Why Shot Noise Does Not Generally Detect Pairing in Mesoscopic Superconducting Tunnel Junctions.

The shot noise in tunneling experiments reflects the Poissonian nature of the tunneling process. The shot-noise power is proportional to both the magnitude of the current and the effective charge of the carrier. Shot-noise spectroscopy thus enables us, in principle, to determine the effective charge q of the charge carriers of that tunnel. This can be used to detect electron pairing in superconductors: In the normal state, the noise corresponds to single electron tunneling (q=1e), while in the paired state, the noise corresponds to q=2e. Here, we use a newly developed amplifier to reveal that in typical mesoscopic superconducting junctions, the shot noise does not reflect the signatures of pairing and instead stays at a level corresponding to q=1e. We show that transparency can control the shot noise, and this q=1e is due to the large number of tunneling channels with each having very low transparency. Our results indicate that in typical mesoscopic superconducting junctions, one should expect q=1e noise and lead to design guidelines for junctions that allow the detection of electron pairing.

Progressive myelinated retinal nerve fibers in a 10-year-old boy with Crouzon syndrome after craniofacial surgery.

Purpose: We present a case of a 10-year-old boy with Crouzon syndrome that demonstrates progressive myelinated retinal nerve fibers (MRNF). Observations: A 10-year-old boy was referred for ophthalmic examination due to clusters of opaque white fibers around his optic nerve. Past surgical history includes craniofacial surgery at 3 years of age secondary to the deteriorating vision from increased intracranial pressure and papilledema. Upon examination (now 6.5 years post-craniofacial surgery), the patient denied any ocular complaints. The fundus examination showed progressively enlarged myelination of the retinal nerve fiber layer (right eye > left eye). Although previous cases of MRNF with Crouzon syndrome have been reported, our case is unique given its post-operative status with early onset of MRNF. Conclusion and importance: This case report documents the photographic progression of bilateral myelinated retinal nerve fibers (MRNF) in a pediatric case of Crouzon syndrome post-craniofacial surgery secondary to increased intracranial pressure and papilledema. Based on our patient, craniofacial decompression surgery may not prevent the development of MRNF. The exact mechanisms of MRNF are still being studied. Further investigations correlating craniofacial surgeries, increased intracranial pressure, and progression of myelinated retinal nerve fibers are needed to understand this process.

Single-electron charge transfer into putative Majorana and trivial modes in individual vortices.

Majorana bound states are putative collective excitations in solids that exhibit the self-conjugate property of Majorana fermions-they are their own antiparticles. In iron-based superconductors, zero-energy states in vortices have been reported as potential Majorana bound states, but the evidence remains controversial. Here, we use scanning tunneling noise spectroscopy to study the tunneling process into vortex bound states in the conventional superconductor NbSe2, and in the putative Majorana platform FeTe0.55Se0.45. We find that tunneling into vortex bound states in both cases exhibits charge transfer of a single electron charge. Our data for the zero-energy bound states in FeTe0.55Se0.45 exclude the possibility of Yu-Shiba-Rusinov states and are consistent with both Majorana bound states and trivial vortex bound states. Our results open an avenue for investigating the exotic states in vortex cores and for future Majorana devices, although further theoretical investigations involving charge dynamics and superconducting tips are necessary.

Interplay of hidden orbital order and superconductivity in CeCoIn5.

Visualizing atomic-orbital degrees of freedom is a frontier challenge in scanned microscopy. Some types of orbital order are virtually imperceptible to normal scattering techniques because they do not reduce the overall crystal lattice symmetry. A good example is dxz/dyz (π,π) orbital order in tetragonal lattices. For enhanced detectability, here we consider the quasiparticle scattering interference (QPI) signature of such (π,π) orbital order in both normal and superconducting phases. The theory reveals that sublattice-specific QPI signatures generated by the orbital order should emerge strongly in the superconducting phase. Sublattice-resolved QPI visualization in superconducting CeCoIn5 then reveals two orthogonal QPI patterns at lattice-substitutional impurity atoms. We analyze the energy dependence of these two orthogonal QPI patterns and find the intensity peaked near E = 0, as predicted when such (π,π) orbital order is intertwined with d-wave superconductivity. Sublattice-resolved superconductive QPI techniques thus represent a new approach for study of hidden orbital order.

