Given the fact that coffee is highly hygroscopic (Ortalá et al ,

Given the fact that coffee is highly hygroscopic (Ortalá et al., 1998), it is probable that the water adsorbed in the samples was the major cause for TAG hydrolysis during storage (Fig. 2), and therefore could have blunted the effects of temperature and atmosphere on TAG reduction during storage. On the other hand, the roasting process promotes

free radical formation and is associated with pyrolysis reactions (Morrice, Deighton, Glidewell, & Goodman, 1993) that can accelerate degradation. Possibly, Androgen Receptor activity inhibition free radicals initially present in all the fresh coffee samples might explain the absence of significant differences between inert and oxidizing atmospheres. The interaction between storage time and atmosphere influenced the total TAG content in the 1st, 3rd, and 4th months of storage of light-medium samples (Fig. 2). During these months, the highest contents of TAG were observed in samples under oxidant atmosphere (Fig. 2 and Table 1). It is possible that losses of more thermolabile compounds in oxidant atmosphere, as previously mentioned (Pérez-Martínez et al., 2008; Toci, 2010), have caused this apparent increment in TAG contents. Sigmoidal kinetic curves were obtained for TAG degradation in both roasting degrees (Fig. 2). This indicates a two-step hydrolysis process. In Fig. 2, two periods of stability may be observed in total contents

of TAG during storage, from 2 to 3 months and from 4 to 6 months of storage for the light-medium sample, and from 1 to 2 months and from 3 to 5 months of storage for the dark-medium sample. PLX4032 These results suggest a decrease in hydrolysis in these periods. Ortalá et al. (1998) also observed a slow kinetic of lipid degradation during the first 100 days (≈3 months) of storage, followed by 100 days of stability. The classical molecular model for lipid oxidation (Frankel, 2005) establishes that reactions occur through

a chain mechanism controlled OSBPL9 by free radical formation, with three typical steps: initiation, propagation, and termination. The main factor affecting the reaction rate was the initiation reaction. On the basis of the model of Koelsch, Downes, and Labuza (1991), as well as on the basis of the present data, it appears that a monomolecular or bimolecular reaction can be responsible for the initiation step of the oxidative chain in coffee, through hydroperoxide decomposition. It depends on the initial concentration of these compounds, as observed in other products. So, during the first months, the initially low hydroperoxide concentration, as also observed by Ortalá et al. (1998) for roasted coffee, favors the monomolecular initiation and, when a critical value is attained, in line with the reaction progress, the bimolecular mechanism becomes more controlled. In the light-medium control sample, FFA content was 0.

Multiple small circular regions of interest (ROIs) of three voxel

Multiple small circular regions of interest (ROIs) of three voxels’ diameter

were positioned to sample the calculated T10, Et and Ct maps in white matter (84 ROIs), cortical gray matter (44 ROIs), deep gray matter (12 ROIs), CSF (10 ROIs) and major vessels (7 ROIs) on the pre-contrast 12° acquisition, using standard templates to ensure consistent sampling of brain regions blind to all other data including knowledge of post-contrast signal change. If necessary, the template ROI location was then adjusted slightly to avoid the recently ischemic lesion; however, ROIs were not adjusted to avoid white matter lesions. Measurements from all Forskolin ROIs were combined for each subject and tissue type to produce overall mean and standard deviation values for T10, Et and Ct. The mean

Et (Etave) and Ct (Ctave) were averaged over all post-contrast time points and along with T10 were averaged over all patients for each tissue type in each of the high- and low Fazekas-rated groups, to give overall mean and standard deviation values for each tissue in each group. A Student’s t test was performed Selleck GSK2118436 to look for significant differences in T10, Etave or Ctave between the low- and high Fazekas-rated groups in each tissue. The sensitivity of the FSPGR acquisition to scanner noise and drift was assessed using data acquired from volunteers and phantoms, processed in exactly the same way as the patient data. For the phantom data, ROIs were placed to cover the phantoms (cylindrical tubes of approximately 2 cm diameter and 10 cm length), and for volunteer data ROIs were placed as described above for the patient case. The contribution to the signal enhancement curves from scanner noise and drift was obtained by calculating the mean and standard deviation of Et for each tissue type (or phantom) over all time points and by analyzing the slope of

