Direct Identification Research Articles

Direct Discretized Kernel Identification for Continuous Agglomeration Processes

Continuous particle agglomeration processes are important size-enlargement unit operations applied in the food, pharmaceutical and agricultural industry. For the improvement of these processes predictive mathematical models are of utmost importance. A widely applied modeling framework is the population balance equation, where the agglomeration kinetics are described by the so-called agglomeration kernel. The identification of functions describing these kinetics has turned out to be a challenging task. Therefore, this article deals with identifying such a kernel function by minimizing the L2-residual between experimentally obtained particle size distributions and simulations. The application of a stochastic gradient descent algorithm with automatic differentiation for minimization allows for the direct identification of the high-dimensional matrix representing the discretized kernel function. The comparison between the simulated and measured size distribution shows that the identified kernel is able to accurately describe the evolution of the particle size distribution. The algorithm presented in this contribution can be applied to a variety of similar processes and the identified kernels can be used in process optimization and automation applications.

Electromyography Endotracheal Tube – Road to Safety for Thyroid Surgery

Thyroidectomy is one among the most commonly performed endocrine surgeries. Iatrogenic injury of the recurrent laryngeal nerve (RLN) is of major concern in thyroid surgery. We report the case of a 37-year-old female with papillary carcinoma of thyroid posted for total thyroidectomy. Although direct identification of the nerve is considered as the gold standard, we discuss the intraoperative monitoring of RLN using electromyography endotracheal tube and its anaesthetic considerations.

Combination of Stochastic State Estimation with Online Identification of the Open-Circuit Voltage of Lithium-Ion Batteries

Typical equivalent circuit models for Lithium-ion batteries are represented in the form of the so-called Thévenin form. These models comprise a state of charge (SOC) controlled voltage source as well as lumped elements such as series resistances as well as at least one RC subnetwork to describe dynamic effects by the terminal current and voltage as input and output of the battery. In classical state estimation approaches, these characteristics are assumed to be identified beforehand, while aging of battery cells is related to a loss of the total capacity, changes in the charging/discharging efficiency, an increase of the Ohmic cell resistance, and/or changes of the time constants of the above-mentioned RC networks. Such variations can be estimated by means of additional parameters that are included in the system's state vector. However, the typically applied approaches do not allow for a direct identification of the nonlinear dependencies of the circuit elements on the SOC and other influence factors such as currents or the cell temperature. Therefore, this paper proposes a real-time capable, two-stage identification of these dependencies on the example of the open-circuit voltage by means of an Unscented Kalman Filter (UKF) approach. In the first stage, the state variables of the dynamic system model are estimated together with a lumped disturbance term (an additive correction of the open-circuit voltage). In the second stage, this disturbance term is used to correct the a-priori knowledge of the open-circuit voltage and to simultaneously express the identification quality in terms of covariances for the coefficients of its piecewise polynomial approximation in each temporal discretization step. The efficiency of the proposed methodology is demonstrated in simulations for an experimentally validated system model.

ОБҐРУНТУВАННЯ ДОЦІЛЬНОСТІ ЗАСТОСУВАННЯ МЕТОДУ ЗВОРОТНІХ ЗВАЖЕНИХ ВІДСТАНЕЙ ДЛЯ КЛАСТЕРИЗАЦІЇ ЙОСИПІВСЬКОГО РОДОВИЩА КАОЛІНУ

Purpose. To describe the procedure for performing kaolin deposit clustering in order to determine the regularities of the distribution of quality indicators, to distinguish promising areas and to calculate the volumes of minerals of different conditions. Methodology. Implementation of systematization, analysis and statistical processing of the results of geological research of the deposit. Identification of criteria for evaluating the qualitative properties of a mineral. Performing interpolation based on the results of geological studies in order to establish the qualitative indicators of the mineral and the regularities of their distribution within the deposit. Justification of the feasibility of using the method of inverse distances weighting to achieve the set goals. Performing deposit clustering and calculating the volume of reserves of different conditions. Results. The main result of deposit clustering is the direct identification of areas within which the secondary conditions of the mineral are located. The results of clustering allow: to display the content of constituent components in the contours of the deposit; identify promising areas for development; to determine the optimal direction of expansion of the mining operations front; determine the optimal location of overburden mining; calculate the volumes of minerals within the deposit under different trademarks; average the mining mass in order to improve its quality. Scientific novelty. The systematization and review of the existing methods of geometrization of mineral deposits has been carried out. The expediency of using the interpolation method to geometrize the complex structure of the Yosypiv deposit of primary kaolin has been investigated empirically. The expediency of using such a method has been substantiated, and the relevance of the obtained results has been assessed. Practical significance. The results obtained during the research make it possible to optimize the design process of a kaolin mining enterprise by obtaining a detailed and visual distribution of the deposit into clusters in accordance with the desired qualitative indicators: mineral composition, chemical composition, physical and mechanical indicators, etc. At the same time, the obtained results make it possible to predict the patterns of distribution of various types of properties within the deposit and to estimate the overall economic effect of its development with a higher degree of accuracy.

