Increasing knowledge and the concern of consumers regarding food

Increasing knowledge and the concern of consumers regarding food quality, food safety and environmental protection have led to an increase in the demand for organic foods over the past few years (Magkos et al., 2006 and Saba and Messina, 2003). Apparently, there is a general perception in the population that organic foods are healthier, tastier and more nutritive than conventionally produced foods (Araújo et al., 2008, Ismail and Fun, 2003 and Saba and Messina, 2003). However, scientific evidence is insufficient to confirm or reject this assumption (Magkos et al., 2006), since comparative data of the two production systems are inadequate or inconsistent due to the heterogeneity PF 2341066 of the

material and research methodology used (Hoefkens et al., 2009 and Kumpulainen, 2001). Different foods are currently produced by organic farming. Although still not completely established, the segment of organic fruit production has grown significantly over the past few years (Borges & Souza, 2005). Fruits are excellent sources of antioxidant vitamins, as well as of other vitamins, minerals, flavonoids, and phytochemicals (Ismail & Fun, 2003). Vitamin C is one of the most important antioxidants found in fruits and vegetables

(Odriozola-Serrano, Hernández-Jover, & Martín-Belloso, 2007). This vitamin is important for human nutrition (Hernández, find more Lobo, & González, 2006) and for the food industry as an additive of processed foods (Rios & Penteado, 2003). The main biologically active form of vitamin C is l-ascorbic acid (AA), but its reversibly oxidised form, dehydroascorbic Dimethyl sulfoxide acid (DHA), also presents vitamin activity (Deutsch, 2000 and Lee and Kader, 2000), a fact demonstrating the need for the determination of these compounds in foods to estimate total vitamin C value. Carotenoids have an important antioxidant potential (Stahl & Sies, 2005),

with the main carotenoids being lycopene (Shami & Moreira, 2004) and β-carotene (Miller, Sampson, Candeias, Bramley, & Rice-Evans, 1996). One of the most important roles of carotenes, especially β-carotene, is its provitamin A activity, considering that vitamin A deficiency is one of the main nutritional problems of populations in developing countries (Rodriguez-Amaya, 1989). Data from epidemiological studies have shown an inverse association between the consumption of fruits and vegetables and the incidence of different diseases such as cardiovascular, ophthalmological and gastrointestinal diseases, neurodegenerative disorders, and some types of cancer (Van Duyn & Pivonka, 2000). Furthermore, it has been suggested that the interaction between different dietary antioxidant compounds such as vitamins C and E and carotenoids, especially lycopene and β-carotene, exerts a synergistic effect on free radicals and, consequently, a health protective effect (Stahl & Sies, 2005).

Linear regression, median,

Linear regression, median, check details interquartile range and range of the sum of dioxins and dl-PCBs are shown in Fig. 2A. Total dioxins and dl-PCBs decreased from 1999 to 2011. Fig. 2B illustrates the contribution of the dioxins fraction and the dl-PCBs fraction to the total TEQ. The median for all years of sum of dioxins and dl-PCBs were 0,9 pg TEQ-WHO 05 g− 1, whilst the median for 2011 specifically was 0.6 pg TEQ-WHO 05 g− 1. From 2002 to 2011, 475 samples were analysed for PCB6. Although some statistical differences were observed, no clear trend in the sum of PCB6 was found

as shown in Fig. 3. The median mass fraction of sum of PCB6 through the years was 5.94 μg/kg w.w. In the period from 2006 to 2011, 324 samples were analysed for various Doxorubicin in vitro pesticides. The sum of DDT is presented as box and whisker plots per year, as well as linear regression in Fig. 4A. The sum of DDT declined from 2002 to 2011, and the median over the years was 9.40 μg/kg w.w. The

levels of the other pesticides were too close to the LOQ for trend analyses. Thus, pesticide data was pooled (except DTT) and statistics were performed on all years combined (Fig. 4B). Hg and dioxins and dl-PCBs were evaluated according to current TWIs. To calculate safe consumption limits, all dioxins and dl-PCBs data were converted to 98 WHO TEQ. The maximum tolerable consumption of Norwegian farmed salmon without reaching the TWI increased over the years and reached 1.3 kg in 2011 (Fig. 5). From 1999 to 2011, dioxins and dl-PCBs represent the limiting factors in terms of safe consumption of Norwegian farmed salmon.

