Local Site Research Articles

Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults.

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVCmax in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.NEW & NOTEWORTHY We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.

Current Emergency Medical Service Vasoactive Use for the Management of Shock.

We sought to describe the indications for vasoactive medication administration, hemodynamic treatment targets, and specific agents used by various international emergency medical service (EMS) providers. In March 2022, we sent an online survey comprising of 20 questions to Medical Directors of EMSs across Australia, the Asia Pacific region, and North America. A total of 108 EMS directors were emailed an invitation to participate. None. Twenty-five EMS medical directors responded. Local site guidelines for vasoactive agent administration were available to 77.3% of providers. Epinephrine was commonly used as first-line vasoactive agent in 52% of questionnaire respondents, followed by norepinephrine (22%), dopamine (18%), and metaraminol (4%). Epinephrine was the most commonly used vasoactive agent across all forms of shock, with a higher proportion of utilization in cases of cardiogenic shock (58%) and patients suffering shock following cardiac arrest (56%). International EMS vasoactive use in the management of shock is heterogeneous. Future randomized controlled trials should aim to elucidate optimal prehospital treatment strategies for shock, including the initiation, choice of agent, and monitoring of vasoactive medication.

Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients

Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides. Primary objective was evaluation of immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was throughout successful, proving the feasibility of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions being the most common adverse event. Only few patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses due to immune-chemotherapy and lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the immunopeptidome-guided warehouse-based vaccine design reported here with a potent novel adjuvant evaluating personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies.Clinical trial registrationwww.clinicaltrialsregister.eu, identifier NCT02802943.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30s. Correspondingly, two-photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Systemic tumor regression with synergy therapy: radiotherapy and CAR-T

Pancreatic ductal adenocarcinoma (PDAC) is one of the most poorly prognostic digestive tract malignancies. CLDN18.2 CAR-T therapy has recently shown promising clinical effects in PDAC. Radiotherapy, a traditional treatment, can induce systemic immune activation and abscopal effects. However, the synergistic effect and mechanism of their combination in PDAC treatment remain poorly understood. In this study, we developed a CLDN18.2-specific CAR-T and applied it to unilateral and bilateral mouse tumor models. Our results demonstrated that this synergy therapy not only improved tumor-killing effects in unilateral tumor-bearing mice but also induced regression in both local and distant tumors in bilateral tumor models. Mechanistically, early radiation-induced apoptosis promoted the proliferation of CD8 + T cells, while increased chemokine CCL2 levels from localized and distant tumor sites facilitated CAR-T and endogenous T cell infiltration, leading to systemic tumor suppression. This study proposes a promising approach for treating metastatic pancreatic cancer by combining radiotherapy and CAR-T therapy, elucidating the mechanism of CAR-T cell-enhanced radiotherapy effects ex vivo, and highlighting a novel strategy for combating metastatic pancreatic cancer.

Dosimetric and biological impact of activity extravasation of radiopharmaceuticals in PET imaging.

