While conductances were identical for all connections between two specific cell populations, the size distribution introduced a moderate variability in cell excitability and PSPs. The pyramidal-to-pyramidal connections had both AMPA and voltage dependent NMDA components. Synapses formed by pyramidal cells onto basket cells were purely AMPA-mediated while the

inhibitory cells formed GABAA type synapses. Excitatory inputs (including noise) were placed on the second apical and on the basal dendritic compartment, while the inhibitory basket cells 3 Methyladenine were connected to the soma. The synapses formed by pyramidal cells were fully saturating in the sense that the conductance gsyn during repetitive firing could

only sum up to the peak conductance resulting from a single presynaptic spike. After a synaptic event conductance decayed back to zero with a time constant τsyn, characteristic of each synapse type ( Table A2 in the Supplementary material). The axonal conduction speed was 0.5 m/s and the synaptic delay 0.5 ms. Synaptic plasticity between pyramidal cells was implemented according to Tsodyks et al.’s model (1998). Depression was multiplicative, i.e. decreasing the synaptic conductance of the synapse by 25% with each incoming spike and decaying back to the initial conductance with the time constant of 0.4 s ( Wang et al., 2006). Augmentation Raf phosphorylation that was used in the periodic replay simulations was additive, where 10% of the initial maximal conductance was added to the augmented maximal conductance for each incoming spike. The decay time constant for augmentation was 6 s ( Thomson, 2000 and Wang et al., 2006). More information on synaptic kinetics can be found in Supplementary material. The pyramidal cells received noise input through excitatory AMPA synapses activated by simulated Poisson spike check details trains with an average firing of 300 s−1 but with very small conductances (~10 times smaller than local pyr–pyr conduction, cf. Table

1). This source alone made the pyramidal cells spike at ~2 s−1. Single minicolumns could be selectively stimulated (Yoshimura et al., 2005) by pyramidal cells representing layer 4 input cells. Each minicolumn had 5 such cells. They were activated to produce 2–3 spikes by independent input spike trains generated by Poisson processes with the average rate of 100 s−1 and the duration of 30 ms, and innervated 30 layer 2/3 cells with feedforward connections (50% connectivity). Typically, 5 out of 9 memory pattern-related minicolumns, each one in a different hypercolumn, were stimulated through layer 4 cells to model a fragmentary input. This setup was found adequate for selectively activating attractors in our layer 2/3 network, though more elaborate models (Sirosh and Miikkulainen, 1994) of layer 4 to 2/3 connectivity exist.

05% bromophenol blue (v/v) and 4% β-mercaptoethanol (v/v), followed by heating at 100 °C for 5 min. The fibronectin hydrolysis was analyzed by 7.5% SDS-PAGE. The Spectra multicolor broad range protein ladder (260–10 kDa) was used as a molecular mass standard. A stock solution of laminin (4 μg/μL) was prepared in 50 mM Tris–HCl pH 7.4, 10 mM NaCl and 2 mM CaCl2. The substrate was incubated with Batroxase at a molar ratio of 1:50 at 37 °C for 2, 6, 12 and 24 h. After incubation, 20 μL of stop solution containing

1 M urea, 4% ß-mercaptoethanol (v/v) and 4% SDS (w/v) was added, and the material was heated for 15 min at 100 °C. The extracellular matrix component digestion was analyzed by 7.5% SDS-PAGE. The Spectra multicolor broad range protein ladder (260–10 kDa) was used as the molecular mass standard. To evaluate

the proteolytic activity of Batroxase on fibrin, a clot was induced by incubating a fibrinogen solution CCI-779 cost (10 mg/mL in HEPES) with thrombin at 37 °C for 1 h. The clot was then dissolved and transferred in 100 μL aliquots to glass tubes and incubated with 5 μg of Batroxase at 37 °C. The reaction was interrupted at different time points (0, 15, 30, 60 and 120 min and 12 h) by adding 20 μL of a solution containing 1 M urea, 4% ß-mercaptoethanol (v/v) and 4% SDS (w/v), and it was left to incubate overnight. The digestion products were analyzed by 7.5% SDS-PAGE. The Page ruler pre-stained protein ladder (170–35 kDa, Fermentas, USA) was used as the molecular mass standards. Human plasminogen (30 μg) was incubated with Batroxase (5 μg) in selleck 10 mM Tris–HCl buffer containing 10 mM CaCl2, pH 8.5, for different time intervals at 37 °C. The reaction was stopped by adding sample buffer containing a reducing agent. The digestion was analyzed by 10% SDS-PAGE. As a positive control, urokinase (625 U/mL) was used as a known plasminogen activator. A 100 μL aliquot of Matrigel (BD Bioscience) in 50 mM Tris–HCl buffer containing 20 mM CaCl2, pH 7.6, was incubated with 10 μg Batroxase at 37 °C,

