cssi/SciSciGPT-SciSciNet huggingface dataset:
Sandbox Prefetching: Safe run-time evaluation of aggressive prefetchers

Memory latency is a major factor in limiting CPU performance, and prefetching is a well-known method for hiding memory latency. Overly aggressive prefetching can waste scarce resources such as memory bandwidth and cache capacity, limiting or even hurting performance. It is therefore important to employ prefetching mechanisms that use these resources prudently, while still prefetching required data in a timely manner. In this work, we propose a new mechanism to determine at run-time the appropriate prefetching mechanism for the currently executing program, called Sandbox Prefetching. Sandbox Prefetching evaluates simple, aggressive offset prefetchers at run-time by adding the prefetch address to a Bloom filter, rather than actually fetching the data into the cache. Subsequent cache accesses are tested against the contents of the Bloom filter to see if the aggressive prefetcher under evaluation could have accurately prefetched the data, while simultaneously testing for the existence of prefetchable streams. Real prefetches are performed when the accuracy of evaluated prefetchers exceeds a threshold. This method combines the ideas of global pattern confirmation and immediate prefetching action to achieve high performance. Sandbox Prefetching improves performance across the tested workloads by 47.6% compared to not using any prefetching, and by 18.7% compared to the Feedback Directed Prefetching technique. Performance is also improved by 1.4% compared to the Access Map Pattern Matching Prefetcher, while incurring considerably less logic and storage overheads.
Arab American Persons' Reported Experiences of Discrimination and Mental Health: The Mediating Role of Personal Control

Reports of prejudice and discrimination against Arab Americans have increased since the events of September 11, 2001 (I. Ibish, 2003). Perceived prejudice events are recognized as stressors that are linked to lowered mental health for those who experience such events (e.g., R. Clark, N. B. Anderson, V. R. Clark, & D. R. Williams, 1999; E. A. Klonoff & H. Landrine, 1995; H. Landrine & E. A. Klonoff, 1996; S. O. Utsey & J. G. Ponterotto, 1996). Thus, this study examined, with a sample of 108 Arab American individuals, (a) the relationship of reported discrimination experiences to self-esteem and psychological distress and (b) the mediating role of sense of personal control in this relationship. Consistent with hypotheses, results of path analyses indicated that sense of personal control mediated fully the link of reported discrimination experiences to self-esteem and mediated partially the link of reported discrimination experiences to psychological distress. The path models accounted for 47%-48% of the variance in self-esteem and 33% of the variance in psychological distress.
Approximations for a Three Dimensional Scan Statistic

Let X ijk ,1 ≤ i ≤ N 1,1 ≤ j ≤ N 2, 1 ≤ k ≤ N 3 be a sequence of independent and identically distributed 0 − 1 Bernoulli trials. X ijk = 1 if an event has occurred at the i,j,k th location in a three dimensional rectangular region and X ijk = 0, otherwise. For 2 ≤ m j ≤ N j − 1,1 ≤ j ≤ 3, a three dimensional discrete scan statistic is defined as the maximum number of events in any m 1×m 2×m 3 rectangular sub-region in the entire N 1×N 2×N 3 rectangular region. In this article, a product-type approximation and three Poisson approximations are derived for the distribution of this three dimensional scan statistic. Numerical results are presented to evaluate the accuracy of these approximations and their use in testing for randomness.
The Limited Effects of Election Reforms on Trust, Efficacy and Engagement

Rules governing the conduct of elections have important consequences for democratic politics, and much can be learned from studying changes in electoral rules. Instances of change (or reform) allow us the possibility of examining how (or whether) new rules might create different outcomes. We begin with a discussion of how electoral reform might occur. We then consider the effects of two major changes in electoral rules - the adoption of proportional representation and the adoption of legislative term limits. We do this to assess whether these reforms have affected efficacy, trust, and voter participation. We suggest that reform efforts such as these may have only minimal effects on engaging citizens with politics.
Fault simulation with test switching for static test compaction

Static test compaction procedures reduce the number of tests in a given test set without reducing the fault coverage. Static test compaction procedures can use the set or the number of faults detected by each test as guidance. Fault simulation without or with limited fault dropping is needed for producing this information. However, it can be time consuming. To compute the information needed for guiding static test compaction efficiently, this paper describes a fault simulation procedure with fault dropping that attempts to balance the sizes of the sets of detected faults. This is achieved by switching the test being simulated as soon as it detects a fault. Differences in the numbers of detected faults, in spite of the attempt to balance them, is attributed to the relative effectiveness of the tests in detecting target faults. The paper shows that reordering a test set based on the results of fault simulation with test switching is effective when applied prior to forward-looking reverse order fault simulation. In general, the procedure can be used in applications where it is advantageous to balance the sets of detected faults.
Effects of purified gonadotrophins on the cholesterol content of the testes of immature rats.

