Light-Triggered PROTAC Nanoassemblies for Photodynamic IDO Proteolysis in Cancer Immunotherapy.

While proteolysis-targeting chimeras (PROTACs) hold great potential for persistently reprogramming the immunosuppressive tumor microenvironment via targeted protein degradation, precisely activating them in tumor tissues and preventing uncontrolled proteolysis at off-target sites remain challenging. Herein, a light-triggered PROTAC nanoassembly (LPN) for photodynamic indoleamine 2,3-dioxygenase (IDO) proteolysis is reported. The LPN is derived from the self-assembly of prodrug conjugates, which comprise a PROTAC, cathepsin B-specific cleavable peptide linker, and photosensitizer, without any additional carrier materials. In colon tumor models, intravenously injected LPNs initially silence the activity of PROTACs and accumulate significantly in targeted tumor tissues due to an enhanced permeability and retention effect. Subsequently, the cancer biomarker cathepsin B begins to trigger the release of active PROTACs from the LPNs through enzymatic cleavage of the linkers. Upon light irradiation, tumor cells undergo immunogenic cell death induced by photodynamic therapy to promote the activation of effector T cells, while the continuous IDO degradation of PROTAC simultaneously blocks tryptophan metabolite-regulated regulatory-T-cell-mediated immunosuppression. Such LPN-mediated combinatorial photodynamic IDO proteolysis effectively inhibits tumor growth, metastasis, and recurrence. Collectively, this study presents a promising nanomedicine, designed to synergize PROTACs with other immunotherapeutic modalities, for more effective and safer cancer immunotherapy.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Self-Assembled Tamoxifen-Selective Fluorescent Nanomaterials Driven by Molecular Structural Similarity.

Most supramolecular systems were discovered by using a trial-and-error approach, leading to numerous synthetic efforts to obtain optimal supramolecular building blocks for selective guest encapsulation. Here, we report a simple coassembly strategy for preparing tamoxifen-selective supramolecular nanomaterials in an aqueous solution. The synthetic amphiphile molecule, 1,1,2,2-tetraphenylethylene (TPE), promotes large tamoxifen aggregate disassembly into smaller, discrete aggregates such as ribbon-like and micellar assemblies in coassembled solutions, enhancing the solubility and dispersion. The TPE moiety exhibits enhanced emission upon tamoxifen interaction, enabling the observation of the coassembled species in an aqueous solution for cell imaging. The tamoxifen-selective fluorescent micelles in the presence of a 1:1 molar ratio of TPE derivative with tamoxifen show enhanced tamoxifen absorption and anticancer effects against MCF-7 breast cancer cells. These supramolecular approaches, based on the coassembly of building blocks with molecular structural similarity, can provide a novel strategy for the efficient development of selective molecular carriers with enhanced biological activities.

Risk factors of hemodialysis catheter dysfunction in patients undergoing continuous renal replacement therapy: a retrospective study.

BACKGROUND: Continuous renal replacement therapy is a relatively common modality applied to critically ill patients with renal impairment. To maintain stable continuous renal replacement therapy, sufficient blood flow through the circuit is crucial, but catheter dysfunction reduces the blood flow by inadequate pressures within the circuit. Therefore, exploring and modifying the possible risk factors related to catheter dysfunction can help to provide continuous renal replacement therapy with minimal interruption. METHODS: Adult patients who received continuous renal replacement therapy at Seoul National University Hospital between January 2019 and December 2021 were retrospectively analyzed. Patients who received continuous renal replacement therapy via a temporary hemodialysis catheter, inserted at the bedside under ultrasound guidance within 12 h of continuous renal replacement therapy initiation were included. RESULTS: A total of 507 continuous renal replacement therapy sessions in 457 patients were analyzed. Dialysis catheter dysfunction occurred in 119 sessions (23.5%). Multivariate analysis showed that less prolonged prothrombin time (adjusted OR 0.49, 95% CI, 0.30-0.82, p = 0.007) and activated partial thromboplastin time (adjusted OR 1.01, 95% CI, 1.00-1.01, p = 0.049) were associated with increased risk of catheter dysfunction. Risk factors of re-catheterization included vascular access to the left jugular and femoral vein. CONCLUSIONS: In critically ill patients undergoing continuous renal replacement therapy, less prolonged prothrombin time was associated with earlier catheter dysfunction. Use of left internal jugular veins and femoral vein were associated with increased risk of re-catheterization compared to the right internal jugular vein.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a ß-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded ß-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the ß-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Comparing the prediction performance of item response theory and machine learning methods on item responses for educational assessments.

