The Close Corporation and the Colorado Lawyer

http://www.heinonline.org/HOL/Page?handle=hein.journals/ucollr39&div=24&collection=journal

The Close Corporation and the Colorado Lawyer

http://www.heinonline.org/HOL/Page?handle=hein.journals/ucollr39&div=24&collection=journal

CASK regulates CaMKII autophosphorylation in neuronal growth, calcium signaling, and learning

Calcium (Ca2+)/calmodulin (CaM)-dependent kinase II (CaMKII) activity plays a fundamental role in learning and memory. A key feature of CaMKII in memory formation is its ability to be regulated by autophosphorylation, which switches its activity on and off during synaptic plasticity. The synaptic scaffolding protein CASK (calcium (Ca2+)/calmodulin (CaM) associated serine kinase) is also important for learning and memory, as mutations in CASK result in intellectual disability and neurological defects in humans. We show that in Drosophila larvae, CASK interacts with CaMKII to control neuronal growth and calcium signalling. Furthermore, deletion of the CaMK-like and L27 domains of CASK (CASK β null) or expression of overactive CaMKII (T287D) produced similar effects on synaptic growth and Ca2+ signalling. CASK overexpression rescues the effects of CaMKII overactivity, consistent with the notion that CASK and CaMKII act in a common pathway that controls these neuronal processes. The reduction in Ca2+ signalling observed in the CASK β null mutant caused a decrease in vesicle trafficking at synapses. In addition, the decrease in Ca2+ signalling in CASK mutants was associated with an increase in Ether-à-go-go (EAG) potassium (K+) channel localisation to synapses. Reducing EAG restored the decrease in Ca2+ signalling observed in CASK mutants to the level of wildtype, suggesting that CASK regulates Ca2+ signalling via EAG. CASK knockdown reduced both appetitive associative learning and odour evoked Ca2+ responses in Drosophila mushroom bodies, which are the learning centres of Drosophila. Expression of human CASK in Drosophila rescued the effect of CASK deletion on the activity state of CaMKII, suggesting that human CASK may also regulate CaMKII autophosphorylation

KCNQ channels regulate age-related memory impairment:KCNQ regulates age-related memory

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment

Supervised Injection Facilities: Legal and Policy Reforms

The US Centers for Disease Control and Prevention reported that more than 70 000 deaths from drug overdoses occurred in 2017, including prescription and illicit opioids, representing a 6-fold increase since 1999. Innovative harm-reduction solutions are imperative. Supervised injection facilities (SIFs) create safe places for drug injection, including overdose prevention, counseling, and treatment referral services. Supervised injection facilities neither provide illicit drugs nor do their personnel inject users. Supervised injection facilities are effective in reducing drug-related mortality, morbidity, and needle-borne infections. Yet their lawfulness remains uncertain. The Department of Justice (DOJ) recently threatened criminal prosecution for SIF operators, medical personnel, and patrons

A high performance k-NN approach using binary neural networks

This paper evaluates a novel k-nearest neighbour (k-NN) classifier built from binary neural networks. The binary neural approach uses robust encoding to map standard ordinal, categorical and numeric data sets onto a binary neural network. The binary neural network uses high speed pattern matching to recall a candidate set of matching records, which are then processed by a conventional k-NN approach to determine the k-best matches. We compare various configurations of the binary approach to a conventional approach for memory overheads, training speed, retrieval speed and retrieval accuracy. We demonstrate the superior performance with respect to speed and memory requirements of the binary approach compared to the standard approach and we pinpoint the optimal configurations. (C) 2003 Elsevier Ltd. All rights reserved

The Steel Tomb

Non-fiction by David Hodg

Program management aid for redundancy selection and operational guidelines

Although this criterion was developed specifically for use on the shuttle program, it has application to many other multi-missions programs (i.e. aircraft or mechanisms). The methodology employed is directly applicable even if the tools (nomographs and equations) are for mission peculiar cases. The redundancy selection criterion was developed to insure that both the design and operational cost impacts (life cycle costs) were considered in the selection of the quantity of operational redundancy. These tools were developed as aids in expediting the decision process and not intended as the automatic decision maker. This approach to redundancy selection is unique in that it enables a pseudo systems analysis to be performed on an equipment basis without waiting for all designs to be hardened

Effects of potassium fertilization of fescue pastures on metabolism of magnesium, calcium and potassium in lactating beef cows

The objectives of this research were to determine what effects high K fertilization of fescue pastures had on plasma levels of Mg, Ca and K and on the metabolism of Mg. Ca and K In beef cows In early lactation. Balance trials were conducted using beef cows with young suckling calves In February and March, 1980 and 1981. Cows were placed on one of two adjacent fescue pastures. Both pastures were fertilized with N (112 kg/hectare) and P (169 kg/hectare). One pasture received no fertilization of K and the other, 224 kg/hectare. The Internal (acid-detergent 11gn1n)-external (Cr203) Indicator technique was used to determine fecal dry matter output and dry matter consumption of the cows. Urine volume was estimated using creatinine ratios. Milk production (calf-suckle technique) was estimated and sampled for all cows. Cows on the control pasture consumed more dry matter and Mg. Cows consuming the K-fertilized pastured had reduced urinary Mg excretion. Indicating reduced absorption of the Mg. Excretion of Mg In the milk remained the same regardless of treatment. Cows on the K-fertilized pasture tended to have depressed plasma Mg values with a higher Incidence of hypomagnesemia. Nine cows on the K-fertilized pasture were hypomagnesemic compared with only four on the control pasture, although no symptoms of grass tetany were seen. This rela-tionship suggests that In a tetany-prone year, the number of cases n nn of grass tetany could be higher because of pasture fertilization with K. There were no differences between treatment in plasma Ca values, but plasma K tended to be higher in cows on the K-fertilized pasture