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[Computer model of the bladder].

The function of the urinary bladder in the spinal segments S2-3 is a relatively simple regulatory system. This fact has enabled us to devise an adapted block scheme and to describe mathematically existing interrelations of its individual components. Thus, an abstract model of the function of the urinary bladder has been developed which was realised on a BASIC-programmed computer. The results obtained with this model simulate the function of filling and emptying of the urinary bladder and permit to understand the details of the function of the nervous system controlling the urinary bladder at this level.

Computers

Computational modeling of human genetic variants in mice.

Mouse models represent a powerful platform to study genes and variants associated with human diseases. While genome editing technologies have increased the rate and precision of model development, predicting and installing specific types of mutations in mice that mimic the native human genetic context is complicated. Computational tools can identify and align orthologous wild-type genetic sequences from different species; however, predictive modeling and engineering of equivalent mouse variants that mirror the nucleotide and/or polypeptide change effects of human variants remains challenging. Here, we present H2M (human-to-mouse), a computational pipeline to analyze human genetic variation data to systematically model and predict the functional consequences of equivalent mouse variants. We show that H2M can integrate mouse-to-human and paralog-to-paralog variant mapping analyses with precision genome editing pipelines to devise strategies tailored to model specific variants in mice. We leveraged these analyses to establish a database containing > 3 million human-mouse equivalent mutation pairs, as well as in silico-designed base and prime editing libraries to engineer 4,944 recurrent variant pairs. Using H2M, we also found that predicted pathogenicity and immunogenicity scores were highly correlated between human-mouse variant pairs, suggesting that variants with similar sequence change effects may also exhibit broad interspecies functional conservation. Overall, H2M fills a gap in the field by establishing a robust and versatile computational framework to identify and model homologous variants across species while providing key experimental resources to augment functional genetics and precision medicine applications. The H2M database (including software package and documentation) can be accessed at https://human2mouse.com.

Journal Article

Computer model to characterize the air volume displaced by the vibrating vocal cords.

We use a vocal-cord/vocal-tract model devised earlier to study acoustic effects of the air volume displaced by the vibrating vocal cords. We consider both lateral and longitudinal motion of the cords. We make computer simulations to establish quantitatively the contribution of the displacement current to the total glottal volume velocity (and hence to the total sound excitation for voiced sounds). The displacement current from both lateral and longitudinal motion is found to be second-order by comparison to the total glottal flow. The displacement contribution can, however, be identified in the time waveforms and spectra of the glottal and mouth volume velocities. We use the computer formulation to synthesize speech sounds with and without the displacement current. Auditory observations and spectral calculations on the synthetic output show the displacement current to be discriminable only in close differential comparisons.

Computers

Correlative statistical analysis and computer modelling of intramembraneous particle distributions in human erythrocyte membranes.

The planar distribution of intramembranous particles on the P faces of freeze-fractured human erythrocyte membranes is characterized by radial distribution, angular distribution and differential density distribution analysis. Various degrees of intramembranous particle aggregation induced by spectrin removal and low pH are differentiated through computation. Random hard disk models with various disk diameters are built for comparison studies. In all samples, the 80 +/- 10 A particles are found to have a preferred neighboring distance of 100 +/- 10 A, but no preferred angular relation is found between neighboring particles. A pattern recognition process using both radial and density distribution analyses reveals that none of the particle distributions observed may be regarded as random. The fact that the particle distributions observed are neither even nor random suggests that factors other than long range electrostatic force alone are involved in determining the particle distribution.

Computers

Model computation of the effect of arbitrary variations in aqueous inflow, outflow conductance, ocular rigidity and episcleral vein pressure on ocular pressure.

Model calculations of the time course of the intraocular pressure are performed in cases where the four determinants mentioned in the title vary, singly or simultaneously, according to specified time functions. Assumptions are 1) that the outflow of the aqueous humor is proportional to the driving pressure, and 2) that the intraocular pressure and volume are related to each other as described by Friedenwald. The mathematical solution if numerical and involves the repetition of the same calculatory step process. It is rendered probable that the maximal inhibitory effect of acetazolamide on the secretion of aqueous humour is reached in less than one minute after the drug has reached the receptors. A programmable calculator with 224 storage locations is used, the programs are given.

Acetazolamide

A computer model for hydrodynamic shearing of DNA (Gibb's phenomenon): Part II.

This paper presents an extension of the distribution proposed during hydrodynamic shearing of DNA. In the Fourier least square approximation of uniform random distribution or a square wave, Gibb's phenomena occur at the boundaries. The same behavior occurs at the boundaries of the DNA strands undergoing hydrodynamic shearing of DNA. This hypothesis is corroborated by results from a computer simulation of hydrodynamic shearing of DNA. The evidence helps confirm the kinetic experiments of Britten and Kohne [4]. Furthermore the results predict that sequence very near the end (0.2 LAMBDA) should be the most intact.

Computers