Wideband Direct Detection Constraints on Hidden Photon Dark Matter with the QUALIPHIDE Experiment.

We report direction detection constraints on the presence of hidden photon dark matter with masses between 20-30 µeV c^{-2}, using a cryogenic emitter-receiver-amplifier spectroscopy setup designed as the first iteration of QUALIPHIDE (quantum limited photons in the dark experiment). A metallic dish sources conversion photons, from hidden photon kinetic mixing, onto a horn antenna which is coupled to a C band kinetic inductance traveling wave parametric amplifier, providing for near quantum-limited noise performance. We demonstrate a first probing of the kinetic mixing parameter χ to the 10^{-12} level for the majority of hidden photon masses in this region. These results not only represent stringent constraints on new dark matter parameter space, but are also the first demonstrated use of wideband quantum-limited amplification for astroparticle applications.

First Constraints from DAMIC-M on Sub-GeV Dark-Matter Particles Interacting with Electrons.

We report constraints on sub-GeV dark matter particles interacting with electrons from the first underground operation of DAMIC-M detectors. The search is performed with an integrated exposure of 85.23 g days, and exploits the subelectron charge resolution and low level of dark current of DAMIC-M charge-coupled devices (CCDs). Dark-matter-induced ionization signals above the detector dark current are searched for in CCD pixels with charge up to 7e^{-}. With this dataset we place limits on dark matter particles of mass between 0.53 and 1000 MeV/c^{2}, excluding unexplored regions of parameter space in the mass ranges [1.6,1000] MeV/c^{2} and [1.5,15.1] MeV/c^{2} for ultralight and heavy mediator interactions, respectively.

Dexmedetomidine for adult cardiac surgery: a systematic review, meta-analysis and trial sequential analysis.

The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of peri-operative dexmedetomidine in adults undergoing cardiac surgery. We searched MEDLINE via Pubmed, EMBASE, Scopus and Cochrane for relevant randomised controlled trials between 1 January 1990 and 1 March 2022. We used the Joanna Briggs Institute methodology checklist to assess study quality and the GRADE approach to certainty of evidence. We assessed the sensitivity of results to false data. We used random-effects meta-analyses to analyse the primary outcomes: durations of intensive care and tracheal intubation. We included 48 trials of 6273 participants. Dexmedetomidine reduced the mean (95%CI) duration of intensive care by 5.0 (2.2-7.7) h, p = 0.001, and tracheal intubation by 1.6 (0.6-2.7) h, p = 0.003. The relative risk (95%CI) for postoperative delirium was 0.58 (0.43-0.78), p = 0.001; 0.76 (0.61-0.95) for atrial fibrillation, p = 0.015; and 0.49 (0.25-0.97) for short-term mortality, p = 0.041. Bradycardia and hypotension were not significantly affected. Trial sequential analysis was consistent with the primary meta-analysis. Adjustments for possible false data reduced the mean (95%CI) reduction in duration of intensive care and tracheal intubation by dexmedetomidine to 3.6 (1.8-5.4) h and 0.8 (0.2-1.4) h, respectively. Binary adjustment for methodological quality at a Joanna Briggs Institute score threshold of 10 did not alter the results significantly. In summary, peri-operative dexmedetomidine reduced the durations of intensive care and tracheal intubation and the incidence of short-term mortality after adult cardiac surgery. The reductions in intensive care stay and tracheal intubation may or may not be considered clinically useful, particularly after adjustment for possible false data.

Transcript abundance of anti-Mullérian hormone and follicle-stimulating hormone receptor predicted superstimulatory response in embryo donor Holstein cows.

The goal was to investigate the relationship among mRNA expressions of anti-Mullérian hormone (AMH), follicle-stimulating hormone receptor (FSHR) and responses to superovulation (SO) in embryo donor dairy cows. Holstein cows (n = 19) were submitted to a standard SO protocol, with twice daily FSH treatments, and artificially inseminated. Prior to SO (Day 0), relative mRNA expressions of AMH and FSHR in blood were determined for all cows. Day 7 embryos were collected and were graded to determine superovulatory response for each donor. Results showed that relative mRNA expressions of AMH and FSHR were positively correlated (R2  = 0.94). Relative mRNA expressions of both AMH and FSHR were positively correlated with total embryos (R2  = 0.68 and 0.69, respectively), total transferable embryos (R2  = 0.92 and 0.97, respectively) and total grade 1 embryos (R2  = 0.54 and 0.59, respectively). Further, transcript abundances of AMH and FSHR positively associated with milk production of donor cows, and meanwhile, they were negatively associated with days in milk (DIM) at submission of cows to SO (p < .05) protocol. The relative mRNA expression of AMH was higher (p < .05) in donor cows <5 years of age. However, age of donor at superovulation did not influence mRNA expression of FSHR. Collectively, we infer that the mRNA expressions of AMH and FSHR prior to superovulation can predict donor cows' positive response to superovulation.