Single-molecule analysis of genome-wide DNA methylation by fiber FISH coupled with atomic force microscopy.

DNA methylation (mainly at 5-methylcytosine, 5mC) plays an essential role in embryonic development and cellular biology. Alterations in DNA methylation are associated with disease development, especially hematologic malignancies. To investigate the potential of 5mC for diagnosis and treatment, accurate determination of 5mC is essential. Standard bisulfite sequencing-based methodologies or various optical/electrochemical biosensors for identifying 5mC have limitations, such as high cost, severe DNA degradation, over-estimation of the true 5mC level, being able to only display the average 5mC level, etc. Here we propose a single-molecule strategy for the direct identification of whole-genome 5mC by the combination of DNA fiber-based fluorescence in situ hybridization (DNA fiber FISH) and atomic force microscopy (AFM). Using extended DNA fibers and anti-5mC antibody for the detection of 5mC, it is possible to map the physical location of 5mC within the genome DNA. Together with AFM, this method can present the morphology of anti-5mC-DNA complexes and detailed spacing distribution of two neighboring 5mC sites on a single DNA molecule. Furthermore, this approach can be used for reporting other epigenetic modifications, not limited to 5mC or one single epigenetic modification. It can be anticipated to contribute to the development of clinical diagnosis of epigenetic-related diseases.

Identification and Quantitation of Taste-Active Compounds in Dried Scallops by Combined Application of the Sensomics and a Quantitative NMR Approach.

Application of the sensomics concept on dried scallops, a Japanese specialty produced from the adductor muscle of scallops, revealed after activity-guided fractionation with subsequent (comparative) taste dilution analyses besides nucleotides, amino acids, organic acids, and inorganic ions, the presence of taste-modulating quaternary ammonium compounds and opines in highly taste-active fractions. In order to recreate the taste of dried scallops, two independent quantitation approaches were applied and compared. The first approach used multiple targeted UHPLC-MS/MS and high-performance ion chromatography methods. Besides already established quantitation methods for basic taste compounds, a new HILIC-UHPLC-MS/MSMRM method for the quantitation of chromatographically challenging opines, using synthesized stable isotope-labeled standards, was developed. Furthermore, a qHNMR approach was applied, enabling a direct identification and quantitation of organic taste compounds in a food extract without prior fractionation using a reference 1H NMR database. Both methods yielded similar quantitative results of taste-active compounds in dried scallop extracts and subsequent taste recombination experiments based on these data were able to recreate the taste of dried scallops.

Performance and Impact on Initial Antibiotic Choice of Direct Identification of Pathogens from Pediatric Blood Culture Bottles Using an In-House MALDI-TOF MS Protocol.

ABSTRACTThe performance and early therapeutic impact of direct identification by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF; DIMT) on pediatric blood culture bottles using in-house-developed methods to obtain microbial pellets for spectrometric analysis have seldom been studied. During a 2-year period (June 2018 to May 2020), DIMT was performed on broths from positive pediatric blood culture bottles using an in-house-developed method. Organism identifications with a score of ≥1.6 were notified to treating clinicians. Therapeutic modifications that occurred after the communication of DIMT were reviewed through the electronic medical records. DIMT was performed on 530 pediatric positive blood culture bottles. Among 505 monomicrobial bottles, identifications from 298 (97.7%) deemed as bloodstream infections (BSI) and 189 (94.5%) as contaminations had DIMT notified to clinicians. All identifications were correct except for one Streptococcus mitis incorrectly reported as Streptococcus pneumoniae. Therapy modifications resulting from DIMT occurred in 27 (8.3%) patients with BSI. Deescalation from effective or ineffective broad-spectrum regimens occurred mainly in Enterococcus faecalis bacteremia, whereas appropriate escalation from an ineffective regimen with narrower spectrum occurred mainly in bacteremia caused by AmpC-β-lactamase-producing Enterobacterales. Escalation therapy was instituted significantly faster than deescalation therapy (median time, 0.75 versus 10.5 h [P = 0.01]). DIMT also enabled clinicians to confirm contamination in nearly one-half of patients with contaminated blood cultures. Our DIMT method applied to positive pediatric blood culture bottles demonstrated reliable performance for the rapid identification of pathogens. Our DIMT approach allowed therapeutic optimization in BSI, especially involving microorganisms with intrinsic antibiotic resistance, and was helpful in the early identification of likely contaminants.IMPORTANCE We demonstrate the performance and early impact on the antimicrobial management of bloodstream infections of an inexpensive, in-house preparation method for direct identification of bloodstream pathogens in pediatric blood culture bottles by matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry.

