Program representation size in an intermediate language with intersection and union types

The CIL compiler for core Standard ML compiles whole programs using a novel typed intermediate language (TIL) with intersection and union types and flow labels on both terms and types. The CIL term representation duplicates portions of the program where intersection types are introduced and union types are eliminated. This duplication makes it easier to represent type information and to introduce customized data representations. However, duplication incurs compile-time space costs that are potentially much greater than are incurred in TILs employing type-level abstraction or quantification. In this paper, we present empirical data on the compile-time space costs of using CIL as an intermediate language. The data shows that these costs can be made tractable by using sufficiently fine-grained flow analyses together with standard hash-consing techniques. The data also suggests that non-duplicating formulations of intersection (and union) types would not achieve significantly better space complexity.National Science Foundation (CCR-9417382, CISE/CCR ESS 9806747); Sun grant (EDUD-7826-990410-US); Faculty Fellowship of the Carroll School of Management, Boston College; U.K. Engineering and Physical Sciences Research Council (GR/L 36963, GR/L 15685

Confronting Financial Crisis: Dodd-Frank\u27s Dangers and the Case for a Systemic Emergency Insurance Fund

Inherent tensions in the financial sector mean that episodes of extreme stress are inevitable, if unpredictable. This is true even when financial regulatory and supervisory regimes are effective in many respects. The government\u27s capacity to intervene may determine whether distress is confined to the financial sector or breaks out into the real economy Although adequate resolution authority to address a failing financial firm is a necessary objective of the current regulatory reforms, a firm-by-firm approach cannot address a major systemic failure. Major blows to the financial system, such as the financial crisis of 2007-2009, may require capital support of the financial sector to prevent severe economic harm. We therefore propose the creation of a Systemic Emergency Insurance Fund ( SEIF or Fund ), initially set at $1 trillion, but periodically rescaled to the size of the U.S. economy. SEIF should be funded (and partially pre-funded) by risk-adjusted assessments on all large financial firms – including hedge funds – that benefit from systemic stability. The Department of the Treasury ( Treasury ) would administer the Fund, the use of which would be triggered by a triple key concurrence among the Treasury, the Federal Deposit Insurance Corporation ( FDIC ), and the Federal Reserve ( Fed ). Unlike taxpayer bailouts, such a fund would mutualize systemic risk among financial firms through a facility overseen by regulators. Moreover, its funding mechanism would give financial firms a greater incentive to warn regulators of growing systemic risk. And this standby emergency authority would avoid the need for high-stakes legislative action mid-crisis, which can be destabilizing even if successful and catastrophic if not. Such an approach is superior to the financial sector nationalization strategy embodied in the newly enacted Dodd-Frank financial reform bill

Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa

Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)-positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV-negative and 15 HIV-positive) and 20 healthy controls were exposed to X-rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV-positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients

Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>= 25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (C-max)/MIC ratio of >= 8 and a minimal concentration o

ALMA Observations of a Quiescent Molecular Cloud in the Large Magellanic Cloud

We present high-resolution (sub-parsec) observations of a giant molecular cloud in the nearest star-forming galaxy, the Large Magellanic Cloud. ALMA Band 6 observations trace the bulk of the molecular gas in $^{12}$CO(2-1) and high column density regions in $^{13}$CO(2-1). Our target is a quiescent cloud (PGCC G282.98-32.40, which we refer to as the "Planck cold cloud" or PCC) in the southern outskirts of the galaxy where star-formation activity is very low and largely confined to one location. We decompose the cloud into structures using a dendrogram and apply an identical analysis to matched-resolution cubes of the 30 Doradus molecular cloud (located near intense star formation) for comparison. Structures in the PCC exhibit roughly 10 times lower surface density and 5 times lower velocity dispersion than comparably sized structures in 30 Dor, underscoring the non-universality of molecular cloud properties. In both clouds, structures with relatively higher surface density lie closer to simple virial equilibrium, whereas lower surface density structures tend to exhibit super-virial line widths. In the PCC, relatively high line widths are found in the vicinity of an infrared source whose properties are consistent with a luminous young stellar object. More generally, we find that the smallest resolved structures ("leaves") of the dendrogram span close to the full range of line widths observed across all scales. As a result, while the bulk of the kinetic energy is found on the largest scales, the small-scale energetics tend to be dominated by only a few structures, leading to substantial scatter in observed size-linewidth relationships.Comment: Accepted by ApJ; 21 pages in AASTeX two-column styl

