Antibiotics with Interleukin-15 inhibition reduces joint inflammation and bone erosions but not cartilage destruction in Staphylococcus aureus-induced arthritis

Background: Staphylococcus aureus-induced arthritis causes rapid joint destruction, often leading to disabling joint damage despite antibiotics. We have previously shown that IL-15 inhibition without antibiotics is beneficial in S. aureus-induced arthritis. We therefore hypothesized that inhibition of IL-15, in combination with antibiotics, might represent a useful therapy that would both reduce inflammation and joint destruction, but preserve the host's ability to clear the infection. Methods: Female wildtype C57BL/6 mice were intravenously inoculated with the TSST-1-producing LS-1 strain of S. aureus with 0.8x108 S. aureus LS-1/mouse. Three days later the treatment was started consisting of cloxacillin followed by flucloxacillin, together with either anti-IL-15 antibodies (aIL-15ab) or control antibodies. Outcomes included survival, weight change, bacterial clearance, and joint damage. Results: The addition of aIL-15ab to antibiotics in S. aureus-induced arthritis reduced synovitis and bone erosions compared to controls. The number of bone-resorbing osteoclasts in the joints was reduced, whereas cartilage destruction was not significantly altered. Importantly, the combination therapy did not adversely affect the clinical outcome of S. aureus-induced arthritis, such as survival, weight change or compromise the host's ability to clear the infection. Conclusions: As the clinical outcome of S. aureus-induced arthritis was not affected, the addition of aIL-15ab to antibiotics ought to be safe. Taken together, the combination of aIL-15ab and antibiotics is a beneficial, but not optimal, treatment of S. aureus-induced arthritis as it reduces synovitis and bone erosions but has a limited effect on cartilage destruction

Neutrino masses from discrete gauge symmetries

We investigate a model with an extra $Z_{2}$ gauge symmetry in the Standard Model. We assume that only the scalars and the leptons carry non-zero charge. The symmetry gives a structure to the mass matrix for the neutrinos. With two extra Higgs singlets and two extra singlet right-handed neutrinos we can build a model that fits the requirements of the MSW-solution of the Solar neutrino problem. With a third singlet right-handed neutrino it is also possible to have a 10 eV neutrino, a dark matter candidate.Comment: SNUTP 92-105, Late

Constitutive modeling for isotropic materials (HOST)

The results of the first year of work on a program to validate unified constitutive models for isotropic materials utilized in high temperature regions of gas turbine engines and to demonstrate their usefulness in computing stress-strain-time-temperature histories in complex three-dimensional structural components. The unified theories combine all inelastic strain-rate components in a single term avoiding, for example, treating plasticity and creep as separate response phenomena. An extensive review of existing unified theories is given and numerical methods for integrating these stiff time-temperature-dependent constitutive equations are discussed. Two particular models, those developed by Bodner and Partom and by Walker, were selected for more detailed development and evaluation against experimental tensile, creep and cyclic strain tests on specimens of a cast nickel base alloy, B19000+Hf. Initial results comparing computed and test results for tensile and cyclic straining for temperature from ambient to 982 C and strain rates from 10(exp-7) 10(exp-3) s(exp-1) are given. Some preliminary date correlations are presented also for highly non-proportional biaxial loading which demonstrate an increase in biaxial cyclic hardening rate over uniaxial or proportional loading conditions. Initial work has begun on the implementation of both constitutive models in the MARC finite element computer code

Modeling The Cutoff Frequency Of Single-Heterojunction Bipolar-Transistors Subjected To High Collector-Layer Current

High current densities in the collector layer reduce the cutoff frequency of heterojunction bipolar transistors. We develop a model based on analytical expressions that describe this reduction. These expressions represent the contributions from each of six regions defined in the output current‐voltage characteristic. The model has parameters determined entirely by device physical makeup. It has no fitting parameters. Its predictions agree well with experimental data taken on two N/p+/n aluminum‐gallium‐arsenide/gallium‐arsenide transistors having abrupt junctions grown by molecular‐beam epitaxy. Because previous models omitted the effects of high current densities, their predictions agree less favorably. The development of the model considers the effects that compound‐semiconductor properties such as velocity overshoot have on the cutoff frequency

Systemic and intraperitoneal interleukin‐6 system during the first year of peritoneal dialysis

