gebhart/patrepeval huggingface dataset:
Thalidomide influences atherogenesis in aortas of ApoE−/−/LDLR−/− double knockout mice: a nano-CT study (2014)

Plaque progression in atherosclerosis is closely connected to angiogenesis due to vasa vasorum (VV) growth. Objective of this study was to determine the unknown long-term effect of thalidomide on adventitial VV neovascularization and plaque progression using nano-focussed computed tomography (nano-CT). Proliferation and migration assays in human coronary artery endothelial cells (HCAEC) measured number of viable cells after incubation with thalidomide. Male ApoE(-/-)/LDLR(-/-) (AL) mice (n = 5) received a thalidomide containing western diet (WD) over 29 weeks. Another five male AL mice (WD without thalidomide) served as control group. Descending aortas were scanned with nano-CT at (1.5 μm)(3) isotropic voxel size. Number and area of adventitial VV as well as plaque cross sectional area were measured. Results were complemented by histology. Thalidomide inhibited proliferation and migration of HCAEC dose-dependently. VV neovascularization decreased in number per cross section (7.66 ± 0.301 vs. 8.62 ± 0.164, p < 0.001) and in cross sectional area (0.0183 ± 0.0011 vs. 0.0238 ± 0.0008 mm(2), p < 0.001). Cross sectional area of plaque decreased significantly when treated with thalidomide (0.57 ± 0.0187 vs. 0.803 ± 0.0148 mm(2), p < 0.001). Nano-CT imaging revealed a reduced plaque growth and VV neovascularization after long-term application of thalidomide. Therefore, nano-CT can be considered as a new method to detect therapeutic effects in experimental models of atherosclerosis.
Preparation and Antioxidative Activity of 1,5-Anhydrofructose. (1999)

A simple enzymic method for the preparation of 1, 5-anhydrofructose (1, 5-AF) and its antioxidative activity were investigated. α-1, 4-glucan lyase (EC 4 .2.2.13, GLase) was extracted and purified from red seaweed, Gracilaria verrrucosa. One-hundred-and-fifty grams of 1, 5-AF was obtained from 360 g of waxy maize starch by digestion with the purified GLase and the following purification of the product by ion-exchange resins and gel filtration. The purity of the product was 98 .6% by HPLC using an ionexchange resin (MC1 GEL CK08S). The product, 1, 5-AF, was identified by IH-13C COSY NMR, and the [α] D25 was -16.8°. The antioxidative activity of 1, 5-AF was examined by comparison with that of ascorbic acid (VC) for preventing the oxidation of linoleic acid . The antioxidative activity of 1, 5-AF was found to be approximately 1.8-fold that of VC by the methods using thiocyanate and 2-thiobarbituric acid.
Molecular and phenotypic characterization of atypical Williams–Beuren syndrome (2013)

Williams-Beuren syndrome (WBS) is a multisystemic genomic disorder typically caused by a recurrent ˜1.5-1.8 Mb deletion on 7q11.23. Atypical deletions can provide important insight into the genotype-phenotype correlations. Here, we report the phenotypic and molecular characterization of a girl with a de novo 81.8 kb deletion in the WBS critical region, which involves the ELN and LIMK1 genes only. The patient presented at 2 months of age with extensive vascular abnormalities, mild facial dysmorphism and delays in her fine motor skills. We discuss potential molecular mechanisms and the role of ELN and LIMK1 in the different phenotypic features. We compare the findings in our patient with previously reported overlapping deletions. The phenotypic variability among these patients suggests that other factors are important in the phenotype and possibly include: position effects related to copy number variation size, variations in the non-deleted alleles, genetic modifiers elsewhere in the genome, or reduced penetrance for specific phenotypes.
Diamond diffractive lens with a continuous profile for powerful terahertz radiation (2020)

An increase in the radiation power of terahertz (THz) sources requires the development of new optics working with it. The laser-assisted replication technique is proposed to fabricate the diamond cylindrical diffractive lens with a continuous profile for the THz range. The procedure involves the inverted structuring of a silicon substrate by laser ablation for its further replication to the diamond surface utilizing the chemical vapor deposition process. Testing of the fabricated lens performed with a free-electron laser at the wavelength of 141 µm has demonstrated high diffraction efficiency (95±5<i>%</i>) and a good agreement between the measured and expected intensity distribution in the focal plane.
Nanomaterial processing using self-assembly-bottom-up chemical and biological approaches (2013)