The increasing use of nuclear medicine and PET imaging has intensified scrutiny of radiotracer extravasation. To our knowledge, this topic is understudied but holds great potential for enhancing our understanding of extravasation in clinical PET imaging. This work aims to (1) quantify the absorbed doses from radiotracer extravasation in PET imaging, both locally at the site of extravasation and with the extravasation location as a source of exposure to bodily organs and (2) assess the biological ramifications within the injection site at the cellular level. A radiation dosimetry simulation was performed using a whole-body 4D Extended Cardiac-Torso (XCAT) phantom embedded in the GATE Monte Carlo platform. A 10-mCi dose of 18F-FDG was chosen to simulate a typical clinical PET scan scenario, with 10% of the activity extravasated in the antecubital fossa of the right arm of the phantom. The extravasation volume was modeled as a 5.5mL rectangle in the hypodermal layer of skin. Absorbed dose contributions were calculated for the first two half-lives, assuming biological clearance thereafter. Dose calculations were performed as absorbed doses at the organ and skin levels. Energy deposition was simulated both at the local extravasation site and in multiple organs of interest and converted to absorbed doses based on their respective masses. Each simulation was repeated ten times to estimate Monte Carlo uncertainties. Biological impacts on cells within the extravasated volume were evaluated by randomizing cells and exposing them to a uniform radiation source of 18F and 68Ga. Particle types, their energies, and direction cosines were recorded in phase space files using a separate Geant4 simulation to characterize their entry into the nucleus of the cellular volume. Subsequently, the phase space files were imported into the TOPAS-nBio simulation to assess the extent of DNA damage, including double-strand breaks (DSBs) and single-strand breaks (SSBs). Organ-level dosimetric estimations are presented for 18F and 68Ga radionuclides in various organs of interest. With 10% extravasation, the hypodermal layer of the skin received the highest absorbed dose of 1.32±0.01Gy for 18F and 0.99±0.01Gy for 68Ga. The epidermal and dermal layers received absorbed doses of 0.07±0.01Gy and 0.13±0.01Gy for 18F, and 0.14±0.01Gy and 0.29±0.01Gy for 68Ga, respectively. In the extravasated volume, 18F caused an average absorbed dose per nucleus of 0.17±0.01Gy, estimated to result in 10.58±0.50 DSBs and 268.11±12.43 SSBs per nucleus. For 68Ga, the absorbed dose per nucleus was 0.11±0.01Gy, leading to an estimated 6.49±0.34 DSBs and 161.24±8.12 SSBs per nucleus. Absorbed doses in other organs were on the order of micro-gray (µGy). The likelihood of epidermal erythema resulting from extravasation during PET imaging is low, as the simulated absorbed doses to the epidermis remain below the thresholds that trigger such effects. Moreover, the organ-level absorbed doses were found to be clinically insignificant across various simulated organs. The minimal DNA damage at the extravasation site suggests that long-term harm, such as radiation-induced carcinogenesis, is highly unlikely.

Site characterization of Sikkim Himalaya using HVSR

The northeastern state of Sikkim lying in central segment of the Himalayan orogen is a seismically active region which was plagued by the recent 2011 Mw6.9 earthquake. Analysis of local earthquakes recorded at the recently deployed seismic network of 27 broadband seismic stations revealed seismogenic zone extending down to lower crustal depths with a predominant strike-slip faulting mechanism. Persistent seismicity in a region with complex tectonic setting makes it imperative to study the site characteristics crucial for determining the local site conditions. Here, we harness the noise and local earthquakes records from the Sikkim network to compute horizontal-to-vertical spectral ratio (HVSR) for site characterization. Local geology and topography are observed to incite distinctly intricate trends in the HVSR curves. The thick sedimentary deposit of the Himalayan foreland basin causes high amplification (∼7) at low resonant frequencies (&lt;1 Hz). The HVSR curves in the western section of Main Central Thrust Zone exhibits distinct double amplification peaks (∼2.5 at 1 Hz and 5 Hz) under the influence of the parallely dipping sheets of the duplex structure. Whereas, the eastern section of Main Central Thrust zone exhibit a rather irregular trend owing to its proximity to the transitioning lithological unit. The central section prone to landslides has characteristic peaks at 2 Hz and 8 Hz, indicative of the geometry of the sliding surface. Effects of towering topography and high wind speeds at corresponding elevations are observed to result in anomalously high amplification (∼25) at low frequencies (&lt; 1 Hz). Directional amplification along discrete azimuth signifies the pronounced effect of topography and geometry of lithotectonic units in site response. Locally varying site response with prevalent seismicity amplifies the seismic hazard risk potential of Sikkim Himalaya.

Nature of the EWS-FLI1 Oncoprotein.