In this study, contaminants were examined in more than 2300 samples, and since most samples were pooled, the total number of fish analysed exceeds 10,000 individual Norwegian farmed salmon. The fish were sampled over a period of 13 years from all regions with aquaculture activity, thereby providing Clostridium perfringens alpha toxin a representative overview of the contaminant levels in Norwegian farmed salmon over the last decade. The amount and types of contaminants investigated were based on EU Council Directive 96/23/EC (EU, 1996). The contaminants chosen were also the same as previously reported in salmonids, both farmed and wild (Hites et al., 2004, Jacobs et al., 2002 and Kelly et al., 2011), as well as in salmon feed (Sissener et al., 2013). In this study, the heavy metals Pb, Cd, Hg and the metalloid As have been measured in fillets from Norwegian farmed Atlantic salmon. The levels of heavy metals described in this paper are comparable to other studies of farmed Atlantic salmon (Foran et al., 2004), as well as for farmed Atlantic-, Coho- and Chinook salmon from British Columbia (Kelly et al., 2008).

g , Unsworth, Redick, et al , 2009) WM processing was also weakl

g., Unsworth, Redick, et al., 2009). WM processing was also weakly and negatively correlated with

capacity and SM. However, WM processing demonstrated a moderate correlation with AC suggesting that AC abilities are needed during the processing components of complex span tasks. Thus, WM processing and WM storage demonstrated differential relations with capacity, AC, and SM, with WM storage being moderately related to all, but WM processing being more related to AC than to capacity or SM. Our next model examined whether WM processing would account for the relation between WM storage and gF or whether both would contribute independently IWR-1 price to gF. To examine this we specified a model in which both WM storage and WM processing predicted gF and WM storage and WM processing were correlated. If WM processing accounts for the relation between

WM storage and gF we should see that WM processing and WM storage are related, but only WM processing significantly predicts gF. If both contribute independently to gF we should see that both predict gF. The fit of the model was acceptable (see Table 3). As shown in Fig. 5 both WM storage and WM processing predicted gF. Collectively, 50% of the variance in gF was accounted for with WM storage uniquely accounting for 18%, WM processing uniquely accounting for 21%, and both shared 11% of the variance. Consistent with prior research these results suggests that WM storage and WM processing make independent contributions to higher-order cognition and in particular to gF (Bayliss et al., 2003, Logie and Duff, 2007, Unsworth et al., 2009 and Waters and Caplan, Y27632 1996). For our final model we examined whether capacity, AC, and SM would

mediate the relations between WM storage and WM processing with gF. That is, similar to the model shown in Fig. 3, we wanted to examine whether capacity, AC, and SM would mediate not only the relation between WM storage and gF, but also the relation between WM processing and gF. Therefore, we specified a model in which WM storage and WM processing were correlated and both predicted capacity, AC, and SM. The paths from WM storage and WM processing to gF were set to zero. Capacity, attention control, and secondary memory, were specified to predict gF. As shown in Table Progesterone 3 the fit of the model was good. Shown in Fig. 6 is the resulting model. As can be seen, WM storage was significantly related to capacity, AC, and SM. Likewise, WM processing was related to capacity, AC, and SM, but the strongest relation was with AC. Furthermore, capacity, AC, and SM all significantly predicted gF with 81% of the variance being accounted for in gF. Importantly, freeing the paths from WM storage and WM processing to gF did not change the model fit (Δχ2(2) = 3.98, p > .14), indicating that the paths were not significant and did not uniquely predict gF.

No restoration project is undertaken in a social vacuum (Knight e

No restoration project is undertaken in a social vacuum (Knight et al., 2010); even stand-level restoration occurs within a system

of governance that regulates relationships among landowners, funding organization(s), implementer, and stakeholders. A global movement of broadening participation in natural resources decision-making has evolved VE-821 supplier towards sharing power and responsibility (Berkes, 2009). Forest Landscape Restoration is a co-management approach that developed in response to large-scale restoration and reforestation programs undertaken by public agencies that provided few local benefits, but generated much local ill will (Barr and Sayer, 2012 and Boedhihartono and Sayer, 2012) because those whose livelihoods depended on the forest or other natural resources felt excluded from the management process (Ellis and Porter-Bolland, 2008 and Colfer, 2011). Such exclusion leads only to conflict and resource degradation (e.g., García-Frapolli et al., 2009 and Sayer et al., 2013) and its legacy of distrust and even animosity may persist (Oestreicher et al., 2009 and Nysten-Haarala, 2013). Despite the movement toward more democratic, participatory forms of resource management,

