A Security Kernel Based on the Lambda-Calculus

Cooperation between independent agents depends upon establishing adegree of security. Each of the cooperating agents needs assurance that the cooperation will not endanger resources of value to that agent. In a computer system, a computational mechanism can assure safe cooperation among the system's users by mediating resource access according to desired security policy. Such a mechanism, which is called a security kernel, lies at the heart of many operating systems and programming environments.The report describes Scheme 48, a programming environment whose design is guided by established principles of operating system security. Scheme 48's security kernel is small, consisting of the call-by-value $lambda$-calculus with a few simple extensions to support abstract data types, object mutation, and access to hardware resources. Each agent (user or subsystem) has a separate evaluation environment that holds objects representing privileges granted to that agent. Because environments ultimately determine availability of object references, protection and sharing can be controlled largely by the way in which environments are constructed. I will describe experience with Scheme 48 that shows how it serves as a robust and flexible experimental platform. Two successful applications of Scheme 48 are the programming environment for the Cornell mobile robots, where Scheme 48 runs with no (other) operating system support; and a secure multi-user environment that runs on workstations

Pair Multiplicities and Pulsar Death

Through a simple model of particle acceleration and pair creation above the polar caps of rotation-powered pulsars, we calculate the height of the pair-formation front (PFF) and the dominant photon emission mechanism for the pulsars in the Princeton catalog. We find that for most low- and moderate-field pulsars, the height of the pair formation front and the final Lorentz factor of the primary beam is set by nonresonant inverse Compton scattering (NRICS), in the Klein-Nishina limit. NRICS is capable of creating pairs over a wide range of pulsar parameters without invoking a magnetic field more complicated than a centered dipole, although we still require a reduced radius of curvature for most millisecond pulsars. For short-period pulsars, the dominant process is curvature radiation, while for extremely high-field pulsars, it is resonant inverse Compton scattering (RICS). The dividing point between NRICS dominance and curvature dominance is very temperature-dependent; large numbers of pulsars dominated by NRICS at a stellar temperature of $10^6$ K are dominated by curvature at $10^5$ K. We apply these results to pulsar death-line calculations and to the issue of particle injection into the Crab Nebula.Comment: 14 pages, 7 figures, to appear in Ap

Selective loss of TGFbeta Smad-dependent signalling prevents cell cycle arrest and promotes invasion in oesophageal adenocarcinoma cell lines.

In cancer, Transforming Growth Factor beta (TGFbeta) increases proliferation and promotes invasion via selective loss of signalling pathways. Oesophageal adenocarcinoma arises from Barrett's oesophagus, progresses rapidly and is usually fatal. The contribution of perturbed TGFbeta signalling in the promotion of metastasis in this disease has not been elucidated. We therefore investigated the role of TGFbeta in Barrett's associated oesophageal adenocarcinoma using a panel of cell lines (OE33, TE7, SEG, BIC, FLO). 4/5 adenocarcinoma cell lines failed to cell cycle arrest, down-regulate c-Myc or induce p21 in response to TGFbeta, and modulation of a Smad3/4 specific promoter was inhibited. These hyperproliferative adenocarcinoma cell lines displayed a TGFbeta induced increase in the expression of the extracellular matrix degrading proteinases, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1), which correlated with an invasive cell phenotype as measured by in vitro migration, invasion and cell scattering assays. Inhibiting ERK and JNK pathways significantly reduced PAI and uPA induction and inhibited the invasive cell phenotype. These results suggest that TGFbeta Smad-dependent signalling is perturbed in Barrett's carcinogenesis, resulting in failure of growth-arrest. However, TGFbeta can promote PAI and uPA expression and invasion through MAPK pathways. These data would support a dual role for TGFbeta in oesophageal adenocarcinoma

Time-dependence in Relativistic Collisionless Shocks: Theory of the Variable "Wisps" in the Crab Nebula

