cssi/SciSciGPT-SciSciNet huggingface dataset:
Atomic Force Microscopy Calibration Methods for Lateral Force, Elasticity, and Viscosity

Due to huge uncertainties in the geometric dimensions of atomic force microscopy (AFM) probes, samples' rheological properties and lateral forces are difficult to measure and compare quantitatively. Hence, mathematical calibration methods fail to calibrate AFM probes accurately. To solve this problem, we will introduce in this paper “blind calibration methods” to determine quantitatively lateral forces, elastic constants and viscosity. For lateral force, a geometry factor is used to calibrate any cantilever using this “blind method”. The essential part of this method is a calibration standard sample that is commercially available. We have chosen silicon for our calibration standard sample and will discuss a cleaning procedure for reproducible lateral force measurements. We will provide an absolute friction value, which will serve as one of three parameters necessary to obtain the geometry factor. The other two components being the normal spring constant and the relative friction signal measured with the cantilever of interest. Further, we will discuss force modulation measurements and the problems that occur around resonances. We will provide a procedure to determine elastic constants also based on the silicon calibration standard. Finally, the “blind calibration method” will also be used to achieve kinematic viscosity values.
The Evaluation of Faculty Performance in Research and Service: Some Practical Benchmarks

This paper attempts to provide practical benchmarks for resolving four issues that are often contentious during the typically annual merit evaluation of marketing fuculty at US business schools. These are: (1) realistic weights for teaching, research and service, (2) consistency in the evaluation of research and service performance, (3) the issue of single versus multiple authorship and, (4) the importance given to various service activities. Specifically, the paper presents and analyzes mail survey data from chairs as well as members of performance evaluation committees of marketing departments at US business schools with and without a doctoral program. Similar data, obtained from finance faculty of the same schools, are also presented for comparison purposes.
Iodinated glycerol has no effect on pulmonary function, symptom score, or sputum properties in patients with stable chronic bronchitis

Study objective It has been reported that therapy with iodinated glycerol (IG) can improve the quality of life for patients with chronic bronchitis. The purpose of this study was to determine the effects of IG therapy on the quality of life, pulmonary function, and on the properties of sputum collected from adults with stable chronic bronchitis. Design Thirty-two week, double-blind, randomized, placebo-controlled cross-over study. Setting A university outpatient pulmonary clinic. Participants Twenty-six adults with stable chronic bronchitis completed the study; 28 completed the first treatment arm. Interventions Sixteen weeks each of placebo or IG 60 mg qid. Measurements First, pulmonary function by spirometry and plethysmography. Second, symptom score measured using a questionnaire. Third, sputum bulk and surface rheology, spinnability, mucociliary transportability and cough transportability. Results There were no significant changes in pulmonary function, clinical scores, or sputum properties related to therapy with IG. There was a significant improvement in the Global Petty score after both IG (p=0.01) and placebo (p Conclusions This study clearly demonstrates that in chronic bronchitis, 16 weeks of therapy with IG does not produce any appreciable effect on pulmonary function, well being, or on sputum viscoelasticity or clearability.
The Role of the Railroads in United States Economic Growth

The railroads played an important role in the economic history of the United States. It was an epic role, involving enterprise on a grand scale, evoking heated passions, and rich in anecdote and drama.
Ex Parte Young: An Interbranch Perspective

Ex parte Young (1908) is an honored icon of the federal courts canon, because it empowers federal courts to enforce the Constitution against the states. But it has had a strange and ironic career. It is not simply because the case was heavily criticized by liberals at the time, since it struck down Progressive Era legislation. Nor was it that liberals, decades later, resurrected the case to empower federal judges to enjoin discriminatory state action during the Civil Rights Era. It is also that the controversy over the decision engaged the critical response of the other branches of the federal government. This article, a contribution to a symposium on the centennial of Ex parte Young, addresses the waxing and waning of the case, focusing on the reaction of the other branches, a reaction that, in various ways, continued for many decades. Part I of the article discusses the varying litigation strategies of litigants, with different ideological agendas, who sought to utilize Ex parte Young-type relief throughout the twentieth century. Part II addresses the response of Congress to the decision, principally by the enactment of the three-judge district court to hear cases seeking that relief. Part III considers how the Executive branch, through the Department of Justice, has responded to the case and its progeny. The article concludes by situating the interbranch reaction to Ex parte Young in the literature on the various relationships and interactions between the courts, Congress, and the Presidency.
Trapping of a catalytic HIV reverse transcriptase*template:primer complex through a disulfide bond.

