Sticky Compliance: An Endowment Account of Expressive Law

This Article extends the literature on expressive law by developing a model of compliance rooted in the endowment effect. The central premise of the model is that compliance with legal rules, while costly from an ex ante perspective, may also endow individuals with a stream of benefits whose ex post value will increase. Examples of compliance-related benefits would include reductions in risk to one’s own health and safety, enhanced reputation (as a law-abiding individual), and even tangible goods. Under this novel account, once an individual has complied with a law, received some associated benefits, and grown attached to such benefits via the endowment effect, violating the law might thereafter entail a net economic loss—even without the sanction that induced compliance in the first place. While the initial threat of sanction plays a key role in this story, the law’s capacity to change individual endowments through forced compliance, and in turn alter preferences, is the expressive engine of the endowment model. The upshot is not only that the compliance decision is about more than just costs, narrowly conceived; it is that the very act of compliance at one time might change the entire cost structure for future decisions about compliance. The Article distinguishes the endowment model from other expressive accounts and offers a series of antismoking examples as suggestive evidence of the model in action

Community Versus Market Values of Life

Individuals and communities make choices affecting the risk of accidental death. Individuals balance risk and cost in market choices, for example, by purchasing costly safety products or taking a dangerous job for higher pay. Communities balance risk and cost through social norms of precaution, which prescribe how much risk people may impose on others and on themselves. For example, social norms dictate that bicyclists should wear helmets and automobile passengers should wear seat belts. In both cases, the balance between the fatality risk and the cost of reducing it reveals an implicit value of a statistical life, or VSL an individual market VSL in the former case, and a community VSL in the latter instance. This Article explores the theoretical differences between community and market VSLs, provides average dollar values for both, and endorses the use of community VSLs in tort (as a measure of damages) and in the regulatory context (as an input to cost-benefit analyses). Our analysis of existing empirical studies reveals an average community VSL of roughly $2-3 million significantly smaller in value than market VSLs, which average roughly$7 million. After presenting and explaining these figures, we argue that courts and regulators should base the legal value of a life on the community value. The principal reasons for adopting community VSLs are validity and consistency. Community VSLs are a valid measure of the implicit value of life because they are derived from social norms, which embody the collective preferences and ideals of communities as refined over time. At a minimum, they are more reliable and meaningful measures of the value of life than the current legal alternatives: in tort, the unaided intuition ofjurors and, in the regulatory context, individual labor-market decisions made with limited information. Community VSLs would also increase internal consistency in tort, by linking the calculation of damages to the same community-centric standards already used to determine reasonable precaution. If adopted in the regulatory context and in tort law, communityVSLswould place bothmechanisms of risk regulation on the same, valid foundation

SEWA MENYEWA BARANG JAMINAN MENURUT PERSPEKTIF FIQH MUAMALAH (Studi Kasus di Desa Maligas Bayu Kab. Simalungun)

Skripsi yang berjudul: “SEWA-MENYEWA BARANG JAMINAN DALAM PERSPEKTIF FIQH MUAMALAH, merupakan studi kasus yang terdapat di Desa Maligas Bayu Kab. Simalungun.” Penelitian ini dilatar belakangi oleh adanya tingkat perekonomian masyarakat di Desa Maligas Bayu Kab. Simalungun yang berbeda-beda ada yang diatas (kaya), menengah (sederhana), dan ada juga yang dibawah. Hal ini dapat dilihat dari profesi dan kegiatan yang dilakukan diantaranya dengan adanya kegiatan sewa-menyewa, Sewa menyewa terjadi akibat manusia membutuhkan sesuatu yang berada dalam kepemilikan orang lain, dengan demikian orang tersebut dapat menggunakan suatu cara transaksi, salah satunya dengan cara sewa- menyewa/ ijarah. Dalam pelaksanaan sewa menyewa barang di Desa Maligas Bayu Kab. Simalungun apabila pihak pertama yang berhutang tidak bisa membayar pinjaman sesuai dengan waktu yang ditentukan oleh pihak kedua yang memberikan pinjaman dan telah disepakati oleh kedua pihak maka pihak kedua dapat mengambil barang atau harta yg berharga milik pihak pertama sebagai jaminan. Adapun permasalahan yang dibahas dalam penelitian ini adalah bagaimana sistem pelaksanaan sewa menyewa barang jaminan yang dilakukan di Desa Maligas Bayu Kab. Simalungun, bagaimana pandangan fiqih muamalah terhadap pelaksanaan sewa menyewa barang jaminan tersebut. Hasil penelitian ini menunjukkan persepsi masyarakat Desa Maligas Bayu Kab. Simalungun tentang pelaksanaan sewa-menyewa barang jaminan, ini dapat dilihat dari hasil wawancara bahwa masyarakat tidak setuju dengan adanya aktivitas sewa-menyewa ini, Dikarenakan walaupun dapat membantu memenuhi kebutuhan akantetapi mengandung unsur kezhaliman karena tidak menghiraukan ijin dari pemilik barang yang akan disewakan, dan hai itu tidak dibenarkan dalam hukum islam