Nanotechnology is touted as the next logical sequence in technological evolution. This has led to a substantial surge in research activities pertaining to the development and fundamental understanding of processes and assembly at the nanoscale. Both top-down and bottom-up fabrication approaches may be used to realize a range of well-defined nanostructured materials with desirable physical and chemical attributes. Among these, the bottom-up self-assembly process offers the most realistic solution toward the fabrication of next-generation functional materials and devices. Here, we present a comprehensive review on the physical basis behind self-assembly and the processes reported in recent years to direct the assembly of nanoscale functional blocks into hierarchically ordered structures. This paper emphasizes assembly in the synthetic domain as well in the biological domain, underscoring the importance of biomimetic approaches toward novel materials. In particular, two important classes of directed self-assembly, namely, (i) self-assembly among nanoparticle-polymer systems and (ii) external field-guided assembly are highlighted. The spontaneous self-assembling behavior observed in nature that leads to complex, multifunctional, hierarchical structures within biological systems is also discussed in this review. Recent research undertaken to synthesize hierarchically assembled functional materials have underscored the need as well as the benefits harvested in synergistically combining top-down fabrication methods with bottom-up self-assembly.
Warfarin and UDP-glucuronosyltransferases: writing a new chapter of metabolism (2010)

The widely prescribed anticoagulant, Coumadin (racemic R/S-warfarin), Bristol-Myers Squibb Company, Clinton, NY has a narrow therapeutic range and wide interindividual response due, in part, to drug metabolism. Early identification of hydroxywarfarins (OHWARs), especially S-7-OHWAR, as major metabolites fostered studies characterizing cytochrome P450s responsible for those reactions. Nevertheless, phase II metabolism by sulfotransferases and, especially uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), marks the next chapter in warfarin inactivation and clearance. Rodents converted OHWARs to glucuronides (O-GLUC), including high levels of 4'-, 7-, and 8-O-GLUC. Similarly, humans generated significant levels of glucuronides following treatment with warfarin. 7-O-GLUC was a major metabolite, while 6- and 8-O-GLUC were minor ones. Surprisingly, warfarin glucuronidation accounted for up to 13% of metabolites. This capacity in humans derives from several UGTs, as shown by studies with recombinant enzymes and racemic warfarin and OHWARs. 7-OHWAR was a high-affinity substrate for UGT1A1, compared to other UGTs. UGT1A1 and UGT1A10 also glucuronidated 6-OHWAR. Of five UGT1A enzymes, UGT1A10 was approximately 7-fold more efficient than the rest. Broad substrate specificity for UGT1A10 derives, in part, from an active site-binding motif, specifically F90-M91-V92-F93. Unlike glucuronidation, less is known about sulfonation of warfarin and its metabolites, except that low capacities are shown by rats and, possibly, humans. Collectively, phase I and II metabolic steps create pathways for inactivating and eliminating warfarin that require elucidation. These findings will ultimately enrich our understanding of warfarin metabolism and facilitate the interpreting of metabolic profiles of patients. This knowledge will possibly avoid complications during warfarin therapy related to metabolism by personalizing therapy for the patient.
Correlation of Microstructure, Rheological and Morphological Characteristics of Synthesized Polypropylene (PP) Reactor Blends Using Homogeneous Binary Metallocene Catalyst (2017)

A novel binary homogeneous catalyst system based on (I): <i>rac</i>-Me₂Si(2-Me-4-PhIn)₂ZrCl₂ and (II): (2-PhIn)₂ZrCl₂ catalysts at various molar ratios was utilized for the synthesis of polypropylene (PP) reactor blends with bimodal molecular weight distribution (MWD). The results of gel permeation chromatography analyses revealed that the catalyst (I) was responsible for the production of <i>i</i>-PP with high molecular weight (MW) while the individual use of catalyst (II) led to the production of an elastomeric PP with relatively low MW. However, application of the binary catalyst system led to high MW bimodal MWD products being highly dependent on the catalysts' molar ratios. Increasing the molar ratio of catalyst (II) to catalyst (I) resulted in a notable enhancement of the products' complex viscosity due to the increased MW, a higher level of chains' entanglements and formation of amorphous blocks along the polymer chains. All products exhibited a single relaxation that shifted towards longer times upon changing the catalysts' molar ratios. Scanning electron microscopy results revealed that the fracture surface of the blends, synthesized by the binary catalyst system, became more heterogeneous in comparison with the products obtained by the individual use of the catalyst (I). The observed heterogeneity was found to increase by increasing the amount of catalyst (II). Such morphological change was further corroborated by the dynamic rheological data, indicating a promising correlation between the linear rheological results and the morphological features of the synthesized PP reactor blends.
MOF-Polymer Hybrid Materials: From Simple Composites to Tailored Architectures (2020)

