Instituto de Física de Buenos Aires

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT's effects. The present findings advance on previous work by confirming a predominant action of DMT-and likely other 5-HT2AR agonist psychedelics-on the brain's transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.

We present an investigation of the fast decompression of a three-dimensional (3D) Bose-Einstein condensate (BEC) at finite temperature using an engineered trajectory for the harmonic trapping potential. Taking advantage of the scaling invariance properties of the time-dependent Gross-Pitaevskii equation, we exhibit a solution yielding a final state identical to that obtained through a perfectly adiabatic transformation, in a much shorter time. Experimentally, we perform a large trap decompression and displacement within a time comparable to the final radial trapping period. By simultaneously monitoring the BEC and the non-condensed fraction, we demonstrate that our specific trap trajectory is valid both for a quantum interacting many-body system and a classical ensemble of non-interacting particles. Copyright © EPLA, 2011.

The photonic spin Hall effect in transmission is a transverse beam shift of the out-coming beam depending on polarization of the incoming beam. The effect can be significantly enhanced by materials with high anisotropy. We report, to the best of our knowledge, the first experimental demonstration of the photonic spin Hall effect in a multilayer hyperbolic metamaterial at visible wavelengths (wavelengths of 520 and 633 nm). The metamaterial is composed of alternating layers of gold and alumina with deeply subwavelength thicknesses, exhibiting extremely large anisotropy. The angle-resolved polarimetric measurements showed the shift of 165 μm for the metamaterial of 176 nm in thickness. Additionally, the transverse beam shift is extremely sensitive to the variations of the incident angle changing theoretically by 270 μm with 1 milli-radian (0.057°). These features can lead to minituarized spin Hall switches and filters with high angular resolution.

The use of low sub-perceptual doses of psychedelics ("microdosing") has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

Work is an essential concept in classical thermodynamics, and in the quantum regime, where the notion of a trajectory is not available, its definition is not trivial. For driven (but otherwise isolated) quantum systems, work can be defined as a random variable, associated with the change in the internal energy. The probability for the different values of work captures essential information describing the behaviour of the system, both in and out of thermal equilibrium. In fact, the work probability distribution is at the core of "fluctuation theorems" in quantum thermodynamics. Here we present the design and implementation of a quantum work meter operating on an ensemble of cold atoms, which are controlled by an atom chip. Our device not only directly measures work but also directly samples its probability distribution. We demonstrate the operation of this new tool and use it to verify the validity of the quantum Jarzynksi identity.

A search is made for potential ccc[over ¯]c[over ¯] tetraquarks decaying into a pair of charmonium states in the four muon final state using proton-proton collision data at sqrt[s]=13 TeV, corresponding to an integrated luminosity of 140 fb^{-1} recorded by the ATLAS experiment at LHC. Two decay channels, J/ψ+J/ψ→4μ and J/ψ+ψ(2S)→4μ, are studied. Backgrounds are estimated based on a hybrid approach involving Monte Carlo simulations and data-driven methods. Statistically significant excesses with respect to backgrounds dominated by the single parton scattering are seen in the di-J/ψ channel consistent with a narrow resonance at 6.9 GeV and a broader structure at lower mass. A statistically significant excess is also seen in the J/ψ+ψ(2S) channel. The fitted masses and decay widths of the structures are reported.

Human brain dynamics and functional connectivity fluctuate over a range of temporal scales in coordination with internal states and environmental demands. However, the neurobiological significance and consequences of functional connectivity dynamics during rest have not yet been established. We show that the coarse-grained clustering of whole-brain dynamic connectivity measured with magnetic resonance imaging reveals discrete patterns (dynamic connectivity states) associated with wakefulness and sleep. We validate this using EEG in healthy subjects and patients with narcolepsy and by matching our results with previous findings in a large collaborative database. We also show that drowsiness may account for previous reports of metastable connectivity states associated with different levels of functional integration. This implies that future studies of transient functional connectivity must independently monitor wakefulness. We conclude that a possible neurobiological significance of dynamic connectivity states, computed at a sufficiently coarse temporal scale, is that of fluctuations in wakefulness.

A bstract A direct search for Higgs bosons produced via vector-boson fusion and subsequently decaying into invisible particles is reported. The analysis uses 139 fb − 1 of pp collision data at a centre-of-mass energy of $$ \sqrt{s} $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msqrt> <mml:mi>s</mml:mi> </mml:msqrt> </mml:math> = 13 TeV recorded by the ATLAS detector at the LHC. The observed numbers of events are found to be in agreement with the background expectation from Standard Model processes. For a scalar Higgs boson with a mass of 125 GeV and a Standard Model production cross section, an observed upper limit of 0 . 145 is placed on the branching fraction of its decay into invisible particles at 95% confidence level, with an expected limit of 0 . 103. These results are interpreted in the context of models where the Higgs boson acts as a portal to dark matter, and limits are set on the scattering cross section of weakly interacting massive particles and nucleons. Invisible decays of additional scalar bosons with masses from 50 GeV to 2 TeV are also studied, and the derived upper limits on the cross section times branching fraction decrease with increasing mass from 1 . 0 pb for a scalar boson mass of 50 GeV to 0 . 1 pb at a mass of 2 TeV.