the signal enhancement profiles using standard linear regression analysis performed with the regression function in Microsoft Excel. These findings were then compared to the patient data. Errors in the estimation of intrinsic tissue parameters (T10, T20, r1 and r2) on the calculation of contrast agent concentration Thalidomide have been extensively studied by Schabel and Parker [19] who derived analytical expressions for the relative bias in the concentration measurement resulting from a biased estimate of the intrinsic tissue parameters. They demonstrated that T10 produces a negative concentration bias that has the greatest influence of all the tissue parameters, r1 also results in a negative concentration bias but to a lesser degree than T10, while r2 produces a fairly negligible positive concentration bias, only becoming significant at very high concentrations. The concentration estimation is independent of T20 in the fast exchange regime and so this parameter need not be considered further.

Such conformational and rotational flexibility has been


Such conformational and rotational flexibility has been

verified, for example, through solution – NMR techniques for M2WJ 332 binding to an artificial 13-base pair construct ( Wang et al., AZD4547 in vivo 2013). In earlier accounts (Vedani et al., 2000, Vedani et al., 2005 and Vedani and Dobler, 2002) we have demonstrated that a 4D representation including all (Boltzmann weighted) feasible poses can provide more accurate estimations of the associated binding affinities. Fig. 8 shows the corresponding 4D ensembles for the very compounds: diethylstilbestrol bound to the estrogen receptor α, genistein bound to the estrogen receptor β, dexamethasone bound to the glucocorticoid receptor and progesterone bound to the progesterone receptor. The individual poses are Boltzmann-weighted, i.e., only the energetically most favorable binding modes contribute significantly to the binding energy. Using the VirtualToxLab, we have estimated the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) ERK inhibitor for over 2500 compounds—drugs, chemicals and natural products—and posted the results on

The aim of the technology is to generate toxicity alerts, i.e., ranking the tested compounds in three groups: toxic potential (TP) ≤ 0.3 (low), 0.3 < TP ≤ 0.6 (moderate) TP > 0.6 (high). Fig. 9 shows the toxic potential for a selection of compounds. More informative than the toxic potential itself is the underlying binding-energy profile (cf. Table 1 for bisphenol A), as it provides specific information at which target protein an elevated binding affinity—potentially triggering an adverse effect—might be expected (cf. also the fingerprinting display CYTH4 mode in Fig. 5). The VirtualToxLab interface allows exporting the individual binding affinities into a csv file and, hence, to compute a customized toxicity alert. Most important, our technology allows rationalizing a given binding affinity

by inspection of the associated protein–ligand complexes in real-time 3D using the embedded 3D/4D viewer or, after exporting the coordinates in PDB format, with any other software of choice. Fig. 10 shows the computed binding mode of the anabolic steroid tetrahydrogestrinone to the androgen receptor. The associated binding affinity of 32 nM compares reasonably well with the experimental value of 8.5 nM. As the docking and scoring algorithms within the VirtualToxLab are based solely on thermodynamic considerations, it is suggested to probe the kinetic stability of the protein–ligand complex of interest by means of molecular-dynamical simulations. If the key interactions (hydrogen bonds, salt bridges, binding to metal ions, hydrophobic contacts) remain stable throughout a decent simulation time (t ≥ 5.

The first aliquot (control) was subjected to a slow freezing

The first aliquot (control) was subjected to a slow freezing selleckchem curve previously described for collared peccaries [7]. In this protocol, the aliquot was stored in a water jacket (30 mL) at 27 °C and equilibrated for 240 min to reach 5 °C in a biological oxygen demand (BOD) incubator (Quimis, Diadema, SP, Brazil). At that point, the sample was added to the extender with 6% glycerol (also at 5 °C), which resulted in a final concentration of 3% glycerol

in the extender, and the sample was then evaluated. Finally, the semen aliquot was divided and packed into 0.25 mL or 0.50 mL plastic straws (IMV Technologies; L’Aigle, France) that were placed horizontally in an insulated box for 20 min, at 3 cm above the nitrogen (N2) vapors, and then