IN A recent study (Tepperman and Tepperman, 1947) it was found that the treatment of immature rats with a commercial gonadotrophin of pituitary origin (Gonadophysin) resulted in an accumulation of cholesterol ester in the testis. Chorionic gonadotrophin (CG) had no such effect, but, in animals primed with Gonadophysin, treatment with chorionic gonadotrophin resulted in a diminution in testis cholesterol ester associated with a marked enhancement of androgen output. Since Gonadophysin produced a marked increase in testis weight and comparatively small changes in seminal vesical weight, it was regarded as predominantly FSH. Chorionic gonadotrophin powerfully stimulated androgen production and the authors, in common with other workers (for example, see Burrows, 1949) believed that the terms “chlorionic gonadotrophin,” “LH,” and “ICSH” were virtually interchangeable designations in the male animal. The design of, the studies reported in 1947, then, was based on these evaluations of the only preparations avail...
Observations on chemotherapy and immunization of birds against psittacosis.

The incidence of psittacosis infection in most captive parrot collections is at present unknown; unfortunately, the trained per­ sonnel and funds needed to perform the necessary serologie and isolation tests that would yield this information are for the most part not available. For this reason an effort had been made to develop a chemotherapeutic regimen for the treatment of all individuals in a given collection of psittacine birds on a combined therapeutic-prophylac­ tic basis, even in the absence of preliminary diagnostic tests.
A concept for quantifying equivalent initial flaw size distribution in fracture mechanics based life prediction models

A stochastic regression analysis technique for the prediction of equivalent initial flaw size (EIFS) distributions based on crack size against time data is presented. This technique correctly accounts for the variability of multiple crack growth drivers to enable a data set independent EIFS distribution. A numerical example illustrates the accuracy of the predicted EIFS distribution in the presence of noise in the crack growth rate data, and shows the applicability of the developed stochastic regression analysis technique to small data sets with large scatter.
A combined pseudoreplica-immunochemical technique for research and diagnostic virology.

Pseudoreplica and immunochemical techniques were combined in a single protocol for identification of virus in research and clinical specimens. Stock preparations of vesicular stomatitis virus (VSV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were used to develop the technique. Traditional pseudoreplicas of viral stock solutions were prepared but not negatively stained. The virus was then immunolabeled in two stages. Virus-specific polyclonal antisera were used in the first stage; colloidal gold congugated antibodies were used as indicator antibody in the second stage. After immunolabeling, the grids were negatigvely stained. As a demonstration of the clinical usefulness of this approach, it was employed to antenatally identify human parvovirus B19 particles in ascites from a 22 week gestational fetus with nonimmune hydrops fetalis. The combined pseudoreplica-immunochemical approach offers several advantages over both the pseudoreplica and immunochemical methods when used in isolation. Advantages include relative purification of samples, concentration of virus, morphological preservation, and enhanced diagnostic specificity.
The Acquisition of Automation Subject to Diminishing Returns

Abstract In this paper, it is assumed that the purchase of automation has the effect of reducing the per unit production and in-process inventory costs. The optimal dynamic mix of automation and manual output is derived to minimize the cost incurred over the planning horizon due to (1) deviating from the future goal levels of output, (2) production, (3) inventory, (4) changing the level of manual output, and (5) acquiring automation. The cost of purchasing automation and the effectiveness of automation on reducing the per unit. production and in-process inventory costs are expressed as functions of time to include the impact of learning or anticipated technological advancement. Furthermore, the effectiveness of automation on reducing the per unit production and in-process inventory costs is assumed to decrease as the level of automation held by the organization increases due to diminishing returns. We show that it is rarely optimal to increase automation without simultaneously modifying the level of manua...
Investigating the Supernatural: From Spiritism and Occultism to Psychical Research and Metapsychics in France, 1853--1931

Issues regarding allegedly supernatural events have provided fodder for debate and conversation over many generations. However, in the middle of the nineteenth century a new wave of interest result...
Photochemical formation and cleavage of C-N bond.

A new photochemical method of C–N bond formation has been developed. A properly substituted trityl alcohol can cleave the benzylic C–O bond and replace it with a C–N bond which is stable under the irradiation conditions. The C–N bond can then be photochemically cleaved with the same light source when the nitrogen is protonated.
A model of binding on DNA microarrays: understanding the combined effect of probe synthesis failure, cross-hybridization, DNA fragmentation and other experimental details of affymetrix arrays

