Transport properties of highly ordered heterogeneous ion-exchange membranes.

Model "ordered" heterogeneous ion exchange membranes are made with ion exchange particles heaving ion exchange capacity in the range 3 to 2.5 meq/gr (dry basis) and diameters ranging from 37 to 7 microm and 2 component room-temperature vulcanizing silicon rubber as a polymeric matrix, by applying an electric field normal to the membrane surface during preparation. These membranes were shown to have an improved ionic conductivity compared with "nonordered" membranes based on the same ion exchange content (for instance, at 10% resin content "nonordered" membranes show <10(-5) mS/cm while "ordered" membranes have conductivity of 1 mS/cm). The transport properties of ordered membranes were compared with those of nonordered membranes, through the current-voltage characteristics. Limiting currents measured for the ordered membranes were significantly higher than those of the nonordered membranes with the same resin concentration. In addition, higher limiting currents were observed in ordered membranes as the resin particles became smaller. Energy dispersion spectrometry analyses revealed that the concentration of cation exchange groups on the membrane surface was higher for ordered membrane as compared to that of nonordered membranes. This implies that the local current density for the conducting domains at the surface of the nonordered membranes is higher, leading to higher concentration polarization and, eventually, to lower average limiting current densities. The effect of ordering the particles on the membrane conductivity and transport properties was studied, and the advantages of the ordered membranes are discussed.

Unlimited relativistic shock surfing acceleration.

Nonrelativistic shock surfing acceleration at quasiperpendicular shocks is usually considered to be a preacceleration mechanism for slow pickup ions to initiate diffusive shock acceleration. In shock surfing, the particle accelerates along the shock front under the action of the convective electric field of the plasma flow. However, the particle also gains kinetic energy normal to the shock and eventually escapes downstream. We consider the case when ions are accelerated to relativistic velocities. In this case, the ions are likely to be trapped for infinitely long times, because the energy of bounce oscillations tends to decrease during acceleration. This suggests the possibility of unlimited acceleration by shock surfing.

Renal glucose reabsorption during hypertonic glucose infusion in female streptozotocin-induced diabetic rats.

Information regarding the renal glucose transport capacity in diabetes mellitus is limited. These data are needed because two weeks following injection of streptozotocin (STZ), mRNA and protein levels of the glucose transporter, GLUT2, are upregulated in the proximal tubule of the rat. Therefore, we measured renal glucose transport and GLUT2 protein levels in female control rats, and in rats one (STZ-1), two (STZ-2), and three weeks (STZ-3) after STZ injection (65 mg kg(-1), i.p.). Progressive amounts of glucose were infused into anesthetized rats via the femoral vein and renal clearances collected. The amount of glucose reabsorbed, factored by the glomerular filtration rate (GFR) was significantly greater in STZ-3 rats compared with all other groups. In addition, the amount of glucose reabsorbed factored by the amount of glucose filtered was decreased in STZ-1 and STZ-2 compared with controls but was increased in STZ-3. By contrast, renal GLUT2 levels were elevated in all the STZ-treated rats. These data suggest that other factors, functioning either in conjunction with or independent of GLUT2, are required to support an elevated renal glucose transport capacity.

Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression.

CD28 is the major costimulatory molecule on T cells. CD28 activation, in conjunction with T-cell receptor engagement, up-regulates transcription of several cytokines, including interleukin-2 (IL-2), through transcriptional activation of the RE/AP composite element. Although CD28 is not normally expressed on B cells or plasma cells, more than 90% of extramedullary myelomas (a late stage B-cell neoplasm) express CD28. The functional significance of this is unknown. The results of this study demonstrate that CD28 stimulates transcriptional activation of RE/AP-based reporters in B cells and myeloma cells. However, CD28 stimulation does not up-regulate IL-2 production in myeloma cell lines, demonstrating that the IL-2 promoter may not be a relevant RE/AP-containing target of CD28 in myelomas. Instead, an RE/AP composite element has been identified within the promoter of the IL-8 gene, a chemokine that promotes angiogenesis. Furthermore, stimulation of endogenous CD28 expressed by 3 myeloma cell lines increased IL-8 production. Therefore, the study demonstrates that CD28 is functional in myelomas to up-regulate transcription of endogenous genes, including IL-8. The proposal is made that aberrant expression of CD28 may play a role in the progression of multiple myeloma.

