Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms

A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was analyzed for structure-activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.     

Optimal two-term offset windowing for fractional delay

Fractional-sample delay in discrete-time systems is often provided by special FIR filters which are asymmetric about mid-sequence. Here we preserve the appeal of sine-sequence fractional delayers (simplicity and single-parameter delay tuning) by devising a two-term raised-cosine window which delivers fractional-delay filters comparable to the best obtainable by highly regarded optimisation approaches     

Is homophobia associated with homosexual arousal?

The authors investigated the role of homosexual arousal in exclusively heterosexual men who admitted negative affect toward homosexual individuals. Participants consisted of a group of homophobic men (n?=?35 ) and a group of nonhomophobic men (n?=?29); they were assigned to groups on the basis of their scores on the Index of Homophobia (W. W. Hudson & W. A. Ricketts, 1980). The men were exposed to sexually explicit erotic stimuli consisting of heterosexual, male homosexual, and lesbian videotapes, and changes in penile circumference were monitored. They also completed an Aggression Questionnaire (A. H. Buss & M. Perry, 1992). Both groups exhibited increases in penile circumference to the heterosexual and female homosexual videos. Only the homophobic men showed an increase in penile erection to male homosexual stimuli. The groups did not differ in aggression. Homophobia is apparently associated with homosexual arousal that the homophobic individual is either unaware of or denies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A neuron membrane mesh representation for visualization of electrophysiological simulations

We present a process to automatically generate three-dimensional mesh representations of the complex, arborized cell membrane surface of cortical neurons (the principal information processing cells of the brain) from nonuniform morphological measurements. Starting from manually sampled morphological points (3D points and diameters) from neurons in a brain slice preparation, we construct a polygonal mesh representation that realistically represents the continuous membrane surface, closely matching the original experimental data. A mapping between the original morphological points and the newly generated mesh enables simulations of electrophysiolgical activity to be visualized on this new membrane representation. We compare the new mesh representation with the state of the art and present a series of use cases and applications of this technique to visualize simulations of single neurons and networks of multiple neurons.     

Null values in nested relational databases

Summary The desire to extend the applicability of the relational model beyond traditional data-processing applications has stimulated interest in nested or non-first normal form relations in which the attributes of a relation can take on values which are sets or even relations themselves. In this paper, we study the role of null values in the nested relational model using an open world assumption. We extend the traditional theory and study the properties of extended operators for nested relations containing nulls. The no-information, unknown, and non-existent interpretation of nulls are discussed and the meaning of empty set is clarified. Finally, contrary to several previous results, we determine that the traditional axiomatization of functional and multivalued dependencies is valid in the presence of nulls.Currently with the Air Force Institute of Technology, AFIT/ENG, Wright-Patterson AFB, OH 45433, USAResearch partially supported by an IBM Faculty Development A ward and NSF grant DCR-8507224     

DDFSGEN

This paper presents a functional compiler for the automatic design of Direct Digital Frequency Synthesizer (DDFS) integrated circuits (ICs) using a ROM based table look-up architecture. The compiler allows the user to specify high-level specifications such as the acceptable spurious response and it generates the IC architecture, floorplan, and layout. To construct the layout for different specifications, a library of parameterized macrocells has been developed in 1.2 m CMOS technology.A test chip with a quadrature DDFS module has been generated, using the compiler, and fabricated. The chip has two input signals: one is for frequency control while the other is for phase initialization. Input and output word lengths are 16 bits and 6 bits respectively. The chip complexity is approximately 12,000 transistors (DDFS core) and the die size is 4.8×2.9mm ². A maximum sample rate of 80 MHz has been attained implying a maximum sine (cosine) output frequency of 40 MHz and a frequency resolution of 1.22 kHz. The maximum spurious level measured is –46 dB.     

An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgsh^Δex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgsh^Δex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgsh^Δex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgsh^Δex5−6 mutant larvae in a context-dependent manner. We expect the sgsh^Δex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.     

Finite-element simulation of induction heat treatment

An efficient finite-element procedure has been developed for the analysis of induction heat treatment problems involving nonisothermal phase changes. The finite-element procedure first simulates the magnetic field developed when currents flow through an induction coil by solving Maxwell’s electromagnetic field equations; at the following step, it calculates the temperature distribution in the workpiece due to eddy currents induced by the magnetic field. The final stage of the simulation involves the determination of the distributions of residual stress, hardness, and microstructure in the workpiece. The finite-element analysis includes temperature-dependent material properties, changes in permeability of the workpiece at the Curie temperature, a mixed hardening rule to describe the material constitutive model, and the incorporation of time-temperature-transformation (TTT) diagram. The procedure was applied to the simulation of the induction hardening of 1080 steel bar. Firstly, the magnetic field and temperatures developed in the workpiece during (a) the induction heating of an infinitely long 1080 steel cylinder by a single encircling coil and (b) the induction heating of a semi-infinite half-space by a single coil suspended above it were calculated using the finite-element procedures. These were validated by comparing them with analytical solutions derived for these configurations using a Green’s function method. Finally, to demonstrate the predictive capability and practical applicability of the current finite-element procedure, two examples pertaining to the induction heat treatment of an infinite 1080 steel bar of square cross section and a notched finite 1080 steel cylinder of circular cross section were analyzed to predict the magnetic field, temperature, and residual stress distributions. The current finite-element procedure could be used as a powerful design tool for linking induction heat treating parameters with the mechanical property attributes of the heat treated component.