The evidence presented above may be compared with conclusions tha

The evidence presented above may be compared with conclusions that have been drawn from studies elsewhere, although regional and local site conditions vary a great deal. Considerable colluvial storage of eroded soil materials has been suggested, particularly in the loess terrains of southern Germany (Bork, 1989, Lang, 2003, Houben, 2003, Houben, 2012 and Dotterweich, 2008) and Belgium (Broothaerts et al., 2013); from the much later phase of cultivation NU7441 ic50 in North America (Happ et al., 1940 and Walter and Merritts, 2008); but also from prehistoric

site studies in the UK (Bell, 1982, Brown and Barber, 1985 and Brown, 1987). On the other hand, French et al. (2005) suggest that in UK chalkland areas early soil erosion and thick colluvial deposits may have been less than previously supposed. Stevens and Fuller (2012), following an analysis of radiocarbon dates for wild and cultivated plant foods, suggest that an agricultural

revolution took place in the UK during the Early-Middle Bronze Age. This shift, from long-fallow cultivation to short-fallow with fixed plots and field systems, fits well with the timing of accelerated floodplain deposition identified in this study, and with the apparent lag between the development of agriculture in the Neolithic and accelerated sedimentation described elsewhere (Houben et al., 2012). However, dated AA deposits, rather than a whole catchment FK228 order sediment budget, have been analyzed here so that the question of whether there actually was lagged remobilization of early colluvial sedimentation, or whether early colluvial deposition was not that extensive in the first place, cannot be answered using our data. Our data set does, however, emphasize the importance of mediaeval erosion as noted in the UK (Macklin et al., 2010) and elsewhere in Europe (Dotterweich, 2008 and Houben et al., 2012). We also draw attention to the variable autogenic conditions involved in alluvial sequestration of AA: catchment size, depositional environments, and the grain sizes involved. Anthropogenic impact and sediment supply are commonly

next discussed in terms of hillslope soil erosion parameters, but channel erosion by network extension and by lateral/vertical erosion were also important sediment sources for later re-deposition. In the Holocene, sediment exchange within alluvial systems supplied large volumes both of coarse and fine material (cf. Passmore and Macklin, 2001, Chiverrell et al., 2010 and Macklin et al., 2013), and for alluvial sedimentation hydrological factors affecting competence-limited channel erosion and network extension are as significant as the supply-limitation factors affecting the input of slope materials. There is a suggestion within our data set that such hydrological factors were important for the early entrainment and deposition of channel bed materials, whether surface soil stripping was important or otherwise ( Fig. 5 and Fig. 6).

These experiments were performed by specialists at the School of

These experiments were performed by specialists at the School of Chemistry’s NMR Unit, University of Edinburgh (Edinburgh, Scotland, UK). The sample was dissolved in 350 μl D2O (Sigma-Aldrich) and placed into a Shigemi tube. Spectra were acquired using 800 or 400 MHz NMR spectrometers (Bruker Daltonics, Bremen, Germany). 1D 1H spectrum was measured using 64 scans, acquisition time of 4.1 s, relaxation time of 5 s, and flip angle of 30°. A 2D Correlation Spectroscopy (COSY) spectrum was acquired

using t1 and t2 acquisition times of 148 and 256 ms, 2 scans per increment and a relaxation time of 2 s resulting in the total acquisition learn more time of 2 h 40 min. The 2D Total Correlation Spectroscopy (TOCSY) spectrum was acquired in 1 h, using t1 and t2 acquisition times of 37 and 256 ms, 4 scans per increment and a DIPSI-2 mixing time of 150 ms. The 2D Nuclear Overhauser Effect Spectroscopy

(NOESY) spectrum was acquired in 3.5 h, using t1 and t2 acquisition times of 37 and 256 ms, 8 scans per increment and a mixing time of 400 ms. The 2D 1H-13C Heteronuclear Single Quantum Coherence (HSQC) spectrum was acquired in 2 h, using t1 and t2 acquisition times of 30 and 128 ms, 12 scans per increment. The 1D 13C NMR spectrum INCB018424 solubility dmso was acquired in 6.5 h using 8k scans, the acquisition time of 340 ms and the relaxation time of 2.5 s. The 400 MHz 1D 1H spectra with and without 31P decoupling were acquired using parameters similar to those used for the 800 MHz 1D 1H spectrum. 31P NMR spectra were acquired in 20 min using 512 scans, acquisition time of 0.5 s and a relaxation IKBKE time of 2 s. The 2D 1H-31P HMBC spectra were acquired in magnitude mode using a phase cycled Heteronuclear Multiple Bond Coherence (HMBC) pulse sequence optimized for

