Absence Of Modulation Research Articles

ANAIS–112 three years data: a sensitive model independent negative test of the DAMA/LIBRA dark matter signal

Weakly interacting massive particles (WIMPs) are well-motivated candidates for dark matter. One signature of galactic WIMPs is the annual modulation expected in a detector’s interaction rate, which arises from Earth’s revolution around the Sun. Over two decades, the DAMA/LIBRA experiment has observed such modulation with 250 kg of NaI(Tl) scintillators, in accordance with WIMP expectations but inconsistent with the negative results of other experiments. The signal depends on the target material, so to validate or refute the DAMA result, the experiment must be replicated using the same material. This is the goal of the ANAIS–112 experiment, currently underway since August 2017 with 112.5 kg of NaI(Tl). In this work, we present a reanalysis of three years of data employing an improved analysis chain to enhance the experimental sensitivity. The results presented here are consistent with the absence of modulation and inconsistent with DAMA’s observation at nearly 3σ confidence level, with the potential to reach a 5σ level within 8 years from the beginning of the data collection. Additionally, we explore the impact of different scintillation quenching factors in the comparison between ANAIS–112 and DAMA/LIBRA.

Single-Crystal Three-Dimensional Covalent Organic Framework Constructed from 6-Connected Triangular Prism Node.

The limited structural diversity of three-dimensional covalent organic frameworks (3D COFs) greatly restricts their application exploration. Therefore, there is an urgent need to expand their library of molecular building blocks, such as the development of highly connected (>4 reaction sites) polyhedral nodes. Herein, by precisely controlling the precursor conformation, we rationally designed a new 6-connected triangular prism node derived from the triphenylbenzene molecule and further used it to construct a novel 3D COF (3D-TMTAPB-COF) via imine condensation reaction. Surprisingly, without the addition of competing reagents, 3D-TMTAPB-COF crystallized directly into single crystals of ∼15 μm in size and was determined to adopt a rare 6-fold interpenetrated (Class IIIa interpenetration) acs topology. In addition, 3D-TMTAPB-COF showed a high SF6 adsorption capacity (60.9 cm3 g-1) and good SF6/N2 selectivity (335) at 298 K and 1 bar, superior to those of most crystalline porous materials. This work not only confirms the possibility of growing large-size single-crystal 3D COFs formed with strong covalent bonds by a solvothermal method in the absence of modulators, but also reports a novel triangular prism node for future construction of 3D COFs with interesting applications.

Structure and dynamics of differential ligand binding in the human ρ-type GABAA receptor

The neurotransmitter γ-aminobutyric acid (GABA) drives critical inhibitory processes in and beyond the nervous system, partly via ionotropic type-A receptors (GABAARs). Pharmacological properties of ρ-type GABAARs are particularly distinctive, yet the structural basis for their specialization remains unclear. Here, we present cryo-EM structures of a lipid-embedded human ρ1 GABAAR, including a partial intracellular domain, under apo, inhibited, and desensitized conditions. An apparent resting state, determined first in the absence of modulators, was recapitulated with the specific inhibitor (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid and blocker picrotoxin and provided a rationale for bicuculline insensitivity. Comparative structures, mutant recordings, and molecular simulations with and without GABA further explained the sensitized but slower activation of ρ1 relative to canonical subtypes. Combining GABA with picrotoxin also captured an apparent uncoupled intermediate state. This work reveals structural mechanisms of gating and modulation with applications to ρ-specific pharmaceutical design and to our biophysical understanding of ligand-gated ion channels.