To obtain more accurate and robust feedback information from the students' assessment outcomes and to communicate it to students and optimize teaching and learning strategies, educational researchers and practitioners must critically reflect on whether the existing methods of data analytics are capable of retrieving the information provided in the database. This study compared and contrasted the prediction performance of an item response theory method, particularly the use of an explanatory item response model (EIRM), and six supervised machine learning (ML) methods for predicting students' item responses in educational assessments, considering student- and item-related background information. Each of seven prediction methods was evaluated through cross-validation approaches under three prediction scenarios: (a) unrealized responses of new students to existing items, (b) unrealized responses of existing students to new items, and (c) missing responses of existing students to existing items. The results of a simulation study and two real-life assessment data examples showed that employing student- and item-related background information in addition to the item response data substantially increases the prediction accuracy for new students or items. We also found that the EIRM is as competitive as the best performing ML methods in predicting the student performance outcomes for the educational assessment datasets.

A Joint Modeling Approach for Longitudinal Outcomes and Non-ignorable Dropout under Population Heterogeneity in Mental Health Studies.

The paper proposes a joint mixture model to model non-ignorable drop-out in longitudinal cohort studies of mental health outcomes. The model combines a (non)-linear growth curve model for the time-dependent outcomes and a discrete-time survival model for the drop-out with random effects shared by the two sub-models. The mixture part of the model takes into account population heterogeneity by accounting for latent subgroups of the shared effects that may lead to different patterns for the growth and the drop-out tendency. A simulation study shows that the joint mixture model provides greater precision in estimating the average slope and covariance matrix of random effects. We illustrate its benefits with data from a longitudinal cohort study that characterizes depression symptoms over time yet is hindered by non-trivial participant drop-out.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials. Real-time imaging and molecular dynamics simulations demonstrate the deswelling of RGD-bearing microgels via visible-light-mediated trans-azobenzene formation. Near-infrared light can induce in situ swelling of RGD-bearing microgels to increase RGD availability and trigger release of loaded interleukin-4, which facilitates the adhesion structure assembly linked with pro-regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD-bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro-inflammatory polarization. These microgels exhibit high stability and non-toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.

Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy.

A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine.

Comparative study of cathepsin B-cleavable linkers for the optimal design of cathepsin B-specific doxorubicin prodrug nanoparticles for targeted cancer therapy.

A carrier-free prodrug nanoparticle has emerged as a potential approach to cancer therapy. It plays a vital role in enhancing the tumor targeting and therapeutic efficacy of the anticancer agent at sites of intention wherein the prodrug nanoparticle is potentially activated. Herein, five derivatives of cathepsin B-cleavable prodrugs are synthesized via chemically conjugating different cathepsin B-cleavable peptides (Phe-Arg-Arg-Gly, Phe-Arg-Arg-Leu, Phe-Arg-Arg-Leu-Gly, Phe-Leu-Arg-Arg-Gly) to doxorubicin (DOX). The peptide-DOX prodrugs can spontaneously assemble into nanoparticles via their intermolecular hydrophobic and π-π stacking interactions. The resulting cathepsin B-cleavable prodrugs nanoparticles formed different nanoparticle structures according to the amphiphilicity and flexibility of different peptides and their particle stability and cellular uptake mechanism are carefully evaluated in vitro. Among five prodrug nanoparticles, the Phe-Arg-Arg-Leu-DOX (FRRL-DOX) nanoparticle was formed to a size of 167.5 ± 12.4 nm and stably maintains its nanoparticle structure in saline media for 3 days. The FRRL-DOX nanoparticle is well taken up by tumoral nuclei and effectively induces cancer cell death with minimal toxicity to normal cells. In addition, the FRRL-DOX nanoparticle shows 2.3-16.3-fold greater tumor-specific accumulation in vivo than other prodrug nanoparticles and free DOX. The therapeutic effect of FRRL-DOX is finally examined, demonstrating 2.1-fold better anticancer efficacy compared to that of free DOX. Notably, the FRRL-DOX nanoparticle does not exert serious toxicity in its repeated intravenous administration at a high dose of up to 10 mg/kg (equiv. to DOX). In conclusion, the peptide sequence for cathepsin B-cleavable prodrug nanoparticle is determined to be successfully optimized in a way of increasing its tumor selectivity and lowering toxicity to normal tissues.

