cssi/SciSciGPT-SciSciNet huggingface dataset:
Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon.

Abstract In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor–enzyme complexes undergo reactivation/aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants ( k i ) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher k i ’s than paraoxon. The higher association constant ( K A ) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants ( k p ) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the k i of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first order aging constants ( k a ) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants ( k r ) but the k a for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging.
American Girls and French Jeunes Filles: Negotiating National Identities in Interwar France

This essay is a transnational and comparative study of how gendered national stereotypes structured the experience of American women who studied in France in the 1920s and 1930s and how this cross-cultural exchange contributed to cultural internationalism. In both the French and American popular imaginations, American girls and French jeunes filles connoted opposite modern and traditional notions of femininity. In the process of negotiating these two competing identities in popular consciousness and in daily life, some American women students came to appreciate the limitations of the stereotypes, as well as more complex underlying cultural differences, notably in their encounters with French youth's heterosocial practices and with French women students. I argue that the outcome of this process included women's construction of alternative identities for themselves and a new tolerance and appreciation for cultural difference that represents a distinctive development toward cultural internationalism. This study challenges the cultural asymmetry of United States and European relations between the wars and locates gender and women at their centre.
Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress

We examined HeLa cell viability and RNA oxidative damage in response to hydrogen peroxide (H2O2) treatment. The level of damaged RNA, measured by the content of 8-hydroxyguanosine (7,8-dihydro-8-oxoguanosine, 8-oxoG), increases depending on H2O2 dosage and is inversely correlated with cell viability. The elevated level of 8-oxoG in RNA decreases after removal of oxidative challenge, suggesting the existence of surveillance mechanism(s) for cleaning up oxidized RNA. Human polynucleotide phosphorylase (hPNPase), an exoribonuclease primarily located in mitochondria, has been previously shown to bind 8-oxoG-RNA with high affinity. The role of hPNPase in HeLa cell under oxidative stress conditions is examined here. Overexpression of hPNPase reduces RNA oxidation and increases cell viability against H2O2 insult. Conversely, hPNPase knockdown decreases viability and increases 8-oxoG level in HeLa cell exposed to H2O2. Our results suggest that hPNPase plays an important role in protecting cells and limiting damaged RNA under oxidative stress.
Effective refractive indices of three-phase optical coatings

To obtain the effective refractive indices of three-phase coating materials, in which multiple scattering can also occur between the two different discrete phases, a multiple scattering formalism for two-phase systems is modified to include the third phase. Numerical results for different refractive indices of various arrangements are presented for a paint coating in which some of the TiO2 pigment particles are replaced by microbubbles.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Estrogens and the Pathophysiology of Parkinson's Disease

Two postmenopausal female Parkinsonian patients experienced exacerbation of symptoms including levodopa-induced “On-Off” following withdrawal or reduction of conjugated estrogen therapy. This report supports animal data implicating female sexual hormones in the pathophysiology of Parkinson's disease and levodopa-induced dyskinesias.
The Effects Of Scattering On The Relative ICI Performance Of Optical And Nn-Wave Systems

The purpose of this paper is to extend the results of a previous paper comparing the LPI performance of optical and millimeter wave satellite systems to include the effects of scattering on optical LPI performance. As before, the LPI figure of merit used to compare the two media is the Circular Equivalent Vulnerability Radius (CEVR) . The CEVR is defined as the radius of a circle which has the same area as the irregularly shaped region within which an airborne interceptor at a fixed altitude can detect the transmitted signal. Typically, this region is projected onto the surface of the earth to provide a degree of normalization with respect to interceptor altitude.
Flanking sequences are required for efficient transcription and stable complex formation for the human tRNAMet3i-coding gene

An analysis of 5' and 3' deletions of the human tRNAiMet3 gene has revealed upstream regions required for efficient transcription and stable complex formation in vitro. The 5' boundary of this essential region lies between nucleotides -39 to -18 (start point = + 1), and it has been shown that 3'-flanking sequences near the first termination site are also important for stable complex formation. The transcriptional efficiency of two non-allelic loci (TMET3 and TMET2) has been compared and TMET2 is more active. An analysis of chimeric (hybrid) genes indicates that much of the difference seen is due to 5'-flanking sequences and that there may be complex interactions between 5' and 3' sequences.
Dining with the Devil: Identity Formations in Juarez, Mexico

This article analyzes popular narratives surrounding the theme of drug lords in the Mexican border city of Juarez and their multifaceted social, ideological, and material effects. This analysis takes into consideration the historical context of eruptions of violence that Juarez has endured in the last few years. Complex formations of the Mexican identity are now being reformulated in hierarchical, gendered, and racialized identities, which project the very strong and powerful social frictions currently emerging from complex socioeconomic factors resulting in mass poverty and migration. These elements are evinced in the narco-narratives within their violent contexts. However, violence in Juarez must not be interpreted as upsurges outside the control of the state, but rather as byproducts of conflict within it (see Das and Poole 2004). Thus, on the border, Juarez becomes a central site, not a periphery, in which economic and political forces materialize in the middle of complex social dynamics.
Ongoing estimation of the epidemic parameters of a stochastic, spatial, discrete-time model for a 1983-84 avian influenza epidemic.