1H-31P coupling constant of 10 Hz. The spectra were acquired in 3.52 h using t1 and t2 acquisition times of 20 and 250 ms; 32 scans per increment were accumulated. The sample was analysed at pH 3.8 and 6.5, by adjusting the pH of the sample (3.8) to 6.5 after titration. In order to evaluate the relevance of ADP to the vasoactive effect of the venom as a whole, concentration-response curves were performed in rat aortic rings, in the absence or presence of suramin, a P2-purinergic receptor antagonist. Increasing cumulative concentrations of Lasiodora sp. venom (0.06-64 μg/ml) or ADP (0.001-316 μM) were added in aortic rings with functional endothelium pre-contracted with phenylephrine (0.1 μM). The experiments were repeated in the presence of suramin (100 μM), added to the bath 20 min prior to the addition of phenylephrine. Results are expressed as means ± standard error of the mean (S.E.M.). Results from contractile experiments were expressed as percentage decrease in the maximal contraction induced by phenylephrine, and the point when the basal line was reached was considered 100% relaxation.

Post-treatment relapse was confirmed in patients with HCV-RNA lev

Post-treatment relapse was confirmed in patients with HCV-RNA level less than 25 IU/mL at the end of treatment and subsequent HCV-RNA level of 25 IU/mL or greater in 2 consecutive measurements. Efficacy analyses were performed using the intent-to-treat population, defined as all randomized selleck chemicals llc HCV genotype 1b–infected patients who received

at least one dose of coformulated ABT-450/ritonavir/ombitasvir. The safety population included all patients who received at least one dose of study drug. A population of 90 patients per treatment arm was calculated to provide greater than 90% power to achieve noninferiority of the active regimen to the historical threshold (64%). SAS software (SAS Institute,

Inc, Cary, NC) for the UNIX operating system was used for all analyses. All statistical tests and all confidence intervals were 2-sided with a significance level of .05. Patient screening began on August 14, 2012, and the final SVR12 data were collected on January 16, 2014. Of 324 patients screened, 187 were randomized and 186 received study drug (91 in group 1, 95 in group 2) (Supplementary Consort Flow Chart). Null responders, partial responders, and relapsers to previous pegIFN/RBV treatment comprised 34.9%, 28.5%, and BMS-907351 chemical structure 36.6% of the study population, respectively,

evenly stratified between treatment arms (Table 1). Reasons for screen failures are provided in the Supplementary Appendix. Seven randomized patients, 3 in group 1 and 4 in group 2, were not included in the intent-to-treat efficacy population. Of these, 6 patients were enrolled before a protocol amendment and received noncoformulated ABT-450/ritonavir/ombitasvir, 3 of whom were genotype 1a; a seventh patient’s HCV subgenotype was not determined. After 12 weeks of treatment, 96.6% (85 of 88; 95% CI, 92.8–100) of group 1 and 100% (91 of 91; 95% CI, 95.9–100) Anidulafungin (LY303366) of group 2 patients achieved SVR12 using the intent-to-treat population for both groups (Figure 1; Table 2, Supplementary Figure 2). For the primary end point, SVR12 rates in both treatment groups were noninferior to the historical SVR rate for telaprevir plus pegIFN/RBV in comparable treatment-experienced patients. Both treatment groups also were superior to the historical rate. Noninferiority of group 2 to group 1 was shown because the treatment difference in SVR12 rates was 3.4% (95% CI, -0.4 to 7.2). No patients from either treatment group experienced on-treatment virologic failure or post-treatment relapse. Of the 3 patients in group 1 who did not achieve SVR12, there were 2 (2.