including restoration, the arrangements are diverse and reflect the governance structure, property rights and relations, and traditions of individual societies. Subsequently, no single arrangement has universal application and there are several potential obstacles to success as described below. Other aspects of social Integrin inhibitor context that affect restoration include tenure and use rights (ownership versus use rights, de jure as opposed to de facto), participation by those affected (including Prior Informed Consent; Barr and Sayer, 2012), and the social capital available (including administrative capacity, technical knowledge, and available resources). In some societies, land ownership and use rights are well defined and enforced by the rule Pyruvate dehydrogenase lipoamide kinase isozyme 1 of law. In other instances, particularly in tropical

countries, tenure relations are complex and corruption is endemic ( Kolstad and Søreide, 2009). Today’s complex ownership, tenure, and use rights may stem from historical development, for example a colonial past that has left a thin veneer of individual ownership over a traditional tenure system based on communal ownership ( Lamb et al., 2005). Further complications arise when ownership of the forest, trees, or fruit from certain trees is separate from tenurial rights to the land for agriculture. Land tenure is generally understood as the mutually accepted terms and conditions under which land is held, used, and traded. It is important to note that land tenure is not a static system; it is a system and process that is continually evolving, influenced by the state of the economy, changing demographics, cultural interactions, political discourse, or a changing natural and physical environment ( Murdiyarso et al.

With MPS, sequences can be analyzed more in depth to determine wh

With MPS, sequences can be analyzed more in depth to determine whether they are genuinely from one of the original contributors of a sample, or instead more likely to be the product of a PCR or sequencing error. Additionally, due to the ability to multiplex more loci than CE affords, broader genetic interrogation can be achieved in a single reaction, thus

conserving precious samples. The reported results comprise only 16 loci, but MyFLq can run with any number of loci. When running MyFLq with a custom loci set, the primers of these loci can be imported. The allele database is not strictly necessary to run the program. In exploratory studies, for example if building a database of known alleles, MyFLq can be run with an empty allele database. The GitHub repository contains example files for users that need either a custom Atezolizumab in vivo locus set or custom allele database. The used allele database was very small as it only compromised the alleles of the five contributors. Sequences click here that are currently not in the database are marked as red bars. These bars are very useful to visually monitor the noise level. In the future, with a larger database, it could be that erroneous sequences are nonetheless present in the database, as they could be true alleles for individuals that are not present in the sample. The solution to that problem could be to mark rare alleles (e.g. alleles with a population prevalence

<1%) with a different color. The combination

of unknown alleles and rare alleles would then indicate the level of noise. A further limitation of the current database is its nomenclature. Currently same-sized alleles get an arbitrary name within the Farnesyltransferase database, which would make it difficult to perform searches in other databases without the original sequence. When an international nomenclature for MPS STR alleles has been established, it will be incorporated in MyFLq. When all allele candidates have been reviewed, the “Make profile” action generates a report with only the selected alleles. This is the profile that a forensic analyst can use to either store in a database, to query against a database, or for direct comparison to a known sample of interest. Future versions of the software will include possibilities to interact directly with sample databases. New feature requests can be made through the GitHub website. MyFLq is the first open-source, web-based forensic MPS DNA analysis software with an easy-to-use graphical user interface. It can run natively on Illumina BaseSpace, or independently on a forensic laboratory’s server. The possibility to run the program directly from the Illumina BaseSpace environment means no extensive bioinformatics skills are required. C.V.N. participated in an internship program at Illumina, Inc. to provide feedback on building a native BaseSpace application to the Illumina developers.