The role of ongoing oscillation in pain perception: Absence of modulation by a concomitant arithmetic task

Sustained nociceptive stimuli have been shown to modulate the amplitude of ongoing neural oscillations in the theta, alpha and beta frequency bands at the frequency of stimulation, suggesting a relationship between these ongoing oscillations and pain perception. Yet, whether these ongoing oscillations are actually related to the pain experience remains unclear. If it were the case, then cognitive processes that are known to affect pain intensity should also affect these ongoing oscillations. To this end, we used electroencephalography (EEG) to investigate whether distraction – an attentional state known to affect pain perception – also modulates the amplitude of these neural oscillations. More specifically, we hypothesized that performing an unrelated arithmetic task during sustained nociceptive stimulation would lead to a decrease in the modulations of ongoing oscillations exerted by the stimulation. To assess the selectivity of this modulation for nociception, we compared the modulations of ongoing oscillations exerted by sustained periodic thermonociceptive and non-nociceptive vibrotactile stimulation (.2 Hz, 75 sec), while participants were either asked to solve an unrelated arithmetic task (distraction task) or received no specific instruction (baseline). The intensity of perception was significantly reduced by the arithmetic task in both the thermonociceptive and the vibrotactile modality, and the sustained periodic stimulation elicited a periodic response at the frequency of stimulation in both modalities. However, the distraction task did not show a differential effect for the two stimulation modalities in any of the frequency bands. The fact that, unlike pain perception, these oscillations did not appear to be affected by the task suggests that they are dissociable from pain perception. Whether a different task (leading to a stronger degree of distraction) could lead to different results is unclear.

Predictive Control of Four-Legged Inverter Using Sliding-Window Discrete Fourier Transform Computation for Harmonic Recession

—Shunt active power filters are the most promising solution for power quality challenges. It injects compensating current at the point of common coupling to recede harmonic content and to attain unity power factor. The proposed control strategy comprises of (a) Model predictive control (MPC) for switching state selection and (b) Sliding-window Discrete fourier transform (SDFT) technique for computing reference compensating current in a four-legged shunt active power filter. This paper incorporates MPC and SDFT control as a single-step algorithm for a four-leg inverter. The absence of modulator, look-up tables and complex mathematical operations support the easy implementation of the proposed controller digitally. The proposed scheme involves unique features like improved cost function in MPC, flexible sampling window size in SDFT, reduced computational complexity and execution time. Also, the compensation principle of the controller requires only line current measurement in contrast to the classical compensation techniques which require the distortion level and reactive power demand of the load. The efficacy of the proposed control method is tested for steady-state, dynamic conditions and parameter uncertainties. The system is validated by simulation using level-2 S-function block in MATLAB/Simulink for various case studies.

Redefining Hypo- and Hyper-Responding Phenotypes of CFTR Mutants for Understanding and Therapy.

Mutations in CFTR cause misfolding and decreased or absent ion-channel function, resulting in the disease Cystic Fibrosis. Fortunately, a triple-modulator combination therapy (Trikafta) has been FDA-approved for 178 mutations, including all patients who have F508del on one allele. That so many CFTR mutants respond well to modulators developed for a single mutation is due to the nature of the folding process of this multidomain protein. We have addressed the question 'What characterizes the exceptions: the mutants that functionally respond either not or extremely well'. A functional response is the product of the number of CFTR molecules on the cell surface, open probability, and conductivity of the CFTR chloride channel. By combining biosynthetic radiolabeling with protease-susceptibility assays, we have followed CF-causing mutants during the early and late stages of folding in the presence and absence of modulators. Most CFTR mutants showed typical biochemical responses for each modulator, such as a TMD1 conformational change or an increase in (cell-surface) stability, regardless of a functional response. These modulators thus should still be considered for hypo-responder genotypes. Understanding both biochemical and functional phenotypes of outlier mutations will boost our insights into CFTR folding and misfolding, and lead to improved therapeutic strategies.

Селектор импульсов для получения фемтосекундного излучения с управляемой фазой несущей относительно огибающей

