A strong argument can be made that physics is, at its core, the study of symmetries. Nonlinear optics is certainly no exception, with an enormous number of distinct processes each depending in its own way on the underlying symmetries of the physical system, the light, or of nature itself. Restricting ourselves to optical harmonic generation, we will explore three unique physical systems as well as three symmetries. In each case, the controlled breaking of that symmetry will lead to optical enhancements, novel nonlinearities, or deep physical insights. Beginning with silicon metasurfaces, we will explore the effects of even and odd spatial symmetries in optical systems. The periodic breaking of this symmetry will lead us to the highly engineerable physics of bound states in the continuum. By studying the harmonic emission from an atomic gas in the volume surrounding the metasurface, we will come to understand that significant nonlinear optical enhancements can be engineered with any linewidth and at any wavelength. In the context of the two-dimensional material hexagonal boron nitride, we will investigate and break crystal inversion symmetries. Using an intense laser tuned to the phonon resonance of hexagonal boron nitride, large amplitude anharmonic ionic motions will provide us a powerful degree of control over the internal symmetries of the system at an atomic level. Breaking this symmetry, we measure short-lived even-order nonlinearities that would otherwise be forbidden in equilibrium. Our observations for second- and third- harmonic generation are confirmed by time-dependent density functional theory. Those simulations further extend the understanding of this symmetry-breaking effect to even higher order processes. Lastly, single-crystal graphene and graphite provide an ideal platform through which to explore time-reversal symmetry. Chiral photons, or optical beams with ellipticity and handedness, are well known to break time-reversal symmetry. While applying high-power, chiral light to graphene, the breaking of time-reversal lifts a degeneracy of the K and K’ valleys in the momentum space Brillouin zone. Lifting this degeneracy, we unveil underlying spatial symmetry properties of graphene in odd-order third- and fifth- harmonic generation which should otherwise be unobservable. We also show experimentally, for the first time, that valley polarization and population can be extracted using our technique.

The search for physics beyond the Standard Model has been a main focus of the scientific community for several decades. Unknown physics in the form of new interactions violating the simultaneous reversal of charge and parity symmetries (CP) would, for example, provide a significant step towards understanding the baryon matter-antimatter asymmetry observed in the Universe. Such parameters are predicted to also manifest themselves in atomic and molecular systems in the form of both: permanent electric dipole moments and nuclear charge distribution asymmetries described by the nuclear Schiff moment. Both can be measured to a high degree of precision in modern experiments, allowing us to place stringent limits on parameters appearing in new fundamental theories. The Cold Molecule Nuclear Time Reversal Experiment (CeNTREX) is the latest approach to probing these effects. CeNTREX is a molecular beam experiment that uses thallium fluoride (²⁰⁵Tl⁹F) as its test species to measure energy shifts induced by the interaction of thallium's nuclear Schiff moment. It does so by performing nuclear magnetic resonance using a separate oscillatory fields technique. The precision of this measurement is dictated by the free precession time and the number of interrogated molecules, and is significantly enhanced by thallium fluoride's inherent properties. Employing novel methods, CeNTREX strives to achieve significant improvements to limits placed on the fundamental parameters. One such method is rotational cooling. It was thoroughly analyzed, simulated and experimentally confirmed - with the help of optical and microwave pumping, we collapsed the initial Boltzmann distribution of molecules amongst their rotational states into one chosen hyperfine state of the ground rotational state manifold. The efficiency of this process depends on multiple factors, the most crucial being the approach towards dark state destabilization and remixing. After careful investigation, we chose the most appropriate method and devised an efficient rotational cooling scheme. Experimental confirmation showed an enhancement factor of r𝑓23.70±1.13, very close to our theoretical predictions. This allows us to conclude that CeNTREX should provide a 2500-fold improvement over the current best measurements of the nuclear Schiff moment in thallium nucleus.