DNA microarrays are used both for research and for diagnostics. In research, Affymetrix arrays are commonly used for genome wide association studies, resequencing, and for gene expression analysis. These arrays provide large amounts of data. This data is analyzed using statistical methods that quite often discard a large portion of the information. Most of the information that is lost comes from probes that systematically fail across chips and from batch effects. The aim of this study was to develop a comprehensive model for hybridization that predicts probe intensities for Affymetrix arrays and that could provide a basis for improved microarray analysis and probe development. The first part of the model calculates probe binding affinities to all the possible targets in the hybridization solution using the Langmuir isotherm. In the second part of the model we integrate details that are specific to each experiment and contribute to the differences between hybridization in solution and on the microarray. These details include fragmentation, wash stringency, temperature, salt concentration, and scanner settings. Furthermore, the model fits probe synthesis efficiency and target concentration parameters directly to the data. All the parameters used in the model have a well-established physical origin. For the 302 chips that were analyzed the mean correlation between expected and observed probe intensities was 0.701 with a range of 0.88 to 0.55. All available chips were included in the analysis regardless of the data quality. Our results show that batch effects arise from differences in probe synthesis, scanner settings, wash strength, and target fragmentation. We also show that probe synthesis efficiencies for different nucleotides are not uniform. To date this is the most complete model for binding on microarrays. This is the first model that includes both probe synthesis efficiency and hybridization kinetics/cross-hybridization. These two factors are sequence dependent and have a large impact on probe intensity. The results presented here provide novel insight into the effect of probe synthesis errors on Affymetrix microarrays; furthermore, the algorithms developed in this work provide useful tools for the analysis of cross-hybridization, probe synthesis efficiency, fragmentation, wash stringency, temperature, and salt concentration on microarray intensities.
The Role of Self-Referent and Other-Referent Knowledge in Perceptions of Group Characteristics

Research on social projection shows that perceptions of group characteristics depend, in part, on people’s perceptions of themselves. According to the principles of inductive reasoning, however, knowledge of other individual group members should also predict perceptions of the group. The present studies directly compared the use of self- and other-referent knowledge. In Study 1, self-judgments predicted group judgments better than judgments about a familiar other person did. When differences in the accessibility and stability of self-referent and other-referent knowledge were controlled, the predictive advantage of self-referent knowledge disappeared. In Study 2, the other person was present during assessment (i.e., visually salient) and other judgments predicted group judgments as well as self-judgments did. Changes in social categorization, however, instead of increases in the individuation of the other person accounted for this finding. It is concluded that projection is best understood as an egocentri...
Cyclo(valine-valine) inhibits Vibrio cholerae virulence gene expression.

Vibrio cholerae has been shown to produce a cyclic dipeptide, cyclo(phenylalanine–proline) (cFP), that functions to repress virulence factor production. The objective of this study was to determine if heterologous cyclic dipeptides could repress V. cholerae virulence factor production. To that end, three synthetic cyclic dipeptides that differed in their side chains from cFP were assayed for virulence inhibitory activity in V. cholerae. The results revealed that cyclo(valine–valine) (cVV) inhibited virulence factor production by a ToxR-dependent process that resulted in the repression of the virulence regulator aphA. cVV-dependent repression of aphA was found to be independent of known aphA regulatory genes. The results demonstrated that V. cholerae was able to respond to exogenous cyclic dipeptides and implicated the hydrophobic amino acid side chains on both arms of the cyclo dipeptide scaffold as structural requirements for inhibitory activity. The results further suggest that cyclic dipeptides have potential as therapeutics for cholera treatment.
Queueing analysis of a server node in transaction processing middleware systems

Quantitative performance modeling of complex information systems is of immense importance for designing enterprise e-business infrastructures and applications. In this paper, we present a traffic model of a server node in a typical transaction processing middleware system as well as a quantitative framework to model and analyze its performance. A multi-class open queueing network model is presented in which multi-class jobs are admitted to a number of server processes sharing hardware resources including the CPU and the disk. We have developed a viable approximation method, which decomposes the dependent components into their independent counterparts while preserving their relevant characteristics. We have conducted queueing-theoretic delay analyses and verified the approach using simulation. Results demonstrate the strength of our approach in predicting delays, elapsed times and other system performance measures.
Thinking About Evolution in Terms of Cellular Computing

The past five decades of molecular genetics have produced many discoveries about genome structure and function that can only be understood from an informatic perspective: --- distinct sequence codes to mark the individual steps in packaging, expression, replication, transmission, repair and restructuring of DNA molecules; --- modularity of data files for RNA and protein products; --- combinatoric organization of signals to format the genome for differential functioning during cellular and organismal cycles; --- direct participation of DNA in the execution of biological algorithms (formation of highly structured nucleoprotein complexes); --- hierarchical organization of genomic subsystems to form higher level system architectures. This review will discuss aspects of genome organization and genome change that require a more formal computational analysis. We will see how modern results indicate that genome evolution has many similarities to computer system engineering. The ability of cells to control the function of natural genetic engineering systems is central to the genome's potential as a Read---Write information storage system.
The availability of enriched stable isotopes: Present status and future prospects

Abstract The ORNL Electromagnetic Isotopic Enrichment Facility (EMIEF) has the foremost capability in the world for large-scale enrichment of stable isotopes. Despite the importance of these isotopes in research and medical applications, the funding levels for EMIEF operation since 1982 have decreased significantly, forcing operation at rates far below replacement of isotopes sold or loaned. The availability of enriched stable isotopes is presented, along with a summary of EMIEF User Group concerns and activities.
Spontaneous isolated superior mesenteric artery dissection: a case report and literature review with management algorithm.

