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Apr 2023 • JOSA A

Reconstruction algorithm using 2N+ 1 raw images for structured illumination microscopy

Xiang Fang, Kai Wen, Sha An, Juanjuan Zheng, Jianlang Li, Zeev Zalevsky, Peng Gao

This paper presents a structured illumination microscopy (SIM) reconstruction algorithm that allows the reconstruction of super-resolved images with 2N + 1 raw intensity images, with N being the number of structured illumination directions used. The intensity images are recorded after using a 2D grating for the projection fringe and a spatial light modulator to select two orthogonal fringe orientations and perform phase shifting. Super-resolution images can be reconstructed from the five intensity images, enhancing the imaging speed and reducing the photobleaching by 17%, compared to conventional two-direction and three-step phase-shifting SIM. We believe the proposed technique will be further developed and widely applied in many fields.

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Apr 2023 • Nature Methods

Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins

Ganesh Agam, Christian Gebhardt, Milana Popara, Rebecca Mächtel, Julian Folz, Benjamin Ambrose, Neharika Chamachi, Sang Yoon Chung, Timothy D Craggs, Marijn de Boer, Dina Grohmann, Taekjip Ha, Andreas Hartmann, Jelle Hendrix, Verena Hirschfeld, Christian G Hübner, Thorsten Hugel, Dominik Kammerer, Hyun-Seo Kang, Achillefs N Kapanidis, Georg Krainer, Kevin Kramm, Edward A Lemke, Eitan Lerner, Emmanuel Margeat, Kirsten Martens, Jens Michaelis, Jaba Mitra, Gabriel G Moya Muñoz, Robert B Quast, Nicole C Robb, Michael Sattler, Michael Schlierf, Jonathan Schneider, Tim Schröder, Anna Sefer, Piau Siong Tan, Johann Thurn, Philip Tinnefeld, John van Noort, Shimon Weiss, Nicolas Wendler, Niels Zijlstra, Anders Barth, Claus AM Seidel, Don C Lamb, Thorben Cordes

Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic …

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Apr 2023 • Optics Express

Optical sensor for remote estimation of CO2 concentration in the blood stream

Daniel Calili, Yevgeny Biederman, Sergey Agdarov, Yafim Biederman, Zeev Zalevsky

Speckle pattern analysis become a widespread method for remote sensing of various biomedical parameters. This technique is based on tracking the secondary speckle patterns reflected from a human skin illuminated by a laser beam. Speckle pattern variations can be translated into the corresponding partial carbon dioxide (CO 2) state (High or Normal) in the bloodstream. We present a novel approach for remote sensing of human blood carbon dioxide partial pressure (PCO 2) based on speckle pattern analyses combined with machine learning approach. The blood CO 2 partial pressure is an important indicative parameter for a variety of malfunctions in the human body.

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Apr 2023 • arXiv preprint arXiv:2304.08834

Non-normalizable quasi-equilibrium states under fractional dynamics

Lucianno Defaveri, Maike AF dos Santos, David A Kessler, Eli Barkai, Celia Anteneodo

We study non-normalizable quasi-equilibrium states (NNQE) arising from anomalous diffusion. Initially, particles in contact with a thermal bath are released from an asymptotically flat potential well, with dynamics that is described by fractional calculus. For temperatures that are sufficiently low compared to the potential depth, the properties of the system remain almost constant in time. We use the fractional-time Fokker-Planck equation (FTFPE) and continuous-time random walk approaches to calculate the ensemble averages of observables. We obtain analytical estimates of the duration of NNQE, depending on the fractional order, from approximate theoretical solutions of the FTFPE. We study and compare two types of observables, the mean square displacement typically used to characterize diffusion, and the thermodynamic energy. We show that the typical time scales for stagnation depend exponentially on the activation energy in units of temperature multiplied by a function of the fractional exponent.

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Apr 2023 • arXiv preprint arXiv:2304.14482

ULTRASAT: A wide-field time-domain UV space telescope

Y Shvartzvald, E Waxman, A Gal-Yam, EO Ofek, S Ben-Ami, D Berge, M Kowalski, R Bühler, S Worm, JE Rhoads, I Arcavi, D Maoz, D Polishook, N Stone, B Trakhtenbrot, M Ackermann, O Aharonson, O Birnholtz, D Chelouche, D Guetta, N Hallakoun, A Horesh, D Kushnir, T Mazeh, J Nordin, A Ofir, S Ohm, D Parsons, A Pe'er, HB Perets, V Perdelwitz, D Poznanski, I Sadeh, I Sagiv, S Shahaf, M Soumagnac, L Tal-Or, J Van Santen, B Zackay, O Guttman, P Rekhi, A Townsend, A Weinstein, I Wold

