cssi/SciSciGPT-SciSciNet huggingface dataset:
ADAMTS13 Expressed In Glioblastoma and Astrocytoma Cells Can Modulate Endothelial Cell Migration

ADAMTS13, the von Willebrand factor (vWF) cleaving protease, regulates platelet aggregation and microthrombi formation by cleaving high-molecular weight vWF multimers. It is expressed primarily in hepatic stellate cells, but is also found in endothelial cells. Recently, ADAMTS13 was reported to be expressed and regulated in astrocytes, microglial, neuroblastoma, and adult human brain endothelial cells. Previous in vitro studies by our group with human umbilical vein endothelial cells (HUVEC) showed that ADAMTS13 can promote angiogenesis via upregulating the secretion of VEGF and phosphorylation of VEGFR2, suggesting that ADAMTS13 may also be involved in physiological processes unrelated to vWF cleavage ( Lee, M., et al. Microvasc Res. 2012, 84, 109-115) . Herein, we report an additional possible role of ADAMTS13 secreted by brain tumor cells to modulate tumor cell angiogenesis. Using a human ADAMTS13 immunoassay, we detected ADAMTS13 in U-87 and LN-229 glioblastoma cell lysates, SW-1088 astrocytoma cell lysates, as well as in the supernatants of all cell lines (> 2.0 ng/mL). Co-incubation of U-87, LN-229, and SW-1088 tumor cell conditioned media with recombinant vWF indicated that brain tumor-secreted ADAMTS13 is biologically active in cleaving vWF multimers (measured by ELISA). Secretion of VEGF was upregulated in LN-229 and SW-1088 cell lines by ADAMTS13. 939 pg/mL and 674 pg/mL of VEGF were measured in LN-229 and SW-1088 cell lysates, respectively, after incubation with 100 ng/mL ADAMTS13. Incubation of LN-229 glioblastoma cells with 10 – 500 ng/mL rh-ADAMTS13 or 50 ng/mL VEGF165 did not affect tumor cell proliferation. No change in tumor cell proliferation was observed when LN-229 cells were incubated with a polyclonal antibody against ADAMTS13 in serum free media supplemented with 10 ng/mL ADAMTS13 or media supplemented with 5% FBS, suggesting that ADAMTS13 secreted by brain tumor cells may be involved in extracellular signaling of endothelial cells. Brain tumor cell secreted-ADAMTS13 induced HUVEC migration in a Matrigel invasion assay. Using a modified Boyden chamber fitted with a Matrigel-coated polycarbonate membrane, LN-229 glioblastoma cells increased HUVEC migration by 83%. LN-229 cells supplemented with 10 ng/mL ADAMTS13 further increased HUVEC migration by 190%, suggesting that tumor cell-secreted ADAMTS13 may modulate EC migration ([Fig. 1][1]). Combined with our previous findings suggesting that recombinant ADAMTS13 modulates EC angiogenesis, brain tumor-secreted ADAMTS13 may also be a regulator for tumor vasculature angiogenesis. ![Figure][2] Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes
The effect of biomass densification on structural sugar release and yield in biofuel feedstock and feedstock blends.

In this work, we examined the behavior of feedstock blends and the effect of a specific feedstock densification strategy (pelleting) on the release and yield of structural carbohydrates in a laboratory-scale dilute acid pretreatment (PT) and enzymatic hydrolysis (EH) assay. We report overall carbohydrate release and yield from the two-stage PT-EH assay for five single feedstocks (two corn stovers, miscanthus, switchgrass, and hybrid poplar) and three feedstock blends (corn stover-switchgrass, corn stover-switchgrass-miscanthus, and corn stover-switchgrass-hybrid poplar). We first examined the experimental results over time to establish the robustness of the PT-EH assay, which limits the precision of the experimental results. The use of two different control samples in the assay enabled us to identify (and correct for) a small bias in the EH portion of the combined assay for some runs. We then examined the effect of variable pretreatment reaction conditions (residence time, acid loading, and reactor temperature) on the conversion of a single feedstock (single-pass corn stover, CS-SP) in order to establish the range of pretreatment reaction conditions likely to provide optimal conversion data. Finally, we applied the assay to the 16 materials (8 feedstocks in 2 formats, loose and pelleted) over a more limited range of pretreatment experimental conditions. The four herbaceous feedstocks behaved similarly, while the hybrid poplar feedstock required higher pretreatment temperatures for optimal results. As expected, the yield data for three blended feedstocks were the average of the yield data for the individual feedstocks. The pelleting process appears to provide a slightly positive effect on overall total sugar yield.
Tablets and Tablet Apps: What Do Hotel Customers Want?

AbstractThis study aims to explore consumers’ preference whether to bring their own tablets or use those provided by hotels, their expectations of hotel tablet apps, and antecedents of their behavioral intention toward hotel tablet apps. This study applied an extended model of the unified theory of acceptance and use of technology to understand consumers’ perceptions of tablet apps. By surveying 1,034 customers, this study found the respondents were more likely to utilize some tablet app features over others and revealed five key antecedents of customers’ behavioral intentions toward hotel tablet apps. The findings will help operators make informed decisions to maximize the benefits of tablet technology investments. The theoretical framework of this study provides a benchmark for other researchers to further investigate this field.
Transcriptome analysis illuminates the nature of the intracellular interaction in a vertebrate-algal symbiosis.