Background An isolated spontaneous superior mesenteric artery (SMA) dissection is the most frequent type of digestive artery dissection. Hepatic, splenic, left gastric, and celiac artery dissections are much less frequently observed. Dissection of the SMA is usually an extension of an aortic dissection. A true isolated SMA dissection is a relatively rare clinical cause of abdominal pathology. Only 106 cases (including the present case) of isolated spontaneous SMA dissection without associated aortic dissection were identified from the literature. Methods Our vascular team managed a 56-year-old woman with spontaneous SMA dissection conservatively. Prior to the initiation of systemic anticoagulation, she underwent diagnostic laparoscopy. A repeat angiogram done at 2 months showed complete resolution of the dissection. She has been repeatedly examined for 5 years, which is the longest follow-up mentioned in the literature. Conclusion To our knowledge, this is the first case wherein laparoscopy was used to confirm the absence of mesenteric ischemia in acute presentation of SMA dissection. Using information from a review of the literature, we have designed a management protocol for this rare condition.
The nonlinear limit-point/limit-circle problem

Problem limit-point/limit-circle byl formulovan v roce 1910 H.Weylem. V minulem stoleti inspiroval několik nových směrů v asymptoticke analýze nelinearnich diferencialnich rovnic.Kniha zacina studiem problemu v linearnim připadě, jak byl H.Weylem původně formulovan. Pokracuje zobecněnim na nelinearni rovnice vyssich řadů. Jsou studovany vztahy mezi vlastnosti limit-point/limit-circle a ohranicenosti, oscilaci a konvergenci k nule řeseni.Vztah mezi problemem limit-point/limit-circle a spektralni teorii je podrobně studovan.
Interactive Soft Tissue Deformation Simulation Using Physically Based Modeling

This paper presents a study on physically based modeling and simulation of soft tissue deformation, with the goal of producing realistic, real-time effects during the simulation. We consider soft tissue deformation as a solid mechanics problem with a linear elastic constitutive law. A point collocation based meshfree method is employed to solve the governing equations. To achieve real-time performance, an octree data structure is used to organize the support sets and the nodes to expedite the computation in the meshfree method. The developed system brings together the surface representation for visualization and meshfree modeling for physically based animation to set up a virtual reality environment for soft tissue surgery simulation.Copyright © 2006 by ASME
IJDL special issue on complex digital objects: Guest editors' introduction

Although the Web of today looks very different from the Web of 10 years ago, digital library (DL) file formats still look much the same. Using terminology from the Open Archival Information System (OAIS), the submission information packages (SIPs) and archival information packages (AIPs) were frequently the same application specific formats of the dissemination information packages (DIPs). Driven by the proliferation of enabling technologies such as XML, Resource Description Format (RDF) and Dublin Core, there has been increasing interest in the DL community to use complex digital objects: objects that aggregate data, metadata and sometimes services into a single, logical digital entity. For example, instead of just a bare PDF file, a complex object could aggregate the PDF, the descriptive metadata (perhaps in multiple formats), provenance and rights statements and links to format conversion services. While the end-user continues to receive the PDF, DLs would ingest and exchange the complex digital object, building extended services based on the additional encapsulated and aggregated data. In much the same way that metadata formats arise from different communities, so have complex digital objects. In the realm of scientific and high-performance computing, data formats such as NetCDF [1], HDF [2], SmartFiles [3] and ELFS [4] have been in widespread use. In the commercial content provider industry, complex objects can be traced to the persistent stores of object-oriented databases
Ultrasonic-sensor deployment strategies and use of smartphone sensors for mobile robot navigation in indoor environment

This paper presents deployment strategies of ultrasonic sensors and a way of using Smartphone sensors to help mobile robot navigation in indoor environments. There are critical needs for cost-effective, reliable, and fairly accurate solutions to meet the demands of indoor robotic applications. Ultrasonic sensors have been popular in detecting simple objects due to the low-cost and simplicity despite their limitations. We propose an efficient way of deployment of ultrasonic sensors for low-cost mobile robots. A Smartphone has many high performance sensors that can be utilized to navigate and localize mobile robots. The sensors include a camera, a gyroscope, and an accelerometer. We analyzed the use of orientation sensor of a Smartphone and compared its performance to a conventional approach. The comparison results were promising. The combination of the efficient way of the sensor deployment and the use of Smartphone sensors shows a possibility of developing a low-cost indoor mobile robotics platform for college education and robotics research laboratories.
Soybean root distribution, top growth and yield responses to ambient ozone and soil moisture stress when grown in soil columns in greenhouses.

Abstract Soybeans ( Glycine max. cv. Williams) were grown to maturity in soil columns within polyvinyl pipe and placed in greenhouses with charcoal filtered (CF) and nonfiltered (NF) air. In each greenhouse plants were grown with and without soil moisture stress (SMS). Targeted soil water potentials at 0·25 m for no SMS and between 0·45 and 0·60 m for the SMS regime were −0·05 and −0·45 M Pa, respectively. The 7 h (1000–1700 h EDT) mean O 3 concentrations (June–October) were 0·039 and 0·009 ppm in NF and CF air, respectively. Ozone and SMS in combination were less than additive in their effects on growth of the plant top and bean yields. Plants in CF air had 70% greater top weight, 58% more bean yield and 43% more root dry weight than in NF air. Both the plant and the seed weight from plants without SMS weighed 35% more than with SMS. Total root length in CF air for plants with and without SMS averaged 1·84 and 1·98 km, respectively, as compared to 1·59 and 1·66 km for plants with and without SMS in NF air. The resultsare different, so far as the combined effects of O 3 and SMS on yield and root growth are concerned, than in a similar field study by Heggestad and co-workers primarily because of the presence of a water table in the field but absence of it in the columns, as planned, in this experiment. It is unique to use large soil columns to study root distribution and length as related to the effects of ambient O 3 alone, and its combination with SMS.
Theoretical Evaluation of a Patient-Artificial Kidney System Using the Kiil Dialyzer.

