cssi/SciSciGPT-SciSciNet huggingface dataset:
Curcumin: A Double Hit on Malignant Mesothelioma

Inflammation is a key mediator in the development of malignant mesothelioma, which has a dismal prognosis and poor therapeutic strategies. Curcumin, a naturally occurring polyphenol in turmeric, has been shown to possess anticarcinogenic properties through its anti-inflammatory effects. Inflammasomes, a component of inflammation, control the activation of caspase-1 leading to pyroptosis and processing of proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the present study, we investigate the role of curcumin in pyroptotic cell death of malignant mesothelioma cells. Using in vitro models with mouse and human malignant mesothelioma cells, curcumin is shown to induce pyroptosis through activation of caspase-1 and increased release of high-mobility group box 1 (HMGB1) without processing of IL-1β and IL-18. Absence of IL-1β processing in response to curcumin-mediated caspase-1 activation is attributed to blockade of pro-IL-1β priming through inhibition of the NF-κB pathway. Furthermore, curcumin's cytotoxicity in malignant mesothelioma cells is demonstrated to be dependent on pyroptosis as inhibition of caspase-1 resulted in protection against curcumin-induced cell death. We also demonstrate that curcumin-mediated caspase-1 activation is oxidant dependent by using N-acetyl-L-cysteine (NAC) to inhibit pyroptosis. PCR array analysis using the human inflammasome template revealed that curcumin significantly downregulated levels of inflammasome-related gene expression involved in inflammation, e.g., NF-κB, toll-like receptors (TLR), and IL-1β. Our data indicate that curcumin has a double effect on malignant mesothelioma cells through induction of pyroptosis while subsequently protecting against inflammation.
Evaluating voltage-tunable materials for RF phase shifter technology

Abstract Today's phased-array antennas use hundreds of radiating elements that use relatively high-loss phase shifters that operate over a limited bandwidth. The number of elements and the phase shifter losses affect the overall cost of the antenna system. Ferroelectric RF phase shifters have the potential to meet the low-loss, low-cost requirements driving many phased-array applications. Some of the issues affecting the development of ferroelectric phase shifters include ferroelectric tunability, dielectric losses, conductor losses, and impedance mismatch. We used the measured tunability (250 kHz, room temperature), dielectric constant, and loss tangent (10 GHz, room temperature) of Ba1-xSrx/TiO3 (0.4x 0.6) with various amounts of MgO additive, 0 to 60 wt.%, to estimate the device performance of microstrip phase shifters. The electromagnetic model of the microstrip (which uses a standard 3-mil-wide 1-oz. copper line, 3-mil-thick BST/MgO composite and the bias criteria of 2 V/μm) has produced performance ...
Myocardial perfusion imaging with technetium-99m sestamibi in patients with cocaine-associated chest Pain

Study objective : To describe the characteristics and outcome in patients presenting to the emergency department with chest pain associated with cocaine use, the majority of whom underwent early rest perfusion imaging. Methods : From January 1994 to June 1996, 218 patients had 241 ED visits for evaluation of symptoms consistent with myocardial ischemia after cocaine use. High-risk patients (N=25) were admitted directly to the CCU for exclusion of myocardial infarction (MI). Moderate- to low-risk patients (N=216) were promptly injected with technetium-99m sestamibi in the ED and underwent gated myocardial perfusion imaging 60 to 90 minutes later. Moderate-risk patients were observed in the CCU, whereas low-risk patients with negative perfusion imaging results were discharged home directly from the ED. Results : A diagnosis of MI was made in 6 patients, 4 of whom had ECG findings consistent with MI. Of the 216 patients who underwent perfusion imaging, 5 had positive study results, including 2 with MI. None of the 38 patients with negative results after perfusion imaging who were admitted to the CCU had a diagnosis of MI. Only 6 of the 67 patients undergoing stress perfusion imaging had reversible perfusion defects. At 30-day follow-up, there were no cardiac events in patients with negative results after rest perfusion imaging. Conclusion : Acute MI is infrequent in patients presenting with cocaine-associated chest pain. Positive results after rest perfusion imaging are uncommon, suggesting that myocardial ischemia is infrequently the cause of cocaine-associated chest pain. Early perfusion imaging may offer an effective alternative to routine CCU admission of patients with cocaine-related cardiac symptoms.
Metabolism of Angiotensin-(1–7) by Angiotensin-Converting Enzyme