Incorporation of geological constraints into geochemical anomaly identification using BME-GWR: A case study from Inner Mongolia of China

Delineation of geochemical anomalies is a fundamental task in mineral and environmental investigation. Mineralization area of interest is mainly controlled by underlying geological environment. These geological constraints facilitate to identify mineralization anomalies and remove pseudo-anomalies. Regional geochemical data is one of most commonly used in deriving mineralization information, which is also considered to be the primary data for direct geochemical anomaly identification. The selected study area, Jining in central Inner Mongolia of China, is mostly covered with Quaternary sediments, whereas is located in the important molybdenum polymetallic mineralized belt. The overburden shields the geochemical signatures from deep, resulting in missing some important information. The NE-trending faults, intersection of faults, Jining formation and mid-acid granites is mainly ore-forming factors in this study area, which are used as the geological constraints for identifying molybdenum polymetallic mineralization. Geographical weighted regression (GWR) generates the mean and variance of probability soft data based on these geological constraints. Bayesian maximum entropy (BME) integrates the constructed soft data with geochemical data for obtaining practical mineralization anomalies. These results shown that the combination of BME and GWR can identify local anomalies and weak anomalies compared with the results obtained from geochemical data alone. Specially, some anomalies of different periods of deposits have been highlighted in the results of BME-GWR model. The discovered deposits correspond tothe identified mineralization anomalies well. The BME-GWR model provides a potentially powerful tool for geochemical anomaly identification under consideration of geological constraints.

Postoperative lumbar spondylodiscitis

Background. Several causes that can trigger POD can be incriminated: the patient's immune status, surgical technical errors, intra-operative contamination, foreign materials microfilm. Extensive analysis is required to eradicate the limited or diffuse infection and manage the optimal therapeutic attitude conservative or by surgery to get: faster recovery time, to improve symptoms, to allow mobilization, to offer a good quality of life and to reduce the average length of hospital stay.
 Objectives. To perform a systematic review of POD outcomes via retrospective analysis of current studies based on the mechanism, the pathogenesis, the management of patient's immunological status, aetiology (microorganism involved, foreign material applied for hemostasis, application of spinal instrumentation, cement, screws, spinal devices), laboratory (TLC, ESR, CRP), MRI/CT-scan, antibiotherapy guidelines and the type of surgery performed: classical or minim-invasive, length of procedure, intraoperative accidents, the experience of the neurosurgeon, post-operative stay in ICU, etc.
 Methods. Several data were taken into account regarding lumbar infections using a comprehensive review of the literature published studies from 1998 to 2021. Demographic data, clinical variables, length of hospital stay, duration of antibiotic treatment, and post-treatment complications were assessed.
 Results. We performed a systematic review concerning 31 studies regarding clinical status, diagnosis and treatment.
 Conclusions. Based on our systematic analysis, training and continuous education in spine surgery are necessary to prevent POD. The diagnosis of lumbar POD is based on history and physical examination, biochemical markers, neuroradiologic studies, using appropriate MRI imaging. Most cases of lumbar POD can be managed by conservative treatment with antibiotics after causative germ isolation and antibiogram. Surgery is performed on patients with conservative treatment failure - resistant to antibiotic therapy, as those with neurological complications: acute paraplegia, pain resistance to analgetics, acute sepsis, abscesses, spinal instability, severe kyphosis. Early surgery with wound irrigation/debridement is more readily able to disrupt biofilm formation and facilitate penetration of systemic antimicrobials to allow for resolution of the infection, vacuum-assisted closure facilitates wound healing and eradicates spinal infections, decrease the rate of complications, permit rapid pain relief while preserving the instrumentation/stability, better clinical outcomes, infection control before extensive destruction of the vertebrae, spinal instability and kyphotic deformity appear. Instrumentation can usually be preserved in patients with early infections (e.g., <6 weeks), but instrumentation removal should be considered for infections presenting in a delayed fashion (e.g., >6 weeks to even years) PSII. Patients should be adequately followed for one postoperative year, to ensure that the infection has been fully eradicated. Implant sonication provides cultures for direct identification of active and/or persistent biofilm, while the introduction of enzymes that dissolve the biofilm matrix (e.g., DNase and alginate lyase) and quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics may further help manage postoperative infection (2)(27-31).