Eradication of latent human immunodeficiency virus (HIV) infection is a global health challenge. Reactivation of HIV latency and killing of virus-infected cells, the so-called “kick and kill” or “shock and kill” approaches, are a popular strategy for HIV cure. While antiretroviral therapy (ART) halts HIV replication by targeting multiple steps in the HIV life cycle, including viral entry, integration, replication, and production, it cannot get rid of the occult provirus incorporated into the host-cell genome. These latent proviruses are replication-competent and can rebound in cases of ART interruption or cessation. In general, a very small population of cells harbor provirus, serve as reservoirs in ART-controlled HIV subjects, and are capable of expressing little to no HIV RNA or proteins. Beyond the canonical resting memory CD4+ T cells, HIV reservoirs also exist within tissue macrophages, myeloid cells, brain microglial cells, gut epithelial cells, and hematopoi-etic stem cells (HSCs). Despite a lack of active viral production, latently HIV-infected subjects con-tinue to exhibit aberrant cellular signaling and metabolic dysfunction, leading to minor to major cellular and systemic complications or comorbidities. These include genomic DNA damage; telo-mere attrition; mitochondrial dysfunction; premature aging; and lymphocytic, cardiac, renal, he-patic, or pulmonary dysfunctions. Therefore, the arcane machineries involved in HIV latency and its reversal warrant further studies to identify the cryptic mechanisms of HIV reservoir formation and clearance. In this review, we discuss several molecules and signaling pathways, some of which have dual roles in maintaining or reversing HIV latency and reservoirs, and describe some evolving strategies and possible approaches to eliminate viral reservoirs and, ultimately, cure/eradicate HIV infection.

Time Reversal (TR) is a technique that may be used to focus an acoustic signal at a particular point in space. While many variables contribute to the quality of TR focusing of sound in a particular room, the most important have been shown to be the number of sound sources, signal bandwidth and absorption properties of the medium [Ribay et al., J. Acoust. Soc. Am. 117(5), 2866-2872 (2005)]. However, the effect of room size on TR focusing has not been explored. Using the image source method algorithm proposed by Allen and Berkley [J. Allen and D. A. Berkley, J. Acoust. Soc. Am. 65(4), 943-950 (1979)], TR focusing was simulated in a variety of rooms with different absorption and volume properties. Experiments are also conducted in a couple rooms to verify the simulations. The maximum focal amplitude, the temporal focus quality, and the spatial focus clarity are defined and calculated for each simulation. The results are used to determine the effects of absorption and room volume on TR. Less absorption increases the amplitude of the focusing and spatial clarity while decreasing temporal quality. Dissimilarly, larger volumes decrease focal amplitude and spatial clarity while increasing temporal quality. This thesis also explores the placement of individual transducers within a room. It also compares the layout of several source transducers used for a reciprocal time reversal process. Maximum focal amplitude and spatial clarity are found to increase when the focus location is dual coplanar to the source location while temporal quality is found to decrease in comparison to the case when source and focal location share only one plane. Maximum focal amplitude is found to be at a minimum when the focus location is at the critical distance and increases closer and farther away from the source, while temporal quality steadily decreases and spatial clarity steadily increases farther from the source. The maximum focal amplitude and the temporal quality are not greatly affected by the type of array layout, but a circular array is ideal for maximizing spatial clarity.

No description available.

Increased physical activity and exercise have been associated with reduction in risk for cardiovascular disease. It has been postulated that increased physical activity along with diet modification and smoking cessation can lead to atherosclerotic regression. The purpose of this review of research was to examine the effects of lifestyle modifications on atherosclerotic progression/regression. Dietary modifications, increasing physical activity levels, and a combination of the two were examined for their effectiveness in altering the progression of atherosclerosis. Twenty- eight studies were examined to determine what lifestyle modifications have proven effective in reducing factors of cardiac disease and atherosclerosis. The findings were consistent in showing that alterations in diet and increased physical activity levels were successful in altering the progression of atherosclerosis. Altering dietary intake of fat amount and type can provide protective effects against plaque formation while physical activity provides a reduction in pro-atherogenic factors. The combination of diet and exercise was associated with initial reductions in atherosclerosis as well as long term effects including a reduction in the degree of vascular stenosis and a decrease in progression or an increase in regression of atherosclerosis when compared to those who did not participate in the interventions. The interventions reviewed in this study included only non-pharmacological forms of management. Dietary restrictions, such as 10% total fat calorie intake, may be difficult for individuals to maintain and commit to long term. The effects of lipid and cholesterol management through the use of medications with diet and exercise modifications should be reviewed.

