Skp has been shown to interact with early OMP folding intermediates at the

periplasmic side of the inner membrane [11, 12] and to keep immature OMPs in a soluble state [13, 14]. DegP on the other hand, was found to bind to and stabilize folded OMP monomers [15] and thus appears to act downstream of Skp in the proposed Skp/DegP pathway for OMP maturation. Conflicting results have been reported regarding the Sirtuin inhibitor involvement of the periplasmic PpiD protein in the biogenesis of OMPs. PpiD is anchored to the inner membrane by an N-terminal transmembrane segment and consists of a single parvulin domain flanked by large N- and C-terminal protein regions. The N-terminal region shares sequence similarity with the N-terminal region of SurA, which comprises the major part of the SurA chaperone module ([16–19]; see additional file 1). Several previous findings suggested that PpiD and SurA have overlapping functions in OMP biogenesis www.selleckchem.com/products/bgj398-nvp-bgj398.html [18]. First, a ppiD mutant was documented to have phenotypes that are similar to those of a surA mutant and are suppressed by multicopy

surA. Second, the simultaneous deletion of ppiD and surA was reported to cause lethality. More recently however, surA ppiD find more mutants were shown to display no visible growth defects [20]. Finally and most importantly, ppiD was isolated as a multicopy suppressor in a surA mutant. Remarkably however, whereas the surA phenotypes result from loss of chaperone function [2], a high PPIase activity of PpiD was identified as the complementing biochemical activity [18]. Most recently, this result was disputed by the finding that the isolated parvulin domain of PpiD is devoid of detectable PPIase activity [19]. Here, we analyzed the functional interplay of PpiD with SurA, Skp, and DegP to define its role in the all E. coli periplasm. Results Re-examination of PpiD function in the biogenesis of OMPs To resurvey the role of PpiD in OMP maturation we analyzed the physiological consequences of both inactivation and overexpression of ppiD in wild-type cells

and in the surA and skp mutants, respectively, using phenotypes known to report on OMP biogenesis and outer membrane integrity, such as σE activity, resistance of the cells to SDS/EDTA and to the antibiotic novobiocin, as well as the levels of major OMPs in their outer membranes. In contrast to previous work [18] we found that expression of multicopy ppiD from the IPTG-inducible P trc promoter does not suppress the surA mutant phenotypes but rather interferes with cell growth (data not shown). We therefore used a plasmid (pPpiD) that carries ppiD under control of its natural promoter, which is positively regulated by the classical cytoplasmic σ32-dependent heat-shock response and by the Cpx two-component system [18, 21]. Consistent with recent observations [20], the inactivation of ppiD in a surA strain did not cause lethality.

Other classes of antihypertensive have compelling contraindications when conditions

such as asthma (unselective β-blockers), pregnancy, hyperkalemia, PCI-32765 ic50 or bilateral renal artery stenosis (ACE inhibitor/ARB) are present [2]. Prescribers should also consider potential AE Baf-A1 cell line profiles when considering antihypertensive treatment, as these can be strong deterrents to patient adherence [49]. CCBs may also be a preferred drug class in many antihypertensive combination strategies (with ACE inhibitors, ARBs, and diuretics) [2]. Combination of nifedipine GITS (gastrointestinal therapeutic system) with either losartan or lisinopril has demonstrated greater BP lowering than https://www.selleckchem.com/products/VX-680(MK-0457).html with either agent alone [50, 51]; in the mulTicenter study evALuating the Efficacy of Nifedipine GITS-Telmisartan combination in BP control and beyond (TALENT), initial combination therapy provided greater and earlier (from 2 weeks) 24-h BP control vs. monotherapy [52]. The Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) study was the only large trial to directly compare RAS blockade in combination

with either a CCB or a diuretic, and demonstrated the benefit of an amlodipine-benazepril combination over a hydrochlorothiazide (HCTZ)-benazepril combination for reducing CV events in high-risk patients with hypertension [48]. However, the combination of RAS blockade with a diuretic has shown beneficial