The study was approved by the Institutional Committee for Animal

The study was approved by the Institutional Committee for Animal Care and Use, Health Sciences Center, Federal University of Rio de Janeiro (Protocol no. IBCCF 046). A suspension of 8 mg of particles/m3 of air was obtained by ultrasonicating 5 mg of the collected dust in 83.3 mL of sterile saline solution (NaCl 0.9%). The dose was calculated based on the body chamber volume (7 L) and on the airflow of the nebulizer (1 mL/min), taking into consideration the high dose reported by Fritschi et al. (2001). The particulate matter was digested in a HNO3–HClO4 mixture and after dissolution was brought to a final volume of 15 mL of HCl 0.1 M. The selleck inhibitor extract was analyzed by flame atomic absorption spectroscopy (VARIAN AA1475, Varian,

Inc., Palo Alto, CA, USA) following recommended standard operating procedures (Varian, 1981)

and previous reports (Trindade et al., 1981 and Azcue et al., 1988). Trace elements, nickel (Ni), manganese (Mn), aluminum (Al), iron (Fe), lead (Pb), chromium (Cr), cadmium (Cd), copper (Cu), zinc (Zn) and mercury (Hg), were measured and the results expressed as μg/g of particles. Three independent samples of the particulate matter were analyzed for this purpose. The distribution of particle sizes, as measured by their volume and surface, and the diameters encompassing 90%, 50% and 10% of the particulate matter were determined by laser diffraction (Long Bench Mastersizer S, Malvern Instruments Ltd., Malvern, Worcestershire, United Kingdom). The particulate matter was visualized by scanning electron microscopy (JEOL 5310, Tokyo, Japan). Twenty-four hours after exposure to either aerosolized sterile saline solution this website (CS and ES) or to 8 mg/m3 of aluminum dust (CA and EA) in a whole-body chamber during 1 h (1 mL/min), the animals were sedated with diazepam (1 mg i.p.), anesthetized with pentobarbital sodium (20 mg/kg body LY294002 weight i.p.), placed in the supine position on a surgical table, tracheotomized, and a snugly fitting cannula (0.8 mm ID) was introduced into the trachea. The animals were then paralyzed with pancuronium bromide

(0.1 mg/kg) and their anterior chest wall was surgically removed. A pneumotachograph (1.5 mm ID, length = 4.2 cm, distance between side ports = 2.1 cm) (Mortola and Novoraj, 1983) was connected to the tracheal cannula for the measurements of airflow (V′). Tidal volume (VT) was determined by digital integration of the flow signal. The pressure gradient across the pneumotachograph was determined by a Validyne MP45-2 differential pressure transducer (Engineering Corp, Northridge, CA, USA). The flow resistance of the equipment (Req), tracheal cannula included, was constant up to flow rates of 26 mL/s and amounted to 0.12 cmH2O/mL/s. Equipment resistive pressure (= ReqV′) was subtracted from pulmonary resistive pressure so that the present results represent intrinsic values. Transpulmonary pressure was measured with a Validyne MP-45 differential pressure transducer (Engineering Corp, Northridge, CA, USA).

The prominent, black, coal deposits beneath alluvial landforms in

The prominent, black, coal deposits beneath alluvial landforms in the Lehigh and Schuylkill River basins serve as an anomalous lithologic fingerprint when compared to the previous ∼12 ka of alluvial deposits consisting of mixed alluvium primarily composed of quartz, mica, feldspars, and clay minerals. The widespread occurrence of coal alluvium in southeastern Pennsylvania has been documented by soil scientists and archeologists for some time (Eckenrode, click here 1982, Fischer et al., 1962, Kinsey and Pollack, 1994, Kopas, 1982, Lewis, 1993, Lewis et al., 1989, Monaghan, 1994a, Monaghan, 1994b, Myers et al., 1992, Myers et al., 1995, Sisler, 1928, Staley, 1974, Vento,

2002,

Wagner, 1989, Wagner, 1993 and Wagner, 1996). The Gibraltar Series soil, which contains a black epipedon composed of coal, has been mapped throughout the Lehigh and Schuylkill River basins (Soil Survey Staff, 2012a and Soil Survey Staff, 2012b). The three sites examined here, Nesquehoning, Oberly Island, and Barbadoes Island, all provide supporting evidence of the GW3965 order widespread presence of coal alluvium and further demonstrate the lateral variability and potential for multiple episodes of deposition. Assuming no stratigraphic inversion has taken place, all coal alluvium overlies Late Woodland prehistoric deposits and, where present, Euro-American plowed A (Ap) horizons. These data suggest the coal was deposited post Late Woodland (1000–1600 AD) and initial Euro-American settlement,

