BINA

Rapid, highly sensitive, and high-throughput detection of biomarkers at low concentrations is invaluable for early diagnosis of various diseases. In many highly sensitive immunoassays, magnetic beads are used to capture fluorescently labeled target molecules. The target molecules are then quantified by detecting the fluorescent signal from individual beads, which is time consuming and requires a complicated and expensive detection system. Here, we demonstrate a high-throughput optical modulation biosensing (ht-OMB) system, which uses a small permanent magnet to aggregate the beads into a small detection volume and eliminates background noise by steering a laser beam in and out of the cluster of beads. Shortening the aggregation, acquisition, and well-to-well scanning transition times enables reading a 96-well plate within 10 minutes. Using the ht-OMB system to detect human Interleukin-8, we …

In early disease stages, biomolecules of interest exist in very low concentrations, presenting a significant challenge for analytical devices and methods. Here, we provide a comprehensive overview of an innovative optical biosensing technology, termed magnetic modulation biosensing (MMB), its biomedical applications, and its ongoing development. In MMB, magnetic beads are attached to fluorescently labeled target molecules. A controlled magnetic force aggregates the magnetic beads and transports them in and out of an excitation laser beam, generating a periodic fluorescent signal that is detected and demodulated. MMB applications include rapid and highly sensitive detection of specific nucleic acid sequences, antibodies, proteins, and protein interactions. Compared with other established analytical methodologies, MMB provides improved sensitivity, shorter processing time, and simpler protocols.

The need for high power density cathodes for Li‐ion batteries can be fulfilled by application of a high charging voltage above 4.5 V. As lithium cobalt oxide (LCO) remains a dominant commercial cathode material, tremendous efforts are invested to increase its charging potential toward 4.6 V. Yet, the long‐term performance of high voltage LCO cathodes still remains poor. Here, an integrated approach combining the application of an aluminum fluoride coating and the use of electrolyte solutions comprising 1:1:8 mixtures of difluoroethylene:fluoroethylene carbonate:dimethyl carbonate and 1 m LiPF6 is reported. This results in superior behavior of LCO cathodes charged at 4.6 V with high initial capacity of 223 mAh g−1, excellent long‐term performance, and 78% capacity retention after 500 cycles. Impressive stability is also found at 450 °C with an initial capacity of 220 mAh g−1 and around 84% capacity retention …

Magnetic hydrogels and soft composites have fuelled the development of next generation biomimetic soft robotics due to their precise control and non-cytotoxic nature. Bare magnetic nanoparticles are difficult to regulate via remote controlling whereas, when these nanoparticles are arrested inside polymeric matrices, the whole system become an artificial soft mussel like integrated system. Concurrently, these polymeric magnetic soft materials are also prone to response of external magnetic field (static or oscillatory). Additive manufacturing via spatial assembly of polymeric precursors followed by actuation like behaviour is quite a new manufacturing technique to fabricate magnetic soft materials. In this review, we focused on the magnetic nanoparticles and their entrapment into polymeric matrices and assessing their applicability in clinical (hyperthermia) as well as shape morphing behaviours. Both the behaviors …

Trypanosoma brucei, the parasite that causes sleeping sickness, cycles between an insect and a mammalian host. However, the effect of RNA modifications such as pseudouridinylation on its ability to survive in these two different host environments is unclear. Here, two genome-wide approaches were applied for mapping pseudouridinylation sites (Ψs) on small nucleolar RNA (snoRNA), 7SL RNA, vtRNA, and tRNAs from T. brucei. We show using HydraPsiSeq and RiboMeth-seq, that the Ψ on C/D snoRNA guiding 2’-O-methylation increased the efficiency of the guided modification on its target, rRNA. We found differential levels of Ψs on these ncRNAs in the two life stages (insect host and mammalian host) of the parasite. Furthermore, tRNA isoform abundance and Ψ modifications were characterized in these two life stages demonstrating stage-specific regulation. We conclude that the differential Ψ modifications …

Stress granules (SGs) can assemble in cancer cells upon chemotoxic stress. Glucocorticoids function during stress responses and are administered with chemotherapies. The roles of glucocorticoids in SG assembly and disassembly pathways are unknown. We examined whether combining glucocorticoids such as cortisone with chemotherapies from the vinca-alkaloid family that dismantle the microtubule network, will affect SG assembly and disassembly pathways and influence cell viability in cancer cells and in human-derived organoids. Cortisone augmented SG formation when combined with Vinorelbine (VRB). Live-cell imaging showed that cortisone increased SG assembly rates but reduced SG clearance rates after stress, by increasing protein residence times within the SGs. Mechanistically, VRB and cortisone signaled through the eIF2α-mediated integrated stress response yet induced different kinases …

The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we used RNA sequencing to survey the T. brucei genome, identifying 1428 previously uncharacterized lncRNA genes. We find that grumpy lncRNA is a key regulator that promotes parasite differentiation into the quiescent stumpy form. This function is promoted by a small nucleolar RNA encoded within the grumpy lncRNA. snoGRUMPY binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. grumpy overexpression reduces parasitemia in infected mice. Our analyses …

Finding relevant research literature in online databases is a familiar challenge to all researchers. General search approaches trying to tackle this challenge fall into two groups: onetime search and life-time search. We observe that both approaches ignore unique attributes of the research domain and are affected by concept drift. We posit that in searching for research papers, a combination of a life-time search engine with an explicitly-provided context (project) provides a solution to the concept drift problem. We developed and deployed a project-based meta-search engine for research papers called Rivendell. Using Rivendell, we conducted experiments with 199 subjects, comparing project-based search performance to one-time and life-time search engines, revealing an improvement of up to 12.8 percent in project-based search compared to life-time search.

