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2021 • Deep Sequencing Data Analysis, 59-80, 2021

Applications of community detection algorithms to large biological datasets

Itamar Kanter, Gur Yaari, Tomer Kalisky

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2021 • RNA Editing: Methods and Protocols, 149-162, 2021

ALU A-to-I RNA editing: millions of sites and many open questions

Amos A Schaffer, Erez Y Levanon

Alu elements are repetitive short interspersed elements prevalent in the primate genome. These repeats account for over 10% of the genome with more than a million highly similar copies. A direct outcome of this is an enrichment in long structures of stable dsRNA, which are the target of adenosine deaminases acting on RNAs (ADARs), the enzymes catalyzing A-to-I RNA editing. Indeed, A-to-I editing by ADARs is extremely abundant in primates: over a hundred million editing sites exist in their genomes. However, despite the radical increase in ADAR targets brought on by the introduction of Alu elements, the few evolutionary conserved editing sites manage to retain their editing levels. Here, we review and discuss the cost of having an unusual amount of dsRNA and editing in the transcriptome, as well as the opportunities it presents, which possibly contributed to accelerating primate evolution.

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2021 • Org. Synth

Synthesis of Tetraaryl-, Pentaaryl-, and Hexaaryl-1, 4-dihydropyrrolo [3, 2-b] pyrroles

OW Kielesiński, CA Barboza, DT Gryko, M Jacquet, M Izzo, S Osella, S Kozdra, PP Michałowski, D Gołowicz, K Kazimierczuk, MT Gorzkowski, A Lewera, M Teodorczyk, B Trzaskowski, R Jurczakowski, J Kargul, M Krzeszewski, AL Dobrzycki, MK Cyrański, A Friedman, NR Samala, HC Honig, M Tasior, L Elbaz, I Grinberg, R Orłowski, JA Clark, JB Derr, EM Espinoza, MF Mayther, O Staszewska-Krajewska, JR Winkler, H Jędrzejewska, A Szumna, HB Gray, VI Vullev, GD Kumar, M Banasiewicz, D Jacquemin, P Gajewski, O Vakuliuk, YM Poronik, GV Baryshnikov, I Deperasińska, H Agren, A Nowak-Król, B Koszarna, TD Lohrey, J Arnold, K Skonieczny, I Papadopoulos, D Thiel, K Gutkowski, P Haines, PM McCosker, AD Laurent, PA Keller, T Clark, DM Guldi, Z Szakács, E Vauthey, ŁG Łukasiewicz, M Rammo, C Stark, A Rebane, Y Qin, C Schnedermann, DG Nocera, OW Morawski, DT Kielesiński, AL Sobolewski, M Pieczykolan, B Sadowski, F Ambicki, SM Tseng, PT Chou, A Minotto, PA Haigh, E Lunedei, I Darwazeh, F Cacialli, M Bugaj, I Benkyi, M Jaszuński, A Stanger, D Sundholm, T Kim, W Kim, D Kim, S Hatanaka, T Ono, Y Yano, Y Hisaeda, M Grzybowski, H Butenschön, JP Lewtak, MK Charyton, J Porph Phthal, DJ Stewart, AT Phillips

DTG Group Daniel Gryko's Group METHODOLOGY → DYES → APPLICATIONS Gryko's Group Home News DTG Members Publications (current) Teaching Vacancies 2021 M. Krzeszewski, M. Tasior, M. Grzybowski, DT Gryko Synthesis of Tetraaryl-, Pentaaryl-, and Hexaaryl-1,4-dihydropyrrolo[3,2-b]pyrroles Org. Synth., 2021, 98, 242-262 KV Vygranenko, YM Poronik, A. Wrzosek, A. Szewczyk, DT Gryko Red emissive sulfone-rhodols as mitochondrial imaging agents Chem. Commun., 2021, 57, 7782-7785 Ł. Kielesiński, OW Morawski, CA Barboza, DT Gryko Polarized Helical Coumarins: [1,5] Sigmatropic Rearrangement and Excited-State Intramolecular Proton Transfer J. Org. Chem., 2021, 86, 6148-6159 M. Jacquet, M. Izzo, S. Osella, S. Kozdra, PP Michałowski, D. Gołowicz, K. Kazimierczuk, MT Gorzkowski, A. Lewera, M. Teodorczyk, B. Trzaskowski, R. Jurczakowski, DT Gryko, J. Kargul Development of a universal …

