BINA

Background- Tissue-integrated micro-electronic devices for neural stimulation hold a great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. Approach- Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23µm pitch) passivated with 3D micro-well-like structures (20µm diameter, 3µm resolution). To this end, a nickel (Ni) evaporated silicon (Si) wafer was sequentially spin-coated with SU-8 and photolithographed layer-by-layer, with a sharp electrode formation achieved through a two-step bi-layer lift-off process using LOR/AZ, followed by Cr/Au thin-layer sputter deposition to increase the adhesion. Next, the device was released by overnight Ni wet-etching using nitric acid, after which it was bio-functionalized with N 2 plasma treatment and the addition of the bio-adhesion molecule arginine-glycine-aspartic acid (RGD). Main results-In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good integration of the device in the rat sub-retinal space and cell migration into the wells. The reported process and optimization steps described here in detail can aid in the design and fabrication of similar neural implants. Conclusions- The reported process and optimization steps …

The surface adsorption of ionic surfactants is fundamental for many widespread phenomena in life sciences and for a wide range of technological applications. However, direct atomic-resolution structural experimental studies of noncrystalline surface-adsorbed films are scarce. Thus, even the most central physical aspects of these films, such as their charge density, remain uncertain. Consequently, theoretical models based on contradicting assumptions as for the surface films’ ionization are widely used for the description and prediction of surface thermodynamics. We employ X-ray reflectivity to obtain the Ångström-scale surface-normal structure of surface-adsorbed films of the cationic surfactant cetyltrimethylammonium bromide (CTAB) in aqueous solutions at several different temperatures and concentrations. In conjunction with published neutron reflectivity data, we determine the surface-normal charge …

In the last 20 years, the use of electron paramagnetic resonance (EPR) has made a pronounced and lasting impact in the field of structural biology. The advantage of EPR spectroscopy over other structural techniques is its ability to target even minor conformational changes in any biomolecule or macromolecular complex, independent of its size or complexity, or whether it is in solution or in the cell during a biological or chemical reaction. Here, we focus on the use of EPR spectroscopy to study transmembrane transport and transcription mechanisms. We discuss experimental and analytical concerns when referring to studies of two biological reaction mechanisms, namely, transfer of copper ions by the human copper transporter hCtr1 and the mechanism of action of the Escherichia coli copper-dependent transcription factor CueR. Last, we elaborate on future avenues in the field of EPR structural biology.

Results: First, we confirmed that A to G alteration in the RNAseq-data are indeed RNA editing and not mismatch mutations. Next, we found that the global blood cytoplasmic editing was higher in leukemic CTCL patients compared to healthy controls (p= 0.006). The expression of ADAR1 and ADAR2 enzymes was not altered, but the expression of the most abundant putative ADAR inhibitor-DDX6, found in the healthy cohort, was reduced in leukemic CTCL patients (p= 8× 10-8). Using Random Forest algorithm with machine learning, we managed to discriminate in all between patients and healthy individuals, based on editing level and regulators. Specific edited genes and ncRNAs are now under evaluation as diagnostic and prognostic biomarkers for leukemic CTCL and their relevancy for T cell exhaustion as was shown in Park et al. Conclusions: We propose that RNA editing is involved in the pathomechanism of …

Anionic redox provides an effective way to overcome the capacity bottleneck of sodium‐ion batteries. A dominant role is played by the arrangement of alkali A and transition metal M in the NaxAyM1‐yO2 superstructure. Here, in situ X‐ray diffraction and ex situ 7Li nuclear magnetic resonance of P2 type Na0.6Li0.2Mn0.8O2 with ribbon‐ordered superstructure illustrate structural changes and explain the evolution of the electrochemical behavior of electrodes comprising this active mass, during cycling. Upon substitution of a small amount of manganese by iron, Na0.67Li0.2Mn0.73Fe0.07O2 is formed with a honeycomb‐ordered superstructure. Experimental characterizations and theoretical calculations elucidate the effect of iron on oxygen redox activity. The iron‐doped material considerably outperforms the undoped Na0.6Li0.2Mn0.8O2 as a cathode material for rechargeable Na‐ion batteries. This research reveals …

