Relative mRNA levels were measured with a SYBR green detection sy

Relative mRNA levels were measured with a SYBR green detection system using ABI 7500 Real-Time PCR (Applied Biosystems, Foster City, CA). All samples were measured in triplicate. The expression of each gene was calculated as a ratio compared with the reference gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [5′-AAC TTT GGC ATT GTG GAA GG-3′ (forward) and 5′-GTC TTC TGG GTG GCA GTG AT-3′ (reverse)] and expressed as fold change

relative to C-SAL. Two-way ANOVA followed by Tukey’s test was used to compare parametric data. For non-parametric MK-2206 concentration data, two-way ANOVA on ranks followed by Dunn’s post hoc test was selected. The significance level was always set at 5%. Parametric data were expressed as mean ± standard error mean (SEM), while non-parametric data were expressed as median (interquartile range). All tests were performed using SigmaStat 3.1 (Jandel Corporation, San Raphael, CA, USA). The pool of intravenously injected BMDMC was characterized by flow

cytometry showing the following subpopulations: total lymphocytes (CD45+/CD11b−/CD29−/CD34−  = 29.7%), T lymphocytes (CD45+/CD3+/CD34− = 5.4%), T helper lymphocytes (CD3+/CD4+/CD8− = 2.4%), T cytotoxic lymphocytes (CD3+/CD4−/CD8+ = 2.3%), monocytes (CD45+/CD29+/CD11b−/CD34−/CD3− = 4.9%), neutrophils (CD45+/CD11b+/CD34−/CD29−/CD14−/CD34−/CD3− = 50.1%), hematopoietic progenitors (CD34+/CD45+ = 0.3%), and other progenitors cells (CD45− = 3.8%). Echocardiography showed that E-SAL had greater right ventricular wall thickness and right ventricular area compared to C-SAL; BMDMC administration significantly reduced these parameters (Table Selleckchem PARP inhibitor 1, Fig. 2). There was no difference between any groups regarding left ventricular repercussions (area, cardiac output or ejection fraction). Morphometric examination of lungs demonstrated that the mean linear intercept, the fraction area of alveolar collapse, hyperinflation,

mononuclear cells and neutrophils in lung tissue, as well as collagen fiber content in alveolar septa Baricitinib and pulmonary vessel wall were higher in E-SAL than C-SAL group. Elastic fiber content was lower in E-SAL than C-SAL, and elastic fiber breakdown was more evident in E-SAL (Table 2, Fig. 3). BMDMC therapy minimized the fraction area of alveolar collapse, hyperinflation, and neutrophil infiltration, the amount of collagen fiber in the alveolar septa and pulmonary vessel wall (Table 2, Fig. 4). It also prevented changes in the fraction area of mononuclear cells and elastic fiber content in the alveolar septa and pulmonary vessel wall. E-SAL group presented increased number of lung apoptotic cells (median [25th–75th interquartile range]: 2.0 [1.75–2.25]) compared to C-SAL (0 [0–0.25]. BMDMC therapy led to a reduction in the number of lung apoptotic cells (1 [0.75–1]) (p = 0.03). Similarly, caspase-3 expression was lower in E-CELL compared to E-SAL ( Fig. 5).

Caveman should have used a numeral (he should have said ‘…three o

Caveman should have used a numeral (he should have said ‘…three of the fences’ rather than ‘…some of the fences’). This response was scored as incorrect. The experimenter then explained that Mr. Caveman does not use number words because he already knows them and he wants to learn other ways of saying things, using words like ‘some’ and ‘all’. After this explanation, the participant did not object again Raf inhibitor to the use of a quantifier instead of a numeral. Both children and adults were highly competent in the control conditions,

rejecting logically false utterances and accepting optimal (logically true and informative) ones at rates over 95%. The only two erroneous responses were elicited from one child rejecting one instance of a scalar expression in an optimal condition (as mentioned above), and another child rejecting one instance of a non-scalar expression in an optimal condition. Turning to responses to the critical underinformative utterances, all trans-isomer ic50 the adult responses were rejections or objections. However, the children rejected underinformative utterances at rates of only 29% (26% and 31% for scalar and non-scalar expressions respectively). Two Mann–Whitney U-tests reveal that the adults performed higher than the children in the underinformative

