cssi/SciSciGPT-SciSciNet huggingface dataset:
Combating Parkinson’s disease-associated toxicity by modulating proteostasis

The incidence of age-associated neurodegenerative disease is growing rapidly, and it is expected to triple by 2050 (1). Currently, there are no cures or treatments that significantly modify disease progression. As researchers develop an in-depth understanding of the mechanisms of neurodegeneration, common features across different diseases are becoming apparent. Chief among them is the presence of protein aggregates, such as amyloid plaques and tau tangles in Alzheimer’s disease (2); α-synuclein–rich Lewy bodies and Lewy neurites in Parkinson’s disease (3); huntingtin aggregates in Huntington’s disease (4); and aggregates of superoxide dismutase 1 (SOD1), TDP43, and FUS in amyotrophic lateral sclerosis (5). Although the precise mechanisms of protein aggregation-associated toxicity remain unclear, the accumulation of aggregated proteins in the diseased neurons indicates imbalances in protein homeostasis (proteostasis) (proteostasis is reviewed in ref. 6). As such, researchers are studying the potential therapeutic strategy of restoring proteostasis to normal levels by boosting the activity of molecular chaperones. One way to do so is to activate HSF1 (heat shock factor protein 1) by inhibiting HSP90 (heat shock protein 90), thereby stimulating the expression of multiple chaperones. Indeed, this strategy has been shown to be effective in fly models of Parkinson’s disease … [↵][1]1To whom correspondence should be addressed. Email: qqhoang{at}iu.edu. [1]: #xref-corresp-1-1
Intergenerational transfers and China’s social security reform

Abstract Most of the studies examining the implications of social security reforms in China use overlapping generations models and abstract from the role of family support. However, in China, family support plays a prominent role in the well-being of the elderly and often substitutes for the lack of government-provided old-age support systems. In this paper, we investigate the impact of social security reform in China in a model with two-sided altruism as well as a pure life-cycle model. We show that the quantitative implications of social security reform, in particular for capital accumulation and output, are very different across the two models.
Neural Discourse Structure for Text Categorization.

We show that discourse structure, as defined by Rhetorical Structure Theory and provided by an existing discourse parser, benefits text categorization. Our approach uses a recursive neural network and a newly proposed attention mechanism to compute a representation of the text that focuses on salient content, from the perspective of both RST and the task. Experiments consider variants of the approach and illustrate its strengths and weaknesses.
Warped Functional Analysis of Variance

This article presents an Analysis of Variance model for functional data that explicitly incorporates phase variability through a time-warping component, allowing for a unified approach to estimation and inference in presence of amplitude and time variability. The focus is on single-random-factor models but the approach can be easily generalized to more complex ANOVA models. The behavior of the estimators is studied by simulation, and an application to the analysis of growth curves of flour beetles is presented. Although the model assumes a smooth latent process behind the observed trajectories, smootheness of the observed data is not required; the method can be applied to irregular time grids, which are common in longitudinal studies.
Resource Allocation in Strategic Factor Markets: A Realistic Real Options Approach to Generating Competitive Advantage:

This paper develops a realistic real option theory of resource allocation decisions in strategic factor markets. Competitive advantage in factor markets is underpinned by market failures that allow firms to acquire assets at less than their value in use. We recognize that market failure may result from uncertainty regarding the current and/or future value of an asset, which map, respectively, to uncertainty as modeled in the feedback learning and real options literatures. The realistic real option framework we develop grafts insights from the strategic factor market, feedback learning, and real option valuation literatures. We argue that competitive advantage may emerge not only from luck, or ex ante differences in information or complementary assets, but also because firms differ in a specific type of learning ability—the ability to integrate new information to exercise a contingent claim on an asset in a factor market. We dimensionalize these differences in terms of information processing and belief upd...
DIGITAL RADIOGRAPHY IN TOTAL HIP ARTHROPLASTY: TECHNIQUE AND CLINICAL RESULTS