Results on Low-Mass Weakly Interacting Massive Particles from an 11 kg d Target Exposure of DAMIC at SNOLAB.

We present constraints on the existence of weakly interacting massive particles (WIMPs) from an 11 kg d target exposure of the DAMIC experiment at the SNOLAB underground laboratory. The observed energy spectrum and spatial distribution of ionization events with electron-equivalent energies >200 eV_{ee} in the DAMIC CCDs are consistent with backgrounds from natural radioactivity. An excess of ionization events is observed above the analysis threshold of 50 eV_{ee}. While the origin of this low-energy excess requires further investigation, our data exclude spin-independent WIMP-nucleon scattering cross sections σ_{χ-n} as low as 3×10^{-41} cm^{2} for WIMPs with masses m_{χ} from 7 to 10 GeV c^{-2}. These results are the strongest constraints from a silicon target on the existence of WIMPs with m_{χ}<9 GeV c^{-2} and are directly relevant to any dark matter interpretation of the excess of nuclear-recoil events observed by the CDMS silicon experiment in 2013.

Strikingly different molecular organization and molecular order of tetracatenar mesogens in columnar mesophases revealed by XRD and 13C NMR.

For a successful design of functional mesogens, it is paramount to understand factors that contribute to molecular organisation such as molecular shape, the non-covalent interactions of the constituent moieties as well as nanosegregation of incompatible molecular parts. In this study on four tetracatenar mesogens, we show that by a slight change in the length of the terminal chain, the molecular organization changes from lamellar to columnar phase and that the orientational order experiences profound change between the lamellar, the center rectangular columnar and the hexagonal columnar mesophases. We consider here, mesogens that exhibit lamellar and columnar mesophases with five phenyl rings in the central rod-like core which are subjected to XRD and high resolution solid state 13C NMR investigations in their mesophases. The XRD studies indicate that the lower homologs exhibit a lamellar mesophase while the higher homologs show either a centre rectangular columnar phase or a 2D hexagonal columnar mesophase. 13C NMR investigations reveal interesting and strikingly different molecular orientations in each of these phases. For example, values of order parameters of one of the phenyl rings in the core region of the mesogens vary from 0.75 and 0.77 for the lamellar mesogens to 0.45 and 0.17 for the centre rectangular columnar and the hexagonal columnar mesogens respectively. While these values indicate that the mesogenic molecules are oriented along the magnetic field as expected in the lamellar phases, the very low order parameter in the hexagonal columnar phase arises due to molecules distributed azimuthally in layers and undergoing motion about the columnar axis which itself is oriented orthogonal to the magnetic field. Such cutting edge information extracted from the combined use of XRD and 13C NMR studies on tetracatenar mesogens is expected to be of significant use for the study of π-conjugated polycatenar systems where functional properties depend on the molecular orientation and order.

