670 research outputs found
Chromosome puff activity and protein synthesis in larval salivary glands of Drosophila melanogaster.
Distinguishing Deductible Repairs from Capitalized Improvements: An Expectations Approach to the New Repair Regulations
This Article explores an economic model of the business use of assets that supports an expectations approach to distinguishing between immediately deductible repairs and capitalized improvements. Under an expectations approach, the classification of an activity as a repair or a capital improvement depends on the taxpayerâs reasonable expectation when first placing the depreciable property in serviceâwhether, upon acquisition of the property, the taxpayer reasonably expected the activity to be required in the future to keep the property operating in its ordinarily efficient operating condition. Many of the rules provided by the new regulations are consistent with this approach. The inconsistent provisions can present problems. Section II of this Article provides a background of deductible repairs and capital improvement. After a brief overview of the purpose for distinguishing deductible repairs from capitalized improvements, this Article begins with an introduction to the expectations approach. An economic analysis that provides a basis for an expectations approach follows. In Section III, this underlying economic theory is used to evaluate whether the new regulations fully implement an expectations approach, leave any gaps, or otherwise create inconsistencies. In particular, this Article compares the regulationsâ application both to an asset that performs as originally expected and to an asset that does not so perform. Section IV concludes
Distinguishing Deductible Repairs from Capitalized Improvements: An Expectations Approach to the New Repair Regulations
This Article explores an economic model of the business use of assets that supports an expectations approach to distinguishing between immediately deductible repairs and capitalized improvements. Under an expectations approach, the classification of an activity as a repair or a capital improvement depends on the taxpayerâs reasonable expectation when first placing the depreciable property in serviceâwhether, upon acquisition of the property, the taxpayer reasonably expected the activity to be required in the future to keep the property operating in its ordinarily efficient operating condition. Many of the rules provided by the new regulations are consistent with this approach. The inconsistent provisions can present problems. Section II of this Article provides a background of deductible repairs and capital improvement. After a brief overview of the purpose for distinguishing deductible repairs from capitalized improvements, this Article begins with an introduction to the expectations approach. An economic analysis that provides a basis for an expectations approach follows. In Section III, this underlying economic theory is used to evaluate whether the new regulations fully implement an expectations approach, leave any gaps, or otherwise create inconsistencies. In particular, this Article compares the regulationsâ application both to an asset that performs as originally expected and to an asset that does not so perform. Section IV concludes
Altered Proliferation, Synthetic Activity, and Differentiation of Cultured Human sebocytes in the Absence of Vitamin A and Their Modulation by Synthetic Retinoids
Human sebocytes maintained in medium containing delipidized serum were studied for ultrastructural characteristics, cell proliferation, lipid synthesis, immunophenotype, and keratin expression before and after the addition of the synthetic retinoids isotretinoin and acitretin (10-8 - 10-5 M).Compared to the properties of sebocytes cultured in normal sebocyte medium (1â2 Ă 10-7 M vitamin A), the use of delipidized serum (undetectable amounts of vitamin A) resulted in prominent decrease of i) proliferation; ii) number of intracellular lipid droplets and synthesis of total lipids, especially triglycerides, squalene, and wax esters; and iii) labeling with monoclonal antibodies identifying progressive and late-stage sebocyte differentiation. Intercellular spaces narrowed and cell-to-cell contacts were established by abundant desmosomes. Lanosterol was induced. Keratins 14, 16, 17, and 18 were upregulated and the keratin 16: keratin 4 ratio, negatively correlating with sebocyte differentiation, increased.Addition of isotretinoin and acitretin exerted a biphasic effect. At concentrations †10-7 M, both compounds enhanced sebocyte proliferation and synthesis of total lipids, especially triglycerides and cholesterol, and decreased Ianosterol, keratin 16, and the keratin 16: keratin 4 ratio. In contrast, retinoid concentrations > 10-7 M inhibited sebocyte proliferation in a dose-dependent manner.Our findings indicate that vitamin A is essential for proliferation, synthetic activity, and differentiation of human sebocytes in vitro. Synthetic retinoids partially reinstate the altered functions of sebocytes maintained in medium containing delipidized serum. In contrast to the previously shown isotretinoin-specific response of cultured sebocytes in the presence of vitamin A, similar effects of isotretinoin and acitretin were obtained in its absence. This suggests different interactions of synthetic retinoids with vitamin A, possibly influencing their efficacy on the sebacceous gland
Genes Encoding Structural Proteins of Epidermal Cornification and S100 Calcium-Binding Proteins Form a Gene Complex (âEpidermal Differentiation Complexâ) on Human Chromosome 1q21
Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilles and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A8, S100A6. Co-localization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex
An immunohistochemical study of the tissue bridging adult spondylolytic defectsâthe presence and significance of fibrocartilaginous entheses
Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. Methods: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. Results: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Conclusions: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligamentâi.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic ga
Real-world evidence from the non-interventional, prospective, German multicentre PERSIST study of patients with psoriasis after 1âyear of treatment with guselkumab
Background PERSIST was a prospective, non-interventional, long-term, German multicentre study of patients with moderate-to-severe psoriasis receiving guselkumab, an approved monoclonal antibody that binds to the p19 subunit of interleukin (IL)-23, in a real-world setting. Objectives Evaluation of the efficacy and safety of guselkumab, and its effect on health-related quality of life (HRQoL), in patients with moderate-to-severe psoriasis who have received 52âweeks of treatment. Methods Patients (â„18âyears old) were prescribed guselkumab as per routine clinical practice. End points assessed include Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), target Nail Psoriasis Severity Index (NAPSI), and the Dermatology Life Quality Index (DLQI). Results Overall, 303 patients were enrolled and treated with guselkumab. Mean disease duration was 21.0âyears, and 77.2% and 51.2% of patients had received â„1 prior conventional systemic or â„1 prior biologic therapy, respectively. Mean PASI score decreased from 16.4 at baseline to 3.0 by Week (W) 28, and further decreased to 2.4 by W52, while the proportion of patients achieving an absolute PASI score of â€1 increased from 1.3% at baseline, to 50.8% at W28 and to 58.4% by W52. PASI90 and PASI100 responses also showed marked improvements between W28 and W52, regardless of biologic treatment history. Clearance of psoriatic skin was observed in difficult-to-treat areas, with the percentage of patients achieving a PGA scoreââ€1 increasing between W28 and W52. Guselkumab improved HRQoL; mean DLQI score decreased from 13.7 at baseline to 2.8 by W28, and further decreased to 2.4 by W52. At W52, 64.6% of patients achieved a DLQI scoreââ€1. The cumulative probability of drug survival was 92.4% at W52. Conclusions Guselkumab is efficacious and well tolerated regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. No new safety signals were observed
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