Induction of NF-kappaB by the Akt/PKB kinase.

The serine/threonine kinase Akt (also known as protein kinase B, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase. Akt can couple to pathways that regulate glucose metabolism or cell survival [1]. Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16 [2] [3] [4]. Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-kappaB family of transcription factors in the Jurkat T-cell line. This induction occurs, at least in part, at the level of degradation of the NF-kappaB inhibitor IkappaB, and is specific for NF-kappaB, as other inducible transcription factors are not affected by Akt overexpression. Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt. Also, Akt does not act alone to induce cytokine promoters and NF-kappaB reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-kappaB induction that could have implications for the control of T-cell growth and survival.

Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation: requirement for CD28 up-regulation of RE/AP.

IL-2 gene transcription in T cells requires both TCR and costimulatory signals. IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation. The addition of rCTLA4Ig, which blocks CD28 binding to its ligand, to the cultures decreased IL-2 promoter activation by >80%. Interestingly, CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells (NFAT) or AP-1 reporters. Therefore, activation of NFAT and AP-1 is insufficient for IL-2 promoter activation. In contrast, an RE/AP reporter was blocked by CTLA4Ig by >90%. Thus, the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites. In addition, these data suggest that transcriptional activation of RE/AP is not mediated by NFAT, because activation of a NFAT reporter is not affected by the addition of CTLA4Ig.

Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism.

Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation of the T cell cytoskeleton and secretory apparatus towards the cell-cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex-dependent process. Such T cell polarization directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and cell-sized latex beads coated with various antibodies as artificial APCs. Here, we report that beads coated with antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes did not depend on activation of additional coreceptors. Moreover, single subunits of the TCR complex, namely TCR-zeta and CD3epsilon, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the immunoreceptor tyrosine-based activation motifs (ITAMs), present three times in TCR-zeta and once in CD3epsilon, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact ITAM. In agreement with this result, lack of functional Lck, the protein tyrosine kinase responsible for ITAM phosphorylation, abolished both MTOC reorientation and polarized actin polymerization. Both inhibitor and transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras activation. Our results suggest that APC-induced T cell polarization is a TCR-mediated event that is coupled to the TCR by the same signaling motif as TCR-induced gene activation, but diverges in its distal signaling requirements.

The splintered holding environment and the vulnerable ego. A case study.

This paper describes the developmental dilemmas of children in long-term foster care whose permanent placement is delayed for years. Developmental theory and clinical research postulate the psychological risks to children who face the continuous threat of primary object loss. The detailed account of Matthew's case illustrates the effects of early neglect, abuse, and multiple separations on ego development. Matthew was removed from his birth mother at thirteen months but was not adopted by his foster mother until he was seven years old. He entered therapy when he was four. The clinical material reveals not only his strong will for survival but also his gradual internalization of the fear of primary object loss, his extreme narcissistic vulnerability, and his hypervigilance concerning danger, abandonment, and annihilation. He had great difficulty controlling his impulses. With some technical modifications, treatment enabled Matthew to strengthen his capacity for object relatedness, self-reflection, and learning. The paper demonstrates how important it is for social welfare agencies and the courts to be more cognizant of developmental theory and to recognize the need for earlier permanent placement determinations.

CD28 mediates transcriptional upregulation of the interleukin-2 (IL-2) promoter through a composite element containing the CD28RE and NF-IL-2B AP-1 sites.

Mutagenesis studies have demonstrated the requirement for the CD28-responsive element (CD28RE) within the interleukin-2 (IL-2) promoter for transcriptional upregulation by CD28. Here, we demonstrate that CD28 responsiveness is conferred by a composite element containing both the CD28RE and the NF-IL-2B AP-1 sites (RE/AP). Mutations at either site within the RE/AP composite element abolish activity. The RE/AP composite element is a site for signal integration within the IL-2 promoter, since its activation is dependent on at least two separate signalling pathways being activated, through the T-cell receptor, CD28, and/or phorbol myristate acetate. Activation is maximal when all three signals occur simultaneously. By using a panel of CD28 cytoplasmic domain mutants, it was found that the transcriptional activation of the RE/AP composite element correlates exactly with the pattern of IL-2 secretion induced by these mutants upon stimulation. Similar to the upregulation of IL-2 secretion, the transcriptional upregulation of the RE/AP composite element by CD28 is FK506 insensitive. The pattern of activation of the RE/AP composite element is different from that observed for either an NFAT or consensus AP-1 site, implying that RE/AP represents a unique element. Using gel shift analysis, we demonstrate that stimulation by CD28 induces the association of the NF-kappaB family member c-Rel to the CD28RE within the RE/AP composite element. The transcriptional upregulation of IL-2 by CD28 appears, therefore, to be mediated through the RE/AP composite element, involving the association of c-Rel with the CD28RE.

