Voltage-induced modulation of interfacial ionic liquids measured using surface plasmon resonant grating nanostructures.

We have used surface plasmon resonant metal gratings to induce and probe the dielectric response (i.e., electro-optic modulation) of ionic liquids (ILs) at electrode interfaces. Here, the cross-plane electric field at the electrode surface modulates the refractive index of the IL due to the Pockels effect. This is observed as a shift in the resonant angle of the grating (i.e., Δϕ), which can be related to the change in the local index of refraction of the electrolyte (i.e., Δnlocal). The reflection modulation of the IL is compared against a polar (D2O) and a non-polar solvent (benzene) to confirm the electro-optic origin of resonance shift. The electrostatic accumulation of ions from the IL induces local index changes to the gratings over the extent of electrical double layer (EDL) thickness. Finite difference time domain simulations are used to relate the observed shifts in the plasmon resonance and change in reflection to the change in the local index of refraction of the electrolyte and the thickness of the EDL. Simultaneously using the wavelength and intensity shift of the resonance enables us to determine both the effective thickness and Δn of the double layer. We believe that this technique can be used more broadly, allowing the dynamics associated with the potential-induced ordering and rearrangement of ionic species in electrode-solution interfaces.

Hot electron-driven photocatalysis and transient absorption spectroscopy in plasmon resonant grating structures.

Plasmon resonant grating structures provide an effective platform for distinguishing between the effects of plasmon resonant excitation and bulk metal absorption via interband transitions. By simply rotating the polarization of the incident light, we can switch between resonant excitation and non-resonant excitation, while keeping all other parameters of the measurement constant. With light polarized perpendicular to the lines in the grating (i.e., TE-polarization), the photocatalytic reaction rate (i.e., photocurrent) is measured as the angle of the incident laser light is tuned through the resonance with the grating. Here, hot holes photoexcited in the metal are used to drive the oxygen evolution reaction (OER), producing a measurable photocurrent. Using TE-polarized light, we observe sharp peaks in the photocurrent and sharp dips in the photoreflectance at approximately 9° from normal incidence, which corresponds to the conditions under which there is good wavevector matching between the incident light and the lines in the grating. With light polarized parallel to the grating (i.e., TM), we excite the grating structure non-resonantly and there is no angular dependence in the photocurrent or photoreflectance. In order to quantify the lifetime of these hot carriers, we performed transient absorption spectroscopy of these plasmon resonant grating structures. Here, we observe one feature in the spectra corresponding to interband transitions and another feature associated with the plasmon resonant mode in the grating. Both features decay over a time scale of 1-2 ps. The spectral responses of grating structures fabricated with Ag, Al, and Cu are also presented.

Path perturbation detection tasks reduce MSTd neuronal self-movement heading responses.

We presented optic flow and real movement heading stimuli while recording MSTd neuronal activity. Monkeys were alternately engaged in three tasks: visual detection of optic flow heading perturbations, vestibular detection of real movement heading perturbations, and auditory detection of brief tones. Push-button RTs were fastest for tones and slower for visual and vestibular heading perturbations, suggesting that the tone detection task was easier. Neuronal heading selectivity was strongest during the tone detection task, and weaker during the visual and vestibular heading perturbation detection tasks. Heading selectivity was weaker during visual and vestibular path perturbation detection, despite our presented heading cues only in the visual and vestibular modalities. We conclude that focusing on the self-movement transients of path perturbation distracted the monkeys from their heading and reduced neuronal responsiveness to heading direction. NEW & NOTEWORTHY Heading analysis is critical for steering and navigation. We recorded the activity of monkey cortical heading neurons during naturalistic self-movement. When the monkeys were required to respond to transient changes in their path, neuronal responses to heading direction were diminished. This suggests that the need to respond to momentary path perturbations reduces your ability to process your heading direction.

Navigational path integration by cortical neurons: origins in higher-order direction selectivity.

Navigation relies on the neural processing of sensory cues about observer self-movement and spatial location. Neurons in macaque dorsal medial superior temporal cortex (MSTd) respond to visual and vestibular self-movement cues, potentially contributing to navigation and orientation. We moved monkeys on circular paths around a room while recording the activity of MSTd neurons. MSTd neurons show a variety of sensitivities to the monkey's heading direction, circular path through the room, and place in the room. Changing visual cues alters the relative prevalence of those response properties. Disrupting the continuity of self-movement paths through the environment disrupts path selectivity in a manner linked to the time course of single neuron responses. We hypothesize that sensory cues interact with the spatial and temporal integrative properties of MSTd neurons to derive path selectivity for navigational path integration supporting spatial orientation.