Reaction-Based Scalable Inorganic Patterning on Rigid and Soft Substrates for Photovoltaic Roofs with Minimal Optical Loss and Sustainable Sunlight-Driven-Cleaning Windows.

Recently developed fabrication methods for inorganic patterns (such as laser printing and optical lithography) can avoid some patterning processes conducted by conventional etching and lithography (such as substrate etching and modulation) and are thereby useful for applications in which the substrates and materials must not be damaged during patterning. Simultaneously, it is also necessary to develop facile and economical methods producing inorganic patterns on various substrates without requiring a special apparatus while attaining the above-mentioned advantages. The present study proposes a reaction-based method for fabricating inorganic patterns by immersing substrates coated with a colloidal nanosheet into an aqueous solution containing inorganic precursors. Silica and TiO2 patterns spontaneously developed during the conversion of each inorganic precursor. These patterns were successful on rigid and flexible substrates. We fabricated these patterns on a wafer-sized silicon and large flexible poly(ethylene terephthalate) film, suggesting the scalability. We fabricated a biomimetic pattern on both sides of a glass window, as a photovoltaic roof, for minimal optical losses to maximally present photovoltaic effects of a solar cell. The TiO2 pattern on glass window exhibits sustainable sunlight-driven-cleaning activity for contaminants. The method could provide a platform for economical high-performance inorganic patterns for energy, environmental, electronics, and other areas.

Patterns of intimacy crisis resolution and their associations with romantic loneliness in Polish and U.S. young adults.

In Erikson's model of development, intimacy and isolation denote polar outcomes of psychosocial crisis in young adulthood. Drawing on this model, the present study used three-wave longitudinal data to examine patterns of the success and lack of success in the resolution of Eriksonian crisis in relation to romantic loneliness as a negative outcome of the intimacy crisis, and compared across Poland and the United States. The data were collected from Polish and U.S. individuals aged 18-40 for Wave 1 (N = 763). Four patterns of the Eriksonian intimacy crisis were identified: (a) stable partnered status; (b) stable single status; (c) transition from single to partnered status; (d) transition from partnered to single status. In both countries, transition from single to partnered status was related to decreased romantic loneliness. Greater initial romantic loneliness was observed among Polish single adults who transited to partnered status in contrast to stable single adults. In turn, the U.S. partnered adults who transited to single status initially experienced lower romantic loneliness than stable single adults. Bivariate latent growth curve models pairing romantic loneliness with relationship satisfaction revealed that higher initial relationship satisfaction was associated with lower initial romantic loneliness, and a greater increase in relationship satisfaction was associated with smaller increases in romantic loneliness. The findings highlight that different resolutions of the intimacy crisis are related to diverse romantic loneliness and relationship satisfaction trajectories and these associations also appear to differ as a function of various marital and loneliness contexts in Poland and the United States. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Selective Anticancer Materials by Self-Assembly of Synthetic Amphiphiles Based on N-Acetylneuraminic Acid.