Real Space Visualization of Entangled Excitonic States in Charged Molecular Assemblies.

Entanglement of excitons holds great promise for the future of quantum computing, which would use individual molecular dyes as building blocks of their circuitry. Studying entangled excitonic eigenstates emerging in coupled molecular assemblies in the near-field with submolecular resolution has the potential to bring insight into the photophysics of these fascinating quantum phenomena. In contrast to far-field spectroscopies, near-field spectroscopic mapping permits direct identification of the individual eigenmodes, type of exciton coupling, including excited states otherwise inaccessible in the far field (dark states). Here we combine tip-enhanced spectromicroscopy with atomic force microscopy to inspect delocalized single-exciton states of charged molecular assemblies engineered from individual perylenetetracarboxylic dianhydride (PTCDA) molecules. Hyperspectral mapping of the eigenstates and comparison with calculated many-body optical transitions reveals a second low-lying excited state of the anion monomers and its role in the exciton entanglement within the assemblies. We demonstrate control over the exciton coupling by switching the assembly charge states. Our results reveal the possibility of tailoring excitonic properties of organic dye aggregates for advanced functionalities and establish the methodology to address them individually at the nanoscale.

Direct Rapid Identification from Positive Blood Cultures by MALDI-TOF MS: Specific Focus on Turnaround Times.

ABSTRACTEarly availability of pathogen identification in bloodstream infections has critical importance in patients' management. This study investigated the accuracy and feasibility of the direct rapid identification (RID) method from positive blood cultures (BCs) by MALDI-TOF MS and its impact on the turnaround time (TAT) compared to the short-term incubation routine identification (SIRID) method. Pellets prepared from 328 BCs using a serum separator tube in the RID method and colonies on agar plates in the SIRID method were identified with MALDI Biotyper. BCs on weekdays from 6 a.m. to 4 p.m. were defined as the daytime signal group (DSG); BCs from 4 p.m. to 6 a.m. were defined as the night signal group (NSG). Comparison between the two methods was performed with 310 monomicrobial BCs. Two hundred ninety-five (95.2%) monomicrobial BCs yielded an identification result with the RID method. Of the 295 BCs, 289 (97.9%) were identified correctly at the species level, 4 (1.4%) were at the genus level, and 2 (0.7%) were misidentified. In the RID method, at score cutoff values of 1.2, 1.3, 1.4 and 1.5, the rates of correct identifications at the species level were 97.9%, 98.9%, 99.3%, and 100%, respectively. The mean TAT in the DSG was significantly lower (P < 0.001) in the RID method (mean: 2.86 h; 95% CI: 2.65 to 3.07) compared to the SIRID method (mean: 19.49 h; 95% CI: 18.08 to 20.89). Correct identification rates at the species level were 100% in Gram-negative bacteria, 88.9% in Gram-positive bacteria, and 93.2% of all BCs isolates with the RID method. The TAT was improved remarkably in DSG, which might contribute to empirical antibiotic therapies of patients.IMPORTANCE Using MALDI-TOF MS directly from BCs reduces the time required for pathogen identification, and the TATs for final identification have been compared with overnight incubation from solid media in previous studies. However, identification from a short incubation of agar plates has been increasingly accepted and successfully implemented in routine laboratories, but there is no data comparing direct MALDI-TOF MS with the short-term incubated agar plates. Our study showed that the TAT improved remarkably by applying a RID method by MALDI-TOF MS twice a day periodically when compared to the SIRID method.

