The inset in Fig. 2A shows a photomicrograph of a cross-section through the area studied that nicely illustrates the CO-stained clusters in the central region. This 100-micron-thick see more section is shown in Fig. 2B in relationship to the surrounding GN and STN. We subdivided the middle region

of CN into 3 zones: a central zone that contains CO-stained barrelettes, a middle zone adjacent to GN, and a lateral zone that extends toward the dorsomedial tail-like region and continues medially where it overlies the cluster-containing central zone. Electrophysiological recording was used to explore these zones, and the resulting physiological map is illustrated in a matrix-like format in Fig. 2C. Electrode penetration no. 1 recorded receptive fields on the hindlimb

and trunk, and this penetration was localized to GN. Penetration no. 2 passed through the medial zone where receptive fields on the ulnar forearm and upper arm, ulnar wrist, and digit and palmar pads were encountered; one dorsomedial site received input from AG-14699 the shoulder and body. Penetration nos. 3 and 4 passed through the central zone where receptive fields were localized to the glabrous digits and pads; sites responsive to dorsal digit input were found superficially in the lateral zone. Penetration no. 5 passed through the lateral zone where receptive fields were found on the radial wrist, radial upper arm, and shoulder; deeper in the penetration, receptive fields were found on dorsal and glabrous digits. A caricature of CN has Epothilone B (EPO906, Patupilone) been

superimposed on the matrix diagram, but appears distorted due to the inherent distortion in the individual cell sizes of the matrix, which is based on the number of receptive fields encountered at each matrix site. A summary map of the forelimb representation that incorporates receptive field data obtained from the 5 forelimb-intact rats is shown in Fig. 3. The receptive fields from each animal have been superimposed on a standardized schematic drawing of CN derived from a smoothed averaged outline of the 5 forelimb-intact CN maps, and this is shown in Fig. 3A. The central zone consists of CO-stained clusters and their immediate surround that is readily demarcated. The lateral edge of the medial zone has been arbitrarily established by placing a 126° line (arrow) that passes through the dorsomedial extent of the central zone and runs parallel to the lateral border that is formed at the CN/GN junction. This line also forms the medial border of the lateral zone. At the lateral edge of the lateral zone, another line is drawn at a 57° angle that forms the base of dorsolateral tail region. Electrode penetrations passing through the medial zone encountered receptive fields on the ulnar aspect of the upper arm, forearm, and wrist, while scattered sites were found in the dorsal-most part that were responsive to input from the shoulder.

(8). This “perfect model” of correlation should be free of bias because the numerator is a function of the model only ( Fig. 11). The variance of the costR¯

across the KPP parameter experiments (Exps. 4–22), divided by the variance of the blended wind experiments (Exps. 23–42), approximates a signal to noise ratio. The result is 0.86, meaning the perfect model correlation cost is more sensitive to blended wind forcing than to KPP perturbations. The cost function is likely most sensitive to parameters that control the physical processes involved in the τ-SST correlation. The greatest cost(R, r) sensitivity – as measured by the difference in cost between its upward and downward perturbations – is to the critical gradient Richardson number, BMS-754807 Ri0 ( Fig. 10b). Shear diffusivity beneath the boundary layer, vs, is modeled as a function of the local gradient Richardson number, Rig. Ri0 modulates the magnitude of shear diffusivity vs for a given amount of vertical shear: vs peaks when Rig = 0 and diminishes to zero when Rig = Ri0. When Ri0 is lowered (Exp. 7), vertical diffusivity vs

is Selleck AZD6244 greatly reduced, and model correlation R decreases. In contrast, increasing Ri0 allows for diffusivity vs over a broader range of Rig, which has little effect on R ocean-wide. While the τ-SST correlation sensitivity ( Fig. 6) and the correlation-based cost [cost(R, r)] sensitivity ( Fig. 10b) reflect ocean-wide patterns, the balance of the processes influencing the τ-SST correlation likely varies temporally and spatially. Indeed, sensitivity to Ri0 is highest near the equator in the Central and Eastern Pacific Bacterial neuraminidase ( Fig. 12) in the area of the Pacific cold tongue, where upwelling from the interior may play a role in the regulation of SST. The model boundary layer is also at its shallowest in this region, with depths averaging 10–25 m, so turbulent eddy penetration into the interior is plausible. Near the equator, wind direction, which is not directly included in the cost function, may also be an important control on