for different time intervals. The reaction was stopped by adding sample buffer containing a reducing agent, and the digestion was analyzed by SDS-PAGE in a 4–15% gradient gel under reducing conditions. As a negative control, Matrigel was incubated with the sample buffer only for 180 min. Leukocyte receptor tyrosine kinase As a positive control, the Matrigel was incubated with 10 μg B. atrox crude venom for 180 min. Platelet-rich plasma (PRP) was prepared from freshly collected human plasma by centrifugation of whole blood at 1000 × g for 10 min. Plasma-poor platelets (PPP) were obtained from PRP by centrifugation at 1000 × g for 15 min. Platelet aggregation was monitored turbidimetrically using an aggregometer (Chrono-Log Corporation). The PRP presented a platelet count of 3 × 105 cells/μL. For each assay, 10 or 20 μg Batroxase was added to 500 μl of PRP, and the aggregation was monitored for 2 min at 37 °C with stirring.

In addition, taking amax,minamax,min, Tmax,minTmax,min, and Rmax,minRmax,min as the maximum and A-1210477 minimum amplitudes, periods and runups of the samples, respectively, the standard deviation of the measurements of these parameters were smaller than 7.4% of |amax,min|amax,min, 8.4% of |Tmax,min|Tmax,min and 4.5% of |Rmax,min|Rmax,min. The standard deviations of the samples s are representative estimates of total

population standard deviation σ(i.e., standard deviation for all waves tested). Therefore, the experiments are repeatable. A relative measure of the wave length should be defined to investigate runup. In the present experiments, variations in water depth (hh) are small ( 0.45m

elevation have been collected, we choose to consider the wave period as a representative selleck products measure of the wave length. The time TbTb it takes for a given wave to travel the length of the beach lblb can be estimated: equation(12) Tb=∫0lbdXgh(1-Xlb)=2lbgh.Considering an average h≈0.58m over the range of experiments, lb=13.7lb=13.7 m, we obtain an approximate Tb≈11s. To second distinguish between long and

very long waves, we used the discriminator T/TbT/Tb as this provides a measure of the influence of beach length on the wave characteristics. For simplicity (and because the proportion of data would not change), we decided to use the critical value of T/Tb=1T/Tb=1 and split the data between long waves (T/Tb<1T/Tb<1) and very long waves (T/Tb>1T/Tb>1). The present experimental cases (T/TbT/Tb vs. a/ha/h) have been placed in Fig. 4. As a first step, the consistency of the new results with previous published studies is assessed. Next, the data is analysed through dimensional analysis taking into account the unique wave characteristics (i.e., in terms of shape, energy, wavelength). Finally, by applying a rigorous regression analysis, empirical runup relationships are derived and their associated uncertainty estimated. For the reader’s convenience, the data (wave parameters as calculated using the aforementioned methods) have been listed in Appendix F. As previous experimental studies of runup largely looked at relatively short solitary waves, the consistency of the present experiments with known runup results can only be assessed using a representative subset of the present data (i.e., elevated waves for which T/Tb<1T/Tb<1).

Median PFS was 4.4 months (HR 0.72 [95% CI: 0.42–1.23]) for BE versus 4.8 months (HR 0.66 [95% CI: 0.38–1.16]) for BC. These data suggested that the BE combination had similar efficacy to chemotherapy in a second-line setting. The BRAIN study of BE in second-line treatment of NSCLC patients with asymptomatic brain metastases (n = 24) demonstrated a median PFS of 6.3 months (95% CI: 2.5–8.4) and a 6-month PFS rate of 58% [23]. INNOVATIONS investigated first-line BE in NSCLC and also showed no benefit Epigenetics Compound Library screening with the BE combination compared with