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is scheduled to be launched to geostationary orbit in 2026. It will carry a telescope with an unprecedentedly large field of view (204 deg) and NUV (230-290nm) sensitivity (22.5 mag, 5, at 900s). ULTRASAT will conduct the first wide-field survey of transient and variable NUV sources and will revolutionize our ability to study the hot transient universe: It will explore a new parameter space in energy and time-scale (months long light-curves with minutes cadence), with an extra-Galactic volume accessible for the discovery of transient sources that is 300 times larger than that of GALEX and comparable to that of LSST. ULTRASAT data will be transmitted to the ground in real-time, and transient alerts will be distributed to the community in 15 min, enabling a vigorous ground-based follow-up of ULTRASAT sources. ULTRASAT will also provide an all-sky NUV image to 23.5 AB mag, over 10 times deeper than the GALEX map. Two key science goals of ULTRASAT are the study of mergers of binaries involving neutron stars, and supernovae: With a large fraction (50%) of the sky instantaneously accessible, fast (minutes) slewing capability and a field-of-view that covers the error ellipses expected from GW detectors beyond 2025, ULTRASAT will rapidly detect the electromagnetic emission following BNS/NS-BH mergers identified by GW detectors, and will provide continuous NUV light-curves of the events; ULTRASAT will provide early (hour) detection and continuous high (minutes) cadence NUV light curves for hundreds of core-collapse supernovae, including for rarer supernova …

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Apr 2023 • Optics Continuum

Towards in-vivo detection of amyloid− β and tau in human CSF using machine learning based Raman spectroscopy

Noam Lhiyani, Abhijit Sanjeev, Avshalom Mor, Yevgeny Beiderman, Javier Garcia, Zeev Zalevsky

This paper aims to present initial proof of concept of a non-invasive early diagnostic tool for Alzheimer disease (AD). The approach is based on the identification using Raman spectroscopy and machine learning algorithms of two proteins that are linked with AD and exist in the cerebrospinal fluid (CSF). As demonstrated in previous studies, the concentration of the proteins amyloid-β and tau may indicate the existence of AD. The proteins’ concentration in the CSF signifies the condition of AD. The current study can contribute to the existing body of knowledge by enabling the development of a non-invasive diagnostic tool that may help with early diagnosis of AD.

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Apr 2023 • Nature Communications

Multifunctional solvent molecule design enables high-voltage Li-ion batteries

Junbo Zhang, Haikuo Zhang, Suting Weng, Ruhong Li, Di Lu, Tao Deng, Shuoqing Zhang, Ling Lv, Jiacheng Qi, Xuezhang Xiao, Liwu Fan, Shujiang Geng, Fuhui Wang, Lixin Chen, Malachi Noked, Xuefeng Wang, Xiulin Fan

The parasitic reactions at the electrolyte/electrode interfaces inhibit the increase of the charging cut-off voltage and the improvement of energy density. Herein, the authors design multifunctional solvent molecules and propose a practical design principle to stabilize the electrolyte/electrode interfaces for high-voltage Li ion batteries.

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Apr 2023 • ChemElectroChem

Degradation Mechanisms of Platinum Group Metal‐Free Oxygen Reduction Reaction Catalyst based on Iron Phthalocyanine

Hilah C Honig, Lior Elbaz

Platinum group metal‐free catalysts have been considered the most promising alternative for platinum‐based catalysts for the oxygen reduction reaction in fuel cells. Despite the significant advancement made in activity, their viability as fuel cell catalysts is still questionable due to their low durability. So far, deciphering the degradation mechanisms of this class of catalysts has been hampered by their undefined structure. Herein, we used a molecular model catalyst, iron‐phthalocyanine, featuring Fe−N4 active sites with resemblance to those in the more active Fe−N−C catalysts, and studied their degradation mechanisms. Based on X‐ray photoelectron spectroscopy and the electrochemical measurements, three main demetallation processes were identified: at potentials higher than 0.65 V vs. RHE, where the metal center is Fe3+, an electrochemical oxidation of the ligand ring is occurring, between 0.6 and 0.2 V …

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Apr 2023 • Frontiers in Genome Editing

CRISPR and beyond: Cutting-edge technologies for gene correction in therapeutic applications

