cssi/SciSciGPT-SciSciNet huggingface dataset:
ALFRED MARSHALL LECTURE INTELLECTUAL PROPERTY RIGHTS PROTECTION IN DEVELOPING COUNTRIES: THE CASE OF PHARMACEUTICALS

Patent enforcement in developing countries generates considerable controversy, especially when patents involve potentially life-saving drugs. This paper argues that common concerns regarding the effects of patents on prices and on research incentives of pharmaceutical multinationals are misplaced. Rather, the most significant effects are likely to concern access to patented drugs in poor countries. Because prices in developing countries are much lower than in the developed world, multinationals may choose to enter such markets with a delay, or not at all, implying a complete loss of access to patented drugs in developing countries. Even when multinationals enter countries like India, their marketing and distribution networks are not currently built out, leading to limited access within the country. Such considerations may provide a justification for policies targeting access in the short and medium run, such as compulsory licensing.
Discrete-time adaptive control using multiple models

In a recent paper [1] the authors proposed a new methodology for the adaptive control of a linear time-invariant plant using multiple models which is significantly different from the “switching” and “switching and tuning” methods which have been in use for over a decade. Extensive simulation studies have also revealed that the performance using the new method is far superior to earlier methods. In this paper an attempt is made to extend the same concepts to the adaptive control of discrete-time systems. It is well known that the control of discrete-time systems is simpler than the control of their continuous-time counterparts, that they find wider application in practice, and that the proofs of stability are substantially simpler. Also, in many cases (e.g. periodic systems) discrete-time control may be possible when even the formulation of tractable problems in continuous-time is impossible. The objective of this paper is to examine how the methodology proposed differs in the two cases with regard to transparency of the principal concepts, and effectiveness in practical applications.
Epigenetic epidemiology of obesity: application of epigenomic technology

Compelling human epidemiologic and animal model data indicate that during critical periods of prenatal and postnatal mammalian development, nutrition and other environmental stimuli influence developmental pathways and thereby induce permanent changes in metabolism and chronic disease susceptibility. The biologic mechanisms underlying such ‘metabolic imprinting’ are poorly understood, but epigenetic mechanisms are likely involved.1 Epigenetics is the study of mitotically heritable alterations in gene expression potential that are not caused by changes in DNA sequence.2 Transient environmental influences during development can cause permanent changes in epigenetic gene regulation, and accumulating evidence links epigenetic dysregulation to human disease.3 The worldwide increase in the prevalence of obesity in recent decades has occurred too rapidly to be explained completely by genetic variation, suggesting the involvement of epigenetic mechanisms. Indeed, data from animal models and humans demonstrate that epigenetic dysregulation can cause obesity.4 Several years ago Levin5 proposed that maternal obesity during pregnancy and lactation might cause metabolic imprinting of neural networks in the offspring, perpetuating, or even amplifying, obesity susceptibility across generations.5 This postulate is supported by recent studies in the mouse, which demonstrate that the formation of hypothalamic projections during early postnatal development is dependent upon cues from outside the brain.6 Leptin-deficient ( ob/ob ) mice fail to form hypothalamic connections necessary for normal energy homeostasis. Remarkably, transient administration of exogenous leptin during postnatal development rescues hypothalamic innervation and normalizes adult body weight.6 Analogously, maternal obesity during pregnancy …
On the failure of glycogen deposition in the livers of scorbutic guinea pigs.

INTRODUCTION ADECREASED amount of glycogen occurs in the liver of the scorbutic guinea pig, and partiy because of this it was suggested that decreased adrenocortical function exists in scurvy. The problem has been carefully reviewed by Morgan (1952). More recently, increased amounts of cortisol (Compound F), have been identified in the blood and urine of scorbutic guinea pigs (Burstein, Dorfman, and Nadel 1954), supporting the suggestion that adrenocortical hormone production was not diminished, but actually was enhanced in scurvy (Clayton and Prunty, 1951; Nadel and Schneider, 1951, 1952). Decreased glycogen in the livers of scorbutic guinea pigs in the presence of increased amounts of circulating cortisol appeared to be paradoxical to us, for it suggested that this glucocorticosteroid was not physiologically able to help deposit glycogen in the liver when the guinea pig was depleted of vitamin C (Nadel and Mulay, 1954). The problem was investigated further by comparing the abilities of vitamin C deficie...
Surname Analysis as a Means of Estimating Minority Elderly: An Application Using Asian Surnames