In non-linear optical processes, such as obtaining attosecond pulses, it is extremely important to control the carrier envelope phase. To do this, various periodic trains of identical femtosecond pulses with a controlled phase can be created. In addition, since there is no frequency comb offset in such sequences, the process of measuring optical frequencies is greatly simplified. The pulse selector has been developed to obtain a sequence of identical femtosecond pulses with a controlled carrier – envelope phase. The selector makes it possible to obtain a “pure” sequence of identical femtosecond pulses at the modulator output (when every 125th pulse is selected from the original sequence with a repetition rate of 250 MHz) in a fairly wide range of control signal phase tuning. This range is 1.3 degrees. The phase tuning of the pulse selector provides the possibility of obtaining one hundred twenty-five such sequences with a phase tuning discreteness of 2π/125. The simplest way to reduce discreteness is to increase the ratio of the pulse repetition rate of a femtosecond laser to the shift of its frequency comb. The phase characteristic of the pulse selector was obtained by registering the time dependence of the synthesized sequence with a selector phase tuning step of 0.1 degrees. We measured the spectra of the sequences at different phases of the pulse selector, as well as the emission spectrum of the master laser at the minimum transmission of the modulator in the absence of modulation. The spectrum with the maximum amplitude corresponded to the case when identical pulses with the highest amplitude were selected from the original sequence. The difference between these spectra made it possible to isolate the spectrum of a pure sequence of identical femtosecond pulses without taking into account the "background" that occurs due to the modulator has a finite attenuation of –20 dB.

Annual modulation results from three-year exposure of ANAIS-112

ANAIS-112 is a dark matter direct detection experiment that operates 112 kg of NaI(Tl) scintillators at the Canfranc Underground Laboratory (LSC, Spain). Its main goal is to test in a model independent way one of the most puzzling results in the present particle physics scenario: the DAMA/LIBRA observation of an annual modulation in the detection rate compatible with that expected for dark matter. This signal is in strong tension with the negative results of other very sensitive experiments. However, until recently a direct comparison using the same target material (NaI(Tl)) was lacking. ANAIS-112 has been taking data since August 2017 in stable conditions with excellent performance. Results from the first three years are compatible with the absence of modulation and incompatible with the DAMA/LIBRA measured modulation at more than 2.5σ C.L. This result supports the projected goal of reaching a 3σ sensitivity to the DAMA/LIBRA result for the scheduled five-year operation.

Background model of the ANAIS-112 dark matter experiment

The ANAIS (Annual modulation with NaI(Tl) Scintillators) experiment aims at the confirmation or refutation of the DAMA/LIBRA positive annual modulation signal in the low energy detection rate. ANAIS-112, consisting of nine 12.5 kg NaI(Tl) modules, is taking data since August, 2017 at the Canfranc Underground Laboratory (LSC) in Spain. Results from the analysis of three years of data are compatible with the absence of modulation. The background model developed for all nine ANAIS-112 detectors was established from commissioning data and non-blinded events in the first year of data taking. Now, background characterization is being improved profiting from the larger accumulated exposure available. Here, the background model is described and comparisons of model and measurements for energy spectra and counting rate time evolution for three-year exposure (considering different analysis conditions) are presented.

Meta-analysis of in vitro and in vivo studies of the biological effects of low-level millimetre waves

BackgroundWith the roll-out of new technologies such as 5G, there has been renewed community concern regarding the adequacy of research on possible health effects from associated radiofrequency radiation, mainly in the millimetre wave (MMW) band.ObjectiveWe conducted a meta-analysis of in vitro and in vivo studies investigating bioeffects of MMWs at low exposure levels.MethodsWe identified 107 in vitro and in vivo studies investigating MMWs and biological effects in which the power density employed has been below 100 W/m2, which is below the current standards for occupational local exposures. Where possible, we estimated the magnitude of the principal effect reported or set this magnitude to zero in studies reporting no significant effects. We also estimated the quality of the studies, based on a methodology used in previous analyses.ResultsWe show a negative correlation between effect size and both power density and specific absorption rate. There was also a significant negative correlation between effect size and quality score. A multivariate analysis revealed that there is an increase in the effect size for certain biological systems being investigated and laboratories in which the work was carried out whilst the quality score for some of these tends to be low. We note that many of the studies were motivated by a desire to elucidate the possible mechanisms in therapeutic devices rather than assessing the safety of telecommunications systems. Finally, it appears that the presence or absence of modulation does not influence the reported effect size.SignificanceMany of the findings of this meta-analysis have not been reported before and have important implications for overall interpretation of in vitro and in vivo data. Overall, the results of this study do not confirm an association between low-level MMWs and biological effects.