outcomes in particular subgroups of patients, such as those with congestive Dichloromethane dehalogenase heart failure [53], and an ACE inhibitor/diuretic combination appears to demonstrate a particular additive efficacy in Black patients [54]. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, an ARB/diuretic combination (losartan/HCTZ) showed significantly better reductions in CV morbidity and mortality for similar BP reduction, largely attributable to superior stroke prevention [55]. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed lower visit-to-visit BP variability with a CCB-ACE inhibitor combination (amlodipine based) vs. a β-blocker-diuretic combination (atenolol based), and the CCB-ACE inhibitor combination was associated with a 34 % reduction in new-onset diabetes [56]. Dual RAS blockade is no longer recommended owing to concerns regarding renal damage and an increased incidence of stroke [57, 58]. International guidelines vary in their recommendations toward initiating monotherapy vs. combination therapy (Table 3).

These enzymes [8, 9] initiate an antioxidant response, which can be beneficial for cancer prevention [13]. However, the Nrf2-ARE pathway has recently been implicated in chemoresistance and the feasibility of Nrf2 inhibition as a strategy for sensitizing cells to chemotherapeutics was demonstrated [13–15]. HMOX1 upregulation has been identified in the adaphostin response in adherent cell lines, but not in hematopoietic cell line models, and it appears that adaphostin

activates a different oxidative stress response in solid tumor models than in leukemia models. Thus, we have selleck kinase inhibitor investigated the mechanism behind HMOX1 induction in the adaphostin-sensitive lung tumor cell line NCI-H522, and demonstrated an enhancement of adaphostin toxicity following inhibition of Nrf2 nuclear translocation with the PI3K inhibitor wortmannin. Methods Drugs and Cell Culture Adaphostin (NSC 680410) and wortmannin (NSC 221019) were obtained from the repository of the National Cancer Institute’s Developmental Therapeutics Program (Rockville, Maryland). Desferrioxamine (DFX) and N-acetyl-cysteine (NAC) were purchased from Sigma® (St. Louis, Missouri). NCI-H522, and the leukemia cell lines, (Jurkat, HL60 and K562) were obtained

from the NCI-60 Human Tumor Cell Line Screen (National Cancer Institute-Frederick, Maryland). Transcriptional Profiling: Microarray Technology Human OperonV2, 20K arrays, BMN 673 in vitro (National Cancer Institute microarray facility/Advanced Technology Center, Gaithersburg, Maryland) were utilized according to published protocols http://​madb.​nci.​nih.​gov/​. Using competitive hybridization

of treated versus untreated samples chemically coupled PAK5 to a Cy™3 or Cy™5 fluorescently labeled dye (Amersham Biosciences, Little Chalfont Buckinghamshire, England) and fluorescence was read on a GenePix 4100A microarray scanner purchased from Axon Instruments (Union City, California). Data was analyzed using the Axon GenePix Pro 4.1 software and data and image files were then uploaded to the National Cancer Institute/Cancer Center for Research Microarray Center mAdB Gateway for analysis and comparison of multiple arrays. Real Time RT-PCR Five hundred nanograms of total RNA for each sample was reverse transcribed using the GeneAmp® PCR System 9700 and TaqMan® Reverse Transcription Reagents kit. Quantitative real time PCR reactions were conducted and EPZ015938 cell line measured using the ABI Prism™ 7700 Sequence Detection System and TaqMan® chemistries using published primers. Samples were tested in triplicate wells for the genes of interest and for the endogenous control, 18 S.

J Infect Dev Ctries 2007, 1:257–262.Angiogenesis inhibitor PubMed 3. Kiiru J, Kariuki S, Goddeeris BM, Butaye P: Analysis of beta-lactamase

