Effect of the search space dimensionality for finding close and faraway targets in random searches.

We investigate the dependence on the search space dimension of statistical properties of random searches with Lévy α-stable and power-law distributions of step lengths. We find that the probabilities to return to the last target found (P_{0}) and to encounter faraway targets (P_{L}), as well as the associated Shannon entropy S, behave as a function of α quite differently in one (1D) and two (2D) dimensions, a somewhat surprising result not reported until now. While in 1D one always has P_{0}≥P_{L}, an interesting crossover takes place in 2D that separates the search regimes with P_{0}>P_{L} for higher α and P_{0}

Landscape-scaled strategies can outperform Lévy random searches.

Information on the relevant global scales of the search space, even if partial, should conceivably enhance the performance of random searches. Here we show numerically and analytically that the paradigmatic uninformed optimal Lévy searches can be outperformed by informed multiple-scale random searches in one (1D) and two (2D) dimensions, even when the knowledge about the relevant landscape scales is incomplete. We show in the low-density nondestructive regime that the optimal efficiency of biexponential searches that incorporate all key scales of the 1D landscape of size L decays asymptotically as η_{opt}∼1/sqrt[L], overcoming the result η_{opt}∼1/(sqrt[L]lnL) of optimal Lévy searches. We further characterize the level of limited information the searcher can have on these scales. We obtain the phase diagram of bi- and triexponential searches in 1D and 2D. Remarkably, even for a certain degree of lack of information, partially informed searches can still outperform optimal Lévy searches. We discuss our results in connection with the foraging problem.

Dissipative Lévy random searches: universal behavior at low target density.

We investigate the problem of survival at the very low target-density limit and report on a second-order phase transition for one-dimensional random searches in which the energy cost of locomotion is a function of the distance traveled by the searcher. Surprisingly, from analytical calculations (also tested numerically) we find identical critical exponents for arbitrary energy cost functions. We conclude that there is a single universality class that describes this process.

Multiple epitopes of HLA-DRB1*0411 are recognized by T-cell clones originated from individuals carrying other DR4 subtypes.

HLA polymorphism dictates the binding and recognition of specific peptides, leading to variations in individual immune responses and may contribute to autoimmune disorders and outcome in organ transplantation. We have studied the molecular basis for the cellular recognition of DRB1*0411 in individuals carrying other sequence-related DR4-alleles by characterization of T-cell clones (TLC). A set of 166 TLC were raised by priming cells from DRB1*0401,0402 and DRB1*0405,0901 individuals and 52 of them recognized DRB1*0411. Five distinct patterns of T-cell allorecognition were found: DRB1*0411 alone, DRB1*0411 and 0405, DRB1*0411 and 0406, DRB1*0411 and 0407 and DRB1*0411, 0406 and 0407, depending on responder phenotypes and epitopes recognized by their T cells. A stretch of 30 amino acids on DRB1*0411 from positions 57 to 86 behaves as a functional domain and residues S57, R71, E74 and V86 seem to be crucial in forming immunogenic determinants recognized by these TLC. The knowledge of shared amino acid residues between closely related DR4 alleles, which show similar patterns of recognition by T cells could also be useful in the selection of prospective donors for clinical transplantation of solid organs or bone marrow.

Microvariation creates significant functional differences in the DR3 molecules.

Two DR3 molecules differ by four amino acids whose side chains point into the DR antigen-binding groove. To begin to assess the role of microvariation on DR3 function, DRB1*0302 residues were replaced with DRB1*0301 residues at beta-chain positions 26, 47, 86, and 47 plus 86. Murine fibroblast cell lines expressing DR(alpha, beta 1*0301), DR(alpha, beta 1*0302), and the four mutant 0302 molecules were examined for alloproliferative DR(alpha, beta 1*0302)-specific TLC stimulation and peptide binding. Changing position 26 had the most profound effect on T-cell recognition (seven of nine TLCs did not respond). Two TLCs did not respond to the mutant 0302V86 molecule and four TLCs that did respond to this mutant lost responsiveness when positions 47 and 86 were mutated together. These data suggest that each of these variant residues, including position 47, influence T-cell recognition. Surprisingly, none of the mutations had an effect on the absolute binding of HA 307-319 (DR[alpha, beta 1*0302] specific) and HSP 3-13 (DR[alpha, beta 1*0301] specific); however, the mutant 0302 molecules changed at position 86 (glycine to valine) consistently bound HA 307-319 at significantly higher levels than DR(alpha, beta 1*0302). These data for position 86 are in contrast to other DR molecules and indicate that peptide contact residues for a specific DR molecule cannot be predicted based on binding results obtained with other DR molecules. These data suggest that each of these variant groove residues, although not accessible to the TCR, contribute to the significant functional differences between the DR3 microvariants through subtle influences on the DR3-peptide complex.