SUMMARY. We formulate a stochastic, spatial, discrete-time model of viral “Susceptible, Exposed, Infectious, Recovered” animal epidemics and apply it to an avian influenza epidemic in Pennsylvania in 1983–84. Using weekly data for the number of newly infectious cases collected during the epidemic, we find estimates for the latent period of the virus and the values of two parameters within the transmission kernel of the model. These data are then jackknifed on a progressive weekly basis to show how our estimates can be applied to an ongoing epidemic to generate continually improving values of certain epidemic parameters.
ROLL COATING IN THE PRESENCE OF A FIXED CONSTRAINING BOUNDARY

When a cylindrical roll rotates about its axis while partially submerged in a liquid, as suggested in Figure 1, a layer of the liquid is entrained and withdrawn from the bath. In the absence of a constraining boundary the coating thickness H is found to exhibit a strong dependence on roll speed, as well as on the fluid viscosity and interfacial tension. In a previous publication (Middleman, 1978) from this laboratory we have presented experimental results and a successful data correlation for the case of a roll operating under such conditions that the boundaries of the fluid reservoir exert no influence on the coating dynamics. In this paper the effect of an adjacent constraining boundary is considered, a mathematical model based on lubrication theory is presented, and the data are found to exhibit the general features predicted by the model. Under some conditions it is observed that a uniform coating is not achieved. Instead, a regular set of lines or “ribs” is developed, in the direction of motion. Figu...
Phased array of large reflectors for deep-space communication

In this paper the problem of uplink array calibration for deep-space communication is considered. A phased array of many modest-size reflectors antennas is used to drastically improve the uplink effective isotropic radiated power of a ground station. A radar calibration procedure for the array phase distribution is presented using a number of in-orbit targets. Design of optimal orbit and the number of calibration targets is investigated for providing frequent calibration opportunities needed for compensating array elements phase center movements as the array tracks a spacecraft. Array far-field focusing based on the near-filed in-orbit (low Earth orbit (LEO)) calibration targets is also presented and array gain degradation analysis based on the position error of the array elements and in-orbit targets has been carried out. It is shown that errors in the in-orbit targets positions significantly degrade the far-field array gain while the errors in array elements positions are not very important. Analysis of phase errors caused by thermal noise, system instability, and atmospheric effects show insignificant array gain degradation by these factors
Epithelioid hemangioendothelioma of the external iliac vein: A primary vascular tumor presenting as traumatic venous obstruction

Abstract A 32-year-old man employed as a laborer presented with the signs and symptoms of iliofemoral venous obstruction of 1 months' duration. Results of initial phlebography from the ankle to the femoral area were normal. No iliac vein anatomy was seen. This led to a group of tests directed toward neuromuscular function, which were unrewarding. On referral to our institution a noninvasive venous vascular laboratory examination was performed, which clearly indicated iliac vein obstruction/stenosis, with a normally patent distal venous system. Subsequent repeat phlebography, including direct femoral vein injection, visualized a mass lesion partially occluding the iliac vein. This lesion was treated with primary excision and segmental venous replacement with an interposition graft of autogeneous internal jugular vein. The excised lesion proved to be an epithelioid hemangioendothelioma of the iliac vein. (J Vasc Surg 1989;10:693–9.)
Implementing a high performance tensor library

Template methods have opened up a new way of building C++ libraries. These methods allow the libraries to combine the seemingly contradictory qualities of ease of use and uncompromising efficiency. However, libraries that use these methods are notoriously difficult to develop. This article examines the benefits reaped and the difficulties encountered in using these methods to create a friendly, high performance, tensor library. We find that template methods mostly deliver on this promise, though requiring moderate compromises in usability and efficiency.
Consensus-Derived Objectives for Drug Information Education

Drug information education is an expectation of all pharmacy curricula. The inconsistencies in current drug information instruction stimulated the creation of an invitational conference with the purpose of defining a set of objectives for didactic and experiential drug information instruction for the year 2000. Twenty-three drug information educators and practitioners participated in the conference. After the adoption of a set of assumptions and through the development of consensus, the conference participants created a goal, general educational objectives, and broad didactic and experiential course outlines. The work of the conference can be used in the development of new courses or the refinement of existing drug information courses in colleges of pharmacy.
Developmental differences in the linkages between anxiety control beliefs and posttraumatic stress in youth.

