Business and Human Rights as a Galaxy of Norms

In the last several years, there has been an increasing tendency to view the impacts of transnational business operations through the lens of human rights law. A major obstacle to holding companies accountable for the harms that they impose, however, has been the separate legal identity of corporate subsidiaries and of contractors in a company\u27s supply chain. France\u27s recently enacted duty of vigilance statute seeks to overcome this obstacle by imposing a duty on companies to identify potential serious human rights violations by their subsidiaries and by companies with which they have an “established commercial relationship.” Failure to engage in such vigilance can subject a company to liability for damages resulting from such failure. This Article situates the new French duty of vigilance within a broader set of norms that can be characterized as the Business and Human Rights Galaxy. This Galaxy consists of five rings that represent standards and expectations ranging from classic enforceable “hard law” to voluntary principles generated by private parties, multi-stakeholder initiatives, and international organizations. The provisions in these rings are related in fluid and dynamic ways and exert varying degrees of gravitational influence on one another. Thus, for instance, what are conventionally regarded as forms of hard law may draw on voluntary private standards in setting expectations for behavior, and soft law norms may be incorporated into legally enforceable contract provisions between companies and their suppliers. This Article suggests that appreciation of these dynamics can furnish guidance in interpreting the novel duty of vigilance that the new French statute establishes. In particular, the common law duty of care and the United Nations Guiding Principles on Business and Human Rights can illuminate the nature and scope of the duty of vigilance. At the same time, the introduction of the new French statute into the Business and Human Rights Galaxy means that it too has the potential to influence provisions in other rings of the Galaxy

Early French Migrations to Northern Maine, 1785-1850

The article explores the origins of the Madawaska settlement in Northern Maine and provides an opportunity to study the process of migration and resettlement

Angiotensin Converting Enzyme Inhibitors as First Line of Therapy in Managing Essential Hypertension In Patients without Compelling Indications.

Hypertension (HTN) is one of the most common chronic diseases seen in ambulatory care. It is a major risk factor for the development of cardiovascular diseases including coronary artery disease (CAD), stroke, and heart failure. According to the recent statistical facts on high blood pressure, 67 million American adults have high blood pressure. High blood pressure costs the nation$47.5 billion annually in direct medical expenses and$ 3.5 billion each year in lost productivity. About half (47%) of people with the disease have their condition under control (Centers for Disease and Prevention). The management of HTN is of particular importance for healthcare providers such as nurse practitioners, due to its prevalence and its modifiable risk factor for cardiovascular conditions. The management of HTN has shifted from a sole focus on blood pressure-lowering to that of prevention of cardiovascular and renal disease. Angiotensin-converting enzyme (ACE) inhibitors play a crucial role in treatment of HTN. In addition, ACE inhibitors are beneficial in the prevention of some comorbidities such as nephropathy, new onset diabetes and progression of pre-hypertension to HTN A comprehensive literature review will be conducted using a wide range of electronic and evidenced-based databases to identify study samples that predominantly focus on ACE inhibitors as first line of therapy in controlling high blood pressure in patients without compelling comorbiditie

Early French Migrations to Northern Maine, 1785-1850

The article explores the origins of the Madawaska settlement in Northern Maine and provides an opportunity to study the process of migration and resettlement

Pengaruh Brand Identity Terhadap Timbulnya Brand Preference Dan Repurchase Intention Pada Merek Toyota

Penelitian ini dilakukan untuk mengetahui pengaruh identitas merk Toyota terhadap timbulnya preferensi merek dan niat pembelian kembali konsumen terhadap merek Toyota. Toyota sebagai penguasa pasar mobil di Indonesia, memiliki keunggulan kompetitif tersendiri dibandingkan dengan pesaingnya. Kepercayaan terhadap merek Toyota juga menimbulkan adanya niat pembelian kembali konsumen terhadap merek tersebut.Teknik analisa yang digunakan dalam penelitian ini adalah kausal asosiatif dengan metode penelitian Structural Equation Model (SEM) untuk meneliti hubungan antara variabel identitas merek dengan preferensi merek dan niat pembelian kembali pada merek Toyota.Hasil penelitian membuktikan bahwa identitas merek berpengaruh secara positif terhadap timbulnya preferensi merek dan niat pembelian kembali pada merek Toyota. Demikian pula preferensi merek berpengaruh positif terhadap niat pembelian kembali pada merek Toyota

B831: The Role of Human Capital in the Adoption of Conservation Tillage: The Case of Aroostook County, Maine, Potato Farmers

Given the continuing potential loss from soil erosion and the significant effort put forth recently to alleviate the problem in Aroostook County, it is important to study ways to improve the success rate of that effort. One way to improve the soil loss problem is for farmers to adopt conservation tillage practices for those areas where there are significant benefits from doing so. The objective of this study is to identify the characteristics important in the adoption decisions of Aroostook County farmers. The Maine results will be compared with results from a study in Iowa to identify any differences in the decisionmaking process in Maine relative to Iowa.https://digitalcommons.library.umaine.edu/aes_bulletin/1021/thumbnail.jp

Capsaicin triggers autophagic cell survival which drives epithelial mesenchymal transition and chemoresistance in bladder cancer cells in an Hedgehog-dependent manner