13 C NMR investigations of molecular order of rod-like, bent-core, and thiophene mesogens.

In this review, methods to obtain the orientational order of topologically variant molecular mesogens using by one- and two-dimensional (2D) solid-state 13 C nuclear magnetic resonance (NMR) spectroscopy are described. Besides 13 C chemical shifts, the 13 C─1 H dipolar couplings measured from 2D-separated local field (SLF) technique are used for computing the order parameters of a variety of mesogens. The investigated molecules are composed of a variable number of rings in the core, that is, core ranging from simply one ring to five rings. Among the mesogens investigated, a special focus has been placed on mesogens with thiophene rings, which are gaining popularity as liquid crystalline organic semiconductors. The replacement of a phenyl ring by thiophene in the core has a dramatic influence on molecular topology, as observed from the measured order parameters. The review highlights the advantages of the 2D SLF method for understanding the local dynamics and for mapping the topology of mesogens through the measured order parameters. SLF NMR studies of as many as 24 molecular mesogens that vary in terms of the molecular structure as well as topology are covered in the review. Order parameters of the rings have been estimated from the 13 C─1 H dipolar couplings in the nematic, smectic A, smectic C, and tilted hexatic phases as well as in B1 and B2 mesophases of various mesogens. It is anticipated that, in the years to come, the 2D SLF method would provide advanced molecular information on structurally complex mesogens that are emerging in liquid crystal science through the incessant efforts of synthetic chemists. The mini review covers the orientational order of topologically variant molecular mesogens determined by 1D and 2D solid-state 13 C NMR spectroscopy. Accordingly, rod-like, bent-core, and thiophene mesogens were subjected to 2D SLF measurements to get the order parameters from which the topology was established. The replacement of phenyl ring by thiophene and its influence on order parameters as well as on molecular topology is also discussed.

Constraints on Light Dark Matter Particles Interacting with Electrons from DAMIC at SNOLAB.

We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the DAMIC detector at SNOLAB of 2-6×10^{-22} A cm^{-2}. We evaluate the charge distribution of pixels that collect <10e^{-} for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c^{-2}. We also present new constraints on hidden-photon dark matter with masses in the range 1.2-30 eV c^{-2}.

Enhancement of the Nuclear Spin Noise Signal Using Wavelet Transform.

Spin noise spectroscopy has attracted considerable attention recently owing partly to intrinsic interest in the phenomenon and partly to its significant application potential. Here, we address the inherent problem of low sensitivity of nuclear spin noise and examine the utility of wavelet transform to mitigate this problem by distinguishing real peaks from the noise contaminated data. Suppression of the random circuit noise and the consequent enhancement of the correlated nuclear spin noise signal have been demonstrated with discrete wavelet transform. Spectra of both 1 H and 13 C nuclear spins have been considered and significant signal enhancements in both the cases have been observed. A detailed analysis of several possible wavelet, thresholding and decomposition solutions have been made to obtain the optimum condition for signal enhancement. It is observed that the application of wavelet transform leaves the spin noise signal line shape essentially unchanged, which is an advantage for several applications involving spin noise spectra.

First Direct-Detection Constraints on eV-Scale Hidden-Photon Dark Matter with DAMIC at SNOLAB.

We present direct detection constraints on the absorption of hidden-photon dark matter with particle masses in the range 1.2-30 eV c^{-2} with the DAMIC experiment at SNOLAB. Under the assumption that the local dark matter is entirely constituted of hidden photons, the sensitivity to the kinetic mixing parameter κ is competitive with constraints from solar emission, reaching a minimum value of 2.2×10^{-14} at 17 eV c^{-2}. These results are the most stringent direct detection constraints on hidden-photon dark matter in the galactic halo with masses 3-12 eV c^{-2} and the first demonstration of direct experimental sensitivity to ionization signals <12 eV from dark matter interactions.

NMR investigations unveil phase composition-property correlations in Sr0.55Na0.45SiO2.775 fast ion conductor.

This paper reports results of 23Na and 29Si solid-state NMR investigations carried out on sodium strontium silicate ion conductor, Sr0.55Na0.45SiO2.775 and presents the first experimental evidence to show that different synthesis conditions induce multiple devitrified phases. Along with 1-dimensional NMR, 23Na MQMAS spectra have been used to identify the phases corresponding to polymorphs of Na2Si2O5, in addition to the crystalline SrSiO3 and the glass/amorphous Na2Si2O5 phases. The surprising observation of about an order of magnitude higher ionic conductivity achieved in devitrified samples is attributed to the growth of the crystalline δ-Na2Si2O5 phase within the amorphous Na2Si2O5 phase domains, identified using NMR. Together with XRD and conductivity measurement data, the study leads to the identification of the chemical phase composition and an understanding of the composition-property-structure correlation in this material. Present findings, while do not show any evidence of Na doping in the SrSiO3 phase confirming earlier reports, explain the large discrepancy in the conductivity reported in the literature.

Molecular level understanding of resistance to nalidixic acid in Salmonella enteric serovar typhimurium associates with the S83F sequence type.