Abstract Background: HIV-1 reverse transcriptase (RT) is a major target for the treatment of acquired immunodeficiency syndrome (AIDS). Resistance mutations in RT compromise treatment, however. Efforts to understand the enzymatic mechanism of RT and the basis for mutational resistance to anti-RT drugs have been hampered by the failure to crystallize a catalytically informative RT–substrate complex. Results: We present here experiments that allow us to understand the reason for the failure to crystallize such a complex. Based on this understanding, we have devised a new approach for using a combinatorial disulfide cross-linking strategy to trap a catalytic RT·template:primer·dNTP ternary complex, thereby enabling the growth of co-crystals suitable for high-resolution structural analysis. The crystals contain a fully assembled active site poised for catalysis. The cross-link itself appears to be conformationally mobile, and the surrounding region is undistorted, suggesting that the cross-link is a structurally passive device that merely acts to prevent dissociation of the catalytic complex. Conclusions: The new strategy discussed here has resulted in the crystallization and structure determination of a catalytically relevant RT·template:primer·dNTP complex. The structure has allowed us to analyze possible causes of drug resistance at the molecular level. This information will assist efforts to develop new classes of nucleoside analog inhibitors, which might help circumvent current resistance profiles. The covalent trapping strategy described here may be useful with other protein–DNA complexes that have been refractory to structural analysis.
Tax Convergence and Globalization

This paper addresses three questions: 1. Is there evidence that the tax systems of different countries have converged (i.e., become more similar) in the period 1980-2010? 2. If so, what is the explanation for this convergence? 3. Is convergence a positive or negative development?
Methodology and demographics of a single blinded, randomized controlled trial of chiropractic compared to physical therapy for balance impairments in community dwelling geriatric patients with or without low back pain

Postural control problems effect between 28% and 35% of individuals over the age 65 and increases with age. Musculoskeletal pain in the elderly impacts 20% to 49% of people between the ages of 65 and 75, is a leading falls risk factor, and a robust predictor of morbidity. Polypharmacy in the management of chronic pain is common in the geriatric population. Conservative treatment options for balance and back pain are underrepresented in scientific literature. The methods and demographics for a prospective, randomized controlled single blinded clinical trial are described. This study evaluated the use of either chiropractic care or physical therapy as a treatment for patients with balance problems and with low back pain (68.5%) or without low back pain (31.5%) in the geriatric population. One hundred and sixty eight consecutively enrolled community dwelling adults between 60 and 85 years old (72.8 +/- 6.8) were randomly assigned to 6 weeks of either chiropractic care or physical therapy (12 - 18 visits). Testing occurred prior to randomization, after 6 weeks of treatment, and again 6 weeks later. Functional and self-report outcome measures for balance included the Berg Balance Scale, Performance Oriented Mobility Assessment, Timed Up and Go Test, and NeuroCom balance tests. Pain was assessed with the Visual Analog Scale, 21-Point Box Scale, and pressure algometry. Quality of life healthcare questionnaires included the Oswestry, the SF-36, and the Falls Efficacy Scale for confidence in performing everyday activities. Data analysis for this intent-to-treat design was a mixed-model analysis of variance (ANOVA) (p < 0.05) and Bonferroni correction (p < 0.017 and p < 0.025). This study was set in a university biomedical and healthcare research facility and university ethics committee approval was obtained and written informed consent was given by all study participants. The methodology of this multimodal treatment protocol for balance disorders and low back pain in the geriatric population and patient demographics are described in this paper. Additional research in this area is needed for this growing at risk population. NCT02031562.
Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection

Despite effective antiretroviral therapy (ART), individuals infected with human immunodeficiency virus (HIV) remain at higher risk for mortality and morbidities commonly associated with aging than the general population [1]. Chronic immune activation is thought to mediate this increased risk [2]. Many have hypothesized that the chronic inflammatory state of HIV infection may drive T-cell senescence, as seen with chronic cytomegalovirus (CMV) infection and among elderly HIV-uninfected individuals [3–5], potentially increasing the risk of infections and malignancies, and further fueling the persistent inflammatory state. T-cell senescence is typically characterized by the accumulation of terminally differentiated CD8+ T cells with shortened telomeres, loss of the costimulatory molecule CD28, and increased expression of CD57, a marker of proliferative history and poor proliferative capacity [6]. Even during suppressive ART, HIV-infected individuals have increased frequencies of CD28−CD8+ T cells [7, 8], but the impact of HIV on CD57 expression on CD8+ T-cell subsets—particularly the effector memory CD8+ T-cell subsets that normally express CD57—is less well documented. We recently demonstrated that although CMV promotes terminal differentiation and the expression of CD57 on CD28−CD8+ T cells, consistent with the “immunosenescent” phenotype of aging, HIV is associated with enrichment for less well-differentiated transitional CD8+ T cells and abnormally low proportions of CD28−CD8+ T cells expressing CD57 [9, 10]. In the current study, we sought to determine whether abnormally low proportions of CD28−CD8+ T cells expressing CD57 (ie, the %CD57+ of CD28−CD8+ T cells) are evident during the first few months of HIV infection, whether early ART initiation (<6 months following estimated date of HIV infection) is capable of reversing this abnormality, and whether persistently low proportions of CD28−CD8+ T cells expressing CD57 predict mortality during treated HIV infection. Because several innate immune activation pathways in HIV infection may contribute to T-cell proliferative defects [11, 12], we also assessed whether soluble markers of innate immune activation were associated with low proportions of CD28−CD8+ T cells expressing CD57.
Large systems and enterprise systems architecture

