BioNetGen 2.2: Advances in Rule-Based Modeling

BioNetGen is an open-source software package for rule-based modeling of complex biochemical systems. Version 2.2 of the software introduces numerous new features for both model specification and simulation. Here, we report on these additions, discussing how they facilitate the construction, simulation, and analysis of larger and more complex models than previously possible.Comment: 3 pages, 1 figure, 1 supplementary text file. Supplementary text includes a brief discussion of the RK-PLA along with a performance analysis, two tables listing all new actions/arguments added in BioNetGen 2.2, and the "BioNetGen Quick Reference Guide". Accepted for publication in Bioinformatic

Developing a Cross-Cultural Competence Scale for Pre-Service Teachers: A Filipino Case Study

As classrooms grow increasingly diverse, cross-cultural competence (CCC) becomes imperative for pre-service teachers to create inclusive, equitable learning environments. Hence, this study focuses on developing a cross-cultural competence scale specifically for pre-service teachers that highlights the dynamic nature of education and the need to foster inclusivity amid increasing classroom diversity, aiming to address gaps concerning assessment tools dedicated explicitly for pre-service teachers. Exploratory factor analysis of an initial 29-item scale assessing knowledge, teaching flexibility, willingness to engage students, and cultural empathy administered to 109 Filipino pre-service teachers' responses ultimately yielded a 22-item, two-factor structure with sound psychometric properties: "Attitudes Toward Culturally Diverse Students" and "Cultural Knowledge and Teaching Flexibility." The factors align well with the conceptual domains of cognitive, affective, and psychomotor learning. This research significantly contributes a contextualized CCC instrument that enhances multicultural education and evaluates pre-service teachers' readiness for diverse classrooms, aligning with the educational dynamic imperative. In summary, this research makes an invaluable contribution to teacher training and multicultural education by developing a targeted and rigorously validated assessment tool

Exploring the Viability of Augmented Reality as a Supplementary Material for Learning Cell Biology and Photosynthesis for Grade 12 Students

Augmented reality (AR) is one of the many emerging digital technologies that specializes in gaming, medicine, entertainment, and education. AR-assisted technologies have undergone studies and were claimed to provide a better learning experience for students and lecturers who integrate its features in modern-day classrooms. An example is Google Expeditions, a cost-effective and accessible alternative; however, further research may be needed on such applications, especially when used solely as a supplement. This study assesses AR\u27s effects on Grade 12 students\u27 academic performance and motivation when used as a supplemental learning material for cell biology and photosynthesis. Assessment scores between those who used augmented reality and those who did not reveal a greater improvement in academic performance of the former group. Furthermore, students reported through the Instructional Materials Motivation Survey (IMMS) that they were motivated by the AR tours used during the experiment. These findings point to the potential benefit of integrating AR-based supplementary materials to promote student learning and motivation

Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study

Objective: To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. Design: Prospective, propensity score matched cohort study. Setting: General teaching hospital in Boston, Massachusetts, United States, 2006-10. Participants: 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measures: The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation 3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. Results: The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation to values less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). Conclusion: The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited

Kir2.1 Interactome Mapping Uncovers PKP4 as a Modulator of the Kir2.1-Regulated Inward Rectifier Potassium Currents

Kir2.1, a strong inward rectifier potassium channel encoded by the KCNJ2 gene, is a key regulator of the resting membrane potential of the cardiomyocyte and plays an important role in controlling ventricular excitation and action potential duration in the human heart. Mutations in KCNJ2 result in inheritable cardiac diseases in humans, e.g. the type-1 Andersen-Tawil syndrome (ATS1). Understanding the molecular mechanisms that govern the regulation of inward rectifier potassium currents by Kir2.1 in both normal and disease contexts should help uncover novel targets for therapeutic intervention in ATS1 and other Kir2.1-associated channelopathies. The information available to date on protein-protein interactions involving Kir2.1 channels remains limited. Additional efforts are necessary to provide a comprehensive map of the Kir2.1 interactome. Here we describe the generation of a comprehensive map of the Kir2.1 interactome using the proximity-labeling approach BioID. Most of the 218 high-confidence Kir2.1 channel interactions we identified are novel and encompass various molecular mechanisms of Kir2.1 function, ranging from intracellular trafficking to cross-talk with the insulin-like growth factor receptor signaling pathway, as well as lysosomal degradation. Our map also explores the variations in the interactome profiles of Kir2.1WT versus Kir2.1Δ314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. Finally, using patch-clamp analysis, we validate the functional relevance of PKP4, one of our top BioID interactors, to the modulation of Kir2.1-controlled inward rectifier potassium currents. Our results validate the power of our BioID approach in identifying functionally relevant Kir2.1 interactors and underline the value of our Kir2.1 interactome as a repository for numerous novel biological hypotheses on Kir2.1 and Kir2.1-associated diseases.This work was supported by the National Institutes of Health (NIH) through the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL122352 awarded to J.J., as well as the National Institute of General Medical Sciences (NIGMS) grant R01GM094231 and the National Cancer Institute (NCI) grant U24CA210967 awarded to A.I.N. R.K. is supported by the NCI support grant P30CA046592 awarded to the University of Michigan Rogel Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.S

Sustained Release of Amnion-Derived Cellular Cytokine Solution Facilitates Achilles Tendon Healing in Rats

Objective: In the United States, around 50% of all musculoskeletal injuries are soft tissue injuries including ligaments and tendons. The objective of this study is to assess the role of amnion-derived cellular cytokine solution (ACCS) in carboxy-methyl cellulose (CMC) gel in the healing of Achilles tendon in a rat model, and to examine its effects on mechanical properties and collagen content. Methods: Achilles tendons of Sprague-Dawley rats were exposed and transected. The distal and proximal ends were injected with either saline or ACCS in CMC, in a standardized fashion, and then sutured using a Kessler technique. Tendons from both groups were collected at 1, 2, 4, 6, and 8 weeks postoperatively and assessed for material properties. Collagen studies were performed, including collagen content, collagen cross-linking, tendon hydration, and immunohistochemistry. Tendons were also evaluated histologically for cross-sectional area. Results: Mechanical testing demonstrated that treatment with ACCS in CMC significantly enhances breaking strength, ultimate tensile strength, yield strength, and Young's modulus in the tendon repair at early time points. In context, collagen content, as well as collagen cross-linking, was also significantly affected by the treatment. Conclusion: The application of ACCS in CMC has a positive effect on healing tendons by improving mechanical properties at early time points. Previous studies on onetime application of ACCS (not in CMC) did not show significant improvement on tendon healing at any time point. Therefore, the delivery in a slow release media like CMC seems to be essential for the effects of ACCS demonstrated in this study

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

Long Wavelength Anomalous Diffusion Mode in the 2D XY Dipole Magnet

In 2D XY ferromagnet the dipole force induces a strong interaction between spin-waves in the long-wavelength limit. The major effect of this interaction is the transformation of a propagating spin-wave into a diffusion mode. We study the anomalous dynamics of such diffusion modes. We find that the Janssen-De Dominics functional, which governs this dynamics, approaches the non-Gaussian fixed-point. A spin-wave propagates by an anomalous anisotropic diffusion with the dispersion relation: $i\omega{\sim}k_{y}^{\Delta_y}$ and $i\omega{\sim}k_{x}^{\Delta_x}$, where ${\Delta_y}=47/27$ and ${\Delta_x}=47/36$. The low-frequency response to the external magnetic field is found.Comment: 34 pages, RevTeX, 2 .ps figures, the third figure is available upon reques

Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process