BC regimen. Median PFS was 3.5 months for BE versus 7.7 months for BC. OS was 12.6 months versus 16.3 months for BE versus BC [28]. The first-line SAKK 19/05 study showed a BE combination resulted in PFS of 4.1 months and OS of 14.1 [24]. In previous studies investigating the use selleck kinase inhibitor of the single-agent TKIs for the treatment of first-line NSCLC, the results in unselected patients were not encouraging [16], [18],

[19] and [29]. While the combination of bevacizumab and erlotinib showed promise in second-line treatment, the TASK and INNOVATIONS studies suggest that the addition of bevacizumab to first-line erlotinib does not improve outcomes for unselected patients with NSCLC. A recent editorial highlighted that combining more agents is not necessarily better when designing clinical trials and using agents with different modes of action should only be done when preclinical data support the combination in that particular setting [30]. This study did not show a PFS benefit for the BE combination in first-line advanced NSCLC compared with BC. Subgroup findings were consistent with the overall population. The premature termination of study Inositol monophosphatase 1 treatment in the BE arm does not allow for a reliable assessment of efficacy in the smaller subgroups of patients, including those with EGFR mutations. Based

on these findings the erlotinib plus bevacizumab combination is not currently recommended for first-line NSCLC. Dr. N. Thatcher has received honoraria from Roche and received payment for consultancy, expert testimony and other remunerations from Roche. Dr. T. Ciuleanu has received honoraria from Roche. Dr. H. Groen has received research funding from Roche and received payment for consultancy from Roche and Pfizer. Dr. G. Klingelschmitt and Dr. A. Zeaiter are employees of Roche. Dr. B. Klughammer is an employee of Roche and owns stocks in F. Hoffmann La Roche. Dr. C.-M. Tsai has received honoraria from Pfizer, Roche, Eli Lilly, Boehringer Ingelheim and Astra Zeneca. Prof. G. Middleton has received honoraria and payment for Advisory roles from Roche. Dr. C.Y. Chung has received other remunerations from Novartis. Dr. D. Amoroso, Dr. T.-Y. Chao, Dr. J. Milanowski, Dr. C.-J. Tsao, Dr. A. Szczesna and Dr. D.S. Heo had no conflicts to declare. This trial was designed, funded and monitored by F. Hoffmann-La Roche Ltd.

This event occurred in 1991 and is extremely meaningful in the whole history of our science. G.N. Kryzhanovsky was a recognized founder and patriarch of ISP, its first President, and then – Honorary President. His name is known and dear to all pathophysiologists. G.N. Kryzhanovsky made an invaluable contribution to the study of the patterns of pathological pain. For a long time he was a President of the Russian Society for the Pain Research. Totally he published over 800 academic papers, including Neratinib nmr 20 capital monographs and textbooks with lasting value for the biomedical sciences. More than 50

years G.N. Kryzhanovsky participated in the editorial board of the leading domestic biomedical journal – “Bulletin of Experimental Biology and Medicine”, he was the deputy GDC-0068 mw editor-in-chief of “Pathogenesis”, a member of the editorial board of the oldest Russian pathophysiological journal: “Pathological Physiology and Experimental Therapy”, a member of the editorial board of

“Neuroimmunology” and other academic periodicals. He was a member of the editorial board of “Pathophysiology” from the day of its foundation. G.N. Kryzhanovsky created a large and fruitful scientific school in General Pathology and Experimental Pathophysiology of the nervous system, which won recognition in Russia and abroad. Under his academic supervision 62 theses were defended. His manual “General Pathophysiology of Nervous System” (1997) became reference book in this field. His disciples work as leaders of research and teaching pathophy-siological teams in many universities and institutes all over the world. The memory of outstanding pathophysiologist and citizen will always remain in our hearts. “
” Xavier Leverve est décédé le 8 novembre des suites d’une terrible maladie contre laquelle il luttait depuis le début de l’année avec un courage et une maîtrise admirables. Fossariinae Il était âgé de 60 ans. Le cursus de Xavier Leverve, médical et scientifique à la fois, est exemplaire. Après ses études de médecine et son internat à Grenoble, il a été chef de clinique-assistant

en réanimation médicale de 1980 à 1983 et a acquis la spécialité de médecine interne. Simultanément, il a mené des études en biologie humaine sous la direction du professeur Yves Minaire et a été nommé docteur es-sciences en 1983 à l’université Lyon-I (Claude-Bernard). En 1985 il est parti pour deux ans à l’université d’Amsterdam, laboratory of biochemistry, section of medical enzymology (professeur JM Tager). De retour à Grenoble en 1985, il retourna à la pratique clinique en réanimation dans le service du Pr Michel Guignier et s’est engagé dans la construction de son propre laboratoire de recherche à l’université Joseph-Fourier. En 1989, il a été nommé professeur de thérapeutique, puis en 1999 professeur de nutrition.