Abstract A mathematical model of the patient-artificial kidney system has been developed that can accurately predict body chemical distribution changes during hemodialysis—over a wide range of system parameters—for urea and creatinine. This article validates the model by using considerable amounts of clinical data from two selected patients and data from only a single dialysis from ten randomly chosen patients. The validated model was used to predict the fraction removed during dialysis of the total amount of urea and creatinine in the body. These data were plotted as a function of: (1) blood-flow rate; (2) length of dialysis; (3) initial blood concentrations; and (4) patient weights. In the vast majority of patients undergoing hemodialysis today with the Kiil Dialyzer, end-dialysis blood concentrations, as well as the amounts of material removed during dialysis, may be accurately predicted. Only the weight of the patient and his blood-flow rate into the dialyzer must be known to accomplish this prediction, since the current treatment result is dialyzer limited (dependent only on the dialyzer parameters).
Local excision and postoperative radiation therapy for rectal adenocarcinoma.

Sixty-seven patients with early-stage adenocarcinoma of the rectum who had lesions thought to be unsuitable for either local excision alone or endocavitary irradiation were treated with local excision followed by postoperative radiation therapy. The purpose of this study was to evaluate the effectiveness of local excision followed by radiation therapy for treatment of rectal adenocarcinoma. The patients were treated between 1974 and 1999; follow-up time was 6 to 273 months (median, 65 months). All living patients had follow-up for at least 2 years. The indications for postoperative irradiation included equivocal or positive margins, invasion of the muscularis propria, endothelial-lined space invasion, poorly differentiated histology, and perineural invasion. Cox proportional hazards regression analysis was performed using six explanatory variables including tumor size, configuration (exophytic vs. ulcerative), histologic differentiation, pathologic T stage, endothelial-lined space invasion, and margin status. The time interval between treatment and development of recurrent disease was in the range of 11 to 48 months. The 5-year results were as follows: local-regional control, 86%; ultimate local-regional control, 93%; distant metastasis-free survival, 93%; absolute survival, 80%; and cause-specific survival, 90%. When the Cox proportional hazards regression analysis was performed for these endpoints, margin status influenced absolute survival (P = 0.0074), cause-specific survival (P = 0.0405), and ultimate local-regional control (P = 0.0439). Tumor configuration marginally influenced cause-specific survival (P = 0.0577). None of the variables had an influence on the endpoints' local-regional control, ultimate local-regional control with sphincter preservation, or distant metastasis. Five patients (7%) had severe complications; no complication was fatal. Local excision and postoperative radiation therapy results in a high probability of local-regional control and survival for selected patients with relatively early-stage rectal adenocarcinoma. Patients with ulcerative tumors may have a lower likelihood of cause-specific survival.
Developing an Evaluation Tool for Assessing Clinical Ethics Consultation Skills in Simulation Based Education: The ACES Project

The American Society for Bioethics and Humanities has created a quality attestation (QA) process for clinical ethics consultants; the pilot phase of reviewing portfolios has begun. One aspect of the QA process which is particularly challenging is assessing the interpersonal skills of individual clinical ethics consultants. We propose that using case simulation to evaluate clinical ethics consultants is an approach that can meet this need provided clear standards for assessment are identified. To this end, we developed the Assessing Clinical Ethics Skills (ACES) tool, which identifies and specifies specific behaviors that a clinical ethics consultant should demonstrate in an ethics case simulation. The aim is for the clinical ethics consultant or student to use a videotaped case simulation, along with the ACES tool scored by a trained rater, to demonstrate their competence as part of their QA portfolio. The development and piloting of the tool is described.
Examination of Immune Competence in Breast Cancer Patients at Six Months Post Surgery and Adjuvant Therapy through Assessment of T Cell and Dendritic Cell Functionality.