N-Acetylneuraminic acid (Neu5Ac), one of the abundant types of sialic acid, is an emerging anticancer agent owing to its ability to target selectins in the plasma membrane of cancer cells. Considering the functionality of Neu5Ac, obtaining novel Neu5Ac-conjugated materials with a selective and an enhanced antitumor activity has remained a challenge. Herein, we report the supramolecular materials of three novel amphiphiles composed of Neu5Ac as a hydrophilic segment and pyrene or adamantane as a hydrophobic segment. The synthetic amphiphiles 1, 2, and 3 self-assembled into ribbons, vesicles, and irregular aggregates in an aqueous solution, respectively. Among the materials, vesicles of amphiphile 2 showed the most substantial selectivity toward cancer cells, followed by cell death due to the production of reactive oxygen species by the pyrene group. The dual advantage of Neu5Ac-selectivity and the pyrene-cytotoxicity of vesicles of amphiphile 2 can provide a strategy for effective anticancer materials.

Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death.

Rationale: Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy. Methods: The functional peptide, consisted of anti-PD-L1 peptide and cathepsin B-specific cleavable peptide, is conjugated to a doxorubicin (DOX), resulting in prodrug nanoparticles of PD-NPs via intermolecular interactions. The antitumor efficacy and immune responses with minimal side effects by PD-NPs combining PD-L1 blockade and ICD are evaluated in breast tumor models. Results: The PD-NPs are taken up by PD-L1 receptor-mediated endocytosis and then induce ICD in cancer cells by DOX release. Concurrently, PD-L1 blockade by PD-NPs disrupt the immune-suppressing pathway of cancer cells, resulting in proliferation and reinvigoration of T lymphocytes. In tumor models, PD-NPs accumulate within tumor tissues via enhanced permeability and retention (EPR) effect and induce immune-responsive tumors by recruiting a large amount of immune cells. Conclusions: Collectively, targeted tumor delivery of anti-PD-L1 peptide and DOX via PD-NPs efficiently inhibit tumor progression with minimal side effects.

Psychometric Analysis of the Dating Anxiety Scale for Adolescents in Samples of Polish and U.S. Young Adults: Examining the Factor Structure, Measurement Invariance, Item Functioning, and Convergent Validity.

This study explored whether the Dating Anxiety Scale for Adolescents (DAS-A), which was originally developed in the United States to assess dating anxiety in adolescents, is appropriate for use in samples of young adults from Poland and the United States. The factor structure, measurement invariance across country, gender and relationship status, degree of precision across latent levels of the DAS and the functioning of individual items, and convergent validity were examined in a sample of 309 Polish and 405 U.S. young adults. The confirmatory factor analysis (CFA) supported the original three-factor measurement model of the DAS. Invariance tests revealed factor loadings and item thresholds that differed across subgroups, supporting partial metric and partial scalar invariance. The MIRT analysis showed that all items adequately discriminated participants with low and high anxiety. Dating anxiety latent factor correlations with mental health and interpersonal competence were significant in the expected negative directions. The results call for careful interpretation of research involving the DAS in cultural, gender, and relationship status groups, particularly when the primary goal is to compare mean levels of dating anxiety. Further development of the scale is recommended before it can be used across country, gender, and relationship status groups.

Parental Responses to Transgender and Gender Nonconforming Youth: Associations with Parent Support, Parental Abuse, and Youths' Psychological Adjustment.

The purpose of this study was to examine parental responses to transgender and gender nonconforming [TGNC] youths' gender identities and explore associations of parent support with parental abuse, depressive symptoms, and LGBT-identity disclosure stress. TGNC youth (N = 129), ages 15-21 (M = 18.00, SD = 1.74), completed surveys (2011-2012); experiences of transfeminine (TF; n = 58) and transmasculine (TM; n = 71) youth were analyzed separately. Among mothers of TF youth, 42.0% of initial and 45.3% of current responses were positive; among fathers, 30.0% of initial and 36.0% of current responses were positive. Among mothers of TM youth, 26.0% of initial and 53.3% of current responses were positive; among fathers, 24.0% of initial and 44.6% of current responses were positive. Among TM youth, higher levels of parental support were associated with more positive responses from mothers and fathers. Among both TF and TM youth, greater parent support was associated with less parental abuse, depressive symptoms, and LGBTQ-identity disclosure stress. Parental responses to youths' gender identities became more positive with time for TF youth; however, approximately 50% of all TGNC youth continued to experience minority stress related to parent rejection. Limitations and implications for practice and research are discussed.