The research presented in this paper focuses on the EWS-FLI1 oncoprotein, a critical factor in Ewing sarcoma, a rare and lethal cancer primarily affecting children and young adults. Through molecular dynamics and quantum mechanics analyses, the study explores the reactivity properties of six snapshots of the EWS-FLI1 oncoprotein, aiming to contribute to the development of targeted therapies. The investigation emphasizes the significance of understanding the molecular behavior of EWS-FLI1 for effective treatment development, utilizing computational methods such as density functional theory. The findings suggest that EWS-FLI1 is a compact, electrophilic protein with localized reactive sites, providing valuable insights for potential drug development and enhancing our knowledge of Ewing sarcoma for targeted treatments.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

Isolation and characterization of halophilic Bacillus thuringiensis from local Egyptian sites and their potential against Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae)

BackgroundBacillus thuringiensis (Bt) serves as a peculiar soil microbe that is Gram-positive, rod-shaped, spore-forming, and aerobic facultative. It endures across a range of conditions and has been demonstrated to be an effective biological pest control agent against several insect pests. The main objective of the study is to isolate and recognize Bt bacteria from saline environments in Egyptian soil for biological surveillance uses.ResultsIsolates three, four, five, ten, eleven, twelve, and thirteen were found to be moderately tolerant, while isolate eight showed highly tolerant, but isolate six was found to be borderline extreme halophile. On the other hand, the other isolates showed extreme halophiles. To find out the presence of crystals, a scanning electron microscope was carried out and the result showed that the crystals ranged from spherical to bi-pyramidal spherical. Molecular analysis was carried out using universal primers to confirm the presence of cry genes. The results showed that 84.6% of the isolates contain cry seven and eight, whereas cry one and four are distributed by 92.3%. Cry two genes were found to be 100 percent in all tested and isolated cultures. Cry genes were present and distribution among isolated was detected using gene-specific primers. cry3Ba1 and cry8B showed the lowest and equal distribution among the isolates, while the cry2Ab2gene frequency distribution was (84.6%) among isolated cultures. Around six cry genes were found to be absent in all isolated cultures. The bioinsecticidal activity and bioassays were carried out to check the potential effect of halophilic Bt isolates against 1st instar larvae of the Fall Armyworm (FAW) Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). Mortality was calculated after infecting S. frugiperda with thirteen Bt isolates. The most virulent Bt isolate was isolate 7, followed by isolate 10, with LC50 values of 9.542 × 107 spores/ml and 1.289 × 108 spores/ml, respectively, after 72 h. Morphological traits of the larvae were carried out, to check the effect of Bt isolates as a biological control against the FAW.ConclusionTo protect and enhance the sustainability of field crops and vegetables, especially in new high salinity lands, from disease-causing insects such as FAW, it is necessary to identify new strains of Bt from these saline lands. In this field, local isolates of Bt from several regions in Egypt known for their high levels of salinity were documented and showed an effective bioinsecticide on FAW larvae.

Response analysis of a long-span cable-stayed bridge with ultra-high piles subjected to near-fault ground motions considering deep-water, sedimentation, local site, and wave-passage effect

The objective of this study is to examine the dynamic response behavior of a long-span cable-stayed bridge with ultra-high piles subjected to near-fault ground motions, comprehensively considering deep-water, sedimentation, local site, and wave-passage effects. Firstly, a 3D finite element (FE) model of the long-span cable-stayed bridge with ultra-high piles (Approximately 105 m) and a tower height of 216.4 m was established using Midas software. The deep-water, sedimentation, local site, and wave-passage effects were synthetically considered in this FE model. The FE model incorporates the sag effect of the stayed cable and the pile-soil interaction, enabling a detailed seismic analysis. Secondly, the examined near-fault ground motions with long-period velocity pulses were selected from the PEER database according to the design acceleration response spectrum with a fortification intensity of VIII degrees. Finally, nonlinear time history analyses of the selected long-span cable-stayed bridge, subjected to spatial near-fault ground motions including local site effect and wave-passage effect, were conducted, and the responses of critical design sections and points in structures were examined and evaluated. The results demonstrate that long-period velocity pulses can significantly affect the structural responses, while deep-water and sedimentation effects do not have a significant impact on the dynamic responses of long-span cable-stayed bridges. For the local site effect, the softer the soil at the support site and the greater the difference in soil conditions at the support, the larger the structural response. Regarding the wave effect, the structural response will increase or decrease depending on the magnitude of the wave speed and the span length between towers.

DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1

RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structural remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in 3’UTR regions. DHX36 binding increases structural accessibility at 3’UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m6A) modification and YTHDF1 binding; and DHX36 induced structural changes may facilitate YTHDF1 binding to m6A sites leading to RNA degradation. Altogether, our findings uncover the structural remodeling effect of DHX36 binding and its impact on RNA abundance through regulating m6A dependent YTHDF1 binding.

Abstract 4135466: Feasibility of Using Existing Infection Surveillance Methods for Percutaneous Coronary Intervention-related Infections

Background: Percutaneous coronary intervention (PCI) is a treatment that requires attention in terms of infection control, as it necessitates aseptic procedures similar to surgical operations. However, surveillance practices for PCI-related infections are uncommon, and no standardized surveillance program has been established. Purpose: To assess the feasibility of using existing surveillance methods to detect PCI-related infectious diseases. Method: To identify PCI-related bloodstream infections of local access sites, four existing case definitions, namely, laboratory-confirmed bloodstream infections (LCBI), clinical sepsis (CSEP), local access site infection (LASI), and exit site infection (ESI), were retrospectively applied to 1,037 patients who underwent PCI between April 2018 and March 2021. Of these, 167 experienced fever, underwent blood culture testing, and/or received antibiotics within 6 days of PCI. To confirm consistent evaluation, two independent infection control experts evaluated each case record according to the four case definitions. Results: Twenty-three patients (2.2%) were diagnosed with PCI-related infections, including two patients according to LCBI, 21 according to CSEP, and none according to LASI and ESI. Thirteen patients (LCBI: 1, CSEP: 12) received circulatory assist devices such as intra-aortic balloon pumping. Of the remaining 11 patients, 10 underwent emergency PCI, and one underwent elective PCI ( P =0.0001). The average length of hospital stay was 16.1 days for patients with PCI-related infections and 4.7 days for non-infected patients ( P &lt;0.05). Conclusion: The positive diagnosis of PCI-related infections was predominantly based on CSEP. Many of these positive patients underwent emergency PCI and/or received circulatory assist devices. The results of the present study warrant further investigations with larger patient cohorts.

Abstract 4136984: Low Occurence of Fetal Extranodal Findings and AV Interval Prolongation in Prospectively Followed High Titer Anti-Ro Pregnancies

. Background: Third-degree atrioventricular block (AVB) is the most common manifestation of Anti-Ro antibody associated fetal cardiac disease. Extranodal findings of isolated cardiac echogenicity, valvulitis with insufficiency and AV interval prolongation have been reported but not described in large prospective series. Aims: To report the occurrence and outcomes of extranodal findings in subjects followed prospectively since 2020 in STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV block Likely to Occur Quickly) and the Registry for Neonatal Lupus (RNL). Methods: We reviewed fetal echo reports from pregnant STOP BLOQ and RNL Anti-Ro antibody subjects. Pregnancies with high (&gt;1000 EU for anti-Ro52 or 60) antibody titers measured in a core research lab underwent surveillance with home fetal heart rate monitoring (FHRM) 3x/day and weekly or bi-weekly fetal echos from 17- 26 gestational weeks. Low titer subjects underwent echo or no surveillance based on local site protocol. We evaluated cardiac function, effusions, cardiac echogenicity and its location, any tricuspid (TV) or mitral (MV) insufficiency trivial or &gt;trivial) and AV conduction times (&lt;150, 150-170 or &gt;170 ms) Results: Echo reports were available in 622 prospectively followed pregnancies (376 high (40/376 with a previously affected child) and 246 low-titer pregnancies. All had subjectively normal ventricular function and none had effusions. Seven fetuses, 2 low and 5 high titer at 19 (range 16.7-21.7) weeks demonstrated cardiac echogenicity (n=6), AV or semilunar valve insufficiency (n=2) or AV interval 150-170 ms (n=2) (Table). Subjects 1 and 2, both high titer and treated with prophylactic Plaquenil (400 mg/d before 10 gestational weeks), had prior fetal AVB. Subject #1 had normal AV conduction but MV and TV echogenicity and moderate insufficiency of both valves which resolved in days after IVIG and dexamethasone (dex) treatment, but 3° AVB developed at 19 weeks after dex wean. Subjects 2-7 received no treatment and extranodal findings did not progress to cardiac dysfunction or AVB. During the same time period, 10 high titer subjects developed 2° or 3° AVB. Conclusion: Anti-Ro associated extranodal findings are rare, occurring in 1% of pregnancies overall and in 5% of pregnancies with a previously affected child. Unlike AVB, extranodal findings can occur in low titer pregnancies. The role of treatment for isolated extranodal findings in the absence of cardiac dysfunction is unclear.

