1%) and EDTA-2K (0 05 mM) dissolved in PBS, and the number of tot

1%) and EDTA-2K (0.05 mM) dissolved in PBS, and the number of total cells, neutrophils, macrophages, lymphocytes, and eosinophils were counted with an automatic erythrocyte analyzer (XT-2000iV, Sysmex Corporation, Hyogo, Japan). Lactate dehydrogenase (LDH) and total protein (TP) concentrations in the supernatant obtained by centrifugation of the BALF were measured with an automatic biochemical analyzer (TBA-200FR, Toshiba Medical Systems Corporation, Tochigi, Japan). Interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-γ, and tumor

necrosis factor (TNF)-α concentrations were measured using MG-132 manufacturer a Rat Cytokine 10-Plex A Panel kit and Bio-Plex Suspension Array System (Bio-Rad Laboratories, Inc., Tokyo, Japan). The trachea, left lung, liver, kidney, spleen, and cerebrum were fixed with 10% (v/v) neutral phosphate-buffered formalin solution, embedded in paraffin, sectioned, and stained with hematoxylin and eosin for histopathological evaluation under the light microscope. Morphology of the MWCNTs in the lung was observed with the light microscope. Sections of the right lung after lavage were fixed with glutaraldehyde and were resin-embedded to give ultrathin sections. Morphology of the individual tubes of instilled MWCNTs in the lung of rats was observed with TEM (JEM-100CX II, JEOL

Ltd., Tokyo, Japan). Statistical analyses of the body and lung weights, as well as the cell numbers and biochemical parameters in the BALF were Alectinib solubility dmso conducted. Statistical significance was determined using multiple comparison tests between the negative control

and MWCNT-exposed groups. First, the Bartlett’s test was conducted. One-way layout analysis of variance was conducted when the variances were equal. Further, Dunnett’s multiple comparison tests were conducted when the differences between the groups were significant. Cell press The Kruskal–Wallis test was used when the variances were not equal and Steel’s multiple comparison tests were conducted when the differences were significant. Statistical significance was determined between the positive and negative control groups using intergroup comparison tests. First, the F-test was conducted; the Student’s t-test was used when the variances were equal, and the Aspin–Welch t-test was used when the variances were not equal. Statistical significances were judged at the 0.05 probability level. SAS System version 6.12 (SAS Institute Japan Ltd., Tokyo, Japan) was used for all the statistical analyses. SEM and TEM images of the bulk and dispersed MWCNT samples are shown in Fig. 1. In the bulk MWCNT samples, MWCNTs were in the form of agglomerates with sizes ranging from 50 to 100 μm, which are formed from tangled individual tubes with lengths of more than 10 μm (Fig. 1a).

The impact scenario model is subsequently linked to the damage ex

The impact scenario model is subsequently linked to the damage extent variables. The model provides a platform to assess the uncertainty about the possible oil outflows in maritime traffic scenarios when only very limited data regarding the ship design Everolimus is available, as is typical in risk assessment of maritime transportation. It also enables insight in the probabilistic nature of possible oil outflows conditional to the impact conditions, which has been illustrated in two example accident scenarios. The model can be

expected to provide a reasonable estimate of possible oil outflows under various scenarios, which mainly follows from the reported validity of the underlying models for collision damage and tank arrangement. The issue of validation of the Bayesian network model was discussed using various validity concepts aimed to increase confidence in selleck screening library the model in absence of data to which the model output can be compared. A systematic analysis of uncertainties and biases in the underlying models and assumptions shows that while the presented model allows a quantification of uncertainty regarding oil

outflows, some reservations need to be made regarding the accuracy of the results. In particular, some evidential uncertainties are present in the damage extent model and the assumptions made regarding the oil outflow calculations lead to an overestimation of the oil outflow. This assessment allows