This framework could account for the strong concreteness effects observed at the “edges” of the temporal lobe (i.e., STG and PHG) in terms of their relative specialisations for verbal versus visual inputs, while predicting equi-modal activations in the centre (ITG and the vATL). Importantly, this framework assumes graded specialisation within a single functional system in the ATL, rather than an absolute learn more division into separate processing modules. Finally, we consider C > A activations observed in other areas of the brain. As in previous studies and meta-analyses, we found C > A effects in angular gyrus, posterior cingulate and mid-PHG. As discussed

in the previous section, the activation of PHG most likely reflects retrieval of stored visual characteristics

of concepts, which is only possible for highly imageable, concrete words (D’Esposito et al., 1997 and Sabsevitz et al., 2005). C > A effects in the angular gyrus and posterior cingulate are harder to interpret. The role of posterior cingulate in semantic cognition is unclear, though it has been suggested that it may be involved in the interface between semantic knowledge and episodic memory (Binder et al., 2009). Stronger claims have been made about the function of Bortezomib mouse angular gyrus. Binder et al. (2009) proposed that the angular gyrus is critically involved in semantic representation Urocanase and that concrete regions activate this region strongly because they have more detailed semantic representations. It is therefore interesting that the activation profile of angular gyrus diverged strongly from that of the vATL, for which a similar representational function has been proposed. There were three findings that suggest the function of the angular gyrus is very different to that of vATL. First, the angular gyrus was not activated in the main contrast of semantics over numbers; in fact, the contrast in this region slightly favoured the numbers (see Fig. 3). This suggests that, in addition to any

putative role in semantic processing, the angular gyrus is at least equally involved in the processing of numerical magnitudes. This was not the case for vATL. Second, angular gyrus showed a clear C > A activation pattern, while the activation in the vATL slightly favoured abstract words (though this effect varied elsewhere in the ATL region). Finally, angular gyrus and vATL showed very different activation patterns with respect to rest, with angular gyrus significantly deactivated by the semantic task while vATL, along with other elements of the semantic network, were positively activated. This result is consistent with the status of angular gyrus as a key element of the default mode network. Binder et al., 2009 and Binder et al.

Samples of OLSx 1–6 were analysed using a Q-Trap mass spectrometer (Applied Biosystems) with the direct infusion of the sample solutions into the electrospray ionisation source operating in the buy ABT-263 negative ion mode. Capillary and cone voltages were set to −4500 V and −50 V, respectively, with a de-solvation temperature of 100 °C. OLSx 3–6 were introduced into an HPLC (Agillent) with a μBondapak C18 analytical column (Waters, 3,9 × 300 mm, 10 μm) and detected in a Q-Trap mass analyser. ESI(−)–MS was carried out with capillary and cone voltages set to −4500 and −50 V, respectively, and a de-solvation temperature of 300 °C. A binary mobile phase of acetonitrile and 1% of

formic acid was employed. A linear gradient was performed starting from 30% of acetonitrile to 100% acetonitrile, in 30 min, and an elution flow rate of 1 ml/min. Tandem mass spectra were acquired using a hybrid high-resolution and high-accuracy (5 ppm) Micromass Q-TOF mass spectrometer (Waters) and via collision-induced dissociation at ca. 15 V. Capillary and cone voltages were set to ±3000 and ±40 V, respectively, for the negative or positive mode of ionisation. INK1197 manufacturer The de-solvation temperature was 100 °C; nitrogen and argon were used as de-solvation or collision