phenotypes and carriage of selected beta-lactamase genes among Escherichia coli strains obtained from Kenyan patients during an 18-year period. BMC Microbiol 2012, 12:155.PubMedCrossRef 4. Sabate M, Navarro F, Miro E, Campoy S, Mirelis Quisinostat B, Barbe J, Prats G: Novel complex sul1-type integron in Escherichia coli carrying bla(CTX-M-9). Antimicrob Agents Chemother 2002, 46:2656–2661.PubMedCrossRef 5. Albrechtova K, Dolejska M, Cizek A, Tausova D, Klimes J, Bebora L, Literak I: Dogs of nomadic pastoralists in northern Kenya are reservoirs of plasmid-mediated cephalosporin- and quinolone-resistant Escherichia coli, including pandemic clone B2-O25-ST131. Antimicrob Agents Chemother 2012, 56:4013–4017.PubMedCrossRef 6. Brooks JT, Shapiro RL, Kumar L, Wells JG, Phillips-Howard PA, Shi YP, Vulule JM, Hoekstra RM, Mintz E, Slutsker L: Epidemiology of sporadic bloody diarrhea in rural Western Kenya. Am J Trop Med Hyg 2003, 68:671–677.PubMed 7. Blango GS-1101 ic50 MG, Mulvey MA: Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics. Antimicrob Agents Chemother 2010, 54:1855–1863.PubMedCrossRef 8. Bejon P, Mwangi I, Ngetsa C, Mwarumba S,

Berkley JA, Lowe BS, Maitland K, Marsh K, English M, Scott JA: Invasive Gram-negative bacilli are frequently resistant to standard antibiotics for children admitted to hospital in Kilifi, Kenya. J Antimicrob Chemother 2005, 56:232–235.PubMedCrossRef 9. Frank T, Gautier V, Talarmin A, Bercion R, Arlet G: Characterization of sulphonamide resistance genes and class 1 integron gene cassettes in Enterobacteriaceae, Central African Republic (CAR). J Antimicrob Chemother 2007, 59:742–745.PubMedCrossRef 10. Gassama A, Aidara-Kane A, Chainier D, Denis F, Ploy MC: Integron-associated antibiotic resistance in enteroaggregative and enteroinvasive Escherichia coli. Microb Drug Resist 2004, 10:27–30.PubMedCrossRef 11. Labar AS, Millman JS, Ruebush

E, Opintan JA, Bishar RA, Aboderin AO, Newman MJ, Lamikanra A, Okeke IN: Regional dissemination of a trimethoprim-resistance gene cassette via a successful transposable element. PLoS One 2012, Megestrol Acetate 7:e38142.PubMedCrossRef 12. Dahmen S, Mansour W, Boujaafar N, Arlet G, Bouallegue O: Distribution of cotrimoxazole resistance genes associated with class 1 integrons in clinical isolates of Enterobacteriaceae in a university hospital in Tunisia. Microb Drug Resist 2010, 16:43–47.PubMedCrossRef 13. Goldstein C, Lee MD, Sanchez S, Hudson C, Phillips B, Register B, Grady M, Liebert C, Summers AO, White DG, Maurer JJ: Incidence of class 1 and 2 integrases in clinical and commensal bacteria from livestock, companion animals, and exotics. Antimicrob Agents Chemother 2001,45(3):723–726.PubMedCrossRef 14.

1d). Fig. 1 a–d Effect of VPA (500 mg/kg daily/2 weeks) with selleck chemicals llc and without DHA (250 mg/kg/day) on serum hepatic enzyme and albumin levels. DHA was given orally 1 h after VPA, then blood was withdrawn from the orbital sinus for determination of enzymes (a–c; γ-GT, ALT, ALP, PCI-32765 respectively) after 1 and 2 weeks, or albumin (d), after 2 weeks. Data represent the mean ± SEM of each group; n = 6–8. Symbols indicate significance against VPA-treated group (asterisks) and normal control group (dollar symbols), γ-GT γ-glutamyl transferase, ALT alanine aminotransferase,

ALP alkaline phosphatase, DHA docosahexaenoic acid, VPA valproate To gain insights into the hepatic molecular and cellular changes occurring following VPA treatment; oxidative stress and endogenous antioxidant levels were monitored, and histopathologic examination of the liver was also conducted. Figure 2a demonstrates CH5183284 price that VPA

evoked a 3-fold rise in MDA levels. This was also accompanied by 35 % reduction in levels of endogenous cellular protector: reduced GSH, Fig. 2b. Fig. 2 a, b Effect of VPA (500 mg/kg daily/2 weeks) with and without DHA (250 mg/kg/day) on liver lipid peroxide (MDA) (a), and reduced glutathione (GSH) (b) levels. After 2 weeks of treatment, animals were sacrificed and a 10 % W/V liver homogenate was assayed for its content of MDA or GSH. Data represent the mean ± SEM of each group; n = 7. Symbols indicate significance against VPA-treated group (asterisks) and normal control group (dollar symbols), DHA docosahexaenoic acid, VPA valproate Downstream from hepatocellular disruption and oxidative stress, we also