a reflection on those elements in the model which would benefit most from a more detailed modeling approach, if further accuracy is desired in the assessment of possible oil outflows. The work presented in this paper has been financially supported by Oxymatrine the project MIMIC “Minimizing risks of maritime oil transport by holistic safety strategies”. The MIMIC project is funded by the European Union and financing comes from the European Regional Development Fund, the Central Baltic INTERREG IV A Programme 2007–2013, the city of Kotka, Kotka-Hamina Regional Development Company (Cursor Oy), Centre for Economic Development, and Transport and the Environment of Southwest Finland (VARELY). Arsham Mazaheri is thanked for obtaining the tank configuration data and Zheng Xing is thanked for coding part of the tank arrangement model. “
“A number of experimental and opportunistic studies have quantified the effects of small boat traffic on the fish-eating, “resident” killer whale populations in the northeastern Pacific (Erbe, 2002, Holt et al., 2008, Lusseau et al., 2009, Williams and Ashe, 2007, Williams et al., 2002a, Williams et al., 2002b and Williams et al., 2006). These studies showed that killer whales avoid boats using stereotyped evasive tactics consistent with horizontal avoidance (i.e.

2C) Fusion protein expression was induced in the E coli strain

2C). Fusion protein expression was induced in the E. coli strain ORIGAMI (DE3) by addition of 0.6 mM IPTG. As shown in Fig. 3A, the 6xHis-Smt3-PnTx3-4 fusion protein was highly expressed. Although a large amount of the recombinant protein was present in the soluble fraction ( Fig. 3A, lane 3), considerable amount of the protein was also present in inclusion bodies ( Fig. 3A, lane 2). Because soluble proteins have the

potential to be in their native conformation, while proteins found in inclusion find more bodies need to be denatured and refolded to assume their native structure, we chose to purify the recombinant PnTx3-4 from supernatant and pellet separately. The soluble recombinant 6xHis-SUMO-PnTx3-4 was purified from the supernatant by affinity chromatography using a Ni-NTA agarose resin. Purified fraction was dialyzed for 24 h to remove the imidazole. This purification step isolated the 6xHis-SUMO-PnTx3-4 from most of the bacterial proteins (Fig. 3B, lane 5). To specifically separate the PnTx3-4 from its N-terminal 6xHis-SUMO tag we digested the peptide with SUMO Protease I, which recognizes the SUMO structure at

the N-terminus of the fusion protein and cleaves the junction (peptide bond linking the last amino acid residue of SUMO to the first amino acid residue of the recombinant peptide). After digestion, PnTx3-4 was then purified Wnt antagonist by reverse phase chromatography in a Waters HPLC system using a discontinuous CH3CN gradient. Two main peaks were observed, one with retention time of about 31 min and the other with retention time of about 41 min (Fig. 3C). Fractions from each peak were pooled and analyzed by SDS-PAGE and Western blot. We determined that the recombinant PnTx3-4 eluted in peak 1, which presented a band of approximately 8 kDa (Fig. 3D, lane

1) that could be recognized by a polyclonal antibody raised against the spider venom (Fig. 3E, lane 2). Approximately 0.6 mg of pure recombinant PnTx3-4 was reproducibly obtained per litter of bacterial culture (Table 2). To investigate whether the recombinant peptide presented biological activity analogous to native PnTx3-4, we tested it initially oxyclozanide in a glutamate release assay (de Castro Junior et al., 2008; Prado et al., 1996). Total glutamate release was measured in mouse cortical synaptosomes depolarized with 33 mM KCl in the presence of 1 mM CaCl2 (Fig. 4A and B). Addition of 16 nM of native PhTx3-4 (purified from the spider venom) decreased glutamate release by 36%. Ca2+ removal from the medium, by adding 2.0 mM EGTA before depolarization with KCl, decreased glutamate release by the same magnitude (Fig. 4A and B), corroborating previous findings that native PnTx3-4 effect is mainly restricted to the Ca2+-dependent (exocytotic) glutamate release (de Castro Junior et al., 2008).

Therefore we hypothesise, in our model, that stresses at the LB a

Therefore we hypothesise, in our model, that stresses at the LB and IF in the scapula have been similarly reduced by an average 22.5% in our Hpr mice (Fig. 7(A) open symbols). Using this information on altered muscle strength and weight, we can correlate the stress distribution in the scapula, and its alterations during rickets, to the evolving mineral particle nanostructure. We plotted mineral particle

alignment and degree of mineralisation versus applied stress for the oldest (10 weeks) wild type and Hpr mice in our data set. In wild type mice we observed a statistically significant (p < 0.05; Student's t-test) difference in mineral degree of orientation between two sites