gas, respectively. The cytotoxicity of propolis extracts and fractions from ODEP was evaluated against four human tumour cell lines: HL-60 (leukemia), HCT-8 (colon), MDA/MB-435 (breast) and SF-295 (brain) obtained from Amisulpride the National Cancer Institute (Bethesda, MD, USA). The general viability of cultured cells was determined by the reduction of the yellow dye 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to a blue formazan product, as previously described by Mosmann (1983). The tumour cells were maintained in RPMI 1640 medium, supplemented with 10% fetal bovine serum, 1% penicillin and streptomycin at 37 °C with 5% CO2. For all experiments

cells were seeded at 0.3 × 106 cells/ml (HL-60, MDA/MB-435 e SF-295) and 0.7 × 105 cells/ml (HCT-8), and incubated during 72 h with propolis extracts (0.001–50 μg/ml ODEP and EEP70) and fractions (0.001–25 μg/ml), under the conditions described above. After centrifugation and solution removing, MTT solution was added and the plates were incubated, centrifuged, and the solids dissolved in pure and sterile DMSO. The absorbance was measured in a plate spectrophotometer DTX-800 (Beckman Coulter) at 595 nm. Doxorubicin (Sigma) was used as a positive control. A total of 80 Swiss mice (male, 25–30 g), obtained from the central animal house of Federal University of Ceará, Brazil, were used. The animals were housed in cages with free access to food and water (conforming to a well-defined rodent diet). All animals were kept under a 12:12 h light–dark cycle (lights on at 6:00 a.m.).

Reports of PFBS in wild mammalian tissues are relatively uncommon in the international literature and has only recently

been found in harbor seals from the Dutch Wadden Sea (1.74–3.28 ng/g spleen) (Van de Vijver et al., 2005), in harbor seals from the German Bight (up to 3.1 ng/g liver) (Ahrens et al., 2009) and in gray seals from the Baltic Sea (up to 3.5 ng/g liver) (Kratzer et al., 2011). The concentrations were approximately the same as in selleck chemical the mink in our study (Table 1), although PFBS was only found in 27–55% of the samples (compared to 89% in our study). In addition, PFBS has been found in sea turtles from the east coast of USA (< 0.02–0.846 and < 0.01–0.195 ng/g serum) (Keller et al., 2012 and O'Connell et al., 2010). In contrast, PFBS was below detection limit in all samples of Arctic and North Atlantic pilot whale, ringed seal, minke whale, harbor porpoise, hooded seal, white-sided dolphin and fin whales (Rotander et al., 2012). Also, PFBS was not detected in ringed seal populations in the Canadian Arctic (Butt et al., 2007 and Butt et al., 2008), nor in common guillemot from the Baltic Sea (Berger, 2008) or harbor porpoise in the North and Baltic Sea (Huber et al., 2012). PFBS is persistent (Quinete et al., 2010), but not expected to be as bioaccumulative as PFAAs with longer carbon chains (Conder et al., 2008). However, as a replacement

for PFOS, the use of this compound will probably increase in the future. Trichostatin A supplier Mink, with its wide geographical distribution and the proximity of its habitat to human activities, could be a suitable sentinel species for monitoring PFBS exposure to mammals. The sampling areas in this study were selected because of their assumed differences in contamination and this was confirmed by the multiple regression Cediranib (AZD2171) model,

which showed that area of sampling was significantly influencing the concentrations of PFHxS, PFOS, PFNA, PFDA and PFUnDA (p = < 0.001–0.01). The multiple regression models explained 18–53% of the variation in the tissue concentrations. Pairwise comparisons of least squares between the areas are given in Table 1. To visualize the variation in contaminant concentrations in the four areas, a PCA model (R2 = 0.52, Q2 = 0.119) containing 3 significant principal components according to cross validation was calculated. Scores and loadings plots of component 1 versus component 2 are given in Fig. 1 and Fig. 2, explaining 23% and 15% of the variance, respectively. The scores plot is a summary of the relationships among the observations (mink). The loadings plot can be used to interpret the patterns seen in the scores plot, as the plots are superimposable. Plots of component 2 versus 3, the descriptive data for the components and the R2 and Q2 calculated for each variable are found in the Supplementary data. In the PCA scores plot (Fig.