INTRODUCTION Despite our best efforts, orthopaedic surgeons do not always achieve desired results in acetabular cup positioning in total hip arthroplasty. New advancements in digital radiography and image analysis software allow contemporaneous assessment of cup position in real-time during the surgical procedure. The purpose of this study was to describe and validate a technique in obtaining a true AP Pelvis radiograph in the lateral decubitus position to accurately assess cup position intra-operatively (Figure 1). METHODS 350 consecutive patients undergoing THA through a soft-tissue sparing posterior approach were prospectively enrolled. Standard pre-operative supine radiographs were taken in the office to serve as a reference for intra-operative pelvic orientation and templating. Intra-operative AP Pelvis radiographs were obtained with the patient in the lateral decubitus position to appropriately match the pre-operative radiograph. Adjustments were made to correct for pelvic rotation by rotating the operating room table forward or backward. Radiographic beam angle adjustments allowed the surgeon to match pre-operative and intra-operative pelvic tilt (Figure 2). Two independent observers measured cup abduction angle. RESULTS 95% of cups were placed within 30–50 degrees of abduction, with a mean angle of 38 degrees (STD +/− 5). 100% of cups measured post-operatively were placed within 3 degrees of their intra-operative measurement. Mean anteversion was 27.5 degrees (STD +/− 3.5). Intra-operative radiographs were repeated in 88% of cases in order to match to the pre-operative radiographs. The cup was repositioned in 28% of cases based on intra-operative measurements. Impingement during range of motion testing occurred in 3% of cases despite acceptable measurements, necessitating cup reposition. The intercross correlation coefficient between the two observers was 0.92. There was one dislocation reported in the 2-year follow-up. Changes in the pelvic inlet and outlet orientation changed the abduction angle measurement in a predictable way. We developed a formula and 3D model to predict the abudction angle based on the pelvic tilt, where a more outlet view would increase the abduction angle measurement (Figure 3). DISCUSSION AND CONCLUSION Advancements in digital radiography allow for real-time cup position assessment, creating the opportunity for the surgeon to make the appropriate changes and confirm precise placement during the procedure. For figures/tables, please contact authors directly.
A new recombination lower bound and the minimum perfect phylogenetic forest problem

Understanding recombination is a central problem in population genetics. In this paper, we address an established computational problem in this area: compute lower bounds on the minimum number of historical recombinations for generating a set of sequences (Hudson and Kaplan in Genetics 111, 147–164, 1985; Myers and Griffiths in Genetics 163, 375–394, 2003; Gusfield et al. in Discrete Appl. Math. 155, 806–830, 2007; Bafna and Bansal in IEEE/ACM Trans. Comput. Biol. Bioinf. 1, 78–90, 2004 and in J. Comput. Biol. 13, 501–521, 2006; Song et al. in Bioinformatics 421, i413–i244, 2005). In particular, we propose a new recombination lower bound: the forest bound. We show that the forest bound can be formulated as the minimum perfect phylogenetic forest problem, a natural extension to the classic binary perfect phylogeny problem, which may be of interests on its own. We then show that the forest bound is provably higher than the optimal haplotype bound (Myers and Griffiths in Genetics 163, 375–394, 2003), a very good lower bound in practice (Song et al. in Bioinformatics 421, i413–i422, 2005). We prove that, like several other lower bounds (Bafna and Bansal in J. Comput. Biol. 13, 501–521, 2006), computing the forest bound is NP-hard. Finally, we describe an integer linear programming (ILP) formulation that computes the forest bound precisely for certain range of data. Simulation results show that the forest bound may be useful in computing lower bounds for low quality data.
Pharyngeal peristaltic pressure variability, operational range, and functional reserve

Intra- and intersubject variability are significant and different at various sites within the contractile pharynx. In addition, significant swallow-to-swallow and subject-to-subject variability exi...
Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway.

Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1). RhoA inhibitor C3 transferase almost completely inhibited dasatinib-induced increase in permeability. Under similar conditions, imatinib had no effect on permeability or activation of RhoA. Since integrin-induced cell spreading suppresses RhoA activation, we examined the effect of dasatinib on cell spreading on fibronectin substrate. Dasatinib impaired endothelial cell spreading in a concentration-dependent manner and induced disorganization of actin fibers. Tyrosine kinases play an essential role in transmitting signals from integrins to RhoA and we examined tyrosine phosphorylation of several cytoskeletal proteins. Dasatinib markedly inhibited tyrosine phosphorylation of p130 Crk-associated substrate (p130cas), paxillin and vinculin. These results suggest that the inhibition of tyrosine phosphorylation of the focal adhesion plaque components by dasatinib may alter the assembly of actin fibers resulting in the activation of RhoA/ROCK pathway. Consistent with these findings, dasatinib-induced increase in the permeability was blocked by ROCK inhibitor y27632. In vivo administration of y27632, significantly inhibited the dasatinib-induced extravasation of Evans blue in mice and dasatinib-induced increase in microvascular permeability was attenuated in ROCK1-deficient mice. These findings suggest that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes.
Understanding black-box predictions via influence functions