It has long been known that immune suppression is induced by the presence of a tumor, resulting in compromised T cell and dendritic cell (DC) functionality. What is not well understood is how soon the immune system recovers normal functionality following surgical removal of tumors and adjuvant therapy. This timing is of critical importance, as the effectiveness of therapeutic immune strategies relies on optimal presentation of antigens and activation of T cells. Blood from breast cancer patients was collected prior to surgery and at 3 and 6 months post adjuvant therapy. Patients were treated with surgery (breast conservation or mastectomy) and chemotherapy (CT) (n=22) or surgery without chemotherapy (n=38). Most patients had radiation therapy (RT). Blood from 22 healthy woman of similar age served as controls. T cell functionality (TCF) was determined following stimulation with plate-bound anti-CD3 (1 µg/ml) and anti-CD28 (0.5 µg/ml) and proliferation was measured by 3 H-thymidine uptake. DC functionality (DCF) was determined by ability to present allo-antigens in a mixed lymphocyte reaction. Values for the normal samples determined the normal ranges (NR). Responses were grouped into 4 categories based on their status at 6 months: Group 1 - remained in NR; Group 2 - climbed into NR; Group 3 - remained below NR; Group 4 - fell below NR. Analysis of immunosuppression will be based on lymphocyte subsets, cytokine, COX-2, and PGE 2 metabolite levels.Forty-three percent of patients had normal levels (Groups 1 and 2) for TCF and 62% for DCF by 6 months post adjuvant therapy, suggesting that breast cancer patients are potentially amenable to vaccine therapy. 28% of patients had both TCF and DCF in NR; 50% had either TCF or DCF in NR; and 22% had neither in NR. The percentage of patients who had TCF in NR by adjuvant therapy was: 35% CT+RT (6/17); 33% CT (1/3); 52% (17/33) RT; and 20% (1/5) neither. The percentage of patients who had DCF in NR by adjuvant therapy was: 67% (10/15) CT+RT; 33% (1/3) CT; 67% (22/33) RT; and 40% (2/5) neither. Proper understanding of the effects of tumor, chemotherapy and radiation therapy on immune function, especially the effects on T cells and DCs, may enable us to identify the appropriate patients in whom to study immunotherapy approaches in women with early breast cancer and to examine strategies to counteract cancer-related defects in immune function. (supported by P50CA116201) Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4131.
Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells

Newborns are prone to microbial infection and have poor memory responses to multiple antigens. We have previously shown that human neonatal blood monocytes exhibit impaired TNF-α responses to most known TLR agonists, including the pure TLR7 agonist imiquimod. Surprisingly, however, neonatal TNF-α responses to the imiquimod congener R-848 (TLR 7/8) were fully intact. We now show that TLR8 agonists, including R-848 (TLR7/8), the imidazoquinoline congeners 3M-003 (TLR7/8) and 3M-002 (TLR8), as well as single-stranded viral RNAs (TLR8) induced robust production of the Th1-polarizing cytokines TNF-α and IL-12 from neonatal antigen-presenting cells (APCs) that substantially exceeds responses induced by TLR-2, -4, or -7 (alone) agonists. TLR8 agonists also effectively induced up-regulation of the costimulatory molecule CD40 on neonatal and adult myeloid dendritic cells (DCs). The strong activity of TLR8 agonists correlates with their induction of p38 MAP kinase phosphorylation and with degradation of IκB-α in both neonatal and adult monocytes. We conclude that TLR8 agonists are uniquely efficacious in activating costimulatory responses in neonatal APCs and suggest that these agents are promising candidate adjuvants for enhancing immune responses in human newborns.
Immunochemical and immunohistochemical studies of cadmium associated proteins in Rana tadpoles.

Abstract Previous observations suggested that Rana tadpoles treated with aqueous cadmium (Cd) accumulate Cd in their liver and mesonephros. In order to study the response to Cd in these tissues we (a) exposed tadpoles in mid-limb bud stages to sublethal quantities of Cd, (b) isolated Cd-associated protein (CAP) from a liver cytosol fraction, (c) prepared a heterologous rabbit antiserum against glutaraldehyde-treated CAP (G-CAP), (d) used the rabbit anti-G-CAP antiserum in order to assess the tissue distribution of CAP in Cd-treated and untreated tadpoles, and (e) assessed species crossreactivities of our anti-G-CAP with CAPs and metallothioneins (MTs) isolated from Cd-treated vertebrate liver cytosol fractions. We found that (a) CAP was present in higher quantities in liver cytosol obtained from Cd-treated tadpoles compared to liver cytosol obtained from untreated control tadpoles, (b) indirect immunofluorescent analysis revealed that CAP was localized in liver hepatocytes and kidney tubule epithelial cells in Cd-treated tadpoles, and (c) the anti-G-CAP crossreacted with rodent and fish CAP. These observations suggest that the developing liver and mesonephros are involved in responses to toxic metals and that our anti G-CAP antiserum may be used to gauge exposure to environmental Cd.
Assembly of the fertilization membrane of the sea urchin: Isolation of a divalent cation-dependent intermediate and its crosslinking in vitro