SST, as easterly winds cause upwelling from the thermocline, and westerly winds impede it. Interestingly, despite not including wind direction in the cost function, observational correlation r and model correlation R are enhanced along the equator ( Fig. 4). This may reflect the dominance of the pattern of easterly winds and the associated divergence and upwelling. It may also reflect the role of the Equatorial Undercurrent in enhancing shear in this area. Because some of the highest correlation-based cost sensitivities are to the structure function for scalars in unstable conditions (ϕsunstϕsunst) and the nonlocal transport term (γs) ( Fig. 10.b. [experiments 13–14 and 15–16]), which are nonzero only in convective conditions, the cost function is likely sensitive to the parameterization of wind-driven evaporation and convection, rather than solely to wind-driven shear turbulence.

Only sustained proliferation in the presence of an inflammation-rich microenvironment is reported to potentiate and/or promote tumor progression ( Coussens and Werb, 2002). Therefore, the lack of hyperplasia and the moderate/marked histiocytic infiltration in the 2-year NTP (2008) bioassay may not be sufficient to promote intestinal cancer in the rat following prolonged SDD exposure. 2 TF analysis also suggests that TP53 and RB1 tumor suppressor activities are inhibited

Volasertib in the mouse ( Table 4). Coupled with MYC activation in both species, the mouse is potentially more at risk for tumor development due to increased oncogene activity and decreased tumor suppressor gene activity. Induction of oxidative stress response genes and changes in GSH and GSSG levels suggest possible oxidative DNA damage. However, there is no increase in intestinal 8-OHdG DNA damage (De Flora et al., 2008, Thompson et al., 2011b and Thompson RG7204 purchase et al., 2012), possibly due to adaptation following long term exposure. Nevertheless, SDD altered the expression of DNA damage and modification genes, including Myc-regulated Apex1, which repairs damaged DNA ( Gelin et

al., 2010 and Watson et al., 2002). In the rat, DNA damage differential gene expression was the greatest at day 8 with negligible changes (at low doses) at day 91. In contrast, the mouse exhibited sustained (albeit lower relative to day induction of DNA damage and repair genes at 91 days ( Kopec et al., 2012), consistent with intestinal tumor development at later time points. This is consistent with gene expression being a more sensitive biomarker for oxidative DNA damage compared to other endpoints like 8-OHdG levels ( Rusyn et al., 2004). Comparative analysis identified several divergently expressed orthologs (Ccl24, C3, Areg, Wfdc1, and Slc25a25). Doxacurium chloride Ccl24, involved in eosinophil recruitment, is induced by IL-4 ( Lezcano-Meza et al., 2003 and Schaefer et al., 2006), consistent with Ccl24

mRNA repression and down-regulation of IL-4 levels in the rat duodenum ( Thompson et al., 2011b and Thompson et al., 2012). Moreover, the rat showed enrichment of complement activation functions with C3 induction, which was repressed in the mouse. C3 is induced by IL-1α in human kidney proximal tubular epithelial cells ( Gerritsma et al., 1996) and by TNFα in human gastric cancer-derived cells ( Kitano and Kitamura, 1993). C3 induction in the rat is consistent with IL-1α induction in the duodenum ( Thompson et al., 2012), while C3 repression is in agreement with decreased TNFα cytokine and mRNA levels in the mouse duodenum ( Kopec et al., 2012 and Thompson et al., 2011b). Although clinical studies show activation of the complement immune system in cancer patients, tumor cells may develop alternative mechanisms to inhibit complement activation ( Pio, 2006). Moreover, complement inhibitors facilitate tumor growth ( Caragine et al.