Throughout the natural world, when different species form a close association, it is known as a symbiosis. One species can depend on another for food, defense against predators or even for reproduction. Corals, for example, incorporate single-celled algae into their own cells. The algae photosynthesize, harnessing energy from sunlight to make sugars and other molecules that also feed the coral cells. In return, corals protect the algae from the environment and provide them with the materials they need for photosynthesis. This type of relationship where one organism lives inside another species is called an endosymbiosis. In animals with a backbone, endosymbioses with a photosynthetic organism are rare. There is only one known example so far, which is between a green alga called Oophila amblystomatis and the spotted salamander, Ambystoma maculatum. The female spotted salamander deposits her eggs in pools of water, and algae enter the eggs, proliferate, and later invade tissues and cells of the developing embryos. However, it is not understood how similar the interaction between the alga and the salamander is to that in coral-algal symbioses, or whether it is rather more similar to a parasitic infection. Burns et al. now address this question by comparing salamander cells harboring algae to those that lacked algae. A technique called RNA-Seq was used to characterize the changes in gene activity that take place in both organisms during the endosymbiosis. The results show that algae inside salamander cells are stressed and they change the way in which they make energy. Instead of carrying out photosynthesis to produce food for the salamander host – as happens in coral-algal interactions – Oophila amblystomatis is fighting to adapt to its new environment and switches to a less efficient energy producing pathway known as fermentation. Burns et al. found that, in striking contrast to the alga, affected salamander cells do not show signs of stress. Instead several genes that are known to suppress immune responses against foreign invaders are expressed to high levels. This may explain how salamander cells are able to tolerate algae inside them. The next challenge is to understand how the alga enters salamander cells. The current work identified some potential routes of entry, and follow up studies are now needed to explore those possibilities.
From Non-minds to Minds: Biosemantics and the Tertium Quid

I present and evaluate the prospects of the biosemantic program, understood as a philosophical attempt to explain the mind’s origins by appealing to something that non-minded organisms and minded organisms have in common: representational capacity. I develop an analogy with ancient attempts to account for the origins of change, clarify the biosemantic program’s aims and methods, and then distinguish two importantly different forms of objection, a priori and a posteriori. I defend the biosemantic program from a priori objections on the grounds that the standard of explanation presupposed by them is inappropriate and leads to absurdities if consistently applied. Once the way is cleared of a priori objections, the success of biosemantics turns on the strength of a posteriori objections, that is, on the program’s empirical adequacy. Here, its prospects are less clear, but I offer reasons, by analogy with chemical combination and other everyday phenomena, to think that minded beings and their representational capacities might well have their origin and explanation in non-minded beings. An evolutionary origin and explanation of mind is plausible, at least as far as naturalistic accounts and explanations go.
Online Documentation and Social Construction

Designing and Writing Online Documentation: Help Files to Hypertext by William Horton is a valuable reference guide. This guide addresses designers and writers of various kinds of text that will appear in some fashion and for a variety of reasons on the display monitor of a computer. (The computer might also have a connection to a network.) This books presents the best of current research and commentary by experts from various fields about the subject of online documentation. I assume this is the opinion of all reviewers of this text. What I want to say in this commentary rests upon the assumption that this text belongs on your shelf.
Categorizing Cognitive Scales of Spatial Information

We investigate the relations between human cognitive scales and spatial information. To help organize spatial information, particularly around how humans perceive and interact with spaces around them, we explore the intersection of Kuhn’s (2012) spatial information taxonomy, and Montello (1993) spatial scale taxonomy. We discuss results and challenges while using this intersection to categorize phenomena from an earthquake case study.
Clinical Features of Non-arteritic Anterior Ischemic Optic Neuropathy

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is the most common type of ischemic optic neuropathy. It usually has classical clinical features which make it easy to diagnose.
Fourteenth-Century England, Medical Ethics, and the Plague

A look at the response of 14th Century England during the plague years provides a historical perspective of the attitude toward epidemics. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Kirlian photography material science, testing and ichnology

Until recently Kirlian photography was used primarily to record effects generated by the application of electrical energy to living tissue and preserving the attendant phenomena on light sensitive film (see Hyzer, 1974). The resulting patterns and colors were interpreted as symptomatic of the status of the parent organism in terms of its quality of life (Aaronson, 1974). The effects of the interaction between life processes and electricity were considered to be inexplicable in terms of established scientific principles; our research suggests that this pessimistic view may no longer be tenable.
Efficient Planning in Non-Gaussian Belief Spaces and Its Application to Robot Grasping