Magnesium ion (Mg2+) is one of the most significant cations in living systems with involvement in many biochemical reactions and cellular processes and hence, sensitive and specific detection of Mg2+ is therefore essential for various applications. Here, we report the solvothermal synthesis of boron‐doped carbon dots (BC10) with more oxygen surface states by using salicylaldehyde and naphthalene‐1‐boronic acid. The as‐prepared BC10 showed greenish‐white luminescence under 365 nm UV illumination with quantum yield (QY) of 5.5 % at optimum dilution with dimethyl sulfur oxide (DMSO) solvent. The BC10 in DMSO (DS‐BC10) have shown high selectivity and sensitivity towards Mg2+ ion through the increased PL intensity due to chelation‐enhanced photoluminescence (CHEP). The enhanced PL intensity was further supported by the increased QY by a factor of 12 after the addition of Mg2+ ions to 65 …

Many organisms have an elastic skeleton that consists of a closed shell of epithelial cells that is filled with fluid, and can actively regulate both elastic forces in the shell and hydrostatic pressure inside it. In this work we introduce a simple network model of such pressure-stabilized active elastic shells in which cross-links are represented by material points connected by non-linear springs of some given equilibrium lengths and spring constants. We mimic active contractile forces in the system by changing the parameters of randomly chosen springs and use computer simulations to study the resulting local and global deformation dynamics of the network. We elucidate the statistical properties of these deformations by computing the corresponding distributions and correlation functions. We show that pressure-induced stretching of the network introduces coupling between its local and global behavior: while the network …

Purpose: Stem cells replacement therapy is becoming a promising pursued avenue for vision restoration in people with degenerative diseases of the outer retina. However, the integration and survival of the transplanted cells and the formation of fully functioning synapses remain a challenge. Our aim is to develop an in-vitro experimental paradigm which will allow us to address these issues while working under experimentally controlled conditions and avoiding immune system reactions faced in-vivoMethods: As a first step, we are utilizing organotypic retinal cultures from transgenic rats expressing the calcium indicator GCaMP6f while monitoring the survival of the retinal ganglion cells (RGCs) using both extracellular recordings (multi electrode arrays), and calcium imaging at various time points.Results: Our calcium imaging revealed robust spontaneous activity of the RGCs up to 72hrs, albeit decreasing throughout …

Information about action costs is critical for real-world AI planning applications. Rather than rely solely on declarative action models, recent approaches also use black-box external action cost estimators, often learned from data, that are applied during the planning phase. These, however, can be computationally expensive, and produce uncertain values. In this paper we suggest a generalization of deterministic planning with action costs that allows selecting between multiple estimators for action cost, to balance computation time against bounded estimation uncertainty. This enables a much richer -- and correspondingly more realistic -- problem representation. Importantly, it allows planners to bound plan accuracy, thereby increasing reliability, while reducing unnecessary computational burden, which is critical for scaling to large problems. We introduce a search algorithm, generalizing , that solves such planning problems, and additional algorithmic extensions. In addition to theoretical guarantees, extensive experiments show considerable savings in runtime compared to alternatives.

High-performance electrolytes are at the heart of magnesium battery development. Long-term stability along with the low potential difference between plating and stripping processes are needed to consider them for next-generation battery devices. Within this work, we perform an in-depth characterization of the novel Mg[Al(hfip)4]2 salt in different glyme-based electrolytes. Specific importance is given to the influence of water content and the role of additives in the electrolyte. Mg[Al(hfip)4]2-based electrolytes exemplify high tolerance to water presence and the beneficial effect of additives under aggravated cycling conditions. Finally, electrolyte compatibility is tested with three different types of Mg cathodes, spanning different types of electrochemical mechanisms (Chevrel phase, organic cathode, sulfur). Benchmarking with an electrolyte containing a state-of-the-art Mg[B(hfip)4]2 salt exemplifies an improved …

Toxin-antitoxin (TA) systems are genetic modules that consist of a stable protein-toxin and an unstable antitoxin that neutralizes the toxic effect. In type II TA systems, the antitoxin is a protein that inhibits the toxin by direct binding. Type II TA systems, whose roles and functions are under intensive study, are highly distributed among bacterial chromosomes. Here, we identified and characterized a novel type II TA system PrrT/A encoded in the chromosome of the clinical isolate 39016 of the opportunistic pathogen Pseudomonas aeruginosa. We have shown that the PrrT/A system exhibits classical type II TA characteristics and novel regulatory properties. Following deletion of the prrA antitoxin, we discovered that the system is involved in a range of processes including (i) biofilm and motility, (ii) reduced prophage induction and bacteriophage production, and (iii) increased fitness for aminoglycosides. Taken together …

