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Biomedical subjects

G Palm

Publications and source records attributed to G Palm.

35 records · Page 2Linked to original sources

A gene fusion system for generating antibodies against short peptides.

A novel method to obtain specific antibodies against short peptides is described, involving synthesis of the corresponding oligodeoxynucleotides followed by cloning into a new set of fusion vectors, pEZZ8 and pEZZ18, based on two synthetic IgG-binding domains (ZZ) of Staphylococcus aureus protein A. The soluble gene fusion product thus obtained, can be collected from the culture medium of Escherichia coli and rapidly recovered in a one-step procedure by IgG affinity chromatography. The system was used to express a fusion protein consisting of the two Z fragments and the C-terminal part [amino acids (aa) 57-70] of human insulin-like growth factor I (IGF-I). This 16-kDa protein was purified by affinity chromatography on IgG Sepharose and antibodies were raised in rabbits. The fusion protein elicited peptide-specific antibodies, as measured by solid-phase radioimmuno assay and Western blotting, reactive with both synthetic C-terminal peptide and the native human IGF-I protein. The results suggests that the gene fusion system can be used for efficient antibody production against short peptides encoded by synthetic oligodeoxynucleotides.

Amino Acid Sequence↗

Spatiotemporal receptive fields: a dynamical model derived from cortical architectonics.

We assume that the mammalian neocortex is built up out of some six layers which differ in their morphology and their external connections. Intrinsic connectivity is largely excitatory, leading to a considerable amount of positive feedback. The majority of cortical neurons can be divided into two main classes: the pyramidal cells, which are said to be excitatory, and local cells (most notably the non-spiny stellate cells), which are said to be inhibitory. The form of the dendritic and axonal arborizations of both groups is discussed in detail. This results in a simplified model of the cortex as a stack of six layers with mutual connections determined by the principles of fibre anatomy. This stack can be treated as a multi-input-multi-output system by means of the linear systems theory of homogeneous layers. The detailed equations for the simulation are derived in the Appendix. The results of the simulations show that the temporal and spatial behaviour of an excitation distribution cannot be treated separately. Further, they indicate specific processing in the different layers and some independence from details of wiring. Finally, the simulation results are applied to the theory of visual receptive fields. This yields some insight into the mechanisms possibly underlying hypercomplexity, putative nonlinearities, lateral inhibition, oscillating cell responses, and velocity-dependent tuning curves.

Afferent Pathways↗

Parallel processing for associative and neuronal networks.

We represent a parallel processing network, consisting of nine microcomputers, for neuron-network simulations and for the realization of an associative computer memory. We add some remarks on the present possibilities to implement larger associative networks and on parallel processing strategies in general.

Association↗

Automatic synthesis of oligodeoxynucleotides and mixed oligodeoxynucleotides using the phosphoamidite method.

A simplified procedure for making and using the deoxynucleoside phosphoamidites (1 a-d) in the automated synthesis of oligodeoxynucleotides has been developed. The reagents prepared show good stability in solution. The reactivity of the reagents was found to be directly proportional to their concentrations, which makes it possible to synthesize mixed oligomers in desired ratios. Oligomers up to 45-mer have been synthesized using a coupling cycle of twenty min.

Chemical Phenomena↗

Isolation of cDNA sequences coding for a part of human tissue plasminogen activator.

We have isolated a cDNA sequence coding for a part of human tissue plasminogen activator. mRNA coding for tissue plasminogen activator was partially purified, copied into double-stranded cDNA, and cloned into Escherichia coli. Two sets of partially overlapping oligodeoxynucleotide mixtures corresponding to all possible coding sequences for a known portion of the tissue plasminogen activator gene were prepared. One set was used as a probe to screen cDNA containing bacterial clones and both were used as probes in hybridization against purified plasmid DNA. Of 4,200 bacterial clones examined, 1 carried a plasmid that hybridized to both sets of oligonucleotides. This plasmid contained a 370-base-pair cDNA insert, which was shown by nucleotide sequence analysis to code for the cleavage site region in the one-chain form of the human tissue plasminogen activator.

Amino Acid Sequence↗

[Malta fever in a brucellosis free region: analysis of a malta fever outbreak in the Göttingen area 1982].

During April/Mai 1982 15 patients were affected with acute Malta fever around Goettingen an area known the be brucellosis-free until then. The source of infections were local flocks of sheep. The infections were mainly acquired when assisting at lamb birth or abortions. Between onset and diagnosis of the disease intervals up to 3 month occurred. Diagnostically crucial were blood cultures and serological tests. Therapy with tetracyclines or co-trimoxazole were effective in all cases. In patients with status febrilis and anamnestic contact with brucellosis-prone animals brucellosis should be considered, even if the local area appears to be brucellosis-free.

Animals↗

Synthesis of mixed oligodeoxyribonucleotides following the solid phase method.