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Dec 2020 • ACS nano

Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis

Chen Tzror-Azankot, Oshra Betzer, Tamar Sadan, Menachem Motiei, Shai Rahimipour, Ayelet Atkins, Aron Popovtzer, Rachela Popovtzer

Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) is a powerful tool for cancer detection, staging, and follow-up. However, 18F-FDG-PET imaging has high rates of false positives, as it cannot distinguish between tumor and inflammation regions that both feature increased glucose metabolic activity. In the present study, we engineered liposomes coated with glucose and the chelator dodecane tetraacetic acid (DOTA) complexed with copper, to serve as a diagnostic technology for differentiating between cancer and inflammation. This liposome technology is based on FDA-approved materials and enables complexation with metal cations and radionuclides. We found that these liposomes were preferentially uptaken by cancer cell lines with high metabolic activity, mediated via glucose transporter-1. In vivo, these liposomes were avidly uptaken by tumors, as compared to liposomes without glucose …

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Dec 2020 • Genome biology

Purifying selection of long dsRNA is the first line of defense against false activation of innate immunity

Michal Barak, Hagit T Porath, Gilad Finkelstein, Binyamin A Knisbacher, Ilana Buchumenski, Shalom Hillel Roth, Erez Y Levanon, Eli Eisenberg

Mobile elements comprise a large fraction of metazoan genomes. Accumulation of mobile elements is bound to produce multiple putative double-stranded RNA (dsRNA) structures within the transcriptome. These endogenous dsRNA structures resemble viral RNA and may trigger false activation of the innate immune response, leading to severe damage to the host cell. Adenosine to inosine (A-to-I) RNA editing is a common post-transcriptional modification, abundant within repetitive elements of all metazoans. It was recently shown that a key function of A-to-I RNA editing by ADAR1 is to suppress the immunogenic response by endogenous dsRNAs. Here, we analyze the transcriptomes of dozens of species across the Metazoa and identify a strong genomic selection against endogenous dsRNAs, resulting in their purification from the canonical transcriptome. This purifying selection is especially strong for long and nearly perfect dsRNAs. These are almost absent from mRNAs, but not pre-mRNAs, supporting the notion of selection due to cytoplasmic processes. The few long and nearly perfect structures found in human transcripts are weakly expressed and often heavily edited. Purifying selection of long dsRNA is an important defense mechanism against false activation of innate immunity. This newly identified principle governs the integration of mobile elements into the genome, a major driving force of genome evolution. Furthermore, we find that most ADAR1 activity is not required to prevent an immune response to endogenous dsRNAs. The critical targets of ADAR1 editing are, likely, to be found mostly in non-canonical transcripts.

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Dec 2020 • Scientific Reports

Autoencoder based blind source separation for photoacoustic resolution enhancement

Matan Benyamin, Hadar Genish, Ran Califa, Lauren Wolbromsky, Michal Ganani, Zhen Wang, Shuyun Zhou, Zheng Xie, Zeev Zalevsky

Photoacoustics is a promising technique for in-depth imaging of biological tissues. However, the lateral resolution of photoacoustic imaging is limited by size of the optical excitation spot, and therefore by light diffraction and scattering. Several super-resolution approaches, among which methods based on localization of labels and particles, have been suggested, presenting promising but limited solutions. This work demonstrates a novel concept for extended-resolution imaging based on separation and localization of multiple sub-pixel absorbers, each characterized by a distinct acoustic response. Sparse autoencoder algorithm is used to blindly decompose the acoustic signal into its various sources and resolve sub-pixel features. This method can be used independently or as a combination with other super-resolution techniques to gain further resolution enhancement and may also be extended to other imaging …

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Dec 2020 • Journal of Experimental Botany

Siliplant1 protein precipitates silica in sorghum silica cells

Santosh Kumar, Nurit Adiram-Filiba, Shula Blum, Javier Arturo Sanchez-Lopez, Oren Tzfadia, Ayelet Omid, Hanne Volpin, Yael Heifetz, Gil Goobes, Rivka Elbaum

Silicon is absorbed by plant roots as silicic acid. The acid moves with the transpiration stream to the shoot, and mineralizes as silica. In grasses, leaf epidermal cells called silica cells deposit silica in most of their volume using an unknown biological factor. Using bioinformatics tools, we identified a previously uncharacterized protein in Sorghum bicolor, which we named Siliplant1 (Slp1). Slp1 is a basic protein with seven repeat units rich in proline, lysine, and glutamic acid. We found Slp1 RNA in sorghum immature leaf and immature inflorescence. In leaves, transcription was highest just before the active silicification zone (ASZ). There, Slp1 was localized specifically to developing silica cells, packed inside vesicles and scattered throughout the cytoplasm or near the cell boundary. These vesicles fused with the membrane, releasing their content in the apoplastic space. A short peptide that is repeated five times …

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Dec 2020 • physica status solidi (a)

Laser recording in chalcogenide glass films: driving forces and kinetics of the mass transfer

Yuri S Kaganovskii, Hadar Genish, Michael Rosenbluh

Herein, precision recording of indented dots and lines in As10Se90 and As2S3 chalcogenide glass films by a focused laser beam is demonstrated and the kinetics and mechanisms of mass transfer under illumination are studied. Due to inhomogeneous intensity distribution and local heating of the film at the focal point, the beam at rest produces an indentation whose depth increases with time and laser power. Illumination by a moving beam leads to formation of groves whose morphology depends on the beam speed and power. At low light intensities, formation of the indentations occurs in the solid phase, due to photoinduced radial diffusion of the film constituents coupled with electrons and holes created by light. The two main driving forces present are: 1) a lateral steady‐state electric field formed due to different mobilities of electrons and holes and 2) driving force of thermodiffusion (Soret effect). At high light …

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Dec 2020 • ACS Applied Nano Materials

Alumina Thin-Film Deposition on Rough Topographies Comprising Vertically Aligned Carbon Nanotubes: Implications for Membranes, Sensors, and Electrodes

Lev Rovinsky, Barun Kumar Barick, Elnatan Lieberman, Efrat Shawat Avraham, Gilbert Daniel Nessim, Tamar Segal-Peretz, Noa Lachman

In this article, the limits of thin-film deposition on very rough topographies are demonstrated by depositing alumina on vertically aligned carbon nanotubes (VACNTs). Vapor deposition techniques are the enabling platforms of the thin-film industry, offering high material versatility and good coverage ability on relatively flat surfaces, leading to frequent use in a large array of applications, especially nanoscale electronic devices such as sensors and electrodes. However, when surface topography exhibits high roughness, even depositions that are not limited to line-of-sight show only partial coverage, significantly hindering performances. Our manufacturing process of VACNT/Al2O3 nanocomposites has three vaporous steps: CNT growth by chemical vapor deposition (CVD), functionalization via controlled thermal oxidation, and atomic layer deposition (ALD) of alumina. The same limited accessibility hinders each of …

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Dec 2020 • Macromolecular Chemistry and Physics

Synthesis of Multi Amino Acid Chiral Polymeric Microparticles for Enantioselective Chemistry

Meir Abuaf, Yitzhak Mastai

Chiral polymeric particles have emerged as a new and exciting field of research and in the last years due to their possible use for many applications in chiral chemistry. In this article, an important question is focused upon that has not been explored in detail in the field of chiral polymeric particles. The main question is whether the chiral composition of the polymeric particles affects their chiral recognition. The hypothesis is that chiral polymeric particles with a variety of different chiral groups will improve chiral recognition and improve their use of enantioselectivity crystallization. Consequently, chiral microparticles based on one up to three different amino acids based monomers are prepared by precipitation polymerization. The chiral microspheres are characterized by dynamic light scattering, scanning electron microscope (SEM), mass spectrometry (MS), and nuclear magnetic resonance (NMR) and display a narrow …

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Dec 2020 • Iscience

Developmentally regulated novel non-coding anti-sense regulators of mRNA translation in Trypanosoma brucei

K Shanmugha Rajan, Tirza Doniger, Smadar Cohen-Chalamish, Praveenkumar Rengaraj, Beathrice Galili, Saurav Aryal, Ron Unger, Christian Tschudi, Shulamit Michaeli

The parasite Trypanosoma brucei is the causative agent of sleeping sickness and cycles between insect and mammalian hosts. The parasite appears to lack conventional transcriptional regulation of protein coding genes, and mRNAs are processed from polycistronic transcripts by the concerted action of trans-splicing and polyadenylation. Regulation of mRNA function is mediated mainly by RNA binding proteins affecting mRNA stability and translation. In this study, we describe the identification of 62 non-coding (nc) RNAs that are developmentally regulated and/or respond to stress. We characterized two novel anti-sense RNA regulators (TBsRNA-33 and 37) that originate from the rRNA loci, associate with ribosomes and polyribosomes, and interact in vivo with distinct mRNA species to regulate translation. Thus, this study suggests for the first-time anti-sense RNA regulators as an additional layer for controlling …

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Dec 2020 • Physical Review D

Realism and causality. II. Retrocausality in energetic causal sets

Eliahu Cohen, Marina Cortês, Avshalom C Elitzur, Lee Smolin

We describe a new form of retrocausality, which is found in the behavior of a class of causal set theories, called energetic causal sets (ECS). These are discrete sets of events, connected by causal relations. They have three orders:(1) a birth order, which is the order in which events are generated; this is a total order which is the true causal order,(2) a dynamical partial order, which prescribes the flows of energy and momentum among events,(3) an emergent causal order, which is defined by the geometry of an emergent Minkowski spacetime, in which the events of the causal sets are embedded. However, the embedding of the events in the emergent Minkowski spacetime may preserve neither the true causal order in (1) nor correspond completely with the microscopic partial order in (2). We call this disordered causality, and we here demonstrate its occurrence in specific ECS models. This is the second in a series of …

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Dec 2020 • Physical Review B

Observations of symmetry-induced topological mode steering in a reconfigurable elastic plate

Kun Tang, M Makwana, Richard V Craster, Patrick Sebbah

We experimentally investigate the valley-Hall effect for interfacial edge states, highlighting the importance of the modal patterns between geometrically distinct regions within a structured elastic plate. These experiments, for vibration, are at a scale where detailed measurements are taken throughout the system and not just at the input/output ports; this exposes the coupling between geometrically distinct modes that underlie the differences between wave transport around gentle and sharp bends.

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Dec 2020 • Brain Research

Computational capacity of pyramidal neurons in the cerebral cortex

Danko D Georgiev, Stefan K Kolev, Eliahu Cohen, James F Glazebrook

The electric activities of cortical pyramidal neurons are supported by structurally stable, morphologically complex axo-dendritic trees. Anatomical differences between axons and dendrites in regard to their length or caliber reflect the underlying functional specializations, for input or output of neural information, respectively. For a proper assessment of the computational capacity of pyramidal neurons, we have analyzed an extensive dataset of three-dimensional digital reconstructions from the NeuroMorpho. Org database, and quantified basic dendritic or axonal morphometric measures in different regions and layers of the mouse, rat or human cerebral cortex. Physical estimates of the total number and type of ions involved in neuronal electric spiking based on the obtained morphometric data, combined with energetics of neurotransmitter release and signaling fueled by glucose consumed by the active brain, support …

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Dec 2020 • Colloids and Surfaces A: Physicochemical and Engineering Aspects

In-situ thin coating of silica micro/nano-particles on polymeric films and their anti-fogging application

Sharon Bretler, Naftali Kanovsky, Taly Iline-Vul, Sarit Cohen, Shlomo Margel

Polymeric films, e.g., polyethylene (PE), coated with a thin layer of silica micro/nano-particles (SiO2 M/NPs) were prepared using a modified Stöber method in the presence of corona treated and non-treated PE films. The obtained films were washed of excess reagents and non-bonded (free) SiO2 M/NPs and dried. Only the corona-treated PE films were coated with a thin layer of SiO2 M/NPs while the non-treated films were almost empty of bound SiO2 particles. PE films composed of bound mesoporous silica NPs were similarly prepared with the addition of cetyltrimethylammonium bromide (CTAB) in the polymerization process. The effect of various polymerization parameters, e.g., tetraethylorthosilicate (TEOS) concentration, ammonium hydroxide concentration and the volume ratio [ethanol]/[water], on the diameter and diameter distribution of the free and surface bound particles were elucidated. Characterization of …

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Dec 2020 • ACS Applied Nano Materials

Carbon dots for heavy-metal sensing, pH-sensitive cargo delivery, and antibacterial applications

Poushali Das, Moorthy Maruthapandi, Arumugam Saravanan, Michal Natan, Gila Jacobi, Ehud Banin, Aharon Gedanken

Currently, the technologies accompanying the usage of waste materials for the fabrication of innovative useful materials have been significantly advanced. For the same purpose, a possible sustainable approach was demonstrated for the utilization of jute caddies, known as jute industry waste. From the industrial waste, carbon dots (CDs) were sonochemically prepared, followed by their surface modification with benzalkonium chloride (BZC) to yield waste jute-derived fluorescent surface-quaternized CDs (JB-CDs), which exhibit excellent water solubility, excitation-dependent emission, and good photostability, and were utilized as a fluorescent nanoswitch to detect inorganic pollutants, such as chromium (VI) [Cr(VI)] ions, in aqueous solutions. JB-CDs can detect Cr(VI) concentrations as low as 0.03 μM through luminescence quenching (“turn-off”) and further recover their fluorescence (“turn-on”) selectively for …

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Dec 2020 • Applied Physics Letters

Thickness dependence of elliptical planar Hall effect magnetometers

Hariharan Nhalil, Proloy T Das, Moty Schultz, Shai Amrusi, Asaf Grosz, Lior Klein

We fabricate elliptical planar Hall effect magnetometers with Permalloy thickness ranging between 25 and 200 nm. We study the thickness dependence of their equivalent magnetic noise by examining the effect of the layer thickness on the signal and noise including Joule heating contributions. Sensors with a thickness of 50 nm achieve equivalent magnetic noise as low as ∼24 pT/ √ Hz at 50 Hz and ∼36 pT/ √ Hz at 10 Hz, which are the best reported values for any type of magnetic sensor of similar or smaller size. These results are achieved without the use of magnetic flux concentrators, which helps to reduce the sensor volume while improving its spatial resolution and reducing the complexity and time of its production and, hence, its potential cost. We discuss different routes for further resolution improvements.

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Dec 2020 • Journal of the American Chemical Society

The impression of a nonexisting catalytic effect: the role of CotB2 in guiding the complex biosynthesis of cyclooctat-9-en-7-ol

Keren Raz, Ronja Driller, Nicole Dimos, Marion Ringel, Thomas Brück, Bernhard Loll, Dan Thomas Major

Terpene synthases generate terpenes employing diversified carbocation chemistry, including highly specific ring formations, proton and hydride transfers, and methyl as well as methylene migrations, followed by reaction quenching. In this enzyme family, the main catalytic challenge is not rate enhancement, but rather structural and reactive control of intrinsically unstable carbocations in order to guide the resulting product distribution. Here we employ multiscale modeling within classical and quantum dynamics frameworks to investigate the reaction mechanism in the diterpene synthase CotB2, commencing with the substrate geranyl geranyl diphosphate and terminating with the carbocation precursor to the final product cyclooctat-9-en-7-ol. The 11-step in-enzyme carbocation cascade is compared with the same reaction in the absence of the enzyme. Remarkably, the free energy profiles in gas phase and in CotB2 …

