MEMRI is a biomarker defining nicotine-specific neuronal responses in subregions of the rodent brain.

Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats. The following were observed. Mn(2+) infusion identified ACB and hippocampal (HIP) neuronal activities following acute nicotine administration. Chronic exposure was achieved by week long subcutaneously implanted nicotine mini-pump. Here nicotine was shown to activate neurons in the ACB, HIP, and the prefrontal and insular cortex. These are all central nervous system reward regions linked to drug addiction. In conclusion, MEMRI is demonstrated to be a powerful imaging tool to study brain subregion specific neuronal activities affected by nicotine. Thus, we posit that MEMRI could be used to assess smoking-associated tolerance, withdrawal and as such serve as a pre-clinical screening tool for addiction cessation strategies in humans

To Reach the Light: The Monumental Byzantine Stairs of Caesarea, a Conservation and Restoration Project

Ancient Caesarea has founded in the years 25-10 BC and named after Emperor Augustus. Throughout history, from the early Roman until the Byzantine period, Caesarea was a major city and one of the largest and most important port cities in the Mediterranean. During the Byzantine period, the city encompassed an area three times larger than that delimited by the Herodian wall and became an important center of Christianity. The monumental stairs led to the Byzantine Octagonal Church built upon giant arch above the remains of the enormous Roman stairs of Augustus temple. Stairs led a large number of people from the vast harbor, to the Temple platform. The Byzantine arch located 17 meters from the ancient quay, is 8 meters width and 4-meter long, built with specific technology from local sandstone named Kurkar. The arch fall after the Byzantine period and the staircases severely damaged due to the long exposure of almost 1500 years and environmental conditions such as capillary rise, daily winds carrying sand, high temperature, moisture, salts, and deliberate destruction, for instance, stones robber and collapse parts from the wall. The characteristics of the Kurkar with sustained deterioration and this environmental condition have led to different conservation problems, at various levels of severity erosion, the disintegration in both bonding materials and stones. The conservation measures' purpose is to stop the ongoing weathering process and prevent a deterioration state of the staircases, to restore the arch and stabilize the structure of the stairs to carry 48 tons of the restore arch. The findings of the project show that a suitable solution to ensure effective and sustainable protection of complicated staircases structure from destruction and various weathering condition to carry new massive arch depends on understanding the ancient application of building technologies and techniques, the use of original bonding material, integrated monitoring, and ongoing maintenance

Controlling the energy flow in nonlinear lattices: a model for a thermal rectifier

We address the problem of heat conduction in 1-D nonlinear chains; we show that, acting on the parameter which controls the strength of the on site potential inside a segment of the chain, we induce a transition from conducting to insulating behavior in the whole system. Quite remarkably, the same transition can be observed by increasing the temperatures of the thermal baths at both ends of the chain by the same amount. The control of heat conduction by nonlinearity opens the possibility to propose new devices such as a thermal rectifier.Comment: 4 pages with figures included. Phys. Rev. Lett., to be published (Ref. [10] corrected

Can disorder induce a finite thermal conductivity in 1D lattices?

We study heat conduction in one dimensional mass disordered harmonic and anharmonic lattices. It is found that the thermal conductivity $\kappa$ of the disordered anharmonic lattice is finite at low temperature, whereas it diverges as $\kappa \sim N^{0.43}$ at high temperature. Moreover, we demonstrate that a unique nonequilibrium stationary state in the disordered harmonic lattice does not exist at all.Comment: 4 pages with 4 eps figure

Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV- 2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage

Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Stage of Replication

Type I interferons (IFNα and β) are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα

Heat transport by lattice and spin excitations in the spin chain compounds SrCuO_2 and Sr_2CuO_3

We present the results of measurements of the thermal conductivity of the quasi one-dimensional spin S=1/2 chain compound SrCuO_2 in the temperature range between 0.4 and 300 K along the directions parallel and perpendicular to the chains. An anomalously enhanced thermal conductivity is observed along the chains. The analysis of the present data and a comparison with analogous recent results for Sr_2CuO_3 and other similar materials demonstrates that this behavior is generic for cuprates with copper-oxygen chains and strong intrachain interactions. The observed anomalies are attributed to the one-dimensional energy transport by spin excitations (spinons), limited by the interaction between spin and lattice excitations. The energy transport along the spin chains has a non-diffusive character, in agreement with theoretical predictions for integrable models.Comment: 12 pages (RevTeX), 8 figure

Simulation of heat transport in low-dimensional oscillator lattices

The study of heat transport in low-dimensional oscillator lattices presents a formidable challenge. Theoretical efforts have been made trying to reveal the underlying mechanism of diversified heat transport behaviors. In lack of a unified rigorous treatment, approximate theories often may embody controversial predictions. It is therefore of ultimate importance that one can rely on numerical simulations in the investigation of heat transfer processes in low-dimensional lattices. The simulation of heat transport using the non-equilibrium heat bath method and the Green-Kubo method will be introduced. It is found that one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) momentum-conserving nonlinear lattices display power-law divergent, logarithmic divergent and constant thermal conductivities, respectively. Next, a novel diffusion method is also introduced. The heat diffusion theory connects the energy diffusion and heat conduction in a straightforward manner. This enables one to use the diffusion method to investigate the objective of heat transport. In addition, it contains fundamental information about the heat transport process which cannot readily be gathered otherwise.Comment: Article published in: Thermal transport in low dimensions: From statistical physics to nanoscale heat transfer, S. Lepri, ed. Lecture Notes in Physics, vol. 921, pp. 239 - 274, Springer-Verlag, Berlin, Heidelberg, New York (2016

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy