Flight investigation of a vertical-velocity command system for VTOL aircraft

A flight investigation was undertaken to assess the potential benefits afforded by a vertical-velocity command system (VVCS) for VTOL (vertical take-off and landing) aircraft. This augmentation system was conceived primarily as a means of lowering pilot workload during decelerating approaches to a hover and/or landing under category III instrument meteorological conditions. The scope of the investigation included a determination of acceptable system parameters, a visual flight evaluation, and an instrument flight evaluation which employed a 10 deg, decelerating, simulated instrument approach task. The results indicated that the VVCS, which decouples the pitch and vertical degrees of freedom, provides more accurate glide-path tracking and a lower pilot workload than does the unaugmented system

A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

Cell-cell contacts play a vital role in intracellular signaling, although the molecular mechanisms of these signaling pathways are not fully understood. E-cadherin, an important mediator of cell-cell adhesions, has been shown to be cleaved by γ-secretase. This cleavage releases a fragment of E-cadherin, E-cadherin C-terminal fragment 2 (E-cad/CTF2), into the cytosol. Here, we study the fate and function of this fragment. First, we show that coexpression of the cadherin-binding protein, p120 catenin (p120), enhances the nuclear translocation of E-cad/CTF2. By knocking down p120 with short interfering RNA, we also demonstrate that p120 is necessary for the nuclear localization of E-cad/CTF2. Furthermore, p120 enhances and is required for the specific binding of E-cad/CTF2 to DNA. Finally, we show that E-cad/CTF2 can regulate the p120-Kaiso-mediated signaling pathway in the nucleus. These data indicate a novel role for cleaved E-cadherin in the nucleus

Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Low-power operation using self-timed circuits and adaptive scaling of the supply voltage

Recent research has demonstrated that for certain types of applications like sampled audio systems, self-timed circuits can achieve very low power consumption, because unused circuit parts automatically turn into a stand-by mode. Additional savings may be obtained by combining the self-timed circuits with a mechanism that adaptively adjusts the supply voltage to the smallest possible, while maintaining the performance requirements. This paper describes such a mechanism, analyzes the possible power savings, and presents a demonstrator chip that has been fabricated and tested. The idea of voltage scaling has been used previously in synchronous circuits, and the contributions of the present paper are: 1) the combination of supply scaling and self-timed circuitry which has some unique advantages, and 2) the thorough analysis of the power savings that are possible using this technique

Quorum Sensing in \u3ci\u3eCandida albicans\u3c/i\u3e: Probing Farnesol’s Mode of Action with 40 Natural and Synthetic Farnesol Analogs

The dimorphic fungus Candida albicans produces extracellular farnesol (3,7, 11-trimethyl-2,6,10-dodecatriene- 1-ol) which acts as a quorum-sensing molecule (QSM) to suppress filamentation. Of four possible geometric isomers of farnesol, only the E,E isomer possesses QSM activity. We tested 40 natural and synthetic analogs of farnesol for their activity in an N-acetylglucosamine-induced differentiation assay for germ tube formation (GTF). Modified structural features include the head group, chain length, presence or absence of the three double bonds, substitution of a backbone carbon by S, O, N, and Se heteroatoms, presence or absence of a 3-methyl branch, and the bulkiness of the hydrophobic tail. Of the 40 compounds, 22 showed QSM activity by their ability to reduce GTF by 50%. However, even the most active of the analogs tested had only 7.3% of the activity of E,E-farnesol. Structure-activity relationships were examined in terms of the likely presence in C. albicans of a farnesol binding receptor protein. Includes supplemental material