Angiotensin converting enzyme (ACE) inhibitors augment circulating levels of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] in man and animals. Increased concentrations of the peptide may contribute to the antihypertensive effects associated with ACE inhibitors. The rise in Ang-(1-7) following ACE inhibition may result from increased production of the peptide or inhibition of the metabolism of Ang-(1-7)-similar to that observed for bradykinin. To address the latter possibility, we determined whether Ang-(1-7) is a substrate for ACE in vitro. In a pulmonary membrane preparation, the ACE inhibitor lisinopril attenuated the metabolism of low concentrations of 125I-Ang-(1-7). The primary product of 125I-Ang-(1-7) metabolism was identified as Ang-(1-5). Using affinity-purified ACE from canine lung, HPLC separation and amino acid analysis revealed that ACE functioned as a dipeptidyl carboxypeptidase cleaving Ang-(1-7) to the pentapeptide Ang-(1-5). The ACE inhibitors lisinopril and enalaprilat (1 micromol/L), as well as the chelating agents EDTA, o-phenanthroline, and DTT (0.1-1 mmol/L) abolished the generation of Ang-(1-5) and did not yield other metabolic products. Ang-(1-5) was not further hydrolyzed by ACE. Kinetic analysis of the hydrolysis of Ang-(1-7) by ACE revealed a substrate affinity of 0.81 micromol/L and maximal velocity of 0.65 micromols min(-1) mg(-1). The calculated turnover constant for the peptide was 1.8 sec(-1) with a catalytic efficiency (Kcat/Km) of 2200 sec(-1) mmol/L(-1). These findings suggest that increased levels of Ang-(1-7) following ACE inhibition may be due, in part, to decreased metabolism of the peptide.
Mechanisms of Ventricular Fibrillation Initiation in MADIT II Patients with Implantable Cardioverter Defibrillators

Background:The availability of stored intracardiac electrograms from implantable defibrillators (ICDs) has facilitated the study of the mechanisms of ventricular tachyarrhythmia onset. This study aimed to determine the patterns of initiation of ventricular fibrillation (VF) in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients along with associated electrocardiogram (ECG) parameters and clinical characteristics. Methods:Examination of stored electrograms enabled us to evaluate the rhythm preceding each episode of VF and to calculate (intracardiac) ECG parameters including QT, QT peak (QTp), coupling interval, and prematurity index. Results:Sixty episodes of VF among 29 patients (mean age 64.4 ± 2.5 years) were identified. A single ventricular premature complex (VPC) initiated 46 (77%) episodes whereas a short-long-short (SLS) sequence accounted for 14 (23%) episodes. Of the 29 patients studied, 23 patients had VF episodes preceded by a VPC only, two patients with SLS only, and four patients with both VPC and SLS-initiated episodes. There were no significant differences between initiation patterns in regards to the measured ECG parameters; a faster heart rate with SLS initiation (mean RR prior to VF of 655 ± 104 ms for SLS and 744 ± 222 ms for VPC) approached significance (P = 0.06). The two patients with SLS only were not on β-blockers compared to 83% of the VPC patients. Conclusion:Ventricular fibrillation is more commonly initiated by a VPC than by a SLS sequence among the MADIT II population. Current pacing modes designed to prevent bradycardia and pause-dependent arrhythmias are unlikely to decrease the incidence of VPC-initiated episodes of VF.
Bosentan and Warfarin Interaction

OBJECTIVE:To report a case of decreased international normalized ratio (INR) in a patient receiving warfarin and bosentan.CASE SUMMARY:A 35-year-old African American woman with a history of primary pulmonary hypertension managed with warfarin, diltiazem, and hydrochlorothiazide was initiated on bosentan therapy. The patient's INR had been stable and within therapeutic range (goal 2.0–3.0) for the previous 3 months with warfarin 27.5 mg/wk, but became subtherapeutic after 10 days of bosentan therapy. Addition of over-the-counter medications, herbal products, vitamins, or dietary changes was denied. The INR remained subtherapeutic for 5 weeks despite weekly warfarin dose increases. After these 5 weeks of dosage increases, the INR became supratherapeutic for 3 weeks, resulting in a subsequent dosage decrease. The resultant warfarin dose required to maintain a therapeutic INR was 45 mg/wk, a 63.6% dosage increase after the initiation of bosentan.DISCUSSION:This case shows that a clinically significant interac...
Global positioning systems data for performance evaluation of HOV and GP lanes on I-66 and I-395/I-95

In this study an empirical analysis is conducted for assessing the performance of high occupancy vehicle (HOV) lanes using Global Positioning System (GPS). Second by second speed, time, and location data were obtained from GPS equipped probe vehicles on HOV lanes with exclusive right of way as well as on HOV lanes that share the right of way with general purpose (GP) lanes. Peak-hour operations of HOV facilities on I-66 and I-395/I-95 corridors in the Washington DC area were used as test beds. Parameters for the performance measures such as travel time, mean journey speed, delay, proportion of stopped time and congestion index were developed and compared for HOV and GP lanes. The data were also used to identify location and the extent of congestion along the study routes. The results of the analysis showed travel times saving, higher journey speeds, less delay, and lower congestion incurred by the probe vehicles on the HOV lanes as compared to the probe vehicles traveling simultaneously on non-HOV lanes
Management of Postsurgical Hyperhidrosis With Direct Current and Tap Water