The lowest P-value of SMTAs was observed for Contig10156-1-OP1 (P

The lowest P-value of SMTAs was observed for Contig10156-1-OP1 (P = 1.47E − 10, R2 = 0.15) associated with seed coat color ( Table 2). The three analytical approaches (SFA, Q GLM, and Q + K MLM) were compared for numbers of SMTAs. The highest number of SMTAs (1141) was detected for the SFA

approach, followed by the Q GLM approach (890). The lowest number of SMTAs (63) was detected by the Q + K MLM approach, which only detected 5.5% and 7.1% of the SMTAs detected by SFA and Q GLM, respectively. These results confirm previous observation that the number of SMTAs estimated with GLM is higher than with MLM [40]. Forty-four common SMTAs involving selleck chemical 38 SNPs were detected by all three methods ( Table 2). Six of the 38 SNPs each had two SMTAs; and the remaining 32 SNPs had one SMTA. The lowest P-value was observed for the association of Contig10156-1-OP1 with the seed coat color trait ((P = 4.91E − 11, Table 2). Most interestingly, nine SMTAs were revealed at P < 0.0001 with all three approaches, considering kinship and/or population structure for this collection. These nine SMTAs include five for seed coat color, one for leaf undulation,

two for leaf anthocyanin, and one for stem anthocyanin. Four SNPs involved in the five SMTAs for seed coat color were previously mapped on Linkage Group 7. Two SNPs mapped on Linkage Group 9 were associated with leaf and stem anthocyanin. Results from the current study were consistent with our previous study using the same Oligo Pool Assay (OPA), LSGermOPA [30]. In that report, leaf type accessions contained high within-horticultural type genetic variability SCH772984 order (24.2%, P > 0.01), which was almost identical to the current analysis (25.3%, P > 0.01) ( Table 1). The high level of genetic diversity

revealed by SNPs was consistent with the high morphological variability observed within this horticultural type. Accessions of this type have leaves that widely differ in shape (entire to highly lobed), margins (straight to highly undulating), size (small to large), or color (various shades of green and various distribution and intensities of anthocyanin) [42]. The high genetic variability Sulfite dehydrogenase within this type is evident from Fig. 1 in which the leaf type accessions distributed across five of the six clades. The butterhead type also possesses high genetic variability within horticultural type. The accessions of this type were clustered in three clades ( Fig. 1). In contrast, a relatively lower level of genetic variability was observed within crisphead horticultural types. However, our current estimation of genetic diversity for this group (19.5%) was higher than previously reported (2.4%) (Table 1). Also, in the current study crisphead type lines were divided into two Clades, I and II. This increased diversity is probably related to a more than 10-fold increase in the number of accessions analyzed (from 5 to 53 accessions).

33 Omission of this study reduced the heterogeneity and had minim

33 Omission of this study reduced the heterogeneity and had minimal effects on the summary risk estimates attained, reinforcing the conclusions drawn. It is not Nivolumab in vivo known why the associations between smoking and Barrett’s esophagus were lower in the Irish study population; the proportion of population-based controls that reported ever smoking was higher (55%) than the other studies (45–47%), but this slightly higher rate is insufficient to mask the association evidenced in the other studies. In addition, the distribution of pack-years of cigarette smoking was similar across control groups and studies,

and provision of individual patient data enabled similar confounding structures to be constructed for study-specific models. FINBAR’s inclusion criteria did restrict recruitment of patients to those with long-segment Barrett’s esophagus (≥3 cm; Table 1); a criterion not used by the other 4 studies included in this analysis. However, this is unlikely to have led to lower estimates of association, given that a previous analysis of Kaiser Permanente Northern California data evidenced a stronger association of cigarette smoking with long-segment Barrett’s esophagus (OR = 1.72; 95% CI: 1.12–2.63) buy GDC-0068 compared with that for short-segment Barrett’s esophagus (<3 cm; OR = 1.19; 95% CI: 0.76–1.85).31 It remains unexplained why the FINBAR estimates

of association were lower relative to the other studies Methane monooxygenase included in this pooled analysis. Analyses stratified by sex suggested that cigarette smoking might be a stronger risk factor for Barrett’s esophagus among men than among women. However, this relationship was only observed when assessing ever cigarette smoking in Barrett’s esophagus cases compared with GERD controls; analyses of pack-years of cigarette smoking and comparisons with population-based controls were null. Given the known genotoxic effects of tobacco smoke, evidence that effects of cigarette smoking are similar in men and women,57 and the number of tests conducted, we believe this result

represents a chance finding. Interaction analyses indicated that heartburn/regurgitation symptoms and ever smoking biologically interact in the risk of Barrett’s esophagus—the attributable proportion of disease among individuals exposed to these 2 factors was estimated to be 0.39 (95% CI: 0.25–0.52). Biological interaction of these variables in this setting is plausible, given evidence that tobacco smoke might not only have direct genotoxic effects,58 but might also induce transient lower esophageal sphincter relaxations,59, 60 and 61 increasing the likelihood, length, and severity of gastroesophageal reflux, a major risk factor for Barrett’s18 and the sequela, esophageal adenocarcinoma.17 Interaction between gastroesophageal reflux symptoms and smoking has been reported previously for Barrett’s esophagus with dysplasia26 and for esophageal adenocarcinoma.62 There were several strengths of this analysis.

