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Biomedical subjects

R Albert

Publications and source records attributed to R Albert.

At least 19 recordsLinked to original sources
PubMed2006

Methods of robustness analysis for Boolean models of gene control networks.

As a discrete approach to genetic regulatory networks, Boolean models provide an essential qualitative description of the structure of interactions among genes and proteins. Boolean models generally assume only two possible states (expressed or not expressed) for each gene or protein in the network, as well as a high level of synchronisation among the various regulatory processes. Two possible methods of adapting qualitative models to incorporate the continuous-time character of regulatory networks, are discussed and compared. The first method consists of introducing asynchronous updates in the Boolean model. In the second method, the approach introduced by Glass is adopted to obtain a set of piecewise linear differential equations that continuously describe the states of each gene or protein in the network. Both methods are applied to a Boolean model of the segment polarity gene network of Drosophila melanogaster. The dynamics of the model is analysed, and a theoretical characterisation of the model's gene pattern prediction is provided as a function of the timescales of the various processes.

Animals↗
PubMed2005

Search in weighted complex networks.

We study trade-offs presented by local search algorithms in complex networks which are heterogeneous in edge weights and node degree. We show that search based on a network measure, local betweenness centrality (LBC), utilizes the heterogeneity of both node degrees and edge weights to perform the best in scale-free weighted networks. The search based on LBC is universal and performs well in a large class of complex networks.

Journal Article↗
PubMed2005

Medicinal chemistry of somatostatin analogs leading to the DTPA and DOTA conjugates of the multi-receptor-ligand SOM230.

The somatostatin field has been a success story in terms of medicinal chemistry and drug discovery offering a variety of therapeutic opportunities. A rational medicinal chemistry approach capitalising on structure activity relationships has led to the discovery of SOM230, a novel, stable cyclohexapeptide somatostatin analog which exhibits multi-receptor binding to human somatostatin receptor (SSTR) subtypes (SSTR 1-5). Recently, we extended this research utilising the hydroxproline urethane extension of SOM230 for the attachment of the chelators DTPA and DOTA, which enable early diagnosis of SSTR positive tumors and radiotherapy.

Chelating Agents↗
PubMed2001

Stick-slip fluctuations in granular drag.

We study fluctuations in the drag force experienced by an object moving through a granular medium. The successive formation and collapse of jammed states give a stick-slip nature to the fluctuations which are periodic at small depths but become "stepped" at large depths, a transition that we interpret as a consequence of the long-range nature of the force chains and the finite size of our experiment. Another important finding is that the mean force and the fluctuations appear to be independent of the properties of the contact surface between the grains and the dragged object. These results imply that the drag force originates in the bulk properties of the granular sample.

Journal Article↗
PubMed2000

Topology of evolving networks: local events and universality

Networks grow and evolve by local events, such as the addition of new nodes and links, or rewiring of links from one node to another. We show that depending on the frequency of these processes two topologically different networks can emerge, the connectivity distribution following either a generalized power law or an exponential. We propose a continuum theory that predicts these two regimes as well as the scaling function and the exponents, in good agreement with numerical results. Finally, we use the obtained predictions to fit the connectivity distribution of the network describing the professional links between movie actors.

Journal Article↗
PubMed2000

The large-scale organization of metabolic networks.

In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.

Animals↗
PubMed2000

Error and attack tolerance of complex networks

Many complex systems display a surprising degree of tolerance against errors. For example, relatively simple organisms grow, persist and reproduce despite drastic pharmaceutical or environmental interventions, an error tolerance attributed to the robustness of the underlying metabolic network. Complex communication networks display a surprising degree of robustness: although key components regularly malfunction, local failures rarely lead to the loss of the global information-carrying ability of the network. The stability of these and other complex systems is often attributed to the redundant wiring of the functional web defined by the systems' components. Here we demonstrate that error tolerance is not shared by all redundant systems: it is displayed only by a class of inhomogeneously wired networks, called scale-free networks, which include the World-Wide Web, the Internet, social networks and cells. We find that such networks display an unexpected degree of robustness, the ability of their nodes to communicate being unaffected even by unrealistically high failure rates. However, error tolerance comes at a high price in that these networks are extremely vulnerable to attacks (that is, to the selection and removal of a few nodes that play a vital role in maintaining the network's connectivity). Such error tolerance and attack vulnerability are generic properties of communication networks.

Journal Article↗
PubMed2000

Dynamics of complex systems: scaling laws for the period of boolean networks

Boolean networks serve as models for complex systems, such as social or genetic networks, where each vertex, based on inputs received from selected vertices, makes its own decision about its state. Despite their simplicity, little is known about the dynamical properties of these systems. Here we propose a method to calculate the period of a finite Boolean system, by identifying the mechanisms determining its value. The proposed method can be applied to systems of arbitrary topology, and can serve as a roadmap for understanding the dynamics of large interacting systems in general.

Journal Article↗
PubMed2000

Jamming and fluctuations in granular drag

We investigate the dynamic evolution of jamming in granular media through fluctuations in the granular drag force. The successive collapse and formation of jammed states give a stick-slip nature to the fluctuations which is independent of the contact surface between the grains and the dragged object, thus implying that the stress-induced collapse is nucleated in the bulk of the granular sample. We also find that while the fluctuations are periodic at small depths, they become "stepped" at large depths, a transition which we interpret as a consequence of the long-range nature of the force chains.