A method for the synthesis of mixed dimers, trimers and oligonucleotides on a solid support using monomeric protected nucleoside phosphochloridites (1a-d) has been developed and the different nucleoside reagents, and the results show that yields of different oligomers in a mixture could be directly correlated to the concentration of the four reagents. Separation of mixed oligomers on a reversed phase C18 column has also been studied.

Chromatography, High Pressure Liquid↗

Evidence, information, and surprise.

A numerical measure for "evidence" is defined in a probabilistic framework. The established mathematical concept of information or entropy (as defined in ergodic theory) can be obtained from this definition in a special case, although in general information in a special case, although in general information is greater than evidence. In another, somewhat complementary, special case a numerical measure for "surprise" is derived from the definition of evidence. Some applications of the new concept of evidence are discussed, concerning statistics in general and the special kind of statistics performed by neurophysiologists, when they analyze the "response" of neurons, and perhaps by the neurons themselves.

Axons↗

Towards a theory of cell assemblies.

The term cell assembly, first introduced by D. O. Hebb, is defined in the framework of graph theory. This definition leads to some beautiful problems concerning the number and size of cell assemblies in large graphs. Some approaches to solve these problems are presented. In particular, the graphs Kn X Km are constructed that have n . m points, n + m - 2 connections per point, and at least 2n + 2m - 4 assemblies. Several new notions of connectivity in directed graphs are introduced and their relationships are investigated. The insight into these notions and their relationships will be helpful for further construction of graphs with many assemblies and/or high connectivity. The resulting graphs are not only important for the idea of cell assemblies in the content of neurodynamics, they may also find applications in the construction of communication networks and associative memories.

Brain↗

On associative memory.

The information storing capacity of certain associative and auto-associative memories is calculated. For example, in a 100 X 100 matrix of 1 bit storage elements more than 6,500 bits can be stored associatively, and more than 688,000 bits in a 1,000 X 1,000 matrix. Asymptotically, the storage capacity of an associative memory increases proportionally to the number of storage elements. The usefulness of associative memories, as opposed to conventional listing memories, is duscussed -- especially in connection with brain modelling.

Animals↗

Analysis of a cooperative stereo algorithm.

Marr and Poggio (1976) recently described a cooperative algorithm that solves the correspondence problem for stereopsis. This article uses a probabilistic technique to analyze the convergence of that algorithm, and derives the conditions governing the stability of the solution state. The actual results of applying the algorithm to random-dot stereograms are compared with the probabilistic analysis. A satisfactory mathematical analysis of the asymptotic behaviour of the algorithm is possible for a suitable choice of the parameter values and loading rules, and again the actual performance of the algorithm under these conditions is compared with the theoretical predictions. Finally, some problems raised by the analysis of this type of "cooperative" algorithm are briefly discussed.

Depth Perception↗

Wiener-like system identification in physiology.

Applications of Wiener-like identification methods to biological systems have revealed several limitations of this technique. These practical limitations correspond to conceptual and mathematical problems intrinsic to this kind of identification of nonlinear systems.

Physiology↗

Pattern separation and synchronization in spiking associative memories and visual areas.

Scene analysis in the mammalian visual system, conceived as a distributed and parallel process, faces the so-called binding problem. As a possible solution, the temporal correlation hypothesis has been suggested and implemented in phase-coding models. We propose an alternative model that reproduces experimental findings of synchronized and desynchronized fast oscillations more closely. This model is based on technical considerations concerning improved pattern separation in associative memories on the one hand, and on known properties of the visual cortex on the other. It consists of two reciprocally connected areas, one corresponding to a peripheral visual area (P), the other a central association area (C). P implements the orientation-selective subsystem of the primary visual cortex, while C was modeled as an associative memory with connections formed by Hebbian learning of all assemblies corresponding to stimulus objects. Spiking neurons including habituation and correlated noise were incorporated as well as realistic synaptic delays. Three learned stimuli were presented simultaneously and correlation analysis was performed on spike recordings. Generally, we found two states of activity: (i) relatively slow and unordered oscillations at about 20-25 Hz, synchronized only within small regions; and (ii) faster and more precise oscillations around 50-60 Hz, synchronized over the whole simulated area. The neuron groups representing one stimulus tended to be simultaneously in either the slow or the fast state. At each particular time, only one assembly was found to be in the fast state. Activation of the three assemblies switched on a time scale of 100 ms. This can be interpreted as self-generated attention switching. On the time scale corresponding to gamma oscillations, cross correlations between local neuron groups were either modulated or flat. Modulated correlograms resulted if the groups coded features corresponding to a common object. Otherwise, the correlograms remained flat. This behavior is in agreement with experimental results, while phase-code models would generally predict modulated correlations also in the case of different objects. Furthermore, we derive a technical version from our biological associative memory model that accomplishes fast pattern separation parallel in O(log2 n) steps for n neurons and sparse coding.

Action Potentials↗