plunged into N2 for storage at −196 °C, following a slow FK506 cost freezing rate at −10 °C/min. The second aliquot was cryopreserved following a fast freezing curve described by Silva et al. [35]. Semen aliquot was stored in the water jacket at 27 °C and equilibrated for 40 min to reach 15 °C in a BOD incubator (Quimis, Diadema, SP, Brazil). Further, BOD incubator was adjusted to establish at 5 °C for 30 min. Then, the glycerol addition and package was conducted as described for the first aliquot. However, the straws were placed at 5 cm above the N2 vapors for 5 min, and then finally plunged into N2 at −196 °C for storage, following a fast freezing rate at −40 °C/min. In both groups, the digital thermometer of the BOD incubator monitored the cooling rate up to 5 °C. Further, the Thymidylate synthase probe of an appropriate thermometer was inserted into the insulated box containing N2 vapors in order to monitor the cooling rates. After 1 week, three 0.25 mL and 0.50 mL straws derived from each of two freezing curves were thawed on a water bath, at 37 °C/1 min, and others at 70 °C/8 s, following a further 30 s at 37 °C. The semen was immediately evaluated, as per the same parameters reported for fresh semen and also for kinematic parameters of sperm motility by computer-assisted semen analysis – CASA, which will be described later. The thawed semen was

diluted in ACP-116c® on a proportion of one part semen to one part extender; then, it was evaluated by CASA, as described by Verstegen et al. [37]. Samples (10 μL) were placed in a Makler chamber, allowed to settle for 1 min and maintained at 38 °C. They were then examined in a phase contrast microcopy system with stroboscopic illumination, coupled with a video camera adapted to the Sperm Class Analyzer (SCA Version 3.2.0; Microptic s.l., Barcelona, Spain). The settings of the instrument were adjusted according to the boar semen, including temperature, 37 °C; frame rate, 25 frames/s; minimum contrast, 75; straightness threshold, 45%; low-velocity average pathway (VAP) cut-off, 10; and medium VAP cut-off, 25. Three independent and nonconsecutive microscopic fields were randomly selected and scanned.

We would like to thank Vincent Récamier, Raphaël Voituriez, Leoni

We would like to thank Vincent Récamier, Raphaël Voituriez, Leonid Mirny, Yitzhak Rabin, Lana Bosanac and Benjamin Guglielmi for stimulating discussions. We also acknowledge financial support from the following grants: ANR-12-BSV8-0015 and ANR-10-LABX-54. “
“Modification of cysteine residues by reactive oxygen species (ROS), reactive nitrogen species (RNS) and electrophiles has emerged as a significant means of altering the structure and function of many proteins [1, 2, 3, 4, 5 and 6]. Reversible oxidation

of certain protein thiol groups plays key signaling ZD1839 mouse roles in a range of physiological processes, for example in the regulation of tyrosine phosphatase activity [7], the redox regulation of transcription factors [8] and in T cell activation during the immune response [9]. The reactivity of protein thiols with ROS, RNS and electrophiles additionally underlies selleckchem their important role in defense against oxidative damage and xenobiotics [1, 2, 3, 4, 5 and 10].

In all of these processes there are a broad range of reactions that can occur to the cysteine thiol (Figure 1). Whether a modification occurs depends on a number of factors including the local environment of the cysteine residue, its proximity to the relevant reactive species, its pKa, solvent exposure and subcellular location [ 1, 6, 11 and 12••]. Additionally, some of these cysteine modifications are reversible by the action of reductive processes through the thioredoxin

and glutathione systems [ 13 and 14]. Reversible thiol modifications include glutathionylation [ 15], mixed disulfide formation with low molecular weight thiols, sulfenic acid formation [ 3], S-nitrosation (S-nitrosylation) [ 16], S-acylation [ 17], sulfenylamide formation [ 18], and the generation of intraprotein and interprotein disulfides [ 19 and 20]. In addition to reversible modifications, there are a number of cysteine adducts that can form irreversibly due about to reactions with electrophiles, which generally produce thioether products [ 10]. Similarly, the prolonged exposure of cysteine residues to ROS and RNS can also lead to the formation of irreversibly modified forms, such as sulfinic or sulfonic acids [ 21 and 22]. These protein modifications may contribute to oxidative damage, to the defense against oxidative stress and xenobiotics, or be part of redox signaling pathways. Consequently, it is of interest to be able to identify both the proteins and the cysteine residues affected, to determine the nature of the modification to the cysteine residue and to quantify the extent of the modification occurring during pathology or redox signaling.

