Validation of counter propagation neural network models for predictive toxicology according to the OECD principles: a case study

The OECD has proposed five principles for validation of QSAR models used for regulatory purposes. Here we present a case study investigating how these principles can be applied to models based on Kohonen and counter propagation neural networks. The study is based on a counter propagation network model that has been built using toxicity data in fish fathead minnow for 541 compounds. The study demonstrates that most, if not all, of the OECD criteria may be met when modeling using this neural network approach.     

Rapid analysis of titer,aggregate, and intact mass of antibody therapeutics using automated multi-dimensional liquid chromatography coupled with native mass spectroscopy

Monoclonal antibodies are tetrameric complex proteins, primarily produced using mammalian cell culture. Attributes such as titer, aggregates, and intact mass analysis are monitored during process development/optimization. In the present study, a novel workflow such that the Protein-A affinity chromatography is performed in the first dimension for purification and titer estimation, whereas size exclusion chromatography is employed in the second dimension to characterize size variants using native mass spectrometry. The present workflow offers a significant advantage over the traditionally used standalone Protein-A affinity chromatography followed by size exclusion chromatography analysis in that it can monitor these four attributes in 8 min while requiring a minimal sample size (10–15 μg) and not requiring any manual peak collection. In contrast, the traditional standalone approach requires manual collection of eluted peaks in Protein-A affinity chromatography followed by buffer exchange to a mass-compatible buffer, which can take up to 2–3 h with considerable risk of sample loss, degradation, and induced modifications. As the biopharma industry moves to make analytical testing efficient, we believe that the approach proposed here would be of significant interest due to its ability to monitor multiple process and product quality attributes in a single workflow and via rapid analysis.     

Instant nano-hydroxyapatite: a continuous and rapid hydrothermal synthesis

Nano-particle hydroxyapatite (HA) rods, were rapidly synthesised using a three pump continuous hydrothermal process (using a water feed at up to 400 degrees C and at 24 MPa): the product was obtained as a highly crystalline and phase pure material, without the need for an ageing step or subsequent heat treatment.     

Analysis of stationary discrete-time GI/D-MSP/1 queue with finite and infinite buffers

This paper considers a single-server queueing model with finite and infinite buffers in which customers arrive according to a discrete-time renewal process. The customers are served one at a time under discrete-time Markovian service process (D-MSP). This service process is similar to the discrete-time Markovian arrival process (D-MAP), where arrivals are replaced with service completions. Using the imbedded Markov chain technique and the matrix-geometric method, we obtain the system-length distribution at a prearrival epoch. We also provide the steady-state system-length distribution at an arbitrary epoch by using the supplementary variable technique and the classical argument based on renewal-theory. The analysis of actual-waiting-time (in the queue) distribution (measured in slots) has also been investigated. Further, we derive the coefficient of correlation of the lagged interdeparture intervals. Moreover, computational experiences with a variety of numerical results in the form of tables and graphs are discussed.     

Luminescence study of cerium-doped La2Hf2O7: Effects due to trivalent and tetravalent cerium and oxygen vacancies

X-ray excited emission spectra, photoluminescence excitation and emission spectra, optical reflectivity spectra, and pulsed X-ray and optical excited luminescence decay measurements are reported for cerium-doped La₂Hf₂O₇ powders prepared by solid state synthesis. A broad luminescence associated with oxygen vacancies is observed in the region 350–750 nm with a peak around 460 nm. The photoluminescence spectra and the number of oxygen vacancies vary for samples annealed in oxidizing or reducing atmospheres and with the temperature of the synthesis process. Increasing the cerium concentration reduces the oxygen-vacancy-related emission due to the presence of Ce⁴⁺. First principles calculations predict that Ce⁴⁺ can substitute in Hf sites; this is confirmed from the optical reflectivity spectrum of cerium-doped La₂Hf₂O₇. Photoluminescence excitation and emission spectra characteristic of Ce⁴⁺ charge transfer transitions and possibly Ce³⁺ are also observed. Although trivalent cerium may be present, no emission observed from cerium-doped La₂Hf₂O₇ can be attributed to Ce³⁺ in La sites.     