Journal Article↗
PubMed1999

Emergence of scaling in random networks

Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach preferentially to sites that are already well connected. A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.

Journal Article↗
PubMed1999

Liquid-induced transitions in granular media.

We investigate the effect of interstitial liquid on the physical properties of granular media by measuring the angle of repose as a function of the liquid content. The resultant adhesive forces lead to three distinct regimes in the observed behavior as the liquid content is increased: a granular regime in which the grains move individually, a correlated regime in which the grains move in correlated clusters, and a plastic regime in which the grains flow coherently. We discuss these regimes in terms of two proposed theories describing the effects of liquid on the physical properties of granular media.

Journal Article↗
PubMed1999

A comparative study of Embelia schiperi and Embelia keniensis on blood glucose and triglycerides in normal and epinephrine-induced hyperglycemic mice.

Intraperitoneal administration of the methanol extract of Embelia schiperi (ES) to normal mice caused a significant decrease in blood glucose (p < 0.01) and a significant increase in triglycerides 4 hours after administration at 100 mg/kg (p < 0.01). The toluene fraction of Embelia keniensis methanol extract (TS) showed hypoglycemic and lipid lowering activity 7 hours after intraperitoneal administration at 100 mg/kg. In addition, TS (100 mg/kg) administration significantly decreased blood glucose in epinephrine-induced hyperglycemic mice (p < 0.01). Moreover, ES tended to increase while TS tended to decrease the blood triglycerides in epinephrine-induced hyperglycemic mice. On the other hand, no changes in blood cholesterol were observed after the administration of ES or TS in normal and epinephrine-induced hyperglycemic mice. We found that two species from Embelia, ES and TS, have different activities on blood glucose and triglycerides in normal and epinephrine-induced hyperglycemic mice.

Animals↗
PubMed1999

[Evaluation and utilization of home visual aids prescribed to the satisfaction of the patients for age-related macular degeneration].

We evaluated the subjective advantage given by optical visual aids to patients affected by Age Related Macular Degeneration (ARMD). A total of 51 patients with ARMD having magnifying visual aids were retrospectively analysed. The 51 patients have been splitted up in 2 groups according to the final macular aspect and 7 subgroups according to their treatment, and have been questioned about the subjective advantage of their optical aids. Out of the 51 patients, 71% were satisfied, 5% were moderately satisfied and 24% were unsatisfied. The group with the lowest visual acuity at 5 meters has a satisfaction percentage only slightly lower (71%) than that with a higher visual acuity (75%). From the patients with a visual acuity superior to 3/10, 58% were affected with a persistence of macular edema. Seventy six percent of the patients with edema and 65% of the patients with a dry macular scar use their low vision aid every day. In summary, an important percentage of the patients are satisfied with their visual aids, independently of the fact that the retina is exsudative or dry, or that the visual acuity is good or bad. It seems useful to propose these optical aids to any patient suffering from ARMD who complains about reading-difficulties.

Aged↗
PubMed1999

New somatostatin analogues for radiotherapy of somatostatin receptor expressing tumours.

Among various newly synthesized chelator-linked octreotide analogues 90Y-[DOTA-DPhe1, Thyr3]-octreotide (90Y-SMT 487) was finally selected for clinical development. In vitro, SMT 487 binds selectively with nanomolar affinity to the somatostatin receptor subtype 2 (IC30 = 0.39 nM +/- 0.02). In vivo, 90Y-[DOTA-DPhe1, Thyr3]-octreotide shows a rapid blood clearance (T1/2 alpha < 5 min) and high accumulation in somatostatin subtype 2 receptor expressing tumours. The in vivo administration of 90Y-[DOTA-DPhe1, Thyr3]-octreotide induces a rapid tumour shrinkage in three different somatostatin receptor positive tumour models: CA20948 rat pancreatic tumours grown in normal rats, AR42J rat pancreatic tumours and NCI-H69 human small cell lung cancer both grown in nude mice. The radiotherapeutic efficacy of 90Y-SMT 487 was enhanced in combination with standard anticancer drugs, such as mitomycin C, which resulted in a tumour decrease of 70% of the initial volume. In the CA 20948 syngeneic rat tumour model, a single treatment with 10 microCi/kg 90Y-SMT 487 resulted in the disappearance of 5 out of 7 tumours. Thus the new radiotherapeutic agent showed its curative potential for the selective treatment of SRIF receptor-expression tumours. Clinical Phase I studies with 90Y-SMT 487 were started in September 1997.

Animals↗
PubMed1998

Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations.

T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values. Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

Administration, Oral↗
PubMed1998

Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.

A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.

Animals↗
PubMed1998

Direct synthesis of [DOTA-DPhe1]-octreotide and [DOTA-DPhe1,Tyr3]-octreotide (SMT487): two conjugates for systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man.

Direct attachment of unprotected DOTA (1,4,7,10-tetraazacyclododecane-N',N",N"',N""-tetraacetic acid) to partially suitably protected octreotide or [Tyr3]-octreotide leads after deprotection to [DOTA-DPhe1]-octreotide (III) and [DOTA-DPhe1,Tyr3]-octreotide (IV). These DOTA-containing somatostatin analogs, when labeled with a radiotherapeutic nuclide, are useful as antitumor agents. The partially protected peptides are accessible via solid phase peptide synthesis (SPPS) followed by selective cleavage under mild acidic conditions from the resin.

Drug Carriers↗