montana L ) EO was subjected to a detailed GC–MS analysis to dete

montana L.) EO was subjected to a detailed GC–MS analysis to determine its chemical composition. As shown in Table 1, 26 compounds were identified, representing 99.48% of the total EO. The average extraction yield of the S. montana EO was 4.7 ml/kg of dried aerial parts in an MFB. The major compound groups were monoterpene hydrocarbons Veliparib in vitro and phenolic compounds. Thymol (28.99 g/100 g), p-cymene (12.00 g/100 g), linalool (11.00 g/100 g) and carvacrol (10.71 g/100 g) were the major chemical constituents. The extraction yield value of S. montana EO was similar to that found by Ćavar, Maksimović, Šolic, Mujkić, and Bešta (2008); however, the yield found in our study was lower than the yield reported

by the following groups: Bezbradica et al., 2005 and Mastelić and Jerković, 2003 and Radonic and Milos (2003). The phytochemical profile of the winter savory EO in this study was in agreement with the results of several authors who have also evaluated this vegetal species ( Mastelić and Jerković, 2003, Radonic and Milos, 2003, Silva et al., 2009 and Skočibušić and Bezić, 2003). In contrast, the savory EO evaluated by Ćavar et al. (2008) was characterized by a high content of alcohols, such as geraniol and terpinen-4-ol. The final composition

of EO is genetically influenced, with additional influence from the following: each organ and its stage of development; the climatic conditions of the plant collection site; the degree of selleck chemical terrain hydration; macronutrient and micronutrient levels; and the plant material’s drying conditions ( Bakkali et al., 2008 and Burt, 2004). Slavkovska et al. (2001) and Mirjana and Nada (2004) reported that the chemical profile of S. montana EO varied according to factors such as the plants’ stage of development and geographic location. The interaction between the effects (essential oil concentration × nitrite levels × storage time) was significant (p ≤ 0.05) for TBARS values. Fig. 2 shows the results for the TBARS values during storage, according to the EO concentration

and sodium nitrite levels Dichloromethane dehalogenase used. The control samples, which were produced without sodium nitrite or EO, differed significantly (p ≤ 0.05) in their lipid oxidation behavior; they suffered a more rapid and intense oxidation than those with added EO. After 20 days of storage, sausages formulated with 7.80 μl/g EO showed lower TBARS values (p ≤ 0.05) among the treatments formulated without sodium nitrite. These results demonstrate the potential antioxidant effect of this EO. The antioxidant activity of savory EO can be credited to the presence of its major phenolic compounds, particularly thymol and carvacrol, and their recognized impact on lipid oxidation ( Table 1). The antioxidant activity of phenolic compounds is related to the hydroxyl groups linked to the aromatic ring, which are capable of donating hydrogen atoms with electrons and stabilizing free radicals ( Baydar et al., 2004, Dorman et al., 2003 and Yanishlieva et al., 2006).

Because of their weight, several species (e g L stagnalis) have

Because of their weight, several species (e.g. L. stagnalis) have difficulty in remaining attached to the vegetation at wave-exposed locations. This ability to cling on to vegetation has proved important for the isopod Idotea balthica (Pallas), particularly Vorinostat manufacturer at wave-exposed sites, as this species prefers the narrow thallus of F. vesiculosus to the broader thallus of Fucus serratus L. ( Engkvist et al. 2004). In addition, some of the observed freshwater species are mostly deposit- and detritus-feeders that benefit from the larger amounts of suspended matter being deposited at wave-sheltered sites. All these factors probably increased the diversity at the sheltered

sites compared to the exposed sites. This study is a thorough investigation of the spring hydrolittoral ecology in the Baltic Sea. Appropriately replicated in time and space and covering the spring development, this study can complement other important studies, e.g. Wærn, 1952, Haage, 1975 and Kautsky and van der Maarel, 1990, and help to acquire a better understanding see more of the spring succession of filamentous algae and the associated macrofauna in this region. The results clearly demonstrate the dominance and succession of filamentous algae in the hydrolittoral zone in spring and may explain the fluctuations in several invertebrate species, especially the grazers, which find shelter