Metal-organic frameworks (MOFs) are inherently crystalline, brittle porous solids. Conversely, polymers are flexible, malleable, and processable solids that are used for a broad range of commonly used technologies. The stark differences between the nature of MOFs and polymers has motivated efforts to hybridize crystalline MOFs and flexible polymers to produce composites that retain the desired properties of these disparate materials. Importantly, studies have shown that MOFs can be used to influence polymer structure, and polymers can be used to modulate MOF growth and characteristics. In this Review, we highlight the development and recent advances in the synthesis of MOF-polymer mixed-matrix membranes (MMMs) and applications of these MMMs in gas and liquid separations and purifications, including aqueous applications such as dye removal, toxic heavy metal sequestration, and desalination. Other elegant ways of synthesizing MOF-polymer hybrid materials, such as grafting polymers to and from MOFs, polymerization of polymers within MOFs, using polymers to template MOFs, and the bottom-up synthesis of polyMOFs and polyMOPs are also discussed. This review highlights recent papers in the advancement of MOF-polymer hybrid materials, as well as seminal reports that significantly advanced the field.
ChemInform Abstract: SILVER‐ASSISTED DIMETHYLSULFOXIDE OXIDATIONS, AN IMPROVED SYNTHESIS OF ALDEHYDES AND KETONES (1974)

Abstract Aus den Bromiden (I) entstehen über die mit DMSO erhaltenen Salze (II) die Aldehyde (III).
Collagen loss in photoaged human skin is overestimated by histochemistry (2000)

It is well known that photoaged skin is characterized by increases in dermal matrix components that include glycosaminoglycans, proteoglycans and masses of abnormal elastic fibers accompanied by substantial collagen loss. Histochemical staining of such tissue gives the impression of "massive" loss of collagen and its replacement by these other matrix components. Early biochemical studies have lent support to this notion with a reported decrease in total collagen of approximately 45% compared to protected skin. More recent studies report considerably less, but varying, amounts of collagen loss. Rarely have the two approaches, histochemistry and biochemical analysis, been used in the same study to examine the same tissue. In this study, collagen loss was quantified biochemically in paired biopsies from sun-protected and sun-exposed arm skin of moderately photoaged female subjects (age 51-77 years). The values obtained were compared with histochemical and immunochemical findings. Quantitatively, collagen loss on a per mg protein basis was small compared to the histochemical appearance.
Contrasting Two- and Three-Dimensional Crystal Properties of Isomeric Dialkyl Phthalates (2007)

Competitive adsorption occurs whenever a solution containing multiple components is in contact with a surface, and the relative adsorption strengths affect both the properties of the interface and the solution. To investigate this phenomenon, the factors influencing relative adsorption strengths of a series of isomeric dialkyl phthalates were determined from their competitive adsorption behavior and interpreted in the context of the thermodynamic properties of the bulk crystals and the structural features of the monolayers. The order of stabilities of the two-dimensional crystals paralleled that of the three-dimensional crystals, as determined by the trends in melting point, enthalpy of melting, and solubility. The magnitude of the stability differences, however, could only be understood through examination of the structures of the monolayers. Thus, the important process of adsorption of solutes from solution must be viewed as a microscopic phenomenon; adsorption strengths are influenced not only by molecular and macroscopic properties but also by the distinct assembly mode of the adsorbed layer.
HPLC determination of fatty acid levels in rats after chronic supplementation of flaxseed oil and dietetic oil. (2009)

