The Effect of Thiol Structure on Allyl Sulfide Photodegradable Hydrogels and their Application as a Degradable Scaffold for Organoid Passaging

Intestinal organoids are useful in vitro models for basic and translational studies aimed at understanding and treating disease. However, their routine culture relies on animal-derived matrices that limit translation to clinical applications. In fact, there are few fully defined, synthetic hydrogel systems that allow for the expansion of intestinal organoids. Here, an allyl sulfide photodegradable hydrogel is presented, achieving rapid degradation through radical addition-fragmentation chain transfer (AFCT) reactions, to support routine passaging of intestinal organoids. Shear rheology to first characterize the effect of thiol and allyl sulfide crosslink structures on degradation kinetics is used. Irradiation with 365 nm light (5 mW cm⁻²) in the presence of a soluble thiol (glutathione at 15 × 10⁻³ m ), and a photoinitiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate at 1 × 10⁻³ m ), leads to complete hydrogel degradation in less than 15 s. Allyl sulfide hydrogels are used to support the formation of epithelial colonies from single intestinal stem cells, and rapid photodegradation is used to achieve repetitive passaging of stem cell colonies without loss in morphology or organoid formation potential. This platform could support long-term culture of intestinal organoids, potentially replacing the need for animal-derived matrices, while also allowing systematic variations to the hydrogel properties tailored for the organoid of interest.     

The influence of buffer/capping-layer-mediated stress on the coercivity of NdFeB films

The influence of buffer/capping-layer-mediated stress on the coercivity of NdFeB films is demonstrated. NdFeB films, 5 μm thick and rich in Nd, were deposited on Si/SiO₂ and Al₂O₃ substrates, with or without buffer/capping layers of Ta. The coercivity of Ta-free samples (～0.5 T) is significantly less than that achieved in samples with Ta present as a buffer and/or capping layer (1.7–1.8 T). The as-sputtered Ta layers are under strong compressive stress due to peening. During post-deposition annealing to crystallize the Nd₂Fe₁₄B phase, stresses are relieved in the Ta layer. This leads in turn to a compressive stress in the NdFeB layer, inducing extrusion of a Nd-rich phase up through the NdFeB layer. The high values of coercivity achieved in Ta-containing structures are attributed to good coverage of individual Nd₂Fe₁₄B grains with the redistributed Nd-rich phase.     

Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion

The possible effects of the polyamine interconversion pathway on tissue polyamine levels, brain edema formation, and ischemic injury volume were studied by using a selective irreversible inhibitor, MDL 72527, of the interconversion pathway enzyme, polyamine oxidase. In an intraluminal suture occlusion model of middle cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05) and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in subcortex (difference not significant). Ischemic injury volume was reduced by 22% in the cortex (p < 0.05) and 17% in the subcortex (p < 0.05) after inhibition of polyamine oxidase by MDL 72527. There was an increase in tissue putrescine levels together with a decrease in spermine and spermidine levels at the ischemic site compared with the nonischemic site after ischemia-reperfusion injury. The increase in putrescine levels at the ischemic cortical and subcortical region was reduced by a mean of 45% with MDL 72527 treatment. These results suggest that the polyamine interconversion pathway has an important role in the postischemic increase in putrescine levels and that blocking of this pathway can be neuroprotective against neuronal cell damage after temporary focal cerebral ischemia.     

A Gd-Film Thermomagnetic Generator in Resonant Self-Actuation Mode

Thermomagnetic generation is a promising technology for conversion of low-grade waste heat into electricity. Key requirements for the development of efficient thermomagnetic generators (TMGs) are tailored thermomagnetic materials as well as innovative designs enabling fast heat transfer. Recently, film-based thermomagnetic generators are developed that operate in the mode of resonant self-actuation enabling high frequency and stroke of a movable cantilever and, thus, efficient conversion of thermal energy into electrical energy. Here, the performance of a Gadolinium (Gd)-film-based TMG that is optimized for resonant self-actuation near room temperature is reported. The Gd-film TMG exhibits large oscillation frequencies up to 106 Hz and large strokes up to 2 mm corresponding to 38% of the oscillating cantilever's length. This performance occurs in a sharply bound range of ambient temperatures with an upper limit near the film's ferromagnetic to paramagnetic transition temperature T_c of 20 °C and of heat source temperatures ranging between 40 and 75 °C. The maximum power per footprint is 23.8 µWcm⁻², at which the Gd film undergoes a temperature change of only 0.9 °C at ≈10 °C above T_c.     

Oxygen consumption prediction models for individual and combination materials handling tasks

An experiment was conducted to develop models to predict oxygen consumption of males and females engaged in common materials handling tasks including lifting, lowering, pushing, pulling, (de)palletising and combination tasks involving lifting or lowering a box and carrying it a set distance and lifting or lowering it to the destination. Nineteen male and 19 female subjects participated in the study. A psychophysical approach was used to set load limits for individual subjects for the oxygen consumption protocol. The 8398 oxygen consumption values collected were entered into the initial regression analyses and 168 potential outliers were removed before the final models were run. In addition to relevant task variables, body weight was a significant predictor variable in all models. The r(2) values for the final models ranged from 0.54 to 0.82 and the root mean square errors ranged from 90.2 ml to 294.8 ml.     

