First Amendment and Foreign-Controlled U.S. Corporations: Why Congress Ought to Affirm Domestic Subsidiaries\u27 Corporate Political-Speech Rights

Political spending in the modern-day, prolonged election cycle continues to exceed historic proportions. With money equated to speech, whether the First Amendment entitles certain contributors to engage in this political activity remains an open question. Unlike France and Israel, which prohibit corporate contributions, and Canada and the United Kingdom, which turn to public funding for campaign finance, the United States has pushed candidates to rely on political party contributions, personal wealth, and the generosity of individuals, political action committees, and corporations. Concerns about corporate and foreign influence on politics have been especially salient during this lengthy economic downturn, as shown by the prominence of the nationwide Occupy Wall Street protests. Those who trumpet restrictions on so-called foreign corporate political influence are concerned with infringements on U.S. sovereign independence and citizens\u27 political self-determination. This Note responds to the uproar against corporate and foreign influence in the wake of Citizens United v. Federal Election Commission, arguing the debate in Congress and, thus, the law, ought to distinguish between domestic subsidiaries of foreign corporations and foreign corporations themselves. Under the current legal regime, no distinction between U.S. corporations and domestic subsidiaries exists; despite proposed legislation to the contrary, it should remain this way

The Role of Chemokines in Acute Liver Injury

Chemokines are small molecular weight proteins primarily known to drive migration of immune cell populations. In both acute and chronic liver injury, hepatic chemokine expression is induced resulting in inflammatory cell infiltration, angiogenesis, and cell activation and survival. During acute injury, massive parenchymal cell death due to apoptosis and/or necrosis leads to chemokine production by hepatocytes, cholangiocytes, Kupffer cells, hepatic stellate cells, and sinusoidal endothelial cells. The specific chemokine profile expressed during injury is dependent on both the type and course of injury. Hepatotoxicity by acetaminophen for example leads to cellular necrosis and activation of Toll-like receptors while the inciting insult in ischemia reperfusion injury produces reactive oxygen species and subsequent production of pro-inflammatory chemokines. Chemokine expression by these cells generates a chemoattractant gradient promoting infiltration by monocytes/macrophages, NK cells, NKT cells, neutrophils, B cells, and T cells whose activity are highly regulated by the specific chemokine profiles within the liver. Additionally, resident hepatic cells express chemokine receptors both in the normal and injured liver. While the role of these receptors in normal liver has not been well described, during injury, receptor up-regulation, and chemokine engagement leads to cellular survival, proliferation, apoptosis, fibrogenesis, and expression of additional chemokines and growth factors. Hepatic-derived chemokines can therefore function in both paracrine and autocrine fashions further expanding their role in liver disease. More recently it has been appreciated that chemokines can have diverging effects depending on their temporal expression pattern and the type of injury. A better understanding of chemokine/chemokine receptor axes will therefore pave the way for development of novel targeted therapies for the treatment of liver disease

Obesity, Inflammatory Signaling, and Hepatocellular Carcinoma—An Enlarging Link

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Upper Limit Set by Causality on the Rotation and Mass of Uniformly Rotating Relativistic Stars

Causality alone suffices to set a lower bound on the period of rotation of relativistic stars as a function of their maximum observed mass. That is, by assuming a one-parameter equation of state (EOS) that satisfies v_sound < c and that allows stars with masses as large as the largest observed neutron-star mass, M_sph^max, we find P[ms] > 0.282 + 0.196 ( M_sph^max/M_odot-1.442). The limit does not assume that the EOS agrees with a known low-density form for ordinary matter, but if one adds that assumption, the minimum period is raised by a few percent. Thus the current minimum period of uniformly rotating stars, set by causality, is 0.28ms (0.29ms for stars with normal crust). The minimizing EOS yields models with a maximally soft exterior supported by a maximally stiff core. An analogous upper limit set by causality on the maximum mass of rotating neutron stars requires a low-density match and the limit depends on the matching density, epsilon_m. We recompute it, obtaining a slightly revised value, M_rot^max \sim 6.1( 2 * 10^14 g/cm^3 epsilon_m )^1/2 M_odot.Comment: 28 pages, LaTeX2e, 8 Postscript figures, submitted to Ap

Genomics and proteomics in liver fibrosis and cirrhosis

Genomics and proteomics have become increasingly important in biomedical science in the past decade, as they provide an opportunity for hypothesis-free experiments that can yield major insights not previously foreseen when scientific and clinical questions are based only on hypothesis-driven approaches. Use of these tools, therefore, opens new avenues for uncovering physiological and pathological pathways. Liver fibrosis is a complex disease provoked by a range of chronic injuries to the liver, among which are viral hepatitis, (non-) alcoholic steatohepatitis and autoimmune disorders. Some chronic liver patients will never develop fibrosis or cirrhosis, whereas others rapidly progress towards cirrhosis in a few years. This variety can be caused by disease-related factors (for example, viral genotype) or host-factors (genetic/epigenetic). It is vital to establish accurate tools to identify those patients at highest risk for disease severity or progression in order to determine who are in need of immediate therapies. Moreover, there is an urgent imperative to identify non-invasive markers that can accurately distinguish mild and intermediate stages of fibrosis. Ideally, biomarkers can be used to predict disease progression and treatment response, but these studies will take many years due to the requirement for lengthy follow-up periods to assess outcomes. Current genomic and proteomic research provides many candidate biomarkers, but independent validation of these biomarkers is lacking, and reproducibility is still a key concern. Thus, great opportunities and challenges lie ahead in the field of genomics and proteomics, which, if successful, could transform the diagnosis and treatment of chronic fibrosing liver diseases

Reactions at Polymer Interfaces: Transitions from Chemical to Diffusion-Control and Mixed Order Kinetics

We study reactions between end-functionalized chains at a polymer-polymer interface. For small chemical reactivities (the typical case) the number of diblocks formed, $R_t$, obeys 2nd order chemically controlled kinetics, $R_t \sim t$, until interfacial saturation. For high reactivities (e.g. radicals) a transition occurs at short times to 2nd order diffusion-controlled kinetics, with $R_t \sim t/\ln t$ for unentangled chains while $t/\ln t$ and $t^{1/2}$ regimes occur for entangled chains. Long time kinetics are 1st order and controlled by diffusion of the more dilute species to the interface: $R_t \sim t^{1/4}$ for unentangled cases, while $R_t \sim t^{1/4}$ and $t^{1/8}$ regimes arise for entangled systems. The final 1st order regime is governed by center of gravity diffusion, $R_t \sim t^{1/2}$.Comment: 11 pages, 3 figures, uses poliface.sty, minor changes, to appear in Europhysics Letter

Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis

Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis. A better understanding of the cell types originating liver cancer can aid in exploring molecular mechanisms of carcinogenesis and therapeutic options. Molecular studies have identified adult hepatocytes as the cell of origin. These cells have been proposed to transform directly into HCC cells (via a sequence of genetic alterations), to dedifferentiate into hepatocyte precursor cells (which then become HCC cells that express progenitor cell markers), or to transdifferentiate into biliary-like cells (which give rise to iCCA). Alternatively, progenitor cells also give rise to HCCs and iCCAs with markers of progenitor cells. Advances in genome profiling and next-generation sequencing have led to the classification of HCCs based on molecular features and assigned them to categories such as proliferation-progenitor, proliferation-transforming growth factor β, and Wnt-catenin β1. iCCAs have been assigned to categories of proliferation and inflammation. Overall, proliferation subclasses are associated with a more aggressive phenotype and poor outcome of patients, although more specific signatures have refined our prognostic abilities. Analyses of genetic alterations have identified those that might be targeted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate dehydrogenases (in approximately 60% of iCCAs) or amplifications at 11q13 and 6p21 (in approximately 15% of HCCs). Further studies of these alterations are needed before they can be used as biomarkers in clinical decision making