1). A 1/20 sloping beach was constructed from concrete. This slope angle is consistent with previous studies where mild slopes have varied from 1/15 (Li and Raichlen, 2003), to 1/20 (Synolakis, 1987) to 1/24 (Klettner, 2010), to 1/35 (Grilli et al., 1994). The water height was measured using 12 resistance probes

distributed along the length of the flume and a probe monitor (manufactured Selleckchem Ribociclib in-house by HR Wallingford). The resistance probes were calibrated prior to each series of experiments due to their sensitivity to the conductivity of water. The sampling frequency was 50 Hz (so a temporal resolution of ±0.02 s), and the accuracy of wave elevation measurements was ±0.005 m. Runup was measured directly using a horizontal tape measure along the flume wall and recording the maximum penetration point of the first swash (accuracy ±0.01 m), along the centre line of the channel i.e., mid-distance between the mTOR signaling pathway flume walls, in order to avoid edge effects. For the runup tests presented in this paper, the surface elevation nearest the wave generator was used to determine the wave parameters (see Fig. 1), and the ratios of a/ha/h ranged between 0.02 and 0.18, for both elevated and N-waves. The advantage of the adopted pneumatic generator is that long and leading

depressed waves could be generated and were stable over the flume length. The wavelengths reproduced were much longer than the ones previously studied. The disadvantage was that some wave reflection occurred at the beach when elevated and leading elevated N-waves were created, due to the relative length of the waves. The measurement of runup is important for comparing the characteristics PRKACG of the present waves with existing studies. Runup was estimated from the measured runup length RlRl and converted to a vertical distance using: equation(7) R=Rltanβ.R=Rltanβ.Wave period and wavelength were retrieved from the wave elevation time series. In many cases the second half of the positive part of the wave does not strictly correspond to the direct signal, due to the reflected waves travelling back from the beach. The period T   and wavelength L   are calculated

using the first half of the positive wave, assuming symmetry (a schematic graph within Fig. 1 illustrates the method used to estimate the wave period): equation(8) T=2(tηmax-t0),T=2tηmax-t0, equation(9) L=cpexpT.L=cpexpT.In (8), tηmaxtηmax is the time of occurrence of the wave peak, and t0t0 corresponds to the time when the value of the wave elevation is 1% of the maximum wave height (tηmax>t0tηmax>t0 and we set T1=tηmax-t0T1=tηmax-t0) prior to tηmaxtηmax. In (9), cpexpcpexp is the wave speed, determined from the experiments, by calculating the temporal correlation between adjacent wave probes. For N-waves, the trough does not trigger any reflections from the slope, so the parameters corresponding to the negative part of the wave are calculated on the full negative profile.

The dissipative term FL includes the bottom friction. It has been dropped

here, so that FL = 0, because the friction will be taken into consideration in the sediment transport module. After simplifying assumptions concerning the small-amplitude wave motion and gentle bottom changes, the governing set of equations driving the orbital motion takes the following form: equation(6) ∂2ξ∂t2+g∂ζL∂x=0,∂2ξL∂t2−∂∂xgh∂ξL∂x=0, where ξ and ζL denote the depth-averaged horizontal and vertical watersurface Doxorubicin clinical trial particle displacements respectively, g is the acceleration due to gravity and h is the still water depth. In an earlier paper (Kapiński & Kołodko 1996) the governing equations were derived for simplified conditions in which the bathymetry consists of two parts: (a) a shallow water area with a constant bottom depth, and (b) a beach slope with a constant inclination. This leads to the following equation: equation(7) R/H=J0βrl+iJ1βrl−1=J02βrl+J12βrl−0.5 where R/H – relative wave run-up height, In the hydrodynamic model the linear shallow-water wave theory has been adopted and applied to describe the learn more wave motion on a beach face. So, the limitations of the validity concerning the swash zone

are the same as for the theory extended to this area. Shuto (1967) observed that the generated wave train in the Lagrangian description differs slightly from the sinusoidal profile. This seemingly minor discrepancy significantly changes the water flow pattern (Kapiński 2006). Therefore, a transfer function of the free water elevation at the seaward boundary was derived and applied here. As a consequence, both modelled initial wave profiles and the water motion are described by Methane monooxygenase the first harmonics as realized in the traditional Eulerian description.

Such advantages of the Lagrangian wave approach, like direct simulation of orbital motion and tracking the motion of a moving shoreline, have been retained here. The forecasting of the cross-shore profile change of a beach face is based on the flow velocity field. The computational domain comprises the permanently submerged part of the beach slope as well as the part that is alternately wet and dry. First, time-dependent orbital velocities ∂ξ/∂t are transformed to flow velocities U. This is carried out for selected locations on the beach slope, from the slope toe to the wave run-up limit. Next, these velocities are used to compute magnitudes of the friction velocity uf, which is the direct driving force for sediment motion. Thus, the Lagrangian displacements ξ are indirectly used in section 2.2 to predict the Eulerian sediment transport rates and bottom profile changes at fixed points on the beach face.