A stress-induced source of phonon bursts and quasiparticle poisoning.

The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called "quasiparticle poisoning". Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.

Task contingencies and perceptual strategies shape behavioral effects on neuronal response profiles.

We presented optic flow simulating eight directions of self-movement in the ground plane, while monkeys performed delayed match-to-sample tasks, and we recorded dorsal medial superior temporal (MSTd) neuronal activity. Randomly selected sample headings yield smaller test responses to the neuron's preferred heading when it is near the sample's heading direction and larger test responses to the preferred heading when it is far from the sample's heading. Limiting test stimuli to matching or opposite headings suppresses responses to preferred stimuli in both test conditions, whereas focusing on each neuron's preferred vs. antipreferred stimuli enhances responses to the antipreferred stimulus. Match vs. opposite paradigms create bimodal heading profiles shaped by interactions with late delay-period activity. We conclude that task contingencies, determining the prior probabilities of specific stimuli, interact with the monkeys' perceptual strategy for optic flow analysis. These influences shape attentional and working memory effects on the heading direction selectivities and preferences of MSTd neurons.

Driving strategy alters neuronal responses to self-movement: cortical mechanisms of distracted driving.

We presented naturalistic combinations of virtual self-movement stimuli while recording neuronal activity in monkey cerebral cortex. Monkeys used a joystick to drive to a straight ahead heading direction guided by either object motion or optic flow. The selected cue dominates neuronal responses, often mimicking responses evoked when that stimulus is presented alone. In some neurons, driving strategy creates selective response additivities. In others, it creates vulnerabilities to the disruptive effects of independently moving objects. Such cue interactions may be related to the disruptive effects of independently moving objects in Alzheimer's disease patients with navigational deficits.

Neural activity during monkey vehicular wayfinding.

Navigation gets us from place to place, creating a path to arrive at a goal. We trained a monkey to steer a motorized cart in a large room, beginning at its trial-by-trial start location and ending at a trial-by-trial cued goal location. While the monkey steered its autonomously chosen path to its goal, we recorded neural activity simultaneously in both the hippocampus (HPC) and medial superior temporal (MST) cortex. Local field potentials (LFPs) in these sites show similar patterns of activity with the 15-30 Hz band highlighting specific room locations. In contrast, 30-100 Hz LFPs support a unified map of the behaviorally relevant start and goal locations. The single neuron responses (SNRs) do not substantially contribute to room or start-goal maps. Rather, the SNRs form a continuum from neurons that are most active when the monkey is moving on a path toward the goal, versus other neurons that are most active when the monkey deviates from paths toward the goal. Granger analyses suggest that HPC firing precedes MST firing during cueing at the trial start location, mainly mediated by off-path neurons. In contrast, MST precedes HPC firing during steering, mainly mediated by on-path neurons. Interactions between MST and HPC are mediated by the parallel activation of on-path and off-path neurons, selectively activated across stages of this wayfinding task.

National estimates of seroincidence and seroprevalence for herpes simplex virus type 1 and type 2 among US military adults aged 18 to 29 years.

BACKGROUND: While population-based seroprevalence studies of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are widespread, seroincidence studies are largely limited to select or high-risk populations. The US military offers a potential population to derive national seroincidence rate estimates for young adults (ages 18-29). METHODS: We used banked, longitudinal serum specimens collected in a cohort of 1094 military personnel aged 18 to 30 years who served between 1989 and 2005 to estimate national HSV-1 and HSV-2 seroincidence and seroprevalence for the young, adult military population, weighted according to the US Census. Serum was tested with indirect ELISA (enzyme-linked immunosorbent assay). RESULTS: Estimated national seroincidence rates for the US young, adult military population were 9.1 per 100 person-years (95% confidence interval: 4.6-13.5) for HSV-1 and 6.2 (95% confidence interval: 3.1-9.3) for HSV-2. Female sex and black race were associated with significantly higher HSV-2 seroconversion rates. Our estimated HSV1/2 seroprevalences were comparable to US national data provided by National Health and Nutrition Examination Surveys' serosurveys except for non-Hispanic blacks and Hispanics. CONCLUSION: Although these US 2000 Census-weighted estimates of HSV-1 and HSV-2 seroincidence apply only to young, military adults, they nonetheless supply, to our knowledge, the only national figures that might be used to predict US national HSV1/2 seroincidence in young adults. Thus, we believe that our findings in this military population can be used to inform the planning of HSV-1 and 2 prevention measures in the general, young-adult US population.

The effect of acute and repeated ischemic preconditioning on recovery following exercise-induced muscle damage.