The limited nature of robot sensors make many important robotics problems partially observable. These problems may require the system to perform complex information-gathering operations. One approach to solving these problems is to create plans in belief-space, the space of probability distributions over the under-lying state of the system. The belief-space plan encodes a strategy for performing a task while gaining information as necessary. Most approaches to belief-space planning rely upon representing belief state in a particular way (typically as a Gaussian). Unfortunately, this can lead to large errors between the assumed density representation of belief state and the true belief state. This paper proposes a new sample-based approach to belief-space planning that has fixed computational complexity while allowing arbitrary implementations of Bayes filtering to be used to track belief state. The approach is illustrated in the context of a simple example and compared to a prior approach. Then, we propose an application of the technique to an instance of the grasp synthesis problem where a robot must simultaneously localize and grasp an object given initially uncertain object parameters by planning information-gathering behavior. Experimental results are presented that demonstrate the approach to be capable of actively localizing and grasping boxes that are presented to the robot in uncertain and hard-to-localize configurations.
Copula as a Measure of Affiliation in First Price Auctions

Estimating distribution of bidders' ex-ante valuation is an important structural parameter in corporate auctions design and setting the optimal reserve price. This parameter is unobserved to researcher as the observed bids are strategic response and at best is a monotonic function of bidders ex ante valuation. This paper presents a simple, copula based, two step semiparametric estimator for structural estimation of distributions of bidders' unobserved valuations in first price auctions. In the first step, the marginal distributions of "valuations" are non-parametrically estimated using the equilibrium distribution of bids. The second stage involves a simple maximum likelihood procedure to estimate the "copula" parameter which measures the association (affiliation) between the valuations. We apply our methodology to data from wildcat oil tract auctions. Wildcat auctions resembles a corporate auction where the target's value is highly uncertain and the market or industry provides a signal about the value of the target. The estimation and testing procedure rejects the hypothesis of independence of signals and opts for non-linear dependence structure in the tails of the distributions. This has important implications for auction choice and mechanism design. The methodology is well suited for corporate nance and market microstructure applications with general informational assumptions. The estimated optimal reserve price found to be much higher than the actual reserve price.
Empress Tree (Paulownia tomentosa Steud.)

The genus Paulownia, a member of the Bignoniaceae, is native to East Asia and has been introduced into Europe and North and South America. P. fortunei, P. kawakamii, P. taiwaniana, and P. tomentosa are the most common species. Common names for the genus include Empress tree, Royal paulownia, Royal Princess tree, Cotton tree, Kiri (Japan), and T’ung (China).
Modeling Self-Protective Behaviors Against Infectious Disease: Estimates of Prevalence Elasticity for Malaria

Vector-borne disease such as malaria, dengue, and diarrhea that are spread by vectors such as mosquitoes and flies are rife in the much of the developing world, potentially impacting more than two-third of the world's population. Economic epidemiology (EE) applies the economic methods originally designed to model market exchanges and adapts them to examine the "non-market" exchanges that underpin the development, spread, and control of infections and diseases. In Philipson's (2000) introduction to EE, he focuses on the critical role of private preventive behaviors in suggesting that public health interventions will be self-limiting. In adapting EE to explore its implications for vector-borne disease, Gersovitz and Hammer (2003) highlight the critical role of prevention and infection externalities and conclude that public intervention is critical. To address this ambiguity regarding the appropriate role for public health interventions, we present the first tests and measures of the relationship between the demand for prevention and disease prevalence, e.g., the prevalence elasticity of demand for prevention. Measuring prevalence elasticity is important because (1) changes in protective behaviors against infectious diseases will alter the rate of transmission and therefore affect the dynamics of disease; and (2) these behaviors involve economics costs, they affect the welfare of the affected population. This paper presents three empirical applications. The first combines data from four different sources to analyze the relationship between malaria prevalence and malaria prevention at the country level. The second and third use cross-sectional microeconomic datasets on malaria prevention and malaria prevalence in Ethiopia and India. These analyses provide consistent evidence supporting the predictions of economic epidemiology models for both malaria and diarrhea. The final part of the paper discusses some of the implications for research and policy.
Low-cost call type classification for contact center calls using partial transcripts.

Call type classification and topic classification for contact center calls using automatically generated transcripts is not yet widely available mainly due to the high cost and low accuracy of call-center grade automatic speech transcription. To address these challenges, we examine if using only partial conversations yields accuracy comparable to using the entire customer-agent conversations. We exploit two interesting characteristics of call center calls. First, contact center calls are highly scripted following prescribed steps, and the customers problem or request (i.e., the determinant of the call type) is typically stated in the beginning of a call. Thus, using only the beginning of calls may be sufficient to determine the call type. Second, agents often more clearly repeat or rephrase what customers said, thus it may be sufficient to process only agents’ speech. Our experiments with 1,677 customer calls show that two partial transcripts comprising only the agents utterances and the first 40 speaker turns actually produce slightly higher classification accuracy than a transcript set comprising the entire conversations. In addition, using partial conversations can significantly reduce the cost for speech transcription.
Types of Scoring Instruments Available

A myriad of scoring instruments exist for use in clinical research. Choosing the appropriate scoring instrument for a study is difficult and requires at least a basic understanding of the instruments available and the pros and cons of each. However, no single scoring instrument is capable of capturing all of the information from a well-designed study, and, thus, the instruments described in this chapter are regularly used in combination. New scoring instruments are constantly being developed. This chapter is meant to serve as an overview of the different types of scoring instruments that currently exist, with special attention devoted to reviewing the patient-reported outcome measures (PROMs) that have been recommended by the American Academy of Orthopaedic Surgeons (AAOS).
12 C(α,γ) 16 O Capture Cross Section Below 3.2 MeV