Nalidixic acid is an antibiotic drug used for treatment of Salmonellosis, a gastrointestinal infection. DNA gyrase subunit A (GyrA) of Salmonella typhimurium is the drug target for nalidixic acid. Resistance of GyrA to nalidixic acid, because of a point mutation in S. typhimurium, was recently reported. Substitution of Phe in place of Ser at locus 83 in GyrA of S. typhimurium has been experimentally associated with nalidixic acid resistance. Despite recent efforts, the mechanism of this resistance is not well understood. In this investigation we used computational techniques to address this shortcoming. Our results showed that contact with residue Arg 91 is certainly important for efficient binding of nalidixic acid to the target protein, and that mutation of this residue results in 180° rotation of the antibiotic in its binding pocket, around its own long axis. It is hoped these findings may enable development of new antibiotics against resistant forms of Salmonella.

Gradient echo single scan inversion recovery: application to proton and fluorine relaxation studies.

Single scan longitudinal relaxation measurement experiments enable rapid estimation of the spin-lattice relaxation time (T1 ) as the time series of spin relaxation is encoded spatially in the sample at different slices resulting in an order of magnitude saving in time. We consider here a single scan inversion recovery pulse sequence that incorporates a gradient echo sequence. The proposed pulse sequence provides spectra with significantly enhanced signal to noise ratio leading to an accurate estimation of T1 values. The method is applicable for measuring a range of T1 values, thus indicating the possibility of routine use of the method for several systems. A comparative study of different single scan methods currently available is presented, and the advantage of the proposed sequence is highlighted. The possibility of the use of the method for the study of cross-correlation effects for the case of fluorine in a single shot is also demonstrated.

Investigation of Paclitaxel Resistant R306C Mutation in ß-Tubulin­A Computational Approach.

Paclitaxel is the most effective chemotherapeutic agent used for the treatment of a broad spectrum of solid tumors. However, observed paclitaxel resistance in clinical trials presents one of the major obstacles for cancer chemotherapy. Most importantly, resistance due to ß-tubulin mutations (R306C) has been intensely debated in recent years. Despite all efforts, mechanism of resistance is still not well understood. In this study, computational techniques were employed to uncover the effect of R306C mutation in the ß-tubulin structure and its function. The tools such as I-Mutant, CUPSAT and Fold-X were employed to address the consequence of R306C mutation in the structural stability of ß-tubulin. Further, molecular docking and molecular dynamics study was employed to understand the functional impact of ß-tubulin mutation. Our results suggest that the R306C mutation causes a significant reduction in the binding affinity between ß-tubulin and paclitaxel. Further, docked complex analysis indicates that destruction of conservative hydrogen bond maintained by the residues Arg282 and Gly360 should be responsible for the large conformation changes of the binding pocket in R306C mutant. Finally, molecular dynamics simulations study confirms the stable binding of paclitaxel with native type ß-tubulin structure rather than mutant (R306C) type. We certainly believe that this study will provide useful guidance for the development of novel inhibitors that are less susceptible to drug resistance.

Monolayer to interdigitated partial bilayer smectic C transition in thiophene-based spacer mesogens: X-ray diffraction and (13)C nuclear magnetic resonance studies.

Mesophase organization of molecules built with thiophene at the center and linked via flexible spacers to rigid side arm core units and terminal alkoxy chains has been investigated. Thirty homologues realized by varying the span of the spacers as well as the length of the terminal chains have been studied. In addition to the enantiotropic nematic phase observed for all the mesogens, the increase of the spacer as well as the terminal chain lengths resulted in the smectic C phase. The molecular organization in the smectic phase as investigated by temperature dependent X-ray diffraction measurements revealed an interesting behavior that depended on the length of the spacer vis-a-vis the length of the terminal chain. Thus, a tilted interdigitated partial bilayer organization was observed for molecules with a shorter spacer length, while a tilted monolayer arrangement was observed for those with a longer spacer length. High-resolution solid state (13)C NMR studies carried out for representative mesogens indicated a U-shape for all the molecules, indicating that intermolecular interactions and molecular dynamics rather than molecular shape are responsible for the observed behavior. Models for the mesophase organization have been considered and the results understood in terms of segregation of incompatible parts of the mesogens combined with steric frustration leading to the observed lamellar order.