Maturation of Tertiary Lymphoid Structures.

Tertiary lymphoid structures (TLS) are organized collections of B and T lymphocytes that arise in nonlymphoid tissue in response to chronic, unresolved inflammation. TLS have structural and functional similarities to germinal centers found in lymph nodes and are believed to support the establishment of lymph node-like adaptive immune responses at local sites of inflammation. However, understanding of the underlying biology of these structures remains limited, particularly the different stages of TLS life cycle and the signals governing the initiation, maturation, and termination of TLS. Here, we review current understanding of the maturation of TLS and the signals and cell types involved in various stages of development with particular emphasis on recent studies of TLS in cancer, where evidence suggests that TLS may play an important role in supporting antitumor immune responses in solid tumors.

Vanadate Inclusion Leading to Red-Ox-Rich Zircon PrCrO4: Synthesis, Magnetic, and Catalytic Properties.

Rare-earth-based ternary compounds with the formula REBO4 (B = V, Cr, P, As) exhibit rich structural chemistry and associated technologically significant properties. Among the rare-earth chromates, realizing PrCrO4 in a single polymorphic modification has been challenging. Herein, we report the successful stabilization of the zircon polymorph of PrCrO4 by introducing 10 mol % of VO43- instead of CrO43- following a solution combustion method. Compositions with progressively higher amounts of vanadate have been synthesized and characterized extensively. XPS analysis of 10 and 50 mol % VO43- substituted PrCrO4 samples ascertained the existence of Pr3+/4+, Cr4+,5+, and V5+ in them, making it a red-ox-rich system. The tetragonal symmetry of PrCr0.50V0.50O4 was confirmed from the HRTEM images and SAED patterns. FTIR and Raman spectral analyses indicated distorted tetrahedral (Cr/VO4) units with a local site symmetry below D2d. Both d-d and f-f transitions of Cr4+ and Pr3+, respectively, were observed in the absorption spectra. Field and temperature-dependent magnetic measurements of PrCr0.50V0.50O4 confirmed its predominant paramagnetic behavior. The samples possessed porous morphology with a reasonable surface area. PrCr1-xVxO4 (x = 0.00-0.50) samples catalyzed the oxidation of phenol. This study demonstrated B-site tuning in ABO4 systems to select a desired polymorph preferentially.

Understanding responses to multi-electrode epiretinal stimulation using a biophysical model.