BACKGROUND: Anxiety control beliefs have emerged as a trans-diagnostic risk factor for anxiety disorders and a potential mechanism of change in cognitive and behavioral therapies. The purpose of this study was to examine the association between anxiety control beliefs and anxiety disorder symptoms following exposure to hurricanes in youth and test a developmental hypothesis about those associations. METHODS: A large school-based sample of (N = 1048) children and adolescents with a history of exposure to natural disaster were assessed with the short form of the Anxiety Control Questionnaire for Children (ACQ-C), symptom measures (PTSD and generalized anxiety disorder symptoms) and level of disaster exposure. Developmental differences in the association between ACQ-C scores and symptoms were tested, as well as the ACQ-C's ability to assess symptoms beyond level of exposure. RESULTS: ACQ-C scores were associated with symptoms beyond level of exposure, but age moderated the strength of the association. Modeling the interaction suggested that the ACQ-C short had incremental validity beyond hurricane exposure in youth over 12 years. CONCLUSIONS: Findings extend previous work to a novel population of youth and add to the developmental understanding of the role of anxiety control beliefs in anxiety regulation. Age differences in the linkages between anxiety control and symptoms is consistent with a developmental model where low perceived control exhibited by younger children may be less indicative of problems with anxiety but may instead be related to normal cognitive development. Language: en
Theory and Generation X

(1997). Theory and Generation X. Journal of Public Administration Education: Vol. 3, No. 3, pp. 397-403.
Analogical cascade: a theory on the role of the thalamo-cortical loop in brain function

The cortico-thalamic connections and the nucleus reticularis thalami (nRt) have gained much attention lately because of their integrative and modulatory functions. This particular architecture has been thought to perform analysis and synthesis of memories, work as active blackboards or a global workspace, or gate attention and give rise to consciousness. In this paper, I show that this circuitry can be implementing a general analogical functionality. The concrete connection between analogical function and its exact neural basis established in this paper can help us better understand the brain function.
Statistical Database Query Languages

Databases that are mainly used for statistical analysis are called statistical databases (SDB). A statistical database management system (SDBMS) may be defined as a database management system that provides capabilities 1) to model, store, and manipulate data in a manner suitable for the needs of SDB users, and 2) to apply statistical data analysis techniques that range from simple summary statistics to advanced procedures. This paper surveys the existing and proposed SDB data definition and data manipulation (i.e., query) languages.
Basal Cell Carcinoma With Pulmonary and Lymph Node Metastasis Causing Death

Background The incidence of metastatic basal cell carcinoma ranges from 0.003% to 0.55%. The 230 reported cases most often occurred in long-standing recurrent lesions and appeared in regional nodes or the lungs. Observations The stromal dependence of the tumor provides an explanation for the nonmetastasizing nature of basal cell carcinoma. The dense fibrous stroma of the lymph node in the case of metastatic basal cell carcinoma reported in the present study is similar to other reported cases with metastases to lymph nodes, bone, bone marrow, glands, and subcutaneous tissue. Conclusions This metastatic basal cell carcinoma demonstrated lymphatic and hematogenous dissemination to the lungs and lymph nodes. A dense accumulation of microvessels was present at the boundary of the tumor nests and dermal stroma and in the stroma surrounding the tumor in the lymph node.
Screening for bipolar disorder in patients treated for depression in a family medicine clinic.

Purpose: The prevalence of bipolar disorder in patients being treated for depression with antidepressants in a family medicine clinic was investigated in this study. Methods: Adult patients with depression who were treated with an antidepressant in a general outpatient family medicine clinic at the University of Texas were screened for bipolar disorder using the Mood Disorder Questionnaire (MDQ), a brief self-report inventory. A subsample of subjects received the Structured Clinical Interview based on the DSM-IV (SCID) to test the operating characteristics of the MDQ in this population. Results: of the patients taking an antidepressant for depression, 21.3% screened positive for bipolar disorder on the MDQ. These patients were somewhat younger, more likely to be white, more likely to be living alone, much less likely to be married, and less likely to be employed than those who screen negative. Nearly two thirds of those screened positive had never received diagnosis of bipolar disorder. The sensitivity and specificity of the MDQ in this population, after adjusting for the sampling protocol, were 0.580 (0.454 to 0.706, 95% CI) and 0.930 (0.878 to 0.981, 95% CI) respectively. Conclusion: Bipolar disorder frequently occurs in patients being treated with antidepressants in primary care settings. Most are unrecognized and undiagnosed. Screening for bipolar disorder in such patients may improve recognition, identification, and appropriate treatment.
James Heckman as a Law & Society Scholar: An Outsider’s Appreciation

James Heckman was the 2000 Nobel Laureate in Economics. This short paper reviews the methodological and substantive contributions Heckman has made to the empirical study of law. Heckman’s work is shown to be important because he has developed techniques to address fundamental problems such as how to separate law as ‘cause’ and as ‘effect.’ His work on selected or choice-based sampling has applications to almost every problem empirical researchers confront, since the sample we can actually observe is almost never randomly drawn from some larger population as classical statistical theory assumes. Substantively, his work on the effects of civil rights laws, job training programs, and other legal interventions in labor markets has profound implications for how we understand law’s power to alter economic relationships. His critique of experimental approaches to studying social behavior has commonalities with ‘interpretivist’ criticism of positivist social science.
The Perils of Law and Medicine: Avoiding Litigation to Promote Patient Safety