Estimates of the age, sex, and geographic distribution of four elderly Asian-origin populations residing in the United States are constructed using surname data obtained for 1990 from the Medicare enrollment files. The generally close correspondence of the results with baseline data for these four groups from the 1990 decennial census demonstrate the applicability of a surname approach. Surname analysis can be used as a means of drawing samples of ethnic minority groups, of estimating the current size of ethnic populations, and as an alternative method of deriving additional demographic information, for example, mortality statistics, for selected groups.
Proprioception Following Anterior Cruciate Ligament Reconstruction

Injury to the anterior cruciate ligament (ACL) is thought to disrupt joint afferent sensation and result in proprioceptive deficits. This investigation examined proprioception following ACL reconstruction. Using a proprioceptive testing device designed for this study, kinesthetic awareness was assessed by measuring the threshold to detect passive motion in 12 active patients, who were 11 to 26 months post-ACL reconstruction, using arthroscopic patellar tendon autograft (n=6) or allograft (n=6) techniques. Results revealed significantly decreased kinesthetic awareness in the ACL reconstructed knee versus the uninvolved knee at the near-terminal range of motion and enhanced kinesthetic awareness in the ACL reconstructed knee with the use of a neoprene orthotic. Kinesthesia was enhanced in the near-terminal range of motion for both the ACL reconstructed knee and the contralateral uninvolved knee. No significant between-group differences were observed with autograft and allograft techniques.
Symposium on Amartya Sen's philosophy: 5 Adaptive preferences and women's options

Any defense of universal norms involves drawing distinctions among the many things people actually desire. If it is to have any content at all, it will say that some objects of desire are more central than others for political purposes, more indispensable to a human being's quality of life. Any wise such approach will go even further, holding that some existing preferences are actually bad bases for social policy. The list of Central Human Capabilities that forms the core of my political project contains many functions that many people over the ages have preferred not to grant to women, either not at all, or not on a basis of equality. To insist on their centrality is thus to go against preferences that have considerable depth and breadth in traditions of male power. Moreover, the list contains many items that women over the ages have not wanted for themselves, and some that even today many women do not pursue – so in putting the list at the center of a normative political project aimed at providing the philosophical underpinning for basic political principles, we are going against not just other people's preferences about women, but, more controversially, against many preferences (or so it seems) of women about themselves and their lives. To some extent, my approach, like Sen's, avoids these problems of paternalism by insisting that the political goal is capability, not actual functioning, and by dwelling on the central importance of choice as a good. But the notion of choice and practical reason used in the list is a normative notion, emphasizing the critical activity of reason in a way that does not reflect the actual use of reason in many lives.
Taxol in ovarian cancer

Taxol is a structurally complex natural plant product with a novel mechanism of action. The supply of this drug is limited by its low abundance in the bark of the slow-growing yew tree from which it is extracted. The chemical complexity of taxol has hampered the development of a feasible process to synthesize large quantities. Analogues are being made from a precursor found in the needles of the yew tree. However, there is a need to develop a more efficient method to provide adequate supplies of this drug. This review article summarizes the preclinical and clinical studies of taxol in ovarian cancer. Phase I studies have identified the drug's toxicities. Neutropenia has been the dose-limiting toxicity in most trials, and premedications and longer infusion schedules have been used to reduce the incidence and severity of hypersensitivity reactions. The intraperitoneal administration of taxol in Phase I studies showed a pharmacologic advantage with acceptable toxicity. Its activity in ovarian cancer was noticed first in Phase I trials at the Albert Einstein College of Medicine and Johns Hopkins University. These observations led to Phase II testing, which documented response rates of 20-35% in patients with relapsed or refractory ovarian cancer. Phase III trials of taxol and cisplatin versus cyclophosphamide and cisplatin in untreated patients with ovarian cancer are in progress. Studies combining taxol with colony-stimulating factors and cisplatin are ongoing. Taxol is an important new drug in ovarian cancer. Its unique mechanism of action and toxicities make it an attractive agent to use in combination with currently active drugs. Future studies will determine the role of taxol in the management of this disease, but the widespread availability of this drug will depend on the development of a feasible synthetic process.
Residual Income Risk, Intrinsic Values, and Share Prices

Empirical accounting research provides surprisingly little evidence on whether accounting earnings numbers capture cross‐sectional differences in risk that are associated with cross‐sectional differences in share prices. We address two questions regarding the risk‐relevance of accounting numbers: (1) Are accounting‐related risk measures (i.e., the systematic risk and total volatility in a firm's time‐series of residual return on equity) associated with the market's assessment and pricing of equity risk? (2) If so, then are these accounting‐related risk measures incrementally associated with the market's assessment and pricing of equity risk beyond other observable factors, such as those in the Fama and French (1992) three‐factor model? We develop an accounting‐fundamentals‐based measure of the market's pricing of risk—the difference between actual share price and a residual income valuation model estimate of share value using risk‐free rates of return. Our results show that both systematic risk and total ...
The effects of neonatal orchidectomy on the developmental pattern of gonadotropin secretion in the male rhesus monkey (Macaca mulatta).