DMH was purchased from Sigma (St. Louis, MO, USA). Male Wistar rats (150–160 g) were housed in a room at a mean constant temperature (22 ± 2 °C) with a 12-h light–dark cycle. They had free access to standard pellet chow and water. Experimental protocols were approved by the Animal Care and PD-1/PD-L1 activation Use Committee (no. 150/2008) from the Medical School, University of São Paulo. Animals were randomly allocated into four groups with six rats in each one. CTRL/C was the control group; CTRL/D received a single dose of DMH (125 mg kg−1; intraperitoneal; i.p.) in the second week from the beginning of the experiment; FLX/C was given a daily

FLX-gavage (30 mg kg−1) for 6 weeks; FLX/D received daily FLX-gavage and a single dose of DMH. Rats were euthanized after 6 weeks from first FLX-gavage. Individual autopsies were subsequently performed, being the colon tissue piecemeal between frozen pieces (−80 °C) and fixed samples in formalin buffered solution by

24 h, as we previously described (Garcia et al., 2006 and Kannen et al., 2011). As we previously described (Moreira et Selleck JNK inhibitor al., 2007), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were quantified in frozen colon samples. They were quantified by comparing the peak areas to standard curves by the computer program Class-LC 10A (Shimadzu, Japan), being the concentrations expressed in ng mg−1 of colon tissue. FLX and N-FLX were isolated from colon tissue samples (30 mg) according to our own method adapted (Borges et al., 2009). A Quattro LC triple quadrupole mass Masitinib (AB1010) spectrometer (Micromass, Manchester, UK) was interfaced via an electrospray ionization (Z-ESI) probe with a Shimadzu (Kyoto, Japan) liquid chromatography, equipped with a LC-AT VP solvent pump unit. FLX, N-FLX, and IS were separated on LiChrospher® 100 PR-8, 5 μm, 125 mm × 4 mm column (Merck, Darmstadt, Germany). A C8 guard column (4 mm × 4 mm i.d., Merck) was used. Samples were separated under isocratic conditions

using a mobile phase consisted of acetonitrile:0.1% trifluoroacetic ammonium acetate aqueous solution (60:40, v/v), at a flow rate of 1.3 mL min−1. Quantification was performed by multiple reaction monitoring (MRM) of the precursor ions and their corresponding product ions. The precursor-to-product ion transitions were monitored at m/z 310 > 44 for FLX, m/z 296 > 134 for N-FLX, and m/z 269 > 182 for IS. A MassLynx data sampling and processing system (Micromass) version 4.1 was used. Stock solutions of FLX and N-FLX containing 200 μg mL−1 were prepared in methanol. IS solution was prepared in methanol at 0.10 μg mL−1. Calibration curves were obtained by analyzing spiked colon samples in duplicate over the concentration range of 6–500 ng of the drug per mg of colon. Total RNA was extracted from frozen colon tissue samples (30 mg) using Trizol (Invitrogen, Carlsbad, CA, USA), according to the manufacturer’s instructions.

The reaction velocity is directly proportional to the enzyme concentration showing a linear dependence, in contrast to the hyperbolic dependence on substrates and cofactors ( Figure 6B). Therefore, the reaction velocity can be regulated by varying the amount of enzyme, adding more if the reaction proceeds too slowly, and less if it is too fast. In general too low amounts of the enzyme are less a problem than too high amounts. The latter convert learn more the substrate instantly, already during the mixing and starting procedure and, at the worst, the reaction will already

be finished at the onset of recording and no reaction can be observed. In such a case inexperienced experimenter add even more enzyme, supposing

a too low enzyme activity. Often a distinct enzyme amount is indicated in the assay protocol; it can also be calculated, as described in the following section. However, since the activity of enzyme preparations does not remain constant, but depends on different conditions, like mode and time of storage, preliminary tests for the control of the actual enzyme activity are strongly recommended. Directly related with the enzyme amount is the observation time. Although defined time periods (seconds or minutes) are specified for calculation of the enzyme activity, there exists no general rule for the time selleck products observing the reaction, only that it must be within the area of the initial linear progression ALOX15 of the velocity, while the following non-linear phase will yield erroneous results. It may be supposed, that the initial