The $^{12}\mathrm{C}(\ensuremath{\alpha},\ensuremath{\gamma})^{16}\mathrm{O}$ capture cross section was measured for $\ensuremath{\alpha}$-particle energies between 1.86 MeV ($\ensuremath{\sigma}=1.1\ifmmode\pm\else\textpm\fi{}0.4$ nb) and 3.11 MeV ($\ensuremath{\sigma}=29\ifmmode\pm\else\textpm\fi{}4$ nb) using a pulsed $^{4}\mathrm{He}^{+}$ beam from the ORNL 6-MV Van de Graaff accelerator and a 23- by 30-cm NaI(Tl) crystal viewed by six matched, bialkali photomultiplier tubes. An upper limit was obtained for the capture cross section at ${E}_{\ensuremath{\alpha}}=1.6$ MeV. The over-all time resolution (full width at half maximum) of the system for 8-10-MeV pulses due to $\ensuremath{\gamma}$ rays is 2.7 nsec. Enriched (99.94%) $^{12}\mathrm{C}$ targets ranging in thickness from 98 to 178 \ensuremath{\mu}g/${\mathrm{cm}}^{2}$ were used. Pulses resulting from fast neutrons [from the $^{13}\mathrm{C}(\ensuremath{\alpha},n)^{16}\mathrm{O}$ reaction] interacting with the NaI(Tl) crystal were further separated from true $\ensuremath{\gamma}$ pulses through the use of a new technique based on rise-time distribution differences of the respective neutron- and $\ensuremath{\gamma}$-ray-produced pulses. The face of the crystal (shielded with a 10.2 cm thickness of $^{6}\mathrm{LiH}$) was 12.2 cm from the target. The astrophysical significance of this reaction in the helium-burning sequence of stellar nucleosynthesis is also discussed.
The TGFβ type I receptor TGFβRI functions as an inhibitor of BMP signaling in cartilage.

The type I TGFβ receptor TGFβRI (encoded by Tgfbr1) was ablated in cartilage. The resulting Tgfbr1 Col2 mice exhibited lethal chondrodysplasia. Similar defects were not seen in mice lacking the type II TGFβ receptor or SMADs 2 and 3, the intracellular mediators of canonical TGFβ signaling. However, we detected elevated BMP activity in Tgfbr1 Col2 mice. As previous studies showed that TGFβRI can physically interact with ACVRL1, a type I BMP receptor, we generated cartilage-specific Acvrl1 (Acvrl1 Col2 ) and Acvrl1/Tgfbr1 (Acvrl1/Tgfbr1 Col2 ) knockouts. Loss of ACVRL1 alone had no effect, but Acvrl1/Tgfbr1 Col2 mice exhibited a striking reversal of the chondrodysplasia seen in Tgfbr1 Col2 mice. Loss of TGFβRI led to a redistribution of the type II receptor ACTRIIB into ACVRL1/ACTRIIB complexes, which have high affinity for BMP9. Although BMP9 is not produced in cartilage, we detected BMP9 in the growth plate, most likely derived from the circulation. These findings demonstrate that the major function of TGFβRI in cartilage is not to transduce TGFβ signaling, but rather to antagonize BMP signaling mediated by ACVRL1.
Promoter hypermethylation of GPX3 as a predictor for chemoresistance and survival in head and neck cancer patients

6027 Background: Resistance of cancer cells to cisplatin and its analogues is the major limitation in clinical application of cisplatin-based chemotherapy. The mechanisms by which cancer cells deve...
Effect of adjunctive pimavanserin on suicidal ideation in patients with major depression: Analysis of the CLARITY study.

Abstract Background Up to 15% of patients with major depressive disorder (MDD) attempt suicide and up to 2% complete suicide. This was a post-hoc analysis aimed to evaluate the risk of suicide ideation and behavior associated with adjunctive pimavanserin treatment in adults with MDD. Methods CLARITY was a randomized, double-blind, placebo-controlled study in patients with MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). For this post-hoc analysis, the primary endpoint was mean change from baseline for HAMD item 3 (suicide). The incidence of suicidal ideation or behavior was also assessed from the Columbia-Suicide Severity Rating Scale (C-SSRS) and reports of adverse events. Results During Stage 1, LS mean change for HAMD Item 3 was reduced from baseline at each week with pimavanserin with a significant difference between pimavanserin and placebo at Week 3 (p=0.012, effect size: 0.431). At any post-baseline assessment, suicidal ideation on the C-SSRS was reported in 28 (18.1%) of patients with placebo and 9 (17.3%) with pimavanserin during Stage 1 and in 7 (20.7%) with placebo and 4 (13.8%) with pimavanserin during Stage 2. No events of suicidal behavior were observed with either placebo or pimavanserin. Limitations : The post hoc nature, exclusion of patients with any history of suicide from the primary study, and the small number of patients who demonstrated evidence of suicidal ideation. Conclusions Adjunctive pimavanserin was not associated with an increase in suicidal ideation in patients with MDD. Further study is needed to verify these results.
Brown, Norman, Biscuits, the Dole and Nodding Donkeys: Texas Politics, 1929–1932: Ed. and with an introduction by Rachel Ozanne, Austin: University of Texas Press, 480 pp., $45.00, ISBN 978-1477319451, Publication Date: October 2019

This old-fashioned, top-down political monograph covers gubernatorial—and, occasionally, presidential—politics in the Lone Star State during the worst years of the Great Depression. The title state...
Impaired renal function is an independent risk factor for complications after surgery for femoral neck fracture.