How can we explain the predictions of a black-box model? In this paper, we use influence functions — a classic technique from robust statistics — to trace a model's prediction through the learning algorithm and back to its training data, thereby identifying training points most responsible for a given prediction. To scale up influence functions to modern machine learning settings, we develop a simple, efficient implementation that requires only oracle access to gradients and Hessian-vector products. We show that even on non-convex and non-differentiable models where the theory breaks down, approximations to influence functions can still provide valuable information. On linear models and convolutional neural networks, we demonstrate that influence functions are useful for multiple purposes: understanding model behavior, debugging models, detecting dataset errors, and even creating visually-indistinguishable training-set attacks.
Determining Application-specific Peak Power and Energy Requirements for Ultra-low Power Processors

Many emerging applications such as IoT, wearables, implantables, and sensor networks are power- and energy-constrained. These applications rely on ultra-low-power processors that have rapidly become the most abundant type of processor manufactured today. In the ultra-low-power embedded systems used by these applications, peak power and energy requirements are the primary factors that determine critical system characteristics, such as size, weight, cost, and lifetime. While the power and energy requirements of these systems tend to be application-specific, conventional techniques for rating peak power and energy cannot accurately bound the power and energy requirements of an application running on a processor, leading to over-provisioning that increases system size and weight. In this paper, we present an automated technique that performs hardware-software co-analysis of the application and ultra-low-power processor in an embedded system to determine application-specific peak power and energy requirements. Our technique provides more accurate, tighter bounds than conventional techniques for determining peak power and energy requirements, reporting 15% lower peak power and 17% lower peak energy, on average, than a conventional approach based on profiling and guardbanding. Compared to an aggressive stressmark-based approach, our technique reports power and energy bounds that are 26% and 26% lower, respectively, on average. Also, unlike conventional approaches, our technique reports guaranteed bounds on peak power and energy independent of an application's input set. Tighter bounds on peak power and energy can be exploited to reduce system size, weight, and cost.
Line-Constrained k-Median, k-Means, and k-Center Problems in the Plane

The (weighted) k-median, k-means, and k-center problems in the plane are known to be NP-hard. In this paper, we study these problems with an additional constraint that requires the sought k facilities to be on a given line. We present efficient algorithms for various distance measures such as L1,L2,L∞. We assume that all n weighted points are given sorted by their projections on the given line. For k-median, our algorithms for L1 and L∞ metrics run in O(min{nk,nklog nlog n,n2O(log klog log n)log n}) time and O(min{nklog n,nklog nlog2n,n2O(log klog log n)log2n}) time, respectively. For k-means, which is defined only on the squared L2 distance, we give an O(min{nk,nklog n,n2O(log klog log n)}) time algorithm. For k-center, our algorithms run in O(nlog n) time for all three metrics, and in O(n) time for the unweighted version under L1 and L∞ metrics. While our results for the k-center problem are optimal, the results for the k-median problem almost match the best algorithms for the corresponding one-dimensio...
Price Elasticity of Alcohol Demand in India

AIMS: Using a household survey conducted in 2014, this study estimates price elasticity of demand (PED) for beer, country liquor and spirits in India. METHODS: Ordinary least-square models were used to estimate the responsiveness in alcohol demand due to price change. A large number of control variables were included to adjust for potential confounding in the model. Inter-district variation in alcohol consumption is adjusted for by including district fixed effects. RESULTS: Alcohol prices are negatively associated with demand for alcoholic beverages. The PED ranged from -0.14 for spirits to -0.46 for country liquor. Low level of education was positively associated with spirits consumption. The magnitude of elasticity varied by rural-urban, education and gender. CONCLUSION: Results indicate that a policy mix of price controls and awareness campaigns would be most effective in tackling the adverse effects of harmful drinking in India. SUMMARY: The demand for beer, country liquor and spirits is negatively associated with its own price. The elasticity estimates ranged from -0.14 for spirits to -0.44 for country liquor. The elasticity estimates varied by rural-urban, gender and by education levels of the drinkers. Language: en
Approximation Algorithms for Precedence-Constrained Scheduling Problems on Parallel Machines that Run at Different Speeds

We present new approximation algorithms for the problem of scheduling precedence-constrained jobs on parallel machines that are uniformly related. That is, there arenjobs andmmachines; each jobjrequirespjunits of processing, and is to be processed on one machine without interruption; if it is assigned to machinei, which runs at a given speedsi, it takespj/sitime units. There also is a partial order ? on the jobs, wherej?kimplies that jobkmay not start processing until jobjhas been completed. We consider two objective functions:Cmax=maxjCj, whereCjdenotes the completion time of jobj, and ?jwjCj, wherewjis a weight that is given for each jobj. For the first objective, the best previously known result is anOm-approximation algorithm, which was shown by Jaffe more than 15 years ago. We give anO(logm)-approximation algorithm. We also show how to extend this result to obtain anO(logm)-approximation algorithm for the second objective, albeit with a somewhat larger constant. These results also extend to settings in which each jobjhas a release daterjbefore which the job may not begin processing. In addition, we obtain stronger performance guarantees if there are a limited number of distinct speeds. Our results are based on a new linear programming-based technique for estimating the speed at which each job should be run, and a variant of the list scheduling algorithm of Graham that can exploit this additional information.
BPS states, torus links and wild character varieties