Essential fatty acids (EFAs) belonging to -3 and -6 families play an important role in vivo, supporting the cardiovascular, reproductive, immune and nervous system functions; an inappropriate balance of these EFAs contributes to the development of diseases, while a proper balance helps maintain and even improve health.The purpose of this research was to study the levels of the principal -3 (ALA: n-lino-lenic acid; EPA: eicosapentaenoic acid; DPA: docosapentaenoic acid; DHA: docosa-hexaenoic acid) and -6 (LA: linoleic acid; AA: arachidonic acid) fatty acids in rat serum and tissues (liver, brain, adipose tissue) after a chronic treatment with flaxseed oil and with a dietetic oil, containing flaxseed oil, fish oil and sunflowers oil. The treatment was planned in order to give to rats the same ALA amount.The biological samples were subjected to liquid-liquid extraction, followed by derivatisation with p-bromophenacyl bromide and then analysed by HPLC/UV on a C18 reversed-phase column under gradient mobile phase conditions.Rats treated with flaxseed oil and dietetic oil showed enhanced levels of n-3 fatty acids compared to the correspondent control group. In serum, ALA levels were slightly higher in the dietetic oil group than in the flaxseed oil group; this fact is probably due to an enhanced absorption and also a decreased metabolism of ALA. The EPA, DPA and DHA serum levels, higher in the dietetic than in the flaxseed group, could derive both from ALA through its metabolism and also from EPA and DHA contained in the fish oil. Brain and adipose tissue showed EPA and DHA levels higher in the dietetic than in the flaxseed group, as occurred for serum samples. Concerning liver samples, the treatment with flaxseed or dietetic oil caused an enhancement for ALA, EPA and DPA levels, while no variations were found for DHA compared to control groups.The data obtained underline that the tested oils can enhance the levels of -3 fatty acids and therefore they could be successfully used in the dietetic treatment of lipid related diseases.
Epidemiological Studies of Arteriosclerosis (I): Association of Aortic Pulse Wave Velocity with Hypertension, Arteriolar Sclerotic Changes in the Retina, and Ischemic ECG Changes (1996)

Studies show that arteriosclerosis advances first in the aorta and then proceeds to the cerebral and coronary arteries. Because the aortic pulse wave velocity (PWV) can be used to estimate the extent of arteriosclerosis in the aorta, the use of PWV may allow earlier detection of arteriosclerotic diseases.This study examined the relationship between PWV and other arteriosclerotic indicators including (1) arteriolar sclerotic changes in the retina as evaluated by Scheie's method (≥grade II); (2) ischemic ECG changes (Minnesota code: 4-1, 4-2, 4-3, 4-4 and/or 5-1, 5-2, 5-3); and (3) hypertension determined as systolic pressure ≥160mmHg and/or diastolic pressure >95mmHg. Subjects were 221, 564 male urban workers, 20-69 years of age, who participated in cardiovascular disease screening in major cities in Japan. This study sample did not include patients with hypertension, diabetes, hyperlipidemia, or gout, or those having a history of cardio- and/or cerebrovascular diseases.We examined the prevalence of each of the above three indicators at various PWV levels (<7.0, 7.0-7.9, 8.0-8.9, 9.0-9.9, ≥10.0m/sec.) in different age groups (20-29, 30-39, 40-49, 50-59, 60-69 years old).The prevalence of each of the three indicators increased exponentially as the PWV became faster in all age groups examined with the exception of the prevalence of hypertension due to elevated diastolic pressure in patients 60-69 years old; the prevalence of each condition increased significantly at PWV scores of 8.0m/sec or greater among those under 60 years old and 9.0m/sec or greater among those 60-69 years old.It is suggested that PWV advances prior to the appearance of the indicators examined and that the use of PWV in mass screenings can contribute significantly to the prevention of arteriosclerotic diseases.
Paradoxical Effects of Green Tea (Camellia Sinensis) and Antioxidant Vitamins in Diabetic Rats (2005)

We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma were increased by diabetes (P < 0.001) but unaffected by treatment. Erythrocyte glutathione and plasma hydroperoxides were improved by the vitamins (P < 0.05) and green tea (P < 0.001). Retinal superoxide production, acellular capillaries, and pericyte ghosts were increased by diabetes (P < 0.001) and improved by green tea and the vitamins (P variable). Lens crystallin fluorescence at 370/440 nm was ameliorated by green tea (P < 0.05) but not the vitamins. Marginal effects on nephropathy parameters were noted. However, suppressed renal mitochondrial NADH-linked ADP-dependent and dinitrophenol-dependent respiration and complex III activity were improved by green tea (P variable). Green tea also suppressed the methylglyoxal hydroimidazolone immunostaining of a 28-kDa mitochondrial protein. Surprising, glycoxidation in tendon, aorta, and plasma was either worsened or not significantly improved by the vitamins and green tea. Glucosepane cross-links were increased by diabetes (P < 0.001), and green tea worsened total cross-linking. In conclusion, green tea and antioxidant vitamins improved several diabetes-related cellular dysfunctions but worsened matrix glycoxidation in selected tissues, suggesting that antioxidant treatment tilts the balance from oxidative to carbonyl stress in the extracellular compartment.
Abstract 4718: Withaferin A, a potent and abundant component of Withania somnifera root extract, reduces myeloid-derived suppressor cell function. (2013)