where low and high stresses are expected ( Fig. 7(A)). Regions with expected increased stresses on the scapula are associated with an increased degree BIBW2992 of mineral particle orientation, as well as mean mineral concentration. However, in Hpr mice, alterations in nanostructural properties are affected by the combined result of weaker skeletal INCB024360 mw muscles and impaired mineralisation. We used the reported grip strength (per unit body weight) of murine model called Hyp homologues of X-linked hypophosphatemic rickets at the same age (10 weeks) [28] as a proxy for muscular force, and compared our experimental data (degree of orientation) with the normalised grip strength and muscle weight for wild type and Hyp mice ( Fig. 7(B)). A positive association between the two muscular parameters (grip strength and muscle weight) and the two mineralisation parameters (degree of orientation and mean mineral concentration) was observed. The grip strength, muscle weight, mineral particle degree of orientation and mineral concentration of Hyp mice were all lower than those of wild type mice. This finding suggests that abnormal changes in muscle forces in disease conditions are associated with reductions in the degree of mineral particle alignment. To demonstrate

the link between increasing muscular force and the development of nano-structural parameters requires that greater muscle strength/mass Protein kinase N1 is associated with higher degree of mineral particle orientation, independent of body size variations. In this study we have demonstrated that degree of orientation, predominant orientation and mean mineral content increases with age in intramembranously ossifying bone. Several previous studies have shown a positive correlation between muscle strength and bone strength index [35] and BMD [30], [31] and [36] independent of measures of body size. However, the correlation between development of muscle strength and nano-structural parameters was not investigated.

The MicroSprayer delivers more aerosolized nanoparticles to the c

The MicroSprayer delivers more aerosolized nanoparticles to the cells than the VITROCELL/PARI BOY system, which is important for cytotoxicity testing. On the other hand application with the MicroSprayer might damage cells by generation of shear stress because high flow rates are needed for effective particle deposition. Decreases in cell viability due to impaction of aerosols have been shown by Mühlhopt et al. BGJ398 (Mülhopt et al., 2007). Although adverse effects on cells cannot be excluded this

study do not provide any indication for cell damage by using the MicroSprayer. Both aerosol generating systems were assessed with respect to cytotoxicity testing. This assessment is an important first step in the toxicological assessment of compounds. Routine cytotoxicity testing, the exposure by addition of the test compounds to the medium above cells seeded in plastic wells (submersed culture), is not physiological for respiratory cells. It may lead to a sub-estimation of their cytotoxicity because a direct contact of the nanoparticles with the plasma membrane is not likely. Therefore, cells cultured in

ALI and exposed to aerosols are recommended for physiologically relevant in vitro testing. This recommendation is supported by data showing the higher induction of the anti-oxidative enzyme HO-1 Seliciclib clinical trial in A549 upon exposure to ZnO nanoparticles in ALI than in submersed culture (Lenz et al., 2009). The higher cytotoxicity of aerosolized polystyrene nanoparticles reported in this study also suggests a stronger effect upon aerosol application. It may be suspected

that for nanoparticles with a greater tendency for aggregation, aminophylline like CNTs, the exposure condition (aerosol or suspension) has a much smaller influence on the cytotoxicity. For cytotoxicity testing, where high concentrations have to be tested to determine safety margins, the use of the MicroSprayer appears indicated because much higher doses than with the VITROCELL/PARI BOY system can be applied and the application itself did not cause adverse effects on cells. These data together with data from other groups (Fiegel et al., 2003, Knebel et al., 2001 and Savi et al., 2008) show that higher aerosol delivery rates can only be obtained by a less physiological application mode. To assess the efficacy of aerosolized nanoparticles at therapeutic doses the VITROCELL/PARI BOY system appears better because it mimics better the low flow velocities in the alveoli. Providing every compartment with one nebulizer could decrease the differences in the deposition rates between the compartments. This work was financed by the Austrian Research Science Grant P22576-B18. The Federal Ministry Transport, Innovation and Technology provided student grants for this work. The authors thank Dr. S. Mautner for help with the manuscript. “
“The level and quality of UV protection provided by sunscreen products have improved considerably over the past three decades.