OBJECTIVES: The aim of this investigation was to determine if acute or repeated applications of ischemic preconditioning (IPC) could enhance the recovery process, following exercise induced muscle damage (EIMD). DESIGN: Randomized control trial. METHODS: Twenty-three healthy males were familiarised with the muscle damaging protocol (five sets of 20 drop jumps from a 0.6 m box) and randomly allocated to one of three groups: SHAM (3 × 5 min at 20 mmHg), Acute IPC (3 × 5 min at 220 mmHg) and Repeated IPC (3 days x 3 × 5 min at 220 mmHg). The indices of muscle damage measured included creatine kinase concentration ([CK]), thigh swelling, delayed onset muscle soreness, counter movement jumps (CMJ) and maximal voluntary isometric contraction (MVIC). RESULTS: Both acute and repeated IPC improved recovery in MVIC versus SHAM. Repeated IPC led to a faster MVIC recovery at 48 h (101.5%) relative to acute IPC (92.6%) and SHAM (84.4%) (P <  0.05). Less swelling was found for both acute and repeated IPC vs. SHAM (P <  0.05) but no group effects were found for CMJ, soreness or [CK] responses (P >  0.05). CONCLUSION: Taken together, repeated IPC can enhance recovery time of MVIC more than an acute application, and both reduce swelling following EIMD, relative to a SHAM condition.

Multiplexed detection and quantification of human antibody response to COVID-19 infection using a plasmon enhanced biosensor platform.

The 2019 SARS CoV-2 (COVID-19) pandemic has illustrated the need for rapid and accurate diagnostic tests. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensor platform was used to rapidly and accurately measure antibodies against COVID-19 in human blood serum and dried blood spot samples. The GC-FP platform measures antibody-antigen binding interactions for multiple targets in a single sample, and has 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein). The GC-FP platform yielded a quantitative, linear response for serum samples diluted to as low as 1:1600 dilution. Test results were highly correlated with two commercial COVID-19 antibody tests, including an enzyme linked immunosorbent assay (ELISA) and a Luminex-based microsphere immunoassay. To demonstrate test efficacy with other sample matrices, dried blood spot samples (n = 63) were obtained and evaluated with GC-FP, yielding 100% selectivity and 86.7% sensitivity for diagnosing prior COVID-19 infection. The test was also evaluated for detection of multiple immunoglobulin isotypes, with successful detection of IgM, IgG and IgA antibody-antigen interactions. Last, a machine learning approach was developed to accurately score patient samples for prior COVID-19 infection, using antibody binding data for all three COVID-19 antigens used in the test.

Receptive field dynamics underlying MST neuronal optic flow selectivity.

Optic flow informs moving observers about their heading direction. Neurons in monkey medial superior temporal (MST) cortex show heading selective responses to optic flow and planar direction selective responses to patches of local motion. We recorded MST neuronal responses to a 90 x 90 degrees optic flow display and to a 3 x 3 array of local motion patches covering the same area. Our goal was to test the hypothesis that the optic flow responses reflect the sum of the local motion responses. The local motion responses of each neuron were modeled as mixtures of Gaussians, combining the effects of two Gaussian response functions derived using a genetic algorithm, and then used to predict that neuron's optic flow responses. Some neurons showed good correspondence between local motion models and optic flow responses, others showed substantial differences. We used the genetic algorithm to modulate the relative strength of each local motion segment's responses to accommodate interactions between segments that might modulate their relative efficacy during co-activation by global patterns of optic flow. These gain modulated models showed uniformly better fits to the optic flow responses, suggesting that coactivation of receptive field segments alters neuronal response properties. We tested this hypothesis by simultaneously presenting local motion stimuli at two different sites. These two-segment stimuli revealed that interactions between response segments have direction and location specific effects that can account for aspects of optic flow selectivity. We conclude that MST's optic flow selectivity reflects dynamic interactions between spatially distributed local planar motion response mechanisms.

Increased prevalence and mortality in undiagnosed celiac disease.

BACKGROUND & AIMS: The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. METHODS: This study included 9133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 gender-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n = 5558) or age at sampling (n = 7210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. RESULTS: Of 9133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2.0-7.5; P < .001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts, respectively, than in the Air Force cohort (both P < or = .0001). CONCLUSIONS: During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years.

Cortical neurons combine visual cues about self-movement.