Bladder cancer (BC) is a common urologic tumor characterized by high risk of recurrence and mortality. Capsaicin (CPS), used as an intravesical drug for overactive bladder, was demonstrated to induce cell death in different cancer cells including BC cells.Here we found that treatment of high-grade BC cells with high dose of CPS triggers autophagy. Infact, the CPS treatment alters the redox homeostasis by inducing production of radicals, mitochondrial depolarization, alterations of ADP/ATP ratio and activation of AMPK pathway stimulating the autophagic process in BC cells. The inhibition of autophagy, by using the specific inhibitor bafilomycin A or Beclin 1 knock-down, enhanced the CPS-induced cell death, demonstrating that CPS-induced autophagy acts as a pro-survival process in BC cells. By using PCR arrays and FACS analysis, we found that the CPS-treated BC cells displayed typical mesenchymal features of the epithelial mesenchymal transition (EMT) as elongated shape and over-expression of vimentin, α5 and β1 integrin subunits, integrin-like kinase and the anti-apoptotic Bcl-2 proteins. Moreover, we demonstrated that CPS treatment stimulates upregulation of Dhh/Ptch2/Zeb2 members of the Hedgehog signaling pathway, increases CD24, VEGFA and TIMP1 and decreases CD44 and ALCAM mRNA expression levels. By PTCH2 knock-down we found that the Hedgehog signaling pathway is involved in the CPS-induced autophagy and EMT phenotype.Finally, we also showed that the CPS-resistant EMT-positive BC cells displayed an increased drug-resistance to the cytotoxic effects of mitomycin C, gemcitabine and doxorubicine drugs commonly used in BC therapy

Axitinib induces DNA damage response leading to senescence, mitotic catastrophe, and increased NK cell recognition in human renal carcinoma cells.

Tyrosine kinase inhibitors (TKIs) including axitinib have been introduced in the treatment of renal cell carcinoma (RCC) because of their anti-angiogenic properties. However, no evidence are presently available on a direct cytotoxic anti-tumor activity of axitinib in RCC.Herein we reported by western blot analysis that axitinib treatment induces a DNA damage response (DDR) initially characterized by γ-H2AX phosphorylation and Chk1 kinase activation and at later time points by p21 overexpression in A-498 and Caki-2 RCC cells although with a different potency. Analysis by immunocytochemistry for the presence of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cellular DNA and flow cytometry using the redox-sensitive fluorescent dye DCFDA, demonstrated that DDR response is accompanied by the presence of oxidative DNA damage and reactive oxygen species (ROS) generation. This response leads to G2/M cell cycle arrest and induces a senescent-like phenotype accompanied by enlargement of cells and increased senescence-associated β-galactosidase activity, which are abrogated by N-acetyl cysteine (NAC) pre-treatment. In addition, axitinib-treated cells undergo to cell death through mitotic catastrophe characterized by micronucleation and abnormal microtubule assembly as assessed by fluorescence microscopy.On the other hand, axitinib, through the DDR induction, is also able to increase the surface NKG2D ligand expression. Accordingly, drug treatment promotes NK cell recognition and degranulation in A-498 RCC cells in a ROS-dependent manner.Collectively, our results indicate that both cytotoxic and immunomodulatory effects on RCC cells can contribute to axitinib anti-tumor activity

Revisiting Sovereign Bankruptcy

Sovereign debt crises occur regularly and often violently. Yet there is no legally and politically recognized procedure for restructuring the debt of bankrupt sovereigns. Procedures of this type have been periodically debated, but so far been rejected, for two main reasons. First, countries have been reluctant to give up power to supranational rules or institutions, and creditors and debtors have felt that there were sufficient instruments for addressing debt crises at hoc. Second, fears that making debt easier to restructure would raise the costs and reduce the amounts of sovereign borrowing in many countries. This was perceived to be against the interests of both the providers of both creditors and major borrowers. This report argues that both the nature and our understanding of sovereign debt problems have changed, over the course of the last decade, in a direction that creates a much stronger case for an orderly sovereign bankruptcy regime today than ten years ago. Pre-crisis policy mistakes are now recognized to be a much more severe problem for borrowing countries than the costs or limited availability of private financing. Recent court rulings – particularly a recent U.S. ruling that gives holdout creditors that decline a restructuring offer the right to interfere with payments to the creditors that accept such an offer. This will complicate efforts to resolve future debt crises on an ad hoc basis. Finally, sovereign debt crises are no longer just a problem in emerging markets, but a core concern in advanced countries as well – particularly in the Euro area. If the Euro is to survive, this will require both better ways to resolve debt crises and stronger, market-based incentives that prevent debt problems from occurring in the first place. To address these problems, policy proposals are presented at two levels: for the Euro area, and globally. A Euro area sovereign debt restructuring regime could be developed by amending the Treaty establishing the European Stability Mechanism (ESM). This would both restrict the scope for lending to highly indebted countries without also restructuring their debts, and protect Euro area members receiving ESM financial assistance from legal action by holdout creditors. At the global level, a number of proposals are discussed, ranging from a coordinated introduction of aggregate collective action clauses that would allow a supermajority of bondholders across all bonds to amend bond payment terms to an amendment of the IMF articles that would limit the legal remedies of holdouts when a debt restructuring proposal has been accepted both by a majority of creditors and endorsed by the IMF