conditions for scalar and non-scalar expressions (both U > 4.95, p < .001, effect size r for non-parametric tests >.78; where >.10 may be considered a small effect, >.30 medium and >.50 large). Within the child group, further pairwise comparisons by Wilcoxon Signed Ranks tests reveal that children performed reliably higher in both the logically false and the optimal conditions compared to the underinformative condition, both for scalars and non-scalars (both W > 3.6, p < .001, r > .8, for false vs. underinformative; both W > 3.6, p < .001, r > .8

for optimal vs. underinformative respectively). Moreover, children’s performance did not significantly differ between scalar and non-scalar expressions in the underinformative condition (W = .84, p > .1). Moreover, the rates of rejection of underinformative utterances Bcl-w were reliably above what one would expect if there was no sensitivity to informativeness at all (=no rejections of underinformativeness: One-sample t-test, both t(19) > 3.1, p < .005, effect size Cohen’sd for parametric tests > .75). Let us also consider participant distribution to examine whether children are uniform in occasionally rejecting underinformative utterances, or whether they cluster in sub-groups. We classified children as consistently underinformative (rejecting 0–1 out of six underinformative utterances) or inconsistent (rejecting 2–4 out of six utterances) or consistently informative (rejecting 5–6 out of six utterances).

The sediments in the reservoir record the multiple ways that urba

The sediments in the reservoir record the multiple ways that urban activity can alter fluxes. Lower sedimentation rates and higher sediment-bound metals selleckchem concentrated early in the record when industrial activity was more prevalent in the watershed; higher sedimentation rates and lower metals registered in more recent times when population in the watershed increased and industrial activities and power generation declined. The reservoir sediment record, coupled with modeling

of modern watershed sediment fluxes, is also useful for guiding management and predicting geomorphic changes that may occur when the old dams are removed and channel connectivity is restored. At a much smaller scale, Mattheus and Norton employ sediment records and erosion modeling to examine sediment generation in urban forests. Their results suggest that urban forests, which cover nearly 30% of US urban areas (Nowak et al., 2001), have unexpectedly high erosion rates relative to other forested landscapes. The authors suggest that these high erosion rates may result from upslope impervious surfaces generating erosive stormwater, or a legacy of ZD1839 manufacturer forest harvest reducing the ecological complexity and erosion resistance of forested slopes. The contributions

by Mann and colleagues and Mattheus and Norton emphasize the importance of quantifying the heterogeneous impacts of human activities over time, even under relatively static land cover conditions. These studies also highlight important insights that can selleck be gained by coupling sediment flux models with empirical data collection. Such multiple method

approaches are an important way forward for anthropogenic geomorphology studies to not only explain past and present impacts, but to make predictions of future forms and processes given increasing interactions between humans and the Earth surface. “
“Wilderness is defined in the U.S. 1964 Wilderness Act legislation “as an area where the earth and the community of life are untrammeled by man, where man himself is a visitor who does not remain.” This is a slightly more poetic rendering than the usual dictionary definitions of “a tract or region uncultivated by human beings” or “an area essentially undisturbed by human activity together with its naturally developed life community.” The common thread in diverse definitions of wilderness is the absence of humans and their influences. Opinions diverge on how strictly to interpret influences, or even on whether wilderness is anything but a social construct or a romantic myth (Lowenthal, 1964).

Instead, the terrace failure shown in Fig 10b is an example of r

Instead, the terrace failure shown in Fig. 10b is an example of restoring and rebuilding of the walls, steps, and cisterns of an old terraced landscape originally planted with lemon trees that will be used as a vineyard. However, the collapse observed in Fig. 10b is indicative of the loss of local lore (oral communication) in building retaining stone walls and of the importance to properly regulate overland flow. The

literature review proposed in Section 1 and the practical examples described in Section 2 underline how human actions connected to the presence and maintenance Ferroptosis inhibitor drugs of terraced structures are capable of accelerating or diverting natural events such as landslides and land degradation. Connected to

these issues, the following section is divided in three parts: first are the non-structural management suggestions for the correct management of terraces; second are the structural measures to be implemented for the management of the dry-stone walls; third are the new remote sensing technologies, such as Airborne Laser Scanner (ALS) and Terrestrial Laser Scanner (TLS), for managing the critical issues related to the terrace landscapes, especially to better understand the surface drainage paths, which is a future challenge for terrace landscape management and planning. buy KU-55933 During the last century, the agriculture system has changed deeply with an increase in productivity.