A number of diverse factors have influenced the development of IBM's Enterprise Systems Architecture. They range from the compatibility and migration considerations so important for preserving customer investments in existing applications and data, to new functional and capacity requirements of our customers, to the implications of emerging technologies and the projection of these into the systems environments of the future. This paper provides an introduction to a collection of technical papers in this issue describing the ESA/370™ facilities. Its purpose is to convey a broad perspective on important factors that will influence the large-systems environment of the future, and to relate those factors to the key elements of the ESA/370 architectural enhancements. It does not attempt to address all of the considerations leading to the development of ESA/370, nor discuss the new features in any depth. Detailed discussion of the specific features, facilities, and design considerations of ESA/370 will be found in other papers in this issue.
Micromachined microsystems: miniaturization beyond microelectronics

The current state of art in the development of micromachined microsystems is reviewed. Micromachining integrated circuit technologies are increasingly used in combination to develop systems that combine both electronic and non-electronic devices for sensing, actuation, and control. Micromachined systems capable of operating on electronic, mechanical, fluidic, optical, and radiative signals have been developed and commercialized. Several examples of emerging systems with application in microinstrumentation, inertial sensing, biomedical devices, wireless communication, and high-density data storage are presented.
Selection of stepsize in the variable-step predictor-corrector method of van wyk

Abstract Van Wyk has proposed and tested some predictor-corrector methods for ordinary differential equations which will allow a different mesh size for each equation in the system. In this paper we will justify in a more rigorous fashion one aspect of Van Wyk's mesh selection criterion — that of local truncation-error estimation. Van Wyk follows the almost universal practice of numerically justifying his truncation-error estimator by displaying small relative errors in the solution. All the numerical testing in this report will compare the truncation-error estimators against the true local truncation error.
A fluxless Au-Sn bonding process of tin-rich compositions achieved in ambient air

A new alternative fluxless bonding process conducted in ambient air is reported based on two different Au-Sn multilayer composite designs that are substantially tin-rich; namely, one with composition of 80 at.% Sn (70.54 wt.% Sn) and 20 at.% Au (29.46 wt.% Au), and another with 95 at.% Sn (91.82 wt.% Sn) and 5 at.% Au. (8.18 wt.% Au). We believe that this is the first time that Au-Sn bonding is achieved in air without the use of flux. The bonding process temperatures chosen for constructing 80 Sn-20 Au and 95 Sn-5 Au joints are 285/spl deg/C and 225/spl deg/C, respectively. Once produced, both types of joints were examined using the scanning acoustic microscopy (SAM) to confirm the bonding quality and the results obtained are nearly void-free. To study the microstructure and composition of the samples the scanning electron microscopy (SEM) equipped with energy dispersive X-ray (EDX) detector were conducted across the 95 Sn-5 Au joint cross-section.
A short proof of the nonexistence of a 2-resolvable balanced incomplete block design with parameters (v,b,r,k,λ)=(10,15,6,4,2)

Abstract The nonexistence of a 2-resolvable balanced incomplete block design with parameters ( v , b , r , k , λ ) = ( 10 , 15 , 6 , 4 , 2 ) was established by Kadowaki in 2001 using a computer search and by Kadowaki and Kageyama in 2008 by a lengthy case-by-case analysis. We give a short proof based on properties of the row sum vectors of submatrices in an incidence matrix.
Treatment of thrombotic saphenous vein bypass grafts using local urokinase infusion therapy with the Dispatch catheter.