Background:The metabolic abnormalities that occur secondary to chronic kidney disease (CKD) increase the risk of femoral neck fractures compared to the general population. The purpose of this study...
Middle Arabian Littoral

The Arabian peninsula has been arid throughout the Holocene. However, in the middle Holocene a period of higher precipitation led to an expansion of grasslands and a consequent increase in both plant and animal populations. It was at this time that human groups began penetrating the Arabian peninsula and exploiting the ocean and coastal resources that figure prominently in the Early Arabian Littoral tradition. A return to a more contemporary climate took place during the Middle Arabian Littoral tradition. Grasslands were reduced, and settlement was largely restricted to a narrow coastal belt where good agricultural soils, a high water table, and ocean and coastal resources allowed sedentary communities to develop.
Primary cilia and autophagic dysfunction in Huntington’s disease

Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by a single-gene mutation: a CAG expansion in the huntingtin (HTT) gene that results in production of a mutated protein, mutant HTT, with a polyglutamine tail (polyQ-HTT). Although the molecular pathways of polyQ-HTT toxicity are not fully understood, because protein misfolding and aggregation are central features of HD, it has long been suspected that cellular housekeeping processes such as autophagy might be important to disease pathology. Indeed, multiple lines of research have identified abnormal autophagy in HD, characterized generally by increased autophagic induction and inefficient clearance of substrates. To date, the origin of autophagic dysfunction in HD remains unclear and the search for actors involved continues. To that end, recent studies have suggested a bidirectional relationship between autophagy and primary cilia, signaling organelles of most mammalian cells. Interestingly, primary cilia structure is defective in HD, suggesting a potential link between autophagic dysfunction, primary cilia and HD pathogenesis. In addition, because polyQ-HTT also accumulates in primary cilia, the possibility exists that primary cilia might play additional roles in HD: perhaps by disrupting signaling pathways or acting as a reservoir for secretion and propagation of toxic, misfolded polyQ-HTT fragments. Here, we review recent research suggesting potential links between autophagy, primary cilia and HD and speculate on possible pathogenic mechanisms and future directions for the field.
Parameters Effecting 2D Barcode Scanning Reliability

Abstract This paper describes a case study to identify the various parameters that affect the scanning reliability of 2D barcodes for high content density applications. A review of the numerous options for 2D symbologies showed that, in theory, these symbologies are capable of encoding relatively large amounts of data, but in practice, barcode scan-ability decreases as the encoded content increases. With specific attention to higher content (or capacity) applications, a case study was performed to identify the 2D symbologies with the highest scanning reliability, to be termed “scan-ability,” as well as the various parameters that impact this scan-ability. The paper is divided into four logical sections. The introduction section covers the goal and the specific requirements of the project. Section 2 discusses in detail the various parameters that impact the scan reliability of high-capacity 2D barcodes. Section 3 focuses on the testing methodology employed and Section 4 summarizes the conclusions of the detailed testing. Based on our requirements, our findings indicated that the best three scan reliability measurements of 96%–99% were all obtained using the PDF417 symbology with different media types and scanners.
Herpes Simplex Virus Type 2 Functions Expressed During Stimulation of Human Cell DNA Synthesis

Experiments were designed to identify herpes simplex virus type 2 (HSV-2)-specific functions expressed during stimulation of human embryo fibroblast DNA synthesis. Cultures were partially arrested in DNA synthesis by pretreatment with 5-fluorouracil and maintenance in low-serum (0.2%) medium during virus infection. Results showed that continuous [methyl-(3)H]thymidine uptake into cellular DNA was ninefold greater in HSV-2-infected than in mock-infected cultures measured after 24 h of incubation at 42 degrees C. Shifting mock-infected cultures from low- to high-serum (10%) medium also caused some stimulation, but [methyl-(3)H]thymidine uptake was only twofold greater than in cells maintained with low serum. Plating efficiencies of both HSV-2-infected and mock-infected cells at 42 degrees C were essentially the same and ranged from 37 to 76% between zero time and 72 h of incubation. De novo RNA and protein syntheses were continuously required for HSV-2 stimulation of cellular DNA synthesis. HSV-2 infection markedly enhanced transport, phosphorylation, and rate of incorporation of [methyl-(3)H]thymidine into cellular DNA, starting at 3 h and reaching a maximum by 12 h; after 12 h, these processes gradually declined to low levels. In mock-infected cells these processes remained at low levels throughout the observation period. Pretreatment of cells with interferon or addition of arabinofuranosylthymine at the time of virus infection inhibited stimulation caused by HSV-2. 5-Bromodeoxyuridine density-labeled experiments revealed that HSV-2 stimulates predominantly semiconservative DNA replication and some DNA repair. Stimulation of [methyl-(3)H]thymidine into cellular DNA correlated with detection of virus-specific thymidine kinase activity. In conclusion, HSV-2 stimulation of cellular DNA synthesis appeared to involve at least four virus-specific functions: induction of thymidine transport, HSV-2 thymidine kinase activity, semiconservative replication, and repair of cellular DNA.
The Science and Art of Conflict Resolution