Case Report: Early Recognition and Repair of Distal Iatrogenic Ureteral Injury During Laparoscopic Rectal Surgery

Background: Ureteral injury is an uncommon complication of the colorectal procedure. The colorectal procedure is the second most common cause of ureteral injury. The laparoscopic approach for colorectal surgery has contributed to the increase of ureteral injury. Delayed diagnosis of the iatrogenic ureteral injury is associated with higher morbidity. However, the early diagnosis of ureteral injury during the operation is difficult. We presented an early recognition and laparoscopic repair of iatrogenic ureteral injury during laparoscopic rectal cancer surgery cases and the strategy for recognizing and managing that injury for the surgeon.Case Presentation: A Male, 34 years old, had an iatrogenic ureteral injury during laparoscopic low anterior resection for rectal cancer. The left distal ureter was transected by an energy device. The diagnosis of ureteral injury was prompt. The repair of the ureter was done endo-laparoscopically. The patient had an uneventful recovery and was discharged on day 6 after surgery.Conclusion: The iatrogenic ureteral injury, although uncommon, is a serious complication of laparoscopic colorectal surgery. Direct visual identification of the distal ureter is mandatory in every rectal surgery. The iatrogenic ureteral injury is not an indication for open conversion when there is an adequate resource to do the endo-laparoscopic ureteral repair.

GTN Damage Modelling of the AA6063 Using Image Processing

In this paper, an innovative way of calculating the Gurson–Tvergaard–Needleman parameter has been developed for AA 6063. AA 6063 is an aluminum alloy comprising the alloying ingredients magnesium and silicon. The Aluminum Association maintains the standard that governs its composition. It has strong mechanical properties and may be heat treated and welded. Image processing technique has been used to calculate the damage constant for the AA 6063. The image of the sample has been taken under a microscope of undeformed and fractured material. Then the images are analyzed using the Open CV tool in a python open-source environment. The initial and final void fraction of the sheet has been calculated. Damage models, particularly the Gurson–Tvergaard–Needleman (GTN) model, are widely used in numerical simulation of material deformations. Each damage model has some constants which must be identified for each material. The direct identification methods are costly and time-consuming. A combination of experimental, numerical simulation and optimization have been used to determine the constants in the current work. Numerical simulation of the dynamic test was performed utilizing the constants obtained from quasi-static experiments. The results showed a high precision in predicting the specimen's profile in the dynamic testing.

Supercapacitance/Resistance Behaviors of Helminth Eggs as Reliable Recognition and Direct Differentiation Probe.

Parasitic helminths are usually known as undesired pathogens, causing various diseases in both human and animal species. In this study, we explore supercapacitance/resistance behaviors as a novel probe for rapid identification and direct differentiation of Fasciola hepatica, Parascaris equorum (with and without larvae), Dicrocoelium dendriticum, Taenia multiceps, and Moniezia expansa eggs. This claim is attributed to some characteristics, such as grave supercapacitance/area, high-energy storage/area, large power/egg, huge permittivity, and great electrical break-down potential, respectively (Fasciola hepatica: 2,158, 0.485, 2.7 × 10–3, 267, 52.6, Parascaris equorum without larvae: 2,825, 0.574, 3.0 × 10–3, 351, 68.4, Parascaris equorum with larvae: 4,519, 0.716, 2.4 × 10–3, 1.96, 97.6, Dicrocoelium dendriticum: 1,581, 0.219, 2.8 × 10–3, 1.96, 48.8, Moniezia expansa: 714, 0.149, 2.2 × 10–3, 0.88, 35.2, Taenia multiceps: 3,738, 0.619, 4.7 × 10–3, 4.63, 84.4), and durable capacitance up to at least 15,000 sequential cycles at different scan rates (between 2.0 × 10−4 and 120.0 V s−1) as well as highly differentiated resistance between 400 and 600 Ω. These traits are measured by the “Blind Patch-Clamp” method, at the giga ohm sealed condition (6.18 ± 0.12 GΩ cm−1, n = 5). Significant detection ranges are detected for each capacitance and resistance with gradient limits as large as at least 880 to 1,000 mF and 400 to 600 Ω depending on the type of helminth egg. The effect of water in the structure of helminth eggs has also been investigated with acceptable reproducibility (RSD 7%–10%, n = 5). These intrinsic characteristics would provide novel facilitators for direct helminth egg identification in comparison with several methods, such as ELISA, PCR, and microscopic methods.

