Population networks: a large-scale framework for modelling cortical neural networks

Artificial neural networks are usually built on rather few elements such as activation functions, learning rules, and the network topology. When modelling the more complex properties of realistic networks, however, a number of higher-level structural principles become important. In this paper we present a theoretical framework for modelling cortical networks at a high level of abstraction. Based on the notion of a population of neurons, this framework can accommodate the common features of cortical architecture, such as lamination, multiple areas and topographic maps, input segregation, and local variations of the frequency of different cell types (e.g., cytochrome oxidase blobs). The framework is meant primarily for the simulation of activation dynamics; it can also be used to model the neural environment of single cells in a multiscale approach. Received: 9 January 1996 / Accepted in revised form: 24 July 1996     

Immunogenicity Studies with Haptenated Melittin Peptides: Implication for Membrane Involvement during the Recognition Step

Melittin peptides carrying 2,4-dinitro-6-carboxyphenyl (Dncp) haptenic groups regularly evoked anti-hapten IgG responses in mice or guinea pigs when the hapten was C-terminally attached. Single haptens on the N-terminal helix in several positions gave poor or no responses in the early stages but adequate titres after prolonged immunization. Peptides with Dncp at the C-terminus as an invariant feature and a second Dncp in various positions along the peptide chain did not fail to produce adequate responses. The hampering effect is not due to a defect at the T-cell level but involves the recognition step on the B-cell. It is implied that the haptenic interaction with the paratope of the recognizing immunoglob ulin on the B-cell involves the cell membrane in an important way. It is also suggested that late antibody responses should not be overlooked during the development of proteinaceous immunogens for vaccination.     

An overall description of retinotopic mapping in the cat's visual cortex areas 17, 18, and 19

Mathematical functions are derived which model the retinotopic mapping in the cat's visual cortical areas 17, 18, and 19. All three mappings are simple modifications of a complex power function with an exponent of 0.43. This function is decomposed so as to give an intermediate stage which is common to all three mappings and can be regarded as a model of the lateral geniculate nucleus mapping. The influence of retinotopic mapping on visual receptive fields was studied. The results show that a dependence of the receptive field properties on the position in the visual field is to be expected.     

Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules

In host and cancer tissues, drug metabolism and susceptibility to drugs vary in a circadian (24 h) manner. In particular, the efficacy of a cell cycle specific (CCS) cytotoxic agent is affected by the daily modulation of cell cycle activity in the target tissues. Anti-cancer chronotherapy, in which treatments are administered at a particular time each day, aims at exploiting these biological rhythms to reduce toxicity and improve efficacy of the treatment. The circadian status, which is the timing of physiological and behavioral activity relative to daily environmental cues, largely determines the best timing of treatments. However, the influence of variations in tumor kinetics has not been considered in determining appropriate treatment schedules. We used a simple model for cell populations under chronomodulated treatment to identify which biological parameters are important for the successful design of a chronotherapy strategy. We show that the duration of the phase of the cell cycle targeted by the treatment and the cell proliferation rate are crucial in determining the best times to administer CCS drugs. Thus, optimal treatment times depend not only on the circadian status of the patient but also on the cell cycle kinetics of the tumor. Then, we developed a theoretical analysis of treatment outcome (TATO) to relate the circadian status and cell cycle kinetic parameters to the treatment outcomes. We show that the best and the worst CCS drug administration schedules are those with 24 h intervals, implying that 24 h chronomodulated treatments can be ineffective or even harmful if administered at wrong circadian times. We show that for certain tumors, administration times at intervals different from 24 h may reduce these risks without compromising overall efficacy.     

DNA Quality Control by a Lesion Sensor Pocket of the Xeroderma Pigmentosum Group D Helicase Subunit of TFIIH

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Highlights? Amino acid changes near the central pore of XPD confer defective excision repair ? These mutants retain DNA helicase activity when tested in an archaeal framework ? The mutants are unable to sense lesions during their ATP-driven tracking movement ? The mutants are unable to build a stable demarcation complex at DNA lesion sites     

Mechanism for 12 Hr Rhythm Generation by the Circadian Clock

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Changes in retinal and choroidal morphology after cerebrospinal fluid pressure reduction: a Beijing iCOP study

正Dear Editor,Glaucoma is a multifunctional neurodegenerative disease and is the leading cause of irreversible blindness. It is characterized by progressive loss of retinal ganglion cells and their axons leading to visual field defects. Two mechanisms of glaucomatous optic nerve damage have been