We present the first results from a dark matter search using six Skipper-CCDs in the SENSEI detector operating at SNOLAB. We employ a bias-mitigation technique of hiding approximately 46% of our total data and aggressively mask images to remove backgrounds. Given a total exposure after masking of 100.72 gram-days from well-performing sensors, we observe 55 two-electron events, 4 three-electron events, and no events containing 4-10 electrons. The two-electron events are consistent with pileup from one-electron events. Among the 4 three-electron events, 2 appear in pixels that are likely impacted by detector defects, although not strongly enough to trigger our "hot-pixel" mask. We use these data to set world-leading constraints on sub-GeV dark matter interacting with electrons and nuclei.

BACKGROUND: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. AIMS: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. "set" and "setting"), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. METHODS: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. RESULTS: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. CONCLUSIONS: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

Background: Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. Methods: This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). Findings: A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Interpretation: Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. Funding: This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

We apply divergence-type theory (DTT) dissipative hydrodynamics to study the $2+1$ space-time evolution of the fireball created in Au$+$Au relativistic heavy-ion collisions at $\sqrt{{s}_{\mathit{NN}}}=200$ GeV. DTTs are exact hydrodynamic theories that do not rely on velocity gradient expansions and therefore go beyond second-order theories. We numerically solve the equations of motion of the DTT for Glauber initial conditions and compare the results with those of second-order theory based on conformal invariance (Baier-Romatschke-Son-Starinets model) and with data. We find that the charged-hadron minimum-bias elliptic flow reaches its maximum value at lower ${p}_{T}$ in the DTT, and that the DTT allows for a value of $\ensuremath{\eta}/s$ slightly larger than that of the BRSS. Our results show that the differences between viscous hydrodynamic formalisms are a significant source of uncertainty in the precise extraction of $\ensuremath{\eta}/s$ from experiments.

Second harmonic generation and two‐photon photoluminescence in CdS quantum dots near metallic nanoparticles are theoretically and experimentally investigated. A control laser field is applied to the hybrid system, which couples with the surface plasmons of the metal nanoparticles. The polarized metal nanoparticles then interact with the quantum dots through dipole–dipole interactions, which enhances the intensity of the second harmonic signal from the quantum dots. The density matrix method is used to numerically simulate the second harmonic signal emitted by the quantum dots. It is found that the enhancement of the second harmonic signal can be switched on and off by changing the control field intensity. Alternatively, the second harmonic signal enhancement can be turned on or off by changing the frequency of the control field. This is an interesting finding which can be used to fabricate nonlinear all optical nanoswitching devices from hybrid systems.

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of nonrapid-eye-movement (NREM) sleep is the shift from high-frequency, low-amplitude wake EEG to low-frequency, high-amplitude sleep EEG dominated by spindles and slow waves. Here we identified signatures of sleep in brain hemodynamic activity, using simultaneous functional MRI (fMRI) and EEG. We found that, at the transition from wake to sleep, fMRI blood oxygen level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (<0.1 Hz) oscillation prominent in light sleep and correlated with the occurrence of spindles, and a high-frequency oscillation (>0.1 Hz) prominent in deep sleep and correlated with the occurrence of slow waves. The two oscillations were both detectable across the brain but exhibited distinct spatiotemporal patterns. During the falling-asleep process, the low-frequency oscillation first appeared in the thalamus, then the posterior cortex, and lastly the frontal cortex, while the high-frequency oscillation first appeared in the midbrain, then the frontal cortex, and lastly the posterior cortex. During the waking-up process, both oscillations disappeared first from the thalamus, then the frontal cortex, and lastly the posterior cortex. The BOLD oscillations provide local signatures of spindle and slow wave activity. They may be employed to monitor the regional occurrence of sleep or wakefulness, track which regions are the first to fall asleep or wake up at the wake-sleep transitions, and investigate local homeostatic sleep processes.

We consider the dissipative charging process of quantum batteries in terms of a collisional model, where the batteries are coupled to a heat bath using nonenergy preserving interactions. First, we show that for low temperatures, the collective process can attain a charging power that increases polynomially with the number of batteries. The scaling we find is ${N}^{3}$ which, while being greater than the bound obtained for unitary processes, has a lower efficiency. Then, we study the dissipative charging process of a single battery using a time-dependent Hamiltonian that generates coherences in the energy basis. In this case, we find that the presence of coherence could enhance the charging power and also its efficiency. Finally, we show how this process can be used in a quantum heat engine that contains the charging process as one of its open strokes.