Plasma concentrations of LH and FSH in immature male rhesus monkeys were determined at weekly intervals from birth until 300 days of age, and the effect of bilateral orchidectomy at 1 week of age on the neonatal pattern of gonadotropin secretion was studied. Plasma FSH and LH concentrations in intact animals were elevated during the first few months of neonatal life but then declined to undetectable values characteristic of the prepubertal state in this species. Neonatal castration, but not sham castration, resulted in a progressive and dramatic rise in circulating gonadotropin concentrations, which plateaued approximately 3 weeks later at values an order of magnitude greater than those observed in intact animals. The hypersecretion of LH and FSH after removal of the gonads was not sustained, however, and by 32 weeks of age plasma gonadotropin concentrations in the agonadal animals were indistinguishable from those in age-matched intact controls. These findings suggest that, in the rhesus monkey, the test...
Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase.

Bacterial l-asparaginases, enzymes that catalyze the hydrolysis of l-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphobl...
A Data-Adaptive Ocean Wave Directional-Spectrum Estimator for Pitch and Roll Type Measurements

Abstract A data-adaptive directional-spectrum estimator is developed for “point” measurement systems such as the pitch and roll buoy and slope array. This estimator, unlike the much employed unimodal cosine power parameterization method of Longuet-Higgins and others, does not make a priori assumptions about the shape of the directional spectrum. Instead improved resolution is obtained with a maximum likelihood method similar to those successfully used with spatial arrays. The numerical algorithm is relatively simple and computationally fast. The capabilities and limitations of the new estimator are illustrated with a variety of synthetic directional spectra. The estimator is applied to field data obtained from a slope array in 9 m depth at Santa Barbara, California and is found to yield physically realistic directional spectra. It marginally resolves two directional modes that topographical features dictate should be separated by approximately 70 degrees.
The Self-Propagating Quasi-Monopolar Vortex

If an azimuthally symmetric barotropic eddy on the f plane is subject to a relatively small amplitude disturbance of unit azimuthal wavenumber (m 5 1), it can propagate very many diameters away from its origin, as shown by a weak nonlinear theory for a piecewise uniform vorticity eddy, and also for one with continuous vorticity inside a finite area. In the former case an initial value contour dynamical calculation shows that the analytical solution is realizable over long distances; the same is true in the latter case, as shown by spectral calculations using the full two-dimensional vorticity equation (with small dissipation). The oceanographic significance of this effect lies in the ability of almost symmetric eddies to self-propagate over large distances and collide with other eddies, currents, and continents; this produces important mixing effects, as illustrated herein. It is also shown how the analysis and the effect is generalizeable to a 1‰-layer density model on the b plane.
Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T 2 -exchange magnetic resonance imaging contrast agents for molecular imaging

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.
Probabilities, Perceptions, Consequences and "Discrimination": One Puzzle about Controversial "Stop and Frisk"

The essay focuses on a particular issue about “stop and frisk” raised by the concern about concentration on young men in racial minorities. Although reference is made to the recent decision in Floyd v. City of New York, my focus is not on what has actually happened in New York and elsewhere, but whether, if there is substantial evidence that a higher percentage of members of a group commit certain kinds of crimes more than members of other groups, it is appropriate for police to stop partly on the basis of whether movements that are somewhat suspicious are made by members of that group, or whether that constitutes inappropriate discrimination.Using an imagined private analogy and made up statistics about levels of criminal behavior and innocence among different groups, I contend that given the level of probability needed for a stop, i.e., “reasonable suspicion,” the likelihood that a group characteristic could figure importantly in the necessary probability is somewhat higher than when a more demanding standard such as “probable cause” is in play. In respect to a person’s gender and age, I suggest that use of that in applying a probability standard is really uncontroversial. But race is different. Both because of the risk of nonobjective appraisals, based partly on prejudices or implicit cultural assumptions, and because of the harmful negative message conveyed to members of minorities subject to stops, I conclude that police should not explicitly use race as a factor (unless they are looking for a person already identified by his race). I also believe this problem is serious enough so that such use should be viewed as a constitutional violation.
The Color of Choice: Race and Charter Schools