In February of 2017 after a period of heavy rainfall, a slope destabilized behind Fremont Hall on the campus of Cal Poly San Luis Obispo. The geology of this slope stability failure is the Franciscan Complex. The Franciscan Complex, when weathered in place, results in clay soil that makes up the typical soil mantle on the hills throughout the region. Peak strength is the typical parameter tested to assess the strength of the soil. For the Franciscan-derived clay, the residual strength is the focus of this study to understand slope failure since the clay is the weakest portion of the matrix in the Franciscan Complex. Both intact and remolded specimens were processed from the samples obtained from the slide for laboratory testing. The tested material is considered representative of the soil found in the Franciscan Complex along the California coast and other similar regions worldwide where the presence of this mélange results in slope instabilities. Three different shearing tests were performed to study the residual strength: direct shear reversal, ring shear, and large-scale direct shear reversal. Sampling soil from the slide took place twice: once in 2017 and once in 2019. A block of soil sampled in 2017 was taken after the toe of the slope was cut for reconstruction which resulted in an exposed slide plane. In 2019, additional samples were retrieved near the toe of the slope after subsequent failure of the slope. Although the material was assumed to be from the slide plane, there is a possibility it may have originated from the surrounding matrix. Intact and remolded specimens were tested in direct shear reversal tests, and remolded specimens were tested in ring shear tests. The 2019 source was tested in the large-scale direct shear reversal tests because the material obtained during 2017 was not enough to replicate the large specimen. Remolded specimens were prepared by passing through sieve No. 40. A secondary set of tests were performed on specimens prepared by passing through sieve No. 200. When comparing remolded against intact specimens, the clasts within the intact material exhibited an influence on the residual strength by an approximate difference of 20%. The results also indicated the liquid limit (LL) had an impact on the residual strength; higher value LL exhibited lower residual strength, and lower value LL exhibited higher residual strength. When comparing the laboratory results against in situ CPT tests, the values from the CPT fell within the range of the laboratory residual strength corresponding to the slide’s depth of movement. The results from testing these specimens showed the soil obtained directly from the slide failure exhibited a residual strength represented as friction angle of 14° ± 2° for intact soil specimens, 11° ± 3° for remolded specimens of the 2017 failure plane passing through No. 40 sieve, and 22° ± 2° for remolded specimens of the 2019 sample location passing though No. 40 sieve. The remolded specimens passing through sieve No. 200 produced even lower results. However, since all clasts were removed by the No. 200 sieve, those results are not considered representative of field conditions. Based on the test results, and the infinite slope limit equilibrium slope stability analysis, a median range of residual strength for this slide is approximately 12.5 to 14.0°.