Direct Probe of Dark Energy Interactions with a Solar System Laboratory

In this NIAC (NASA Innovative Advanced Concepts) study, we embrace the challenge of direct detection of the galileon dark energy field in the Vainshtein model. We developed a mission concept to directly measure the galileon field using the solar system as a laboratory. The experiment scheme involves precise measurements of the trace of the total scalar force gradient tensor. A tetrahedral constellation off our spacecraft measures the "local" traces while orbiting about 1 AU (Astronomical Unit) away from the Sun and faraway from planets (Figure 1). The trace measurement is insensitive to the much stronger gravity field which satisfies the inverse square law and thus is traceless. Atomic test masses and atom interferometer measurement techniques are used as precise drag-free inertial references while laser ranging interferometers are employed to connect among atom interferometer pairs in spacecraft for the differential gradient force measurements. We conclude that such a mission is scientifically and technologically feasible. We show that a mission of 3-year measurement time would be able to provide high confidence statements (over 3 standard deviations) about the existence and strength of the cubic galileon field of the Sun. In addition, such a mission would also provide rich and diverse scientific data for testing any gravitational theory in general beyond the Newtonian gravity, hunting for ultra-light fields of dark matter, and detecting gravitational waves in the mid-frequency band between those of LIGO (Laser Interferometer Gravitational-Wave Observatory) and LISA (Laser Interferometer Space Antenna). For these reasons, we will term the mission concept Gravity Observation and Dark energy Detection Explorer in the Solar System (GODDESS)

Mapping meningeal vasculature in non-human primates

Background. The blood-brain barrier has been the focus of most prior work examining intracranial vasculature in the context of various brain diseases.1 Recently, meningeal vasculature has become more widely recognized as a key contributor to brain clearance and its immune function.2 Meninges are highly vascularized and complex tissue. Vessels of the outer dural layer comprise an extensive, parallel intracranial vascular bed, which lies outside the brain and subarachnoid space. In addition to the blood vasculature, meninges harbor lymphatic channels that potentially provide extra capacity for clearance of proteinaceous fluid and immune cell trafficking. Most of our knowledge of the meningeal vasculature, including lymphatics, comes from rodent models. Rodent meninges are readily available, small, thin and optically transparent. These characteristics permit imaging in whole-mount flat preparations.3 Technical barriers, however, remain high for imaging studies of the meninges of larger mammals. This is especially true for primates, and ultimately humans. Non-human primate (NHP) and human dura is large, thick and opaque, with a high content of connective tissue. These characteristics limit options for routine high-resolution imaging and leave unanswered questions about the architecture of blood and lymphatic vessels in primate dura. So far, the presence of lymphatic vessels in primates has been demonstrated by non-invasive techniques like magnetic resonance imaging (MRI) or on sections of paraffin-embedded specimens. Neither of the techniques fully addresses spatial and phenotypical features of the vascular networks. In our work, we provide solutions for these technical barriers using new clearing and imaging protocols to successfully visualize blood and lymphatic vessels in NPH dura in their entirety. Methods. Here we used novel approaches to tissue clearing and resonance scanning confocal imaging of large areas with sickness over 1000 M. Results. Our approach revealed extensive and dense vascular networks in NHP dura probed with vascular marker CD31 (Figure 1). Image clarity and resolution is sufficient for visualization of the smallest vessels. In the dura, blood vessels are mostly represented by veins. Vascular networks can be further analyzed with semi-automated tracing and quantitative metrics in 3D space. We showed that lymphatic vessels in NPH dura are located similarly to that in rodents: in the area of the superior sagittal sinus (SSS) and along the middle meningeal artery (MMA). They are also present in the major dural fold, tentorium cerebelli, which is underdeveloped in rodents. Unlike previously described in mice, these vessels are negative for LYVE-1 lymphatic marker but strongly positive for podoplanin. In the area of SSS, there is a large plexus of branching irregular blind-ended sacs with a wide range of diameters. Vessels in the MMA region have a different appearance. Two vessels always run along the veins flanking MMA that follow the artery branching. Our protocol also permits imaging of the extracellular matrix and the cells that reside in the dural environment. Conclusions. We developed clearing, mounting and imaging protocols that permitted panoramic fluorescence-based microscopy of NPH dura. These new techniques are directly applicable to primate models of neurodegenerative diseases with a focus on the complex interplay between meningeal arteries, veins, and lymphatics