About 70% of the Swedish productive forest land is certified according to either FSC or PEFC, or both systems. The average proportion retained area per clearcut is 3% (Swedish Forest Agency, 2012). In January 2005 a storm, “Gudrun”, hit southern Sweden and 70 million m3 trees fell, equivalent Tyrosine Kinase Inhibitor Library clinical trial to twice the amount of the normal annual cut in the storm area (Swedish Forest Agency, 2006),

and also strongly affecting retention amounts and patterns. Based on data from the long-term Swedish National Forest Inventory (NFI), we here assess what can be achieved by the retention approach. The aim is to quantify the development over time of retained living trees (solitary and small tree groups) and dead trees after final harvest, with a focus on young forests (0–10 years old). We want to describe such changes in relation to regions, stand age classes, ownership categories, tree diameter, tree species (living trees), tree position (dead trees; standing or lying) and decay class (dead trees). Since Sweden was so early in application of the retention approach, results anti-CTLA-4 monoclonal antibody can demonstrate more general trends and help assess and predict development in countries and regions in which the retention approach has been introduced more recently. Forests cover about 55%

of Sweden’s land area of 41 million ha (Swedish Forest Agency, 2012) and more than 90% of the productive forest land is managed more or less intensely with the clearcutting method, introduced large-scale in the 1950s. Practices have since then been largely similar for small private forest owners, large forestry companies and other forest owners. After clearcutting and soil preparation, regeneration is secured through planting (or sometimes with natural regeneration) of the conifers Picea abies (L.) Karst. and Pinus sylvestris L., later followed by pre-commercial thinning and thinning. Also N-acetylglucosamine-1-phosphate transferase birch, Betula pendula Roth.,Betulapubescens Ehrh. is favoured to some extent.

Rotation times vary between 60 and 100 years. NFI started 1923 and performs annual inventories of all land in Sweden, providing data at national and regional levels, with focus on forest and other wooded land. The present design was introduced in 1983 (Ranneby et al., 1987). Data on trees, forests and management history are recorded by field teams in a stratified random systematic cluster design with partial replacement, and in plots with radius of 7 m, 10 m or 20 m, depending on variable. Permanent plots are surveyed every 5–10 years, and at least 5 years of data are usually needed for reliable estimates (Axelsson et al., 2010). The list of recorded variables in the NFI is extensive, covering both forestry and environmental aspects. Living and dead tree volumes and numbers can be compiled for regions, ownership categories and age classes.

However, it is in combination with the full assessment of the genetic status, through the genetic parameters indicated, that a complete evaluation of population

condition at the local level may be achieved. The use of already existing UMI-77 purchase information regarding the demographic and genetic conditions of a population is not advisable to inform current status, unless this information is recent (less than a decade old). Otherwise, climatic change and anthropogenic influence may deem the literature outdated. On the other hand, older data are indispensable for establishing temporal comparisons needed to identify trends in population condition. Trees in plantations and on-farm will be one of the major assets of a future global and local economy relying on renewable resources. Through appropriate management of genetic

resources (which constitute an indicator area of its own), the benefits of tree planting can be increased many fold. A valuation of this effort in terms of the extent and development of selected tree planting activities and the use of relevant reproductive material can provide a direct indicator of benefit. It may also serve as a verifier for the management of the genetic resource itself (i.e. response), but it is important to emphasize the level of benefit that can be achieved. The Planted Forest Programme of FAO (FAO, Planted Forest Programme, 2013) has compiled and analyzed information Selleckchem Kinase Inhibitor Library on planted forests for more than a decade. In addition, an increasing amount of information on trees outside forests is becoming available (Zomer et al., 2009). The relative contribution of planted forests to the global production of wood serves as a general indicator of the importance of tree plantations. In 2005, forest plantations covered some 260 million ha or 7% of the global forest area, but produced 1.2 billion m3 of industrial round wood or about two thirds of the total global round wood production (Evans, 2009). By 2030 the production from plantations may

surpass 2 billion m3 of industrial round wood. Given the increasing O-methylated flavonoid importance of planted forests, information on trends in genetic diversity, deployment and productivity of a selection of planted tree species could be a feasible indicator of benefit. The benefit of genetic diversity as a resource is directly expressed in the value of tree breeding. The profitability of breeding is well established (e.g., Daniels, 1984, Foster et al., 1995, Mckeand et al., 2006, Rosvall, 2011 and Willan, 1988). Through a fairly simple process it is possible to achieve 35–80% gain with very high returns of investment (see Foster et al., 1995). The basic requirement is of course the availability of genetic diversity.