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy. Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood–brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain. Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair. Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

Alkaline electrolyte membrane electrolyzers are a promising technology to efficiently produce clean hydrogen without the use of critical raw materials. At the heart of these electrolyzers are the electrocatalysts, which facilitate the cathodic and anodic reactions, with the latter oxygen evolution reaction (OER) being the most sluggish. In recent years, aerogels have become a very well-studied class of materials due to their unique properties, including very high surface area. Until now, aerogels have not been used to catalyze the OER by themselves but were mainly considered catalyst supports. Here, mixed-metal nickel–iron oxide aerogels were synthesized with a modified epoxide route synthesis and tested as OER catalysts. Depending on the Ni/Fe ratio, they show very high catalytic activity and low overpotential to reach 10 mA cm–2 (at η = 380 mV). This activity is beyond that of the existing state-of-the-art platinum …

The surface adsorption of ionic surfactants is fundamental for many widespread phenomena in life sciences and for a wide range of technological applications. However, direct atomic-resolution structural experimental studies of noncrystalline surface-adsorbed films are scarce. Thus, even the most central physical aspects of these films, such as their charge density, remain uncertain. Consequently, theoretical models based on contradicting assumptions as for the surface films’ ionization are widely used for the description and prediction of surface thermodynamics. We employ X-ray reflectivity to obtain the Ångström-scale surface-normal structure of surface-adsorbed films of the cationic surfactant cetyltrimethylammonium bromide (CTAB) in aqueous solutions at several different temperatures and concentrations. In conjunction with published neutron reflectivity data, we determine the surface-normal charge …

Background-Tissue-integrated micro-electronic devices for neural stimulation hold a great potential in restoring the functionality of degenerated organs, speci cally, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality.Approach-

Most of the charge transport properties in halide perovskite absorbers are measured by transient measurements with pulsed excitations; however, most solar cells in real life function in steady-state conditions. In contrast to working devices that include selective contacts, steady-state measurements need as high as possible photoconductivity (σph), which is typically restricted to the absorber alone. In this paper, we enabled steady-state charge transport measurement using atomic layer deposition (ALD) to grow a conformal, ultra-thin (~4nm) ZnO electron transport layer that is laterally insulating due to its thickness. Due to the highly alkaline behavior of the ZnO surfaces, it readily reacts with Halide Perovskites (HaP). ALD process was used to form an Aluminum oxynitride (AlON) thin (~2nm) layer that passivates the ZnO-HaP interface. We show that the presence of the AlON layer prevents HaP degradation caused by …

The coherence holography offers an unconventional way to reconstruct the hologram where an incoherent light illumination is used for reconstruction purposes, and object encoded into the hologram is reconstructed as the distribution of the complex coherence function. Measurement of the coherence function usually requires an interferometric setup and array detectors. This paper presents an entirely new idea of reconstruction of the complex coherence function in the coherence holography without an interferometric setup. This is realized by structured pattern projections on the incoherent source structure and implementing measurement of the cross-covariance of the intensities by a single-pixel detector. This technique, named structured transmittance illumination coherence holography (STICH), helps to reconstruct the complex coherence from the intensity measurement in a single-pixel detector without an interferometric setup and also keeps advantages of the intensity correlations. A simple experimental setup is presented as a first step to realize the technique, and results based on the computer modeling of the experimental setup are presented to show validation of the idea.

We explore the extreme value (EV) statistics of correlated random variables modeled via Langevin equations. Starting with an Ornstein-Uhlenbeck process, we find that when the trajectory is sampled discretely, long measurement times make the EV distribution converge to that originating from independent and identically distributed variables drawn from the process' equilibrium measure. A transition occurs when the sampling interval vanishes, for which case the EV statistics corresponds to that of the continuous process. We expand these findings to general potential fields, revealing that processes with a force that diminishes for large distances exhibit an opposite trend. Hence, we unveil a second transition, this time with respect to the potential's behavior at large displacements.

