Designing the ammonium cation to achieve a higher hydrophilicity of bistriflimide-based ionic liquids.

In this work, we have found complete water miscibility for a priori, water immiscible (highly hydrophobic) ionic liquids by chemical manipulation of the quaternary ammonium cation grafted with hydroxyethyl moieties. Specifically, we were able to obtain bistriflimide-based ionic liquids completely miscible with water, even below room temperature. The underlying reason is the full integration of the OH groups of the cation in the continuous H-bonded network of water.

From lime to silica and alumina: systematic modeling of cement clinkers using a general force-field.

Thirteen different cement-clinker crystalline phases present in the lime-silica-alumina system have been systematically modeled using a simple and general force field. This constitutes a new type of approach towards the study of lime-silica-alumina systems, where the simpler and more transferable Lennard-Jones potential was used instead of the more traditional Buckingham potential. The results were validated using experimental density and structural data. The elastic properties were also considered. Six amorphous phases (corresponding to calcium/silicon ratios corresponding to belite, rankinite, wollastonite and alumina-doped amorphous wollastonite with 5%, 10% and 15% alumina content) were also studied using molecular dynamics simulations. The obtained MD trajectories were used to characterize the different crystalline and amorphous phases in terms of the corresponding radial distribution functions, aggregate analyses and connectivity among silica groups. These studies allowed a direct comparison between the crystalline and amorphous phases and revealed how the structure of the silica network was modified in the amorphous materials or by the inclusion of other structural units such as alumina. The knowledge at an atomistic level of such modifications is paramount for the formulation of new cement-clinker phases.

Properties of nanoparticles prepared from NdFeB-based compound for magnetic hyperthermia application.

Nanoparticles were prepared from a NdFeB-based alloy using the hydrogen decrepitation process together with high-energy ball milling and tested as heating agent for magnetic hyperthermia. In the milling time range evaluated (up to 10 h), the magnetic moment per mass at H = 1.59 MA m(-1) is superior than 70 A m(2) kg(-1); however, the intrinsic coercivity might be inferior than 20 kA m(-1). The material presents both ferromagnetic and superparamagnetic particles constituted by a mixture of phases due to the incomplete disproportionation reaction of Nd(2)Fe(14)BH(x) during milling. Solutions prepared with deionized water and magnetic particles exposed to an AC magnetic field (H(max) ~ 3.7 kA m(-1) and f = 228 kHz) exhibited 26 K ≤ ΔT(max) ≤ 44 K with a maximum estimated specific absorption rate (SAR) of 225 W kg(-1). For the pure magnetic material milled for the longest period of time (10 h), the SAR was estimated as ~2500 W kg(-1). In vitro tests indicated that the powders have acceptable cytotoxicity over a wide range of concentration (0.1-100 µg ml(-1)) due to the coating applied during milling.

Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population.

We studied the role of bone marrow B cell production in the renewal of peripheral B cells and the feedback mechanisms that control the entry of newly formed B cells into the peripheral B cell pools. When resting lymph node B cells are injected into B cell-deficient hosts, a fraction of the transferred cells expands and constitutes a highly selected population that survives for prolonged periods of time by continuous cell renewal at the periphery. Although the number of donor B cells recovered is low, a significant fraction shows an activated phenotype, and the serum immunoglobulin (Ig)M levels are as in normal mice. This population of activated B cells is resistant to replacement by a new cohort of B cells and is able to feedback regulate both the entry of newly formed B cells into the peripheral pool and terminal differentiation. These findings suggest that peripheral B cell selection follows the first come, first served rule and that IgM-secreting cells are generated from a pool of stable activated B cells with an independent homeostasis.

Very rapid decay of mature B lymphocytes in the spleen.

