Reduction theorems for operators on the cones of monotone functions

For a quasilinear operator on the semiaxis a reduction theorem is proved on the cones of monotone functions in Lp - Lq setting for 0 < q < ∞, 1<= p < ∞. The case 0 < p < 1 is also studied for operators with additional properties. In particular, we obtain critera for three-weight inequalities for the Hardy-type operators with Oinarov' kernel on monotone functions in the case 0 < q < p <= 1.

Core Functions of the Health Service Report

The Government Decision1 on the Structural, Organisational, Financial Management and Systems Reform of the Health Sector of June, 2003 acknowledged that in order to increase the effectiveness of the health service generally, and its capacity to deliver the reform agenda, it was important that the service was fully concentrated on addressing its core health objectives. The Minister for Health and Children and Minister for Finance felt that there could be scope to transfer certain functions out of the health service and locate them more appropriately within other functional areas of Government. As part of the overall decision, it was agreed that a working group would be established, to include the Departments of Health and Children, Finance and An Taoiseach, to examine the scope for transfer of certain activities to other, more appropriate, Departments and agencies and that on completion of this review, the Minister for Health and Children would bring proposals to Government. Read the Report (PDF, 70kb)  

Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05) on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease.

E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases.

E2F transcriptional regulators control human-cell proliferation by repressing and activating the transcription of genes required for cell-cycle progression, particularly the S phase. E2F proteins repress transcription in association with retinoblastoma pocket proteins, but less is known about how they activate transcription. Here, we show that the human G1 phase regulator HCF-1 associates with both activator (E2F1 and E2F3a) and repressor (E2F4) E2F proteins, properties that are conserved in insect cells. Human HCF-1-E2F interactions are versatile: their associations and binding to E2F-responsive promoters are cell-cycle selective, and HCF-1 displays coactivator properties when bound to the E2F1 activator and corepressor properties when bound to the E2F4 repressor. During the G1-to-S phase transition, HCF-1 recruits the mixed-lineage leukemia (MLL) and Set-1 histone H3 lysine 4 methyltransferases to E2F-responsive promoters and induces histone methylation and transcriptional activation. These results suggest that HCF-1 induces cell-cycle-specific transcriptional activation by E2F proteins to promote cell proliferation.

Krein's strings whose spectral functions are of polynomial growth

In case Krein's strings with spectral functions of polynomial growth a necessary and su fficient condition for the Krein's correspondence to be continuous is given.

Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

On the analysis of travelling waves to a nonlinear flux limited reaction-diffusion equation

In this paper we study the existence and qualitative properties of travelling waves associated to a nonlinear flux limited partial differential equation coupled to a Fisher-Kolmogorov-Petrovskii-Piskunov type reaction term. We prove the existence and uniqueness of finite speed moving fronts of C2 classical regularity, but also the existence of discontinuous entropy travelling wave solutions.

Wellposedness of a nonlinear, logarithmic Schrödinger equation of Doebner-Goldin type modeling quantum dissipation

This paper is concerned with the modeling and analysis of quantum dissipation phenomena in the Schrödinger picture. More precisely, we do investigate in detail a dissipative, nonlinear Schrödinger equation somehow accounting for quantum Fokker–Planck effects, and how it is drastically reduced to a simpler logarithmic equation via a nonlinear gauge transformation in such a way that the physics underlying both problems keeps unaltered. From a mathematical viewpoint, this allows for a more achievable analysis regarding the local wellposedness of the initial–boundary value problem. This simplification requires the performance of the polar (modulus–argument) decomposition of the wavefunction, which is rigorously attained (for the first time to the best of our knowledge) under quite reasonable assumptions.

Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity.

Brooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13. The encoded protein functions as ubiquitin-specific protease (UBP), which negatively regulates NF-kappaB and c-Jun N-terminal kinase (JNK) signaling. We investigated five families affected with these skin neoplasms and identified four premature stop codons and the novel missense mutation D681G in a family in which 11 of 12 investigated tumors were trichoepitheliomas. CYLD protein harboring this missense mutation had a significant reduced ability to inhibit TNF receptor-associated factor (TRAF)2- and TRAF6-mediated NF-kappaB activation, tumor necrosis factor-alpha (TNFalpha)-induced JNK signaling, and to deubiquitinate TRAF2. CYLD-D681G was coimmunoprecipitated by TRAF2, but was unable to cleave K63-linked polyubiquitin chains. Aspartic acid 681 is highly conserved in CYLD homologues and other members of the UBP family, but does not belong to the Cys and His boxes providing the CYLD catalytic triad (Cys601, His871, and Asp889). As reported previously, the homologous residue D295 of HAUSP/USP-7 forms a hydrogen bond with the C-terminal end of ubiquitin and is important for the enzymatic activity. These results underline that D681 in CYLD is required for cleavage of K63-linked polyubiquitin chains.