No / Acute administration of the psychotomimetic phencyclidine (PCP) can mimic some features of schizophrenia, while a repeated treatment regimen of PCP may provide a more effective way to model in animals the enduring cognitive dysfunction observed in many schizophrenic patients. The present study aims to investigate behavioural and neuropathological effects of sub-chronic PCP administration. The cognitive deficit induced by sub-chronic PCP was examined using a previously established operant reversal-learning paradigm. Subsequently, the effect of sub-chronic PCP on parvalbumin-immunoreactive (parvalbumin-IR) neurons was assessed using immunohistochemical techniques. Rats were trained to respond for food in an operant reversal-learning paradigm for approximately 6 weeks, followed by sub-chronic administration of PCP (2mg/kg) or vehicle twice daily for 7 days followed 7 days later by behavioural testing. Six weeks post PCP, brains were analysed using immunohistochemical techniques to determine the size and density of parvalbumin-IR in the frontal cortex and hippocampus. Sub-chronic PCP significantly reduced (p <0.001) percentage correct responding in the reversal phase relative to the initial phase, an effect that persisted throughout the experimental period (4 weeks). The density of parvalbumin-IR neurons was reduced in the hippocampus, with significant reductions in the dentate gyrus and CA2/3 regions (p <0.001). There were significant changes in the frontal cortex, with a reduction (p <0.01) in the M1 (motor area 1) region and increases in the M2 (motor area 2) region and cingulate cortex (p <0.01-p <0.001). These results parallel findings of profound hippocampal and more subtle cortical deficits of parvalbumin-IR neurons in schizophrenia, and provide evidence to suggest that sub-chronic PCP can induce a lasting cognitive deficit, an effect that may be related to the observed neuronal deficits.

Yes / Background: Asenapine is a new pharmacological agent for the acute treatment of schizophrenia and bipolar disorder. It has relatively higher affinity for serotonergic and α2-adrenergic than dopaminergic D2 receptors. We evaluated the effects of asenapine, risperidone, and olanzapine on acute and subchronic psychotomimetic-induced disruption of cued reversal learning in rats. Methods: After operant training, rats were treated acutely with D-amphetamine (0.75 mg/kg intraperitoneally [i.p.]) or phencyclidine (PCP; 1.5 mg/kg i.p.) or sub-chronically with PCP (2 mg/kg i.p. for 7 days). We assessed the effects of acute coadministration of asenapine, risperidone, or olanzapine on acute D-amphetamine– and PCP-induced deficits and the effects of long-term coadministration of these agents (for 28 additional days) on the deficits induced by subchronic PCP. Results: Deficits in reversal learning induced by acute D-amphetamine were attenuated by risperidone (0.2 mg/kg i.p.). Acute PCP-induced impairment of reversal learning was attenuated by acute asenapine (0.025 mg/kg subcutaneously [s.c.]), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.). Subchronic PCP administration induced an enduring deficit that was attenuated by acute asenapine (0.075 mg/kg s.c.) and by olanzapine (1.5 mg/kg i.p.). Asenapine (0.075 mg/kg s.c.), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.) all showed sustained efficacy with chronic (29 d) treatment to improve subchronic PCP-induced impairments. Conclusion: These data suggest that asenapine may have beneficial effects in the treatment of cognitive symptoms in schizophrenia. However, this remains to be validated by further clinical evaluation. / This research was supported by Schering-Plough Corporation, now Merck & Co., Inc. and Pfizer Inc.

Yes / Phencyclidine (PCP) produces cognitive deficits of relevance to schizophrenia in animal models. The aim was to investigate the efficacy of the D1-like receptor agonist, SKF-38393, to improve PCPinduced deficits in the novel object recognition (NOR) and operant reversal learning (RL) tasks. Rats received either sub-chronic PCP (2 mg/kg) or vehicle for 7 days, followed by a 7-day washout. Rats were either tested in NOR or the RL tasks. In NOR, vehicle rats successfully discriminated between novel and familiar objects, an effect abolished in PCP-treated rats. SKF-38393 (6 mg/kg) significantly ameliorated the PCP-induced deficit (Pb0.01) an effect significantly antagonised by SCH-23390 (0.05 mg/kg), a D1-like receptor antagonist (Pb0.01). In the RL task sub-chronic PCP significantly reduced performance in the reversal phase (Pb0.001); SKF-38393 (6.0 mg/kg) improved this PCPinduced deficit, an effect antagonised by SCH-23390 (Pb0.05). These results suggest a role for D1-like receptors in improvement of cognitive function in paradigms of relevance to schizophrenia.