Ayal Hendel, Rasmus O Bak

Gene editing promises the ultimate cure for genetic diseases by directly correcting disease-causing variants. However, the first clinical trials have chased the “low hanging fruit” using editing strategies that rely on gene disruption by introducing double-strand DNA breaks that lead to insertions and deletions (indels) by the NHEJ pathway. Since NHEJ is constitutively active throughout the cell cycle and the default DNA repair pathway, this is by far the most efficient type of conventional gene editing as opposed to homology-directed repair (HDR). HDR relies on delivery of an exogenous repair template and this pathway is active only in the S and G2 phases of the cell cycle. These two parameters constitute challenges in clinical use of HDR since exogenous DNA is toxic in most therapeutically relevant cell types and since the inherent competition between NHEJ and HDR can be a bottleneck. However, HDR benefits from enabling precise edits to be made to the genome, thereby representing true gene editing with control over the outcome. Still, in both these modalities the DNA breaks are considered a potential source of genotoxicity due to the possibility of off-target edits and chromosomal aberrations such as translocations and chromothripsis. Next-generation gene editing tools like Base and Prime Editing that rely on DNA single strand nicking reduce the risk of such harmful events but are still limited in the scope of the edits they can generate (Anzalone et al., 2020). The newest types of editors based on CRISPR-associated transposases or CRISPR-directed integrases facilitate larger edits but are still under development and immature for clinical …

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Apr 2023 • Optics Continuum

Designing an optical phase element for field of view enhancement by using wavelength multiplexing

Vismay Trivedi, Abhijit Sanjeev, Zeev Zalevsky

Enhancing the image quality of the captured image is one of the prime objectives of modern image acquisition systems. These imaging systems can be broadly divided into two subsystems: an optical subsystem and a digital subsystem. There are various limitations associated with the optical and digital subsystems. One of the crucial parameters that are affected by the limitation of the physical extent of the recording or capturing system is the field of view (FOV). A reduced FOV can lead to loss of information thereby increasing the time for post-processing of images as well as introducing mechanical scanning to achieve a larger FOV. A simple yet efficient technique for FOV enhancement is demonstrated in this paper. An optical element is designed in such a way that it diffracts different wavelengths in the desired manner and the information from different regions of the object is carried by different wavelengths which …

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Apr 2023 • Frontiers in Immunology

Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

Modi Safra, Zvi Tamari, Pazit Polak, Shachaf Shiber, Moshe Matan, Hani Karameh, Yigal Helviz, Adva Levy-Barda, Vered Yahalom, Avi Peretz, Eli Ben-Chetrit, Baruch Brenner, Tamir Tuller, Meital Gal-Tanamy, Gur Yaari

The success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance. We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls. In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients. These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.

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Apr 2023 • arXiv preprint arXiv:2304.08834

Non-normalizable quasi-equilibrium states under fractional dynamics

Lucianno Defaveri, Maike AF dos Santos, David A Kessler, Eli Barkai, Celia Anteneodo

We study non-normalizable quasi-equilibrium states (NNQE) arising from anomalous diffusion. Initially, particles in contact with a thermal bath are released from an asymptotically flat potential well, with dynamics that is described by fractional calculus. For temperatures that are sufficiently low compared to the potential depth, the properties of the system remain almost constant in time. We use the fractional-time Fokker-Planck equation (FTFPE) and continuous-time random walk approaches to calculate the ensemble averages of observables. We obtain analytical estimates of the duration of NNQE, depending on the fractional order, from approximate theoretical solutions of the FTFPE. We study and compare two types of observables, the mean square displacement typically used to characterize diffusion, and the thermodynamic energy. We show that the typical time scales for stagnation depend exponentially on the activation energy in units of temperature multiplied by a function of the fractional exponent.

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Apr 2023 • Advanced Optical Materials

Characterization of Nanometric Thin Films with Far‐Field Light

Hodaya Klimovsky, Omer Shavit, Carine Julien, Ilya Olevsko, Mohamed Hamode, Yossi Abulafia, Hervé Suaudeau, Vincent Armand, Martin Oheim, Adi Salomon

The characterization of ultrathin transparent films is paramount for various optoelectronic materials, coatings, and photonics. However, characterizing such thin layers is difficult and it requires specialized clean‐room equipment and trained personnel. Here, a contact‐less, all‐optical method is introduced and validated for characterizing nanometric transparent films using far‐field optics. A series of nanometric, smooth, and homogeneous layered samples are fabricated first, alternating transparent spacer and fluorescent layers in a controlled manner. Fluorescence radiation pattern originating from the thin fluorophore layers is then recorded and analyzed and quantitative image analysis is used to perform in operando measurements of the refractive index, film homogeneity and to estimate axial fluorophore distances at a sub‐wavelength scale with a precision of a few of nanometers. The results compare favorably to …