well after 1600 AD, a maximum age range of ∼400 years. These observations clearly demonstrate that the coal alluvium is a stratigraphic event documented throughout the Lehigh and Schuylkill River basins that Galeterone has a conservative age range estimate of 1600 AD – recent. Historic documents provide further insight into the chronological, spatial and behavioral context of these deposits (see below). The 18th–early 20th century history of coal mining in portions of the Lehigh and Schuylkill headwaters provides ample evidence to link the stratigraphic coal event with human-induced change (discussed below). Thus, we propose elevating this stratigraphic coal event to an Anthropogenic Event, herein referred to as the Mammoth Coal Event (MCE). The term, “Mammoth Coal” is derived from the Mammoth coal bed occurring in the Pennsylvanian-age Llewellyn Formation. The Mammoth bed was of primary economic importance in the Pennsylvania anthracite fields and had an average coal seam thickness of ∼6 m (Eggleston et al., 1999) (Fig. 1). The mining and sporadic use of coal began in the late 18th century in Pennsylvania (Eavenson, 1942, Eckhart, 1992, Edmunds, 2002, Powell, 1980 and Towne, 2012).

g , Oosterberg and Bogdan, 2000) In the Mississippi delta, nutri

g., Oosterberg and Bogdan, 2000). In the Mississippi delta, nutrient excess delivered via diversions to freshwater marshes have been blamed for their apparent

vulnerability to hurricanes (e.g., Kearney LBH589 et al., 2011). For successful schemes of channelization, a comprehensive adaptive management plan for water, sediment and nutrients would be needed to protect the ecological characteristics in addition of maintaining the physical appearance of the delta plain. If increases in the sediment trapped on the fluvial delta plain may aid to balance the effects of sea level rise, a similar approach for the external, marine delta plain would completely change the landscape of that region. Composed of fossilized sandy beach and barrier ridges that receive little new sand once encased on the delta plain, the marine delta would be transformed by channelization into an environment akin to the fluvial delta with lakes and marshes. In the absence of other solutions, such as hard protection dikes and short of abandonment, channelization could potentially raise the ground locally on these strandplains and barrier plains. Instead, with no new sediment input, the marine delta would

in time result in its partial drowning; sand ridge sets of higher relief will transform into barrier systems and thus, with water on both sides, become dynamic again rather than being fossilized on the delta plain. This will provide in turn some protection to the remaining selleck mainland delta coast because Doxacurium chloride dynamic barrier systems with sand sources nearby (i.e., the delta lobes themselves) are

free to adjust to dynamic sea level and wave conditions by overwash, foredune construction, and roll over. However, it is clear that the most vulnerable part of the Danube delta is the deltaic coastal fringe where most of sediment deficit is felt. In order to tackle erosion along the delta coast, a series of large scale diversion solutions have been proposed since the early 20th century (see e.g., compilation by Petrescu, 1957). However, the entire Danube currently debouches only about half the amount of sediment that Chilia distributary used to deliver annually to construct its lobe in pre-damming era! Our study suggests instead that small but dense diversions similar to the natural Chilia secondary channels, thus another type of channelization mimicking natural processes, may minimize erosion in the nearshore. Hard structures such as breakwaters and groins that curtail offshore and alongshore sediment loss may also provide some temporary, if imperfect, relief. However, waves along the coast of Danube delta are a very efficient and relentless sediment redistribution machine, and in the long run erosion will remain a problem. Erosion of moribund lobes, such as it appears to be the case with the current St. George lobe, can provide enough sand if it is abandoned. Reworking of the St.

The potential of ADW to maintain GSH at reasonably high levels is

The potential of ADW to maintain GSH at reasonably high levels is of importance against BPA induced toxicity. Therefore,

the ability of ADW in preventing BPA induced GSH depletion by about 80% is very significant in restoring the cell viability. The GSSG formation was inhibited by ADW and this may be attributed to the formation of GSH conjugates rather than oxidation to GSSG in BPA induced toxic conditions. Earlier it was shown that Ashwagandha leaf extract and withanone, a major constituent in the leaf was beneficial to normal human fibroblasts and it showed, it was helpful to increase life span of fibroblasts by the reducing molecular damage and rendered protection against oxidative stress [41] and [42]. In yet another study, Selleck Bortezomib it was clearly demonstrated that withanone significantly rescued the damages caused by methoxyacetic acid mediated mitochondrial dysfunction through inhibition of excessive reactive oxygen species which were detrimental to mitochondrial function [43]. Beside these, cells secrete strong antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase to combat severe oxidative stress during diseased/toxic conditions. Earlier it is reported that BPA exposure results severe ROS production and results in the inhibition of antioxidant enzymes [44]. In agreement with earlier reports the antioxidant enzymes viz;