Background and Purpose. Excessive sweating, known as hyperhidrosis, involves the eccrine sweat glands of the axillae, soles, palms, and/or forehead. The use of iontophoresis to reduce or eliminate excessive sweating has been described since 1952. The purpose of this case report is to describe the use of tap water galvanism (TWG) using direct current (DC) with a patient who had postsurgical hyperhidrosis. Case Description. The patient was a 36-year-old male electrician with traumatic phalangeal amputation and postsurgical development of hyperhidrosis. Tap water galvanism was administered using a DC generator, 2 to 3 times per week for 10 treatments. The patient's hands were individually submerged in 2 containers of tap water with the electrodes immersed directly into the containers. Each hand was treated with 30 minutes of TWG at 12 mA. Hyperhidrosis was measured by a 5-second imprint and subsequent tracing of the left hand placed on dry paper toweling. Outcomes. The patient's hyperhidrosis decreased from the full left palmar pad, with a surface area of 10.3×12.0 cm, to a reduced area of wetness that covered a 2.2-×2.7-cm area. The patient returned to work as an electrician without needing absorbent gloves, which had prevented him from performing electrical work. Discussion. Following use of TWG, the patient's palmar hyperhidrosis returned to normhidrosis.
A rapid method for the identification of acidic, neutral, and basic drugs in postmortem liver specimens by toxi-lab

A rapid, qualitative method for the identification of drugs and drug metabolites in postmortem liver specimens has been developed using the Toxi-Lab | drug screening system. A single-step liquid-liquid extraction, using heptane/dichloromethane, was employed for acidic/neutral drugs. Basic/neutral drugs were extracted with 1-chlorobutane and subjected to back-extraction and lipid clean-up. Chromatographic separation and drug identification required no further modifications of the Toxi-Lab procedure. The method, including tissue preparation, requires approximately 2 hr, is compatible with GLC analysis, and utilizes minimal sample size. The assay allows detection of 5 to 20 ~g of drug/g of tissue. The use of this assay in forensic analyses is discussed.
A great religious octopus: Church and State at Virginia's constitutional convention, 1901-1902

A hundred years ago Virginia drafted a new state constitution designed to disfranchise African American voters. That objective was transparent from the outset of the convention. As John Goode, the presiding officer, assumed his seat, he called black suffrage “a great crime against civilization and Christianity.” At the age of seventy-two, Goode was the grand old man of the convention. A graduate of the University of Virginia and life-long Democrat, he had served in the state legislature, the Secession Convention of 1861, the Confederate legislature, and the U.S. House of Representatives before his appointment as Solicitor General of the United States in 1885. Goode reflected the mentality of the vast majority of convention delegates when he stated that African Americans were incapable of education or citizenship. “The omniscient Ruler of the Universe … made [them] inferior,” he proclaimed, and sometime in the future, when the North knew better, the Fifteenth Amendment would be repealed.
The developmental stages of synaptic plasticity

The brain is programmed to drive behaviour by precisely wiring the appropriate neuronal circuits. Wiring and rewiring of neuronal circuits largely depends on the orchestrated changes in the strengths of synaptic contacts. Here, we review how the rules of synaptic plasticity change during development of the brain, from birth to independence. We focus on the changes that occur at the postsynaptic side of excitatory glutamatergic synapses in the rodent hippocampus and neocortex. First we summarize the current data on the structure of synapses and the developmental expression patterns of the key molecular players of synaptic plasticity, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as pivotal kinases (Ca(2+)/calmodulin-dependent protein kinase II, protein kinase A, protein kinase C) and phosphatases (PP1, PP2A, PP2B). In the second part we relate these findings to important characteristics of the emerging network. We argue that the concerted and gradual shifts in the usage of plasticity molecules comply with the changing need for (re)wiring neuronal circuits.
INTERFAZ DE BAJO COSTO USANDO UN PUERTO PARALELO Y VISUAL BASIC

The design of a low-cost interface is described that uses the parallel port of a PC to control experiments that require from 1 to 8 outputs in combination with 1 to 4 inputs using the programming language Visual Basic ® 2008 Express Edition that is freely distributed. This interface allows for controlling response-input consoles and experimental chambers that can be used in experiments with humans and nonhuman animals using only a computer. To facilitate the application of the interface in experiments on behavior analysis, the use of micro switches and photobeam sensors for recording responses as well as the use of devices controlled via micro relays is described.
A Microwave Infrared Threshold Technique to Improve the GOES Precipitation Index

Abstract A method to improve the GOES Precipitation Index (GPI) technique by combining satellite microwave and infrared (IR) data is proposed and tested. Using microwave-based rainfall estimates, the method, termed the Universally Adjusted GPI (UAGPI), modifies both GPI parameters (i.e., the IR brightness temperature threshold and the mean rain rate) to minimize summation of estimation errors during the microwave sampling periods. With respect to each grid, monthly rainfall estimates are obtained in a manner identical to the GPI except for the use of the optimized parameters. The proposed method is compared with the Adjusted GPI (AGPI) method of Adler et al. (1993), which adjusts the GPI monthly rainfall estimates directly using an adjustment ratio. The two methods are compared using the First Algorithm Intercomparison Project (AIP/1) dataset, which covers two month-long periods over the Japanese islands and surrounding oceanic regions. Two types of microwave-related errors are addressed during the compar...
Dexamethasone inhibits mucosal adaptation after small bowel resection

The present study examined the effects of dexamethasone on mucosal adaptation after massive small bowel resection. Rats underwent 80% jejunoileal resection or a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight, DNA content, and protein content in the duodenojejunal and ileal mucosa in both sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone infusion. By contrast, enzyme activities were elevated only in the ileal mucosa of dexamethasone-infused sham-operated rats compared with sham-operated control rats, and dexamethasone did not elevate enzyme activities in resected rats. We further examined whether the inhibitory effects of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF BP-1 serum levels were elevated by dexamethasone treatment with a concomitant depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF BP-4 levels did not change. These results suggest that the growth-inhibiting effects of dexamethasone in small intestinal mucosa may be partially mediated by decreased serum IGF levels or by alterations in IGF activity associated with changes in serum levels of IGF BPs.
Cerberus nanoemulsions produced by multidroplet flow-induced fusion.