Supramolecular Two-Dimensional Systems and Their Biological Applications.

Various biological systems rely on the supramolecular assembly of biomolecules through noncovalent bonds for performing sophisticated functions. In particular, cell membranes, which are 2D structures in biological systems, have various characteristics such as a large surface, flexibility, and molecule-recognition ability. Supramolecular 2D materials based on biological systems provide a novel perspective for the development of functional 2D materials. The physical and chemical properties of 2D structures, attributed to their large surface area, can enhance the sensitivity of the detection of target molecules, molecular loading, and bioconjugation efficiency, suggesting the potential utility of functional 2D materials as candidates for biological systems. Although several types of studies on supramolecular 2D materials have been reported, supramolecular biofunctional 2D materials have not been reviewed previously. In this regard, the current advances in 2D material development using molecular assembly are discussed with respect to the rational design of self-assembling aromatic amphiphiles, the formation of 2D structures, and the biological applications of functional 2D materials.

Myticusin-beta, antimicrobial peptide from the marine bivalve, Mytilus coruscus.

We isolated and purified an antimicrobial peptide (AMP) from the mantle of the hard-shelled mussel, Mytilus coruscus. The peptide was purified through C18 reversed-phase high-performance liquid chromatography, and displayed antibacterial activity. Total molecular mass of 11,182 Da was determined using matrix-assisted laser desorption ionization time-of-flight mass spectrophotometry. The N-terminal 23-amino acid sequence of its purified peak was obtained through Edman degradation, revealing 82% identity with myticusin-1 of M. coruscus. Complete sequence of the target peptide was determined through cDNA cloning and rapid amplification of cDNA ends. The complete sequence comprised 574 bp with a 387-bp open reading frame (ORF) encoding 24 amino acids of a signal peptide and 104 amino acids of a mature peptide, which was named myticusin-beta. Furthermore, we discovered two novel isoforms of myticusin-beta. We constructed and expressed recombinant myticusin-beta, which displayed antimicrobial activity against gram-positive (Bacillus cereus, Bacillus subtilis, Clostridium perfringens, Staphylococcus aureus, Streptococcus iniae, Streptococcus mutans) and gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Vibrio alginolyticus, Klebsiella pneumoniae). Purified recombinant myticusin-beta also showed anti-parasitic activity at various concentrations. A short AMP analog was designed and synthesized based on the sequence of myticusin-beta, with markedly improved antimicrobial activity. Expression of myticusin-beta was detected in the mantle at the highest level, followed by hemocytes. The results obtained in this work suggest that myticusin-beta is an immune-related AMP of M. coruscus and an effective alternative to antibiotics.

A Multidimensional IRT Approach for Dynamically Monitoring Ability Growth in Computerized Practice Environments.

Adaptive learning systems have received an increasing attention as they enable to provide personalized instructions tailored to the behaviors and needs of individual learners. In order to reach this goal, it is desired to have an assessment system, monitoring each learner's ability change in real time. The Elo Rating System (ERS), a popular scoring algorithm for paired competitions, has recently been considered as a fast and flexible method that can assess learning progress in online learning environments. However, it has been argued that a standard ERS may be problematic due to the multidimensional nature of the abilities embedded in learning materials. In order to handle this issue, we propose a system that incorporates a multidimensional item response theory model (MIRT) in the ERS. The basic idea is that instead of updating a single ability parameter from the Rasch model, our method allows a simultaneous update of multiple ability parameters based on a compensatory MIRT model, resulting in a multidimensional extension of the ERS ("M-ERS"). To evaluate the approach, three simulation studies were conducted. Results suggest that the ERS that incorrectly assumes unidimensionality has a seriously lower prediction accuracy compared to the M-ERS. Accounting for both speed and accuracy in M-ERS is shown to perform better than using accuracy data only. An application further illustrates the method using real-life data from a popular educational platform for exercising math skills.