Highly Reliable Magnetic Memory-Based Physical Unclonable Functions.

Magnetic random-access memory (MRAM), which stores information through control of the magnetization direction, offers promising features as a viable nonvolatile memory alternative, including high endurance and successful large-scale commercialization. Recently, MRAM applications have extended beyond traditional memories, finding utility in emerging computing architectures such as in-memory computing and probabilistic bits. In this work, we report highly reliable MRAM-based security devices, known as physical unclonable functions (PUFs), achieved by exploiting nanoscale perpendicular magnetic tunnel junctions (MTJs). By intentionally randomizing the magnetization direction of the antiferromagnetically coupled reference layer of the MTJs, we successfully create an MRAM-PUF. The proposed PUF shows ideal uniformity and uniqueness and, in particular, maintains performance over a wide temperature range from -40 to +150 °C. Moreover, rigorous testing with more than 1584 challenge-response pairs of 64 bits each confirms resilience against machine learning attacks. These results, combined with the merits of commercialized MRAM technology, would facilitate the implementation of MRAM-PUFs.

Retrospective Study on Genetic Diversity and Drug Resistance among People Living with HIV at an AIDS Clinic in Beijing.

(1) Background: The objective of this study was to investigate the prevalence of genetic diversity and drug resistance mutations among people living with HIV (PLWH) attending clinics in Beijing. (2) Methods: A retrospective analysis was conducted on PLWH admitted to the Fifth Medical Center of People's Liberation Army (PLA) General Hospital between 1 March 2013 and 31 July 2020. The participants were analyzed for pretreatment drug resistance (PDR) and acquired drug resistance (ADR). Nested polymerase chain reaction (PCR) was utilized to amplify the pol gene from plasma RNA samples obtained from the participants. Genotypic and HIV drug resistance were determined using the Stanford University HIV Drug Resistance Database. Univariate and multifactorial logistic analyses were used to assess the risk factors for PDR. (3) Results: The overall prevalence rates of PDR and ADR were 12.9% and 27.8%, respectively. Individuals treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) exhibited the highest prevalence of mutations. Specific mutation sites, such as V179D for NNRTIs and M184V and K65R for nucleoside reverse transcriptase inhibitors (NRTIs), were identified as prevalent mutations. Individuals treated with efavirenz (EFV) and nevirapine (NVP) were found to be susceptible to developing resistance. The multifactorial regression analyses indicated that the factors of circulating recombination form (CRF) genotype CRF07-BC and a high viral load were associated with an increased risk of PDR. CRF01-AE and CRF07-BC were the most prevalent HIV genotypes in our study. (4) Conclusions: The distribution of HIV genotypes in Beijing is complex. There is a need for baseline screening for HIV drug resistance among ART-naive individuals, as well as timely testing for drug resistance among ART-experienced individuals.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

IMPORTANCE: The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

Creation and regulation of ion channels across reconstituted phospholipid bilayers generated by streptavidin-linked magnetite nanoparticles.

In this work, we explore the nature of ion-channel-like conductance fluctuations across a reconstituted phospholipid bilayer due to insertion of ∼100 nm sized, streptavidin-linked magnetite nanoparticles under static magnetic fields (SMFs). For a fixed bias voltage, the frequency of current bursts increases with the application of SMFs. Apart from a closed conductance state G(0) (≤14 pS), we identify four major conductance states, with the lowest conductance level (G(1)) being ∼126 pS. The number of channel events at G(1) is found to be nearly doubled (as compared to G(0)) at a magnetic field of 70 G. The higher-order open states (e.g., 3G(1), 5G(1)) are generally observable at larger values of biasing voltage and magnetic field. When the SMF of 145 G is applied, the multiconductance states are resolved distinctly and are assigned to the simultaneous opening and closing of several independent states. The origin of the current bursts is due to the instantaneous mechanical actuation of streptavidin-linked MNP chains across the phospholipid bilayer. The voltage-controlled, magnetogated ion channels are promising for diagnoses and therapeutic applications of excitable membranes and other biological systems.

Rapid fabrication and piezoelectric tuning of micro- and nanopores in single crystal quartz.

We outline the fabrication of piezoelectric through-pores in crystalline quartz using a rapid micromachining process, and demonstrate piezoelectric deformation of the pore. The single-step fabrication technique combines ultraviolet (UV) laser irradiation with a thin layer of absorbing liquid in contact with the UV-transparent quartz chip. The effects of different liquid media are shown. We demonstrate that small exit pores, with diameters nearing the 193 nm laser wavelength and with a smooth periphery, can be achieved in 350 µm thick quartz wafers. Special crater features centring on the exit pores are also fabricated, and the depth of these craters are tuned. Moreover, by applying a voltage bias across the thickness of this piezoelectric wafer, we controllably contract and expand the pore diameter. We also provide a sample application of this device by piezoelectrically actuating alamethicin ion channels suspended over the deformable pore.

Mechanical actuation of ion channels using a piezoelectric planar patch clamp system.

High-throughput screening of ion channels is now possible with the advent of the planar patch clamp system. This system drastically increases the number of ion channels that can be studied, as multiple ion channel experiments can now be conducted in parallel. However, due to tedious, usually pressure-driven mechanotransduction techniques, there has been a slow integration of this technology into the field of mechanosensitive ion channels. By implementing a piezoelectric quartz substrate into a planar patch clamp system, we show that the patch clamp substrate itself can be used to mechanically actuate ion channels. The piezoelectric substrate transduces an external, applied electric field into a mechanical tension, so precise actuation of the membrane can be accomplished. By applying this electric field only to the outer edges of the substrate, no ulterior electric field is created in the vicinity of the membrane during actuation. Further, with resonant frequencies ranging from 1 kHz to 200 MHz, quartz substrates can be used to apply a wide range of time-varying tensions to cell membranes. This will allow for new and instructive investigations into the dynamic mechanotransductive properties of ion channels.

Semiconductor nanomembrane tubes: three-dimensional confinement for controlled neurite outgrowth.

In many neural culture studies, neurite migration on a flat, open surface does not reflect the three-dimensional (3D) microenvironment in vivo. With that in mind, we fabricated arrays of semiconductor tubes using strained silicon (Si) and germanium (Ge) nanomembranes and employed them as a cell culture substrate for primary cortical neurons. Our experiments show that the SiGe substrate and the tube fabrication process are biologically viable for neuron cells. We also observe that neurons are attracted by the tube topography, even in the absence of adhesion factors, and can be guided to pass through the tubes during outgrowth. Coupled with selective seeding of individual neurons close to the tube opening, growth within a tube can be limited to a single axon. Furthermore, the tube feature resembles the natural myelin, both physically and electrically, and it is possible to control the tube diameter to be close to that of an axon, providing a confined 3D contact with the axon membrane and potentially insulating it from the extracellular solution.

Single-ion channel recordings on quartz substrates.

We show that a single-crystal quartz substrate provides a working platform for ion channel research. Single-crystal quartz is piezoelectric, so it can be nanomechanically actuated to perform precise membrane deformations. This, along with its superior noise properties, makes single-crystal quartz ideal for analyzing mechanosensitive ion channels.

Laser drilling of nano-pores in sandwiched thin glass membranes.

We report on a novel method of using an excimer laser to drill ultra-small pores in borosilicate glass membranes. By introducing a thin layer of liquid between sandwiches of two glass slides, we can shrink the pore size and smoothen the surface on the exit side. We are able to push the minimal exit pore diameter down to 90 nm, well below the laser wavelength of 193 nm. This is achieved with substrates over 150 microm thick. Compared to other methods, this technique is fast, inexpensive, and produces high quality smooth pores.