We describe results from time-dependent numerical modeling of the collisionless reverse shock terminating the pulsar wind in the Crab Nebula. We treat the upstream relativistic wind as composed of ions and electron-positron plasma embedded in a toroidal magnetic field, flowing radially outward from the pulsar in a sector around the rotational equator. The relativistic cyclotron instability of the ion gyrational orbit downstream of the leading shock in the electron-positron pairs launches outward propagating magnetosonic waves. Because of the fresh supply of ions crossing the shock, this time-dependent process achieves a limit-cycle, in which the waves are launched with periodicity on the order of the ion Larmor time. Compressions in the magnetic field and pair density associated with these waves, as well as their propagation speed, semi-quantitatively reproduce the behavior of the wisp and ring features described in recent observations obtained using the Hubble Space Telescope and the Chandra X-Ray Observatory. By selecting the parameters of the ion orbits to fit the spatial separation of the wisps, we predict the period of time variability of the wisps that is consistent with the data. When coupled with a mechanism for non-thermal acceleration of the pairs, the compressions in the magnetic field and plasma density associated with the optical wisp structure naturally account for the location of X-ray features in the Crab. We also discuss the origin of the high energy ions and their acceleration in the equatorial current sheet of the pulsar wind.Comment: 13 pages, 4 figures, accepted to ApJ. High-resolution figures and mpeg movies available at http://astron.berkeley.edu/~anatoly/wisp

Evidence for variable selective pressures at MC1R

It is widely assumed that genes that influence variation in skin and hair pigmentation are under selection. To date,the melanocortin 1 receptor (MC1R) is the only gene identified that explains substantial phenotypic variance inhuman pigmentation. Here we investigate MC1R polymorphism in several populations, for evidence of selection.We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations underrelaxation of strong functional constraint outside Africa

A questionnaire elicitation of surgeons' belief about learning within a surgical trial

PMID: 23145113 [PubMed - indexed for MEDLINE] PMCID: PMC3493499 Free PMC ArticlePeer reviewedPublisher PD

Anterior knee pain from the evolutionary perspective

Background This paper describes the evolutionary changes in morphology and orientation of the PFJ using species present through our ancestry over 340 million years. Methods 37 specimens from the Devonian period to modern day were scanned using a 64-slice CT scanner. 3D geometries were created following routine segmentation and anatomical measurements taken from standardised bony landmarks. Results Findings are described according to gait strategy and age. The adoption of an upright bi-pedal stance caused a dramatic change in the loading of the PFJ which has subsequently led to changes in the arrangement of the PFJ. From Devonian to Miocene periods, our sprawling and climbing ancestors possessed a broad knee with a shallow, centrally located trochlea. A more rounded knee was present from the Paleolithic period onwards in erect and bipedal gait types (aspect ratio 0.93 vs 1.2 in late Devonian), with the PFJ being placed lateral to the midline compared to the medial position in quadrapeds. The depth of the trochlea groove was maximal in the Miocene period of the African ground apes with associated acute sulcus angles in Gorilla (117°) becoming more flattened towards the modern human (138°). Conclusions The evolving bipedal gait lead to anteriorisation of the patellofemoral joint, flattening of the trochlea sulcus, in a more lateral, dislocation prone arrangement. Ancestral developments might help explain the variety of presentations of anterior knee pain and patellofemoral instability

Scientific names of organisms : attribution, rights, and licensing

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Research Notes 7 (2014): 79, doi:10.1186/1756-0500-7-79.As biological disciplines extend into the ‘big data’ world, they will need a names-based infrastructure to index and interconnect distributed data. The infrastructure must have access to all names of all organisms if it is to manage all information. Those who compile lists of species hold different views as to the intellectual property rights that apply to the lists. This creates uncertainty that impedes the development of a much-needed infrastructure for sharing biological data in the digital world. The laws in the United States of America and European Union are consistent with the position that scientific names of organisms and their compilation in checklists, classifications or taxonomic revisions are not subject to copyright. Compilations of names, such as classifications or checklists, are not creative in the sense of copyright law. Many content providers desire credit for their efforts. A ‘blue list’ identifies elements of checklists, classifications and monographs to which intellectual property rights do not apply. To promote sharing, authors of taxonomic content, compilers, intermediaries, and aggregators should receive citable recognition for their contributions, with the greatest recognition being given to the originating authors. Mechanisms for achieving this are discussed

Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children