Visual cues about self-movement are derived from the patterns of optic flow and the relative motion of discrete objects. We recorded dorsal medial superior temporal (MSTd) cortical neurons in monkeys that held centered visual fixation while viewing optic flow and object motion stimuli simulating the self-movement cues seen during translation on a circular path. Twenty stimulus configurations presented naturalistic combinations of optic flow with superimposed objects that simulated either earth-fixed landmark objects or independently moving animate objects. Landmarks and animate objects yield the same response interactions with optic flow; mainly additive effects, with a substantial number of sub- and super-additive responses. Sub- and super-additive interactions reflect each neuron's local and global motion sensitivities: Local motion sensitivity is based on the spatial arrangement of directions created by object motion and the surrounding optic flow. Global motion sensitivity is based on the temporal sequence of self-movement headings that define a simulated path through the environment. We conclude that MST neurons' spatio-temporal response properties combine object motion and optic flow cues to represent self-movement in diverse, naturalistic circumstances.

A fluorescent plasmonic biochip assay for multiplex screening of diagnostic serum antibody targets in human Lyme disease.

Lyme disease (LD) diagnosis using the current two-tier algorithm is constrained by low sensitivity for early-stage infection and ambiguity in determining treatment response. We recently developed a protein microarray biochip that measures diagnostic serum antibody targets using grating-coupled fluorescent plasmonics (GC-FP) technology. This strategy requires microliters of blood serum to enable multiplexed biomarker screening on a compact surface and generates quantitative results that can be further processed for diagnostic scoring. The GC-FP biochip was used to detect serum antibodies in patients with active and convalescent LD, as well as various negative controls. We hypothesized that the quantitative, high-sensitivity attributes of the GC-FP approach permit: 1) screening of antibody targets predictive for LD status, and 2) development a diagnostic algorithm that is more sensitive, specific, and informative than the standard ELISA and Western blot assays. Notably, our findings led to a diagnostic algorithm that may be more sensitive than the current standard for detecting early LD, while maintaining 100% specificity. We further show that analysis of relative antibody levels to predict disease status, such as in acute and convalescent stages of infection, is possible with a highly sensitive and quantitative platform like GC-FP. The results from this study add to the urgent conversation regarding better diagnostic strategies and more effective treatment for patients affected by tick-borne disease.

Hot Electron Driven Photocatalysis on Plasmon-Resonant Grating Nanostructures.

We demonstrate the hot electron injection of photoexcited carriers in an Ag-based plasmon resonant grating structure. By varying the incident angle of irradiation, sharp dips are observed in the reflectance with p-polarized light (electric field perpendicular to grating lines) when there is wavevector matching between the incident light and the plasmon resonant modes of the grating and no angle dependence is observed with s-polarized light. This configuration enables us to compare photoelectrochemical current produced by plasmon resonant excitation with that of bulk metal interband absorption simply by rotating the polarization of the incident light while keeping all other parameters of the measurement fixed. With 633 nm light, we observed a 12-fold enhancement in the photocurrent (i.e., reaction rate) between resonant and nonresonant polarizations at incident angles of ±7.6° from normal. At 785 nm irradiation, we observed similar resonant profiles to those obtained with 633 nm wavelength light but with a 44-fold enhancement factor. Using 532 nm light, we observed two resonant peaks (with approximately 10× enhancement) in the photocurrent at 19.4° and 28.0° incident angles, each corresponding to higher order modes in the grating with more nodes per period. The lower enhancement factors observed at shorter wavelengths are attributed to interband transitions, which provide a damping mechanism for the plasmon resonance. Finite difference time domain (FDTD) simulations of these grating structures confirm the resonant profiles observed in the angle-dependent spectra of these gratings and provide a detailed picture of the electric field profiles on and off resonance.

Cortical neuronal responses to optic flow are shaped by visual strategies for steering.

We hypothesized that neuronal responses to virtual self-movement would be enhanced during steering tasks. We recorded the activity of medial superior temporal (MSTd) neurons in monkeys trained to steer a straight-ahead course, using optic flow. We found smaller optic flow responses during active steering than during the passive viewing of the same stimuli. Behavioral analysis showed that the monkeys had learned to steer using local motion cues. Retraining the monkeys to use the global pattern of optic flow reversed the effects of the active-steering task: active steering then evoked larger responses than passive viewing. We then compared the responses of neurons during active steering by local motion and by global patterns: Local motion trials promoted the use of local dot movement near the center of the stimulus by occluding the peripheral visual field midway through the trial. Global pattern trials promoted the use of radial pattern movement by occluding the central visual field midway through the trial. In this study, identical full-field optic-flow stimuli evoked larger responses in global-pattern trials than in local motion trials. We conclude that the selection of specific visual cues reflects strategies for active steering and alters MSTd neuronal responses to optic flow.

Distraction osteogenesis for correction of distal radius deformity after physeal arrest.