Stellar Lyman-alpha Emission Lines in the Hubble Space Telescope Archive: Intrinsic Line Fluxes and Absorption from the Heliosphere and Astrospheres

We search the Hubble Space Telescope (HST) archive for previously unanalyzed observations of stellar H I Lyman-alpha emission lines, our primary purpose being to look for new detections of Lyman-alpha absorption from the outer heliosphere, and to also search for analogous absorption from the astrospheres surrounding the observed stars. The astrospheric absorption is of particular interest because it can be used to study solar-like stellar winds that are otherwise undetectable. We find and analyze 33 HST Lyman-alpha spectra in the archive. All the spectra were taken with the E140M grating of the Space Telescope Imaging Spectrograph (STIS) instrument on board HST. The HST/STIS spectra yield 4 new detections of heliospheric absorption (70 Oph, Xi Boo, 61 Vir, and HD 165185) and 7 new detections of astrospheric absorption (EV Lac, 70 Oph, Xi Boo, 61 Vir, Delta Eri, HD 128987, and DK UMa), doubling the previous number of heliospheric and astrospheric detections. When combined with previous results, 10 of 17 lines of sight within 10 pc yield detections of astrospheric absorption. This high detection fraction implies that most of the ISM within 10 pc must be at least partially neutral, since the presence of H I within the ISM surrounding the observed star is necessary for an astrospheric detection. In contrast, the detection percentage is only 9.7% (3 out of 31) for stars beyond 10 pc. Our Lyman-alpha analyses provide measurements of ISM H I and D I column densities for all 33 lines of sight, and we discuss some implications of these results. Finally, we measure chromospheric Lyman-alpha fluxes from the observed stars. We use these fluxes to determine how Lyman-alpha flux correlates with coronal X-ray and chromospheric Mg II emission, and we also study how Lyman-alpha emission depends on stellar rotation.Comment: 56 pages, 15 figures; AASTEX v5.0 plus EPSF extensions in mkfig.sty; accepted by ApJ

Altered cholinergic innervation in De Novo Parkinson's disease with and without cognitive impairment

BACKGROUND: Altered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention. OBJECTIVE: The aim was to assess regional cholinergic innervation status in de novo patients with PD, with and without cognitive impairment. METHODS: Fifty-seven newly diagnosed, treatment-naive, PD patients (32 men, mean age 64.6 ± 8.2 years) and 10 healthy controls (5 men, mean age 54.6 ± 6.0 years) were included. All participants underwent cholinergic [18 F]fluoroethoxybenzovesamicol positron emission tomography and detailed neuropsychological assessment. PD patients were classified as either cognitively normal (PD-NC) or mild cognitive impairment (PD-MCI). Whole brain voxel-based group comparisons were performed. RESULTS: Results show bidirectional cholinergic innervation changes in PD. Both PD-NC and PD-MCI groups showed significant cortical cholinergic denervation compared to controls (P < 0.05, false discovery rate corrected), primarily in the posterior cortical regions. Higher-than-normal binding was most prominent in PD-NC in both cortical and subcortical regions, including the cerebellum, cingulate cortex, putamen, gyrus rectus, hippocampus, and amygdala. CONCLUSION: Altered cholinergic innervation is already present in de novo patients with PD. Posterior cortical cholinergic losses were present in all patients independent of cognitive status. Higher-than-normal binding in cerebellar, frontal, and subcortical regions in cognitively intact patients may reflect compensatory cholinergic upregulation in early-stage PD. Limited or failing cholinergic upregulation may play an important role in early, clinically evident cognitive impairment in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society