Photoionization of the water molecule with XCHEM.

We have evaluated total and partial photoionization cross sections, ß asymmetry parameters, and molecular frame photoelectron angular distributions (MFPADs) of the water molecule by using the XCHEM methodology. This method accounts for electron correlation in the electronic continuum, which is crucial to describe Feshbach resonances and their autoionization decay. We have identified a large number of Feshbach resonances, some of them previously unknown, in the region between 12.2 and 18.7 eV, for which we provide energy positions and widths. Many of these resonances lead to pronounced peaks in the photoionization spectra, some of them remarkably wide (up to 0.2 eV, for resonances converging to the third ionization threshold), which should be observable in high-energy resolution experiments. We show that, in the vicinity of these peaks, both asymmetry parameters and MFPADs vary very rapidly with photoelectron energy, which, as in atoms and simpler molecules, reflects the interference between direct ionization and autoionization, which is mostly driven by electron correlation.

Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)2Sr2CuO6+δ.

The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.

TMEM16E regulates endothelial cell procoagulant activity and thrombosis.

Endothelial cells (ECs) normally form an anticoagulant surface under physiological conditions, but switch to support coagulation following pathogenic stimuli. This switch promotes thrombotic cardiovascular disease. To generate thrombin at physiologic rates, coagulation proteins assemble on a membrane containing anionic phospholipid, most notably phosphatidylserine (PS). PS can be rapidly externalized to the outer cell membrane leaflet by phospholipid "scramblases," such as TMEM16F. TMEM16F-dependent PS externalization is well characterized in platelets. In contrast, how ECs externalize phospholipids to support coagulation is not understood. We employed a focused genetic screen to evaluate the contribution of transmembrane phospholipid transport on EC procoagulant activity. We identified 2 TMEM16 family members, TMEM16F and its closest paralog, TMEM16E, which were both required to support coagulation on ECs via PS externalization. Applying an intravital laser-injury model of thrombosis, we observed, unexpectedly, that PS externalization was concentrated at the vessel wall, not on platelets. TMEM16E-null mice demonstrated reduced vessel-wall-dependent fibrin formation. The TMEM16 inhibitor benzbromarone prevented PS externalization and EC procoagulant activity and protected mice from thrombosis without increasing bleeding following tail transection. These findings indicate the activated endothelial surface is a source of procoagulant phospholipid contributing to thrombus formation. TMEM16 phospholipid scramblases may be a therapeutic target for thrombotic cardiovascular disease.

Synthetic approach toward spiro quinoxaline-ß-lactam based heterocyclic compounds: Spectral characterization, SAR, pharmacokinetic and biomolecular interaction studies.

Series of spiro quinoxaline-ß-lactam based heterocyclic compounds (QL 1 - QL 21) were synthesized and characterized by spectroscopic techniques like 1H-NMR, LC-MS, FT-IR spectroscopy and elemental analysis. The binding mode and binding strength between compounds and calf thymus-DNA were estimated by UV-visible spectroscopy, viscosity measurement and molecular docking studies. The compounds bind with the DNA through partial intercalation mode. In the absorption titration experiment, the Kb values for all the synthesized compounds were found in the range of 0.24-0.64 × 105 M-1. The protein binding studies of all the synthesized compounds were evaluated by absorption titration experiment, and the Kb value for all the compounds was obtained in the range of 0.030-1.571 × 104 M-1. The compounds were screened against two Gram (+ve) and three Gram (-ve) bacteria for antimicrobial activity. The MIC values for all the synthesized compounds were found in 95-255 µM. The LC50 values (cytotoxicity) of the synthesized compounds (QL 1-QL 21) were found in the range of 4.00-12.89 µg/mL. The ADME study was carried out using the online platform SwissADME and admetSAR to evaluate the pharmacokinetic profile of all the synthesized compounds. All the compounds were screened for anticancer activity against the human osteosarcoma (MG-63) cell line. The result shows that all the compounds exhibit effective anticancer activity.Communicated by Ramaswamy H. Sarma.