A string theoretic framework is constructed relating the cohomology of wild character varieties to refined stable pair theory and torus link invariants. Explicit conjectural formulas are derived for wild character varieties with a unique irregular point on the projective line. For this case, this leads to a conjectural colored generalization of existing results of Hausel, Mereb and Wong as well as Shende, Treumann and Zaslow.
Constructing a perfect matching is in random NC

We show that the problem of constructing a perfect matching in a graph is in the complexity class Random NC; i.e., the problem is solvable in polylog time by a randomized parallel algorithm using a polynomial-bounded number of processors. We also show that several related problems lie in Random NC. These include:
A Cross-cultural Evaluation of Ethnic Identity Exploration and Commitment.

We evaluated the unique contribution of the two subscales of the Multigroup Ethnic Identity Measure–Revised (MEIM-R), Exploration and Commitment, to mental and behavioral health outcomes among non-Hispanic White, ethnic minority, and mixed-race college students. Monoracial ethnic minority and mixed-race students reported higher Exploration scores in comparison to monoracial non-Hispanic White students. Monoracial ethnic minority students reported higher Commitment scores in comparison to monoracial non-Hispanic White and mixed-race students. Among the total sample, higher Exploration scores were associated with greater anxiety symptoms, suggesting that ethnic identity exploration may result in heightened levels of distress.
Minimally invasive distal pancreatectomy: greatest benefit for the frail

The benefits of minimally invasive distal pancreatectomy (MIDP) over open surgery continue to be investigated. Frailty is a known predictor of postoperative outcome. We hypothesized that the benefit of minimally invasive distal pancreatectomy is the greatest for the frailest of patients. Data from the pancreas-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014 were reviewed. A modified frailty index (mFI) with 11 preoperative variables previously validated for use in NSQIP was used to determine the correlation between frailty and postoperative outcomes, including Clavien grade IV complications. Patients were classified into non-frail (mFI = 0) or frail (mIF > 0), in which they were subclassified into mildly frail (mFI 1 or 2) or severely frail (mFI = 3). A total of 1,038 distal pancreatectomies (DP) were included in the analysis, of which 387 were minimally invasive (MIDP: laparoscopic: 285, robotic: 102), 558 open DP (ODP), and 93 MIDP converted to open (MIDPcODP: laparoscopic: 80, robotic: 13). More than 90% of patients had an mFI of 0 or 1 (mFI 0 = 473 (45.6%), 1 = 466 (44.9%), 2 = 94 (9.1%), and 3 = 5 (0.5%), respectively). Overall, 4.6% of patients experienced Clavien grade IV complications and 1.1% a mortality. Non-frail patients experienced a similar rate of grade IV Clavien complications with MIDP vs. ODP vs. MIDPcOP (2.3 vs. 2.3 vs. 4.9%; p = 0.6), whereas frail patients (mFI > 0) had a lower rate of complications with MIDP (2.4 vs. 8.3 vs. 11.5; p = 0.007). Worsening frailty correlated with an increase in complications (non-frail: 2.5%; mildly frail: 6.3%; severely frail: 20%; p = 0.005). MIDP is associated with a lower risk of Clavien grade IV complications compared to ODP for frail patients, especially for benign disease. Thus, minimally invasive approach may mitigate risk in frail patients.
Blind Separation of Heart Sounds

This paper presents a theoretical foundation for the newly developed methodology that enables the prediction of blood pressures based on the heart sounds measured directly on the chest of a patient. The key to this methodology is the separation of heart sounds into first heart sound and second heart sound, from which components attributable to four heart valves, i.e.: mitral; tricuspid; aortic; and pulmonary valve-closure sounds are separated. Since human physiology and anatomy can vary among people and are unknown a priori, such separation is called blind source separation. Moreover, the sources locations, their surroundings and boundary conditions are unspecified. Consequently, it is not possible to obtain an exact separation of signals. To circumvent this difficulty, we extend the point source separation method in this paper to an inhomogeneous fluid medium, and further combine it with iteration schemes to search for approximate source locations and signal propagation speed. Once these are accomplished, the signals emitted from individual sources are separated by deconvoluting mixed signals with respect to the identified sources. Both numerical simulation example and experiment have demonstrated that this approach can provide satisfactory source separation results.
Reflective metal/semiconductor tunnel junctions for hole injection in AlGaN UV LEDs