Through extreme flow-induced fusion and rupturing of microscale droplets within a mixture of two or more oil-in-water emulsions, each having a different type of mutually immiscible oil, we create complex oil-in-water nanoemulsions composed of multicomponent compartmentalized nanodroplets. The extreme flow temporarily overcomes the repulsive barrier between oil droplets, arising from stabilizing surfactant molecules on the droplet interfaces, thereby causing multidroplet fusion as well as droplet fission down to the nanoscale. After the droplets leave the vicinity of extreme flow, they remain stable against subsequent coarsening and coalescence. Using this highly parallel, top-down, nonequilibrium synthetic approach, we create bulk quantities of engulfed-linear Cerberus oil-in-water nanoemulsions. Each Cerberus nanodroplet contains three different immiscible oils that form complex-shaped internal compartments, as revealed by cryogenic transmission electron microscopy (cryo-TEM). Within a given Cerberus nan...
When to replicate or adapt organizational routines: The case of franchising

When organizational routines need to be transferred from one organizational unit to another, a central question is whether it is best for them to be replicated exactly, or whether they should be ad...
Granulomatous periorificial dermatitis: a variant of granulomatous rosacea in children?

Background: We report a case of granulomatous periorificial dermatitis (GPD). A 13-year-old Jamaican boy presented with pink to flesh-colored perioral and periocular papules that erupted during a summer visit to Jamaica. The child was initially diagnosed with sarcoidosis and treated with oral corticosteroids, but the eruption recurred 2 years later. He was referred to Dermatology. Biopsy of one of the facial papules revealed a dense granulomatous infiltrate with surrounding prominent lymphocytes. A diagnosis of GPD was made. Objective and Conclusion: Also known as facial Afro-Caribbean childhood eruption (FACE), GPD occurs in prepubertal children. It can be confused with sarcoidosis, infection, and granulomatous rosacea but contains lymphocytes around the granulomas and lacks the systemic involvement seen in sarcoidosis. Cultures are invariably negative. The histologic features of GPD and granulomatous rosacea can be identical, and certain treatments may exacerbate the condition, highlighting the importance of clinical correlation. The correct diagnosis is important to minimize treatment as GPD is ultimately self-limited. Antecedents: Nous rapportons un cas de dermatite periorificielle granulomateuse (DPG). Un enfant jamaieain de 13 ans a developpe des papules periorales et periculaires variant entre le rose et la couleur cher durant un sejour en Jamaique. II a recu un traitement oral aux steroides a la suite d'un premier diagnostic de sareoidose. Apres une nouvelle eruption 2 ans plus tard, il a ete refere a un dermatologue. La biopsie de l'une des papules faciales a revele un infiltrat granulomateux dense avec d'importants lymphocytes adjacents. On a pose alors le diagnostic de DPG. Objectif et conclusion: La DPG survient chez les preadolescents et peut etre confondue avec la sarcoidose, une infection, ou un cas de rosacee granulomateuse; toutefois la DPG presente des lymphocytes entourant les granulomes et n'a pas le caraetere systemique d'une sarcoidose. Les cultures sont toujours negatives. Les caraeteristiques histologiques de la DPG et de la rosacee granulomateuse peuvent etre identiques et certains traitements peuvent exacerber le cas, soulignant l'importance du recoupement clinique. Un diagnostic exact est important afin de pouvoir minimiser le traitement etant donne le que la DPG est resolutive.
Analyzing Analytics

Many organizations today are faced with the challenge of processing and distilling information from huge and growing collections of data. Such organizations are increasingly deploying sophisticated mathematical algorithms to model the behavior of their business processes to discover correlations in the data, to predict trends and ultimately drive decisions to optimize their operations. These techniques, are known collectively as analytics, and draw upon multiple disciplines, including statistics, quantitative analysis, data mining, and machine learning. In this survey paper, we identify some of the key techniques employed in analytics both to serve as an introduction for the non-specialist and to explore the opportunity for greater optimizations for parallelization and acceleration using commodity and specialized multi-core processors. We are interested in isolating and documenting repeated patterns in analytical algorithms, data structures and data types, and in understanding howthese could be most effectively mapped onto parallel infrastructure. To this end, we focus on analytical models that can be executed using different algorithms. For most major model types, we study implementations of key algorithms to determine common computational and runtime patterns. We then use this information to characterize and recommend suitable parallelization strategies for these algorithms, specifically when used in data management workloads.
Abstract P1-04-01: Breast milk exosomes promote breast cancer progression