Patient safety has become a prominent policy issue, and recognition of medical error as the progenitor of a majority of patient injury around the world has been recognized. Currently, there is no effective means by which the problem of medical error is broadly addressed. Both legal and medical systems contribute to this result. However, an approach recognizing the systems nature of error and injury and the need for open communication, assessment, and focus on corrective action while providing rapid compensation for the injured party is essential to promote progress in this area. Use of communications methods such as mediation have significant promise to learn from medical error and injury. Both patients and providers have reported satisfaction using this approach; the process is flexible and informal; parties can discuss issues that are important to them, including a determination of important information that can provide clues to understanding and improving safety efforts; the forum can be confidential; and settlement can include a wide array of alternatives, including apology. By promoting communication, parties in the health delivery enterprise may be brought together for the joint benefit of all in our society, now, and in the future.
Syncope: How Should It Be Evaluated Today?

Syncope is defined as a sudden transient loss of consciousness and postural tone that spontaneously resolves without electrical or chemical cardioversion. Clinical assessment is usually sufficient to separate syncope from other states of altered consciousness such as dizziness, vertigo, seizure, coma and narcolepsy. Syncope is a common problem in all age groups. In the U.S. it accounts for approximately 1% of hospital admissions and 3% of emergency room visits. Syncope is common in young adults (12%–48% of healthy young adults report loss of consciousness) although most do not seek medical attention. In one study of elderly, people over age 75 years had an annual incidence of 6%; 23% had previous lifetime syncopal episodes.
Abstract 370: Interferon Regulatory Factors 3 and 7 Regulate Vein Graft Remodeling and Vascular Inflammation

Introduction: Type I interferons (IFN) are implicated in the development of vascular proliferative diseases. Pathway analysis by gene set enrichment analysis of hypercholesterolemic ApoE3*Leiden murine vein grafts revealed that the type I IFN pathway belonged to the top 15 of significant regulated pathways. The transcriptional regulators of type I IFN and type I IFN responsive genes are the interferon regulatory factors (IRF). Activation of TLR3 results in activation of type I IFN in a IRF3 and IRF7 dependent manner. TLR3 has been shown to be protective in vascular remodeling. The aim of this study was to investigate the role of IRF3 and IRF7 on vein graft remodeling. Methods and Results: The importance of IRFs in vein graft remodeling is illustrated by the increase in vein graft thickening in Irf3-/- and Irf7-/- mice in comparison to control mice (n=9/group, Irf3-/- ; 39%, p=0.185, Irf7-/- ; 68% p=0.003). Also an increase in outward remodeling ( Irf3-/- ; 26%, p=0.081, Irf7-/- ; 42%, p=0.049) was observed comparable to that of Tlr3-/- (n=8, 52%, p<0.001) Immunohistochemical analysis revealed that both Irf3-/- and Irf7-/- mice showed a significant higher influx of macrophages in the vessel wall than the control mice whereas the Irf7-/- mice also showed a significant decrease in collagen content. RNA levels of typical type I IFN responsive genes such as Mx1, Ifit1-3 and Oas2 were down regulated in the knockout vein grafts in comparison to control vein grafts. Activation of both Irf3-/- and Irf7-/- bone marrow derived macrophages with LPS and poly:(IC) resulted in a significant increase in TNFα production. Conclusions: IRFs regulates vein graft remodeling since Irf3-/- and especially Irf7-/- vein grafts show increased vessel wall thickening and outward remodeling. This increased remodeling is the result of a pro-inflammatory response as reflected by the increase in macrophages in the vein graft wall.
BW Manufacturing Company

A small manufacturer of gas grills is making final changes to its 2009 operating budget and considering several changes in pricing, advertising, and product availability. This short case addresses the topic of contribution analysis as an easy way to analyze profit planning issues such as adding or dropping a product or service; changing a price; adding or decreasing expected volumes; or preparing a profit budget. In this situation there are three products, each with different proportions of variable and fixed costs. The product with the highest profit/unit on a full cost basis has the lowest contribution/unit on a variable cost basis, and vice versa. Four different marketing plans are proposed before one is finally adopted as the plan for the year. At year end, the actual results can be compared to the budget and to a flex or adjusted budget based on the actual product volumes realized. The numbers are simple and the students can readily see the benefit of variable costing.
Research on Combination of Ultrasonic and Mechanic Polishing

To improve the material removal rate(MRR),this paper discussed a new ultrasonic polishing in which the ultrasonic energy was introduced to the interface of common polishing,and compared this new polishing process with the common polishing process in the MRR.It has been proved that the MRR of machining were improved greatly;The conclusion that the combining polishing is superior to mechanical polishing was reached.This paper also applies a simple analysis on the mechanism of the new coalescence process which is useful to industrial products and theory research.
Some Problems of Pharmacy Management in Primary Hospital