phase should be rather short, but this is not indispensable. If in a special assay the linear initial phase lasts for only 10 s, this will be a barely observable period for the conventional assay methods. However, tenfold reduction of the enzyme amount will expand the linear period to 100 s, a hundredfold reduction even to about 17 min, a fairly long time for observation. But, on the other hand to obtain the same intensity for the signal the long observation time of 17 min, instead of 10 s, must be accepted. The reaction proceeds very slowly and, finally, with very low enzyme amounts the signal will not be detectable at all. To intensify the signal the sensitivity of the detection method can be increased, but only within a distinct range, until the basic noise of the method exceeds the signal intensity (Figure 2). Therefore a suitable combination of enzyme amount and observation time should be tried out; longer observation times save enzyme, but are time consuming. Computer-controlled instruments like spectrophotometers usually have available programs calculating the enzyme velocity immediately after the assay. This is convenient, but should not be used uncritically.

The PLSS sections, the census tract polygons, and the GUs of California C646 price (Johnson and Belitz, 2014) were merged to create a composite polygon dataset. The area of each new resulting sliver polygon was calculated. Using this calculated area and the density function for wells within a section (ρWs)(ρWs) the number of domestic wells per sliver polygon was computed. Similarly, the number of households using domestic well water were also computed

for any given boundary. This was accomplished by using the number of domestic wells in a polygon and multiplying it by the CRcCRc essentially assigning population to only domestic wells where applicable. In essence, the township ratio estimates the number of wells in a section. The census ratio estimates the number of households to assign to each well. In census tracts that did not contain any domestic wells, households were distributed uniformly. Summing up the domestic wells or households for all the polygons within a given geographic boundary will result in the number of wells or households for that geographic boundary. The number of households were summed for each Groundwater Unit and ranked. Aggregating to Groundwater Units enabled the comparison between units and the ability to differentiate high-use areas

and low-use areas. MAPK inhibitor Of the 741,262 WCRs provided by DWR, 635,736 WCRs were geocoded (Fig. 1). Most were located to the center of a 1 mi2 PLSS section, and some were located to the center of the 1/16th of a section, mostly in the Central Valley. The remaining WCRs could not be geocoded Amisulpride because they were missing or had incomplete PLSS information. San Luis Obispo County can be seen with an absence of plotted WCRs, particularly noticeable at the county margins. The number of WCRs in each of the 4692 townships ranged from zero to 8212, with an average of 134 WCRs. The spatially distributed, randomized system for selecting a WCR resulted in 41,671 WCRs being viewed, approximately 6% of the total number of WCRs (Fig. 2). The 41,671 WCRs viewed were classified into 9 categories: domestic (13,557), monitoring (8164),

irrigation (4257), test (2162), municipal supply (814), industrial (397), stock (307), and other, including cathodic protection and oil and gas (7128). 4885 of the viewed WCRs did not contain a drillers’ log. The domestic wells were further subdivided into individually owned wells (10,839) and wells owned by entities such as corporations (2718) on the basis of owner information reported on the WCR. The individually owned domestic wells (Fig. 2) were used in the subsequent analyses and are referred to simply as domestic wells in this paper. The total number of townships with one or more domestic wells was 2369, slightly more than ½ the state’s townships, and the township ratio in these townships ranged from 0.01 to 1, with an average value of 0.526 (Fig. 3).

Subjects were randomly assigned to receive subcutaneous injections of either placebo or denosumab 60 mg every 6 months for 36 months. All women received daily supplementation of calcium (≥ 1000 mg) and vitamin D (≥ 400 IU). The methods and results of the overall study have been previously reported [20]. Study centers in the FREEDOM study with expertise

and access to a qualified QCT scanner invited subjects to participate in a QCT substudy of the lumbar spine and hip measurements. The methods and primary results selleck kinase inhibitor of this QCT substudy have been reported [25]. In this substudy of the FREEDOM study, hip QCT scans were used to non-invasively further assess changes in hip vBMD and BMC associated with placebo and denosumab treatment over 36 months. The FREEDOM study included postmenopausal women aged 60 to 90 years with a DXA BMD T-score

of <− 2.5 at either the lumbar spine or total hip, and not <− 4.0 at either site. Women were excluded if they had any severe or > 2 moderate vertebral fractures, had conditions that affected bone metabolism, had taken oral bisphosphonates for > 3 years, or received intravenous bisphosphonates, fluoride, or strontium treatment for osteoporosis Sorafenib within the last 5 years. The protocol was approved by an independent ethics committee or institutional review board at each study site prior to study commencement. The study was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki, and registered at ClinicalTrials.gov (NCT00089791). QCT scans of the left hip were performed at 120 kV with a pitch of 1 using 170 mAs, reconstructed using a 200 mm field of view, a slice thickness of 1 or 1.25 mm, and a medium kernel at baseline, and at months 12, 24, and 36.