, 2011); this complex interface is characteristic of ‘real world’

, 2011); this complex interface is characteristic of ‘real world’ social interactions, but difficult to access using conventional neuropsychological stimuli. In this study we assessed mentalising in music using a novel paradigm based on the attribution of affective mental states in a cohort of patients with bvFTD and in healthy older control subjects. Neuroanatomical correlates of mentalising ability in the patient group were assessed using voxel-based morphometry (VBM) on structural brain MRI data. Based on previous evidence

concerning ToM processing in FTLD (Gregory et al., 2002; Kipps and Hodges, 2006; Adenzato et al., 2010), we hypothesised that attribution of mental states (but not

other kinds of attributions) Inhibitor Library to musical stimuli would be selectively vulnerable in bvFTD. We further hypothesised that performance on the mentalising task would correlate with grey matter volume in medial PFC, OFC and anterior temporal regions previously implicated in both ToM and emotion recognition in music, in FTLD and in the healthy brain (Menon AZD6244 price and Levitin, 2005; Zahn et al., 2007, 2009; Steinbeis and Koelsch, 2009; Eslinger et al., 2011; Omar et al., 2011). Twenty consecutive patients fulfilling consensus criteria for bvFTD (Rascovsky et al., 2011) were recruited from the tertiary-level Specialist Cognitive Disorders Clinic at the National Hospital for Neurology

and Neurosurgery, London, United Kingdom (details summarised in Table 1). All bvFTD patients had structural MRI evidence of frontal lobe atrophy with or without accompanying temporal lobe atrophy, in support of the syndromic diagnosis Florfenicol of bvFTD. Twenty healthy control subjects with no history of neurological or psychiatric illness were also recruited (Table 1). No subject had a history of clinically significant hearing loss. All subjects had an assessment of general neuropsychological functions (Table 1), including the Awareness of Social Inference Test (TASIT; McDonald et al., 2003). Patients’ carers completed the Cambridge Behavioural Inventory (CBI; Wedderburn et al., 2008) as an index of behavioural symptoms; item 78 on the CBI (‘Appears indifferent to the worries and concerns of family members’) was selected for further analysis as the item most relevant to ToM. All participants were native to Britain, except one subject who had been resident within the United Kingdom for 15 years, and all had lifelong exposure to Western music. Most subjects had fewer than two years formal music training, corresponding to the ‘least trained’ (novice, non-musician) category of musical experience described by Halpern et al. (1995). Informed consent was obtained for all subjects and the study was approved by the local research ethics committee under Declaration of Helsinki guidelines.

S3) In comparison, inhibition of NF-κB by the same dose of QNZ s

S3). In comparison, inhibition of NF-κB by the same dose of QNZ significantly prevented the induction of p21 by ANE, confirming the validity of the above experiments (Fig. 3 C, S4A). Because the induction is independent of reactive oxygen species-mediated DNA damage, ANE may upregulate NF-κB signaling to directly increase p21 (Fig. S4B). NF-κB inhibition also obviously increased ANE cytotoxicity but not PARP cleavage, an indicator of apoptosis (Fig. 3D, S4 C). Although all these results suggested ANE indeed activated NF-κB to modulate cell functions, NF-κB is not directly involved in the upregulation of IL8 transcription. ANE might also induce a few inflammatory cytokines

via a mechanism in addition to NF-κB. Like Akt, phosphorylation of STAT3 (Y705) was also decreased by ANE under lower serum condition (Fig. 4A, S5). Despite that ANE treatment significantly reduced the phosphorylation of total Ku-0059436 nmr STAT3 (Y705), the