In this work, we investigate the use of nanoscale polarization engineering to achieve efficient hole injection from metals to ultra-wide bandgap AlGaN, and we show that UV-reflective aluminum (Al) layers can be used for hole injection into p-AlGaN. The dependence of tunneling on the work function of the metal was investigated, and it was found that highly reflective Al metal layers can enable efficient hole injection into p-AlGaN, despite the relatively low work function of Al. Efficient tunneling hole injection was confirmed by light emission at 326 nm with an on-wafer peak external quantum efficiency and a wall-plug efficiency of 2.43% and 1.33%, respectively. A high power density of 79.0 W/cm2 was measured at 1200 A/cm2. The metal/semiconductor tunnel junction structure demonstrated here could provide significant advantages for efficient and manufacturable device topologies for high power UV emitters.
A Velocity-Adaptive, Microprocessor-Based, Vehicle Lateral Controller

Abstract A velocity-adaptive lateral controller was designed to meet requirements pertaining to lateral-position tracking accuracy, ride comfort, and an insensitivity to both changes in critical vehicle parameters and disturbance forces. This controller was implemented using a 16-bit microcomputer (which was based on an Intel 8086 microprocessor) and installed in a dual-mode test vehicle. The controller/vehicle combination was evaluated under field conditions at the Transportation Research Center of Ohio. A wire-follower configuration was employed to provide both a lateral reference and a lateral position error (ΔS f ). The vehicle was automatically steered on straight sections of roadway at speeds up to 35.8 m/s, and small-radius (100-m) curves were traversed at speeds up to 17.9 m/s. Excellent lateral control -- close tracking (|ΔS f | RMS 2 ) and a good insensitivity to disturbance forces -- resulted. The selected control algorithm, which involved an inverse compensation stage for velocity-independent performance and a lead/lag stage for both good tracking and ride comfort, was realized using some 10 percent of the available computation time. Thus, the microcomputer could also be employed for such tasks as vital function monitoring (e.g., oil pressure, alternator output and engine temperature), and serve as a source of intelligence on-board the vehicle. The latter could be especially important in reducing the response time to various emergencies.
The Interdependence Between Wage Indexation and Exchange Market Intervention

Abstract This paper analyzes the interdependence between wage indexation and exchange market intervention as tools of macroeconomic stabilization policy in a small open economy subject to stochastic disturbances. It shows how the choice of either policy instrument impinges on the effectiveness of the other. If the domestic money wage is fully indexed to some arbitrary weighted average of the domestic and foreign price levels, then exchange market intervention is rendered totally ineffective insofar as the stabilization of the real part of the domestic economy is concerned. Likewise, if the monetary authority intervenes in the exchange market so as to exactly accommodate for nominal movements in the demand for money, thereby rendering the excess demand for money dependent only upon real variables, then any form of wage indexation is totally ineffective for the stabilization of the real part of the system. In either polar case, the respective instrument can stabilize the domestic price level. A number of specific propositions with respect to the stabilization of domestic and foreign disturbances are also derived.
Using TOP-C and AMPIC to port large parallel applications to the computational grid

Porting large parallel applications to new and various distributed computing platforms is a challenging task from a software engineering perspective. The primary aim of this paper is to demonstrate how the development time to port very large applications to the Computational Grid can be significantly reduced. TOP-C and AMPIC are software packages that have each seen successful applications in their respective domains of parallel computing and process creation/communication over the Computational Grid. We combined the two packages in 1 man-week, thereby leveraging several man-years of previous independent software development. As a real world test case, the 1,000,000 line Geant4 sequential application was then deployed over the Computational Grid in 3 man-weeks by using TOP-C/AMPIC. The cluster parallelization of Geant4 using TOP-C is now included as part of the Geant4 4.1 distribution, and the integration of TOP-C/AMPIC and the Globus protocols will additionally enable the use of the fundamental Grid middleware services in the future.
Omnidirectional reflector using a low refractive index material

