A Revisitation of Kernel Synchronization Schemes

In an operating system kernel, critical sections of code must be protected from interruption. This is traditionally accomplished by masking the set of interrupts whose handlers interfere with the correct operation of the critical section. Because it can be expensive to communicate with an off-chip interrupt controller, more complex optimistic techniques for masking interrupts have been pro-posed. In this paper we present measurements of the behavior of the NetBSD 1.2 kernel, and use the measurements to explore the space of kernel synchronization schemes. We show that (a) most critical sections are very short, (b) very few are ever interrupted, (c) using the traditional synchronization technique, the synchronization cost is often higher than the time spent in the body of the critical section, and (d) under heavy load NetBSD 1.2 can spend 9% to 12% of its time in synchronization primitives. The simplest scheme we examined, disabling all interrupts while in a critical section or interrupt handler, can lead to loss of data under heavy load. A more complex optimistic scheme functions correctly under the heavy workloads we tested and has very low overhead (at most 0.3%). Based on our measurements, we present a new model that offers the simplicity of the traditional scheme with the performance of the optimistic schemes. Given the relative CPU, memory, and device performance of today’s hardware, the newer techniques we examined have a much lower synchronization cost than the traditional technique. Under heavy load, such as that incurred by a web server, a system using these newer techniques will have noticeably better performance.Engineering and Applied Science

Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.MethodsPatients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.ResultsOf the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.ConclusionsThis study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment

An epilepsy-associated SV2A mutation disrupts synaptotagmin-1 expression and activity-dependent trafficking

The epilepsy-linked gene , has a number of potential roles in the synaptic vesicle (SV) life cycle. However, how loss of SV2A function translates into presynaptic dysfunction and ultimately seizure activity is still undetermined. In this study, we examined whether the first SV2A mutation identified in human disease (R383Q) could provide information regarding which SV2A-dependent events are critical in the translation to epilepsy. We utilized a molecular replacement strategy in which exogenous SV2A was expressed in mouse neuronal cultures of either sex, which had been depleted of endogenous SV2A to mimic the homozygous human condition. We found that the R383Q mutation resulted in a mislocalization of SV2A from SVs to the plasma membrane, but had no effect on its activity-dependent trafficking. This SV2A mutant displayed reduced mobility when stranded on the plasma membrane and reduced binding to its interaction partner synaptotagmin-1 (Syt1). Furthermore, the R383Q mutant failed to rescue reduced expression and dysfunctional activity-dependent trafficking of Syt1 in the absence of endogenous SV2A. This suggests that the inability to control Syt1 expression and trafficking at the presynapse may be key in the transition from loss of SV2A function to seizure activity. SV2A is a synaptic vesicle (SV) protein, the absence or dysfunction of which is linked to epilepsy. However, the series of molecular events that result in this neurological disorder is still undetermined. We demonstrate here that the first human mutation in SV2A identified in an individual with epilepsy displays reduced binding to synaptotagmin-1 (Syt1), an SV protein essential for synchronous neurotransmitter release. Furthermore, this mutant cannot correct alterations in both Syt1 expression and trafficking when expressed in the absence of endogenous SV2A (to mimic the homozygous human condition). This suggests that the inability to control Syt1 expression and trafficking may be key in the transition from loss of SV2A function to seizure activity

Issues in Extensible Operating Systems

Operating systems research has traditionally consisted of adding functionality to the operating system or inventing and evaluating new methods for performing functions. Regardless of the research goal, the single constant has been that the size and complexity of operating systems increase over time. As a result, operating systems are usually the single most complex piece of software in a computer system, containing hundreds of thousands, if not millions, of lines of code. Today’s operating system research is directed at finding new ways to structure the operating system in order to increase its flexibility, allowing it to adapt to changes in the application set it must support. This paper discusses the issues involved in designing such extensible systems and the array of choices facing the operating system designer. We present a framework for describing extensible operating systems and then relate current operating systems to this framework.Engineering and Applied Science

Counterfactual Explanations via Locally-guided Sequential Algorithmic Recourse

Counterfactuals operationalised through algorithmic recourse have become a powerful tool to make artificial intelligence systems explainable. Conceptually, given an individual classified as y -- the factual -- we seek actions such that their prediction becomes the desired class y' -- the counterfactual. This process offers algorithmic recourse that is (1) easy to customise and interpret, and (2) directly aligned with the goals of each individual. However, the properties of a "good" counterfactual are still largely debated; it remains an open challenge to effectively locate a counterfactual along with its corresponding recourse. Some strategies use gradient-driven methods, but these offer no guarantees on the feasibility of the recourse and are open to adversarial attacks on carefully created manifolds. This can lead to unfairness and lack of robustness. Other methods are data-driven, which mostly addresses the feasibility problem at the expense of privacy, security and secrecy as they require access to the entire training data set. Here, we introduce LocalFACE, a model-agnostic technique that composes feasible and actionable counterfactual explanations using locally-acquired information at each step of the algorithmic recourse. Our explainer preserves the privacy of users by only leveraging data that it specifically requires to construct actionable algorithmic recourse, and protects the model by offering transparency solely in the regions deemed necessary for the intervention.Comment: 7 pages, 5 figures, 3 appendix page

Population dynamics of rhesus macaques and associated foamy virus in Bangladesh.