Background: The stimulation of extant neoplastic cells vs. their inhibition during breast involution is a key concept in whether pregnancy and lactation decrease or increase breast cancer risk. The time of weaning, a period of breast involution and remodeling, appears critical to future breast cancer risk, as during involution the breast microenvironment becomes tumor promotional. Both matrix metalloproteinases (MMPs) and transforming growth factor (TGF)β isoforms have been implicated in this process. We previously reported that TGFβ2 (but not TGFβ1) expression was significantly higher in milk collected from the cancer containing (vs. matched clinically normal) breast of women diagnosed with cancer during lactation. Hypothesis: TGFβ2 in milk exosomes from healthy lactating women modulates the development and progression of breast cancer. Methods: Matched (early, mature and wean-early involution) milk samples were collected from 13 lactating women, exosomes isolated and the levels of five (MMP2, 3, 9; TGFβ1, 2) proteins measured. Based on the results, additional wean samples were analyzed for TGFβ2 expression and samples divided based on their TGFβ2 expression. The highest and lowest TGFβ2 expressing milk exosome samples were co-cultured with MCF-7 breast cancer cells grown in exosome-depleted media. Cell proliferation was measured after 24h. Confocal microscopy was performed after 72h to evaluate epithelial to mesenchymal transition (EMT) in the cells. A TGFβ2 neutralizing blocking antibody was applied after 72 h co-culture. Results: The greatest increase in expression (four-fold) at the time of involution was in TGFβ2. Confocal microscopy performed 24h after co-culture confirmed the uptake of the exosomes (both those expressing hi and lo TGFβ2) in the MCF-7 cells. There was a significant increase in cell proliferation compared to control (p Impact: Pregnancy has a lasting influence on breast cancer risk, and pregnancy associated breast cancers (PABCs) diagnosed after delivery are generally aggressive, with a poor prognosis. Part of the reason for the development of PABCs, and the aggressive nature of PABCs may be the influence of high-expressing TGFβ2 exosomes in the milk on the breast ductal epithelium. Citation Format: Sauter ER, Qin W, Dasgupta S. Breast milk exosomes promote breast cancer progression. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-04-01.
A Clay source provenance survey in Northwest Alaska: Late Holocene ceramic production in the Arctic

Ceramic compositional analysis can contribute to the study of late Holocene Arctic hunter-gatherer social interaction through reconstruction of past ceramic distribution patterns. The results of an ethnographically informed clay source survey in Northwest Alaska are presented here. The survey provided contextual data on clay depositional environments, clay variability, and local environmental factors that influenced pre-contact clay availability. Geochemical analysis of clays and tempers clarified the location of ceramic production zones. Concurrence between survey results and ethnographic data highlights the persistence of clay knowledge despite post-contact absence of pottery making. This research demonstrates that ethnographically informed source survey can aid in interpreting ceramic geochemical data and yield important insights into pre-contact ceramic production processes.
General Reactive Power Optimization of Whole Distribution Network Based on Improved Niche Genetic Algorithm

A reactive power optimization method for whole distribution network is proposed,which divides whole distribution network into three levels,i.e.,high voltage level,medium voltage level and low voltage level,in accordance with its own features each sub-network is re-divided into optimum units. According to the principle of optimizing from bottom to top,during the reactive power optimization of network in higher voltage level the influence of reactive power optimization of the sub-network in lower voltage level should be taken into account to make the calculation results more accurate and reliable. The reactive power optimization of each optimum unit is implemented by improved niche genetic algorithm in which the distinguishing criterion of individual distance is set as dynamic function,thus the individual distance can be traced more flexibly and accurately,the convergence is fast and global optimal solution can be found. Calculation results of a certain distribution network validate the superiority of the proposed reactive power optimization method for whole distribution network.
DNA Photofootprinting with Rh(phi)2bpy3

This chapter describes one method for high resolution photofootprinting of proteins or small drugs bound to DNA (1). DNA footprinting is an electrophoretic method that permits the visualization (footprint) of the binding site of a molecule site-specifically bound to DNA. The method entails the nonspecific cleavage of a radioactively end-labeled DNA containing the site-specifically bound molecule. Protection from this sequence neutral cleavage at the binding site reveals the footprint. Photofootprinting differs from other conventional footprinting techniques in that DNA cleavage occurs directly on irradiation of a photocleaving reagent, which binds to the target DNA sequence. Alternative photofootprinting methods produce DNA cleavage indirectly by creating photo-damaged DNA adducts that are labile to base treatment after irradiation of the DNA (2,3). Traditional footprinting procedures utilize either a protein like DNase I for cleavage or small molecule reagents that cleave DNA under specific chemical conditions (4–8).
Panel Discussion A Will the Business Cycle Ever Be Obsolete in Industrial Societies? I

Varied answers to this question can be derived from the papers at this conference. On one hand the answer depends on how one defines cycles. If one views cycles as some regular phenomenon demarcated by time duration as people used to do - that is, set up a chronology beginning at the long end of the spectrum with Kondratieff or long-wave cycles of fifty years or more and then Kuznets cycles (of twenty years), Juglar cycles (of nine years), Kitchin cycles (of three to four years), inventory cycles (eighteen months) etc., the answer might be yes. However, as exhibited in the discussion on long waves or the recent literature critically evaluating NBER reference-cycle chronologies, there is considerable doubt that such phenomena exist. If one views cycles as economic fluctuations - irregular disturbances - then it seems likely we will always have them as long as we live in a stochastic world with changing tastes, technologies, national disasters, wars, imperfect government policies, etc.
Abstract 2212: Induction of α5β1 integrin expression rescues geriatric CAR-T cell function