The immune system matures throughout childhood to achieve full functionality in protecting our bodies against threats. The immune system has a strong reciprocal symbiosis with the host bacterial population and the two systems co-develop, shaping each other. Despite their fundamental role in health physiology, the ontogeny of these systems is poorly characterized. In this study, we investigated the development of the BCR repertoire by analyzing high-throughput sequencing of their receptors in several time points of young C57BL/6J mice. In parallel, we explored the development of the gut microbiome. We discovered that the gut IgA repertoires change from birth to adolescence, including an increase in CDR3 lengths and somatic hypermutation levels. This contrasts with the spleen IgM repertoires that remain stable and distinct from the IgA repertoires in the gut. We also discovered that large clones that germinate …

We consider the effect of periodic conditional no-click measurements on a quantum system. What is the final state of such a driven system? When the system has some symmetry built into it, the final state is a dark state provided that the initial state overlaps with this nondetectable fragment of the Hilbert space. We find two classes of such states: generic dark states that are found also for nonperiodic measurements, and Floquet dark states that are directly controlled by the periodicity of the measurements and which do not rely on the underlying symmetry of the Hamiltonian. A different behavior is found in the absence of dark manifolds, where for specific periodicities of the measurements we find nontrivial oscillatory dynamics, controlled by the measurement rate. Finally, when the control parameters are tuned, the eigenvalues of the survival operator coalesce to zero, and then one finds exceptional points with a large …

BackgroundRNA editing is an inflammatory modulator with high activity in the cardiovascular system. It is mainly active in noncoding genomic areas, but also invokes changes in coding genes, mimicking a mutation and altering protein function. Although RNA editing is implicated in atherosclerosis and cardiomyopathy, its role in atriopathy and AF is unknown.Objective

Background. Collagen protein plays a notable role maintaining firm skin. Topical creams containing collagen fibers are widely available, but their usefulness is questionable due to limited skin penetration. When applied in a cream, collagen does not penetrate the skin leaving the skin structure unaffected.Objective. We formulated micronized collagen in a cream base. Using human skin samples, we sought to investigate the ability of the micronized collagen cream to penetrate human skin. Methods. Particle sizes of micronized marine collagen were evaluated using electron microscopy. Optical profilometry was conducted to evaluate skin topography and roughness. The antioxidant activity of the collagen was evaluated using the electron paramagnetic resonance technique by measuring the changes in free radical production. Collagen penetration depth in human skin samples was monitored using a non-invasive optical technique known as iterative multiplane optical property extraction, which works based on the detection of laser light phase changes following the presence of collagen particles in deep skin layers.Results. According to the electron microscopy, collagen particles were found to be of various sizes, the smallest being about 120nm in diameter. Skin topography measurements revealed that the treated collagen cream increased skin smoothness of the samples. Our results derived from the iterative multiplane optical property extraction indicated that micronized collagen in a cream base penetrates both the stratum corneum and the deep epidermal layers toward the dermis.Conclusion. Our investigation suggests that the collagen in the …

Toxin-antitoxin (TA) systems are genetic modules that consist of a stable protein-toxin and an unstable antitoxin that neutralizes the toxic effect. In type II TA systems, the antitoxin is a protein that inhibits the toxin by direct binding. Type II TA systems, whose roles and functions are under intensive study, are highly distributed among bacterial chromosomes. Here, we identified and characterized a novel type II TA system PrrT/A encoded in the chromosome of the clinical isolate 39016 of the opportunistic pathogen Pseudomonas aeruginosa. We have shown that the PrrT/A system exhibits classical type II TA characteristics and novel regulatory properties. Following deletion of the prrA antitoxin, we discovered that the system is involved in a range of processes including (i) biofilm and motility, (ii) reduced prophage induction and bacteriophage production, and (iii) increased fitness for aminoglycosides. Taken together …

Epithelial–mesenchymal Transition (EMT) is a multi-step process that involves cytoskeletal rearrangement. Here, developing and using an image quantification tool, Statistical Parametrization of Cell Cytoskeleton (SPOCC), we have identified an intermediate EMT state with a specific cytoskeletal signature. We have been able to partition EMT into two steps:(1) initial formation of transverse arcs and dorsal stress fibers and (2) their subsequent conversion to ventral stress fibers with a concurrent alignment of fibers. Using the Orientational Order Parameter (OOP) as a figure of merit, we have been able to track EMT progression in live cells as well as characterize and quantify their cytoskeletal response to drugs. SPOCC has improved throughput and is non-destructive, making it a viable candidate for studying a broad range of biological processes. Further, owing to the increased stiffness (and by inference invasiveness …