Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

Simultaneous machining of parallel grooves in SnO(2) thin films using a Nd:YAG laser and a kinoform

A kinoform is used to split the beam of a Nd:YAG laser into six beams. The laser beams are, by means of optical fibers and collimating-focusing optics, transferred to the surface to be machined. Thus multiple grooves can be machined simultaneously. For demonstration, 100-μm-wide grooves are simultaneously machined into a SnO(2) thin film deposited on a glass substrate. The resulting grooves are well isolated. This result shows that the technique could be used, for example, in solar cell manufacturing to increase the efficiency of laser scribing.     

Dynamics of glucose-induced insulin release from mouse islets transplanted under the kidney capsule

Mouse pancreatic islet grafts under the kidney capsule of syngeneic hosts were removed and perifused in vitro 1-40 weeks after the transplantation. In comparison with fresh islets, 12- to 40-week-old grafts exhibited an attenuated first phase of glucose-stimulated insulin release. In grafts 1, 12, 28, or 40 weeks old, but not in fresh islets, the mean secretory rate during the initial 10 min of stimulation was significantly lower than that during the subsequent 15 min. When expressed in relation to insulin content, the insulin output in response to 11 mmol/L glucose was no less from grafts than from fresh islets; in grafts 12 or 40 weeks old at 16.7 mmol/L glucose, the fractional output above baseline was significantly diminished during the initial 10 min, but not subsequently. Immediately on switching from basal to stimulatory glucose concentration, there was a transient drop in insulin secretion from the grafts, especially after more than 12 weeks of transplantation and in response to 16.7, as compared with 11, mmol/L glucose. When glucose was switched back from stimulatory to basal concentration, grafts also frequently exhibited a transient increase in the insulin secretory rate. Neither initial drops nor "off responses" were seen in untransplanted islets. The modifications of the secretory dynamics in islet grafts suggest that transplantation influences the balance between the stimulatory and inhibitory influences of glucose on the beta-cell's secretory machinery.     

The Effect of Subfilter-Scale Physics on Regularization Models

The subfilter-scale (SFS) physics of regularization models are investigated to understand the regularizations’ performance as SFS models. Suppression of spectrally local SFS interactions and conservation of small-scale circulation in the Lagrangian-averaged Navier-Stokes α-model (LANS-α) is found to lead to the formation of rigid bodies. These contaminate the superfilter-scale energy spectrum with a scaling that approaches k ⁺¹ as the SFS spectra is resolved. The Clark-α and Leray-α models, truncations of LANS-α, do not conserve small-scale circulation and do not develop rigid bodies. LANS-α, however, is closest to Navier-Stokes in intermittency properties. All three models are found to be stable at high Reynolds number. Differences between L ² and H ¹ norm models are clarified. For magnetohydrodynamics (MHD), the presence of the Lorentz force as a source (or sink) for circulation and as a facilitator of both spectrally nonlocal large to small scale interactions as well as local SFS interactions prevents the formation of rigid bodies in Lagrangian-averaged MHD (LAMHD-α). LAMHD-α performs well as a predictor of superfilter-scale energy spectra and of intermittent current sheets at high Reynolds numbers. It may prove generally applicable as a MHD-LES.     

Digital Game Dynamics Preferences and Player Types

In this study, we examine digital game preferences by identifying game dynamics, i.e. player–game interaction modes, of 700 contemporary digital games, and players' (N = 1717) desire to play games with specific types of dynamics. Based on statistical analysis of the data, 5 game dynamics preference categories (“assault,” “manage,” “journey,” “care,” and “coordinate”) and 7 player types were revealed. The results show that identifying player types requires including both preferred and undesired game dynamics categories in the analysis. The findings unveil digital gaming as a more multifaceted phenomenon than common stereotypes suggest. The original game preferences model we present in this study can be conceptualized as a complementary approach for motivations to play and player behavior studies.     

Classification of metabolic and respiratory demands in fire fighting activity with extreme workloads

Fire fighting work comprises work tasks requiring an energy yield at maximal or close to maximal levels of the individual. Due to the very nature of fire fighting more complex physiological variables are difficult to measure. We measured metabolic and respiratory responses in 15 male, professional fire fighters during simulated work tasks on a test ground. Work time was on the average 22 min with individual components of work tasks lasting 2-4 min. The mean oxygen consumption for the whole exercise (22 min) was 2.75+/-0.29 l/min. The most demanding work task demanded an oxygen uptake of 3.55+/-0.27 l/min. Corresponding values for respiratory minute volumes were 82+/-14 and 102+/-14l/min, respectively. Heart rates averaged 168+/-12 for the whole test and 179+/-13 beats/min for the heaviest work task. Two new classes for classification of intensive and exhausting, short term physical work are proposed for inclusion in ISO8996 and values for relevant parameters are proposed.     

Voltage sensitivity of the osteoclast calcium receptor

We demonstrated previously that osteoclasts possess a divalent cation-sensitive "receptor", the Ca2+ receptor. Activation of the Ca2+ receptor by the surrogate cation Ni2+ was shown to elicit an increase in cytosolic [Ca2+] to a peak value followed by an exponential decline. In the present study we examined the influence of surface membrane voltage on the kinetics of Ca2+ receptor inactivation. The K+ ionophore, valinomycin was applied to intercept the declining phase of the cytosolic [Ca2+] transient elicited by application of between 50 microM- and 5 mM-[Ni2+]. This resulted in a sustained elevation of cytosolic [Ca2+] or even a 'hump' followed by a gradual decline. Such a kinetic alteration persisted in a Ca(2+)-free solution, but was abolished in high extracellular [K+] (105 mM). Thus, we demonstrate for the first time to our knowledge, a modulatory effect of membrane potential on the function of the osteoclast Ca2+ receptor.     

Predicting dementia from the Mini-Mental State Examination in an elderly population: the role of education

Steroid hormone regulation and cell-type specific expression of the jun-D protooncogene in rat uterus was examined. Adult, ovariectomized rats were injected with progesterone, testosterone, 17beta-estradiol (E2-17beta), 16alpha-estradiol (E2-16alpha), dexamethasone or cycloheximide. Uteri were collected between 0 and 6 h post-treatment. Northern blot analysis of uterine RNA revealed that induction of jun-D was specific for estrogenic steroids, as progesterone and testosterone had no effect on expression of this member of the jun gene family. Treatment with E2-17beta increased jun-D mRNA levels by approx. 5-fold, with expression reaching peak levels at 3 h after treatment and declining thereafter. Administration of E2-16alpha, a short-acting estrogen that does not cause uterine cell proliferation, increased expression of jun-D but with different kinetics compared to the long-acting E2-17beta. The mRNA levels of jun-D increased by 3-fold 1 h after administration of E2-16alpha but declined soon after. Slight induction of jun-D mRNA by dexamethasone was apparent, but to a much lesser extent compared to estrogen. The protein synthesis inhibitor, cycloheximide, did not block jun-D induction, indicating that this is an "immediate early" response. Expression of Jun-D protein was examined by immunohistochemical methods. E2-17beta treatment activated jun-D primarily in the nuclei of luminal and glandular epithelial cells of the endometrium. These results demonstrate that hormonal induction of jun-D is specific for estrogens and that uterine expression of this protooncogene occurs in a cell-type specific manner.