Increasingly, public education funds are given to charter schools. One long standing concern with the charter school movement is its impact on segregation in schooling and its compliance with the Fourteenth Amendment. This Article examines three Equal Protection issues raised by charter schools. (1) Can charter schools be exclusively geared toward one racial or ethnic group - whether it be African American, American Indian, Asian, Latino, or white - even if the schools employ a racially neutral student admissions policy? (2) Are states engaged in unconstitutional race-conscious decision making when they require (as twelve states do) that their charter schools seek racial and ethnic balance? (3) What is the appropriate relationship between charter schools and school desegregation? In my analysis, I undertake a purely interpretive aim: how would the Supreme Court's Equal Protection jurisprudence answer these questions. Interestingly, application of Supreme Court discrimination jurisprudence to charter schools reveals that states can pursue integration in their charter schools, but only by limited means, and that some, but not all, all-race or all-ethnicity charter schools likely violate the Equal Protection Clause. Further, school desegregation principles adequately protect the school desegregation process and should not unduly interfere with the charter school movement. Thus, applying Supreme Court jurisprudence, on its own terms, to charter schools reveals a Supreme Court that is, to a limited degree, pro-integration, but opposed to any explicit attempt at segregation, even if that segregation is done in the best interests of the child, and particularly if that segregation involves minority segregation. Those who support charter schools as an avenue to create schools designed to educate one race or ethnicity may need to re-think their position.
Electronic Structure Studies of Diamond/Metal Interfaces

We have begun to investigate theoretically the electronic properties of several ideal epitaxial interfaces of diamond with Ni and Cu, both of which enjoy a close lattice match. Of particular interest is the mechanism responsible for formation of the Schottky barrier, which is not yet fully understood at the microscopic level. We find that both the barrier height and the chemical bonding at the interface are strongly dependent on interface orientation (i.e., the relative positioning of the two surfaces). For orientations near the minimum total energy geometry, the calculated Fermi level is apparently pinned around 1.7 and 2.1 eV for the (111) and (001) interfaces, respectively, relative to the valence band maximum. For orientations not near the total energy minimum, the calculated barrier height is zero. A tentative explanation for this difference is proposed.
Communitarian Ethics and the Sociology of Morals: Alasdair MacIntyre and Emile Durkheim

Abstract The recent communitarian perspective in philosophical ethics raises the question of the sociology of morals proposed by Emile Durkheim. Durkheim's critique of ethics is compared with that of Alasdair MacIntyre and the “sociological presupposition” of each is identified. Ethical relativism is evaluated in both Durkheim and MacIntyre. Durkheim's universalism is compared with and found preferable to MacIntyre's elitism. The article concludes with suggestions for a rapprochement between philosophical ethics and the sociology of morals.
The phase I clinical compound SNS-595 acts during S-phase and causes a sustained G2 arrest

Proc Amer Assoc Cancer Res, Volume 46, 2005 2293 Although recent research has identified cancer therapies with non-cytotoxic mechanisms, there is still a need to discover and develop the next generation of cytotoxics with strong activities, manageable toxicities, and novel mechanisms of action. SNS-595 is a first-in-class naphthyridine compound that demonstrates potent cytotoxic activity as well as robust antineoplastic activity in several syngeneic and human xenograft tumor models, and is currently in phase I clinical trials for solid tumors. In vitro, SNS-595 has been observed to induce G2 cell cycle arrest and subsequent apoptosis in various cancer cells, including many multi-drug resistant lines. The effect of SNS-595 on cell cycle progression and checkpoint stimulation has been characterized and compared to the effects of a number of therapeutically relevant cell cycle modulators (cisplatin, docetaxol, gemcitabine, etoposide, doxorubicin, irinotecan, bleomycin, and mitomycin C). Cell cycle progression was analyzed using both DNA content and the cell cycle markers cyclins A, B, and E. In asynchronous populations, SNS-595 treatment causeed a full G2 arrest in all cell lines tested. This arrest was accompanied by rapid apoptosis as determined by DNA fragmentation. In synchronized cell populations treated with SNS-595, cells cycled normally until they reached S phase, which was 30% longer than in untreated cells. Checkpoint markers (chk kinases, cdc25 phosphatases, cdc2, and p21) appeared rapidly upon entering S phase, and the cells eventually reached a sustained and irreversible arrest with 4N DNA content. SNS-595 is shown to be distinct from the other G2 arrestors tested in that it causes p21 expression early in S phase and a significant S-phase lag. SNS-595 is also differentiable from other S-phase active compounds in showing a definitive arrest at G2 as opposed to a varied G1/S/G2 arrest profile. Further research into the stimulation of checkpoint and apoptotic pathways by SNS-595 will lead to a more detailed understanding of this compound’s potent anticancer activity.
Romanticizing the Chinese Landscape