OBJECTIVE:To provide reference for the improvement of pharmacy management in primary hospital.METHODS:Some problems about pharmacy management and its operation process in primary hospital were introduced briefly.Reasons of above problems were investigated and analyzed,and relevant countermeasures were put forward.RESULTS CONCLUSION:Pharmacy management of primary hospital should be strengthened,standardized and improved.More efforts should be put into the pharmacy work of primary hospital in order to make primary hospital become a great contributor for primary medical care.
Determination of 15 kinds of semi-volatile organic compounds in water by gas chromatography-mass spectrometry method

[Objective]To discuss the use of gas chromatography-mass spectrometry method for the determination of 15 kinds of semi-volatile organic compounds in water.[Methods]The mixed standard solution including 15 kinds of semi-volatile organic compounds was prepared for determination,with full scan mode and external standard method.[Results] Correlation coefficient of standard curve was above 0.987,the recoveries were 88.6%-127.7%,relative standard deviation was between 2.69%-13.64%,the detection limit was 0.006-0.012 μg/ml.[Conclusion]The method is rapid,with high separating efficiency and suitable for determination of semi-volatile organic compounds in water.
A new method for temporary left ventricular bypass. Preclinical appraisal.

Surgical patients who cannot be weaned from cardiopulmonary bypass during operation or who develop balloon-dependent left ventricular failure postoperatively are now considered unsavable. However, in those with potentially reversible ventricular dysfunction, recovery might be possible if an improved means of temporary circulatory support were available. Toward this end, a pneumatically actuated, left ventricular assist pump was developed and evaluated in 20 consecutive calf experiments. The device, containing a flexible polyurethane pumping chamber, was positioned on the chest wall and connected to the left ventricular apex and descending thoracic aorta by two Dacron valved conduits (xenograft valves). All animals survived a 14 to 30 day pumping interval, and 7 underwent successful removal of the device by division of the Dacron conduits below skin level. As a prelude to human investigation, pumps were implanted during a series of routine autopsies through midline sternotomy incison. The device was positioned on the right anterolateral chest wall, with two valved conduits traversing the mediastinum to connect the pump to the left ventricular apex and ascending aorta.
Abstract IA40: Patient-derived tumorgrafts from primary peripheral T-cell lymphoma represent innovative models to design patients' tailored therapies.

Peripheral T-cell Lymphoma (PTCL) are a heterogeneous group of tumors with a dismal clinical outcome. The poor response of PTCL patients to conventional treatments is in part due to the lack of known pathogenetic mechanisms and reliable/reproducible in vitro or in vivo models. To overcome some of these limitations, we have constructed a library of Patient Derived Tumografts (PDT) from Anaplastic Large Cell Lymphoma patients in highly immunocompromised mice (NSG). Engraftment lymphoma were serially propagated and interrogated by using massive parallel sequencing platforms [RNAseq and WES], and by additional genomic and immunophenotype strategies. Our data demonstrate conserved similarities between PDT and their corresponding primary lymphoma and the presence of novel recurrent somatic lesions. Co-clinical trials of PDT bearing mice showed responses to therapies analogous to those seen in donor patients and could predict alternative and more successful therapeutic strategies. ALCL PDT represent informative models to discover patient restricted/pathogenetic lesions and to design more efficient and/or tailored therapies for naive and chemorefractory PTCL individuals. Citation Format: Giorgio Inghirami. Patient-derived tumorgrafts from primary peripheral T-cell lymphoma represent innovative models to design patients9 tailored therapies. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA40.
Virus-Like Particles (VLPs) in Supramolecular Chemistry

Virus capsids, and other related protein cages, are remarkable examples of natural supramolecular assemblies. These systems self-assemble from a distinct number of subunits to form well-regulated and often highly symmetrical quaternary structures. They exhibit sophisticated functionalities such as protection of cargo molecules (e.g., their genome), targeting host cells and triggered release of their cargo. Scientists have drawn inspiration from protein cages and utilize them as platforms to explore this new area of materials science. The interior cavities of protein cages can be used as size-constrained reaction volumes to encapsulate cargo molecules. The exterior surfaces can be engineered to direct the interaction of the cage to the external environment such as for cell-targeting and programmed stimulation of immunological responses. Individual protein cages are also viewed as ideal building blocks for higher-order assembly of ordered arrays.
Disruption of MYD88 Pathway Signaling Leads to Loss of Constitutive IRAK1, NF-κβ and JAK/STAT Signaling and Induces Apoptosis of Cells Expressing the MYD88 L265P Mutation in Waldenstrom's Macroglobulinemia