PURPOSE: To present intermediate-term follow-up for pediatric patients following correction of forearm deformity with the use of distraction osteogenesis after distal radius physeal arrest in the setting of trauma. METHODS: Retrospective review of a single surgeon's experience using a circular external fixator to correct forearm deformity in four patients whose average age at time of application was 13.8 years. All patients were evaluated clinically with radiographs, physical examination, and functional outcome assessments including the Short-Form 12, Disabilities of the Arm, Shoulder and Hand, and Mayo Wrist score. RESULTS: At the time of intermediate-term follow-up, at a mean of 112 months, all patients were nearly pain free (average visual analog scale of 1). All were willing to undergo the same treatment again. Wrist flexion increased 11 degrees , extension decreased 2 degrees , radial deviation decreased 14 degrees , ulnar deviation increased 7 degrees , and pronation and supination both decreased 5 degrees on average. The radius was lengthened an average of 7 mm, with an average preoperative ulnar variance of +7 mm and an average postoperative ulnar variance of +1 mm. Mean outcome scores were as follows: Short-Form 12 was 82, Disabilities of the Arm, Shoulder and Hand was 11, and Mayo Wrist was 76. Three of four patients experienced treatment-related complications, whereas two of four required unplanned returns to the operating room. CONCLUSIONS: The use of distraction osteogenesis is a reasonable alternative to osteotomy, bone grafting, and internal fixation in pediatric patients with severe forearm deformity and dysfunction after physeal arrest in the setting of trauma. This procedure is burdened with complications and requires a committed patient and surgeon. It provides good correction of deformity and relief of pain, and maintains functional range of motion while avoiding the use of permanent orthopedic implants. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Identification of two catalases in Azotobacter vinelandii: a KatG homologue and a novel bacterial cytochrome c catalase, CCCAv.

Azotobacter vinelandii produces two detectable catalases during growth on minimal medium. The heat-labile catalase expressed during exponential growth phase was identified as a KatG homologue by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a mixed protein sample. The second catalase was heat resistant and had substantial residual activity after treatment at 90 degrees C. This enzyme was purified by anion-exchange and size exclusion chromatography and was found to exhibit strong absorption at 407 nm, which is often indicative of associated heme moieties. The purified protein was fragmented by proteinase K and identified by LC-MS/MS. Some identity was shared with the MauG/bacterial cytochrome c peroxidase (BCCP) protein family, but the enzyme exhibited a strong catalase activity never before observed in this family. Because two putative c-type heme sites (CXXCH) were predicted in the peptide sequence and were demonstrated experimentally, the enzyme was designated a cytochrome c catalase (CCC(Av)). However, the local organization of the CCC(Av) heme motifs differed significantly from that of the BCCPs as the sites were confined to the C-terminal half of the catalase. A possible Ca2+ binding motif, previously described in the BCCPs, is also present in the CCC(Av) peptide sequence. Some instability in the presence of EGTA was observed. Expression of the catalase was abolished in cccA mutants, resulting in a nearly 8,700-fold reduction in peroxide resistance in stationary phase.

RpoS expression and the general stress response in Azotobacter vinelandii during carbon and nitrogen diauxic shifts.

The general stress response mediated by the sigma factor RpoS is important for survival of bacteria in adverse environments. A mutant unable to produce RpoS was constructed using the diazotrophic bacterium Azotobacter vinelandii strain UW. Under nondesiccating, solid-medium growth conditions the wild type was culturable for 16.5 years, while the rpoS mutant remained viable for only 10 months. The rpoS mutant exhibited reduced survival compared to the wild type following hydrogen peroxide stress, and stationary phase cells were killed rapidly by 15 mM H2O2. Three catalases (Kat1, Kat2, and Kat3) were expressed in the wild type under the conditions used. Kat2 was expressed in exponential phase during shake flask growth and could be induced under highly aerated conditions in all growth phases, suggesting that there was induction by reactive oxygen intermediates. Kat3 was possibly an isoform of Kat2. In contrast, Kat1 was expressed in an RpoS-dependent manner during the mid-exponential to late stationary phases. RpoS expression did not occur exclusively in stationary phase but was influenced by changes in carbon and nitrogen source availability. There was 26- to 28-fold induction of the RpoS protein during acetate-to-glucose and ammonium-to-N2 diauxic shifts. Following recovery of growth on the alternative carbon or nitrogen source, RpoS protein concentrations declined rapidly to a basal level. However, rpoS mRNA levels did not correlate directly to RpoS levels, suggesting that there was posttranscriptional regulation. Evidence obtained using the RpoS-dependent reporter Kat1 suggested that there is regulation of the RNAP:RpoS holoenzyme at the level of complex formation or activity.