Chimeric antigen receptors expressing T cells (CAR-Ts) are a promising form of immunotherapy for solid tumors. The majority of cancer patients in the United States are over 65 years old. The impact of age-related physiologic changes on cancer therapy and immunotherapy in particular require further study. We tested our hypothesis that CAR-T from geriatric donors (gCAR-T, n = 8, >65 years) are functionally impaired relative to CAR-T from younger donors (yCAR-T, n = 8, 18-45 years). T cells were genetically modified to express CAR specific for carcino-embryonic antigen (CEA), presently in use in our phase I trials. CAR-T cells were expanded ex vivo with IL2 (3000IU/ml) or IL15 (5ng/ml) for 20 days. Higher transduction efficiencies (36.9%+4.3 yCAR-T vs 21.3%+2.2 gCAR-T, p = 0.002) and improved cell expansion (2.5 fold in IL2, p = 0.01, two-tailed t-test) were observed in yCAR-T cells compared to gCAR-T. To define the underlying signaling mechanisms that led to increased proliferation in yCAR-T cells, we examined pERK, pAKT, pSTAT3 and pSTAT5. Following activation with anti-CD3, yCAR-T demonstrated significantly increased levels of pERK (13.4 fold in IL2, p = 0.03 and 2.3 fold in IL15, p = 0.04), pAKT (4.2 fold in IL2, p = 0.04 and 3.0 fold in IL15, p = 0.04), pSTAT3 (1.5 fold in IL2, p = 0.02 and 2.9 fold in IL15, p = 0.01) and pSTAT5 (5.7 fold in IL2, p = 0.02 and 2.1 fold in IL15, p = 0.03) compared to gCAR-T. Furthermore, yCAR-T contained higher proportions of CD4 effector cells (EC) (p = 0.003), CD4 effector memory (EM) cells (p = 0.002) and CD8 effector memory cells (EM) (p = 0.002). In accordance with higher numbers of CD4 and CD8 EM, yCAR-T demonstrated higher levels of CEA specific cytotoxicity compared to gCAR-T (1.3-fold over gCAR-T, p = 0.03), with maximum cytotoxicity observed in IL15 treated yCAR-T cells. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin (1.3+0.1 ng/ml, p = 0.01) and granzyme B (0.4+0.03 ng/ml, p = 0.02). Unmodified geriatric T cells (gT) had decreased α5β1 integrin expression as compared to unmodified young T cells (yT) (yT cells 44.4 +4.2 vs gT cells 22.3 +2.0, p = 0.0003), a known mediator of retroviral transduction. We found that M-CSF or TGF-β1 rescued CAR expression by gCAR-T (yCAR-T 36.9+4.3, gCAR-T 29.9+1.0, gT+M-CSF 41.4+1.0, gT+TGF-β1 40.1+2.0, p Citation Format: Prajna Guha, Marissa Cunetta, Ponnandai Somasundar, N J. Espat, Richard P. Junghans, Steven C. Katz. Induction of α5β1 integrin expression rescues geriatric CAR-T cell function. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2212.
STOCHASTIC INTEGRALS AND DERIVATIVES

A stochastic integral is a random variable. A stochastic integral is defined in the sense of convergence in probability and gives a sufficient condition for its existence. A process X(t) is said to be homogeneous if the distribution function of the increment X(t +τ)-X(t) depends only on the length x of the interval but is independent of the endpoint t. The two intervals are said to be non-overlapping if they have no interior point in common. A process X(t) is called a process with independent increments if the increments over non-overlapping intervals are stochastically independent. A second-order process X(t) is said to be differentiable in the quadratic mean. The differentiability can also be defined in the sense of some other mode of convergence and could then also apply to processes that are not necessarily of the second order.
Utilizing Neural Networks to Predict Freezing of Gait in Parkinson's Patients

With the appropriate mathematical models, data from wearable devices can be used to help Parkinson's patients live safer and more independent lives. Inspired by this idea, the purpose of this study was to determine the viability of neural networks in predicting Freezing of Gait (FoG), a symptom of Parkinson's disease in which the patient's legs are suddenly rendered unable to move. A class of neural networks known as layered recurrent networks (LRNs) was applied to an open-source FoG experimental dataset donated to the Machine Learning Repository of the University of California at Irvine. The independent variables in this experiment -- the subject being tested, neural network architecture, and down sampling of the majority classes -- were each varied and compared against the performance of the neural network in predicting impending FoG events. It was determined that single-layered recurrent networks are a viable method of predicting FoG events given the volume of the training data available, though results varied between patients.
Imaginary Fate in the Origin of the Community Property Sharing Principle

The sharing principle is the idea that a married woman could earn and own property during marriage independent of a husband. My paper locates the community property sharing principle as a family practice that was brought out of Nordic tribal history by the Visigoths in the 3d through 6th centuries C.E. to the Iberian Peninsula. Eventually, the sharing principle was incorporated into the law of early modern Spain, later to be implemented in North America during Spain's colonial era. Today, the sharing principle (in gender neutral form) is the living law of nine U.S. community property states and multiple countries.
Language Ideologies in a U.S. State-Funded International School: The Invisible Linguistic Repertoires of Bilingual Refugee Students.

