Computational Aspects of Protein Functionality

The purpose of this short article is to examine certain aspects of protein functionality with relation to some key organizing ideas. This is important from a computational viewpoint in order to take account of modelling both biological systems and knowledge of these systems. We look at some of the lexical dimensions of the function and how certain constructs can be related to underlying ideas. The pervasive computational metaphor is then discussed in relation to protein multifunctionality, and the specific case of von Willebrand factor as a ‘smart’ multifunctional protein is briefly considered. Some diagrammatic techniques are then introduced to better articulate protein function

On the Nesterov-Todd Direction in Semidefinite Programming

On the Nesterov-Todd Direction in Semidefinite Programmin

Smooth-muscle-associated contractile protein in renal mesenchymal tumour cells and in transformed cells from DMN-injected rats.

Cryostat sections and established in vitro cultures of dimethylnitrosamine(DMN)-induced renal mesenchymal tumours and monolayer cultures of transformed kidney cells derived from rats treated with a carcinogenic dose of DMN were examined by indirect immunofluorescence with human serum containing smooth muscle antibody. Eight mesenchymal tumours examined showed filamentous cytoplasmic staining of spindle cells infiltrating between renal tubules, whilst in normal kidneys interstitial cells were only weakly positive. In established in vitro cultures from 6 mesenchymal tumours, different patterns of staining were observed in morphologically different cell forms, ranging from fine filamentous staining in giant cells to diffuse cytoplasmic fluorescence in small bipolar cells, and cell outline staining in polygonal cells. In addition filamentous staining of microvillous projections and nucleolar staining were observed in some tumour cells. Monolayer cultures of transformed kidney cells showed strong staining of coarse, randomly-orientated cytoplasmic filaments, whilst fibroblasts cultured from normal rat kidney demonstrated an ordered array of fine, parallel filaments. Specificity of the immunofluorescent staining reaction was established by failure to obtain staining with normal serum, with smooth muscle antibody serum neutralized by homogenates of smooth muscle or extracts containing actin derived from smooth muscle. These results indicate that there is an apparent increase of actin-like contractile microfilaments in transformed cells and in renal mesenchymal tumours. The cytoplasmic contracile microfilaments in these cells may play a role in tumour cell mobility and invasion

Angiogenically active vascular endothelial growth factor is over-expressed in malignant human and rat prostate carcinoma cells

Vascular endothelial growth factor (VEGF) is one of the most potent factors for stimulating angiogenesis, an essential process required for expansion of primary tumour and dissemination of malignant cells. To investigate the possible role of VEGF in facilitating metastasis of prostate cancer via stimulating angiogenesis, we have used Northern and slot blotting, reverse transcription polymerase chain reaction, nucleotide sequence analysis and enzyme-linked immunosorbent assay to compare the VEGF expression in series of human and rat cell lines with either benign or malignant characteristics. We have also employed the chick chorioallantoic membrane (CAM) assay to measure the angiogenic activity of the VEGF derived from both benign and malignant cells. The level of VEGF mRNA expressed in the seven malignant human and rat cell lines is 3.5- to 10-fold higher than that expressed in the benign cell lines. The three metastatic variants, generated by transfection of a benign cell line with DNA extracted from prostate carcinoma cells, expressed 2.5 to 5 times more VEGF mRNA than their parental benign cells. While VEGF 121 and 165 were predominantly expressed by both the benign and malignant cells, the transcript representing VEGF 189 isoform was only detected in the malignant cells. At protein level, three human malignant cell lines produced more VEGF (2.7–7.9 ng ml−1) than the benign cell line (1.3 ng ml−1). CAM assay detected a VEGF-dependent angiogenic activity in the medium from malignant cells, but only a relatively weak VEGF-independent activity in the medium from benign cells. These results demonstrated that malignant cells did over-express VEGF and only the VEGF derived from malignant cells was angiogenically active. Thus, we suggest that the VEGF produced by malignant cells might play an important role in facilitating metastasis of prostatic cancer. © 2000 Cancer Research Campaig

Tidal signals in ocean-bottom magnetic measurements of the Northwestern Pacific: observation versus prediction

Motional induction in the ocean by tides has long been observed by both land and satellite measurements of magnetic fields. While these signals are weak (∼10 nT) when compared to the main magnetic field, their persistent nature makes them important for consideration during geomagnetic field modelling. Previous studies have reported several discrepancies between observations and numerical predictions of the tidal magnetic signals and those studies were inconclusive of the source of the error. We address this issue by (1) analysing magnetometer data from ocean-bottom stations, where the low-noise and high-signal environment is most suitable for detecting the weak tidal magnetic signals, (2) by numerically predicting the magnetic field with a spatial resolution that is 16times higher than the previous studies and (3) by using four different models of upper-mantle conductivity. We use vector magnetic data from six ocean-bottom electromagnetic (OBEM) stations located in the Northwestern Pacific Ocean. The OBEM tidal amplitudes were derived using an iteratively re-weighted least-squares (IRLS) method and by limiting the analysis of lunar semidiurnal (M2), lunar elliptic semidinurnal (N2) and diurnal (O1) tidal modes to the night-time. Using a 3-D electromagnetic induction solver and the TPX07.2 tidal model, we predict the tidal magnetic signal. We use earth models with non-uniform oceans and four 1-D mantle sections underneath taken from Kuvshinov and Olsen, Shimizu etal. and Baba etal. to compare the effect of upper-mantle conductivity. We find that in general, the predictions and observations match within 10-70 per cent across all the stations for each of the tidal modes. The median normalized percent difference (NPD) between observed and predicted amplitudes for the tidal modes M2, N2 and O1 were 15 per cent, 47 per cent and 98 per cent, respectively, for all the stations and models. At the majority of stations, and for each of the tidal modes, the higher resolution (0.25°×0.25°) modelling gave amplitudes consistently closer to the observations than the lower resolution (1°×1°) modelling. The difference in lithospheric resistance east and west of the Izu-Bonin trench system seems to be affecting the model response and observations in the O1 tidal mode. This response is not seen in the M2 and N2 modes, thereby indicating that the O1 mode is more sensitive to lithospheric resistanc