The maintenance many of terraced structures became problematic due to the hard mechanization of these areas and the reduction of people in agriculture (Mauro, 2011). The rapid disappearance and undermanagement of the traditional terraced agricultural landscapes became a worldwide concern, and how to balance the needs between conservation and development has become a major policy issue. Non-structural management approaches have begun worldwide. In 2002, the Food and Agriculture Organization of the United Nations (FAO) launched the Globally Important Agricultural Heritage Systems (GIAHS) project, with the aim of mobilizing global awareness and support for dynamic conservation and adaptive management of agricultural systems and their resulting landscapes (Dela Cruz and Koohafkan, 2009). The cultural importance of the terraces was also underlined by UNESCO, which over the years has started projects for the management of world heritage sites of terraced areas (i.e., the Honghe Hani Rice Terraces in China, the Wachau Cultural Landscape in Austria, the Konso Cultural Landscape in Ethiopia, the Upper Middle Rhine Valley in Germany, the Tokaj Wine Region in Hungary, the Cinque Terre and Costiera Amalfitana in Italy, the Rice Terraces of the Philippine Cordilleras in the Philippines, the Alto Douro Wine Region in Portugal and the vineyard terraces of Lavaux in Switzerland).

Sand released by the erosion of paleo-lobes such as St George I o

Sand released by the erosion of paleo-lobes such as St George I or Sulina (Fig. 1) periodically transferred sand downcoast to construct baymouth barriers and forming the Razelm, Sinoe and Zmeica lagoons (Giosan et al., 2006a and Giosan et al., 2006b). If left to natural forces, such a large scale alongshore sediment transfer may begin as soon as the St. George II lobe is de facto abandoned ( Constantinescu et al., in preparation), once Sacalin Island will attach to the shore with its southern tip or will drown in place. For all periods considered in this study, the shoreline behavior generally

mirrored and was therefore diagnostic for nearshore morphological changes. One exception has been the region downcoast of the St. learn more George mouth where wave sheltering by the updrift delta coast and changes in coastal orientation led to the development of a more complex series of longshore transport cells and an alternation of progradation and retreat sectors. Also several other local mechanisms may be acting to reduce the erosion see more rates locally along the coast. For example, erosion appears to be minimal along the coast of the Chilia lobe where a series of secondary distributaries

still debouche small amounts of sediment. Controlled by the post-damming decrease in fluvial sediment, the sectors of the coast with natural deltaic progradation have shrunk drastically to the two largest secondary mouths of the Chilia distributaries that have become themselves wave dominated. The coast at the St. George mouth has been quite stable probably due to groin-type effects of the river plume and the mouth subaqueous bars and levees (Giosan, 2007). However, the dramatic increase in nearshore erosion

for the anthropogenic Guanylate cyclase 2C period was in large part due to the de facto abandonment of the St. George lobe ( Constantinescu et al., in preparation). Minor depocenters along the coast are not now the result of delta front development per se, but reflect either redirecting of eroded sediments offshore by the Sacalin barrier or trapping near large scale jetties. All in all, the dynamics of the Danube delta coastal fringe clearly shows that the natural pattern of delta coast evolution was a carefully balanced act of deposition and erosion rather than a uniform progradation of the shoreline. And this was aided not only by brute, direct fluvial sediment unloading at the coast but also by more subtle morphodynamic sediment trapping mechanisms. Still the overall budget of the deltaic coastal fringe was in deficit loosing sediment alongshore and offshore. When we take into account the long term history of the Danube delta in addition to insights gained in the current study, we can develop a novel conceptual understanding of its evolution as a function sediment partition between the delta plain and the delta coastal fringe as well as between major and minor distributaries.