Percutaneous treatment of thrombotic stenoses or total occlusions in aged saphenous vein bypass grafts is associated with a significant incidence of complications primarily related to distal embolization. The purpose of this study was to assess the efficacy of local urokinase delivery with the Dispatch catheter prior to balloon angioplasty and/or intragraft stent placement as a new technique of vein graft revascularization. Local urokinase delivery with the Dispatch catheter was performed in 15 saphenous vein grafts (mean age = 11.7 ± 2.5 yr) in 13 patients with unstable or postinfarction angina. The target lesion was a total occlusion in 5 of the procedures and a severe vein graft stenosis in the remaining 10. In all cases, urokinase was administered directly to the site of the stenosis/occlusion via the Dispatch catheter at 0.5 cc/min and at a concentration of 30,000 units/cc. The mean urokinase infusion time for the 15 procedures was 33 ± 10 min (range = 10–60 min) and the mean urokinase dose was 495,000 ± 158,000 units (range = 150,000–900,000 units). Following Dispatch therapy, mean minimal lumen diameter increased from 0.34 ± 0.32 to 1.81 ± 0.78 mm (P < 0.01), mean TIMI flow increased from 1.9 ± 1.4 to 2.8 ± 0.8 (P < 0.06), and mean thrombus score was reduced from 2.3 ± 0.6 to 0.3 ± 0.8 (P < 0.01). Mild no reflow was noted in two cases, although no patient demonstrated angiographic evidence of gross distal embolization. One of the patients with no reflow also demonstrated a small increase in cardiac enzymes. Subsequent balloon angioplasty/stent placement was successful in 14 of the 15 procedures (93% success rate). This preliminary report suggests that pretreatment of thrombotic saphenous vein graft stenoses with local urokinase delivery via the Dispatch catheter may decrease intragraft thrombus and possibly decrease the incidence of vascular complications associated with percutaneous intervention. This technique may allow for recanalization of totally occluded vein grafts with large clot burdens by using significantly less urokinase and shorter drug administration times than conventional infusion protocols. Cathet. Cardiovasc. Diagn. 41:261–267, 1997. © 1997 Wiley-Liss, Inc.
Toward a model of the everyday life information needs of urban teenagers, part 1: Theoretical model

This is the first part of a two-part article that offers a theoretical and an empirical model of the everyday life information needs of urban teenagers. The qualitative methodology used to gather data for the development of the models included written surveys, audio journals, written activity logs, photographs, and semistructured group interviews. Twenty-seven inner-city teens aged 14 through 17 participated in the study. Data analysis took the form of iterative pattern coding using QSR NVivo 2 software (QSR International, 2002). The resulting theoretical model includes seven areas of urban teen development: the social self, the emotional self, the reflective self, the physical self, the creative self, the cognitive self, and the sexual self. The researchers conclude that the essence of teen everyday life information seeking (ELIS) is the gathering and processing of information to facilitate the teen-to-adulthood maturation process. ELIS is self-exploration and world exploration that helps teens understand themselves and the social and physical worlds in which they live. This study shows the necessity of tying youth information-seeking research to developmental theory in order to examine the reasons why adolescents engage in various information behaviors.
Human papillomavirus vaccine acceptance among young men in Bangalore, India

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. It can lead to anogenital cervical and head and neck cancer with higher risk of malignant disease in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. In India 73000 of the 130000 women diagnosed with cervical cancer die annually. Gardasil((R)) a vaccine available against HPV types 6 11 16 and 18 is approved for use in women in India but not men. A backlash to post-licensure trials has created a negative public opinion of the vaccine for women. Vaccinating boys and men is an alternate approach to prevent cervical cancer in women. This study gauges facilitators and barriers to vaccination acceptance among men in Bangalore India. MATERIALS AND METHODS: Young men presenting to a dermatology clinic or an ART center in Bangalore India answered a seven-point survey assessing acceptance of the HPV vaccine perceived barriers to vaccination and acceptance of vaccination for their children. Ninety-three general dermatology patients and 85 patients with HIV/AIDS participated. RESULTS: There was a high degree of vaccine acceptance for both groups 83 and 98% respectively. Vaccine side effects and cost were cited as key barriers to vaccination and doctor recommendation and government approval were the main facilitators. CONCLUSION: There is potential for high acceptability of the HPV vaccine among men in India. These results can facilitate further study of vaccine acceptance among males and physician opinion and knowledge about HPV vaccine use. Vaccination of males is a hopeful strategy to protect men and women from HPV-related malignancies. (c) 2014 The International Society of Dermatology.
Uterine peroxidase activity in malignant, hyperplastic, and atrophic endometrium

Abstract Uterine peroxidase activity in endometrial adenocarcinoma, hyperplasia, and atrophy has been studied. This investigation supplements previous studies which have defined uterine peroxidase activity in the normal menstrual cycle, in women receiving an oral progestogen, and in women with premenopausal dysfunctional uterine bleeding. The potential significance of uterine peroxidase activity as an index of the relationship between estrogen and the endometrium is discussed.
Applying Lean Six Sigma for innovative change to the post-anesthesia care unit

Many healthcare organizations are building or renovating patient care facilities. Using Lean Six Sigma methods, nurse leaders can eliminate unnecessary waste and improve work and patient care environments. Starting with a key department like the post-anesthesia care unit is a good way to expose staff and leaders to the potential of Lean.
The intercalated discs of atrophied heart muscle