Abstract Myeloid cells play a crucial role in growth and metastasis of malignant tumors. Tumor infiltrating myeloid cells includes myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAMS) and dendritic cells (DC). These cells infiltrate into tumor and suppress tumor immunity by their inherent immune suppressive activity which is enhanced by interactions with each other (cross-talk). Therapeutic strategies targeting manipulation of these cells are being developed. The root extract of the plant Withania somnifera (Ashwagandha) (WRE) has been reported to reduce tumor cell proliferation and angiogenesis. Whether the anti-tumor effects of WRE are due to direct effects on malignant cells, or whether WRE also impacts immune suppressive myeloid cells is unknown. We hypothesize that WRE or its constituents impact tumor infiltrating myeloid cells and thereby boost anti-tumor immunity. HPLC and mass spectrometry analysis revealed that Withaferin A (WA) is the most abundant constituent of Withania somnifera root powder (ChromaDex, Inc. Irvine, CA). In comparison with the other constituents, WA has the most potent effect on reducing suppressive functions of myeloid cells. A prominent effect of MDSC is their production of IL-10 which increases upon cross-talk with macrophages, thus polarizing immunity to a tumor promoting type-2 phenotype. WA reduces inherent and cross-talk induced IL-10 secretion from MDSC in a dose dependent manner. Macrophage secretion of IL-6 and TNFα cytokines that are characteristic of M1-type macrophages and that also increase MDSC accumulation and function, are also reduced by WA. Much of the T cell suppressive activity of MDSC is due to MDSC production of reactive oxygen species (ROS), and WA significantly reduces MDSC production of ROS. Thus adjunctive treatment with WA has the potential to concomitantly reduce myeloid cell mediated immune suppression, to polarize immunity towards a tumor-rejecting type I phenotype, and to facilitate the development of anti-tumor immunity. Supported by NIH RO1CA115880, RO1CA84232, and American Cancer Society IRG-97-153-07 Citation Format: Pratima Sinha, Suzanne Ostrand-Rosenberg. Withaferin A, a potent and abundant component of Withania somnifera root extract, reduces myeloid-derived suppressor cell function. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2013-4718
Optimum predictors of therapeutic outcome in HCV patients in Pakistan (2015)

Hepatitis C virus (HCV) constitutes a major public health issue in Pakistan. Interferon α and ribavirin is used widely in routine practice in HCV infected patients in Pakistan.Treatment prediction is an important tool in therapy management. The present study aims to evaluate trends of predictive variables of treatment outcome in patients with different genotypes. The analysis comprised of 921 patients infected with different HCV genotypes. All the patients received IFN α-2b combined with ribavirin for 24 weeks. Overall, 60.2% patients achieved Sustained virologic response (SVR). In females sustained virologic response (SVR) was higher in age group <40 years (77.2%) than ≥40-50 years (60%) but in male SVR was almost equal in both age groups. We also found higher SVR with low pretreatment viral load (72.4%, P < 0.0001). Sustained Virologic Response in genotype 3a was 63.1%, 3b was 55%, 1a was 36.3% and 1b was 35% 3a +3b was 55.0% and 1a+3a was 42.9%. According to multivariable logistic regression analysis age < 40 years (2.0; 95%CI, 1.49-2.84; P = 0.0001), low pretreatment RNA level<800,000 IU/ml (4.0; 95%CI, 2.64-6.17; P = 0.0001), early virologic response at week 12 (12.3; 95%CI, 8.18-18.58; P < 0.0001) and non-fatty liver (2.5; 95%CI, 3.6-6.2; P = 0.005) showed significance for SVR. Nucleotide substitution in 5'UTR before treatment failed to show any characteristic pattern that has correlation with sustained response. Subtype 3a showed 95% presence among patients with age <40 years while older patients showed 79.9%.