Conflict Resolution in the Twenty-first Century: Principles, Methods, and Approaches. By Bercovitch Jacob, Jackson Richard. Ann Arbor, MI: University of Michigan Press, 2009. 226 pp., $29.95 paperback (ISBN-13: 978-0-472-05062-8). The goal of this book is stated clearly at the outset and is intended to achieve “a truly comprehensive survey and analysis of the major methods of conflict resolution” (p. 1). The survey and analysis is structured in such a way as to address an important question for scholars and practitioners of conflict resolution alike. The question is what are the most effective methods to resolve interstate and internal or civil conflicts in the twenty-first century? The authors claim in the first chapter that the task of resolving internal conflict is perhaps more challenging than in the past given that the fundamental nature of internal conflict has changed in the twenty-first century. Civil conflicts are no longer primarily disagreements over territory (p. 8) but are now caused by differences over issues of ethnicity, religiosity, and identity. According to the authors, internal conflicts represent significant threats to the peace and security of states and individuals via destabilizing refugee flows, the exportation of political instability, and in the creation of safe havens for those groups intent on conducting asymmetric warfare. The authors persuasively argue that finding an answer or a set of answers to the question of which methods are most effective in resolving civil conflicts, despite their incredible complexity, is thereby crucial on both strategic and moral grounds. The view that the nature of internal conflicts has changed leads the authors to advance an intriguing claim and one that is a distinguishing feature of this book: New conflicts demand that we develop and employ new conflict resolution techniques, including preventive or nonofficial (Track II) diplomacy or humanitarian intervention. The primary reason is that newer methods of conflict resolution may be more effective in truly resolving conflict than so-called traditional techniques, such …
Abstract 4082: CD47 blockade to enhance adaptive anti-tumor immune responses

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The success of immunotherapy has been hindered by the ability of tumors to evade or inhibit the host immune system. One strategy tumors use to achieve this is upregulation of CD47, a cell surface protein that delivers a “don't eat me” signal. CD47 binds to SIRP-alpha on the surface of macrophages and disables their phagocytic function. Previous data showed CD47 blockade enhanced phagocytosis of tumor cells in vitro and improved survival of mice transplanted with human tumors. However, CD47 blockade has yet to be examined in a fully syngeneic system where the potential for tumor phagocytosis by macrophages and/or dendritic cells to promote presentation of tumor antigens to T cells can be defined. It has been reported that CD47 blockade can hinder T cell activation; however, this also has not been examined in a syngeneic system. Our hypothesis was that inducing tumor cell phagocytosis by CD47 blockade would enhance T-cell-mediated anti-tumor responses. Our data show that CD47 was expressed on the EL4 thymoma and B16-F10 melanoma cell lines that are syngeneic to H-2b, as well as on their ovalbumin-expressing derivatives EG7 and B16-OVA. CD47 also was expressed on CD8+ T cells and was further upregulated upon stimulation, suggesting it might play a role in immune effector function. However, in our hands CD47 blockade using antibody MIAP-301 did not inhibit activation of CD8+ T cells in vitro, and in preliminary experiments, CD47 blockade appeared to enhance activation of antigen-specific CD8+ T cells in vivo. Ongoing work is evaluating the effects of CD47 blockade and phagocytosis on antigen presentation in vitro and the effects of CD47 blockade on the generation of tumor-specific CD4 and CD8 T cells in vivo. We also plan to confirm that T cells activated under conditions of CD47 blockade can recognize endogenous tumor antigens to which there may be self-tolerance. Supported by an HHMI Medical Student Fellowship (to KA), by the GREYlong Foundation, and by grant P01 AI035296 (to MFM). Citation Format: Katie L. Anderson, Daisuke Ito, Debra C. Lins, Julie M. Curtsinger, Matthew F. Mescher, Jaime F. Modiano. CD47 blockade to enhance adaptive anti-tumor immune responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4082. doi:10.1158/1538-7445.AM2014-4082
Concrete Vaulted Construction in Imperial Rome: Innovations in Context

1. Introduction 2. Centering and formwork 3. Ingredients: mortar and caementa 4. Amphoras in vaults 5. Vaulting ribs 6. Metal clamps and tie bars 7. Vault behavior and buttressing 8. Structural analysis: history and case studies 9. Innovations in context.
Small State Foreign Policy: The Diplomatic Recognition of Taiwan