Disease-driven T cell activation predicts immune responses to vaccination against melanoma.

Tumor vaccines may induce activation and expansion of specific CD8 T cells which can subsequently destroy tumor cells in cancer patients. This phenomenon can be observed in approximately 5-20% of vaccinated melanoma patients. We searched for factors associated with T cell responsiveness to peptide vaccines. Peptide antigen-specific T cells were quantified and characterized ex vivo before and after vaccination. T cell responses occurred primarily in patients with T cells that were already pre-activated before vaccination. Thus, peptide vaccines can efficiently boost CD8 T cells that are pre-activated by endogenous tumor antigen. Our results identify a new state of T cell responsiveness and help to explain and predict tumor vaccine efficacy.

The role of APRIL and BAFF in lymphocyte activation.

The TNF family ligands BAFF (also called BLyS) and APRIL regulate lymphocyte survival and activation. BAFF binds to three receptors, BAFF-R, TACI and BCMA, whereas APRIL interacts with TACI, BCMA and proteoglycans. The contribution of BAFF and APRIL to B-cell and plasma-cell survival, CD154 (CD40L)-independent antibody isotype switching, germinal center maintenance, T-dependent and T-independent antibody responses, and T cell co-stimulation are relatively well understood. Constitutive BAFF produced by stromal cells determines the size of the peripheral B cell pool, whereas inducible BAFF produced by myeloid and other cells supports local survival of B lymphocytes and can be associated with development of autoimmunity when deregulated.

An algebraic operator approach to the analysis of Gerber-Shiu functions

We introduce an algebraic operator framework to study discounted penalty functions in renewal risk models. For inter-arrival and claim size distributions with rational Laplace transform, the usual integral equation is transformed into a boundary value problem, which is solved by symbolic techniques. The factorization of the differential operator can be lifted to the level of boundary value problems, amounting to iteratively solving first-order problems. This leads to an explicit expression for the Gerber-Shiu function in terms of the penalty function.

CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts.

To investigate the role of the coreceptor CD8 and lipid rafts in cytotoxic T lymphocyte (CTL) activation, we used soluble mono-and multimeric H-2Kd-peptide complexes and cloned S14 CTL specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite (PbCS) peptide 252-260 [PbCS(ABA)]. We report that activation of CTL in suspension requires multimeric Kd-PbCS(ABA) complexes co-engaging TCR and CD8. Using TCR ligand photo-cross-linking, we find that monomeric Kd-PbCS(ABA) complexes promote association of TCR/CD3 with CD8/p56lck. Dimerization of these adducts results in activation of p56lck in lipid rafts, where phosphatases are excluded. Additional cross-linking further increases p56lck kinase activity, induces translocation of TCR/CD3 and other signaling molecules to lipid rafts and intracellular calcium mobilization. These events are prevented by blocking Src kinases or CD8 binding to TCR-associated Kd molecules, indicating that CTL activation is initiated by cross-linking of CD8-associated p56lck. They are also inhibited by methyl-beta-cyclodextrin, which disrupts rafts and by dipalmitoyl phosphatidylethanolamine, which interferes with TCR signaling. Because efficient association of CD8 and p56lck takes place in rafts, both reagents, though in different ways, impair coupling of p56lck to TCR, thereby inhibiting the initial and essential activation of p56lck induced by cross-linking of engaged TCR.

Fonctions du plancher pelvien: de la phase expulsive à la consultation du post-partum [Pelvic floor functions: from the beginning of the second phase of labor to the postpartum consultation].

Vaginal delivery can cause lesions of the various pelvic structures responsible for the mechanisms of continence. These lesions may perhaps be prevented in the future by measuring pressure generated during childbirth. Tear of the anal sphincter during childbirth is a marker of a global impairment of the urinary, ano-rectal and sexual pelvic functions in the short and medium term. Persistence of a defect of the anal sphincter is frequent in spite of immediate suture. The correlation between these defects and ano-rectal incontinence are not established in our experience. The quality of the contraction of the sphincter complex and pubo-rectal sling seems to play a more important role in ano-rectal continence after a traumatic childbirth.