Perit Dial Int. 2006 Jan-Feb;26(1):53-63. Systemic and intraperitoneal interleukin-6 system during the first year of peritoneal dialysis. Pecoits-Filho R, Carvalho MJ, Stenvinkel P, Lindholm B, Heimbürger O. Division of Renal Medicine and Baxter Novum, Karolinska Institutet, K-56, Huddinge University Hospital, 141 86 Stockholm, Sweden. [email protected] Comment in: Perit Dial Int. 2006 Jan-Feb;26(1):35-7. Abstract OBJECTIVE: To investigate if intraperitoneal and systemic interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) are related to each other and to peritoneal solute transport rate (PSTR). DESIGN: Longitudinal study in retrospectively selected patients. SETTING: Peritoneal dialysis (PD) unit of a university-based hospital. PATIENTS AND METHODS: 31 PD patients on treatment with conventional glucose-based solutions participated in a longitudinal study. IL-6 and sIL-6R were measured in plasma and overnight effluent, both at baseline and after 12 +/- 2 months on PD. C-reactive protein (CRP) and serum albumin were used as surrogate markers of inflammation. PSTR of small solutes was evaluated using the dialysate-to-plasma ratio (D/P) of creatinine after a 4-hour dwell; PSTR of large solutes was evaluated using the 24-hour D/P ratio of albumin. RESULTS: D/P creat increased over time (0.67 +/- 0.15 vs 0.80 +/- 0.11, p or = median had higher (p or = median [24.7 (16.5 - 38.5) pg/mL] compared to patients with IL-6 < median [14.1 (10 - 25.7) pg/mL]. Neither CRP nor albumin changed over time on PD, although they were closely linked to plasma IL-6 levels. A strong positive correlation was found between D/P creat and dialysate IL-6 (rho = 0.77, p < 0.0001) at baseline, but not at 1 year. In contrast, there was a significant correlation between D/P creat and dialysate sIL-6R (rho = 0.39, p < 0.05) at 1 year, but not at baseline. At 1 year, 17 patients with increasing PSTR had higher increases in dialysate IL-6 (28 +/- 26 vs -21 +/- 78 pg/mL, p < 0.05) and levels of dialysate sIL-6R (693 +/- 392 vs 394 +/- 274 pg/mL, p = 0.05) compared to patients with stable PSTR (n = 11). Patients who had peritonitis presented higher baseline serum IL-6 concentration (6.8 +/- 1.0 pg/mL) compared with patients without peritonitis (4.0 +/- 0.6 pg/mL, p < 0.05). Finally, both at baseline and after 1 year, there were significant correlations between plasma and dialysate IL-6 (rho = 0.46, p < 0.05, and rho = 0.40, p < 0.05) respectively. CONCLUSIONS: These findings indicate that, (1) intraperitoneal and systemic inflammation increase in PD patients during the first year of therapy; (2) intraperitoneal and systemic inflammation may be interrelated and the IL-6 system may be the link; (3) the IL-6 system (both intraperitoneal and systemic) is associated with PSTR, particularly in the early phase of PD treatment, in which small and large solute transport are linked. Signs of a transition between acute and chronic inflammation were observed in the follow-up evaluation. Inflammation may, at least in part, be responsible for the development of a high PSTR, and this could be one reason for the high mortality in patients with high PSTR. PMID: 16538876 [PubMed - indexed for MEDLIN

Measurements of hybrid fertility and a test of mate preference for two house mouse races with massive chromosomal divergence

Abstract Background Western house mice Mus musculus domesticus are among the most important mammalian model species for chromosomal speciation. Hybrids between chromosomal races of M. m. domesticus suffer various degrees of fertility reduction between full fertility and complete sterility, depending on the complexity of the chromosomal differences between the races. This complexity presents itself in hybrids as meiotic configurations of chromosome chains and rings, with longer configurations having a stronger impact on fertility. While hybrids with short configurations have been intensively studied, less work has been done on hybrids with very long configurations. In this study, we investigated laboratory-reared wild mice from two chromosomally very different races in Switzerland found in close proximity. Hybrids between these races form a meiotic chain of fifteen chromosomes. We performed a detailed analysis of male and female hybrid fertility, including three generations of female backcrosses to one of the parental races. We also tested for possible divergence of mate preference in females. Results While all male F1 hybrids were sterile with sperm counts of zero, 48% of female F1 hybrids produced offspring. Their litter sizes ranged from one to three which is significantly lower than the litter size of parental race females. When hybrid females were backcrossed to a parental race, half of the offspring resembled the parental race in karyotype and fertility, while the other half resembled the F1 hybrids. In the preference test, females of both races indicated a lack of a preference for males of their own karyotype. Conclusions Although the fertility of the F1 hybrids was extremely low because of the complexity of the chromosomal differences between the races, reproductive isolation was not complete. As we did not find assortative female preferences, we expect that contact between these races would lead to the production of hybrids and that gene flow would occur eventually, as fertility can be restored fully after one backcross generation

Sawja: Static Analysis Workshop for Java

Static analysis is a powerful technique for automatic verification of programs but raises major engineering challenges when developing a full-fledged analyzer for a realistic language such as Java. This paper describes the Sawja library: a static analysis framework fully compliant with Java 6 which provides OCaml modules for efficiently manipulating Java bytecode programs. We present the main features of the library, including (i) efficient functional data-structures for representing program with implicit sharing and lazy parsing, (ii) an intermediate stack-less representation, and (iii) fast computation and manipulation of complete programs

Pointwise estimates for the Bergman kernel of the weighted Fock space

We prove upper pointwise estimates for the Bergman kernel of the weighted Fock space of entire functions in $L^2(e^{-2\phi})$ where $\phi$ is a subharmonic function with $\Delta \phi$ a doubling measure. We derive estimates for the canonical solution operator to the inhomogeneous Cauchy-Riemann equation and we characterize the compactness of this operator in terms of $\Delta \phi$