In this study, I investigated language ideologies in a state-funded International Baccalaureate Primary Years Programme school in the United States. I conducted ethnographic observations, focus groups, and interviews in a fourth grade classroom in one of the largest refugee resettlement areas in the country. Findings indicate that although the school positioned bilingualism as linguistic capital, the linguistic repertoires of multilingual refugee students were made invisible by three inter-related processes: linguistic tokenism, linguistic subordination, and linguistic compartmentalization. These results highlight the urgency for schools offering the IB PYP to implement language policy, curriculum, and instruction that explicitly support immigrant and refugee children’s multiple linguistic backgrounds.
Outcomes of patients with malignant pleural mesothelioma (MPM) following the approval cisplatin/pemetrexed: Experience of a comprehensive cancer center.

e17528 Background: Mesothelioma is a rare cancer that is estimated to occur in about 2,500 people in the United States every year. MPM is the most common type of mesothelioma. Until 2003 there was ...
Hierarchical Adaptive Control System Design and Application

Abstract This paper presents a new adaptive hierarchical control technique that adjusts its structure in order to maintain good performance over a wide variation of plant operating conditions. In contrast to the conventional approach of designing a compensator based upon a single control algorithm, this method combines a range of control algorithms in a complementary manner, each of which makes different assumptions about the regulated process. The hierarchical control structure includes a fuzzy controller which requires little process knowledge in order to provide an effective control, a multiple model adaptive controller which provides credible performance when the model bank adequately spans the expected plant variations and the plant behaves reasonably close to the model on which the compensator design was based, and a direct model reference adaptive controller which assumes that the plant transfer function satisfies specific sufficiency conditions. This paper presents an application of the hierarchical control structure as a regulator for a drug delivery system.
An Iterative Kalman Smoother for Robust 3D Localization and Mapping

In this paper, we present an iterative Kalman smoother (IKS) for robust 3D localization and mapping, using visual and inertial measurements. Contrary to extended Kalman filter (EKF) methods, smoothing increases the convergence rate of critical parameters (e.g., IMU’s velocity and camera’s clock drift), improves the positioning accuracy during challenging conditions (e.g., scarcity of visual features), and allows the immediate processing of visual observations. As opposed to existing smoothing approaches to VINS, based on the inverse filter (INVF), the proposed IKS exhibits superior numerical properties, allowing efficient implementations on mobile devices. Furthermore, we propose a classification of visual observations, for smoothing algorithms applied to VINS, based on their: (i) Track length, allowing their efficient processing as multi-state constraints, when possible and (ii) First observation, allowing their optional re-processing. Finally, we demonstrate the robustness of the proposed approach, over challenging indoor VINS scenarios, including, system (re)-initialization, and scarcity of visual observations.
Associations of neonatal adiponectin and leptin with growth and body composition in African American infants

BACKGROUND Cord blood adiponectin and leptin concentrations are associated with birth weight and adiposity. Birth size and rate of infant weight gain are associated with future obesity risk. However, it is unclear whether biomarkers reflecting the intrauterine environment are predictive of infant prospective body composition change. OBJECTIVES To examine whether cord blood adiponectin and leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months of age. METHODS Participants (n = 36) were healthy African American infants. Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2 weeks and 3 months, infant body composition was assessed via air displacement plethysmography. Weight-for-length z-scores (WLZ) were calculated using World Health Organization standards. Multiple linear regression was used to examine associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat-free mass at 2 weeks, and the conditional change in these variables from 2 weeks to 3 months (body composition at 3 months adjusted for body composition at 2 weeks). RESULTS Adiponectin was positively associated with FM at 2 weeks (r = 0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks to 3 months of age (r = -0.38, P < 0.05). Leptin was not significantly associated with infant body composition. CONCLUSIONS Adiponectin may be a marker for FM accrual in African American infants, a relatively understudied population with a high long-term obesity risk. Mechanistic studies are needed to determine whether adiponectin directly influences infant growth or is simply a maker reflective of other ongoing biological changes after birth.
Patterning method impact on sub-36nm pitch interconnect variability

As advanced semiconductor technologies continue to shrink, there is a continued need for interconnect performance and variability to keep pace. Traditional area scaling alone cannot control the increased process variation at advanced nodes. We examine the impact that patterning scheme has on the final interconnect resistance, capacitance and RC variability at sub-36nm pitches. Industry standard patterning schemes are evaluated using the Monte Carlo method. Single exposure (direct print), litho-etch-litho-etch, self-aligned double patterning and self-aligned quadruple patterning (SAQP) are considered. In the context of these patterning schemes, lithographic variation and spacer thickness uniformity (where applicable) are evaluated.
Rotations and Quaternions