Foamy viruses are complex retroviruses that have been shown to be transmitted from nonhuman primates to humans. In Bangladesh, infection with simian foamy virus (SFV) is ubiquitous among rhesus macaques, which come into contact with humans in diverse locations and contexts throughout the country. We analyzed microsatellite DNA from 126 macaques at six sites in Bangladesh in order to characterize geographic patterns of macaque population structure. We also included in this study 38 macaques owned by nomadic people who train them to perform for audiences. PCR was used to analyze a portion of the proviral gag gene from all SFV-positive macaques, and multiple clones were sequenced. Phylogenetic analysis was used to infer long-term patterns of viral transmission. Analyses of SFV gag gene sequences indicated that macaque populations from different areas harbor genetically distinct strains of SFV, suggesting that geographic features such as forest cover play a role in determining the dispersal of macaques and SFV. We also found evidence suggesting that humans traveling the region with performing macaques likely play a role in the translocation of macaques and SFV. Our studies found that individual animals can harbor more than one strain of SFV and that presence of more than one SFV strain is more common among older animals. Some macaques are infected with SFV that appears to be recombinant. These findings paint a more detailed picture of how geographic and sociocultural factors influence the spectrum of simian-borne retroviruses

Final Results From the Circumarctic Lakes Observation Network (CALON) Project

Since 2012, the physical and biogeochemical properties of ~60 lakes in northern Alaska have been investigated under CALON, a project to document landscape-scale variability of Arctic lakes in permafrost terrain. The network has ten nodes along two latitudinal transects extending inland 200 km from the Arctic Ocean. A meteorological station is deployed at each node and six representative lakes instrumented and continuously monitored, with winter and summer visits for synoptic assessment of lake conditions. Over the 4-year period, winter and summer climatology varied to create a rich range of lake responses over a short period. For example, winter 2012-13 was very cold with a thin snowpack producing thick ice across the region. Subsequent years had relatively warm winters, yet regionally variable snow resulted in differing gradients of ice thickness. Ice-out timing was unusually late in 2014 and unusually early in 2015. Lakes are typically well–mixed and largely isothermal, with minor thermal stratification occurring in deeper lakes during calm, sunny periods in summer. Lake water temperature records and morphometric data were used to estimate the ground thermal condition beneath 28 lakes. Application of a thermal equilibrium steady-state model suggests a talik penetrating the permafrost under many larger lakes, but lake geochemical data do not indicate a significant contribution of subpermafrost groundwater. Biogeochemical data reveal distinct spatial and seasonal variability in chlorophyll biomass, chromophoric dissolved organic carbon (CDOM), and major cations/anions. Generally, waters sampled beneath ice in April had distinctly higher concentrations of inorganic solutes and methane compared with August. Chlorophyll concentrations and CDOM absorption were higher in April, suggesting significant biological/biogeochemical activity under lake ice. Lakes are a positive source of methane in summer, and some also emit nitrous oxide and carbon dioxide. As part of the Indigenous Knowledge component,76 Iñupiat elders, hunters and berry pickers have been interviewed and over 75 hours of videotaped interviews produced. The video library and searchable interview logs are archived with the North Slope community. All field data is archived at ACADIS, and further information is at www.arcticlakes.org

TraCE: Trajectory Counterfactual Explanation Scores

Counterfactual explanations, and their associated algorithmic recourse, are typically leveraged to understand, explain, and potentially alter a prediction coming from a black-box classifier. In this paper, we propose to extend the use of counterfactuals to evaluate progress in sequential decision making tasks. To this end, we introduce a model-agnostic modular framework, TraCE (Trajectory Counterfactual Explanation) scores, which is able to distill and condense progress in highly complex scenarios into a single value. We demonstrate TraCE's utility across domains by showcasing its main properties in two case studies spanning healthcare and climate change.Comment: 7 pages, 4 figures, appendi

The UV-Optical Galaxy Color-Magnitude Diagram. I. Basic Properties

We have analyzed the bivariate distribution of galaxies as a function of ultraviolet-optical colors and absolute magnitudes in the local universe. The sample consists of galaxies with redshifts and optical photometry from the Sloan Digital Sky Survey (SDSS) main galaxy sample matched with detections in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands in the Medium Imaging Survey being carried out by the Galaxy Evolution Explorer (GALEX) satellite. In the (NUV − r)_(0.1) versus M_(r,0.1) galaxy color-magnitude diagram, the galaxies separate into two well-defined blue and red sequences. The (NUV − r)_(0.1) color distribution at each M_(r,0.1) is not well fit by the sum of two Gaussians due to an excess of galaxies in between the two sequences. The peaks of both sequences become redder with increasing luminosity, with a distinct blue peak visible up to M_(r,0.1) ~ − 23. The r_(0.1)-band luminosity functions vary systematically with color, with the faint-end slope and characteristic luminosity gradually increasing with color. After correcting for attenuation due to dust, we find that approximately one-quarter of the color variation along the blue sequence is due to dust, with the remainder due to star formation history and metallicity. Finally, we present the distribution of galaxies as a function of specific star formation rate and stellar mass. The specific star formation rates imply that galaxies along the blue sequence progress from low-mass galaxies with star formation rates that increase somewhat with time to more massive galaxies with a more or less constant star formation rate. Above a stellar mass of ~10^(10.5) M_☉, galaxies with low ratios of current to past averaged star formation rate begin to dominate