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Dec 2020 • Nature Energy

Minimum doping densities for p–n junctions

Thomas Kirchartz, David Cahen

MATTERS ARISING NATURE ENERGY volume 9, where σn and σp are the capture cross-sections for electrons and holes into the defect that dominates recombination. To avoid the condition nσn= pσp, doping may be helpful, as shown in Fig. 2, because it induces an asymmetry at least in n versus p, that may help to reduce the absorber volume where nσn= pσp to a small region 10. Thus, p–n junctions in lead-halide perovskites could indeed be helpful to achieve higher efficiencies if deep defect densities and carrier mobilities are not adversely affected by higher doping densities and if those higher doping densities can actually be achieved technologically.This last point may well be key, as ap–n junction is not a thermodynamically stable situation; rather it is a kinetically stabilized one 11. The relatively high diffusion coefficients for atomic/ionic species in the lead-halide perovskites that have been reported in the …

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Dec 2020 • Scientific reports

Human kidney clonal proliferation disclose lineage-restricted precursor characteristics

Osnat Cohen-Zontag, Rotem Gershon, Orit Harari-Steinberg, Itamar Kanter, Dorit Omer, Oren Pleniceanu, Gal Tam, Sarit Oriel, Herzel Ben-Hur, Guy Katz, Zohar Dotan, Tomer Kalisky, Benjamin Dekel, Naomi Pode-Shakked

In-vivo single cell clonal analysis in the adult mouse kidney has previously shown lineage-restricted clonal proliferation within varying nephron segments as a mechanism responsible for cell replacement and local regeneration. To analyze ex-vivo clonal growth, we now preformed limiting dilution to generate genuine clonal cultures from one single human renal epithelial cell, which can give rise to up to 3.4* 10 6 cells, and analyzed their characteristics using transcriptomics. A comparison between clonal cultures revealed restriction to either proximal or distal kidney sub-lineages with distinct cellular and molecular characteristics; rapidly amplifying de-differentiated clones and a stably proliferating cuboidal epithelial-appearing clones, respectively. Furthermore, each showed distinct molecular features including cell-cycle, epithelial-mesenchymal transition, oxidative phosphorylation, BMP signaling pathway and cell …

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Dec 2020 • Journal of nanobiotechnology

Ultrasensitive haptoglobin biomarker detection based on amplified chemiluminescence of magnetite nanoparticles

Narsingh R Nirala, Yifat Harel, Jean-Paul Lellouche, Giorgi Shtenberg

Haptoglobin is an acute-phase protein used as predicting diagnostic biomarker both in humans (i.e., diabetes, ovarian cancer, some neurological and cardiovascular disorders) and in animals (e.g., bovine mastitis). The latter is a frequent disease of dairy industry with staggering economical losses upon decreased milk production and increased health care costs. Early stage diagnosis of the associated diseases or inflammation onset is almost impossible by conventional analytical manners. The present study demonstrates a simple, rapid, and cost-effective label-free chemiluminescence bioassay based on magnetite nanoparticles (MNPs) for sensitive detection of haptoglobin by employing the specific interaction of hemoglobin-modified MNPs. The resulting haptoglobin-hemoglobin complex inhibits the peroxidase-like activity of luminol/H2O2-hemoglobin-MNPs sensing scheme and reduces the chemiluminescence intensities correspondingly to the innate haptoglobin concentrations. Quantitative detection of bovine haptoglobin was obtained within the range of 1 pg mL−1 to 1 µg mL−1, while presenting 0.89 pg mL−1 limit of detection. Moreover, the influence of causative pathogenic bacteria (i.e., Streptococcus dysgalactiae and Escherichia coli) and somatic cell counts (depicting healthy, sub-clinical and clinical mastitis) on the emitted chemiluminescence radiation were established. The presented bioassay quantitative performances correspond with a standardized assay kit in differentiating dissimilar milk qualities. Overall, the main advantage of the presented sensing concept is the ability to detect haptoglobin, at clinically relevant concentrations …

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