Two proposed natural causes for an observed increase in CO2 aroun

Two proposed natural causes for an observed increase in CO2 around 8000 years ago (natural loss of terrestrial biomass and changes in ocean carbonate chemistry) are considered and rejected. Instead, the rise in CO2

is attributed to the widespread initial pre-industrial forest clearance in Eurasia associated with the expansion of agricultural landscapes (Ruddiman, 2003). This increase in CO2 is characterized as being “imperceptibly gradual, and partially masked by a larger cooling trend” (2003, p. 285). The supporting evidence offered for deforestation associated with agriculture being the cause of the observed CO2 rise at ca. 8000 B.P. is also admittedly limited: “these estimates of land clearance and carbon emissions are obviously just rough first approximations” (2003, p. 277), consisting of general observations regarding the DZNeP concentration initial expansion of agricultural societies out of the Near East into Europe and their subsequent intensification,

as well as similar but less well documented trends in China and India. Like Certini and Scalenghe, ecologists Christopher Doughty, Adam Wolf, and Christopher B. Field (2010) use a pedospheric ABT-263 research buy indicator to mark the beginning of the Anthropocene, but focus on a much smaller, regional scale of proposed human impact. Their proposed marker for the onset of the Anthropocene is a large increase in Birch (Betula) pollen from Alaska and the Yukon during a narrow 1000 year period at ∼13,800 B.P. They suggest that this increase in Betula modified the land surface

albedo (i.e. reduced reflectivity), resulting in a projected regional warming of up to 1 °C. Given the general temporal correlation between this documented increase in Betula and the extinction of mammoths, they hypothesize that reduced herbivory associated with the disappearance of megafauna played a causal role in the expansion of birch forests and the resultant rise in regional temperature levels. The extinction of mammoths is then linked to human predation, and they propose that humans contributed to global warming: We hypothesize that the extinction of mammoths increased Edoxaban Betula cover, which would have warmed Siberia and Beringia by on average 0.2 degrees C, but regionally by up to 1 degree C. If humans were partially responsible for the extinction of mammoths, then human influences on global climate predate the origin of agriculture. ( Doughty et al., 2010) They go on to conclude that this anthropogenic regional warming trend represents the onset of the Anthropocene: “Together, these results suggest that the human influence on climate began even earlier than previously believed (Ruddiman, 2003), and that the onset of the Anthropocene should be extended back many thousand years.” (Doughty et al., 2010).

70% was achieved using 10% of PVA without compromising protein st

70% was achieved using 10% of PVA without compromising protein stability. We tried to increase the protein loading to 5%, but surprisingly the encapsulation failed when the protein nanoparticles suspended in PLGA solution were added to the PVA solution. However, using PLGA with a co-polymer ratio of 50:50 resulted in nanoencapsulation, but the encapsulation efficiency needed improvement. PARP inhibitor drugs When we increased the volume of the diffusing phase to accomplish faster particle hardening,

the encapsulation efficiency increased substantially to >80% at a 1:40 volume ratio of dispersing-to-diffusing phase (Table 4). We also tested the polymer concentration in this context. It has been shown that a higher polymer concentration leads to higher encapsulation efficiency and larger size of the nanoparticles [31,32]. At a high PLGA concentration, the viscosity of the diffusing phase increases which

should result in improved encapsulation by reduction of lysozyme nanoparticles leaking into the dispersing phase. Indeed, we found increasing lysozyme encapsulation efficiency at increasing polymer concentration as expected (Table 5). In a similar fashion encapsulation efficiency was improved for a-chymotrypsin. Changing the polymer concentration proved only somewhat successful in this case, possibly because at increased PLGA concentrations the polymer shell thickness also increased [33]. The encapsulation efficiency remained with a maximum of 30% too low for practical purposes (Table 5). Reducing the particle size Selleckchem A 1210477 of a-chymotrypsin by employing a lower protein concentration of 15 mg/ml (Table 2) resulted in an improved encapsulation efficiency of 74% (Table 6). The data show how sensitive the results respond to encapsulation conditions in this method highlighting the fact that encapsulation likely has to be optimized in a similar fashion Cobimetinib cost as described here for other proteins. However, there are only a few processing parameters requiring adjustment

and the process is straight forward and reproducible as demonstrated by the small standard deviations obtained for encapsulation parameters under optimized conditions. The optimum conditions to encapsulate lysozyme and a-chymotrypsin in PLGA nanoparticles are summarized in Table 7. The size of the protein loaded PLGA particles obtained by dynamic light scattering was ca. 300–400▒nm in diameter (Table 7). However, while lysozyme encapsulation afforded a highly active enzyme, substantial enzyme inactivation and formation of buffer-insoluble aggregates were observed for a-chymotrypsin. The formation of buffer-insoluble aggregates and loss in specific activity found for a-chymotrypsin is similar to results obtained before upon a-chymotrypsin encapsulation in PLGA microspheres using a s/o/w technique [27,28,[34], [35] and [36]]. The use of stabilizing additives (e.g.