Histologic and histomorphometric evaluation of peri-implant bone subjected to immediate loading: An experimental study with Macaca fascicularis

Purpose: Immediately loaded splinted implants can become osseointegrated when they are placed in the anterior part of the mandible. The concept of immediate loading has not been well examined in the posterior mandible. The aim of this study was to evaluate the hard tissue reactions around immediately loaded implants placed in the posterior mandible in the monkey model. Materials and Methods: Six adult M. fascicularis monkeys were used in this study. Thirty-six Ankylos implants (Degussa Dental, Hanau-Wolfgang, Germany) were placed after extraction of the second premolar, first, and second molar teeth and complete healing of the sockets. Control (C) group implants were placed and, after osseointegration, were loaded for 1 month using temporary acrylic resin prostheses and later for 2 months using splinted metal crowns. In the contralateral region of the mandible, test (T) group implants were placed and loaded immediately with the same sequence as carried out for the C implants. After sacrifice of the animals, specimens were examined histologically and evaluated histomorphometrically. Results: All implants were osseointegrated. Compact, cortical bone In contact with the implant surface without any gaps or connective tissue formation was demonstrated. Discussion: Histomorphometric findings of the bone-implant-contacts showed no significant differences between the T and C group implants. Peri-implant mineralized bone areas presented statistically significant differences and showed a higher density of bone between the threads of immediately loaded implants (P < .05). Conclusions: Immediately loaded splinted implants in the posterior mandible can become osseointegrated with a hard tissue peri-implant response similar to that of delayed loaded implants. Moreover, immediate loading seems to increase the ossification of the alveolar bone around endosseous implants. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Stable periodic waves in coupled Kuramoto-Sivashinsky - Korteweg-de Vries equations

Periodic waves are investigated in a system composed of a Kuramoto-Sivashinsky - Korteweg-de Vries (KS-KdV) equation, which is linearly coupled to an extra linear dissipative equation. The model describes, e.g., a two-layer liquid film flowing down an inclined plane. It has been recently shown that the system supports stable solitary pulses. We demonstrate that a perturbation analysis, based on the balance equation for the field momentum, predicts the existence of stable cnoidal waves (CnWs) in the same system. It is found that the mean value U of the wave field u in the main subsystem, but not the mean value of the extra field, affects the stability of the periodic waves. Three different areas can be distinguished inside the stability region in the parameter plane (L,U), where L is the wave's period. In these areas, stable are, respectively, CnWs with positive velocity, constant solutions, and CnWs with negative velocity. Multistability, i.e., the coexistence of several attractors, including the waves with several maxima per period, appears at large value of L. The analytical predictions are completely confirmed by direct simulations. Stable waves are also found numerically in the limit of vanishing dispersion, when the KS-KdV equation goes over into the KS one.Comment: a latex text file and 16 eps files with figures. Journal of the Physical Society of Japan, in pres

Stable two-dimensional solitary pulses in linearly coupled dissipative Kadomtsev-Petviashvili equations

A two-dimensional (2D) generalization of the stabilized Kuramoto - Sivashinsky (KS) system is presented. It is based on the Kadomtsev-Petviashvili (KP) equation including dissipation of the generic (Newell -- Whitehead -- Segel, NWS) type and gain. The system directly applies to the description of gravity-capillary waves on the surface of a liquid layer flowing down an inclined plane, with a surfactant diffusing along the layer's surface. Actually, the model is quite general, offering a simple way to stabilize nonlinear waves in media combining the weakly-2D dispersion of the KP type with gain and NWS dissipation. Parallel to this, another model is introduced, whose dissipative terms are isotropic, rather than of the NWS type. Both models include an additional linear equation of the advection-diffusion type, linearly coupled to the main KP-NWS equation. The extra equation provides for stability of the zero background in the system, opening a way to the existence of stable localized pulses. The consideration is focused on the case when the dispersive part of the system of the KP-I type, admitting the existence of 2D localized pulses. Treating the dissipation and gain as small perturbations and making use of the balance equation for the field momentum, we find that the equilibrium between the gain and losses may select two 2D solitons, from their continuous family existing in the conservative counterpart of the model (the latter family is found in an exact analytical form). The selected soliton with the larger amplitude is expected to be stable. Direct simulations completely corroborate the analytical predictions.Comment: a latex text file and 16 eps files with figures; Physical Review E, in pres