What is a rotation? A turn, an angle change, an event in which an object starts here and ends up there, where “here” and “there” are points that lie on a circular arc. It is hard to imagine a rotation without a journey, but for the most part, we care about where things start and where they end up, not how they actually found their way to their final positions.
Musi: Facilitating Asynchronous Practice Between Classical Musicians

Classical musicians spend a significant amount of their time practicing alone, which requires both intrinsic and extrinsic motivation to persevere. Recent technological interventions in the field support musicians by focusing heavily on critiquing technique, not emotional expression, or require significant investments in additional audio-visual equipment. We present Musi, a system that connects musicians through asynchronous sharing of recordings to support development of musical expression and collaboration within ensembles. Musi simplifies current processes of recording, sharing, and reflecting on practice sessions, and features a novel interface that enables users to control the system's features using their feet, allowing users to keep their hands and attention focused on their instruments. The system was prototyped and tested with undergraduate music majors at the University of Michigan, Ann Arbor.
Abstract 15497: Genetic Modifiers of Glucose Response to GIK and Their Association With Cardiovascular Outcomes

Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect clinical outcomes in acute coronary syndrome (ACS). The I mmediate M yocardial M etabolic E nhancement D uring I nitial A ssessment and T reatment in E mergency care (IMMEDIATE) Trial compared out-of-hospital initiation of GIK to Placebo in patients with suspected ACS. In an IMMEDIATE sub-study (n=318), we explored genetic effects on plasma glucose during 12hr GIK infusion. Patients were genotyped for 132,634 variants (minor allele frequency, MAF≥0.05) assayed on Cardiometabochip and Exome Chip. Associations between glucose-associated variants and progression to myocardial infarction (MI, 66.7%) and infarct size (n=66) were assessed. Blood glucose was measured shortly after infusion initiation, and at 6hrs and 12hrs. Regressions adjusted for treatment, time between treatment initiation and blood draw, age, sex, race, and diabetes. Glucose was higher with GIK than placebo at 6hrs (P=0.002; 159.6 vs. 218.7 mg/dL), but not 12hrs (P=0.60; 152.9 vs. 174.3 mg/dL). A variant near ADCYAP1 , rs7229849 (MAF=0.14), modified glucose response to intervention. In GIK, but not placebo, each copy of the rs7229849 minor allele conferred a 1.5-fold initial-to-6hr rise (P for interaction, P-int=2.9x10-6) and a 1.2-fold 6-12hr fall (P-int=0.04) in glucose. This allele was also associated with a larger infarct in GIK (13.3% of LV per copy) and a smaller infarct in Placebo (-5.9% LV per copy; P-int=0.045). ADCYAP1 increases glucose-stimulated insulin release in vitro and in vivo . Near ACSL1 , rs12641551 (MAF=0.38) was associated with differences in 6-to-12hr glucose (P-int=2.8x10-5; 1.38-fold rise per copy in GIK, no difference in placebo) and showed an opposite effect on infarct size by treatment (P-int=0.01; GIK=10.0%, Placebo= -7.0% of LV per copy). ACSL1 is implicated in insulin resistance and cardiac arrest resuscitation success. Differences in glucose, but not outcomes, were observed for 12 SNPs within or near SETX , XPO4 , STRADA , TAS1R3 , DNAH5 , AKAP12 , PTPRG, LCA5, MAGI1, ARFGEF2, PTCSC3, and ABCB11 (P≤5.0x10-7). Our findings suggest that gene variants in glucose metabolism pathways may modify glucose response to 12hr GIK infusion, and contribute to cardiovascular outcomes in ACS.
Subclassifications of Retinitis Pigmentosa from two-Color Scotopic Static Perimetry

On the basis of evaluations of rod sensitivity relative to cone sensitivity determined from Perimetric dark-adapted absolute threshold measures to a short wavelength stimulus and a long wavelength stimulus, we have identified two forms of dominant retinitis pigmentosa (RP) and two forms of recessive and (or simplex) RP. Here we present examples of early and advanced cases from recessive and simplex pedigrees that illustrate the two forms of RP appear to represent different disease mechanisms, rather than different stages of disease progression.
Mesh Matching – Creating Conforming Interfaces between Hexahedral Meshes

This paper presents a new method for handling non-conforming hexahedral-to-hexahedral interfaces. One or both of the adjacent hexahedral meshes are locally modified to create a one-to-one mapping between between the mesh nodes and quadrilaterals at the interface allowing a conforming mesh to be created. In the finite element method, non-conforming interfaces are currently handled using constraint conditions such as gap-elements, tied contacts, or multi-point constraints. By creating a conforming mesh, the need for constraint conditions is eliminated resulting in a smoother, more precise numerical solution. The method presented in this paper uses hexahedral dual operations, including pillowing, sheet extraction, dicing and column collapse operations, to affect the local mesh modifications. In addition, an extension to pillowing, called sheet inflation, is introduced to handle the insertion of self-intersecting and self-touching sheets. The quality of the resultant conforming hexahedral mesh is high and the increase in number of elements is moderate.
Minimizing Social Desirability Bias in Measuring Sensitive Topics: The Use of Forgiving Language in Item Development

Social science research has long been concerned with attitudes, beliefs, and behaviors that are potentially objectionable, immoral, or illegal. These types of topics include, for example, racism, a...