Abstract 597 Introduction: Through whole genome sequencing of bone marrow lymphoplasmacytic cells (LPCs) from WM patients, we recently identified a broadly expressed somatic variant (MYD88 L265P) which was present in 90% of WM patients, as well as in BCWM.1 and MWCL-1 WM cells. The presence of this variant has been reported to confer oncogenic activity in cell lines derived from patients with DLBCL ABC subtype lymphomas by induction of IRAK 1/4 kinase activity, and downstream signaling via NF-κβ (Ngo et al, Nature 2011, 470:115-119). We therefore sought to delineate the activity of agents which either disrupt MYD88 homodimerization, a prerequisite to IRAK 1/4 auto-phosphorylation, or by direct inhibition of IRAK 1/4 kinase activity in WM. Patients and Methods: Primary WM LPCs were isolated from bone marrow biopsy specimens from WM patients, and CD19 + B-cells were isolated from the peripheral blood of healthy donors. The mutational status of MYD88 was identified by Sanger sequencing, which confirmed the presence of the L265P mutation in BCWM.1 and MWCL-1 cells, and absent in Ramos and MM1S cells. Western blot and phospho-flow studies using phospho-specific antibodies were performed for signaling proteins downstream of MYD88, cell killing evaluated by Annexin V/PI staining and AlamarBlue, and IgM and IL-6 release determined after treatment with and without inhibitors of MYD88 homodimerization (IMG-2005-5, IMGENEX, San Diego CA), and IRAK 1/4 kinase function (407601, EMD, Gibbstown, USA). Results: Phosphorylation of the MYD88 downstream signaling proteins IRAK1, IκBα, NFκβ-p65 and STAT3 was greater in MYD88 L265P expressing BCWM.1 and MWCL-1 cells, and primary WM patient LPC, versus MYD88 wild type expressing Ramos, MM1S, and healthy donor CD19 + B-cells. Inhibition of MYD88 homodimerization and IRAK 1/4 kinase activity led to decreased phosphorylation of IRAK1, IκBα, NFκβ-p65 and STAT3 in BCWM.1 and MWCL-1 cells. Importantly, both inhibitors induced robust apoptosis of BCWM.1 and MWCL-1 cells, and primary WM LPCs bearing the MYD88 L265P mutation in comparison to Ramos, MM1S, or healthy donor CD19 + B-cells. Activation of caspase-3 and PARP, decreased BCL-2 expression, and decreased release of IL-6 and IgM accompanied treatment of WM cells following treatment with inhibitors of MYD88 homodimerization and/or IRAK 1/4 kinase activity. Conclusion: Disruption of MYD88 pathway signaling leads to loss of constitutive IRAK1, NF-κβ and JAK/STAT activation and induces apoptosis of cells expressing the MYD88 L265P mutation in WM. The results of this study provide novel insights into the pathogenesis of WM, and provide a framework for the clinical investigation of inhibitors of the MYD88 pathway in WM. Disclosures: No relevant conflicts of interest to declare.
Estimation of Time Varying Delays in Linear Stochastic Systems

Abstract A class of estimators is presented for the estimation of unknown time varying delays in a linear discrete time stochastic system. The proposed suboptimum maximum likelihood (SML) techniques are shown to be realized by parallel Kalman Filtering (PKF) coupled with a suboptimum Viterbi Algorithm (SVA). The SVA estimates the delay sequence and the Kalman Filter bank generates all the components needed by the SVA. The analysis and simulations show that the sub-optimum estimators closely approximate the optimum maximum likelihood estimator while possessing significant computational advantages. The relation between performance of the algorithm and the output distinguishableity is derived.
Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics

ummary Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS-13. In general, severe deficiency of plasma ADAMTS-13 activity ( 10 IU dL−1) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. Although plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS-13 mutations, daily therapeutic plasma exchange remains the initial treatment of choice for acquired TTP with demonstrable autoantibodies. Immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide and splenectomy, etc., should be considered to eliminate autoantibodies for a sustained remission. Other emerging therapeutic modalities, including recombinant ADAMTS-13, adeno-associated virus (AAV) 8-mediated gene therapy, platelet-delivered ADAMTS-13, and antagonists targeting the interaction between platelet glycoprotein 1b and VWF are under investigation. This review highlights the recent progress in our understanding of the pathogenesis and diagnosis of, and current and potential novel therapies for, hereditary and acquired TTP.
American Sāmoan Legal History: 1900–1941

Kruse examines German Sāmoa’s Supreme Court and Land Commission decisions that found land claim cases were difficult to adjudicate without written land deeds or surveys. The Supreme Court created land classifications that segmented and converted customary lands; Kruse contends the Supreme Court interpreted custom to create a legal status of “rightful owner” by extending social and political parameters of mātai pule. The chapter details how by the 1890s, the diminishing rights of the mātai over the conveyance or transfer of lands, coupled with the new system of land classifications, led to the splitting of communal lands. Kruse argues that the German Sāmoa court decisions were readily accepted by American Sāmoa’s Naval court, legitimizing individual land rights. Detailing the intention of the Naval Court to legitimize adverse land possession that they believed would civilize and stabilize land titles and that also included laws to force plantation cultivation to pay copra taxes.
Association between hyperinsulinaemia and laminitis severity at the time of pituitary pars intermedia dysfunction diagnosis

