Stains Induce Apoptosis and Autophagy in Primary and Transformed Mast Cells

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis in both primary and transformed mast cells. An IC50 was achieved between 1-5μM in both systems, and apoptosis was preceded by mitochondrial dysfunction and caspase release. In addition to apoptosis, our work also uncovered evidence of autophagy, which can serve as a compensatory mechanism during apoptosis. Interestingly, autophagy appeared to be cyto-protective in the primary cells yet cytotoxic in transformed mast cells. These findings offer insight into the mechanisms of mast cell survival and support the possible utility of statins in mast cell-associated allergic and neoplastic diseases

Transatlantic Differences in Labour Markets: Changes in Wage and Non-Employment Structures in the 1980s and the 1990s

Rising wage inequality in the U.S. and Britain and rising continental European unemployment have led to a popular view in the economics profession that these two phenomena are related to negative relative demand shocks against the unskilled, combined with flexible wages in the Anglo-Saxon countries, but institutional rigidities in continental Europe ('Krugman hypothesis'). This paper tests this hypothesis based on seven large person-level data sets for the 1980s and the 1990s. I use a more sophisticated categorisation of low-skilled workers than previous studies, which highlights the distinction between German workers with and without apprenticeship training. I find evidence for the Krugman hypothesis when Germany is compared to the U.S. However, supply changes differ considerably between countries, with Britain experiencing enormous increases in skill supply explaining the relatively constant British skill premium in the 1990shttp://deepblue.lib.umich.edu/bitstream/2027.42/40148/3/wp762.pd

Amperean pairing and the pseudogap phase of cuprate superconductors

The enigmatic pseudogap phase in underdoped cuprate high T_c superconductors has long been recognized as a central puzzle of the T_c problem. Recent data show that the pseudogap is likely a distinct phase, characterized by a medium range and quasi-static charge ordering. However, the origin of the ordering wavevector and the mechanism of the charge order is unknown. At the same time, earlier data show that precursive superconducting fluctuations are also associated with this phase. We propose that the pseudogap phase is a novel pairing state where electrons on the same side of the Fermi surface are paired, in strong contrast with conventional BCS theory which pair electrons on opposite sides of the Fermi surface. In this state the Cooper pair carries a net momentum and belong to a general class called pair density wave (PDW). The microscopic pairing mechanism comes from a gauge theory formulation of the resonating valence bond (RVB) picture, where electrons traveling in the same direction feel an attractive force in analogy with Ampere's effects in electromagnetism. We call this Amperean pairing. Charge order automatically appears as a subsidiary order parameter. Our theory gives a prediction of the ordering wavevector which is in good agreement with experiment. Furthermore, the quasiparticle spectrum from our model explains many of the unusual features reported in photoemission experiments. The Fermi arc and the unusual way the tip of the arc terminates also come out naturally. We also discuss how the onset of the Kerr effect in this state can be accommodated. Finally, we propose an experiment which can directly test the notion of Amperean pairing.Comment: (v4) added phase diagram, Appendix A on the incompatibility of CDW model, and more discussion of low-temperature properties; (v3) expanded supplementary section, added figures and discussion on Fermi arc; (v2) added references, improved figures, corrected typo in Eq.(4

Reversal by Recusal? Comer V. Murphy Oil U.S.A., Inc. And The Needfor Mandatory Judicial Recusal Statements

[Excerpt] In many cases, if not most, voluntary judicial recusal is both an efficient use of judicial resources and an exceptional safeguard to the legitimacy of the federal judiciary. However, voluntary judicial recusal poses its own unique problems when the withdrawing judge declines to issue a statement explaining the statutory grounds for his or her recusal. Unlike when a party seeks to disqualify a judge by motion—where the reasons for recusal will, at a minimum, be set out in the motion papers—when a judge voluntarily recuses, there is not necessarily any record created as to the reasons for the recusal. Such recusals leave litigants in the dark, creating numerous practical problems where the recusal itself has collateral consequences. These problems are compounded when, prior to recusal, the judge has already taken meaningful action in the case. This article will analyze the recent case of Comer v. Murphy Oil USA Inc. in an effort to illustrate several of the many reasons why federal judges, upon voluntary recusal, should be required to issue a statement identifying the statutory provision requiring their disqualification. The article will also argue that where a judge is recusing him or herself from a case where the basis of the recusal may be waived, the parties should be permitted to demand, and receive, a statement sufficiently detailed so as to permit them to waive the conflict if they so choose. To put the arguments in context, this article will first lay out the highly unusual procedural history of Comer v. Murphy Oil USA, Inc. Next, the article will use the facts of Comer to illustrate several problems created, exacerbated, or made insoluble by voluntary recusal without the issuance of a recusal statement. Finally, the article will propose two statutory provisions for suggested inclusion in the federal judicial recusal statutes. Those provisions would require judges to issue basic recusal statements whenever they become disqualified and more detailed statements in appropriate circumstances without requiring a level of detail that would over burden the judiciary or impinge too far upon the privacy interests of individual federal judges

Game Changer

Why the rapidly evolving landscape for clients requires creative new moves from lawyers and the profession

Diversity and structure of human T-Cell receptor β-chain variable region genes

The nucleotide sequences of 27 T-cell receptor β cDNA clones isolated from a human peripheral lymphocyte library were determined and compared to five additional published sequences. These cDNA clones represent 22 distinct T-cell receptor β-chain variable region (Vβ) gene segment sequences, which fall into 15 different Vβ gene subfamilies, each containing six or fewer members. From this analysis, we estimate that the repertoire of expressed human Vβ genes is <59, apparently much smaller than the immunoglobulin heavy chain and light chain variable region (VH and VL) repertoires. Variability plots comparing these human Vβ regions with each other and with published mouse Vβ regions provide evidence for only four hypervariable regions homologous to those seen in comparisons of immunoglobulin V regions. Somatic hypermutation appears to be used infrequently, if at all, in these Vβ genes