The three different formulations tested in this study were (a) fo

The three different formulations tested in this study were (a) formulation “Gelatin”: 260 mg Sunphenon 90DCF-T in gelatin capsules, (b) formulation “HPMCgell”: 260 mg Sunphenon-90DCF-T in HPMC capsules with Gemcitabine molecular weight gellan gum as the gelling agent and (c) formulation

“HPMC”: 260 mg Sunphenon-90DCF-T in HPMC capsules without gelling agent. All capsules were size 0 and transparent. The formulations were prepared manually using a capsule filling machine (Capsunorm 2000, Tecnyfarma, Barcelona, Spain). The compendial media – 0.1 mol/l hydrochloric acid (pH 1.2), acetate buffer (pH 4.5) and phosphate buffer (pH 6.8) – were prepared according to USP 32. Fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) were prepared from simulated intestinal fluid (SIF) powder (Biorelevant.com, Croydon, Surrey, UK) [11]. Capsule disintegration was tested according to USP 32 chapter <2040> with a disintegration tester ZT120 and tube/rack assembly Apparatus B (Erweka GmbH, Heusenstamm, Germany). Chapter <2040> also discusses the acceptance criteria for dietary supplements. The test for hard shell capsules was applied and as the USP advises to omit the

use of discs for botanical dosage forms; capsules were placed in a metal spiral capsule sinker (ProSense BV Dissolution Accessories, Oosterhout, LY294002 cell line the Netherlands) to prevent floating which is a slight modification of the description in <2040>. This modification avoids the mechanical impact discs during each stroke

and at the same time keeps the capsules submerged to ensure ample fluid contact. The recorded capsule disintegration time is the time at which the capsule was visually observed to be completely disintegrated, even if some pieces of the capsule shell remained on the mesh of the test basket. Disintegration of the formulations was assessed in two immersion fluids: the USP recommended 0.05 mol/l acetate buffer as well as in demineralised water, both preheated to 37 °C. All experiments were performed as n = 6 and the mean and standard deviation were calculated. A calibrated dissolution tester “VK 1700” (Varian Inc., Cary NC, USA) was used for GPX6 all dissolution studies. The formulations were tested using the paddle method plus sinker (USP Apparatus 2), employing 900 ml of dissolution medium equilibrated to 37 ± 0.5 °C and a rotational speed of 75 rpm. Spiral capsule sinkers (ProSense BV Dissolution Accessories, Oosterhout, the Netherlands) were used to prevent capsules from floating. Samples were taken after 5, 10, 20, 30, 45, 60 and 120 min by withdrawal of 2 ml at each sampling point and the volume withdrawn was replaced with fresh pre-warmed medium. Each sample was immediately filtered through a 0.2 μm PVDF filter (Type Acrodisc LC, Pall Life Sciences, Uithoorn, The Netherlands) and directly analyzed by HPLC and/or appropriately diluted with buffer media prior to UV–vis spectrophotometer analysis.

L’étude anatomopathologique de la lésion montrait qu’il s’agissai

L’étude anatomopathologique de la lésion montrait qu’il s’agissait d’une tumeur à cellules fusiformes dont le phénotype était celui des tumeurs stromales GIST. L’immuno-marquage montrait que les cellules étaient fortement positives pour les anticorps anti-CD 117 et anti-CD 34, faiblement positives pour l’antiprotéine S 100, et négatives pour les anti-actines

musculaires lisses alpha-desmine. L’index mitotique était inférieur à mitose/10 champs. L’évolution postopératoire a été favorable. Nous avons adressé le malade par la suite à un dermatologue pour prise en charge de sa maladie de Von Recklinghausen cutanée et nous avons proposé une surveillance annuelle par un entéroscanner. La neurofibromatose de type I,