In two earlier papers1 I presented evidence in support of my interpretation of intercalated discs as irreversible contraction bands. In a more recent paper the idea was tested by appearances in a natural experiment, namely, extremely hypertrophied heart muscle.2 The conditions here obtaining were in perfect accord with, and confirmed the plausibility of, my previous interpretation. Since then I have had opportunity to study lesser degrees of hypertrophy, as well as an excellent specimen of atrophy3 (weight of heart 180 grams). It is the purpose of this note to complete my report of observations on intercalated discs by a record of my findings in atrophied heart muscle, and to reemphasize the point that all the evidence, including ontogenetic, comparative anatomical and pathological (experimental—including the phenomena of fragmentation and segmentation) data points to the same conclusion, namely, that the so-called “discs” are aggregations of irreversible contraction foci on the myofibrillae in the form of...
HEART DISEASE ON HEARTBREAK HILL: ATYPICAL ACUTE CORONARY SYNDROME DURING THE BOSTON MARATHON

Acute complications of underlying coronary artery disease are the most common cause of sudden death during long-distance running events. Their incidence is rising as the participant pool becomes larger, older, and more medically diverse. A 57 year-old healthy woman developed nausea, mild chest and
Anticancer and Antioxidant Activity of Lindera strychnifolia Extracts

Anticancer and antioxidant activities of 5 fractions(petroleum ether,chloroform,ethyl acetate,1-butanol,water) of ethanol extract of Lindera strychnifolia were investigated.The results of anticancer assay show that petroleum ether fraction has the strongest cytotoxic activity on 4 human cancer cell lines tested.HepG2(IC50:(71.9±1.1) mg·L-1) is most vulnerable to the cytotoxic effect of petroleum ether fraction.And the petroleum ether fraction induces apoptosis in HepG2.The results of antioxidant assay show that the ethyl acetate fraction exhibits strongest antioxidant activity among all the samples of Lindera strychnifolia.
Medicaid Expenditures for Fee-for-Service Enrollees with Behavioral Diagnoses: Findings from a 50 State Claims Analysis

Medicaid is an important funder of care for individuals with behavioral (psychiatric and/or substance use) diagnoses, and expenditures will likely increase with expansion of services under the Affordable Care Act. This study provides national estimates of Medicaid expenditures using a comprehensive sample of fee-for-service Medicaid enrollees with behavioral diagnoses. Data for analysis came from 2003 to 2004 Medicaid Analytic eXtract (MAX) files for 50 states and the District of Columbia. Individuals with behavioral diagnoses had high rates of chronic medical comorbidities, and expenditures for medical (non-behavioral) diagnoses accounted for 74 % of their health care expenditures. Total Medicaid expenditure was approximately 15 billion dollars (equivalent to 18.91 billion in 2016 dollars) for individuals with any behavioral diagnosis. Medicaid fee-for-service beneficiaries with behavioral diagnoses have a high treated prevalence of individual medical comorbid conditions, and the majority of health care expenditures in these individuals are for medical, rather than behavioral health, services.
Brain and Language

Publisher Summary This chapter discusses the relationship between brain and language. The typically asymmetric distribution of language functions in the brain is perhaps the most important component of the concept of hemispheric dominance or specialization. However, the lateralization of language seems to be neither consistent nor unidirectional across different linguistic levels, and much of the evidence is, to say the least, controversial. Positron emission tomography (PET) and electroencephalography (EEG) studies clearly show right-hemisphere changes in activity in homologous cortical locations to the left-hemisphere sites during all language tasks even during the simple naming tasks. It can, therefore, be concluded that there is much more to the right hemisphere's contribution to language than superficially tapped by the lesion studies. The fact that the left-hemisphere PET changes are often larger than the right-hemisphere PET changes in a language task seems a weak basis on which to assume that the change in metabolism exclusively or even primarily reflects language processing.
Nanoelectronic Heterodyne Sensor: A New Electronic Sensing Paradigm

ConspectusNanoelectronic devices based on nanomaterials such as nanowires, carbon nanotubes, graphene, and other 2D nanomaterials offer extremely large surface-to-volume ratios, high carrier mobility, low power consumption, and high compatibility for integration with modern electronic technologies. These distinct advantages promise great potential for nanoelectronic devices as next generation chemical and biological sensors. Currently, majority of existing nanoelectronic sensors are direct current (DC) sensors, which rely ubiquitously on detection of conductance change associated with molecular adsorption. However, despite the simplicity of the conventional DC sensing technology, it also has severe limitations such as the Debye screening effect in ionic solutions, and the speed-sensitivity trade-off for the detection of charge-neutral molecules. Hence, the development of nanoelectronic sensors calls for new sensing platform technologies that can truly showcase the advantages of electronic sensors.In this ...
In Reply to Myers et al.

I thank Dr. Myers and colleagues for their thoughtful letter describing their own experience grappling with authorship order “within and across” disciplines. In response, I first wish to commend the writers for their forthright account of their experience. This topic is seldom discussed, and only ra
Commercial Health Plan Coverage of Selected Treatments for Opioid Use Disorders from 2003 to 2014.