Despite the post-World War II emergence of many small states and growing economic interdependence, small state foreign policy still gets short shrift in international studies. This article seeks to enhance our understanding of the subject by examining the diplomatic recognition of Taiwan. At the time of writing, 23 countries in the world have picked Taiwan over China. This is puzzling at first sight, since China is much more powerful than Taiwan, and a vast majority of countries pick China over Taiwan. This article shows that a full understanding must simultaneously take into account the systemic, domestic and individual levels of analysis. This research lends itself to structural realism, which stresses the role of structural factors in foreign policies, especially among small states. On the domestic level of analysis, this study identifies three important factors: ideology, economy and geography. For structural and cultural reasons, major leaders of Taiwan’s diplomatic allies are found to have loomed large in the diplomatic recognition of Taiwan.
Control of Compression System Surge and Rotating Stall: A Laboratory-Based "Hands-On" Introduction

Certain compression system aerodynamic instabilities manifest themselves as compressor stall phenomena. The most common of these phenomena are rotating stall and surge. These phenomena correspond to relatively high-frequency and high-amplitude flow oscillation. At the very least, these oscillations result in a dramatic loss of compression system performance and operating efficiency. However, in some instances these oscillations can result in catastrophic system failure. For these reason, rotating stall and surge must be avoided at all cost in compressor operation. Hence, modeling, dynamics, and control of these phenomena are of significant interest to industry. The purpose of this paper and its accompanying video is to provide a tutorial introduction to rotating stall and surge in compression systems. Both centrifugal and axial compressors are considered. The main goal here is to provide a rather complete phenomenological description of the physical phenomena. Emphasis is placed on those aspects of the phenomena which can and must be exploited to develop dynamical models of these phenomena which are suitable for use in control system design. A secondary goal is to overview recent progress in active control of surge and rotating stall. Emphasis is placed on recent work by the authors in active control of surge and rotating stall using 1D effectors. The videotape [1] which accompanies this paper consists of several clips. These clips display the following 1) videotaped flow visualization experiments, 2) videotaped computer animations of experimental data, and 3) videotaped control hardware experiments.
Characterization of cytotoxicity induced by sphingolipids in multidrug-resistant leukemia cells

Certain sphingolipids (SLs) exert fundamental roles in differentiative, growth-inhibitory and apoptotic pathways induced by a number of agents in leukemia cells. Multidrug-resistance (MDR) is a major cause of therapeutic failure in leukemia. SLs are among the diverse substrates for the MDR p-170 glycoprotein drug-efflux pump. We tested the hypothesis that expression of MDR would thereby block the cytotoxicity induced by the SLs sphingosine, sphinganine and N-hexanoyl-sphingosine. An MDR-expressing subline of murine P388 leukemia cells demonstrated an ED50 value > or = 2 log10 higher than the parental line in response to doxorubicin. In contrast, the ED50 values for each of the SLs were only approximately 1.5 to two-fold higher in the MDR line than in the parental; induction of DNA damage by SLs was comparable or actually greater in MDR compared to parental cells. Therefore, expression of MDR does not significantly affect the cytotoxic function of these SLs, nor do these SLs likely contribute to MDR.
De novo sequencing of neuropeptides using reductive isotopic methylation and investigation of ESI QTOF MS/MS fragmentation pattern of neuropeptides with N-terminal dimethylation.

A stable-isotope dimethyl labeling strategy was previously shown to be a useful tool for quantitative proteomics. More recently, N-terminal dimethyl labeling was also reported for peptide sequencing in combination with database searching. Here, we extend these previous studies by incorporating N-terminal isotopic dimethylation for de novo sequencing of neuropeptides directly from tissue extract without any genomic information. We demonstrated several new sequencing applications of this method in addition to the identification of the N-terminal residue using the enhanced a1 ion. The isotopic labeling also provides easier and more confident de novo sequencing of peptides by comparing similar MS/MS fragmentation patterns of the isotopically labeled peptide pairs. The current study on neuropeptides shows several distinct fragmentation patterns after N-terminal dimethylation which have not been reported previously. The y(n-1) ion is enhanced in multiply charged peptides and is weak or missing in singly charged...
Hydrodynamic Interaction Between a Platelet and an Erythrocyte: Effect of Erythrocyte Deformability, Dynamics, and Wall Proximity

We present three-dimensional numerical simulations of hydrodynamic interaction between a red blood cell (RBC) and a platelet in a wall-bounded shear flow. The dynamics and large deformation of the RBC are fully resolved in the simulations using a front-tracking method. The objective is to quantify the influence of tank treading and tumbling dynamics of the RBC, and the presence of a bounding wall on the deflection of platelet trajectories. We observe two types of interaction: A crossing event in which the platelet comes in close proximity to the RBC, rolls over it, and continues to move in the same direction; and a turning event in which the platelet turns away before coming close to the RBC. The crossing events occur when the initial lateral separation between the cells is above a critical separation, and the turning events occur when it is below the critical separation. The critical lateral separation is found to be higher during the tumbling motion than that during the tank treading. When the RBC is flowing closer to the wall than the platelet, the critical separation increases by several fold, implying the turning events have higher probability to occur than the crossing events. On the contrary, if the platelet is flowing closer to the wall than the RBC, the critical separation decreases by several folds, implying the crossing events are likely to occur. Based on the numerical results, we propose a mechanism of continual platelet drift from the RBC-rich region of the vessel towards the wall by a succession of turning and crossing events. The trajectory deflection in the crossing events is found to depend nonmonotonically on the initial lateral separation, unlike the monotonic trend observed in tracer particle deflection and in deformable sphere-sphere collision. This nonmonotonic trend is shown to be a consequence of the deformation of the RBC caused by the platelet upon collision. An estimation of the platelet diffusion coefficient yields values that are similar to those reported in experiments and computer simulations with multicellular suspension.
Long-term Follow-up of Patients After Surgical Treatment for Isolated Pulmonary Valve Stenosis