Abstract To analyze the mechanism of assembly of the fertilization membrane of the sea urchin Strongylocentrotus purpuratus, we inhibited the ovoperoxidase that catalyzes dityrosine formation to isolate an uncrosslinked, soft fertilization membrane (SFM). The SFM intermediates were stabilized by divalent cation-dependent interactions: in the absence of divalent cations, the SFM became amorphous and less refractile and released proteins into the surrounding medium. We term the remaining structures "wraiths." The rate of this disaggregation was increased in solutions of low ionic strength, but 510 mM divalent cations (Ca 2+ , Mg 2+ , Mn 2+ or Ba 2+ ) prevented disaggregation. Wraiths could be reassembled into structures that resembled SFM by readdition of divalent cations. The SFM contained active ovoperoxidase and could be hardened in vitro by washing away the ovoperoxidase inhibitor and adding H 2 O 2 . After hardening, certain proteins of over 100 kd were excluded from SDS-polyacrylamide gels, suggesting that these proteins contain the substrates for crosslinking. We propose that the SFM is a divalent cation-dependent intermediate on the pathway of fertilization membrane assembly containing tyrosyl residues that are appropriately juxtaposed for crosslinking.
Justifying Outcomes Versus Processes: Distributive and Procedural Justice Beliefs as Predictors of Positive and Negative Affectivity

System justifying beliefs can have adaptive consequences for individuals that include enhanced coping and decreased emotional distress. The present study examined whether individual differences in two kinds of system justifying beliefs uniquely predict dispositional affect. Participants from across the United States were recruited via internet to complete dispositional measures of procedural and distributive justice beliefs, and also brief measures of positive and negative affectivity. While belief in fair outcomes (distributive just world beliefs) was generally associated with greater positive affectivity, belief in fair processes (procedural just world beliefs) was modestly associated with decreased negative affectivity. In addition, positive and negative affectivity were predicted by interactions between procedural and distributive just world beliefs, with each accentuating the general emotional benefit provided by the other. Finally, an interactive effect of procedural just world beliefs and social class was obtained for positive affectivity, with greater positive affectivity occurring for disadvantaged (lower income) individuals who had strong procedural just world beliefs. In general, these results suggest the potential for unique and interactive relationships between particular system justifying beliefs and measures of emotion, especially among members of advantaged versus disadvantaged groups.
Autocrine CSF1R signaling mediates switching between invasion and proliferation downstream of TGFβ in claudin-low breast tumor cells

Patient data suggest that colony-stimulating factor-1 (CSF1) and its receptor (CSF1R) have critical roles during breast cancer progression. We have previously shown that in human breast tumors expressing both CSF1 and CSF1R, invasion in vivo is dependent both on a paracrine interaction with tumor-associated macrophages and an autocrine regulation of CSF1R in the tumor cells themselves. Although the role of the paracrine interaction between tumor cells and macrophages has been extensively studied, very little is known about the mechanism by which the autocrine CSF1R signaling contributes to tumor progression. We show here that breast cancer patients of the claudin-low subtype have significantly increased expression of CSF1R. Using a panel of breast cancer cell lines, we confirm that CSF1R expression is elevated and regulated by TGFβ specifically in claudin-low cell lines. Abrogation of autocrine CSF1R signaling in MDA-MB-231 xenografts (a claudin-low cell line) leads to increased tumor size by enhanced proliferation, but significantly reduced invasion, dissemination and metastasis. Indeed, we show that proliferation and invasion are oppositely regulated by CSF1R downstream of TGFβ only in claudin-low cell lines. Intravital multiphoton imaging revealed that inhibition of CSF1R in the tumor cells leads to decreased in vivo motility and a more cohesive morphology. We show that, both in vitro and in vivo, CSF1R inhibition results in a reversal of claudin-low marker expression by significant upregulation of luminal keratins and tight-junction proteins such as claudins. Finally, we show that artificial overexpression of claudins in MDA-MB-231 cells is sufficient to tip the cells from an invasive state to a proliferative state. Our results suggest that autocrine CSF1R signaling is essential in maintaining low claudin expression and that it mediates a switch between the proliferative and the invasive state in claudin-low tumor cells downstream of TGFβ.
Structure of the Eastern Seattle Fault Zone, Washington State: New Insights from Seismic Reflection Data

We identify and characterize the active Seattle fault zone (SFZ) east of Lake Washington with newly acquired seismic reflection data. Our results focus on structures observed in the upper 1 km below the cities of Bellevue, Sammamish, Newcastle, and Fall City, Washington. The SFZ appears as a broad zone of faulting and folding at the southern boundary of the Seattle basin and north edge of the Seattle uplift. We interpret the Seattle fault as a thrust fault that accommodates north–south shortening by forming a fault-propagation fold with a forelimb breakthrough. The blind tip of the main fault forms a synclinal growth fold (deformation front) that extends at least 8 km east of Vasa Park (west side of Lake Sammamish) and defines the south edge of the Seattle basin. South of the deformation front is the forelimb breakthrough fault, which was exposed in a trench at Vasa Park. The Newcastle Hills anticline, a broad anticline forming the north part of the Seattle uplift east of Lake Washington, is interpreted to lie between the main blind strand of the Seattle fault and a backthrust. Our profiles, on the northern limb of this anticline, consistently image north-dipping strata. A structural model for the SFZ east of Lake Washington is consistent with about 8 km of slip on the upper part of the Seattle fault, but the amount of motion is only loosely constrained.
Normal generalized selfadjoint operators in Krein spaces