ABSTRACTOpioid use disorders (OUDs) are receiving significant attention in the U.S. as a public health crisis. Access to treatment for OUDs is essential and was expected to improve following implementation of the federal parity law and the Affordable Care Act. This study examines changes in coverage and management of treatments for OUDs (opioid treatment programs (OTPs) as a covered service benefit, buprenorphine as a pharmacy benefit) before, during, and after parity and ACA implementation. Data are from three rounds of a nationally representative survey conducted with commercial health plans regarding behavioral health services in benefit years 2003, 2010, and 2014. Data were weighted to be representative of health plans’ commercial products in the continental United States (2003 weighted N = 7,469, 83% response rate; 2010 N = 8,431, 89% response rate; and 2014 N = 6,974, 80% response rate). Results showed treatment for OUDs was covered by nearly all health plan products in each year of the survey, but ...
Ccl5 establishes an autocrine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival.

// Yuan Pan 1 , Laura J. Smithson 1 , Yu Ma 1 , Dolores Hambardzumyan 2 , David H. Gutmann 1 1 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA 2 Department of Oncology, Aflac Cancer and Blood Disorders Center, Emory University, GA, USA Correspondence to: David H. Gutmann, email: gutmannd@wustl.edu Keywords: chemokine, glioma, neurofibromin, mTOR, CD44 Received: October 24, 2016 Accepted: March 13, 2017 Published: March 23, 2017 ABSTRACT Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a median survival of 15 months. These poor clinical outcomes have prompted the development of drugs that block neoplastic cancer cell growth; however, non-neoplastic cell-derived signals (chemokines and cytokines) in the tumor microenvironment may also represent viable treatment targets. One such chemokine, Ccl5, produced by low-grade tumor-associated microglia, is responsible for maintaining neurofibromatosis type 1 (NF1) mouse optic glioma growth in vivo . Since malignant gliomas may achieve partial independence from growth regulatory factors produced by non-neoplastic cells in the tumor microenvironment by producing the same cytokines secreted by the stromal cells in their low-grade counterparts, we tested the hypothesis that CCL5/CCL5-receptor signaling in glioblastoma creates an autocrine circuit important for high-grade glioma growth. Herein, we demonstrate that increased CCL5 expression was restricted to both human and mouse mesenchymal GBM (M-GBM), a molecular subtype characterized by NF1 loss. We further show that the NF1 protein, neurofibromin, negatively regulates Ccl5 expression through suppression of AKT/mTOR signaling. Consistent with its role as a glioblastoma growth regulator, Ccl5 knockdown in M-GBM cells reduces M-GBM cell survival in vitro , and increases mouse glioblastoma survival in vivo . Finally, we demonstrate that Ccl5 operates through an unconventional CCL5 receptor, CD44, to inhibit M-GBM apoptosis. Collectively, these findings reveal an NF1 -dependent CCL5-mediated pathway that regulates M-GBM cell survival, and support the concept that paracrine factors important for low-grade glioma growth can be usurped by high-grade tumors to create autocrine regulatory circuits that maintain malignant glioma survival.
Shedding Light on Daylight Saving Time

In this report, the JPMorgan Chase Institute measures the impacts of Daylight Saving Time (DST) on consumer spending. Using a sample of over 380 million daily credit and debit card transactions, made by over 2.5 million de-identified customers, we compared consumer spending in Los Angeles, a city that observes DST, to that of Phoenix, a city that does not observe DST. We organize our results into three findings. First, the onset of DST in Los Angeles increases daily card spending per capita by 0.9 percent, while the end of DST reduces daily card spending per capita by 3.5 percent. Second, in Los Angeles, DST is more likely to be associated with changes in daily card spending per capita directed towards goods rather than services. Third, daily card spending per capita in Los Angeles drops significantly more during the work week in response to the end of DST. This report indicates that economic impact of DST is not uniform; the impact on a given city is an empirical question. It is also important to note that there are other reasons to support DST beyond the impacts on consumer spending.
The Power of One: The Strategy Diamond Framework

The diamond framework can be used to develop strategies in multibusiness enterprises at all organizational levels and across markets or products. This note demonstrates how the framework yields insights that managers and executives need in order to make critical strategic decisions. The power of a single integrated approach lies in its transformative ability to unite a firm with one template based on a common language and shared lexicon. Excerpt UVA-S-0237 Feb. 7, 2014 THE POWER OF ONE: THE STRATEGY DIAMOND FRAMEWORK Organizations need a coherent strategy to achieve their objectives. In “Are You Sure You Have a Strategy?,” Donald C. Hambrick and James W. Fredrickson present an eminently practical approach to developing a clear strategic plan. They identify five elements of strategy: arenas—where a firm should be active; vehicles—how it can enter the arenas; differentiators—how it can win in its markets; staging—sequence and speed of moves; and, at the core of their framework, economic logic—how the firm plans to obtain its returns. Together these five facets form a strategy diamond framework. The diamond framework can be used to develop strategies in multibusiness enterprises at all organizational levels and across markets or products. This note demonstrates how the framework yields insights that managers and executives need in order to make critical strategic decisions. The power of a single integrated approach lies in its transformative ability to unite a firm with one template based on a common language and shared lexicon. First, we will examine the components of the diamond framework and then show specific applications. These include how to create an integrative organizational strategy, how to plan for strategic change over time, and how to apply the framework both for competitor analysis and for comparison of your firm's strategy with those of your partners and other stakeholders. . . .
Automatic Extraction of Deep Phenotypes for Precision Medicine in Chronic Kidney Disease