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Apr 2023 • MRS Bulletin, 1-2, 2023

In remembrance: George Crabtree (1944–2023) Gentleman–scientist at the forefront of sustainable energy

Elizabeth Kocs, David Cahen, Dave Ginley


Apr 2023 • MRS Bulletin, 2023

In remembrance: George Crabtree (1944-2023)

Elizabeth Kócs, David Cahen, Dave Ginley

A stunning loss to the scientific community and to humanity, the news of George Crabtree’s recent demise came as a shock to his numerous colleagues and friends. George was the epitome of an inspirational visionary and an astounding human being, as well as a force for critical and interdisciplinary scientific thought. Remembered by all as approachable, warm, wonderful, kind, curious, fearless, insightful, articulate, inspiring, inclusive, empathetic, intelligent, and impactful, George was the consummate scientist, gentleman, and leader with a deep appreciation for diverse thought, dialogue, and approaches. With so many dimensions to George, we will always remember him as our friend, a thoughtful scholar, a kind soul, and for his smile and laugh. His sudden recent death on January 23, 2023 affected many of us individually and impacted the entire materials research community. George’s immense contributions to …

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Apr 2023 • Pharmaceutics 15 (5), 1329, 2023

Homology-Directed-Repair-Based Genome Editing in HSPCs for the Treatment of Inborn Errors of Immunity and Blood Disorders

Daniel Allen, Nechama Kalter, Michael Rosenberg, Ayal Hendel

Genome engineering via targeted nucleases, specifically CRISPR-Cas9, has revolutionized the field of gene therapy research, providing a potential treatment for diseases of the blood and immune system. While numerous genome editing techniques have been used, CRISPR-Cas9 homology-directed repair (HDR)-mediated editing represents a promising method for the site-specific insertion of large transgenes for gene knock-in or gene correction. Alternative methods, such as lentiviral/gammaretroviral gene addition, gene knock-out via non-homologous end joining (NHEJ)-mediated editing, and base or prime editing, have shown great promise for clinical applications, yet all possess significant drawbacks when applied in the treatment of patients suffering from inborn errors of immunity or blood system disorders. This review aims to highlight the transformational benefits of HDR-mediated gene therapy and possible solutions for the existing problems holding the methodology back. Together, we aim to help bring HDR-based gene therapy in CD34+ hematopoietic stem progenitor cells (HSPCs) from the lab bench to the bedside.

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Apr 2023 • Sustainable Energy Storage in the Scope of Circular Economy: Advanced Materials and Device Design

Solid Batteries Chemistries Beyond Lithium

Mary York, Karl Larson, Kailot C Harris, Eric Carmona, Paul Albertus, Rosy Sharma, Malachi Noked, Ela Strauss, Heftsi Ragones, Diana Golodnitsky

Rechargeable beyond‐lithium batteries are promising low‐cost alternatives to lithium and Li‐ion technology for large‐scale applications and potential high‐voltage energy storage systems. Sodium‐, potassium‐, and magnesium‐ion batteries are gaining increased attention since these metals and their salts are less expensive, ecofriendly, and more abundant than lithium. High‐performance electrolytes, compatible with anode and cathode, are key to the success of advanced, beyond‐lithium batteries. Recently discovered alkali‐ion and alkaline‐earth‐ion conducting solid electrolytes have become the focus of research by both scientific and industrial communities because of their high safety and energy density. Unlike liquid‐electrolyte systems, the performance of a solid electrolyte dominates the overall performance of a battery. In this …

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Apr 2023 • Journal of Functional Biomaterials 14 (4), 215, 2023

Proteinoid Polymers and Nanocapsules for Cancer Diagnostics, Therapy and Theranostics: In Vitro and In Vivo Studies

Ella Itzhaki, Yuval Elias, Neta Moskovits, Salomon M Stemmer, Shlomo Margel

Proteinoids—simple polymers composed of amino acids—were suggested decades ago by Fox and coworkers to form spontaneously by heat. These special polymers may self-assemble in micrometer structures called proteinoid microspheres, presented as the protocells of life on earth. Interest in proteinoids increased in recent years, in particular for nano-biomedicine. They were produced by stepwise polymerization of 3–4 amino acids. Proteinoids based on the RGD motif were prepared for targeting tumors. Nanocapsules form by heating proteinoids in an aqueous solution and slowly cooling to room temperature. Proteinoid polymers and nanocapsules suit many biomedical applications owing to their non-toxicity, biocompatibility and immune safety. Drugs and/or imaging reagents for cancer diagnostic, therapeutic and theranostic applications were encapsulated by dissolving them in aqueous proteinoid solutions. Here, recent in vitro and in vivo studies are reviewed.