OBJECTIVE To determine the long-term outcome of patients after surgical repair for pulmonary valve stenosis (PVS). PATIENTS AND METHODS Fifty-three patients (30 males; mean ± SD age, 10±13 years; range, 5 days to 50 years) were identified who had surgical treatment for PVS between 1951 and 1982. The status of each patient was determined by medical record review. RESULTS The mean ± SD age at follow-up was 43±15 years (age range, 19-77 years). Mean follow-up was 33 years (range, 18-51 years). At a median follow-up of 34 years, 35 reinterventions had been performed in 28 patients (53%), including pulmonary valve replacement for free pulmonary regurgitation in 21 patients (mean interval after initial surgery, 33 years; range, 14-45 years), open valvotomy in 5 and pulmonary balloon valvuloplasty in 3 for residual PVS, closure of atrial septal defect in 2, right ventricular outflow tract reconstruction in 1, closure of iatrogenic ventricular septal defect in 1, ligation of aortopulmonary fistula in 1, and tricuspid valve annuloplasty with simultaneous coronary artery bypass grafting in 1. In addition, atrial and ventricular arrhythmias were common, occurring in 20 patients (38%). Patients who underwent reintervention were more likely to have undergone closed pulmonary valvotomy as the initial repair ( P =.008). CONCLUSION Although overall survival after surgical treatment of isolated PVS remains excellent, many patients undergo late reintervention after 30 years of follow-up, emphasizing the need for lifelong cardiac follow-up.
Influence of epithelial lining fluid lipids on NO2-induced membrane oxidation and nitration

Abstract Within the pulmonary epithelial lining layer (ELF), antioxidants such as ascorbic acid (AH2) and glutathione (GSH) react with inhaled nitrogen dioxide (•NO2) to produce reactive oxygen species (ROS) that induce cellular oxidation. Because the ELF contains unsaturated fatty acids (UFA), which potentially react with •NO2 and/or the antioxidant-derived ROS, we studied the influence of aqueous phase model UFA [egg phosphatidylcholine (EggPC) liposomes] on exposure-induced oxidation and nitration of membranes. Our lung surface model used gas phase •NO2 exposures of immobilized red cell membranes (RCM) overlaid with defined aqueous phases. Acetyl cholinesterase (AChE) activity, TBARS, and 3-nitrotyrosine (3-NT) were used to assess protein and lipid oxidation and RCM nitration, respectively. During •NO2 exposure, AH2 and GSH induced AChE loss and TBARS, which were unchanged with buffer only. Exposures of EggPC generated extensive TBARS but not AChE loss; addition of AH2/GSH to EggPC resulted in smaller AChE declines and fewer TBARS. 3-NT formation occurred with or without EggPC, low concentration antioxidants, SOD, catalase, or DTPA, but was inhibitable by desferrioxamine or high antioxidant concentrations. The data suggest that reaction/diffusion limitations govern •NO2 distribution, that •NO2 per se directly nitrates tyrosine residues within hydrophobic regions, and that the induction of secondary oxidative processes is dependent on nonlinear relationships among •NO2 flux rates, antioxidant concentrations, and diffusivity of secondary reactive species.
Unraveling the Aflatoxin−FAPY Conundrum: Structural Basis for Differential Replicative Processing of Isomeric Forms of the Formamidopyrimidine-Type DNA Adduct of Aflatoxin B1

Aflatoxin B1 (AFB) epoxide forms an unstable N7 guanine adduct in DNA. The adduct undergoes base-catalyzed ring opening to give a highly persistent formamidopyrimidine (FAPY) adduct which exists as a mixture of forms. Acid hydrolysis of the FAPY adduct gives the FAPY base which exists in two separable but interconvertible forms that have been assigned by various workers as functional, positional, or conformational isomers. Recently, this structural question became important when one of the two major FAPY species in DNA was found to be potently mutagenic and the other a block to replication [Smela, M. E.; Hamm, M. L.; Henderson, P. T.; Harris, C. M.; Harris, T. M.; Essigmann, J. M. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 6655−6660]. NMR studies carried out on the AFB−FAPY bases and deoxynucleoside 3‘,5‘-dibutyrates now establish that the separable FAPY bases and nucleosides are diastereomeric N5 formyl derivatives involving axial asymmetry around the congested pyrimidine C5−N5 bond. Anomerization of the pr...