653. Direct Identification of Microorganisms in Positive Blood Cultures by the BioFire® FilmArray® Blood Culture Identification Panel Leads to Faster Optimal Antibiotic Therapy: A Before–After Study

BackgroundRapid pathogen identification from positive blood cultures may help optimize empiric antibiotic therapy quickly by reducing unnecessary broad spectrum antibiotic use and may improve patient outcomes. The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) identifies 24 pathogens directly from positive blood cultures without subculture. 3 resistance genes are included. We aimed to compare the time to optimal antibiotic therapy between BF-FA-BCIP and conventional identification.MethodsWe performed a single-center retrospective case-control before-after study of 386 cases (November 2018 to October 2019) with BF-FA-BCIP compared to 414 controls (August 2017 to July 2018) with conventional identification. The primary study endpoint was the time from blood sampling to implementation of optimal antimicrobial therapy. Secondary endpoints were time to effective therapy, length of hospital stay, and in-hospital and 30-day mortality. Outcomes were assessed using cause-specific Cox Proportional Hazard models and logistic regressions.ResultsWe included 800 patients with comparable baseline characteristics. Main sources of blood stream infection (BSI) were urinary tract infection and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7% for case and control groups, respectively). Overall, 212 positive blood cultures were considered as contaminations. Identification results were available after a median of 21.9 hours by the BF-FA-BCIP and 44.3 hours by the conventional method. Patients with BF-FA-BCIP received the optimal therapy after a median of 25.5 hours (95%CI 21.0 - 31.2) as compared to 45.7 hours (95%CI 37.7 - 51.2) in the control group (Figure 1). We found no effect of the identification method on secondary outcomes.Kaplan-Meier curve representing the probability of implementing the optimal therapy at any given time according to the identification method (Standard vs. BF-FA-BCIP). Shaded ribbons represent the 95 % confidence interval (CI). The vertical dashes represent censored data. The vertical dotted lines represent the median time, i.e. the time at which 50 % of the patients obtained the optimal therapy, for the two methods. Median (95 % CI) time to optimal therapy is 45.7 (37.7 - 51.4) hours with the Standard method and 25.5 (21.0- 31.2) hours with Biofire. The tables below the curves present the numbers expecting optimal therapy according to the bacteria identification method, as well as the number of censored data in parenthesis. Panel A shows data from 0 to 900 hours. Panel B shows the data from 0 to 90 hours to better visualize how the probability to implement optimal therapy varies in the first 72 hours.ConclusionIn conclusion, rapid pathogen identification by BF-FA-BCIP was associated with an almost 24h earlier initiation of the optimal antibiotic therapy in BSI. However, the overall benefit for individual patients seems to be limited. Future studies should assess the cost-effectiveness and impact on the prevention of antibiotic resistance using this diagnostic approach.Disclosures All Authors: No reported disclosures

Neutral Mechanical Plane Shifting in Bending Elastomer Film Revealed by Quantification of Internal Strain

Flexible electronic devices composed of soft materials, such as polymers and elastomers, require high mechanical durability to maintain their performance during cyclic bending, where large bending can lead to fracture. To design the appropriate structure for such devices, it is essential to utilize a neutral mechanical plane (NMP) in which the strain becomes zero inside bending materials. Despite the importance of identifying the NMP position for this utilization, the NMP position in soft materials has rarely been studied experimentally because of the difficulty in measuring internal strain in largely bending materials. Herein, the NMP position of bending polydimethylsiloxane (PDMS) film, which is a common soft material used in flexible electronic devices, is experimentally quantified via internal strain measurement with a cholesteric liquid crystal sensor. This is the first reported identification of the NMP position, revealing that bending of the PDMS film reversibly shifts the NMP position within ≈11% of the film thickness toward the inner bending surface. Considering this large NMP shift, a flexible electronic device with high mechanical durability is fabricated. The direct identification of the NMP position, which is enabled by the internal strain measurement, facilitates the development of device designs for flexible electronic devices.