Neural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike. However, this multi-site activation hypothesis is difficult to verify experimentally. We developed a biophysical model to study retinal ganglion cell (RGC) responses to multi-electrode stimulation and validated it using data collected from ex vivo preparations of the macaque retina using a microelectrode array (512 electrodes; 30µm pitch; 10µm diameter). First, the model was validated by using it to reproduce essential empirical findings from single-electrode recording and stimulation, including recorded spike voltage waveforms at multiple locations and sigmoidal responses to injected current. Then, stimulation with two electrodes was modeled to test how the positioning of the electrodes relative to the cell affected the degree of response nonlinearity. Currents passed through pairs of electrodes positioned near the cell body or far from the axon (>40 µm) exhibited approximately linear summation in evoking spikes. Currents passed through pairs of electrodes close to the axon summed linearly when their locations along the axon were similar, and nonlinearly otherwise. Over a range of electrode placements, several distinct, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. Similar trends were observed for three-electrode stimuli. All of these trends in the simulation were consistent with experimental observations. Significance . These findings support the multi-site activation hypothesis for nonlinear activation of neurons, providing a biophysical interpretation of previous experimental results and potentially enabling more efficient use of multi-electrode stimuli in future neural implants.

Observation of Highly Spin-Polarized Dangling Bond Surface States in Rare-Earth Pnictide Tellurides.

To generate and manipulate spin-polarized electronic states in solids are crucial for modern spintronics. The textbook routes employ quantum well states or Shockley/topological type surface states whose spin degeneracy is lifted by strong spin-orbit coupling and inversion symmetry breaking at the surface/interface. The resultant spin polarization is usually truncated because of the intertwining between multiple orbitals. Here a unique type of surface states is realized, namely, dangling bond surface states in a family of ternary rare-earth pnictide tellurides RePnTe (Re = La, Gd, Ce; Pn = Sb, Bi), with robust band structure and sizeable spin splitting. Spin and angle-resolved photoemission spectroscopy measurements reveal high spin polarization and distinct spin-momentum locking texture, which, according to the theoretical analysis, arise from local site asymmetry and surface-purified spin-orbital texture. The work extends the so-called "hidden spin polarization" from the bulk to the surface, presenting an intriguing spin-orbital-momentum-layer locking phenomenon, which may shed lights on potential spintronic applications.

Recombination efficiency in c-plane (In,Ga)N/GaN quantum wells: saturation of localisation sites versus Auger–Meitner recombination

Abstract Light emitting diodes based on c-plane (In,Ga)N/GaN quantum wells (QWs) can have &gt;90% emission efficiency at modest current densities but this drops significantly at higher excitation, an effect known as efficiency droop that limits device efficacy at high brightness. Several explanations for this have been proposed including the saturation of carrier localisation sites at high excitation densities, resulting in a greater exposure of carriers to defects and hence a significant increase in the associated non-radiative recombination processes. Here, power- and temperature-dependent photoluminescence spectroscopy of c-plane (In,Ga)N/GaN QWs is used to investigate the relationship between the saturation of localised states and emission efficiency. For the samples studied, we find that the saturation of localised sites broadly coincides with the onset of efficiency droop. However, it is also found that as the localised states saturate with increasing excitation, the relative contribution of defect-associated non-radiative processes to overall recombination decreases rather than increases. Based on these observations and on modelling of recombination processes in the QW, it is concluded that the saturation of localised states does not significantly contribute to the reduction in emission efficiency at high excitation. Our studies rather suggest that defect-related non-radiative recombination is out-competed by radiative and Auger–Meitner recombination at the carrier densities required for saturation.

Quasi-in-situ observations of microstructural evolution during cyclic deformation of a Mg-Zn-Ca alloy

Quasi-in-situ electron backscatter diffraction (EBSD) was employed to investigate the microstructural evolution of a homogenized coarse-grained Mg-1.2Zn-0.1Ca alloy during cyclic deformation at a strain amplitude of 0.8 %. The random orientations of grains along with the soft state of the alloy resulted in symmetrical hysteresis loops and cyclic hardening. Besides the occurrence of twinning-detwinning, basal <a>/pyramidal II <c+a> and pyramidal I <a> slip systems were primarily activated. Grain boundaries with a higher misorientation angle of >35° served as preferential sites for strain localization.