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy. Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood–brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain. Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair. Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

An electrocatalyst composed of RuO2 surrounded by interfacial carbon, is synthesized through controllable oxidization‐calcination. This electrocatalyst provides efficient charge transfer, numerous active sites, and promising activity for pH‐universal electrocatalytic overall seawater splitting. An electrolyzer with this catalyst gives current densities of 10 mA cm−2 at a record low cell voltage of 1.52 V, and shows excellent durability at current densities of 10 mA cm−2 for up to 100 h. Based on the results, a mechanism for the catalytic activity of the composite is proposed. Finally, a solar‐driven system is assembled and used for overall seawater splitting, showing 95% Faraday efficiency.

Human body is a complex system composed of various chemicals, and thus inserting any foreign chemicals can lead to long-lasting damage. One such process is tattooing, which is widely common among all sections of human society. Nevertheless, there is a huge demand for safe tattoo removal, intending to target only the ink particles and protect the skin components. This work discusses the development of a non-invasive technique to assess tattoo ink location in the deep tissue layers. Tattoo ink was injected systematically from 1-6 mm depth, parallel to the surface of an ex vivo porcine skin. The adopted methodology of the crossover point-based diffuse reflectance (DR) technique could effectively and precisely detect the tattoo ink location in the depths. A good quantitative agreement between the detected ink location and injected ink depth on cross-section tattooed skins were observed. The DR technique thus …

In the last 20 years, the use of electron paramagnetic resonance (EPR) has made a pronounced and lasting impact in the field of structural biology. The advantage of EPR spectroscopy over other structural techniques is its ability to target even minor conformational changes in any biomolecule or macromolecular complex, independent of its size or complexity, or whether it is in solution or in the cell during a biological or chemical reaction. Here, we focus on the use of EPR spectroscopy to study transmembrane transport and transcription mechanisms. We discuss experimental and analytical concerns when referring to studies of two biological reaction mechanisms, namely, transfer of copper ions by the human copper transporter hCtr1 and the mechanism of action of the Escherichia coli copper-dependent transcription factor CueR. Last, we elaborate on future avenues in the field of EPR structural biology.

The Aharonov-Bohm effect is a fundamental topological phenomenon with a wide range of applications. It consists of a charge encircling a region with a magnetic flux in a superposition of wavepackets having their relative phase affected by the flux. In this work, we analyze this effect using an entropic measure known as realism, originally introduced as a quantifier of a system's degree of reality and mathematically related to notions of global and local quantum coherence. More precisely, we look for observables that lead to gauge-invariant realism associated with the charge before it completes its loop. We find that the realism of these operators has a sudden change when the line connecting the center of both wavepackets crosses the solenoid. Moreover, we consider the case of a quantized magnetic field source, pointing out similarities and differences between the two cases. Finally, we discuss the implications of these results to the understanding of the effect.

Various conditions cause dispersions of particulate matter to circulate inside the anterior chamber of a human eye. These dispersed particles might reduce visual acuity or promote elevation of intraocular pressure (IOP), causing secondary complications such as particle related glaucoma, which is a major cause of blindness. Medical and surgical treatment options are available to manage these complications, yet preventive measures are not currently available. Conceptually, manipulating these dispersed particles in a way that reduces their negative impact could prevent these complications. However, as the eye is a closed system, manipulating dispersed particles in it is challenging. Standing acoustic waves have been previously shown to be a versatile tool for manipulation of bioparticles from nano-sized extracellular vesicles up to millimeter-sized organisms. Here we introduce for the first time a novel method utilizing standing acoustic waves to noninvasively manipulate intraocular particles inside the anterior chamber. Using a cylindrical acoustic resonator, we show ex vivo manipulation of pigmentary particles inside porcine eyes. We study the effect of wave intensity over time and rule out temperature changes that could damage tissues. Optical coherence tomography and histologic evaluations show no signs of damage or any other side effect that could be attributed to acoustic manipulation. Finally, we lay out a clear pathway to how this technique can be used as a non-invasive tool for preventing secondary glaucoma. This concept has the potential to control and arrange intraocular particles in specific locations without causing any damage to …