[Lymphocyte imbalance in autoimmunity]. / La desregulación linfocitaria en autoinmunidad.

A subset of normal peripheral B lymphocytes expresses a T surface antigen recognized by monoclonal CD5. They form rosettes with mouse erythrocytes (MRBC). Other studies suggest that these B cells may have regulatory and helper properties. An expanded subset of lymphocytes forming MRBC was demonstrated in the peripheral blood of 31 Systemic Lupus Erythematosus (SLE) patients (14.4 +/- 2.8%) compared with normal controls (4.3 +/- 1.4%) and patients with tuberculosis (6.4 +/- 1.7%). Increased MRBC values correlated with disease severity. Investigation of cell surface antigen expression was attempted with enriched sedimented fractions using several monoclonal antibodies and immunofluorescent staining. Complete inhibition of MRBC formation was obtained with monoclonal antibodies against CD5, CD3 and CD8 while partial inhibition was observed with anti-Ia and no activity with CD4 and CD10 antibodies. Indirect evidence supports the concept that antilymphocyte antibodies cause T and B cell depletion and dysfunction. Sera from 12 patients with SLE and 28 with leprosy (LL) were analyzed for antibodies to lymphocytes in the microcytotoxicity assay: 87% of SLE and 57% of LL were positive. Lymphocytotoxic activity towards each cell type of a panel with 98 different HLA antigens was essentially the same and most sera were not specific for either T or B cells. Lymphocytotoxic sera from SLE and LL contained antibodies which inhibited MRBC formation.

La desregulación linfocitaria en autoinmunidad. / [Lymphocyte imbalance in autoimmunity]

A subset of normal peripheral B lymphocytes expresses a T surface antigen recognized by monoclonal CD5. They form rosettes with mouse erythrocytes (MRBC). Other studies suggest that these B cells may have regulatory and helper properties. An expanded subset of lymphocytes forming MRBC was demonstrated in the peripheral blood of 31 Systemic Lupus Erythematosus (SLE) patients (14.4 +/- 2.8

) compared with normal controls (4.3 +/- 1.4

) and patients with tuberculosis (6.4 +/- 1.7

). Increased MRBC values correlated with disease severity. Investigation of cell surface antigen expression was attempted with enriched sedimented fractions using several monoclonal antibodies and immunofluorescent staining. Complete inhibition of MRBC formation was obtained with monoclonal antibodies against CD5, CD3 and CD8 while partial inhibition was observed with anti-Ia and no activity with CD4 and CD10 antibodies. Indirect evidence supports the concept that antilymphocyte antibodies cause T and B cell depletion and dysfunction. Sera from 12 patients with SLE and 28 with leprosy (LL) were analyzed for antibodies to lymphocytes in the microcytotoxicity assay: 87

of SLE and 57

of LL were positive. Lymphocytotoxic activity towards each cell type of a panel with 98 different HLA antigens was essentially the same and most sera were not specific for either T or B cells. Lymphocytotoxic sera from SLE and LL contained antibodies which inhibited MRBC formation.