Triple-layer omni-directional reflectors (ODRs) consisting of a semiconductor, a transparent quarter-wavelength dielectric layer and metal layer have high reflectivities at all angles of incidence. In this paper, triple-layer ODRs are demonstrated that incorporate nanoporous SiO/sub 2/, a novel low-refractive-index (low-n) material with refractive indices n /spl Lt/ 1.46 as well as dense SiO/sub 2/ (n = 1.46). GaP and Ag serve as the semiconductor and metal layer materials, respectively. An angle-integrated transverse electric (TE) mode reflectivity of R/sub avg/|/sub TE/ = 99.9 % and transverse magnetic (TM) mode reflectivity R/sub avg/|/sub TM/ = 98.9 % are calculated for the triple-layer ODRs employing nanoporous SiO/sub 2/. Reflectivity measurements, including the angular dependence of R, are presented. Novel hybrid ODRs consisting of semiconductor, a several micron thick low-n dielectric material layer, a distributed Bragg reflector (DBR) and metal layer have outstanding reflectivities for all incident angles. GaP and Ag serve as the semiconductor and metal layer, respectively. Nanoporous SiO/sub 2/ is used as the low-n material. TiO/sub 2/ and dense SiO/sub 2/ serve as the DBR materials. The angle-intergrated reflectivities of the TE and TM modes are calculated to be larger than 99.9% for the hybrid ODRs. The results indicate the great potential of the ODRs for light-emitting diodes with high light extraction efficiency.
Use of Polyethylene Glycol-Modified Uricase (PEG-Uricase) to Treat Hyperuricemia in a Patient With Non-Hodgkin Lymphoma

Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.
Gender Testing in the Olympics

Since 1968 the International Olympics Committee (IOC) has required that individuals taking part in women's sporting events present evidence of "their femininity or female gender." Competitors must report to the "Gender Verification Office," where "determination of X and Y chromatin will be conducted on a smear of buccal mucosa membrane." "If the test is inconclusive, the competitor must undergo further tests as determined by the IOC Medical Commission." Because results are not made public, the efficacy of this policy is unknown. "Gender" testing superficially strikes one as intuitively logical. That men might masquerade as women is not unthinkable in a luminous event like the Olympics. Moreover, genetic males raised as females may indeed have unfair athletic advantages as a result of increased muscle mass. An example is 5a-reductase deficiency, an autosomal recessive disorder in which 46,XY individuals are often raised as females only to virilize at puberty. As de la
Testicular Neoplasm Diagnosed by Ultrasound

The diagnosis of testicular cancer is usually made by the findings of a testicular mass on physical examination. in rare cases a young man will present with retroperitoneal nodes and a normal testicular examination. in such cases a testicular ultrasound may localize the testis which harbors a subclinical neoplasm. in addition serum markers of B-HCG and AFP are essential. As a screening procedure a urine pregnancy test is helpful, since it can be obtained quickly while quantitative B-HCG and APF results are delayed.
Optimal Control of a Production Line with Adjustable Service Rates

Abstract This paper derives an analytical model of a class of production lines characterized by adjustable service rates. From this model, operating guidelines are derived for maximization of throughput or minimization of in-process inventory.
Falsely Normal Value in Fluorometric Transferase Screening of Galactosemic Blood. A Cautionary Note

A blood sample from a galactosemic infant gave a normal result with the fluorescent screening test for galactose-1-phosphate uridyl transferase. The generation of fluorescence from this sample was found to be a property of the plasma; the erythrocytes manifested no galactose-1-phosphate uridyl transferase activity. The plasma was found to contain a high level of isocitrate dehydrogenase, presumably a result of the infant’s liver disease, and of isocitrate, presumably derived from citrate in the anticoagulant solution by action of aconitase derived from leukocytes which lysed during shipment. The oxidation of the isocitrate by the dehydrogenase apparently resulted in reduction of NADP to NADPH. False negative results have not been reported previously using the fluorescent transferase assay. They can be avoided in the future by using EDTA rather than citrate as an anticoagulant, particularly if blood samples are to be shipped at ambient temperature.
The ESG Integration Paradox

Today, most investment managers have something to say about environmental, social and governance (ESG) issues, and written ESG policies are ubiquitous. Yet, a written policy is not a reliable indicator of a firm's commitment. Actual ESG incorporation practices vary greatly, with most investment managers falling well short of full integration. Only a few firms seem to be using ESG factors to deliver alpha, hence, the paradox. If not implemented wholeheartedly, responsible investing can lead to lower financial returns. So, why have so few investment managers gone all the way? The paradox involves a “valley” of lower returns where portfolios first absorb the costs of ESG integration before the promised benefits materialize. In the early days of ethical investing, the focus was on using negative screens to exclude certain companies for moral or ethical reasons but lower financial returns are inherent to exclusionary screening. Hard exclusions force managers to tradeoff certain risks for others. So, for example, if the market discounts tobacco stock prices to account for changing consumer behavior, eventually tobacco stock prices become attractive again as, indeed, has been the case over the last two decades. Exclusionary screening alone is a self‐limiting strategy. By contrast, ESG strategies range from active ownership and engagement, to positive screening (selecting for certain attributes), to relative weighting (sometimes called “best‐in‐class selection”), to risk factor investing, to full integration. Because the relationship between an asset manager's ESG efforts and its risk‐adjusted performance is not classically linear, asset owners should look for managers that are on the upward slope of the ESG intensity curve and are fully committed to advancing up it.
Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results