appelée aussi périphérique ou maladie de Recklinghausen, concerne une naissance sur MDV3100 3000, résulte d’une transmission autosomique dominante, peut être sporadique, et implique une anomalie sur le chromosome 17. Les atteintes digestives de la maladie de Recklinghausen surviennent à l’âge moyen de la vie, cas de notre observation clinique, en général bien plus tard que les lésions cutanées, et BLZ945 research buy peuvent être divisées en quatre entités [1] : • les lésions du système nerveux digestif intrinsèque et de ses tissus de support ; Une atteinte digestive est présente chez environ 7 à 25% des malades atteints de maladie de Von Recklinghausen. À côté du tube digestif qui est le plus souvent concerné, le foie et le pancréas peuvent également être atteints [3]. La notion de malignité these doit être présente à l’esprit car globalement le risque de tumeurs malignes au cours de la maladie de Recklinghausen serait quatre fois plus élevé que dans la population générale [4]. Les circonstances diagnostiques des tumeurs stromales GIST sont variables : découverte fortuite, douleurs, syndrome de masse, anémie, hémopéritoine, et surtout hémorragie digestive qui est le symptôme le plus fréquent [1], [2] and [3].

Un des points particuliers de notre observation est la révélation de cette tumeur digestive de façon fortuite par un tableau de péritonite appendiculaire. Comme dans notre observation, la plupart d’entre elles présentent cependant le profil immuno-histochimique caractéristique des GIST, défini notamment par l’expression du marqueur C-Kit et de la protéine CD34 [3] and [4]. Toutes les études évoquent les difficultés du diagnostic histologique, celles à faire la part entre malignité et bénignité et donc les incertitudes pronostiques : la combinaison d’un index mitotique supérieur à cinq mitoses pour 50 champs à fort grossissement et une taille supérieure à 5 cm sont très en faveur de la malignité [1], [4] and [5].

On the other hand, a trial of treatment with recombinant periosti

On the other hand, a trial of treatment with recombinant periostin in a preclinical infarct model has been started; since periostin is essential for cardiac repairing after an acute myocardial infarction [23] and [24]. Cho et al. transferred periostin-overexpressing mesenchymal cells, resulting the improved cardiac function [39]. These examples of diagnostic or clinical applications of anti-periostin antibody or recombinant periostin may promote further development of periostin for these applications in the dental field. To take radiographs of 6- and 28-week old wild-type

and periostin−/− mice, we used an X-ray imaging system, the μFX-1000 (Fujifilm, Tokyo, Japan). The skeletons were fixed in 4% PFA, and subsequently exposed to X-rays at 0.1 mA and 25 kV for 5 s. The radiographs were scanned with BAS-2000 IP Reader (Fujifilm). Image analyses were www.selleckchem.com/products/cilengitide-emd-121974-nsc-707544.html performed with Photoshop for cropping and linear contrast adjustment. Care and experiments with animals were in accordance with the guidelines of the animal care and use committees at Tokyo Institute of Technology. Generation of periostin−/− mice was described previously [24]. This work was Cytoskeletal Signaling inhibitor supported by grants-in-aid (to A.K.) for scientific research from the Ministry of Education, Science, Culture, and Sports of Japan. None declared. We acknowledge the outstanding contributions

from our many colleagues. “
“Periostin is a 90 kDa secreted extracellular matrix (ECM) protein, which was originally cloned as the product of a gene, osteoblast-specific factor 2 (Osf-2), by subtraction hybridization and second differential screening

between cDNA libraries of MC3T3-E1 and NIH3T3 [1]. Perisotin comprises 4 fasciclin domains that promote cellular adhesion and migration and collagen fibrillogenesis; it is widely expressed in the cells of connective tissues, including fibroblasts and osteoblasts. Periostin was named so because of its preferential expression in the periodontal ligament and periosteum. Because both the periodontal ligament and periosteum are sensitive to mechanical stimuli, such as mastication, orthodontic tooth movement, and physical exercise, this protein is believed to primarily play a role in tooth and bone remodeling under mechanical stress. To investigate the involvement of periostin under mechanical stress, it was demonstrated that the forced mechanical stress upregulates periostin transcription during experimental tooth movement [2]. In contrast, occlusal hypofunction decreases the expression of both periostin and twist, a basic helix-loop-helix transcription factor, which is known to bind to the periostin promoter and upregulate its transcription [3]. Periostin is categorized as one of the matricellular proteins: a class of ECM-related molecules defined by their ability to modulate cell-matrix interactions.