To determine the persistence of immunocompetent B lymphocytes at the periphery, regardless of cell division, we have followed the decay of lipopolysaccharide (LPS)-reactive B cells in LPS-nonresponder, histocompatible hosts. Both the numbers of transferred cells and of those persisting in the recipients could be determine with precision by limiting dilution analysis of the various cell populations. Decay rates of 50% per day were determined. Because we can exclude immune elimination of donor cells and the numbers of transferred cells were too low to result in gross alterations of the physiologic turnover rates, we conclude that the majority of LPS-reactive B lymphocytes and a large part of the whole B cell compartment show this astonishingly high rate of decay. The method introduced here might prove useful in a variety of clonal assays, as it can detect cells present at a very low frequency.

Differential expression of VH gene families in peripheral B cell repertoires of newborn or adult immunoglobulin H chain congenic mice.

The pattern of VH gene family expression in the primary B cell repertoire of the mouse is strain dependent. In C57Bl/6 mice, the VH J558 family is expressed by more than 45% of the cells, while the expression of VH 7183, VH Q52, and VH 36-60 families together does not exceed 20%. In BALB/c mice, relative expression of VH J558 is lower than 35%, while the sum of the other three families reaches 25%. To assess which genetic loci control strain-specific VH gene family expression, we studied VH gene family usage in splenic B cell repertoires of different congenic strains of mice. Changes in major histocompatibility complex or immunoglobulin (Ig) K light chain genes did not modify VH gene family expression in adult mice. Differences at the IgH locus, however, modified VH gene family usage. In 1-d-old mice, the strain-specific VH gene family expression pattern is determined by the IgH haplotype. In adult mice, the VH gene family expression pattern of resting B cells is independent of the IgH locus and follows the genetic background of the congenic strain, while it is determined by the IgH haplotype among Ig-secreting spleen cells. In F1(B6 x BALB/c) mice, each of the two spleen B cell populations, sorted on the basis of mu heavy chain allotype expression, shows an independent VH gene family expression pattern, determined by the IgH locus. The implications of these results in the control of VH gene family expression, and in the selection of peripheral B cell repertoires are discussed.

Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance.

We studied the interactions of male-specific T cell receptor (TCR)-alpha/beta-transgenic (TG) cells with different concentrations of male antigen in vivo. We constructed mouse chimeras expressing different amounts of male antigen by injecting thymectomized, lethally irradiated mice with various ratios of male (immunoglobulin [Ig] Ha) and female (IgHb) bone marrow. These chimeras were injected with male-specific TCR-alpha/beta-trangenic cells. These experiments allowed us to monitor antigen persistence and characterize antigen-specific T cells in terms of their frequency, reactivity, and effector functions (as tested by elimination of male B cells in vivo). In the absence of antigen, virgin TG cells persisted but did not expand. Transient exposure to antigen resulted in cell expansion, followed by the persistence of increased numbers of antigen-reactive T cells. In contrast, antigen persistence was followed by two independent mechanisms of tolerance induction: anergy (at high antigen concentrations), where T cells did not differentiate into effector functions but persisted in vivo as unresponsive T cells, and exhaustion (at lower antigen concentrations), where differentiation into effector functions (B cell elimination) occurred but was followed by the disappearance of antigen-specific T cells.

T cell homeostasis: thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors.

We developed a novel experimental strategy to study T cell regeneration after bone marrow transplantation. We assessed the fraction of competent precursors required to repopulate the thymus and quantified the relationship between the size of the different T cell compartments during T cell maturation in the thymus. The contribution of the thymus to the establishment and maintenance of the peripheral T cell pools was also quantified. We found that the degree of thymus restoration is determined by the availability of competent precursors and that the number of double-positive thymus cells is not under homeostatic control. In contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely independent of the number of precursors and of the number of thymus cells. Peripheral "homeostatic" proliferation and increased export and/or survival of recent thymus emigrants compensate for reduced T cell production in the thymus. In spite of these reparatory processes, mice with a reduced number of mature T cells in the thymus have an increased probability of peripheral T cell deficiency, mainly in the naive compartment.

Differential requirements for survival and proliferation of CD8 naïve or memory T cells.