La desregulación linfocitaria en autoinmunidad / Lymphocyte imbalance in autoimmunity

Una pequeña proporción de linfocitos B presente en ganglios y sangre periférica humana tiene la propiedad de formar rosetas con eritrocitos de ratón (RR) y expresar en la superficie de su membrana un antígeno de 67 Kda perteneciente a la serie T (Pan T) que es reconocido por el monoclonal CD5. Se valoró en sangre periférica de pacientes con Lupus Eritematoso Sistémico (LES) la capacidad de formar RR. Treinta y un LES tenían un valor de 14,4 + o - 2,8% que fue comparado con controles normales: 4,3 + o - 1,4 (p<0,001) y pacientes con tuberculosis activa 6,4 + o - 1,7%. La expansión de esta subpoblación en el LES correlacionó con la severidad de la enfermedad. En experimentos de inhibición obteniéndose efecto parcial con la y ninguna actividad con CD4 y CD10. Hay evidencias que apoyan el concepto de que los anticuerpos antilinfocitarios producirían disfunción y depleción específica de subpoblaciones T y B linfocitarias. Los sueros de 12 pacientes con LES y de 28 con lepra lepromatosa (LL) fueron investigados para la presencia de estos anticuerpos con el método de microcitotoxicidad. La mayoría de los sueros con LES (87%) y un 57% de los LL fueron positivos en este ensayo. No hubo diferencias en la actividad cuando se los enfrentó con un panel de 98 diferentes antígenos HLA y tampoco hubo reactividad selectiva para linfocitos T o B. En un sistema de inhibición de RR, tanto los sueros de LES como los de LL, mostraron interferencia en la formación de rosetas, lo que sugiere la presencia de... (AU)

La desregulación linfocitaria en autoinmunidad / Lymphocyte imbalance in autoimmunity

Una pequeña proporción de linfocitos B presente en ganglios y sangre periférica humana tiene la propiedad de formar rosetas con eritrocitos de ratón (RR) y expresar en la superficie de su membrana un antígeno de 67 Kda perteneciente a la serie T (Pan T) que es reconocido por el monoclonal CD5. Se valoró en sangre periférica de pacientes con Lupus Eritematoso Sistémico (LES) la capacidad de formar RR. Treinta y un LES tenían un valor de 14,4 + o - 2,8% que fue comparado con controles normales: 4,3 + o - 1,4 (p<0,001) y pacientes con tuberculosis activa 6,4 + o - 1,7%. La expansión de esta subpoblación en el LES correlacionó con la severidad de la enfermedad. En experimentos de inhibición obteniéndose efecto parcial con la y ninguna actividad con CD4 y CD10. Hay evidencias que apoyan el concepto de que los anticuerpos antilinfocitarios producirían disfunción y depleción específica de subpoblaciones T y B linfocitarias. Los sueros de 12 pacientes con LES y de 28 con lepra lepromatosa (LL) fueron investigados para la presencia de estos anticuerpos con el método de microcitotoxicidad. La mayoría de los sueros con LES (87%) y un 57% de los LL fueron positivos en este ensayo. No hubo diferencias en la actividad cuando se los enfrentó con un panel de 98 diferentes antígenos HLA y tampoco hubo reactividad selectiva para linfocitos T o B. En un sistema de inhibición de RR, tanto los sueros de LES como los de LL, mostraron interferencia en la formación de rosetas, lo que sugiere la presencia de...

HLA antigens and other genetic markers in the Mapuche Indians of Argentina.

A total of 107 Mapuche Indians living in western Argentina were studied with respect to 16 genetic systems. For HLA, there were a few differences in relation to previous studies; and considering the averages observed in 15 other South American tribes, Mapuche Indians showed low values for A2, A9 and C3, but high ones for A28 and B16. This is the first report of the presence (in low frequencies, 1-6%) of alleles C2, C6 and C7, as well as of DR antigens (most frequent alleles DR4 and DR2) in South American Indians. Some peculiar reactions shown by products of locus B suggest the presence of antigens that are characteristic of the Mapuche. As for the other systems, the frequencies of R1 (Rh) and PGM1(1) were lower but those for r (Rh), GLO1 and Hp1 were higher than the averages obtained considering previous studies of this ethnic group. Other salient findings were the variability observed in the PGM2 and C3 systems, and the low prevalence of Bfs.