ratio of nuclear to cytoplasmic localization of unphosphorylated STAT3 was not altered (Fig. 4B). As a control, ANE enhanced nuclear translocation of Snail proteins. Moreover, inhibition of STAT3 dimerization by NSC74859, which reduces DNA-binding STAT3 with IC50 of 86 μM, reduced the activation of IL8 promoter (Fig. 4 C) [22]. In contrast, inhibition of STAT3 phosphorylation Pifithrin-�� cost by JAK inhibitor I, a pan JAK inhibitor with IC50 value between 1-15 nM, did not detectably downregulate the reporter activity (Fig. 4 C) [23]. This result suggests STAT3 is required for ANE-induced IL8 transcription but JAK-mediated Y705 phosphorylation is dispensable. Similar effects also could be seen in the transcripts level of IL6 although the case of IL8 was inconsistent possibly because the mRNA stability may be independently regulated (data not shown) [24]. These results increase

a possibility that ANE enhances inflammation in oral mucosa at least Montelukast Sodium via facilitating dephosphorylation of nuclear STAT3. Activated STAT3 is associated with inflammation during tumor progress [25]. However, ANE may modulate the transcription of a few inflammatory cytokines by enhancing Y705 dephosphorylation of STAT3 since un- and phosphorylated STAT3 had been reported to differently regulate several downstream targets [26]. In this study, we provided a few examples to prove serum concentration influenced the effects of ANE in cultured cells. The effects of ANE under different serum condition give a rational explanation to the various alterations in betel quid chewers. In serum-starved cells, ANE caused cell ballooning and nuclear pyknosis. Theoretically, the environment that oral epithelial cells reside in is impossible to be stringently serum free. However, epithelial tissue normally is avascular and less accessible to the circulating nutrients in blood stream. A previous research indicated the epidermis in average has lower ratio of interstitial fluid than dermis [27]. Because in our results even 0.

N was exceeded several times in the second half of January In t

N. was exceeded several times in the second half of January. In the three storm situations analysed in this work, the basin filling is represented by the starting (reference) sea level prior to the occurrence of the storm-caused changes (Table 2). In all

three situations, the level was similar to the mean sea level (500 cm N.N.), except for the level of 476 cm at Świnoujście on 13 January 1993. The role of tangential wind stresses in the emergence of drift currents and their resultant contribution to the rise or fall of sea level in the ports of an area is understandable; the magnitude of a rise or fall depends not only on the wind speed, but also on the wind duration, direction, wind fetch over the sea surface, and compensatory flows in the inshore zone. The

click here wind effects are directly related to the pressure distribution over an area. If water molecules move onshore, the presence of land will contribute to the kinetic energy of the flow being transformed into forces raising those molecules up to a ‘higher level’, i.e. the emergence of a surge in the inshore zone. If the wind blows seawards, the sea level in the inshore zone selleck screening library will fall. However, as shown by tide gauge records, true sea level surges and falls can be several times higher than the values resulting from the action of tangential wind stress upon the fluid surface

(Wiśniewski & Holec 1983). Suursaar et al. (2003) pointed out that the highest surge events on the west Estonian coast are associated with deep cyclones producing strong SW and W winds in suitably oriented bays such as Pärnu Bay. As reported by Suursaar et al. (2006), cyclone Gudrun, which occurred in January 2005, caused the heaviest storm surge along the coasts of the Gulf of Riga. The sea level at Pärnu was 2.75 m higher than the mean level there. In the Gulf of Finland, acetylcholine new records of sea level increase were measured as well, e.g. in Helsinki (1.51 m). Skriptunov & Gorelits (2001) showed that significant wind-induced variations in the water level near the River Neva as well as their magnitude and duration result from the wind regime and the morphology of the near-mouth offshore zone. Averkiev & Klevanny (2007) analysed the effects of atmospheric pressure as well as wind direction and speed on the sea level in the Gulf of Finland. They showed the cyclone trajectory to be potentially important in generating storm surges particularly damaging for St. Petersburg (Russia). The problem of sea level deformation by concentric, mesoscale, fast- moving deep baric lows was tackled by Lisowski (1960, 1961, 1963), Wiśniewski & Holec (1983)Wiśniewski (1996, 1997, 2003, 2005), Wiśniewski & Kowalewska-Kalkowska (2001, 2003, 2007), Wiśniewski & Wolski (2009).