QCT technicians were trained on the techniques and procedures, including Pyruvate dehydrogenase lipoamide kinase isozyme 1 subject positioning and phantom calibration scanning. Scanner stability and cross-calibration were longitudinally assessed during the study. Scans were analyzed in a blinded-to-treatment manner by a central laboratory (Synarc Inc., Newark, CA, USA) and analyzed using MIAF software. MIAF enables automated 3-dimensional segmentation of the hip, dividing the proximal femur into anatomical and compartment regions. In this study, the total hip volume of interest (VOI) was analyzed, which is approximately equivalent to the total hip region of interest with DXA. The QCT total hip integral VOI was segmented into trabecular, subcortical, and cortical bone compartments (Fig. 1). The periosteal and endosteal surfaces defining the cortical compartment were segmented as described previously [27]. Then the trabecular compartment was obtained by a homogeneous 2 mm peeling process from the endosteal surface. The selection of 2 mm peeling was based on phantom measurements to account for blurring artifacts introduced by the limited spatial resolution of the CT scanner.

, 2009); however, recent studies in murine models of asthma have suggested that AE might have a possible anti-inflammatory effect on chronic allergy airway inflammation (Pastva et al., 2004, Vieira

et al., 2007, Vieira et al., 2011 and Silva et al., 2010). Our group and others have shown some effects Bortezomib cost of AE on chronic allergic lung inflammation (Pastva et al., 2004, Vieira et al., 2007, Vieira et al., 2008, Vieira et al., 2011 and Silva et al., 2010). However, many criticisms have been raised concerning the mouse model of asthma involving the use of ovalbumin. Wenzel and Holgate (2006) suggest that mouse models of asthma provide insights into immunologic processes but have shortcomings that continue to limit the understanding and treatment of human asthma. Several reasons are given as limitations: (i) mouse models of asthma require artificial intra-peritoneal allergen sensitization and adjunctive stimulation and provoke a systematic BMS-777607 ic50 rather than a

pulmonary allergic sensitization, which can even extend to include cardiovascular effects (Bice et al., 2000); (ii) the site of inflammation is mainly located in the parenchyma and the lung vascular vessels instead of the airways as occurs in human asthma (Wenzel and Holgate, 2006); and (iii) mice have lower levels of eosinophils in the airways following antigen challenge compared to guinea pigs and humans with asthma (Korsgren et al., 1997). Our results showed that sensitized guinea pigs submitted to AE training had a reduction in eosinophil migration as well as in the migration of lymphocytes to the airways,

which reinforced previous studies showing that AE reduces eosinophilic inflammation in mouse models of asthma (Pastva et al., 2004 and Vieira et al., 2007). However, the reduction in lymphocyte migration to the airways following AE was previously unknown and is interesting because lymphocytes orchestrate eosinophilic migration. To better understand the effect of AE on reducing eosinophilic migration, we quantified the expression of Th2 cytokines. The results show that AE reversed the OVA-induced expression of IL-4 and IL-13, suggesting an important effect of AE on the pro-inflammatory cytokines involved in Astemizole allergic airway inflammation. Despite the fact that AE has been shown to reduce IL-4 expression in mouse studies (Pastva et al., 2004, Vieira et al., 2007, Vieira et al., 2008 and Vieira et al., 2011), this is the first study in guinea pigs to show that AE can also reduce the expression of IL-13. IL-13 is an important interleukin in the pathophysiology of asthma that modulates eosinophilic inflammation and mucus hypersecretion (Zhu et al., 1999). In addition, a study by Willis-Karp et al. demonstrated that these pro-asthmatic effects of IL-13 are independent of IgE production (Wills-Karp et al., 1998).