superoxide dismutase, catalase and glutathione peroxidase activities were severely diminished with addition of BPA. While addition of ADW to cells treated with BPA showed increased antioxidant enzyme activities along with increased mitochondrial selleck chemicals llc functions. The increase in the antioxidant enzyme activities adds

to the fact that ADW restores and replenishes the antioxidant system and aids to restore normal mitochondrial functions in BPA intoxicated cells. Thus it is concluded that ADW exerts a strong cellular rejuvenation and acts as an antidote against NOAEL concentrations of BPA in HepG2 cells. Nil “
“Piroxicam, a classical NSAID, is a choice for most clinicians in arthritis and from similar clinical conditions. The possible risk of gastro-toxic effects and ulceration of gastric mucosa imposed by this drug [47] has recently restricted its use. This drug induced gastric damage is possibly caused due to oxidative stress built up in vivo in the course of its metabolism or action. Earlier studies indicated gastro-protective PGE2 synthesis leads to decreased gastro-intestinal motility, reduced blood flow and ischemia in the stomach [5].Such changes generate free hydroxyl radical (.OH) in gastric tissues. Thus, the main causative factor behind piroxicam mediated gastro-toxicity and gastric ulceration has been recognised to be .OH [8]. Leaves of the curry plant (Murraya koenigii), well known for their culinary use, have been reported to be effective in many diseased conditions [2] and [22].

, 2007, Lowe et al , 2012, Menéndez and Woodworth, 2010 and Woodw

, 2007, Lowe et al., 2012, Menéndez and Woodworth, 2010 and Woodworth and Blackman, 2004) suggests that the rise in mean sea level is generally the dominant cause of any observed increase in the frequency of extreme events. In addition, using model projections of storm tides in southeast Australia to 2070, McInnes et al. (2009) showed that the increase in the frequency of flooding events was dominated by sea-level rise. There are therefore significant unknowns associated with the shape and extent of the uncertainty distribution of the projections of sea-level rise. Improved allowances for sea-level GSK2656157 in vitro rise require better estimates of future sea level and, just as importantly,

of its uncertainty distribution and the behaviour of its upper

tail. “
“Evidence-based practice (EBP) involves clinical reasoning in three major domains: best-available scientific evidence, clinical judgment (experience), and patient’s perspective (Figure 1). Evidenced-based wound care seeks to integrate clinical wisdom with the best available science to optimize patient care with safety, statistical power and efficacy brought to bear on the problem at hand, the wound(s).1 This paper provides perspective primarily in the domain of best-available scientific evidence as it pertains to whirlpool (WP) use in wound care. Whirlpool, one of the oldest types of hydrotherapy, was originally used by physical find more therapists (PTs) to treat patients with burns in need of extensive debridement. In many areas of the United States, WP remains an active component of wound care as a means for the removal of necrotic cellular debris and contamination. With the advent of other options, using water as a cleansing agent, it is important to critically analyze the literature reporting the effects of WP. The following summarizes the evidence pertaining to both the goals and the adverse events associated with WP therapy. The full-body WP (Figure 2), and the

Hubbard tank, quickly spearheaded Rolziracetam the development of smaller extremity tanks (Figure 3).2 and 3 The shared goals of WP therapy are to remove gross contaminants and toxic debris including surface bacterial, increase local circulation, decrease wound pain, decrease suppuration, decrease fever, help soak and gently remove dressings, and ultimately accelerate healing.2 and 4 Typically, it is prescribed for non-healing wounds or to remove a substantial amount of necrotic tissue. The limb or extremity is submersed for 10–20 minutes in water at 92°–96 °F, with or without agitation and antimicrobial agents.5 The presence of bacteria and/or biofilm can both be obstacles to healing. All wounds have some level of contamination which does not equate to ‘infection’. Critical bacterial colonization occurs when the number of microbes and/or their byproducts exceed the capability of the host to generate a healing response significant enough to effect wound closure.