Isolation and Characterization of the Human CP49 Gene Promoter

PURPOSE. This study focuses on the identification of regulatory elements that contribute to lens-specific expression of the human CP49 gene within the 5Ј-flanking DNA sequences. METHODS. The DNA sequence upstream of the human CP49 coding region was subcloned as a set of 5Ј and 3Ј deletion series. The constructs were transfected into lens (N/N1003A) and nonlens (NIH3T3) cell lines and chicken primary lens cultures, to test for promoter activity and specificity. To further test the specificity, a portion of the 5Ј flanking DNA sequence was used to drive transgene expression in mice. The flanking DNA sequence was analyzed for potential transcription factorbinding sites. RESULTS. The 5Ј-flanking DNA preferentially activated reporter gene expression in a lens-preferred manner when transfected into cultured cells. Transgene expression driven by the CP49 promoter region was lens specific. Analysis of the proximal promoter sequence revealed the presence of potential binding sites for the AP-1, AP-2, and OCT-1 transcription factors and the absence of TATA and CAAT boxes. CONCLUSIONS. The sequence upstream of the CP49 gene possesses promoter activity and is able to drive lens-preferred expression in both transfection and transgenic experiments. Promoter activity is dependent on the presence of the proximal 300 bp directly upstream of the coding region. O cular lens development commences with a thickening of the anterior surface ectoderm that establishes the boundary of the presumptive lens as the lens placode. Invagination of the thickened ectoderm creates the lens pit, which is then pinched off from the ectoderm as a hollow sphere of cells known as the lens vesicle. The epithelial cells at the posterior end of the lens vesicle undergo terminal differentiation to form primary lens fiber cells. During this process, the cells elongate to fill the lumen of the lens vesicle. The anterior portion of the lens is lined by a single layer of epithelial cells that remain mitotically active and undergo differentiation at the equator, or bow region, of the lens to continually add secondary fiber cells to the lens mass. In addition to cell elongation the differentiation process of lens epithelial cells to lens fiber cells involves the loss of the nucleus and other membrane-bound organelles and alterations in gene expression. 1 Lens fiber cell formation results in the upregulation of a limited collection of genes that includes members of the soluble crystallin gene family, major intrinsic protein (MIP), and the core components of the lens fiber-specific beaded filament CP49 and CP115. 2 The CP49 and CP115 genes have been classified as divergent members of the intermediate filament family on the basis of conserved primary DNA sequence and gene structure. 7 Mutations in the CP49 have been linked to cataract formation, suggesting a role for the beaded filament, which is critical to lens clarity. 10 -13 The mutation or absence of any one of these factors in mice, accomplished through targeted gene deletion, results in abnormal eye and/or lens development, ranging from defective lens fiber cell differentiation to the complete absence of the lens. In this study, the 5Ј-flanking and intronic DNA sequences of the human CP49 gene have been analyzed for potential regulatory elements. The transfection of cell lines and primary lens cultures and the production of transgenic animals were performed to test the proximal promoter for contributions to the cell type and differentiation-stage-specific expression pattern observed for the human CP49 gene. The results of these experiments suggest that the 5Ј-flanking DNA proximal to the human coding sequence confers lens-preferred expression of reporter genes. Sequence analysis of the 5Ј-flanking region does not identify consensus binding sites for transcription factors used in the regulation of crystallin genes, suggesting the possibility of separate control mechanism(s) for crystallin and noncrystallin gene regulation within the lens fiber cell

Immunomodulatory role of Keratin 76 in oral and gastric cancer

Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs

Persistent DNA Damage after High Dose In Vivo Gamma Exposure of Minipig Skin

Exposure to high doses of ionizing radiation (IR) can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin.IR-induced DNA damage, repair and cellular survival were studied in 15 cm(2) of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF) formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of <1% of keratinocytes at 28-70 days. The latter contained large RIFs that included ATM-p, indicating the accumulation of complex DNA damage. At 96 days most of the cells with RIFs had disappeared. The frequency of active-caspase-3-positive apoptotic cells was 17-fold increased 3 days after IR and remained >3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+) were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days.Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research

Differential Modulation of Keratin Expression by Sulforaphane Occurs via Nrf2-dependent and -independent Pathways in Skin Epithelia

In this study the authors address the mechanistic basis of the therapeutic benefit afforded by treatment with the naturally occurring small molecule sulforaphane in the context of a keratin-based skin blistering disease, epidermolysis bullosa simplex

A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion. Following 7 days of culture with TGFβ1, 41 IPF- and fibrosis-associated genes were significantly upregulated. Immunohistochemical staining demonstrated increased expression of ECM proteins and fibroblast-specific protein after TGFβ1-stimulation. Collagen secretion was significantly increased following TGFβ1-stimulation. These pro-fibrotic responses were attenuated by senicapoc, but not by dexamethasone. This 7 day ex vivo model of human lung fibrogenesis recapitulates pro-fibrotic events evident in IPF and is sensitive to KCa3.1 channel inhibition. By maintaining the complex cell-cell and cell-matrix interactions of human tissue, and removing cross-species heterogeneity, this model may better predict drug efficacy in clinical trials and accelerate drug development in IPF. KCa3.1 channels are a promising target for the treatment of IPF.This work was supported by The Dunhill Medical Trust, project grant R270/1112, the MRC, project grant MR/K018213/1, and The British Lung Foundation, grant PPRG15-8. The work was also supported in part by the National Institute for Health Research Leicester Respiratory Biomedical Research Unit