Using feedforward neural networks and forward selection of input variables for an ergonomics data classification problem

A method was developed to accurately predict the risk of injuries in industrial jobs based on datasets not meeting the assumptions of parametric statistical tools, or being incomplete. Previous research used a backward‐elimination process for feedforward neural network (FNN) input variable selection. Simulated annealing (SA) was used as a local search method in conjunction with a conjugate‐gradient algorithm to develop an FNN. This article presents an incremental step in the use of FNNs for ergonomics analyses, specifically the use of forward selection of input variables. Advantages to this approach include enhancing the effectiveness of the use of neural networks when observations are missing from ergonomics datasets, and preventing overspecification or overfitting of an FNN to training data. Classification performance across two methods involving the use of SA combined with either forward selection or backward elimination of input variables was comparable for complete datasets, and the forward‐selection approach produced results superior to previously used methods of FNN development, including the error back‐propagation algorithm, when dealing with incomplete data. © 2004 Wiley Periodicals, Inc. Hum Factors Man 14: 31–49, 2004.     

Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women

The protease thrombin seems to play a central role in events following neural injury, whereby the enzyme can act, in concert with other molecules as a hormone or as a growth factor. In cells derived from the nervous system, thrombin induces changes in morphology and proliferation. The signalling mechanisms involved in these thrombin-activated processes are still unclear. In the present study we investigated Ca2+ signals in fura-2 loaded rat astrocytes in primary culture. Brief stimulation of astrocytes with thrombin induced a dose-dependent transient elevation of [Ca2+]i, best fitted by a double-sigmoidal curve giving two EC50 values of 3 pM and 150 pM. Continuous superfusion of cells with thrombin induced Ca2+ responses with three different types of kinetics. In 48% of the cells tested a single transient rise superimposed with fast fluctuations of [Ca2+]i was seen. The following complex long-term changes of [Ca2+]i, dependent on the presence of the agonist thrombin, were observed: i) a biphasic [Ca2+]i elevation, characterized by an initial peak followed by a sustained plateau phase (in 43% of the cells) and ii) oscillations of [Ca2+]i (in 9% of the cells). The observed Ca2+ responses were inhibited by the phospholipase C (PLC) inhibitor U-73122 and the thrombin inhibitor protease nexin-1/glia-derived nexin. The synthetic thrombin receptor activating peptide could mimic the thrombin-induced changes of [Ca2+]i. In astrocytes in Ca2+-free medium, thrombin induced a sharp single transient Ca2+ rise, without superimposed fluctuations. After depletion of intracellular Ca2+ stores with thapsigargin the Ca2+ response to thrombin was diminished or completely suppressed indicating that thrombin induces the release of Ca2+ from intracellular stores. During long-term Ca2+ responses, omission of extracellular Ca2+ resulted in a reversible interruption of the signal. In conclusion our results demonstrate that thrombin by activation of its plasma membrane receptor induces through activation of PLC different types of Ca2+ responses. The complex Ca2+ signals are generated by an interplay of InsP3-mediated Ca2+ release from intracellular stores and Ca2+ entry across the plasma membrane.     

Transient shear waves in a wedge subjected to rapid tearing

The surface of an elastic wedge is subjected to sudden antiplane surface tractions and displacements sufficient to cause tearing. The subsequent crack instability is investigated. The wedge faces subtend an angle κπ with the line of antisymmetry, along which the crack propagates with a constant velocity v. For the externally applied disturbances that are considered here, and for constant crack tip velocities, the particle velocity and $\text{?t}{}_{\mathrm{\theta z}}$ are functions of $\text{r}\text{t}$ and θ only, which allows Chaplygin's transformation and conformai mapping to be used. The theory of analytic functions is then used. For various values of the crack propagation velocity, the dependence of the elastodynamic stress intensity factor, and energy flux into the crack tip, on the wedge angle 2κπ is investigated.     

Notch sensitivity and brittleness in fracture testing of S2 columnar freshwater ice

Two loading configurations (four-point-bend, three-point-bend) were used in the laboratory at Clarkson to test for the fracture toughness of carefully grown S2 columnar freshwater ice. For one specific crack orientation and one grain size, the crack length was varied ranging from very short to very deep. The crack length effects were studied in this way for three specimen sizes (the in-plane dimensions of the specimen size were geometrically scaled; the specimen thickness was essentially constant). These crack length and specimen size tests are primarily directed towards designing fracture toughness tests for ice that both satisfy small scale yielding requirements and provide material properties (in the sense of (1)) — toughness values independent of the size and geometry of the specimen. Considerations of sufficient notch sensitivity in terms of brittleness numbers provide a means to determine the necessary specimen size. The results reported in this paper suggest that the specimen sizes used in testing S2 ice to date have largely been sub-size.