The results show that the polyols yield using the untreated origi

The results show that the polyols yield using the untreated original stover sugars was only 34.42%. The polyols yield increased to 58.54% after the stover suagar hydrolysate was decolorized, Dapagliflozin molecular weight and to 67.22% after the hydrolysate was decolorized and desalted, which was close to that using corn-based glucose (71.42%). The results indicate that the two purification steps were important for keeping a high polyols yield when the stover sugars were used as the feedstock. Fig. 4 shows the recycling of the Raney nickel catalyst #12-2 using different sugar feedstocks. The activity of the catalyst maintained stable with respect to polyols yield in the four successive runs when the corn-based

glucose was used. When the original stover sugars were used, the polyols yield decreased sharply with only twice recycling of the catalyst, indicating the purification of stover sugar hydrolysate was absolutely necessary to keep the expensive catalyst to maintain a high catalytic activity. When the stover sugars were purified by decolorization, the activity of the nickel catalyst maintained stable in the three successive runs selleck inhibitor of hydrogenolysis, but the polyols yield was pretty lower. When the stover sugars were purified by both delocorization and desalting, the polyols

yield was maintained at high level in the four successive runs. The mixtures of the short-chain polyols could be obtained by vacuum distillation and then directly used as precursors for synthesizing the unsaturated polyester resins with a relative low value added. Alternatively, the hydrogenolysis products could be fractionated into different pure ingredients with high value added applications. The pigmented compounds (mostly in the

form of lignin sulfonate salts) and the enzyme proteins in the stover sugar hydrolysate tend to deposit TCL on the surface of the catalyst particles and inhibit its activity [24] and [27]. The results in Table 1 and Table 2 show that the decolorization step by activated charcoal adsorbed most of the pigmented substances and proteins, and led to the significant increase of polyols yield. The ionic strength of the reaction system significantly affects the catalyst structure and activity [23], [24] and [28]. The ions in the hydrolysate included the cation metal ions such as Fe2+, Na+, Ca2+, Mg2+ etc., and the anion ions such as SO42−, Cl− etc. The sulfate salts from the pretreatment tend to absorb to the metal surface and then poison the catalyst irreversibly [28]. Desalting step by exchange resins removed most cation and anion ions effectively, thus the ionic strength of the hydrolysate was significantly decreased. The catalytic efficiency of the nickel catalysts was greatly improved accordingly. The Raney nickel catalyst belongs to a commonly used catalyst for hydrogenation of glucose, xylose, furfural etc.

A study of 342 rheumatoid patients showed that 11 8% of doxycycli

A study of 342 rheumatoid patients showed that 11.8% of doxycycline users had some sort of side effect.2 Major side effects were nausea (15.5%), other skin abnormalities (10%), photosensitivity (8.2%), and dizziness (8.2%). The major side effect was Poly-Morph Nuclear Leukocytes (PMNL) suspensions, which were exposed to ultraviolet (UV) light showed an increase in oxygen consumption. The PMNL were then damaged when the light was suddenly shut off. It is not known if PMNLs are involved in skin damage in a photosensitive reaction3 although this is not completely

understood, it is thought PI3K Inhibitor Library to be due to the change during irradiation of molecular oxygen to excited oxygen species. One theory is that UVA radiation penetrates deeper into the skin in a spectrum of 320–400 nm (tetracycline is at 289–342 nm).4 After UV irradiation the drug molecule is in an excited energy state and causes chemical reactions as they relax to their energetic base level, which results in a synthesis of photoproducts that act as antigens, which cause an allergic reaction.5 Photo onycholysis has been reported

multiple times before. The mechanism is unknown but is thought to be caused by the Cobimetinib order unprotecting from sun light of the nail bed that has less melanin and therefore less UV protection.6 This case study shows a possible complication and its resolution of symptoms. Patients on doxycycline should be made aware of the effect of the sun light on the skin and should avoid sun exposure while receiving the medication. “
“Current Rebamipide Opinion in Chemical Biology 2014, 20:9–15 This review comes from a themed issue on Molecular imaging Edited

by Christian Eggeling and Mike Heilemann For a complete overview see the Issue and the Editorial Available online 25th April 2014 1367-5931/$ – see front matter, © 2014 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cbpa.2014.03.019 Mitochondria usually exist within cells as an extended, dynamic, interconnected network of tubules that is intimately integrated with other cellular compartments [1]. An outer membrane and a highly folded inner membrane constitute the intricate inner architecture of mitochondria. The invaginations of the inner membrane, called cristae, are not simply random wide infolds. Rather they are topologically complicated and their shape and number is adapted to the cellular requirements. The inner membrane hosts the oxidative phosphorylation system (OXPHOS). This system facilitates energy conversion resulting in the production of ATP, which makes mitochondria indispensable ‘power plants’ of eukaryotic cells. Since the 1950s, various forms of electron microscopy (EM) have provided a detailed view on the membrane architecture of these organelles (reviewed, for example, in [2 and 3]).