ABSTRACTThrough an analysis of Thomas Allom and George Newenham Wright’s four-volume China, in a Series of Views, Displaying the Scenery, Architecture, and Social Habits of That Ancient Empire (1843), this essay argues that mid-nineteenth-century domestic Sinology appropriated Romantic ideology and poetry to situate China within the British Empire. While Britain’s Chinese colonial acquisitions never extended beyond the infamous ceding of Hong Kong at the end of the Opium War (1839–1842), the British military victory over China provided domestic Sinologists with the latitude to admire the “exotic” locale while couching this admiration in familiar imperialist rhetoric. In so doing, domestic Sinology – both visual and textual – imaginatively surrenders the entirety of China, not just Hong Kong, to British rule. As Allom and Wright’s text demonstrates, domestic Sinology often relied upon Romantic ideology and literature to achieve this imaginative acquiescence. This incongruous use of Romanticism made it comp...
Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG.

Abstract Adjuvant intravesical BCG therapy is an effective means of treating superficial bladder tumors. The mechanism by which BCG mediates antitumor activity is not known; however, clinical and animal studies suggest that immunological responsiveness to BCG antigens correlates with antitumor activity. In this report the detection of interleukin 2 (IL-2, a lymphokine produced in response to BCG) in urine specimens of patients treated with intravesical BCG is reported. Patients with superficial transitional cell carcinoma of the bladder received intravesical BCG once each week for six weeks. No intradermal injections were administered. Urine specimens were obtained prior to BCG instillation and four, eight and 24 hours afterwards. The specimens were dialysed, concentrated five-fold and assayed for the presence of IL-2 in a biological assay using an IL-2 dependent cultured T-cell line. IL-2 was detected in urine but not serum after intravesical BCG instillation. IL-2 was characterized by absorption against an IL-2-dependent T cell line and neutralization by monoclonal anti-IL-2 antibodies. No IL-2 was detected in specimens obtained prior to BCG instillation or from donors with no detectable bladder pathology. One of 10 urine specimens from patients with urinary tract infections had detectable IL-2 levels. IL-2 production generally peaked during the fourth to sixth intravesical BCG treatment. Production was short-term in that IL-2 levels peaked four to eight hours after BCG instillation and were rarely (six of 54 specimens) observed 24 hours after instillation. Mean IL-2 levels were higher in patients who were rendered tumor free after BCG therapy but statistical significance was not achieved. Ten of 12 patients (83%) who responded to BCG therapy had urine IL-2 levels ≥1.6 units/ml. at least once during the six week treatment period while two of six (33%) patients not responding to therapy had similar urine IL-2 levels. These results show that intravesical BCG therapy induces the production of lymphokines including IL-2. The presence of BCG-induced lymphokines may be associated with anti-tumor activity.
Microkinetic Modeling of Lean NOx Trap Sulfation and Desulfation.

A microkinetic reaction sub-mechanism designed to account for the sulfation and desulfation of a commercial lean NOx trap (LNT) is presented. This set of reactions is appended to a previously developed mechanism for the normal storage and regeneration processes in an LNT in order to provide a comprehensive modeling tool. The reactions describing the storage, release, and reduction of sulfur oxides are patterned after those involving NOx, but the number of reactions is kept to the minimum necessary to give an adequate simulation of the experimental observations. Values for the kinetic constants are estimated by fitting semi-quantitatively the somewhat limited experimental data, using a transient plug flow reactor code to model the processes occurring in a single monolith channel. Rigorous thermodynamic constraints are imposed in order to ensure that the overall mechanism is consistent both internally and with the known properties of all gas-phase species. The final mechanism is shown to be capable of reproducing the principal aspects of sulfation/desulfation behavior, most notably (a) the essentially complete trapping of SO2 during normal cycling; (b) the preferential sulfation of NOx storage sites over oxygen storage sites and the consequent plug-like and diffuse sulfation profiles; (c) the degradation of NOx storage and reduction (NSR) capability with increasing sulfation level; and (d) the mix of H2S and SO2 evolved during desulfation by temperature-programmed reduction.
ACOs Holding Commercial Contracts Are Larger And More Efficient Than Noncommercial ACOs