The requisite molecular interactions for CD8 T cell memory were determined by comparison of monoclonal naïve and memory CD8(+) T cells bearing the T cell receptor (TCR) for the HY antigen. Naïve T cells required only the right major histocompatibility complex (MHC) class I-restricting molecule to survive; to expand, they also needed antigen. In contrast, for survival, memory cells did not require the restricting MHC allele, but needed only a nonspecific class I; for expansion the correct class I, but not antigen, was required. Thus, maintenance of CD8 T cell memory still required TCR-MHC class I interactions, but memory T cells may have a lower functional activation threshold that facilitates secondary responses.

Peripheral T cell survival.

T cell survival in the periphery is an active process, depending on continuous TCR engagement by peptide-MHC complexes and/or response to environmental cytokines. Naive T cells require interactions with the MHC restricting element. The survival requirements of memory T cells are as yet insufficiently characterized, but MHC-restricted interactions are not necessary.

Immunoglobulin VH gene expression following hemorrhage.

Hemorrhage has multiple effects on immunologic response, including alteration of B cell repertoires. In limiting dilution studies, decreased absolute frequencies of splenic clonal precursors specific for bacterial antigens were found after blood loss. In order to better define the effects of hemorrhage on B cell function, we examined immunoglobulin VH gene family expression following blood loss using both in situ hybridization and the RNA colony blot technique. No changes in VH gene family utilization were found after hemorrhage. These results demonstrate that the hemorrhage induced alteration in B cell function involves all VH gene families, without modifying distributive frequencies in VH gene family expression.

Transfer of T or CD8+ cells from hemorrhaged mice produce alterations in bacterial antigen specific plasma cell repertoires in normal syngeneic recipients.

Hemorrhage has multiple effects on immunologic response, including alteration of B cell repertoires and T cell function. This study examined possible relationships between these two phenomena by determining the effects of T cells and T cell subsets transferred from hemorrhaged donors into normal, unhemorrhaged syngeneic recipients on B cell repertoires. Mice given total T or CD8+ cells from hemorrhaged animals then immunized with the bacterial polysaccharide antigen levan had a decreased percentage of plasma cells producing antibody to levan compared to that in mice given T or CD8+ cells from unhemorrhaged animals. These effects of post hemorrhage CD8+ cells were not seen after transfer into nu/nu mice, indicating that these cells did not directly affect B cell function, but rather required other T cell populations in order to alter the B cell repertoire. These results demonstrate that hemorrhage-induced alterations in bacterial antigen specific B cell repertoires may result from T and CD8+ cell mediated changes in T-B interactions.

Kinetics of the inflammatory response in subcutaneous cysticercosis induced in mice by Taenia crassiceps.

The larval stage of Taenia crassiceps has been used to study human cysticercosis as these larvae have antigenic similarity to the cysticerci of Taenia solium. The aim of this study was to evaluate the histopathological and immunological changes that followed the inoculation of T. crassiceps cysticerci into the subcutaneous tissue of C57BL/6 mice. Microscopically, granulomas formed of neutrophils and macrophages developed at the sites of inoculation. The serum concentration of the cytokine interferon (IFN)-γ increased throughout the course of infection, while the serum concentration of interleukin-4 increased during the period of transition from the initial phase (7-30 days postinoculation [dpi]) to the late phase (60-90 dpi) of infection. Destruction of the parasite therefore appears to be associated with an increase in IFN-γ, suggesting that a type 1 immune response is important in the control of the parasite.

Hierarchical classification of G-protein-coupled receptors with data-driven selection of attributes and classifiers.

We address the important bioinformatics problem of predicting protein function from a protein's primary sequence. We consider the functional classification of G-Protein-Coupled Receptors (GPCRs), whose functions are specified in a class hierarchy. We tackle this task using a novel top-down hierarchical classification system where, for each node in the class hierarchy, the predictor attributes to be used in that node and the classifier to be applied to the selected attributes are chosen in a data-driven manner. Compared with a previous hierarchical classification system selecting classifiers only, our new system significantly reduced processing time without significantly sacrificing predictive accuracy.