Double-mechanical-oscillator cooling by breaking the restrictions of quantum backaction and frequency ratio via dynamical modulation

It is well known that the ground-state cooling of a single mechanical oscillator is limited by some strict conditions in the conventional sideband cooling method, such as small cavity decay, weak effective coupling, and minimum cooling phonon occupancy. Here we propose an effective scheme to greatly improve the ground-state cooling of two mechanical oscillators in a compound three-mode optomechanical system. By introducing the frequency modulation and the bias gate voltage modulation switch into the system, it is demonstrated that the scheme is well suitable for simultaneously cooling the two mechanical oscillators whether their frequencies are identical or largely different. Compared with previous schemes without modulation, our scheme can be achievable in a much wider parameter zone but shows a more ideal cooling effect, i.e., ranging from weak coupling to ultrastrong coupling and from the resolved-sideband regime to the unresolved-sideband regime. Moreover, the minimum cooling phonon occupancies obtained in our scheme for identical mechanical frequencies successfully break the quantum backaction limit defined in the absence of modulation. More importantly, even in the conventional unstable zone, our scheme is still workable and the steady ground-state cooling can be achieved perfectly. Our scheme opens up an alternative method for simultaneously cooling multiple mechanical oscillators with lower cooling phonon occupancy even breaking the quantum backaction limit but with fewer parametric limitations.

Rayleigh-Bénard magnetoconvection with temperature modulation.

Floquet analysis of modulated magnetoconvection in Rayleigh-Bénard geometry is performed. A sinusoidally varying temperature is imposed on the lower plate. As Rayleigh number Ra is increased above a critical value Rao, the oscillatory magnetoconvection begins. The flow at the onset of magnetoconvection may oscillate either subhar- monically or harmonically with the external modulation. The critical Rayleigh number Rao varies non-monotonically with the modulation frequency ω for appreciable value of the modulation amplitude a. The temperature modulation may either postpone or prepone the appearance of magnetoconvection. The magnetoconvective flow always oscillates harmonically at larger values of ω. The threshold Rao and the corresponding wavenumber k o approach to their values for the stationary magnetoconvection in the absence of modulation (a = 0), as ω → ∞. Two different zones of harmonic instability merge to form a single instability zone with two local minima for higher values of Chandrasekhar's number Q, which is qualitatively new. We have also observed a new type of bicritical point, which involves two different sets of harmonic oscillations. The effects of variation of Q and Pr on the threshold Rao and critical wavenumber k o are also investigated.

Modulation of orbitally forced ENSO variation by Tibetan Plateau topography

The modulation of the orbitally induced variation in the El Niño/Southern Oscillation (ENSO) by Tibetan Plateau (TP) topography was investigated with four fully coupled ocean–atmosphere model experiments under the modern boundary conditions. The modeled orbitally induced ENSO change was strongly affected by the presence of the TP. Specifically, in the experiments with orbital forcing at 6 ka in comparison to the counterpart experiments with modern orbital forcing, it was shown that the orbitally forced ENSO variability was slightly weakened by 3% in the presence of the TP but increased significantly by 13% in the simulation of the absence of the TP. This difference was primarily attributed to the anomalous zonal winds over the tropical central-to-eastern Pacific in response to the increased summertime incoming insolation, which was intrinsically related to the different changes in the Asian monsoon and tropical Pacific Walker circulation. Under the absence of modulation by the TP, the anomalous westerly winds dominated the equatorial Pacific and favored the development of a stronger El Niño event and, in turn, the further intensification of La Niña due to the stronger heat discharge during the recession of the stronger El Niño. In contrast, the simulation with the presence of the TP showed the enhanced easterly wind anomalies in the boreal summer over the tropical Pacific, which further reduced (increased) the magnitude of the El Niño (La Niña) event in the subsequent winter. These results suggest that the TP is a potentially crucial boundary condition for evaluating the changes in the ENSO dynamics on orbital scales during the Cenozoic.