Accountable care organizations (ACOs) have diverse contracting arrangements and have displayed wide variation in their performance. Using data from national surveys of 399 ACOs, we examined differences between the 228 commercial ACOs (those with commercial payer contracts) and the 171 noncommercial ACOs (those with only public contracts, such as with Medicare or Medicaid). Commercial ACOs were significantly larger and more integrated with hospitals, and had lower benchmark expenditures and higher quality scores, compared to noncommercial ACOs. Among all of the ACOs, there was low uptake of quality and efficiency activities. However, commercial ACOs reported more use of disease monitoring tools, patient satisfaction data, and quality improvement methods than did noncommercial ACOs. Few ACOs reported having high-level performance monitoring capabilities. About two-thirds of the ACOs had established processes for distributing any savings accrued, and these ACOs allocated approximately the same amount of savings to the ACOs themselves, participating member organizations, and physicians. Our findings demonstrate that ACO delivery systems remain at a nascent stage. Structural differences between commercial and noncommercial ACOs are important factors to consider as public policy efforts continue to evolve.
Successes and lessons learned from OOI end-to-end system data quality audit

The Ocean Observatories Initiative (OOI) consists of seven research sites with over 800 instruments collecting ocean, seafloor, and meteorological data in the world's oceans, extending from the Irminger Sea to the Southern Ocean. The scale with which data are produced from the instruments and their platforms presents key challenges, including how to (1) build data and information management infrastructure that associates measurements from multiple instruments for concurrent observations, (2) develop data delivery mechanisms that meet a variety of needs, (3) ensure timely release of data, and (4) formulate capabilities to provide stable, longterm support for research and societal needs. As a strategy for maintenance of the sustained, large-scale, and variety of scientific observations collected, the OOI Cyberinfrastructure (CI) developed an end-to-end system designed to store, query, process, and disseminate the compiled information. These resources include raw instrument values and derived data products, metadata associated with instrument and platform deployments (e.g., deployment dates, water depths, instrument manufacturer, etc.), calibration coefficients, data provenance and descriptors of computational algorithms and transformation functions, and other related outputs. As with many data and information management systems, the need to monitor and improve upon the performance of the various interrelated components of the CI is an integral part in establishing the success of the system. For this reason, the data evaluation team at Rutgers initiated an end-to-end system data quality audit that ensures the system can accurately and completely deliver data within the required specifications. This was applied to a subset of representative platforms for all instrument types. Thus, based on specific system failures that can prevent production of quality data products, we prepared a set of tests and built tools that function as a troubleshooting method for system repair and enhancement. The method was used to report on the system's ability to: (a) Respond to data queries (b) Provide links to data product files (c) Produce all relevant data products (d) Produce correct provenance information (e) Produce quality science data products (f) Parse data with the correct specifications and the correct number of particles (g) Calculate different data levels with correct dimensions and units
Wall-Resolved Large-Eddy Simulation of Flow Separation Over NASA Wall-Mounted Hump

This paper reports the findings from a study that applies wall-resolved large-eddy simulation to investigate flow separation over the NASA wall-mounted hump geometry. Despite its conceptually simple flow configuration, this benchmark problem has proven to be a challenging test case for various turbulence simulation methods that have attempted to predict flow separation arising from the adverse pressure gradient on the aft region of the hump. The momentum-thickness Reynolds number of the incoming boundary layer has a value that is near the upper limit achieved by recent direct numerical simulation and large-eddy simulation of incompressible turbulent boundary layers. The high Reynolds number of the problem necessitates a significant number of grid points for wall-resolved calculations. The present simulations show a significant improvement in the separation-bubble length prediction compared to Reynolds-Averaged Navier-Stokes calculations. The current simulations also provide good overall prediction of the skin-friction distribution, including the relaminarization observed over the front portion of the hump due to the strong favorable pressure gradient. We discuss a number of problems that were encountered during the course of this work and present possible solutions. A systematic study regarding the effect of domain span, subgrid-scale model, tunnel back pressure, upstream boundary layer conditions and grid refinement is performed. The predicted separation-bubble length is found to be sensitive to the span of the domain. Despite the large number of grid points used in the simulations, some differences between the predictions and experimental observations still exist (particularly for Reynolds stresses) in the case of the wide-span simulation, suggesting that additional grid resolution may be required.
A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient) at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a 'carcinogenic risk score'. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.
Charles Malik and the Origins of a Christian Critique of Orientalism in Lebanon and Britain