Chronic Kidney Disease (CKD) is one of the deadliest diseases in the world, with 10% of the global population affected by the disease. Identifying subpopulations with characteristic disease progressions is important to find more efficient treatments for patients with this disease. The abundance of electronic health records (EHR) data can be used to find meaningful subtypes for CKD but comes with challenges during analysis, including irregular data sampling, and skewness in the data collected over time. In this paper, multiple regression techniques were used to fill in the missing estimated glomerular filtration rate (or eGFR -- a key measure for kidney function) trajectory data, so it can be clustered effectively. Clustering is applied to the enhanced data to obtain six subtypes, which capture crucial trends in the disease progression of patients. Moreover, the characteristics of patients in each of the subtypes had minor differences from others. These characteristics demonstrate risk factors and positive lifestyles choices of patients with CKD, which can help develop new treatments for CKD.
Describing the Community in Thorough Detail

Community study as a method focuses holistically on how people think and act in their every-day lives, in their natural settings. An inductive process is used to learn the meanings attached to things in their lives. If a community is selected carefully it can serve as a representative cultural or societal sample. For a community study the researcher is the research instrument who typically becomes immersed in the place, even for a short while. The researcher inter-acts with people, shares daily life, and participates in community experiences with at least some of the inhabitants. In this process, termed participant observation, data are collected systematically and unobtrusively (Taylor and Bogdan, 1998). Being an observer has moral and ethical problems, and communities are not likely to agree with all or some of what is found [c.f., famous example of (1968)]. A community study can provide vivid rich detail that uniquely in social science research makes a place come alive, due to the field immersion of the researcher. A typical criticism is that a researcher produces a sympathetic portrait of a place, due to a lack of detachment (Bell and Newby, 1972). The aim is to describe the uniqueness of a community studied but simultaneously show that it is representative of a problem or phenomena in, and theory about, the wider society.
"I Believe What I See": College Students' Use of Media, Issue Engagement, and Perceived Responsibility Regarding Campus Sexual Assault.

The topic of campus sexual assault has received much media attention recently, prompting scholars to examine media effects on students’ attitudes and behaviors. A survey of 567 American college students examined how their media exposure is related to issue engagement, perceived responsibility, and acceptance of rape myths. Results indicated that reading newspaper stories about campus sexual assault might contribute to college students’ victim blaming. Among other media channels examined, social media were found to be highly correlated with students’ engagement with the issue. We also found that victim blaming and acceptance of rape myths could be reduced by raising students’ perceived importance of the issue. Theoretical and practical implications are discussed in detail.
Form and characteristics of the cardiovascular conditional response in Rhesus monkeys.

Three Rhesus monkeys restrained in primate chairs were exposed to several Pavlovian control procedures, followed by 13 sessions of cardiac conditioning under a delay paradigm. The conditional stimulus (CS) was a vertical line and the unconditional stimulus (US) was electric foot shock. Heart rate (HR) was analyzed in successive fivesecond intervals beginning five seconds before CS onset. The major finding was that the conditional response was consistently biphasic and consisted of an initial acceleration followed by deceleration toward the baseline, but rarely reaching it before onset of US. The subjects differed in magnitude of acceleration and subsequent deceleration as well as the location of the maximum rate in the CS-US interval. A breakdown of trials on the basis of the pre-CS HR revealed that the magnitude of effect was inversely related to the pre-CS rate.
Coronary circulation: Pressure/flow parameters for assessment of ischemic heart disease

Both invasive and non-invasive parameters have been reported for assessment of the physiological status of the coronary circulation. Fractional flow reserve and coronary (or myocardial) flow reserve may be obtained by invasive or non-invasive means. These metrics of coronary stenosis severity have achieved wide clinical acceptance for guiding revascularization decisions and risk stratification. Other indices are obtained invasively (e.g., instantaneous wave-free ratio, iFR; hyperemic stenosis resistance) or non-invasively (e.g., PET absolute myocardial blood flow (mL/min/g)) and have been used for the same purposes. Both iFR, and whole-cycle distal coronary to aortic mean pressure (Pd/Pa) are measured under basal condition and used for assessment of hemodynamic stenosis severity as is index of basal stenosis resistance (BSR). These metrics typically are dichotomized at an empirically derived cut point into "normal" and "abnormal" categories for purposes of clinical decision making and data analysis. Once dichotomized the indices do not always point in the same direction and so confusion may arise. This review, therefore, will present basic principles relevant to understanding commonly employed metrics of the physiological status of the coronary circulation, potential strengths and weaknesses, and hopefully an improved appreciation of the clinical information provided by each.
Path forward for softwarization to tackle evolving hardware