Predictive Duty Cycle Control for Four-Leg Inverters With ${LC}$ Output Filter

Three-phase four-leg inverter is a well-known solution to handle unbalanced and nonlinear loading conditions in three-phase transformerless uninterruptible power supply applications. For such power converters, finite control set model predictive control (FCS-MPC) is considered as a promising control alternative due to its simplicity, fast dynamic response, and capability to include nonlinearities and constraints. However, the absence of modulator in FCS-MPC implementation leads to several shortcomings, such as higher load voltage total harmonic distortion (THD), large tracking error of control objectives, and variable switching frequency. Furthermore, the fourth leg operates with a higher average switching frequency than the other three main legs, which complicates the $LC$ filter design. To overcome the aforementioned shortcomings, a new predictive duty cycle control is proposed in this article. Extensive experimental results are shown to verify that the proposed method can achieve enhanced steady-state performance with significant reduced load voltage THD and tracking error under different operating conditions, such as nonlinear single-/three-phase unbalanced load and single-phase short-circuit fault, while preserving the fast dynamic performance of FCS-MPC. Steady-state and dynamic performances of the proposed method are compared to FCS-MPC and double-vector MPC approaches to validate the superiority of the proposed scheme.

Allosteric modulators restore orthosteric agonist binding to mutated CB1 receptors.

To determine if diminished orthosteric agonist binding due to mutations in extracellular loops 1 or 2 of the cannabinoid receptor 1 (CB1 ) can be overcome by an allosteric modulator and restore agonist binding. Binding assays were performed using a range of concentrations of orthosteric compound, in the presence or absence of a set concentration of the allosteric modulator PSNCBAM-1 to determine the EC50 in its absence or presence. Single mutations in extracellular loop 1 or 2 of CB1 showed weak or no binding of agonist CP55940 to the receptor. Interestingly, upon addition of the allosteric modulator PSNCBAM-1, this binding was restored typically to wild-type CB1 levels. In a few cases, the allosteric modulator ORG27569 was compared with PSNCBAM-1 for CP55940 binding and it also restored binding. Further, wild-type levels of inverse agonist bound the CB1 mutants in the absence of modulator, suggesting the mutants were originally folded like the wild type. Based on our findings, we provide evidence of a therapeutic application for allosteric modulators in situations where a mutation in the receptor may hinder its function. By utilizing allosteric modulators, restoration of orthosteric binding may be possible.

Time-energy filtering of single electrons in ballistic waveguides

Characterizing distinct electron wave packets is a basic task for solid-state electron quantum optics with applications in quantum metrology and sensing. A important circuit element for this task is a non-stationary potential barrier that enables backscattering of chiral particles depending on their energy and time of arrival. Here we solve the quantum mechanical problem of single-particle scattering by a ballistic constriction in an fully depleted quantum Hall system under spatially uniform but time-dependent electrostatic potential modulation. The result describes electrons distributed in time-energy space according to a modified Wigner quasiprobability distribution and scattered with an energy-dependent transmission probability that characterizes constriction in the absence of modulation. Modification of the incoming Wigner distribution due to external time-dependent potential simplifies in case of linear time-dependence and admits semiclassical interpretation. Our results support a recently proposed and implemented method for measuring time and energy distribution of solitary electrons as a quantum tomography technique, and offer new paths for experimental exploration of on-demand sources of coherent electrons.

First Results on Dark Matter Annual Modulation from the ANAIS-112 Experiment.

ANAIS is a direct detection dark matter experiment aiming at the testing of the DAMA/LIBRA annual modulation result, which, for about two decades, has neither been confirmed nor ruled out by any other experiment in a model independent way. ANAIS-112, consisting of 112.5kg of sodium iodide crystals, has been taking data at the Canfranc Underground Laboratory, Spain, since August 2017. This Letter presents the annual modulation analysis of 1.5years of data, amounting to 157.55kg yr. We focus on the model independent analysis searching for modulation and the validation of our sensitivity prospects. ANAIS-112 data are consistent with the null hypothesis (p values of 0.67 and 0.18 for [2-6] and [1-6]keV energy regions, respectively). The best fits for the modulation hypothesis are consistent with the absence of modulation (S_{m}=-0.0044±0.0058 cpd/kg/keV and -0.0015±0.0063 cpd/kg/keV, respectively). They are in agreement with our estimated sensitivity for the accumulated exposure, which supports our projected goal of reaching a 3σ sensitivity to the DAMA/LIBRA result in five years of data taking.

