Dopamine and the regulation of cell proliferation in gerbil (Meriones unguiculatus) pyloric mucosa

The epithelium of the digestive system mucosa consists of a highly dynamic cell population. The conditions under which mitotic activity in the gastrointestinal epithelium is regulated is as yet poorly understood. Nevertheless, it is assumed that some biogenic amines might be involved. Having demonstrated that dopaminergic cells occur in the stomach of gerbils (Meriones unguiculatus), in the present study we examined the influence of dopamine antagonist haloperidol on the proliferation of epithelial cells in the mucosa of the stomach. Proliferating cells were detected immunocytochemically and quantified after in-vivo labeling with 5-bromo-2'-desoxyuridine in both haloperidol- and saline-treated animals. The results show that acute doses of haloperidol significantly increases the proliferation rate in the pyloric mucosa, suggesting that dopamine plays a probable modulatory role in the regulation of mitotic activity. These findings are discussed with regard to the role of paraneurons in regulating epithelial mitosis.     

Fanconi anemia complementation group E: clinical and cytogenetic data of the first patient

The clinical and cytogenetic data of the first patient proven to belong to the fifth Fanconi anemia complementation group are described. The Turkish boy presented with psychomotoric retardation, growth retardation, retarded bone age, brachycephaly, hypotelorism, epicanthus, syndactyly, brachydactyly, renal dystopia, and cryptorchism. In addition, an asymmetrical skeletal anomaly was seen with a double distal phalanx of the left thumb and hypoplasia of the right thumb. Typical hematological features of the disorder developed, at the age of 2.5 years, about 1 year after diagnosis. Cytogenetic studies confirmed the clinical diagnosis and revealed a spontaneous chromosomal instability and hypersensitivity to the cross-linking agents diepoxybutane and Trenimon. The findings in the patient, who is considered to be the standard for the fifth Fanconi anemia complementation group, are compared with data reported for other patients affected with Fanconi anemia.     

Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.     

On parsing two-level grammars

Summary Making use of the fact that two-level grammars (TLGs) may be thought of as finite specification of context-free grammars (CFGs) with infinite sets of productions, known techniques for parsing CFGs are applied to TLGs by first specifying a canonical CFG G — called skeleton grammar — obtained from the cross-reference of the TLG G. Under very natural restrictions it can be shown that for these grammar pairs (G, G) there exists a 1 — 1 correspondence between leftmost derivations in G and leftmost derivations in G. With these results a straightforward parsing algorithm for restricted TLGs is given.     

Design and testing of the Minotaur advanced grid-stiffened fairing

A composite grid-stiffened structure concept was selected for the payload fairing of the Minotaur launch vehicle. Compared to sandwich structures, this concept has an advantage of smaller manufacturing costs and lighter weight. To reduce weight the skin pockets are allowed to buckle visibly up to about 0.5 cm peak displacement.

Various failure modes were examined for the composite grid-stiffened structure. The controlling criterion for this design was a joint failure in tension between the ribs and skin of the structure. The identification of this failure mechanism and the assessment of bounding strains required to control it required extensive test and analysis effort. Increasing skin thickness to control skin buckling resulted in reduced strains between the skin and ribs.

Following the identification of the relevant failure criteria, a final design for the fairing was generated. The resulting 6 m tall fairing was constructed of a tow-placed carbon fiber composite grid structure that was over-wrapped to create a laminated skin. Upon completion of curing and machining, the fairing was cut in half to create the classic “clam-shell” fairing. Static qualification testing demonstrated the structural integrity of the fairing, thereby proving the design and manufacturing process. Loads were applied incrementally in a static loading scenario. The applied load envelope exceeded worst-case dynamic flight conditions with an added safety factor of 25%. At peak load the fairing maintained structural integrity while remaining within the required displacement envelope for payload safety.

Data were collected during the test from a variety of sensors including traditional displacement transducers and strain gages. In addition, full field displacement was monitored at critically loaded fairing sections by means of digital photogrammetry. This paper summarizes the test results, presents the overall performance of the fairing under the test loads, correlates test response and analysis, and identifies lessons learned.

Work continues at the Air Force Research Laboratory (AFRL) and Boeing to identify means of further controlling tensile failure of the un-reinforced polymer bonded joint between the ribs and skin. Stiffening of skin adjacent to the joints and introduction of lightweight foam jackets at the interior of the fairing both show promise of delaying joint failure to higher loads.     

Surface Actuation of Lightweight Mirrors with Shape Memory Alloy

The ability to create lightweight mirrors that can maintain surface accuracy is a major technical challenge for future space telescopes. Processing-induced errors and surface errors due to temperature excursions and gravity sag (zero gravity in space) make it impossible to correct the surface of thin mirror face-sheets by conventional point actuators. The challenges are compounded by the requirements for mirrors to have adequate stiffness for pointing accuracy. An experimental and analytical study was conducted to explore the feasibility of correcting the shape of lightweight (≈1 kg/m2) mirrors using a “Nitinol” (nickel-titanium) shape memory alloy (SMA). Shape memory alloys are increasingly used as smart devices in aerospace applications. Their primary advantage over other smart materials (i.e., piezo-ceramics and piezo-polymers) is in their ability to undergo large strains and displacements and thus enable the development of smart mechanisms. Active shape correction is the only means of mitigating heat and zero-gravity-induced distortions in space-based optical imaging systems. The repeatability and reliability of a possible actuation system based on properties of the SMA wires were studied by testing the stress-strain and stress recovery behavior under controlled conditions. Embedded SMA wires were then used to actuate a composite beam, and the movement induced by actuation was monitored with the Moiré interferometry method.