Rational Designed Hybrid Peptides Show up to a 6-Fold Increase in Antimicrobial Activity and Demonstrate Different Ultrastructural Changes as the Parental Peptides Measured by BioSAXS

Antimicrobial peptides (AMPs) are a promising class of compounds being developed against multi-drug resistant bacteria. Hybridization has been reported to increase antimicrobial activity. Here, two proline-rich peptides (consP1: VRKPPYLPRPRPRPL-CONH2 and Bac5-v291: RWRRPIRRRPIRPPFWR-CONH2) were combined with two arginine-isoleucine-rich peptides (optP1: KIILRIRWR-CONH2 and optP7: KRRVRWIIW-CONH2). Proline-rich antimicrobial peptides (PrAMPs) are known to inhibit the bacterial ribosome, shown also for Bac5-v291, whereas it is hypothesized a “dirty drug” model for the arginine-isoleucine-rich peptides. That hypothesis was underpinned by transmission electron microscopy and biological small-angle X-ray scattering (BioSAXS). The strength of BioSAXS is the power to detect ultrastructural changes in millions of cells in a short time (seconds) in a high-throughput manner. This information can be used to classify antimicrobial compounds into groups according to the ultrastructural changes they inflict on bacteria and how the bacteria react towards that assault. Based on previous studies, this correlates very well with different modes of action. Due to the novelty of this approach direct identification of the target of the antimicrobial compound is not yet fully established, more research is needed. More research is needed to address this limitation. The hybrid peptides showed a stronger antimicrobial activity compared to the proline-rich peptides, except when compared to Bac5-v291 against E. coli. The increase in activity compared to the arginine-isoleucine-rich peptides was up to 6-fold, however, it was not a general increase but was dependent on the combination of peptides and bacteria. BioSAXS experiments revealed that proline-rich peptides and arginine-isoleucine-rich peptides induce very different ultrastructural changes in E. coli, whereas a hybrid peptide (hyP7B5GK) shows changes, different to both parental peptides and the untreated control. These different ultrastructural changes indicated that the mode of action of the parental peptides might be different from each other as well as from the hybrid peptide hyP7B5GK. All peptides showed very low haemolytic activity, some of them showed a 100-fold or larger therapeutic window, demonstrating the potential for further drug development.

Innate Immunity Modulating Impurities and the Immunotoxicity of Nanobiotechnology-Based Drug Products.

Innate immunity can be triggered by the presence of microbial antigens and other contaminants inadvertently introduced during the manufacture and purification of bionanopharmaceutical products. Activation of these innate immune responses, including cytokine secretion, complement, and immune cell activation, can result in unexpected and undesirable host immune responses. These innate modulators can also potentially stimulate the activation of adaptive immune responses, including the formation of anti-drug antibodies which can impact drug effectiveness. To prevent induction of these adverse responses, it is important to detect and quantify levels of these innate immunity modulating impurities (IIMIs) that may be present in drug products. However, while it is universally agreed that removal of IIMIs from drug products is crucial for patient safety and to prevent long-term immunogenicity, there is no single assay capable of directly detecting all potential IIMIs or indirectly quantifying downstream biomarkers. Additionally, there is a lack of agreement as to which of the many analytical assays currently employed should be standardized for general IIMI screening. Herein, we review the available literature to highlight cellular and molecular mechanisms underlying IIMI-mediated inflammation and its relevance to the safety and efficacy of pharmaceutical products. We further discuss methodologies used for direct and indirect IIMI identification and quantification.

Spatiotemporal Analysis of Waves in Compressively Driven Magnetohydrodynamics Turbulence

Abstract Using direct numerical simulations (DNSs), the interaction between linear waves and turbulence under the compressible magnetohydrodynamic (CMHD) approach was studied. A set of DNSs in three dimensions for a spatial resolution of 1283 and 2563 were performed. A parametric study was carried out varying the sonic Mach number, the mean-magnetic field, and the compressibility amplitude of the forcing. Spatiotemporal spectra of the magnetic energy were built and analyzed, allowing for direct identification of all wave modes in a CMHD turbulent system and quantification of the amount of energy in each mode as a function of the wavenumber. Thus, linear waves were detected, that is Alfvén waves and fast and slow magnetosonic waves. Furthermore, different responses of the plasma were found according to whether the Mach number or the mean-magnetic field was varied. On the other hand, making use of spatiotemporal spectra and two different integration methods, we accurately quantified the amount of energy present in each of the normal modes. Finally, although the presence of linear waves was observed, in all the cases studied the system was mainly dominated by the nonlinear dynamics of the plasma.

Fukaya A∞-structures associated to Lefschetz fibrations. V

We (re)consider how the Fukaya category of a Lefschetz fibration is related to that of the fiber. The distinguishing feature of the approach here is a more direct identification of the bimodule homomorphism involved.