Negligible Variation and the Change of Variables Theorem

In this note we prove a necessary and sufficient condition for the change of variables formula for the HK integral, with implications for the change of variables formula for the Lebesgue integral. As a corollary, we obtain a necessary and sufficient condition for the Fundamental Theorem of Calculus to hold for the HK integral

THE MAST CELLS AND MASTOCYTOSIS

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The impact of economic activities on the social and political structures of Kuwait (1896-1946)

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Altering DNA Base Excision Repair: Use of Nuclear and Mitochondrial-Targeted N-Methylpurine DNA Glycosylase to Sensitize Astroglia to Chemotherapeutic Agents

Primary astrocyte cultures were used to investigate the modulation of DNA repair as a tool for sensitizing astrocytes to genotoxic agents. Base excision repair (BER) is the principal mechanism by which mammalian cells repair alkylation damage to DNA and involves the processing of relatively nontoxic DNA adducts through a series of cytotoxic intermediates during the course of restoring normal DNA integrity. An adenoviral expression system was employed to target high levels of the BER pathway initiator, N-methylpurine glycosylase (MPG), to either the mitochondria or nucleus of primary astrocytes to test the hypothesis that an alteration in BER results in increased alkylation sensitivity. Increasing MPG activity significantly increased BER kinetics in both the mitochondria and nuclei. Although modulating MPG activity in mitochondria appeared to have little effect on alkylation sensitivity, increased nuclear MPG activity resulted in cell death in astrocyte cultures treated with methylnitrosourea (MNU). Caspase-3 cleavage was not detected, thus indicating that these alkylation sensitive astrocytes do not undergo a typical programmed cell death in response to MNU. Astrocytes were found to express relatively high levels of antiapoptotic Bcl-2 and Bcl-XL and very low levels of proapoptotic Bad and Bid suggesting that the mitochondrial pathway of apoptosis may be blocked making astrocytes less vulnerable to proapoptotic stimuli compared with other cell types. Consequently, this unique characteristic of astrocytes may be responsible, in part, for resistance of astrocytomas to chemotherapeutic agents

DNA oligonucleotides with A, T, G or C opposite an abasic site: structure and dynamics

Abasic sites are common DNA lesions resulting from spontaneous depurination and excision of damaged nucleobases by DNA repair enzymes. However, the influence of the local sequence context on the structure of the abasic site and ultimately, its recognition and repair, remains elusive. In the present study, duplex DNAs with three different bases (G, C or T) opposite an abasic site have been synthesized in the same sequence context (5′-CCA AAG[subscript 6] XA[subscript 8]C CGG G-3′, where X denotes the abasic site) and characterized by 2D NMR spectroscopy. Studies on a duplex DNA with an A opposite the abasic site in the same sequence has recently been reported [Chen,J., Dupradeau,F.-Y., Case,D.A., Turner,C.J. and Stubbe,J. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4′-oxidized abasic sites. Biochemistry, 46, 3096–3107]. Molecular modeling based on NMR-derived distance and dihedral angle restraints and molecular dynamics calculations have been applied to determine structural models and conformational flexibility of each duplex. The results indicate that all four duplexes adopt an overall B-form conformation with each unpaired base stacked between adjacent bases intrahelically. The conformation around the abasic site is more perturbed when the base opposite to the lesion is a pyrimidine (C or T) than a purine (G or A). In both the former cases, the neighboring base pairs (G6-C21 and A8-T19) are closer to each other than those in B-form DNA. Molecular dynamics simulations reveal that transient H-bond interactions between the unpaired pyrimidine (C20 or T20) and the base 3′ to the abasic site play an important role in perturbing the local conformation. These results provide structural insight into the dynamics of abasic sites that are intrinsically modulated by the bases opposite the abasic site.National Institutes of Health (U.S.) (Grant GM 34454)National Institutes of Health (U.S.) (Grant GM 45811)National Institutes of Health (U.S.) (Grant RR-00995)France. Recherche, Ministère de laFrance. Ministère de l'éducation national

A Robust Case of Allergic Contact Dermatitis to Propolis

Allergic contact dermatitis (ACD) occurs when an individual comes into cutaneous contact with a substance to which he or she has been sensitized to, causing a delayed-type hypersensitivity reaction. While the diagnosis may in some cases be easily suspected due to a classic history and exam, not all cases are obvious. Patch testing is an extremely useful process that allows for the diagnosis of ACD to be made while also identifying the specific chemical trigger. Present in beeswax and composed of a mixture of resins, waxes, oils, pollen, and various organic compounds, propolis is a well-known cause of ACD. Here we present the case of ACD to propolis in an unusual product and with impressive clinical findings. A 58 year-old woman of Native American descent with a history of Sjogren\u27s syndrome presented to Dermatology for a one year history of a painful and pruritic rash on her lips and face. She had temporary improvement with a previous course of prednisone followed by relapse upon tapering, but otherwise the rash had been worsening despite the use of high-potency topical steroids. She was also using bear grease and lip butter as moisturizers. On physical exam she had a well-demarcated symmetric perioral erythematous lichenified scaly plaque, as well as confluent erythema and scaling of her mucosal lips. After tinea incognito was ruled out by fungal culture, she subsequently underwent patch testing for suspected ACD. The diagnosis was confirmed with positive reactions at both the 2 day and 7 day reads to propolis and her bear grease and lip butter, both of which contained beeswax. The patient had complete resolution shortly after discontinuation of these products, and she was advised to avoid other products that contain propolis. With a soft and pliable texture and pleasant aroma, propolis is present in many creams, ointments, waxes, lipsticks, and balms. Moreover, with it\u27s reported anti-inflammatory and antimicrobial properties, it can also be found in various cosmeceutical, naturopathic, and homeopathic products. Made from bear fat and beeswax, the bear grease product the patient was using was advertised as having natural healing benefits and was purchased at a Native American craft store. This case is unique, as it represents a common allergen found in an uncommon vehicle. Moreover, it illustrates the importance of taking a comprehensive history when assessing for ACD, as well as the utility of patch testing.https://scholarlycommons.henryford.com/merf2020caserpt/1111/thumbnail.jp