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Apr 2023 • arXiv preprint arXiv:2304.14482

ULTRASAT: A wide-field time-domain UV space telescope

Y Shvartzvald, E Waxman, A Gal-Yam, EO Ofek, S Ben-Ami, D Berge, M Kowalski, R Bühler, S Worm, JE Rhoads, I Arcavi, D Maoz, D Polishook, N Stone, B Trakhtenbrot, M Ackermann, O Aharonson, O Birnholtz, D Chelouche, D Guetta, N Hallakoun, A Horesh, D Kushnir, T Mazeh, J Nordin, A Ofir, S Ohm, D Parsons, A Pe'er, HB Perets, V Perdelwitz, D Poznanski, I Sadeh, I Sagiv, S Shahaf, M Soumagnac, L Tal-Or, J Van Santen, B Zackay, O Guttman, P Rekhi, A Townsend, A Weinstein, I Wold

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is scheduled to be launched to geostationary orbit in 2026. It will carry a telescope with an unprecedentedly large field of view (204 deg) and NUV (230-290nm) sensitivity (22.5 mag, 5, at 900s). ULTRASAT will conduct the first wide-field survey of transient and variable NUV sources and will revolutionize our ability to study the hot transient universe: It will explore a new parameter space in energy and time-scale (months long light-curves with minutes cadence), with an extra-Galactic volume accessible for the discovery of transient sources that is 300 times larger than that of GALEX and comparable to that of LSST. ULTRASAT data will be transmitted to the ground in real-time, and transient alerts will be distributed to the community in 15 min, enabling a vigorous ground-based follow-up of ULTRASAT sources. ULTRASAT will also provide an all-sky NUV image to 23.5 AB mag, over 10 times deeper than the GALEX map. Two key science goals of ULTRASAT are the study of mergers of binaries involving neutron stars, and supernovae: With a large fraction (50%) of the sky instantaneously accessible, fast (minutes) slewing capability and a field-of-view that covers the error ellipses expected from GW detectors beyond 2025, ULTRASAT will rapidly detect the electromagnetic emission following BNS/NS-BH mergers identified by GW detectors, and will provide continuous NUV light-curves of the events; ULTRASAT will provide early (hour) detection and continuous high (minutes) cadence NUV light curves for hundreds of core-collapse supernovae, including for rarer supernova …

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Apr 2023 • Electrochimica Acta

Correlation between the electrochemical response and main components structure in solutions for rechargeable Mg batteries based on THF and the reaction products of tBuMgCl and …

Sankalpita Chakrabarty, Yuri Glagovsky, Ananya Maddegalla, Natalia Fridman, Dmitry Bravo-Zhivotovski, Doron Aurbach, Ayan Mukherjee, Malachi Noked

The electrochemical response of ethereal solutions containing magnesium organohaloaluminate complexes has drawn great interest in recent decades owing to their relevance to rechargeable magnesium batteries, as demonstrated with solutions containing complexes formed by reacting R2Mg and AlCl2R moieties in ethers like tetrahydrofuran (THF). However, most of previous reports focused on battery related performances, and less on the structure of the active species. Herein, we focus on (1) identifying electroactive species and (2) correlating the electrochemical properties of their solutions to the preparation modes: either through reactions of their precursors in THF, or by dissolving isolated crystallized products in the ether solvent. Specifically, we explore the products of the reaction of the Grignard reagent t-BuMgCl with AlCl3 (1:1) in THF, and how their presence in solutions affect their electrochemical …

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Apr 2023 • Optics Continuum

Designing an optical phase element for field of view enhancement by using wavelength multiplexing

Vismay Trivedi, Abhijit Sanjeev, Zeev Zalevsky

Enhancing the image quality of the captured image is one of the prime objectives of modern image acquisition systems. These imaging systems can be broadly divided into two subsystems: an optical subsystem and a digital subsystem. There are various limitations associated with the optical and digital subsystems. One of the crucial parameters that are affected by the limitation of the physical extent of the recording or capturing system is the field of view (FOV). A reduced FOV can lead to loss of information thereby increasing the time for post-processing of images as well as introducing mechanical scanning to achieve a larger FOV. A simple yet efficient technique for FOV enhancement is demonstrated in this paper. An optical element is designed in such a way that it diffracts different wavelengths in the desired manner and the information from different regions of the object is carried by different wavelengths which …

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