Medroxyprogesterone acetate in reindeer bulls: testes histology, cfos activity in the brain, breeding success, and semen quality.

A previous study reported that a 400-mg dose of medroxyprogesterone acetate (MPA) reduced male reindeer aggression and blocked development of secondary sexual characteristics but did not completely impair fertility. Here we have repeated that protocol in two separate trials. In 2017, tissues and blood samples, collected from MPA and control (CTL) reindeer bulls, euthanized at 30 and 60 d post-treatment were used to evaluate testes histology and morphometrics, cfos activity in the brain and androgen levels. While testes weight tended to decline from August to September in both groups, indices of spermatogenesis remained high. By September, indices of spermatogenesis were declining in both groups with sperm density lower (P = 0.05) in MPA compared to CTL bulls. Aug CTL bulls had the highest concentrations of androstenedione (A4) (P = 0.009) and testosterone (T) (P = 0.08), whereas these androgens were baseline in Aug MPA bulls. By September, A4 and T levels in CTL bulls declined to levels measured in MPA bulls. Cfos activity had a greater number (P = 0.02) of cfos positive neurons in the central amygdala in MPA compared to CTL bulls, suggesting a heightened fear response among the MPA bulls. In the second trial (2019), MPA-treated bulls, with (E, n = 4) and without (IE, n = 4) breeding experience, were blood sampled at key points from July through September when they were put in individual harems with estrous-synchronized cows. Concentrations of T were greatest (P < 0.001) among E bulls prior to MPA treatment but 1 mo after treatment, both T and A4 were baseline in all eight reindeer. Semen collected by electroejaculation at 60 d post-MPA treatment revealed only minor differences in sperm abnormalities between E and IE bulls using both fresh and frozen/thawed semen. Only three bulls (2 E and 1 IE) sired offspring. Breeding success was not related to previous breeding experience, body weight, or bull age. The failure of some MPA bulls to breed appears to be a behavioral, not a physiological, limitation. Limited application of MPA is clearly a useful tool for managing rut-aggression in non-breeding reindeer. However, the possibility that semen could be collected from MPA-treated bulls using restraint and mild sedation rather than general anesthesia should be investigated. This could improve the quality of semen collection while enhancing the safety of both handlers and animals.

A single 400 mg dose of MPA given to reindeer bulls just before the onset of rut eliminates aggressive behavior and suppresses androgen concentrations without dramatic differences in the gross or histological structure of the testes within the first 30 d of treatment. By 60 d post-treatment, there is evidence of smaller testes size and decreased sperm density in treated bulls. However, if given the opportunity, some treated bulls can still successfully breed. Breeding success in MPA bulls was not solely related to previous breeding experience, body weight, or bull age. Androgen concentrations and semen characteristics did not vary with previous breeding experience. Failure of some treated bulls to breed appears to be a behavioral limitation. Differences in brain activity between control and treated bulls were few except for increased cfos activity in the central amygdala of MPA bulls, potentially increasing the fear response in these reindeer.

Amalgamation of solid dispersion and melt adsorption techniques for augmentation of oral bioavailability of novel anticoagulant rivaroxaban.

The objective of the present study was to evaluate the potential of solid dispersion adsorbate (SDA) to improve the solubility and bioavailability of rivaroxaban (RXN). SDA of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were the amount of carrier (X1) and amount of adsorbent (X2). The responses measured were the time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of the crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbent significantly (P < 0.05) influence both dependent variables. Post-compression data signifies that the compressibility behavior of prepared tablets was within the official standard limits. A significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (> 85% in 10 min) as compared to the pure drug, marketed product, and directly compressible tablet. Cytotoxicity studies confirmed the nontoxicity of prepared RXN SDA tablets. RXN SDA tablets exhibited 2.79- and 1.85-fold higher AUC in comparison to RXN suspension and Xarelto tablets respectively indicating improved oral bioavailability. Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets in comparison to RXN suspension further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.

Imaging moiré deformation and dynamics in twisted bilayer graphene.