investigated whether VPA liver intoxication had involved inflammatory signals and/or neutrophil infiltration into the liver; and if so, how these signals may be modified by DHA. Accordingly, in liver cell homogenates, VPA upregulated the expression of proinflammatory cytokine TNFα (5-fold, p < 0.05). This was paralleled by a ~ 6.1-fold rise in this cytokine level in the serum (p < 0.05, Fig. 3a, b). Considering time-course dependency, DHA managed to blunt the rise in TNFα effectively, after both 1 and 2 weeks, 5-Fluoracil datasheet although effects of DHA were more pronounced after 1 week. Co-treatment with DHA largely suppressed the VPA-induced hepatocytic production of TNFα in both the liver and the serum, implying also that rises in the serum are most likely linked to those in the liver. Moreover, an enzyme marker of neutrophil infiltration with known contributions to both inflammation and oxidative stress, that is myeloperoxidase (MPO), had an appreciably enhanced activity in liver homogenates (4.2-fold; p < 0.05). This response was likewise highly sensitive to co-treatment with DHA (p < 0.05), thus also revealing the versatility whereby DHA protects liver cells against VPA-induced injury. Fig.

Archaea 2008,2(3):193–203.PubMedCrossRef 17. Rother M, Metcalf

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CM, Thomsen J, Ehlers C, Vogel J, Schmitz RA: Deep sequencing analysis of the Methanosarcina mazei Gö1 transcriptome in response to nitrogen availability. Proc Natl Acad Sci USA 2009,106(51):21878–21882.PubMedCrossRef 22. Karr EA, Sandman K, Lurz R, Reeve JN: TrpY Regulation of trpB2 transcription in Methanothermobacter thermautotrophicus . J Bacteriol 2008,190(7):2637–2641.PubMedCrossRef 23. Bell SD: Archaeal transcriptional regulation – variation on a bacterial theme? Trends Microbiol 2005,13(6):262–265.PubMedCrossRef 24. Xie Y, Reeve JN: Transcription by an archaeal RNA Polymerase is slowed ZD1839 ic50 but not blocked by an archaeal nucleosome. J Bacteriol 2004,186(11):3492–3498.PubMedCrossRef 25. Santangelo

TJ, Reeve JN: Archaeal RNA polymerase is sensitive to intrinsic termination directed by transcribed and remote sequences. J Mol Biol 2006, 355:196–210.PubMedCrossRef 26. Storz Cell press G, Tartaglia LA, Ames BN: Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation. Science 1990,248(4952):189–194.PubMedCrossRef 27. Hellman LM, Fried MG: Electrophoretic mobility shift assay (EMSA) for detecting protein-nucleic acid interactions. Nat Protocols 2007,2(8):1849–1861.CrossRef 28. Lessner DJ, Ferry JG: The archaeon Methanosarcina acetivorans contains a protein disulfide reductase with an iron-sulfur cluster. J Bacteriol 2007,189(20):7475–7484.PubMedCrossRef 29. Pryor EE Jr, Waligora EA, Xu B, Dellos-Nolan S, Wozniak DJ, Hollis T: The transcription factor AmrZ utilizes multiple DNA binding modes to recognize activator and repressor sequences of Pseudomonas aeruginosa virulence genes. PLoS Path 2012,8(4):e1002648.CrossRef 30. Lundin M, Nehlin JO, Ronne H: Importance of a flanking AT-rich region in target site recognition by the GC box-binding zinc finger protein MIG1. Mol Cell Biol 1994,14(3):1979–1985.PubMed 31. Cook WJ, Kar SR, Taylor KB, Hall LM: Crystal structure of the cyanobacterial metallothionein repressor SmtB: a model for selleckchem metalloregulatory proteins.