Similar to all activities requiring physical exertion This mecha

Similar to all activities requiring physical exertion. This mechanism seems to be supported by tests carried out by Myers et al. (2008) who found raised heart rates and oxygen usage during transits on board high speed marine craft. Various injuries and injury mechanisms are associated with WBV and repeated shock. With very few studies into the effects of repeated impacts associated with high speed marine craft motions, in spite of

the reported significant risk of injury, limited data is available to identify the injury mechanisms. This is further compounded by the ethical difficulties in reproducing the dangerous click here motions in a laboratory. Indicative scales of vibration magnitudes and typical acceleration limiting criteria have been developed as shown in Table 6. However, measures based on individual motion magnitudes, ignoring vibration frequency, duration, direction, posture and transfer points, cannot adequately describe motion severity. Frequency weighting can improve their representation of motion severity, however CP-868596 mouse the results then become highly dependent on the manner in which the weightings are calculated (Griffin, 1990). Although

lower back pain, diagnosable as damage to vertebrae or intervertebral discs, is one of the most commonly reported effects of whole body vibration, no specific dose–effect relationship, relating injury to vibration exposure has been identified (Stayner, 2001). Although Bovenzi and Betta (1994) report that there is a linear relationship between posture and the prevalence of lower back pain. Typically lower back pain is associated with vibration magnitudes between 1.0 m/s2 and 10 m/s2, rather than exposure durations (Griffin, 1990, Stayner, 2001 and Myers et al., 2008) and posture is considered a compounding Beta adrenergic receptor kinase factor in almost all epidemiological studies (Stayner, 2001). Posture has also been suggested to decrease the spine’s ability to resist

loads by a factor of up to 100 (Seidel et al., 1998) and that sitting can place additional stress on the musculature and intervertebral discs of the lumbar spine (Stayner, 2001). Mathematical modelling, replicating the mechanisms of vibration within the human body have been attempted by Pankoke et al. (1998) amongst others. However, conclusive results are difficult to obtain due to the invasive nature of any attempt to validate the results. Performance and safety concerns regarding high speed marine craft motion exposures are widespread and with the increasing legislation, including the EU directive (European Union, 2002) and operators cost concerns, including the possibilities of insurance pay-out, sick pay and operational failure, there is a need to either isolate the occupants from the motion exposure or reduce the motion exposure.

ostreatus was cultivated in substrates with seed cake added to di

ostreatus was cultivated in substrates with seed cake added to different proportions of eucalypt sawdust, corncob, eucalypt bark and coffee husk. The purpose of adding these agroindustrial residues was to balance the carbon

and nitrogen ratio, which may stimulate the mycelial growth ( Nunes et al., 2012). The substrate compositions that were selected for this study were based on the results of these previous experiments were jatropha seed cake (Sc), Sc + 10 (g/100 g) of eucalypt sawdust (ScEs), Galunisertib datasheet Sc + 10 (g/100 g) of eucalypt bark (ScEb) and Sc + 30 (g/100 g) of coffee husk + 30 (g/100 g) of rice bran (ScCh). In these substrates, the isolate Plo 6 had better biomass production and greater degradation rate of lignocellulosic compounds when compared to other tested substrates ( Da Luz, 2009). The substrates were humidified with water at 75% of the retention capacity and 1.5 kg of each substrate was placed in polypropylene bags. Next, the bags containing the substrates were autoclaved at 121 °C for 2 h. After sterilization, the substrates were inoculated with 70 g of spawn and incubated at 25 °C for 60 d. Samples for analyses