Abstract Goals To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not. Methods The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973–2008. We excluded patients with metastatic disease, age Principle results There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19–1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31–1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p Conclusion There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods.
Design Of Masonry Walls For Blast Loading

The arching action theory of masonry walls presented in a previous paper is applied to the problem of blast resistant design. Based on this theory, an equation of motion is developed for a masonry beam of solid cross-section restrained by essentially rigid supports. This equation is solved for a simplified but realistic form of blast loading. The results obtained permit either the design of a wall for a given loading or the determination of the maximum loading which a given wall can withstand. The theory is extended by an approximate method to wall panels supported on four sides. Comparison is made with test data for walls subjected to full scale atomic and high explosive blasts.
IMPACT OF TIBIA BEARING CONFORMITY ON POSTERIOR-STABILISED KNEE KINEMATICS

INTRODUCTION Clinical studies have shown that the knee tends to experience laterally higher AP motion (posterior directed) than medially (Asano at al., 2001; Dennis et al., 2005; Hill et al., 2000; Moro Oka et al., 2007). Traditional posterior stabilized (PS) total knee arthroplasty (TKA) designs allow deep flexion stability and femoral rollback once cam/spine engagement occurs, however mechanical stability provided by tibial bearing conformity during early to mid-flexion is highly variable. In this study a computer knee model is used to compare AP kinematics in PS TKA designs while evaluating multiple sagittal tibia bearing conformities. We hypothesized that highly conforming designs would be necessary to promote AP stability prior to cam/spine engagement. METHOD A specimen specific computer model consisting of the femur, tibia and fibula, as well as the contribution of the ligaments and capsule was virtually implanted with TKA designs of the appropriate size at 5° tibia slope with the posterior cruciate ligament sacrificed. A single PS femoral component was evaluated with five PS tibia bearing designs with variable sagittal conformity ratios ranging from 1.05:1 to 2.2:1 (conformity ratio = tibia bearing sagittal radius / femur sagittal condylar radius). Designs were fully conforming frontally, with cam/spine engagement beyond 90° flexion. In all designs, lateral conformity ratios were increased relative to medial conformity ratios to facilitate lateral femoral rollback. Resultant AP kinematic predictions were obtained for femoral Low Points (LP) during 1) envelope of motion during internal external (IE) laxity evaluation and 2) knee bend functional activity. RESULTS Designs with increased conformity resulted in improved AP stability in early to mid-flexion. In the envelope of laxity evaluations (Figure 1), the Medial LP laxity was similar for the 1.05:1 and 1.15:1 designs (approximately 2–3mm from extension to flexion), but then increased for the 1.35:1, 1.55:1, and 2.20:1 designs. Lateral LP laxity was more similar in all designs, however the designs with lower medial conformity ratio tended to have a greater Lateral LP laxity. During the Knee Bend activity (Figure 2), minimal ( DISCUSSION This study demonstrates that similar knee kinematics in PS TKA can be achieved over a small range of sagittal conformities, when designs approach 1:1 conformity. More conforming medial geometries can lead to greater lateral LP motion, suggesting greater medial conformity is necessary to replicate normal knee kinematics. Further work could evaluate impact of other factors such as tibia slope, further refinement in conformity, and additional specimen sizes. For any figures or tables, please contact authors directly (see Info & Metrics tab above).
A Pyrrhic Victory? Bank Bailouts and Sovereign Credit Risk

We model a loop between sovereign and bank credit risk. A distressed financial sector induces government bailouts, whose cost increases sovereign credit risk. Increased sovereign credit risk in turn weakens the financial sector by eroding the value of its government guarantees and bond holdings. Using credit default swap (CDS) rates on European sovereigns and banks, we show that bailouts triggered the rise of sovereign credit risk in 2008. We document that post-bailout changes in sovereign CDS explain changes in bank CDS even after controlling for aggregate and bank-level determinants of credit spreads, confirming the sovereign-bank loop.
Have we finally bridged the digital divide? Smart phone and Internet use patterns by race and ethnicity

Two decades ago an influential article documented the alarming disparities that existed in access to computers and the Internet between African-Americans and whites (Hoffman and Novak, 1998). Using the latest U.S. Census Bureau/Bureau of Labor Statistics data on computer and Internet access, I find that the “digital divide” has not been bridged and remains as large as it was two decades ago. African-Americans and Latino-Americans are less likely to use the Internet on smart phones, computer, tablets or other devices than are whites. A statistical decomposition analysis reveals that income and education inequalities are the leading causes of the disparities in access to technology. The findings have implications for policies that subsidize broadband to low-income families.
Bank Lending Standards and Borrower Accounting Conservatism