albolutescens (5 M) 29′ Stromata discoid to flat pulvinate; yellow, turning ochre, rust to brown upon drying; on a white subiculum on bark of conifers in the upper montane zone of the Alps and in Northeast Europe; conidiation effuse, polypaecilum-like, i.e. with apically branched phialides H. subalpina (5 M) 30 Stromata appearing waxy or gelatinous; growth slow, on CMD colony radius <3 mm after 3 days at Trichostatin A 25°C; conidiophores odd verticillium-like, selleck chemicals llc conidia hyaline 31 30′ Stromata not appearing waxy or gelatinous (except for older stromata

of H. silvae-virgineae; see [52]); growth faster, anamorphs different 32 31 Stromata incarnate or reddish, turning orange- to reddish brown, often yellowish when young; ostiolar dots absent, perithecial contours evident, minute; stromata often with violaceous-brown folds when dry and old; on wood and bark of various trees H. tremelloides (5 M) 31′ Stromata white, yellowish to honey-coloured, reddish brown when old; on Sambucus nigra H. sambuci (5 M) 32 Stromatal surface hairy, at least when young (section Trichoderma, H. crystalligena; also stromata of H. pachybasioides and H.

pachypallida (see [47] and [63]) are sometimes velutinous in young stages); ostiolar dots invisible or inconspicuous, at least when young and fresh 33 32′ Stromatal surface glabrous under a lens; stromata pulvinate, turbinate or discoid 46 33 Stromata distinctly Selleck LCZ696 pulvinate when fresh, dark reddish brown to violaceous-brown when dry, often covered by powder of white crystals; ostiolar dots becoming distinct with age, particularly when dry; ascospores small, distal ascospore cell 2.5–4 × 2.5–3 μm; colony on CMD finely zonate, of radial fan-shaped segments, sometimes forming crystals in the agar; conidia hyaline H. crystalligena (4B) 33′ Stromatal shape and colour variable; crystalline covering absent or rare; ostiolar dots generally inconspicuous; ascospores larger; conidia green (sect. Trichoderma) 34 34 Stromata effuse, extending to >3 cm, white with next unevenly distributed ochre

to orange-brown fertile patches; margin fraying out as white mycelium attached to the substrate H. ochroleuca (1 T) 34′ Stromata smaller, typically less than 1 cm long, often subeffuse when young 35 35 Stromata more or less reddish brown or variable within specimens; conidia smooth or ornamented 36 35′ Stromata orange, orange-brown, or violaceous-brown to dark brown, more or less uniform within specimens; conidia smooth 39 36 Conidia smooth 37 36′ Conidia verruculose or verrucose 38 37 Stromata reddish brown with a brick-red component; conidia subglobose; conidiophores with conspicuously widely spaced short branches; colony radius 45–48 mm on CMD at 25°C after 3 days; teleomorph rare H.

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in vitro and in vivo infection in women. J Bacteriol 2008, 190:3129–3139.PubMedCentralPubMedCrossRef 15. Andrews JS, Rolfe SA, Huang WE, Scholes JD, Banwart SA: Biofilm formation in environmental bacteria is influenced by different macromolecules depending on genus and species. Environ Microbiol 2010, 12:2496–2507.PubMedCrossRef 16. Chhibber S, Nag D, Bansal S: Inhibiting biofilm fomration by Klebsiella pneumoniae B5055 using an iron antagonizing molecule and a bacteriophage. BMC Microbiol 2013, 13:174.PubMedCentralPubMedCrossRef

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The study was registered with the EU Clinical Trials Register (EudraCT no.: 2009-016959-21). Study Sample Women going through the menopause were enrolled in the study if they were aged ≥50 years; if they had experienced amenorrhea for >12 months; and if, during

a routine gynecologic consultation, they had spontaneously complained of hot flashes that had started <2 years previously and had significant repercussions on their social and/or professional life of ≥40 mm on a Visual Analog Scale (VAS) ranging from 0 to 100 mm, with a mean frequency of ≥5 hot flashes per day during the 48 hours preceding study enrollment. Women were excluded if they were receiving or had #P-gp inhibitor randurls[1|1|,|CHEM1|]# ever received HRT; if they were receiving or had received (within 2 weeks prior to enrollment) β-alanine (Abufène®), food supplements (phytoestrogens, etc.), vitamin E, or courses of acupuncture aimed at relieving hot flashes; or if they were receiving or had received (within 1 week prior to enrollment)