We study the asymptotic dynamics of arbitrary linear quantum open systems that are periodically driven while coupled with generic bosonic reservoirs. We obtain exact results for the heat flowing from each reservoir, and these results are valid beyond the weak-coupling or Markovian approximations. We prove the validity of the dynamical third law of thermodynamics (Nernst unattainability principle), showing that the ultimate limit for cooling is imposed by a fundamental heating mechanism that dominates at low temperatures, namely the nonresonant creation of excitation pairs in the reservoirs induced by the driving field. This quantum effect, which is missed in the weak-coupling approximation, restores the unattainability principle, the validity of which was recently challenged.

We demonstrate experimentally the lateral circular birefringence of a tunable birefringent polymer, the first example of the spin Hall effect of light in a polymeric material, and we demonstrate that this light shift can be significantly enhanced by tuning the effective birefringence in the polymer. We report experimental observations of this effect using polarimetric techniques and quantum-weak-measurement techniques, reporting a weak amplification factor of 200.

Abstract This paper presents the observation of four-top-quark ( $$t\bar{t}t\bar{t}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> </mml:mrow> </mml:math> ) production in proton-proton collisions at the LHC. The analysis is performed using an integrated luminosity of 140 $$\hbox {fb}^{-1}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mtext>fb</mml:mtext> <mml:mrow> <mml:mo>-</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> </mml:math> at a centre-of-mass energy of 13 TeV collected using the ATLAS detector. Events containing two leptons with the same electric charge or at least three leptons (electrons or muons) are selected. Event kinematics are used to separate signal from background through a multivariate discriminant, and dedicated control regions are used to constrain the dominant backgrounds. The observed (expected) significance of the measured $$t\bar{t}t\bar{t}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> </mml:mrow> </mml:math> signal with respect to the standard model (SM) background-only hypothesis is 6.1 (4.3) standard deviations. The $$t\bar{t}t\bar{t}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> </mml:mrow> </mml:math> production cross section is measured to be $$22.5^{+6.6}_{-5.5}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>22</mml:mn> <mml:mo>.</mml:mo> <mml:msubsup> <mml:mn>5</mml:mn> <mml:mrow> <mml:mo>-</mml:mo> <mml:mn>5.5</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>6.6</mml:mn> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:math> fb, consistent with the SM prediction of $$12.0 \pm 2.4$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>12.0</mml:mn> <mml:mo>±</mml:mo> <mml:mn>2.4</mml:mn> </mml:mrow> </mml:math> fb within 1.8 standard deviations. Data are also used to set limits on the three-top-quark production cross section, being an irreducible background not measured previously, and to constrain the top-Higgs Yukawa coupling and effective field theory operator coefficients that affect $$t\bar{t}t\bar{t}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> <mml:mi>t</mml:mi> <mml:mover> <mml:mrow> <mml:mi>t</mml:mi> </mml:mrow> <mml:mrow> <mml:mo>¯</mml:mo> </mml:mrow> </mml:mover> </mml:mrow> </mml:math> production.

We briefly review an important shortcoming---unearthed in previous works---of the standard version of the inflationary model for the emergence of the seeds of cosmic structure. We consider here some consequences emerging from a proposal inspired on ideas of Penrose and Di\'osi [R. Penrose, The Emperor's New Mind. Concerning Computers, Minds and Laws of Physics (1989).][R. Penrose, in Physics meets Philosophy at the Planck Scale: Contemporary Theories in Quantum Gravity, edited by C. Callendar and N. Huggett (2001), pp. 290--+.][L. Di\'osi, Phys. Lett. A 120, 377 (1987).][L. Di\'osi, Phys. Rev. A 40, 1165 (1989).] about a quantum-gravity induced reduction of the wave function, which has been put forward to address the shortcomings, arguing that its effect on the inflaton field is what can lead to the emergence of the seeds of cosmic structure [A. Perez, H. Sahlmann, and D. Sudarsky, Classical Quantum Gravity 23, 2317 (2006).]. The proposal leads to a deviation of the primordial spectrum from the scale-invariant Harrison-Zel'dovich one, and consequently, to a different CMB power spectrum. We perform statistical analyses to test two quantum collapse schemes with recent data from the CMB, including the 7-yr release of WMAP and the matter power spectrum measured using LRGs by the Sloan Digital Sky Survey. Results from the statistical analyses indicate that several collapse models are compatible with CMB and LRG data, and establish constraints on the free parameters of the models. The data put no restriction on the timescale for the collapse of the scalar field modes.