The alpha-effect in cyclic secondary amines: new scaffolds for iminium ion accelerated transformations

Five-membered secondary amine heterocycles containing an α-heteroatom were prepared and shown to be ineffective as catalysts for the iminium ion catalysed Diels–Alder reaction between cinnamaldehyde and cyclopentadiene. Their six-membered counterparts proved to be highly active catalysts. In stark contrast, the catalytic activity observed when comparing the non α-heteroatom cyclic amines proline methyl ester and methyl pipecolinate showed the five-membered ring amine was significantly more active. Concurrent density functional theoretical calculations suggest a rationale for the observed trends in reactivity, highlighting that LUMO activation through an iminium ion intermediate plays a key role in catalytic activity

Interactions of short-term and chronic treadmill training with aging of the left ventricle of the heart

With aging, there is a decline in cardiac function accompanying increasing risk of arrhythmias. These effects are likely to be mechanistically associated with age-associated changes in calcium regulation within cardiac myocytes. Previous studies suggest that lifelong exercise can potentially reduce age-associated changes in the heart. Although exercise itself is associated with changes in cardiac function, little is known about the interactions of aging and exercise with respect to myocyte calcium regulation. To investigate this, adult (12 months) and old (24 months) C57/Bl6 mice were trained using moderate-intensity treadmill running. In response to 10 weeks’ training, comparable cardiac hypertrophic responses were observed, although aging independently associated with additional cardiac hypertrophy. Old animals also showed increased L- and T-type calcium channels, the sodium–calcium exchange, sarcoendoplasmic reticulum calcium ATPase, and collagen (by 50%, 92%, 66%, 88%, and 113% respectively). Short-term exercise training increased D-type and T-type calcium channels in old animals only, whereas an increase in sodium–calcium exchange was seen only in adult animals. Long-term (12 months) training generally opposed the effects of aging. Significant hypertrophy remained in long-term trained old animals, but levels of sarcoendoplasmic reticulum calcium ATPase, sodium–calcium exchange, and collagen were not significantly different from those found in the adult trained animals

Postural Stability is Reduced in People with Multiple Sclerosis due to Walking-imposed Fatigue

The most limiting symptoms reported by individuals with multiple sclerosis (MS) are impaired balance and symptomatic fatigue. We have reported greater postural sway and reduced stability following local muscular fatigue in individuals with MS, suggesting that these symptoms may be related. However, it is unknown whether a similar relationship exists with modest increases in fatigue resulting from an activity of daily living (ADL). Thus, the purpose of this study was to determine whether walking has a greater impact on balance during postural tasks in people with MS (PwMS) compared to those without. Seven PwMS (43±12 yrs, 6F/1M) and 10 controls (CON; 42±12 yrs, 7F/3M) performed postural tasks (quiet stance, fixed/maximal reaches) pre/post 30 minutes of treadmill walking at a range of speeds (0.6-1.4 m/s). Individuals rated their fatigue pre/post walking using a Visual Analog Scale. Kinematic data were recorded using a passive marker system (Qualysis AB) and kinetic data were recorded using two forceplates (AMTI), one under each foot. The net center of pressure was analysed using a time to contact analysis to assess postural stability. Following prolonged walking PwMS demonstrated greater reductions in stability than the CON group during the most challenging task (P=0.04), that may be related to increased fatigue (P\u3c0.0001) following walking. PwMS demonstrated greater stability than the CON group for maximal reaches (backward, P=0.009; forward, P=0.03 frontal plane only), which may be explained by reduced reach distances performed by the PwMS (backward, P=0.2; forward, P=0.008). These findings suggest that PwMS place a higher priority on stability, than maximal reach distance, which could relate to fall-related fear or specific disease-related limitations. These findings indicate that postural stability is reduced in PwMS following a common ADL, thus individuals with MS should be counseled on the increased likelihood of balance loss with heightened fatigue, even at relatively low levels

Occasional papers

no.4 (1994

Lipid coated liquid crystal droplets for the on-chip detection of antimicrobial peptides

We describe a novel biosensor based on phospholipid-coated nematic liquid crystal (LC) droplets and demonstrate the detection of Smp43, a model antimicrobial peptide (AMP) from the venom of North African scorpion Scorpio maurus palmatus. Mono-disperse lipid-coated LC droplets of diameter 16.7 ± 0.2 μm were generated using PDMS microfluidic devices with a flow-focusing configuration and were the target for AMPs. The droplets were trapped in a bespoke microfluidic trap structure and were simultaneously treated with Smp43 at gradient concentrations in six different chambers. The disruption of the lipid monolayer by the Smp43 was detected (<6 μM) at concentrations well within its biologically active range, indicated by a dramatic change in the appearance of the droplets associated with the transition from a typical radial configuration to a bipolar configuration, which is readily observed by polarizing microscopy. This suggests the system has feasibility as a drug-discovery screening tool. Further, compared to previously reported LC droplet biosensors, this LC droplet biosensor with a lipid coating is more biologically relevant and its ease of use in detecting membrane-related biological processes and interactions has the potential for development as a reliable, low-cost and disposable point of care diagnostic tool

Temperature dependent absorption cross-sections of HNO3 and N2O5

Absorption cross-sections for HNO3 and N2O5 have been measured in the wavelength region 220-450 nm, using a dual beam diode array spectrometer with a spectral resolution of 0.3 nm. The results for both compounds are in good agreement with recommended values at room temperature. However, the cross-sections of both HNO3 and N2O5 show a marked reduction with decreasing temperature in the range 295-233 K. The calculated photolysis rate of HNO3 at the low temperatures and high solar zenith angles characteristic of the polar winter and spring is significantly lower than previously estimated

A Corpus Investigation of Syntactic Embedding in Piraha

The Pirahã language has been at the center of recent debates in linguistics, in large part because it is claimed not to exhibit recursion, a purported universal of human language. Here, we present an analysis of a novel corpus of natural Pirahã speech that was originally collected by Dan Everett and Steve Sheldon. We make the corpus freely available for further research. In the corpus, Pirahã sentences have been shallowly parsed and given morpheme-aligned English translations. We use the corpus to investigate the formal complexity of Pirahã syntax by searching for evidence of syntactic embedding. In particular, we search for sentences which could be analyzed as containing center-embedding, sentential complements, adverbials, complementizers, embedded possessors, conjunction or disjunction. We do not find unambiguous evidence for recursive embedding of sentences or noun phrases in the corpus. We find that the corpus is plausibly consistent with an analysis of Pirahã as a regular language, although this is not the only plausible analysis