The field of Oriental studies was the main context in which amateur and professional scholars developed the academic study of Islam before World War II. The role of religion in the rise of this discipline is now widely acknowledged, but the role of religion, particularly Christianity, in the critique and transformation of Orientalism after World War II has never been explored. Given the prevalence of Christian scholars in Islamic studies after 1945, why has this been the case?
Ferrous Iron Oxidation under Varying pO2 Levels: The Effect of Fe(III)/Al(III) Oxide Minerals and Organic Matter

Abiotic Fe(II) oxidation by O2 commonly occurs in the presence of mineral sorbents and organic matter (OM) in soils and sediments; however, this tertiary system has rarely been studied. Therefore, we examined the impacts of mineral surfaces (goethite and γ-Al2O3) and organic matter [Suwannee River fulvic acid (SRFA)] on Fe(II) oxidation rates and the resulting Fe(III) (oxyhydr)oxides under 21 and 1% pO2 at pH 6. We tracked Fe dynamics by adding 57Fe(II) to 56Fe-labeled goethite and γ-Al2O3 and characterized the resulting solids using 57Fe Mossbauer spectroscopy. We found Fe(II) oxidation was slower at low pO2 and resulted in higher-crystallinity Fe(III) phases. Relative to oxidation of Fe(II)(aq) alone, both goethite and γ-Al2O3 surfaces increased Fe(II) oxidation rates regardless of pO2 levels, with goethite being the stronger catalyst. Goethite surfaces promoted the formation of crystalline goethite, while γ-Al2O3 favored nano/small particle or disordered goethite and some lepidocrocite; oxidation of Fe...
Health-related quality of life among adults with diverse rare disorders.

Twenty-five to 30 million Americans live with a rare disease (RD) and share challenges unique to RD. The majority of research on RDs has focused on etiology, treatment and care, while the limited health-related quality of life (HRQL) research has been restricted to single RDs, small samples, or non-validated measures. This study reports HRQL among adults with diverse RDs, and compares their scores to those of the U.S. population and people with common chronic health conditions. We conducted a cross-sectional survey of adults living in the U.S. diagnosed with any RD. Participants were recruited through RD organizations and completed the online survey between December 2016 and May 2017 (n = 1218). HRQL was assessed using the standardized Patient-Reported Outcomes Measurement Information System (PROMIS). RDs were classified into categories defined by Orphanet. Means and 95% confidence intervals were calculated for the main sample and for RD categories and were compared to published U.S. population norms and common chronic disease norms. Intercorrelations were conducted between HRQL, demographics, and RD experiences. When compared to the norms for the U.S. population and for those with common chronic diseases, mean HRQL scores were significantly poorer across all six PROMIS domains for the main sample, and were usually poorer when analyzed by sub-sets of specific RD classifications. People with rare systemic and rheumatologic, neurological, and immune diseases had the poorest HRQL. Participants had poorer HRQL if they had multiple RDs, lower income, were female, or older. Having symptoms longer was associated with worse HRQL, however, having a formal diagnosis longer was associated with better HRQL. This study is the first to examine HRQL in a large, heterogeneous sample of RDs using validated measures. There is a significant disparity in HRQL among people with RD compared to the general population and people with common chronic diseases. Poor HRQL could be attributed to challenges accessing diagnoses, medical information, treatment, psychosocial support, and coping with stigma and uncertainty. As most individuals with RDs will not be cured in their lifetimes, identifying ways to improve HRQL is crucial to patient-centered care and should be a funding priority.
An Informational Theory of Counterfactuals

Backtracking counterfactuals are problem cases for the standard, similarity based, theories of counterfactuals e.g., Lewis (Nous13.4, 455–476, 1979). These theories usually need to employ extra-assumptions to deal with those cases (e.g., Lewis’ “standard resolution of vagueness”). Hiddleston (Nous 39(4), 632–657, 2005) proposes a causal theory of counterfactuals that, supposedly, deals well with backtracking. The main advantage of the causal theory is that it provides a unified account for backtracking and non-backtracking counterfactuals (no extra-assumption is needed). In this paper, I present a backtracking counterfactual that is a problem case for Hiddleston’s account. Then I propose an informational theory of counterfactuals, which deals well with this problem case while maintaining the main advantage of Hiddleston’s account (the unified account for backtracking and non-backtracking counterfactuals). In addition, the informational theory offers a general theory of backtracking that provides clues for the semantics and epistemology of counterfactuals. I propose that backtracking is reasonable when the (possibly non-actual) state of affairs expressed in the antecedent of a counterfactual transmits less information about an event in the past than the actual state of affairs.
Migration and Social Regionalism: Labour Migration as an Unintended Consequence of Globalization in Mexico, 1980-2000