In 'magic angle' twisted bilayer graphene (TBG) a flat band forms, yielding correlated insulator behavior and superconductivity. In general, the moiré structure in TBG varies spatially, influencing the overall conductance properties of devices. Hence, to understand the wide variety of phase diagrams observed, a detailed understanding of local variations is needed. Here, we study spatial and temporal variations of the moiré pattern in TBG using aberration-corrected Low Energy Electron Microscopy (AC-LEEM). We find a smaller spatial variation than reported previously. Furthermore, we observe thermal fluctuations corresponding to collective atomic displacements over 70 pm on a timescale of seconds. Remarkably, no untwisting is found up to 600 ∘C. We conclude that thermal annealing can be used to decrease local disorder. Finally, we observe edge dislocations in the underlying atomic lattice, the moiré structure acting as a magnifying glass. These topological defects are anticipated to exhibit unique local electronic properties.

Direct evidence for Cooper pairing without a spectral gap in a disordered superconductor above Tc.

The idea that preformed Cooper pairs could exist in a superconductor at temperatures higher than its zero-resistance critical temperature (Tc) has been explored for unconventional, interfacial, and disordered superconductors, but direct experimental evidence is lacking. We used scanning tunneling noise spectroscopy to show that preformed Cooper pairs exist up to temperatures much higher than Tc in the disordered superconductor titanium nitride by observing an enhancement in the shot noise that is equivalent to a change of the effective charge from one to two electron charges. We further show that the spectroscopic gap fills up rather than closes with increasing temperature. Our results demonstrate the existence of a state above Tc that, much like an ordinary metal, has no (pseudo)gap but carries charge through paired electrons.

Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of Adenovirus Vector-Based COVID-19 Vaccines?

MYTH: Corticosteroid injection for the treatment of pain is known to decrease the efficacy of the adenovirus vector-based vaccines for COVID-19. FACT: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an adenovirus vector-based COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Janssen and AstraZeneca vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to and no less than 2 weeks following a COVID-19 adenovirus vector-based vaccine dose, whenever possible. We emphasize the importance of risk/benefit analysis and shared decision making in determining the timing of corticosteroid injections for pain indications in relation to receipt of a COVID-19 vaccine given that patient-specific factors will vary.

Treatment-resistant schizophrenia - A RCT on the effectiveness of repeated-dose sodium nitroprusside.

OBJECTIVES: Sodium nitroprusside (SNP) has shown efficacy in schizophrenia in early stages of the disease in a previous study, but in more recent studies it has not shown efficacy in patients with longer disease duration. In present study, we evaluated the efficacy of repeated-dose SNP in treatment-resistant schizophrenia. METHODS: This was a double-blind, randomized, placebo-controlled trial. Twenty DSM-IV schizophrenia subjects, aged 18-60 years, with a history of nonresponse to ≥2 trials of antipsychotics of adequate dose and duration (≥6 weeks) were enrolled. Participants received SNP or placebo 4-hour infusions at 0.5 µg/kg/min. A total of 4 infusions and 4 follow-up evaluations, with an interval of 2 weeks, were performed. Severity of symptoms were assessed by using Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS-18) and Clinical Global Impression (CGI) scales. RESULTS: SNP and placebo groups did not differ at baseline or in change from baseline for PANSS-total (F = 0.525; p = 0.841), PANSS-positive (F = 0.32; p = 0.958), PANSS-negative (F = 1.05; p = 0.483), BPRS (F = 0.615; p = 0.734), or CGI-S (F = 1.11; p = 0.416) scores. SNP was well tolerated and showed a good safety profile. CONCLUSION: Although preliminary, the present findings suggest that SNP is not efficacious in TRS, reinforcing previous studies that have not demonstrated symptom improvement in chronic schizophrenia subjects. At this time, it is conceivable to speculate that efficacy of SNP might be restricted to early stages of disease.

Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of mRNA COVID-19 Vaccines?

MYTH: Corticosteroid injection for the treatment of pain and inflammation is known to decrease the efficacy of the messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19). FACT: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an mRNA COVID-19 vaccine decreases the efficacy of the vaccine.However, based on the known timeline of hypothalamic-pituitary-adrenal (HPA) axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Pfizer-BioNTech and Moderna vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to a COVID-19 mRNA vaccine dose and no less than 1 week following a COVID-19 mRNA vaccine dose, whenever possible.