among the algae. The study indicates that the general experience of wave impact on hydrolittoral communities from oceanic areas is also applicable in the northern Baltic proper, despite its low salinity and the absence of tides. We are grateful to colleagues and staff at the Askö Research Laboratory for their generous assistance with the fieldwork. “
“Ciliates play an important role in transferring the production of pico- and nanoplankton to meso- and macrocarnivores (Stoecker and Michaels, 1991 and Pierce and Turner, 1993). Ota & Taniguchi (2003) suggested that ciliate populations in the East China Sea may control primary producers through intensive grazing and also act as important nutrient regenerators. Because of their ubiquitous distribution, small size and rapid metabolic and growth

rates, Non-specific serine/threonine protein kinase ciliates are considered a key part of the aquatic ecosystem (Dolan 1999). Some ciliates, such as the red-tide ciliate Mesodinium rubrum, belong to harmful algae bloom (HAB) species in the ocean. Blooms of M. rubrum are recurrent events in the world, sometimes extending over hundreds of square kilometres ( Lindholm 1990). They have been found off Peru ( Ryther 1967), in the Ria de Vigo ( Villarino et al. 1995), and also in Southampton Water ( Hayes et al. 1989), where such blooms occur every year from late May to August, peaking in abundance in July ( Williams 1996). Dapeng’ao cove has been subject to eutrophication due to elevated nutrient discharges from aquaculture and to the human population growth in this region since the 1990s (Wang et al. 2006).

We have concentrated on the polychaete

We have concentrated on the polychaete selleck chemical families Spionidae, Sabellidae and Serpulidae and we are heavily indebted to overseas experts who helped in the development of the guide Kupriyanova et al. (2013).

This guide was beta tested during a two day workshop held prior to the 11th International Polychaete Conference, Sydney, August 2013 and then updated and released in December 2013 ( It is now available for sale. We hope to be able to update this guide over time and perhaps even to expand it to include other marine groups. “
“The Macondo 252 petroleum oil spill was unprecedented, and is considered the largest environmental disaster in the United States. Approximately 4.9 million barrels (200 million US gallons) of crude oil were released into the Gulf

(Graham et al., 2011 and Harzl and Pickl, 2012). Coastal shorelines in Louisiana, Mississippi, Alabama and Florida were oiled. A large underwater plume of oil was identified in the deep waters of the Gulf, and it had essentially the same signature as the oil from the Macondo well (Camilli et al., 2010, Mitra et al., 2012 and White Crizotinib manufacturer et al., 2012). Water polyaromatic hydrocarbon (PAH) levels at four sampling sites along the Gulf coast were significantly elevated during the spill (Allan et al., 2012). The Exxon Valdez oil spill (EVOS) occurred in March, 1989, and 262 barrels or 11 million US gallons of crude oil were released around Prince William Sound, Alaska. Oil exposure resulted in significant mortality and physical and genetic abnormalities in Pacific herring (Marty et al., 1999). Many environmental pollutants cause immunosuppression in fish, leading to increased disease susceptibility, and PAHs are immunosuppressant (reviewed in Carlson and Zelikoff, 2008). In Puget Sound, WA, increased disease occurrence was associated with PAH exposure in flatfish and immuno-suppression of anadromous fish (reviewed in Johnson et al., 2008). Laboratory next studies demonstrated

that oil exposure resulted in decreased inflammatory cells, leading to immunosuppression (Carls et al., 1998 and Thorne and Thomas, 2008). PAHs are a component of crude oil and are carcinogenic, mutagenic, and negatively impact the marine environment. When dispersants are applied to the crude oil, the PAH bioconcentration is significantly higher resulting in higher fish mortality (Milinkovitch et al., 2011 and Allan et al., 2012). Genomic assessment of Gulf killifish tissues revealed that oil exposure caused significant changes in the biology of that fish (Whitehead et al., 2011). In general, embryos, larva and juvenile fish are more affected than other marine animals (Marchini et al., 1992 and George-Ares and Clark, 2000).