Bank lending standards vary over time. Periods in which firms find it relatively easy to borrow are followed by periods in which banks scrutinize borrowers more and tighten lending. We predict that...
Spinal Stereotactic Body Radiotherapy in the United States: A Decade-Long Nationwide Analysis of Patient Demographics, Practice Patterns, and Trends Over Time

Abstract Nationwide utilization of spinal stereotactic body radiotherapy (SBRT) is not known; to address this void, the National Cancer Data Base (NCDB) from 2004 to 2013 was used for analysis. Spinal SBRT was defined as 1–5 fractions (14–32 Gy) delivered to the cervical, thoracic, lumbar or sacral spine. From 2004 to 2013, 1044 patients received spinal SBRT, most commonly in single-fraction (38%), three-fraction (26%) and five-fractions (25%). Metastatic spinal disease most commonly originated from the lung (34%), kidney (14%), and blood (9%). The most common insurance status receiving spinal SBRT was private (44%) followed by Medicare (43%), with Medicaid (8%) a distant third. Fifty-six percent of patients were male, and 55% of patients were younger than age 65. 80% of patients were Caucasian, with 13% being African-American. The vast majority (74%) of patients had no Charlson/Deyo comorbidities. The incidence of spinal SBRT gradually increased over time, rising from 2% to 20% of cases from 2004 to 2013. Comprising only 1.4% of spinal metastases radiation in 2004, SBRT rose to a 5.8% share in 2013. In conclusion, SBRT for spine metastases in the United States has more than quadrupled in utilization over a recent ten-year span. Although the majority of spinal SBRT is multi-fraction, the most popular fractionation scheme was single-fraction. It has been most commonly used for Caucasian men under age 65 with private/Medicare insurance and no comorbidities. By far the most common origin of spinal metastases treated by SBRT was the lung, followed by renal cancer. These results provide a baseline for further prospective investigation.
Art and Territoriality in the Lower Pecos Archaic

The approximate prehistoric territorial limits of an Archaic belief system in the lower Pecos area of Texas is hypothesized on the basis of the geographic distribution of a distinctive pictograph s...
Should Local Governments be Included in the Constitution? A Comparative Analysis Between the U.S. and Brazilian Supreme Courts’ Reasoning Regarding Annexation Laws

Annexation of local governments is a contentious topic. Litigation of annexation often addresses important constitutional provisions, such as property rights, federalism, limitations to police powers, equality and, more specifically, the Voting Rights Act. The United States Constitution is famously silent about local governments. In light of this omission and considering individual constitutional rights, would it make a difference to have local governments in the constitutional text? And to whom would it matter the most? This research developed an original dataset to answer those questions. This article focuses on annexation as proxy for local powers, and it compares the U.S. federalism scheme with the Brazilian unprecedented experience of leveling local governments alongside the states and the federal union in the Constitution of 1988. This research is unique in its comparison of the reasoning of the U.S. Supreme Court (U.S.S.C.) and its Brazilian counterpart, the Supremo Tribunal Federal (S.T.F.), with regard to annexation laws. The main contributions of this study to the literature are straightforward. First, it advances the literature on constitutional design by focusing on local governments, instead of states and the federal union. Second, and related to such an advancement, this paper departs from traditional federalism comparisons which were restricted to developed countries. Third, this research provides evidence contradicting previous claims that the U.S. constitutional omission of local governments was a failure of constitutional design relating to future matters. In addition, this study analyzes the consequences of the Brazilian constitutional design. This article concludes that there is no evidence supporting the proposition that the inclusion of municipalities as federal actors is necessarily superior to the current comparative trend that uses the dual spheres system of the U.S. federalism as a paradigm. Therefore, this research leads to unexpected results and provides evidence that contradicts the understanding of the U.S. constitutional omission of local governments as a failure of constitutional design.
Aggregated Royalties for Top-Down FRAND Determinations: Revisiting “Joint Negotiation”

In an environment in which widely adopted technical standards may each be covered by large numbers of patents, there have been increasing calls for courts to determine “fair, reasonable, and nondiscriminatory” (FRAND) royalties payable to holders of standards-essential patents (SEPs) using “top-down” methodologies. Top-down royalty approaches begin with the aggregate royalty that should be payable with respect to all SEPs covering a particular standard, and then allocate a portion of the total to individual SEPs. Top-down approaches avoid many drawbacks associated with bottom-up approaches in which royalties for individual SEPs are assessed, often in an inconsistent and piecemeal manner, without regard for the other SEPs that cover the standard. Yet despite the potential benefits of top-down methodologies, one of the most promising means for determining aggregate royalty levels—joint agreement by the members of the relevant standards-development organization (SDO)—has gained little traction. The idea of S...