Background Hyperinsulinaemia is the suspected component of insulin dysregulation having the strongest association with laminitis and occurs variably in equids with pituitary pars intermedia dysfunction (PPID). Objectives We hypothesised that magnitude of hyperinsulinaemia correlates with laminitis severity in PPID-affected equids. Furthermore, we hypothesised that owners can be unaware of chronic endocrinopathic laminitis. Study design Cross-sectional study. Methods Serum insulin concentrations, owner-reported laminitis history and radiographic evidence of laminitis were determined in 38 client-owned horses and ponies with confirmed PPID. Laminitis severity was classified into four categories (normal [nonlaminitic], mild, moderate or severe laminitis) based on degree of distal phalangeal rotation. Animals were also categorised as normoinsulinaemic ( 50 μU/ml). One-way ANOVA, t tests and Fisher's exact tests were performed. Results While owners reported laminitis in 37% of animals, 76% were laminitic based on study criteria (P = 0.01). Owners reported laminitis more frequently in hyperinsulinaemic vs. normoinsulinaemic animals; recognition increased with severity of hyperinsulinaemia (P = 0.03). Mean insulin concentrations were higher in equids with moderate to severe radiographic laminitis (geometric mean 74.1, 95% confidence interval (CI) 38.4-143.1 uU/ml) vs. those classified radiographically as normal to mild (31.9, 95% CI 21.1-48.1 uU/ml P = 0.03). Main limitations Dynamic insulin testing was not performed; some normoinsulinaemic animals might have had subtle insulin dysregulation. Conclusions Although radiographic abnormalities were present in most animals at the time of PPID diagnosis, chronic laminitis remained unrecognised by many owners. Owner awareness of laminitis increased with severity of hyperinsulinaemia and higher insulin concentrations were detected in association with more severe radiographic changes. The Summary is available in Chinese - See Supporting Information.
Excessive daytime sleepiness, objective napping and 11-year risk of Parkinson's disease in older men.

Background It is unknown whether subjective daytime sleepiness or objective napping could precede the risk of Parkinson's disease (PD) in the long term. Methods We studied 2920 men (mean age 76 years) without a history of PD and followed them for 11 years. Excessive daytime sleepiness (EDS) was defined as having an Epworth Sleepiness Scale score >10. Objective naps were defined as ≥5 consecutive minutes of inactivity as measured by actigraphy, and napping duration was the accumulated time of naps outside the main sleep period. We used logistic regression to compare PD risk across four groups: no EDS& napping <1 h/day (N = 1739, 59.5%; referent group), EDS& napping <1 h/day (N = 215, 7.4%), no EDS& napping ≥ 1 h/day (N = 819, 28.1%) and EDS& napping ≥ 1 h/day (N = 147, 5.0%). Results We identified 106 incident PD cases over 11 years. After multivariable adjustment, men with napping ≥ 1h/day alone were twice as likely [odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.25-3.08], and men with both EDS and napping ≥ 1 h/day were almost three times as likely to develop PD (2.52, 1.21-5.27), compared with the referent group. Compared with those with naps for <30 min, men who napped for ≥1 h/day had more than double the risk of PD. No association was found for EDS alone and PD risk. Further adjustment for chronotype and circadian stability, or excluding PD cases identified within 2 years after napping measurements, showed similar results. Conclusions Objective long napping rather than subjective EDS was prospectively associated with a higher risk of PD in older men. Objective measures of napping might be valuable as a preclinical marker for PD.
Fusing social justice with social scientific perspectives to teach content analysis in Media Theory and Methods

Course Media Theory and MethodsObjectives (1) To understand and apply social justice perspectives and pedagogical strategies to the study of content analysis. (2) To recognize and transform how soc...
Assessing Stagnation Conditions and Identifying Trends in Magnetized Liner Inertial Fusion