In order to analyze the bone matrix mineralization, mechanical pr

In order to analyze the bone matrix mineralization, mechanical properties and intra-specimen variations at the microscopic scale, tibiae were collected from four mice (2 males, 2 females), randomly selected from the wild type group and from

the oim group. The bones were fixed in 70% ethanol (1 week), dehydrated using a graded ethanol series (70, 80, 95 and 99% for 48 h in each), and substituted with xylene (24 h). The specimens were then infiltrated for 48 h in two successive changes of pure methyl methacrylate (MMA) replaced by two changes of MMA + α-azo-iso-butyronitrile www.selleckchem.com/products/epacadostat-incb024360.html (24 h) and finally polymerized slowly at 37 °C (all chemicals purchased from VWR, UK). The tibiae were sectioned transversally at the mid-diaphysis with a low speed diamond saw (Isomet, Buehler GmbH, Germany) and the cross-sections were ground with increasingly finer RGFP966 in vitro grades of carbide papers (from P500 to P4000) and finally polished with diamond slurry (diameter: 0.25 and 0.05 μm). The tibia mid-diaphyseal cross-sections were carbon coated and analyzed using qBSEM in an EVO®MA15 scanning electron microscope (Zeiss UK Ltd., UK) operated at 20 kV, at a working distance of 13 mm, and a beam current of 0.5 nA. The qBSEM digital images were recorded with a nominal magnification

of 137 × (field width: 2.133 mm, pixel size: 1.04 μm). The image backscattered electron (BSE) current signal (digitized in gray levels) were standardized against the BSE signals of monobromo and monoiodo dimethacrylate standards which span the signal range found for mineralized tissues: 0 (black, monobrom) representing osteoid and 255 (white, monoiod) representing Tacrolimus (FK506) highly mineralized bone [28] and [29]. To facilitate visualization, the gray-level range was also divided into 8 equal size classes

(1–32, 33–64, 65–96, 97–128, 129–160, 161–192, 193–224, 225–255), representing no mineralization (class 1) to very high bone mineralization (class 8). The distribution of pixels into the different bone mineralization classes was then calculated and provides an estimate of the amount and distribution of bone mineral within a sample. For numerical analysis, each cross section image was automatically divided by a custom Matlab program into 12 areas corresponding to the periosteal, mid-cortex and endosteal sectors of the anterior, lateral, posterior and medial cross section quadrants. The mean pixel gray-level value in each sector was then calculated as an estimate of the mean amount of bone mineral in this sector. Nanoindentation tests were conducted on the same tibia mid-diaphyseal cross-sections to a maximum load of 8 mN at a constant loading rate of 800 μN/s in the longitudinal axis using the TI700 UBI (Hysitron, MN, USA) with a Berkovich diamond tip.

Each of these tests focused on a local region of the ocean where

Each of these tests focused on a local region of the ocean where observations may be compared in a fair way to a column ocean model and avoid non-local fluxes and

long-term/large-scale system adjustments. For these tests, there was a great deal of uncertainty in the ability selleckchem to observe each experiment’s forcings, and flux corrections were needed in order to attain a reasonable agreement to data. With that caveat, it was found that the KPP provides excellent predictions of the time evolving structure of the observed response. For low latitudes, an alternate strategy was employed to test the KPP. Out of concern that uncertainties in wind forcing were too large, Large Eddy Simulations (LES) were used to simulate observations (Large and Gent, 1999). This is reasonable as LES resolve much of the length and time scales involved in turbulent processes whose net effects KPP is supposed to represent. Because of computational limitations, LES simulations of Large and Gent

(1999) CHIR-99021 in vivo were limited in space and time and therefore would not capture the longer-term structures and feedbacks that could likely be present in the world’s ocean. In this present study we want to revisit the question of the potential for observational data to constrain uncertainties in KPP mixing physics. In particular we focus in on the issue of how to make a fair comparison between the output of the MITgcm and 65 moored buoys in the TAO/TRITON array in the Tropical Pacific on short (i.e. less than seasonal) time

scales. Later we will use this short-term metric, in addition to metrics that we have devised for longer time scales (Zedler et al., submitted for publication), as a basis for using Anacetrapib Bayesian inference to explore parameter space of the KPP within the MITgcm. Our particular approach for sampling does not require the construction of a statistical surrogate model (Jackson et al., 2004 and Jackson et al., 2008), but the success of its search depends on the reasonableness of how candidate model configurations are tested against data. In this case, there is a certain danger that a close match to observational data could be attained for spurious reasons, perhaps related to errors in our knowledge of the wind forcing, or the many ways a model can exploit compensating errors to get a good match to observational data. We therefore are motivated to create a metric that involves a more direct test of KPP mixing physics by focusing on short time scales and the relationships between wind forcing and the response of sea surface temperatures.