Circulating HO-1 levels are not associated with plasma sFLT-1 and GTn HMOX1 polymorphism in preeclampsia

ABSTRACTObjectives: We aimed to assess the plasma HO-1 level and its interrelationship with the plasma sFLT-1 level in preeclamptic and healthy pregnant women with different variants of microsatellite polymorphism (GTn) located in the promoter region of the HMOX-1 gene.Methods: HO-1 and sFLT-1 were measured by ELISA. HMOX1 genotyping was performed using fragment analysis.Results: We found similar and higher levels of plasma HO-1 and sFLT-1, respectively, in preeclampsia. Similar genotypes and alleles frequencies were found in both groups and the absence of modulation of HO-1 levels by genotypes were observed.Conclusion: The plasma HO-1 levels are not increased in preeclampsia women and neither related to sFLT-1 levels and GTn polymorphism.

A Semi Nonnegative Matrix Factorization Technique for Pattern Generalization in Single-Pixel Imaging

A single-pixel camera is a computational imaging device that only requires a single point detector to capture the image of a scene. This device measures the inner product of the scene and the spatial light modulator patterns. The image of the scene can be recovered through postprocessing the measurements obtained for a set of different patterns. Independent of the strategy used for image recovery, real acquisitions require the spatial light modulator patterns to be positive. In addition, the dark current measured in the absence of modulation must be rejected. To date, both experimental issues have been addressed empirically. In this paper, we solve these from a general perspective. Indeed, we propose to seek positive patterns that are linear combinations of the desired patterns (with negative values), and the linear transformation matrices are chosen to reject the dark current. We refer to the problem of finding the positive patterns and the linear combinations as “pattern generalization.” To the best of our knowledge, this is the first time that this problem has been introduced. In addition, we show that pattern generalization can be solved using a semi nonnegative matrix factorization algorithm. The data obtained from simulations demonstrate that our approach performs similarly to or better than conventional methods, while using fewer measurements.

Genistein represses PEPCK-C expression in an insulin-independent manner in HepG2 cells and in alloxan-induced diabetic mice.

Genistein has been reported to exert beneficial effects on type 2 diabetes mellitus (T2DM); however, the underlying molecular mechanisms involved therein have not been clearly elucidated. To address this question, the effect of genistein on the expression of phosphoenolpyruvate carboxykinase (PEPCK), and glucose production in HepG2 cells and in alloxan-induced diabetic mice was investigated. HepG2 cells were exposed to different concentration of genistein in presence or absence of modulators, and the expression of cytosolic PEPCK (PEPCK-C) and the signaling pathways was studied. Further, the biological relevance of the in vitro study was tested in alloxan-induced diabetic mice. Genistein lowered PEPCK-C expression and glucose production in HepG2 cells accompanied with increased in phosphorylation states of AMPK, MEK½, ERK½, and CRTC2. Treatment with the AMPK inhibitor (compound C) enhanced genistein-induced MEK½ and ERK½ activity indicating a potential cross-talk between the two signaling pathways. In vivo, genistein also reduced fasting glucose levels accompanied with reduced PEPCK-C expression and increased in AMPK and ERK½ phosphorylation states in the liver of genistein-treated alloxan-induced diabetic mice. Genistein fulfills the criteria of a suitable anti-diabetic agent by reducing glucose production and inhibiting PEPCK-C expression in HepG2 cells and also in alloxan-induced diabetic mice. These results indicate that genistein is an effective candidate for preventing T2DM through the modulation of AMPK-CRTC2 and MEK/ERK signaling pathways, which may allow a novel approach to modulate dysfunction in hepatic gluconeogenesis in T2DM.