((SMD)-M06-2X/SDD (Au), 6-311+G(d,p)//ZORA-BLYP-D3(BJ)/TZ2P), considering HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation) regarding five different radicals. The results of this case study suggest that the antioxidant potential of chemical motifs should not be considered as an additive property when designing a chimeric compound, but rather that the relevance of a molecular topology is derived from a chemical motif combined with an opportune chemical space of the molecule. Thus, the direct contributions of single functional groups which are generally thought of as antioxidants per se do not guarantee the efficient radical scavenging potential of a molecular species.

Venom-derived peptides targeting ion channels involved in pain are regarded as a promising alternative to current, and often ineffective, chronic pain treatments. Many peptide toxins are known to specifically and potently block established therapeutic targets, among which the voltage-gated sodium and calcium channels are major contributors. Here, we report on the discovery and characterization of a novel spider toxin isolated from the crude venom of Pterinochilus murinus that shows inhibitory activity at both hNa V 1.7 and hCa V 3.2 channels, two therapeutic targets implicated in pain pathways. Bioassay-guided HPLC fractionation revealed a 36-amino acid peptide with three disulfide bridges named μ/ω-theraphotoxin-Pmu1a (Pmu1a). Following isolation and characterization, the toxin was chemically synthesized and its biological activity was further assessed using electrophysiology, revealing Pmu1a to be a toxin that potently blocks both hNa V 1.7 and hCa V 3. Nuclear magnetic resonance structure determination of Pmu1a shows an inhibitor cystine knot fold that is the characteristic of many spider peptides. Combined, these data show the potential of Pmu1a as a basis for the design of compounds with dual activity at the therapeutically relevant hCa V 3.2 and hNa V 1.7 voltage-gated channels., (© 2023 Federation of European Biochemical Societies.)

Protein Film Electrochemistry is a technique in which a redox enzyme is directly wired to an electrode, which substitutes for the natural redox partner. In this technique, the electrical current flowing through the electrode is proportional to the catalytic activity of the enzyme. However, in most cases, the amount of enzyme molecules contributing to the current is unknown and the absolute turnover frequency cannot be determined. Here, we observe the formation of electrocatalytically active films of E. coli hydrogenase 1 by rotating an electrode in a sub-nanomolar solution of enzyme. This process is slow, and we show that it is mass-transport limited. Measuring the rate of the immobilization allows the determination of an estimation of the turnover rate of the enzyme, which appears to be much greater than that deduced from solution assays under the same conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Metal-based formate dehydrogenases are molybdenum or tungsten-dependent enzymes that catalyze the interconversion between formate and CO 2 . According to the current consensus, the metal ion of the catalytic center in its active form is coordinated by 6 S (or 5 S and 1 Se) atoms, leaving no free coordination sites to which formate could bind to the metal. Some authors have proposed that one of the active site ligands decoordinates during turnover to allow formate binding. Another proposal is that the oxidation of formate takes place in the second coordination sphere of the metal. Here, we have used electrochemical steady-state kinetics to elucidate the order of the steps in the catalytic cycle of two formate dehydrogenases. Our results strongly support the "second coordination sphere" hypothesis., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)