Assignment of the (13)C NMR spectrum by correlation to dipolar coupled proton-pairs and estimation of order parameters of a thiophene based liquid crystal.

Materials with widely varying molecular topologies and exhibiting liquid crystalline properties have attracted considerable attention in recent years. (13)C NMR spectroscopy is a convenient method for studying such novel systems. In this approach the assignment of the spectrum is the first step which is a non-trivial problem. Towards this end, we propose here a method that enables the carbon skeleton of the different sub-units of the molecule to be traced unambiguously. The proposed method uses a heteronuclear correlation experiment to detect pairs of nearby carbons with attached protons in the liquid crystalline core through correlation of the carbon chemical shifts to the double-quantum coherences of protons generated through the dipolar coupling between them. Supplemented by experiments that identify non-protonated carbons, the method leads to a complete assignment of the spectrum. We initially apply this method for assigning the (13)C spectrum of the liquid crystal 4-n-pentyl-4'-cyanobiphenyl oriented in the magnetic field. We then utilize the method to assign the aromatic carbon signals of a thiophene based liquid crystal thereby enabling the local order-parameters of the molecule to be estimated and the mutual orientation of the different sub-units to be obtained.

Structural investigation of resorcinol based symmetrical banana mesogens by XRD, NMR and polarization measurements.

Synthesis and structural characterization of two novel symmetrical banana mesogens built from resorcinol with seven phenyl rings linked by ester and imine with a terminal dodecyl/dodecyloxy chain has been carried out. Density functional theory (DFT) has been employed for obtaining the geometry optimized structures, the dipole moments and (13)C NMR chemical shifts. The HOPM and DSC studies revealed enantiotropic B2 and B7 phases for the dodecyl and dodecyloxy homologs respectively. The powder X-ray studies of both the mesogens indicate the presence of layer ordering. The polarization measurements reveal an anti-ferroelectric switching for the B2 phase of the dodecyl homolog whose structure has been identified as SmCSPA. The B7 phase of the dodecyloxy homolog was found to be non-switchable. High resolution (13)C NMR study of the dodecyl homolog in its mesophase has been carried out. (13)C-(1)H dipolar couplings obtained from the 2-dimensional separated local field spectroscopy experiment were used to obtain the orientational order parameters of the different segments of the mesogen. Very large (13)C-(1)H dipolar couplings observed for the carbons of the central phenyl ring (9.7-12.3 kHz) in comparison to the dipolar couplings of those of the side arm phenyl rings (less than 3 kHz) are a direct consequence of the ordering in the banana phase and the shape of the molecule. From the ratio of the local order parameter values, the bent-angle of the mesogen could be determined in a straight forward manner to be 120.5°.

Exploring the impact of F270V mutation in the ß-tubulin (Bos Taurus) structure and its function: a computational perspective.

Paclitaxel is the most effective chemotherapeutic agent used for the treatment of a broad spectrum of solid tumors. However, observed paclitaxel resistance in clinical trials presents one of the major obstacles for cancer chemotherapy. Most importantly, resistance due to ß-tubulin mutations (F270V) has been intensely debated in recent years. Despite all efforts, mechanism of resistance is still not well understood. In this study, computational techniques were employed to uncover the effect of F270V mutation in the ß-tubulin structure and its function. The tools such as MuStab, CUPSAT and I-Mutant were employed to address the consequence of F270V mutation in the structural stability of ß-tubulin. Further, molecular simulation study was employed to understand the functional impact of ß-tubulin mutation. We believe that this study will provide useful guidance for the development of novel inhibitors that are less susceptible to drug resistance.

Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches.

Crizotinib is the potential anticancer drug used for the treatment of non-small cell lung cancer (NSCLC) approved by FDA in 2011. The main target for the crizotinib is anaplastic lymphoma kinase (ALK). Evidences available indicate that double mutant ALK (L1196M and G1269A) confers resistance to crizotinib. However, how mutation confers drug resistance is not well-understood. Hence, in the present study, molecular dynamic (MD) simulation approach was employed to study the impact of crizotinib binding efficacy with ALK structures at a molecular level. Docking results indicated that ALK double mutant (L1196M and G1269A) significantly affected the binding affinity for crizotinib. Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex. These results may be immense importance for the molecular level understanding of the crizotinib resistance pattern and also for designing potential drug molecule for the treatment of lung cancer.