were taken at intervals of 15 d. Phytase activity (myo-inositol hexakisphosphate phosphohydrolase, EC 3.1.3.8) was determined using Taussky–Schoor Enzalutamide nmr reagent according to Harland and Harland (1980). To extract the enzyme, 3 g of the substrate was transferred to Erlenmeyer flasks (125 mL) containing 10 mL of sodium chloride (1 g/100 mL). The flasks were kept in a shaker for 1 h at 100 rpm, and the extracts were filtered through Millipore membranes (Whatman 1). The filtrate was centrifuged for 5 min at 2000 × g. The reaction to determine phytase activity contained 100 μL of the filtrate and 1 mL of sodium phytate solution (0.5 g/100 g, Sigma). This reaction was incubated in a water bath at 60 °C for 10 min, and then 1 mL of trichloroacetic acid (10 g/100 mL) and 5 mL of Taussky–Schoor

reagent were added. The phosphorus content was determined with a spectrophotometer (Thermo, Evolution 60) at 500 nm. The standard curve for phosphorus quantification was made using dibasic potassium phosphate (Sigma) with concentrations Tolmetin ranging from 0.004 to 0.02 g/100 mL. One unit of phytase was defined as the amount of enzyme required to release 1 μmol of inorganic phosphate per min from sodium phytate at 37 °C. To determine phytic acid content, 3 g of each substrate was transferred to Erlenmeyer flasks (125 mL) containing 25 mL hydrochloric acid (4 g/100 mL, Vetec). These flasks were kept in a shaker for 16 h at 220 rpm. The supernatants were transferred to centrifuge tubes (50 mL) containing 1 g of sodium chloride (Vetec), centrifuged at 1000 × g for 20 min and frozen at −20 °C for 30 min. After thawing, the supernatants were centrifuged under the same conditions and filtered through Millipore membranes (Whatman GF/D, 4.7 cm). The filtrate (1 mL) was diluted in 24 mL of deionized water.

Certain imaging modalities such as magnetic resonance imaging, tr

Certain imaging modalities such as magnetic resonance imaging, transcranial ultrasound, and single-photon emission computed tomography can be useful in making diagnostic decisions in some cases of PD. Devaki Shilpa Surasi, Patrick J. Peller, Zsolt Szabo, Gustavo Mercier, and Rathan M. Subramaniam The clinical diagnosis of Parkinson disease (PD) is difficult, as several other neurodegenerative and basal ganglia disorders have similar clinical presentations. Dopamine transporter single-photon emission computed tomography has been proposed as possible diagnostic tool to help

differentiate idiopathic PD from essential tremor and other disorders that present with parkinsonian symptoms. In addition, it is valuable in the diagnosis of dementia with Lewy bodies, differentiating Selleckchem ABT 888 it from other causes of dementia such as Alzheimer disease. Shichun Peng, Doris J. Doudet, Vijay Dhawan, and Yilong Ma This article discusses the current use of PET imaging in the evaluation of dopamine function in Parkinson disease (PD). The article reviews the major radioligands targeting dopaminergic systems in patients with parkinsonian disorders. The primary objective is to show the novel

clinical applications of molecular imaging in the diagnosis and assessment of motor and nonmotor symptoms in PD.

Index  487 “
“Li Q, Zhou XD, Kolosov VP, Perelman JM. AZD0530 solubility dmso Nicotine suppresses inflammatory factors in HBE16 airway epithelial cells after exposure to cigarette smoke extract and lipopolysaccharide. Transl Res 2010;156:326-34. In our December 2010 publication in Translational Research, we incorrectly stated that cigarette Cobimetinib clinical trial smoke extract (CSE) was “supplied by Professor C-H Cho (Department of Pharmacology, University of Hong Kong).” Although Dr Cho prepared the CSE samples, he did not directly provide us with them. Instead, they were obtained by Dr Zhou who had access to the samples while a research fellow at Hong Kong University from 2005 to 2006. “
“Chronic obstructive pulmonary disease (COPD) is a complex systemic disease, that until recently, was underrecognized, underappreciated, and poorly understood. Bonet first described COPD as early as 1679 when he discussed “voluminous lungs,” and yet it wasn’t until the 1960s that physicians began to create formalized definitions of the clinical syndrome they were encountering.1 These initial definitions focused on either clinical characteristics (such as cough and dyspnea) or anatomic features (such as enlargement of alveolar spaces) and, in some sense, neglected expanded features that could be useful in identifying and understanding the disease.