Magnetized Liner Inertial Fusion (MagLIF) is a magneto-inertial fusion concept, which is presently being studied on the Z Pulsed Power Facility. The concept utilizes an axial magnetic field and laser heating to produce fusion-relevant conditions at stagnation despite a peak magnetically driven implosion velocity of less than 100 km/s. Initial mymargin experiments demonstrated the viability of the concept but left open questions about the amount of laser energy coupled to the fuel and the role that mix played in the stagnation conditions. In this paper, simple methodologies for estimating the laser energy coupled to the fuel and determining the stagnation pressure and mix are presented. These tools enabled comparisons across many experiments to establish performance trends, as well as allow comparisons with 2-D magnetohydrodynamics simulations. The initial experiments were affected by low laser energy coupling (0.2–0.6 kJ), which resulted in reduced neutron yields (1– $2\times 10^{12}$ ). In addition, all early experiments utilized mid-Z (aluminum) fuel-facing components. Mixing from these components had a significant impact on stagnation and increased with laser energy. Lower neutron yields (1– $3\times 10^{11}$ ) were measured with higher laser coupling (0.8–1.2 kJ), which significantly deviated from the predicted scaling. When all fuel-facing components were made from a low-Z material (beryllium), neutron production increased ( $3.2\times 10^{12}$ ) and scaled as expected with laser energy; experimental yields were approximately 40% of simulated yields. In addition, roughly I4 yield scaling was observed in experiments, where the load current was varied from 16–18 MA. These results represent the first step in experimental demonstration of stagnation performance scaling with input parameters in MagLIF.
R&D Performance, Collaborative Arrangements and the Market for Know-How: A Test of the

This paper examines the relative performance of vertically integrated projects versus collaborative projects in the bio-pharmaceuticals industry. Using Akerlof's (1970) model of the impact of asymetric information on quality, this paper suggests that a potential "lemons" problem exists in the market for know-how. It hypothesizes that projects with poorer prospects for reaching the market tend to be licensed to collaborative partners while those with better prospects are commercialized internally. This hypothesis is tested with data on 260 bio-pharmaceutical projects that have either been successfully completed or terminated in progress over the past 10 years. After controlling for a variety of factors, the paper shows evidence of an apparent "lemons" problem in the market for know-how in biotechnology: the rate of termination for partnered projects is significantly higher than the failure rate of projects undertaken via vertical integration. Further empirical analysis also suggests that the higher rate of failure of partnered projects is attributable to ex-ante project selection biases rather than differences in ex-post execution of partnered versus non-partnered projects. Implications for technology strategy and future research are discussed.
tert-Butyl peroxy radical: ground and first excited state energetics and fundamental frequencies.

Alkylperoxy radicals (RO2˙) are key intermediates in combustion and atmospheric oxidation processes. As such, reliable detection and monitoring of these radicals can provide a wealth of information about the underlying chemistry. The tert-butyl peroxy radical is the archetypal tertiary peroxy radical, yet its vibrational spectroscopy is largely unexplored. To aid in future experimental investigations, we have performed high-level theoretical studies of the fundamental vibrational frequencies of the ground- and first excited states. A conformer search on both electronic surfaces reveals single minimum-energy structures. We predict an A2A' ← X[combining tilde]2A'' adiabatic excitation energy of 7738 cm-1via focal point analysis, approximating the CCSDT(Q)/CBS level of theory. This excitation energy agrees to within 17 cm-1 of the most accurate experimental measurement. We compute CCSD(T) fundamental vibrational frequencies via second-order vibrational perturbation theory (VPT2), using a hybrid force field in which the quadratic (cubic/quartic) force constants are evaluated with the ANO1 (ANO0) basis set. Anharmonic resonance polyads are treated with the VPT2 + K effective Hamiltonian approach. Among the predicted fundamental frequencies, the ground state O-O stretch, excited state O-O stretch, and excited state C-O-O bend fundamentals are predicted at 1138, 959, and 490 cm-1, respectively. Basis set sensitivity is found to be particularly great for the O-O stretches, similar to what has already been noted in smaller, unbranched peroxy radicals. Exempting these O-O stretches, agreement with the available experimental fundamentals is generally good (±10 cm-1).
Motivated Perspective Taking: Why Auditors Asked to Take an Investor’s Perspective Assess Negative Audit Adjustments as Less Material

To remedy their concern that auditors underreact to material misstatements, audit regulators and commentators propose prompting auditors to more fully take an investor’s perspective (e.g., PCAOB 2012; Bricker 2016). By contrast, we predict that so prompting auditors will backfire, making them less (more) heavily weight indicia that misstatements are (not) material. We further predict auditors will apply this asymmetric weighting instrumentally—to a greater degree when needed—to justify reaching management-preferred conclusions. We test this prediction on incharge seniors in two experiments in which they assess the likelihood that audit adjustments are material. Between-participants, we manipulate whether or not auditors are prompted to take an investor’s perspective and, within-participants, whether audit adjustments would or would not violate a qualitative criterion (in particular, whether they would or would not break a favorable profitability trend). Study 1 uses a context in which relatively low motivated perspective taking is needed, as the audit adjustment is (just) below tolerable misstatement. Investor-prompted auditors assess these adjustments as less likely to be material than do control-condition auditors, but only when the qualitative criterion is not violated. Study 2 adds a between-participate manipulation of whether the audit adjustment is just below or well above tolerable misstatement. Consistent with an instrumental increase in their degree of motivated perspective taking, investor-prompted auditors assess audit adjustments that simultaneously transition from just below to well above tolerable misstatement and from not violating to violating a qualitative criterion as significantly less likely to be material.