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Among the craft recipes for artisans collected in the 4th-century Egyptian documents the Leyden and Stockholm papyri, there is one calling for adding animal milk to orchil for wool dyeing. To understand the rationale for this practice, wool yarns were dyed with and without goat milk added to orchil dyebaths, each made using lichens from three different sources. The results showed orchil containing milk dyed yarns a noticeably deeper red hue. The colorants extracted from the dyed yarns were analyzed by liquid chromatography-diode-array-detector-mass spectrometry to assess the relative amounts of nine identifiable orceins. The data showed that the yarns dyed with milk gave extracts exhibiting several fold more α-aminoorcein and α-hydroxyorcein, with only small differences in the other seven. Scanning electron microscopic analysis of a representative pair of dyed yarns showed that milk promoted surface changes in the fiber that may indicate increased cutaneous damage. Hypotheses for the milk’s effects on orchil dyeing were proposed that included the formation of milk–protein complexes with the two enriched orceins that possibly enhanced wool binding and/or better wool uptake of free and/or complexed orceins due to biodegradation of the wool’s surface cuticle caused by microbial growth promoted by the addition of milk.

This paper describes the identification of dyes on fifty yarn samples from a tapestry created by the well-known 17th-century Flemish workshop of the Mattens family. The design of the tapestry is based on the first of ten drawings known as the Acts of the Apostles by the famed 16th-century Italian painter Raphael. The drawings were commissioned by Pope Leo X and translated into tapestries by Pieter van Aelst; these original tapestries are still in the collection of the Vatican Museums. The present work was reproduced over a century later from the original drawing and is one in a possible set of nearly fifty known copies of the original tapestry cycle. Most of the Mattens yarn samples were found to be dyed by weld, indigo, and madder, as well as a few using brazilwood and lichen, but no insect dyes were detected. A significant finding in the present study was the detection of the dye component pseudoindirubin 1, alongside indigotin and indirubin, as well as yarns that only yielded the latter two dyes. The implication of using this new marker as objective evidence of the use of both woad and most likely Asian indigo is explored. The historical and conservation significance of the dyestuffs identified is also discussed.

Analysis of purple dyestuff from a tin labeled “1 oz. Cudbear, No. 1 N. F. Powdered”, marketed by the American business S. B. Penick & Company, “Manufacturers of fine drugs and chemicals”, confirmed that the material was indeed a lichen dyestuff. It contains the same major orcein components identified in several other lichen dyes and dyed samples dating from the mid-19th century to today. These dyestuffs were analyzed using several analytical techniques. Fluorescence and fiber optic reflectance spectroscopic data for all the samples were similar. High performance liquid chromatography with diode array detection coupled to mass spectrometry confirmed that this commercial American cudbear was very similar to the samples from the United Kingdom but rather different from the archil-dyed reference yarns from Europe. The significance of the observations is discussed, and chemical structures are proposed for several of the unknown dye components detected in this study.

The accessioning of ancient textiles into museum collections often requires objective information regarding the object’s appropriateness and authenticity before purchase or gift acceptance. In the case of colored fabrics, the identification of dyestuffs consistent with the attributed time period and culture builds confidence and reduces the chances of the object being a simple forgery or fake produced using modern materials. Moreover, this information adds to the technical, cultural, and conservation knowledge regarding the object. Increasingly, chronometric age estimates in the form of radiocarbon dating are also needed to establish the object’s age or to further prove the materials match the purported date range of the textile. Each of these analyses consumes a small sample of the object, and typically they are conducted separately by different laboratories on individual sample yarns. This report demonstrates for the first time the sequential, combined analysis of dyes by liquid chromatography-diode array detection-mass spectrometry and radiocarbon dating of the same residual dye-extracted sample. The chemicals and solvents used in various dye extraction protocols are shown not to contaminate the extracted yarns for radiocarbon dating purposes. The approach was used in the authentication study of an ancient Nazca tunic made from natural fibers (wool) and dyes (indigoids, anthraquinones, and flavonoids) shown to have most likely been produced between 595 and 665 CE.

The exploitation of natural sources and later synthetic molecules to generate blue to purple coloration in textiles has a long history in the dyer’s craft. Natural indigoids such as indigo, woad, and Tyrian or shellfish purple served this purpose for millennia, but in the late 1800s synthetic analogs, in particular indigotin, quickly replaced natural sources. Halogenated versions of the dye were also created, and some like 5,5′-dibromoindigo were brought to market. Interestingly, these have not been significantly discussed in the literature, nor have they been found in forensic or technical art history investigations of textiles until now. This paper reports the first identification in a museum context of this unusual synthetic brominated analog of indigo, discovered on three twentieth century Japanese yukata. Analytical data collected on reference materials using liquid chromatography-mass spectrometry, UV–visible spectroscopy, Raman microspectroscopy, Fourier transform infrared spectroscopy, and X-ray fluorescence spectroscopy are provided to assist with future identifications of this relatively unknown colorant. Density functional theory applied to 5,5′-dibromoindigo was used to confirm the experimental Raman spectrum.