Increased labor migration from Mexico to the United States between 1980 and 2000 stemmed in large part from macroeconomic policy reforms, implemented at the domestic and international levels, that we now associate with economic "globalization." These reforms were ushered in by the era of "deep economic integration" - the period beginning in the early 1980s in which domestic economic crises in many developing countries, including Mexico, set the stage for market liberalization supported by the advice and counsel of the Bretton Woods institutions. For Mexico, the adoption of the NAFTA played a central role in effecting market liberalization and setting the stage for labor migration. Far from being the sole factor, however, the NAFTA interacted with a host of other important reforms in Mexico's investment, fiscal, and exchange rate regimes. And while conventional economic theory might have predicted that market liberalization would substitute migration, events as they actually unfolded proved migration and liberalization to be complements rather than substitutes. By demonstrating the link between migration and economic liberalization across the Mexico - U.S. border, this chapter emphasizes the importance of understanding the connections between trade and labor in both scholarship and practice, and as such seeks to support emerging, interdisciplinary labor law and policy discourse. Too often, these fields have remained separated despite their overlapping analytical and empirical parameters. Beyond specialized scholarship and practice, however, the chapter seeks to comment on broader political debates over the sensitive topic of immigration. These debates too often portray migration influxes as exogenous phenomena, as opposed to effects of law and policy choices made by government actors in trade, investment, and related areas.
The exquisitely cooperative nature of Orai1 channel activation

Most animal cells exhibit a conserved mechanism for Ca2+ entry, termed store-operated Ca2+ entry (SOCE), that is activated by depletion of endoplasmic reticulum (ER) Ca2+ stores in response to stimulation of cell surface receptors coupled to G proteins or tyrosine kinases ([Prakriya and Lewis, 2015
The influence of natural organic matter on the adsorption of microcystin-LR by powdered activated carbon

In this study, microcystin-LR (MC-LR) adsorption to four different types of powdered activated carbon (PAC) was evaluated to provide insight into the use of PAC to treat water containing MC-LR. MC-LR adsorption to the four PAC types (wood, coal blend, bituminous coal, and coconut shell) was studied in equilibrium and kinetic batch experiments utilizing a model water with different natural organic matter (NOM) concentrations (0, 5 and 10 mg L−1) and pH (5.2, 8.5 and 9.5). The effect of NOM type was evaluated by comparing MC-LR uptake in model water amended with Suwannee river fulvic acid or a NOM extracted from a natural water experiencing an algal bloom. The results demonstrated that the wood-based PAC removed MC-LR at the highest rate and to the greatest extent, which likely reflects that wood-based PAC typically contains a greater proportion of mesopores than the other types of PAC in this study. MC-LR removal was significantly reduced in the presence of NOM, with the impact being slightly higher for the algal-derived NOM compared to Suwannee river fulvic acid. MC-LR removal decreased with decreasing pH in the presence of NOM, but increased with decreasing pH in the absence of NOM. This suggests competition with NOM not only varies depending upon the source of NOM, but also on the solution pH as NOM interactions with PAC will vary with pH. Thus, properly determining PAC doses to treat MC-LR must account for the presence of NOM as well as the pH-dependent interactions of NOM with PAC as these interactions strongly influence MC-LR adsorption.
A Moldy Application of MALDI: MALDI-ToF Mass Spectrometry for Fungal Identification

As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of yeasts and even dimorphic and filamentous fungi in cultures, while slower, is now being realized, with many of the same benefits as have been recognized on the bacterial side. In this review, the use of MALDI-ToF MS for identification of yeasts, and dimorphic and filamentous fungi grown in culture will be reviewed, with strengths and limitations addressed.
A Model Framework for Stochastic Representation of Uncertainties Associated with Physical Processes in NOAA’s Next Generation Global Prediction System (NGGPS)

AbstractIn this study, we propose a physical-process-based stochastic parameterization scheme using cellular automata for NOAA’s Next Generation Global Prediction System. The cellular automata, use...