Even though legacy scientific code bases have long lifetimes and not going away anytime soon, by 2030, disruptive technologies would have dramatically changed softwarization. Are we ready to tackle tomorrow’s hardware? Relying on traditional programming paradigms will no longer suffice. We need to explore software abstractions and advanced smart techniques in compiler and runtime systems to effectively exploit tomorrow’s hardware. With the advent of neuromorphic chips and quantum computers as effective accelerators to which traditional X86 systems could offload relevant computations, we need to rethink the impact of these disruptive technologies on today’s software and fundamental programming abstractions.
Privacy-Preserving Data Integration Using Decoupled Data

Data from social network websites are an excellent source of information for studying human behavior and interactions. Typically, when analyzing such data, the default mode of access is de-identified data, which provides a level of privacy protection. However, due to its inability to link to other data, de-identified data has limitations with regard to answering broad and critically important questions about our complex society. In this study, we investigate the properties of information related to privacy, and we present a novel model of data access called decoupled data access for studying personal data using these properties. “Decoupling” refers to separating out the identifying information from the sensitive data that needs protection. We suggest that decoupled data access can provide flexible data integration with error management while providing the same level of privacy protection as de-identified data. We further test the ability of different mechanisms to hinder inference of identity when names are revealed for data integration. Our results show that through chaffing, not specifying the universe around the data, and revealing names in isolation, the real identities of names for both common and rare names can be protected.
Ecological interface design (EID) and the management of large numbers of intelligent agents

Agent-based automation is an emerging technology that presents new challenges if humans are to manage it effectively. Current automation has been plagued with mode errors, misuse and disuse. The properties of agent-based automation that make it most useful, those of an adaptive self-organizing system may lead to a poor calibration of operators’ trust in the automation and a magnification of automation-related problems. The focus of ecological interface design to graphically display the underlying system constraints offers a promising design strategy to promote effective use of agent-based automation.
Development and Analysis of Defect Tolerant Bipartite Mapping Techniques for Programmable cross-points in Nanofabric Architecture

Chemically Assembled Electronic Nanotechnology (CAEN) using bottom-up approach for digital circuit design has imposed new dimensions for miniaturization of electronic devices. Crossbar structures or Nanofabrics using silicon nanowires and carbon nanotubes are the proposed building blocks for CAEN, sizing less than 20 nm, allowing at least 1010 gates/cm2. Along with the decrease in size, defect rates in the above architectures increase rapidly, demanding for an entirely different paradigm for increasing yields, viz. greater defect tolerance, because the defect rates can be as high as 13% or more. In this paper, we propose a non-probabilistic approach for defect tolerance and evaluate it in terms of its coverage for different sizes of fabric and different defect rates.
Abstract IA20: Lineage plasticity in antiandrogen resistance

Resistance to the novel androgen receptor (AR)-directed therapies enzalutamide and abiraterone acetate can evolve with an aggressive clinical phenotype and atypical histology, including neuroendocrine features. Genomic studies have also revealed enrichment in TP53 and RB1 alterations in advanced metastatic CRPC when compared with primary disease. In recent work, the Sawyers and Goodrich groups have independently shown that concurrent loss of TP53 and RB1 confers resistance to antiandrogen and lineage plasticity through upregulation of the transcription factor SOX2. These studies implicate key tumor suppressors in lineage switching in resistant prostate cancer, and suggest that antiandrogen resistance may be targeted by epigenetic agents in advanced disease. Citation Format: Wassim Abida. Lineage plasticity in antiandrogen resistance [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA20.
Descending Control Mechanisms and Chronic Pain

The goal of the review was to highlight recent advances in our understanding of descending pain-modulating systems and how these contribute to persistent pain states, with an emphasis on the current state of knowledge around “bottom-up” (sensory) and “top-down” (higher structures mediating cognitive and emotional processing) influences on pain-modulating circuits. The connectivity, physiology, and function of these systems have been characterized extensively over the last 30 years. The field is now beginning to ask how and when these systems are engaged to modulate pain. A recent focus is on the parabrachial complex, now recognized as the major relay of nociceptive information to pain-modulating circuits, and plasticity in this circuit and its connections to the RVM is marked in persistent inflammatory pain. Top-down influences from higher structures, including hypothalamus, amygdala, and medial prefrontal areas, are also considered. The challenge will be to tease out mechanisms through which a particular behavioral context engages distinct circuits to enhance or suppress pain, and to understand how these mechanisms contribute to chronic pain.