Investigation of phase segregation in Zn1−xMgxO systems

The present work reports on the synthesis of the Zn_1?xMg_xO (x = 0, 0.02, 0.05, 0.10, 0.15 and 0.20) samples by sol–gel method and the investigations on their structural, morphological and optical properties. X-ray diffraction (XRD) data analysis confirms the formation of pure ZnO phase below 10% Mg doping and MgO related phases appears in 10% doped sample indicating that phase segregation of MgO starts at x ≥ 0.10 samples. The phase segregation observed through XRD analysis is also supported by results from Scanning Electron Microscopy (SEM), Raman spectroscopy and photoluminescence studies. Furthermore, the enhancement in optical band gap, with Mg doping, from 3.1 ± 0.1 eV to 3.5 ± 0.1 eV has been observed through UV–Vis spectroscopic analysis. Above results have been discussed on the basis of defects level observed through Raman and photoluminscence studies.     

Rheology of polymer blends: non-linear model for viscoelastic emulsions undergoing high deformation flows

Non-linear rheology of a mixture of two viscoelastic immiscible liquids undergoing high deformation flow was considered. Using Grmela's formalism (Grmela 1986, 1989, 1993a, b) and the coarse grained picture given by Onuki (1987) and Doi and Ohta (1991), we have derived a set of highly non-linear time-dependent transport equations that take into account a direct coupling between the rheology and morphology. Breakup, coalescence, and the high deformation of the interface were considered. Models of Doi and Ohta (1991), Lee and Park (1994), and Grmela et al. (1998) are recovered as special cases. The parameters of?the model were given a physical meaning in both shear and elongational flows and the predictions of the model were ¶compared to the predictions of the previous models on the basis of experimental results obtained on two model?blends PDM/PB polydimethylsiloxane/poly(1-butene) and PP/PS polypropylene/polystyrene blends.     

High-throughput capillary electrophoresis analysis of biopharmaceuticals utilizing sequential injections

The complexity of biotherapeutic products implies an ever-increasing list of product quality attributes that need to be monitored and characterized. In addition, the growing interest in implementing process analytical technology in biopharmaceutical production has further increased the testing burden, together with the need for rapid testing that can facilitate real-time or near-real-time decision-making. Capillary electrophoresis (CE) has made a place in biopharmaceutical analysis but is regarded as a low-throughput method, with the instrument dead time constituting more than 80% of the total time of analysis. In this study, the dead time of CE was utilized to analyse 3 mAb samples in a single-CE run. This approach resulted in an up to 77% reduction in the total analysis time and increased the productivity by up to 300%, compared to traditional single CE-ultraviolet runs, without compromising resolution or relative peak areas. Additionally, good method reproducibility was observed. The compatibility of the method has been demonstrated with protein A eluate and cation exchange chromatography fractions. We, thus, propose that sequential injections can be applied for fast and robust CE analysis of biopharmaceuticals.     

Role of Macromolecules in Medical Application: Challenges and Opportunities

The concept of macromolecules, which is applied to synthetic and natural polymers, allows for various contemporary polymeric materials and inventive uses. A dynamic structure of macromolecules called the extracellular matrix (ECM) maintains tissues and organs functioning. The cell therapy procedure known as wound healing involves depositing ECM components such as collagen, fibronectin, and laminin. The clinical assessment and management of wounds remain challenging despite the introduction of numerous therapeutic regimens because of their laboriously prolonged treatment requirements and complex wound-healing mechanisms using macromolecules of a specific type, such as proteins, carbohydrates, lipids, and nucleic acids. Additionally, proteins affect the wound site's mechanical characteristics, such as tensile strength, elasticity, and permeability, which impact the effectiveness and success of wound healing. The main goal of this article is to give a current overview of how therapeutic alternatives have evolved using cutting-edge innovative techniques for the healing and treatment of wounds. In this article, we have covered different types of macromolecules, how diet affects the wound, what causes wounds, and how macromolecules can help, and how to treat wounds.     

Molecular Flytraps Held Together by Platinum–Platinum Intermetallic Bonds

Metal-metal bonds have rarely been explored as active elements in supramolecular assemblies despite their unique potential to introduce responsive behavior. In this report, a dynamic molecular container composed of two cyclometalated Pt units is constructed using Pt−Pt bonds. This molecule—the flytrap—has a flexible jaw composed of two [18]crown-6 ethers that can adapt their shape to bind large inorganic cations with sub-micromolar affinity. Along with the spectroscopic and crystallographic characterization of the flytrap, we report its photochemical assembly, which allows the capture of ions and their transport from solution to the solid state. In addition, we have been able to recycle the flytrap to regenerate its starting material due to the reversible nature of the Pt−Pt bond. We believe that other molecular containers and materials for harvesting valuable substrates from solution could be assembled using the advances presented here.