other homeopathic treatments aimed at relieving hot flashes. Other exclusion criteria included menopause induced artificially by surgery, chemotherapy, or radiotherapy; hot flashes that could be iatrogenic in origin or could be caused by an associated pathology; receiving treatments that could reduce the frequency of hot flashes, such as antihypertensive treatment with clonidine, antidepressant treatment with SNRIs (venlafaxine), SSRIs (citalopram, paroxetine), mirtazapine (a noradrenergic and specific serotonergic antidepressant), Liproxstatin-1 solubility dmso or antiepileptic treatment with gabapentin;

and a risk Molecular motor of not complying with the protocol. All patients were able to understand, read, and write French, were affiliated with a social security plan, and gave their written informed consent to participate in the study. Study Treatments The treatment evaluated in this study, BRN-01 (Acthéane®, a homeopathic medicine registered in France for menopausal hot flashes and manufactured by Laboratoires Boiron, Sainte Foy-lès-Lyon, France), was in the form of tablets consisting of dilutions of the following five homeopathic medications: Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH). The placebo tablets were identical in appearance to the active tablets but included only saccharose (75%), lactose (24%), magnesium stearate E572 (1%), and purified water without any homeopathic dilutions. All treatments were in the same packaging. Laboratoires Boiron provided BRN-01, its matching placebo, and financial support for the study. Randomization and allocation were carried out centrally by Laboratoires Boiron and generated using the random function of SAS (version 9.2) software.

It is possible that even though PDMS completely filled into the holes, we did not see PDMS pillars because they were broken during demolding. To verify this, we took SEM images of the master mold after PDMS filling and demolding, which revealed no PDMS left behind on the master

mold. Figure 3 SEM images of PDMS pillars molded into the toluene (a, b) or hexane (c, d) treated mold. The pillar diameters are (a) 580 nm, (b) 150 nm (smaller holes not filled), (c) 820 nm, and (d) 180 nm (smaller holes not filled). Samples were tilted 45° for SEM imaging. Discussion In order to explain the enhanced PDMS filling by solvent MGCD0103 clinical trial surface treatment, we conducted water contact angle measurement on the three surfaces: FOTS-treated silicon, toluene- and FOTS-treated silicon, and hexane- and FOTS-treated silicon. The average measured contact angles are 107.8°, 104.1°, and 105.9° for the three surfaces, respectively. Though P005091 price water contact angle is expected to differ greatly from PDMS contact angle as the two materials are very different, our measurement indicates an increase of surface energy upon additional solvent treatment, which could lead to

MMP inhibitor an increase or even change of sign of capillary force that is proportional to γ sa − γ sl (here, γ sa is the surface energy of the mold, and γ sl is the interface energy of PDMS and the mold). This surface energy increase can be explained by the fact that significant percentage of FOTS is actually physically adsorbed (rather than chemically bonded)

onto the mold surface and can thus be dissolved by the solvent, which results in the exposure of underneath bare silicon. More complete coverage by chemically bonded FOTS can be obtained through multi-cycle treatment, with each cycle consisting of FOTS treatment followed by dissolving physisorbed molecules. Yang et al. has reported that water filling speed into Astemizole a parylene microscale channel was increased by 2 orders by pretreating the channel with water, which was attributed to the water molecules’ adsorption inside the channel and the resulted modification of parylene’s surface energy [12]. As aforementioned, the PDMS filling into the silicon mold structures was improved by diluting it with a solvent such as toluene or hexane, which was attributed to the decrease of its viscosity [4]. Indeed, it is known that diluting PDMS drastically reduces its viscosity. For instance, its viscosity is reduced to 0.020 Pa · s by diluting it with heptane at 1:2 (PDMS/heptane) ratio [13], and for PDMS oligomers, the viscosity decreased from 0.362 to 0.050 Pa · s when diluted with toluene at 69% by weight [14]. It is fair to estimate that Sylgard 184 PDMS’s viscosity is decreased by 1 order if diluted with toluene at 40 wt% (60% toluene, as is the case for [4]).