Abstract A full description is given of n -selfadjoint normal operators in Krein spaces of finite defect, as well as in general Krein spaces. Both real and complex Krein spaces are considered.
Complement regulates inhalation tolerance at the dendritic cell/T cell interface

Pulmonary exposure to innocuous aeroallergens is a common event leading to inhalation tolerance. Distinct subsets of pulmonary dendritic cells (DC) and regulatory T cells (T(Reg)) play critical roles in mediating and maintaining such tolerance. In asthmatics, the same aeroallergens drive a maladaptive, Th2-biased immune response resulting in airway inflammation and airway hyper-reactivity. The mechanisms underlying the breakdown of inhalation tolerance, leading to the Th2-driven inflammation in rising numbers of asthmatic patients from industrialized countries remain elusive. The recent resurgence of interest in the role of the innate immune mediators in regulating adaptive immune response has sparked studies aimed at identifying the role of complement in allergic asthma. In this context, an unexpected role for the anaphylatoxin C5a receptor in allergic sensitization has been found. In models of experimental allergic asthma, ablation of C5aR signaling during initial allergen exposure either induced or enhanced Th2 sensitization. Mechanistically, C5aR signaling directly affected the function of distinct pulmonary DC subsets that induce or control allergen-induced adaptive immune responses. Signaling pathways downstream of C5 may also impact the function of T(Reg), as T(Reg) from C5 sufficient, but not from C5 deficient mice, suppress DC activation and subsequent development of Th2-driven inflammation. The emerging paradigm is that constitutive local generation of C5a and C5aR signaling in airway DCs controls inhalation tolerance directly as well as indirectly through sensitization of airway DCs for T(Reg)-mediated immunosuppression.
Complications of umbilical artery catheterization in a model of extreme prematurity

Umbilical artery catheter (UAC) use is common in the management of critically ill neonates; however, little information exists regarding the anatomic and vascular effects of UAC placement in premature newborns. Baboons were delivered at 125 days of gestation (term=185 days), treated with surfactant, had UACs placed and were ventilated for either 6 or 14 days. Animals were assigned to short-term (6 days, n=6) and long-term (14 days, n=30) UAC placement. At necropsy, aortas were removed with UACs still in place. Histological examination of upper, middle and lower aorta specimens stained with hematoxylin and eosin and immunolabeled to detect smooth muscle (α-actin) was carried out in a blinded manner. Controls were delivered at 125, 140 and 185 days and the aortas acquired immediately after birth. None of the non-catheterized control animals (125 days, n=4; 140 days, n=5; and 185 days, n=5) had aortic vessel thrombi or vascular wall abnormalities. All 6 animals with short-term (6/6, 100%) and 18 animals with long-term (18/30, 60%) UAC placement displayed aortic thrombi and neointimal proliferation of the vascular wall. The majority (60%) of analyzed animals with UAC placement displaying neointimal hyperplasia were immunopositive for α-actin, indicating the presence of smooth muscle in these lesions. Our findings suggest that both short- and long-term UAC use is associated with aortic wall pathological abnormalities compared with control animals. This study emphasizes the judicious use and early removal of UACs if possible in order to potentially prevent significant hemostatic and aortic wall vascular complications.
Toward exhaustive gating of flow cytometry data

Flow cytometry is a high-throughput technology that measures protein expressions at the single-cell level. A typical flow cytometry experiment on one biological sample provides measurements of several protein markers on or inside hundreds of thousands of individual cells in that sample. Analysis of such data often aims to identify subpopulations of cells with distinct phenotypes. Currently, the most widely used analysis in the flow cytometry community is manual gating on a sequence of biaxial plots, which is highly subjective and labor intensive. To address those issues, the majority of efforts in the literature have been devoted to automate the gating analysis using clustering algorithms. However, completely removing the subjectivity can be quite challenging. This paper describes an opposite approach. Instead of automating the analysis, we aim to develop novel visualizations to facilitate manual gating. The proposed method views a flow cytometry data of one biological sample as a high-dimensional point cloud of cells, derives the skeleton of the cloud, and unfolds the skeleton to generate a 2D visualization.
A new rapid microassay for enzymatic reactions involving glyoxylate

Abstract A rapid, microassay for enzymatic reactions involving glyoxylate is discussed. This assay is based on the quantitative determination of residual glyoxylate— 14 C following isolation by thin-layer chromatography.
Necessary and sufficient conditions for high-dimensional salient feature subset recovery

We consider recovering the salient feature subset for distinguishing between two probability models from i.i.d. samples. Identifying the salient set improves discrimination performance and reduces complexity. The focus in this work is on the high-dimensional regime where the number of variables d, the number of salient variables k and the number of samples n all grow. The definition of saliency is motivated by error exponents in a binary hypothesis test and is stated in terms of relative entropies. It is shown that if n grows faster than max{ck log((d-k)/k), exp(c′k)} for constants c, c′, then the error probability in selecting the salient set can be made arbitrarily small. Thus, n can be much smaller than d. The exponential rate of decay and converse theorems are also provided. An efficient and consistent algorithm is proposed when the distributions are graphical models which are Markov on trees.