[A new method of assessing contrast sensitivity in patients with eye diseases]. / Novyi metod issledovaniia kontrastnoi chuvstvitel'nosti v klinike glaznykh boleznei.

A new method for examining spatial contrast sensitivity (SCS) is described, making use of the display of an IBM-compatible computer, on which sinusoidal patterns are presented: achromatic and chromatic red, green, blue against the black background at a frequency of 0.5 to 22 cycles/degree. In health similarity of curves to the achromatic and chromatic patterns was observed, with the maximal sensitivity at spatial frequencies from 2 to 8 cycles/degree and a reduction at low and high spatial frequencies. In patients with the initial open-angle glaucoma the SCS at the high spatial frequencies was reduced for all colors with "dips" at the medium spatial frequencies in response to the blue pattern. In patients with albinism the SCS to achromatic and chromatic patterns were appreciably decreased in the entire range of spatial frequencies and absent at all in the range of high spatial frequencies. The method is recommended for investigating the channels of achromatic and chromatic spatial sensitivity, detecting the contribution of color receptors to the color contrast, and for the initial diagnosis of diseases of the retina and optic nerve.

c-rel regulation of IL-2 gene expression may be mediated through activation of AP-1.

T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-kappa B family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation approximately 17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.

On the reconstructive matching of multidimensional objects.

To determine a known object position and orientation within a scene is a task of fundamental importance. A scheme called reconstructive matching (RM), which is inherently invariant to shift, rotation, and optionally to scale changes is introduced. RM decomposes the matching within the source space into a set of mutually independent processes of dimensionality reduced by one. Applied to computerized tomography (CT), the approach allows CT object matching prior to their reconstruction.

Identification and cloning of the G3B cDNA encoding a 3' segment of a protein binding to GATA-3.

The transcription factor GATA-3 contributes to the expression of several genes critical for T-cell function and development, including the T-cell receptor alpha and beta chains. We report here the isolation of a human cDNA clone which encodes a 3' segment of a novel protein with three zinc fingers. This protein, which we termed G3B, can interact with GATA-3 in vitro. Its mRNA is expressed in T and B cells. Thus, G3B may represent a potential regulator of GATA-3 function.

Approach to automatic analysis of Young's fringes in speckle photography.

A new flexible automatic method for analysis of Young's fringes that allows software, electronic hardware, and optoelectronic realizations is proposed. A displacement vector is sought in the two-dimensional spatial frequency domain, the separate slices of which are obtained through multiple use of the one-dimensional Fourier transform of the Radon-transformed fringe image. An estimate of fringe angle and spacing is found from a projection with the principal Fourier spectrum peak. Afterward its position is repeatedly refined until the desired accuracy is reached. Although the method is relevant mainly to speckle photography, our approach is also applicable to fringe patterns that are generated by a computer. The problem of fringe visibility is widely discussed, and a new estimate is proposed.

The community as a strategic site for refining high perinatal risk assessments and interventions.

This paper describes a community-based agency's approach to reducing perinatal risk among populations at high medical, familial and environmental risk. Following a descriptive analysis of 96 families enrolled in a maternal outreach program, a case study illustrates how client-sensitive strategies are applied to successfully engage a traumatized population. The intensity and duration of the interventions, the extensive outreach efforts to the family and the dedication and commitment of the staff are not easily replicated but invaluable in helping providers and researchers understand to what extent the impact of severe deprivations and risk can be mediated and potential damage to the newborn prevented. The paper concludes that community-based agencies in partnership with social and clinical researchers from a tertiary care setting provide the key for developing more effective, integrated perinatal care by virtue of the critical density of hard-to-reach patients who can be followed by providers and clinical researchers.