CT–MR fusion has become a

CT–MR fusion has become a Fulvestrant solubility dmso valuable tool in postimplant assessment and improves accuracy of postimplant dosimetry compared with approaches that use CT imaging only [11], [12] and [13]. Because MRI is limited by cost and availability, exploration of other imaging modalities may be helpful. Information from the preoperative transrectal ultrasound (TRUS), such as prostate length, shape, and volume, can be incorporated into postimplant assessment and may be an improvement over the use of CT imaging alone. A recent study by Smith et al. (8) in patients undergoing TRUS, CT, and MRI 30 days after BT showed less contouring variability and

closer correspondence between TRUS and MRI than that between either of these modalities and CT. This suggests that TRUS may be a viable and convenient alternative to MRI in settings where MRI is not available and should improve on the accuracy of CT-based contouring. The purpose of this study is to compare dosimetry obtained using fusion of the preimplant TRUS and Day 30 postimplant CT (CT–TRUS fusion) to fusion of the Day 30 CT to MRI (CT–MR fusion). Twenty men undergoing permanent 125I seed BT at the British Columbia

Cancer Agency Center for the Southern Interior between January and June 2011 were included in this study. No patients received androgen deprivation therapy (ADT) or external beam radiotherapy. The prescription dose of the 125I ROS1 BT implant was 144 Gy. Loose seeds were used for all 20 patients. Patients were eligible if urethrography was performed at the time of

Osimertinib preoperative TRUS and if catheterization was performed with CT imaging 30 days postimplant. All patients at our institution undergo TRUS planning before implantation, generating axial images every 5 mm, including one slice above and below the prostate gland. Urethrography with aerated gel is performed for planning purposes to permit limitation of the urethral dose to 125% of the prescribed dose in the preplan. CT and MRI are generally performed 30 days postimplant, using the following MR sequence: fast spin-echo T2-weighted (1.5 T), repetition time = 4500 ms, echo time = 90 ms, echo train length = 10, field of view = 20 × 20 cm, 3 mm slice thickness, 0 mm gap, and bandwidth = 80 Hz/pixel. The CT and MR images are manually fused for dosimetric assessment, using the seed positions on CT and signal voids on MR as fiducial markers. Catheterization for urethral identification at the time of the Day 30 CT is performed to facilitate calculation of urethral dose. For this study, the TRUS and CT images were fused manually based on the urethral position as determined by TRUS urethrography and the position of the Foley catheter on 1-month CT. Fusion was performed by overlying the sagittal images in the plane of the urethra to superimpose the urethral curvature to bring the base and apex into alignment (Fig. 1).

3) Hierarchy is now clearly established, the core concepts are i

3). Hierarchy is now clearly established, the core concepts are identified, essential elements to answer the focus question are present on the map with adequate terminology and appropriate connectors are used. We observe that the concept of “cellular respiration” is present on

the map. It is not required to answer the focus question, but nevertheless indicates more integrated and complex learning. Based on the taxonomy proposed by Krathwohl and co-workers, this study proposes a precise, rigorous, and operational characterization of skills exercised during the MS-275 price elaboration of context-dependent and hierarchically structured concept maps. As described above, this is an instructional and metacognitive Panobinostat tool proposing a possible path for knowledge construction. In addition it allows sCM designers to pay attention to the cognitive processes and types of knowledge

involved during the process of sCM elaboration. As described, organizing sCM requires acquisition of specific terms, adequate exemplifying, explaining and comparing different scientific notions, terms or concepts. In addition, learners have to reorganize and connect elements together (transfer of knowledge) to answer a particular new focus question. During this process, skills of different taxonomic levels are exercised. Most of them correspond to high order thinking skills and involve complexes cognitive processes. The cognitive efforts required to develop these are hard to achieve. Constructing sCM is rarely a purely individual task, but rather engages both students and teachers in an active cognitive processing (Novak, 2010 and Nesbit and Adescope, 2006). Indeed, it forces them to pay attention to and discuss between peer students, peer student–teachers or peer expert teachers, which information to keep as relevant, how to graphically integrate it into existing knowledge and which connector will be used, in order to precisely answer the focus question. As observed in psychology (Duro et Carbohydrate al., 2013) or in medical courses (West et al., 2000), whilst people advocate the value of their

choices to connect any particular concept with one other in a specific way, or to choose specific concept or connecting word, meaningful learning is fostered in general, and critical thinking in particular. For all these reasons, the process of map construction is at least as important as the final product (Kinchin, 2008), and “the benefits of spending time on integrating prior understanding are likely to exceed the benefits of acquiring new knowledge that mainly remain isolated and unconnected” (Kinchin, 2010). This point is fundamental and served as the basis in elaboration of sCM matrix. The tasks learner accomplish when constructing sCM helps them to move from a linear knowledge to a structured network. This evolution in the structure of knowledge allows threshold concepts to emerge (Kinchin, 2010).