In a previous study we found that nanofibrous poly( l -lactic acid) (PLLA) scaffolds mimicking collagen fibers in size were superior to solid-walled scaffolds in promoting osteoblast differentiation and bone formation in vitro . In this study we used an in vivo model to confirm the biological properties of nanofibrous PLLA scaffolds and to evaluate how effectively they support bone regeneration against solid-walled scaffolds. The scaffolds were implanted in critical-size defects made on rat calvarial bones. Compared with solid-walled scaffolds, nanofibrous scaffolds supported substantially more new bone tissue formation, which was confirmed by micro-computed tomography measurement and von Kossa staining. Goldner's trichrome staining showed abundant collagen deposition in nanofibrous scaffolds but not in the control solid-walled scaffolds. The cells in these scaffolds were immuno-stained strongly for Runx2 and bone sialoprotein (BSP). In contrast, solid-walled scaffolds implanted in the defects were stained weakly with trichrome, Runx2, and BSP. These in vivo results demonstrate that nanofibrous architecture enhances osteoblast differentiation and bone formation.

Summary LY2603618 is an inhibitor of checkpoint kinase 1 (CHK1), an important regulator of the DNA damage checkpoints. Preclinical experiments analyzed NCI-H2122 and NCI-H441 NSCLC cell lines and in vitro/in vivo models treated with pemetrexed and LY2603618 to provide rationale for evaluating this combination in a clinical setting. Combination treatment of LY2603618 with pemetrexed arrested DNA synthesis following initiation of S-phase in cells. Experiments with tumor-bearing mice administered the combination of LY2603618 and pemetrexed demonstrated a significant increase of growth inhibition of NCI-H2122 (H2122) and NCI-H441 (H441) xenograft tumors. These data informed the clinical assessment of LY2603618 in a seamless phase I/II study, which administered pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) and escalating doses of LY2603618: 130–275 mg. Patients were assessed for safety, toxicity, and pharmacokinetics. In phase I, 14 patients were enrolled, and the most frequently reported adverse events included fatigue, nausea, pyrexia, neutropenia, and vomiting. No DLTs were reported at the tested doses. The systemic exposure of LY2603618 increased in a dose-dependent manner. Pharmacokinetic parameters that correlate with the maximal pharmacodynamic effect in nonclinical xenograft models were achieved at doses ≥240 mg. The pharmacokinetics of LY2603618, pemetrexed, and cisplatin were not altered when used in combination. Two patients achieved a confirmed partial response (both non-small cell lung cancer), and 8 patients had stable disease. LY2603618 administered in combination with pemetrexed and cisplatin demonstrated an acceptable safety profile. The recommended phase II dose of LY2603618 was 275 mg.

Summary Purpose To investigate the toxicity profile, activity, pharmacokinetics, and pharmacodynamics of pemetrexed in leukemia. Patients and Methods Patients with refractory or relapsed acute leukemia were eligible. A phase I 3+3 design was implemented. Pemetrexed was infused intravenously (IV) over 25 min with vitamin supplementation. Courses were repeated every 3 to 4 weeks according to toxicity and efficacy. The starting dose of 900 mg/m 2 was escalated by approximately 33% until the dose-limiting toxicity (DLT) was determined. Results Twenty patients with acute myeloid (AML) or lymphocytic (ALL) leukemia received therapy. The main non-hematologic adverse event was liver dysfunction at several dose levels, including 2 DLTs at 3,600 mg/m 2 . One patient with ALL (3,600 mg/m 2 dose level) achieved a partial response. Pemetrexed pharmacokinetics were linear with escalated dosing. Elevated plasma deoxyuridine was observed in a subset of patients following pemetrexed infusion, but was not correlated with dose levels. Changes in the nucleotide pools of circulating mononuclear cells were observed, but were variable. Conclusions The recommended phase II dose of pemetrexed for future leukemia studies is 2,700 mg/m 2 IV over 25 min every 3 to 4 weeks with vitamin supplementation. Deoxyuridine levels did not increase with increasing pemetrexed dose, suggesting pemetrexed inhibition of thymidylate synthase (TS) may be saturated by the 900 mg/m 2 dose level. However, no firm conclusion can be made regarding TS saturation in tumor cells. While tolerable, pemetrexed monotherapy had limited activity in this highly refractory population. Exploration of pemetrexed in combination with other active agents in leukemia is a reasonable future endeavor.

This paper describes the identification of dyes on fifty yarn samples from a tapestry created by the well-known 17th-century Flemish workshop of the Mattens family. The design of the tapestry is based on the first of ten drawings known as the Acts of the Apostles by the famed 16th-century Italian painter Raphael. The drawings were commissioned by Pope Leo X and translated into tapestries by Pieter van Aelst; these original tapestries are still in the collection of the Vatican Museums. The present work was reproduced over a century later from the original drawing and is one in a possible set of nearly fifty known copies of the original tapestry cycle. Most of the Mattens yarn samples were found to be dyed by weld, indigo, and madder, as well as a few using brazilwood and lichen, but no insect dyes were detected. A significant finding in the present study was the detection of the dye component pseudoindirubin 1, alongside indigotin and indirubin, as well as yarns that only yielded the latter two dyes. The implication of using this new marker as objective evidence of the use of both woad and most likely Asian indigo is explored. The historical and conservation significance of the dyestuffs identified is also discussed.

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilonamino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N∈-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N∈-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N∈-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N∈-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.