cssi/SciSciGPT-SciSciNet huggingface dataset:
Differential Impact of Systolic and Diastolic Blood Pressure Level on JNC-VI Staging

The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure into stages on the basis of both systolic (SBP) and diastolic (DBP) blood pressure levels. When a disparity exists between SBP and DBP stages, patients are classified into the higher stage ("up-staged"). We evaluated the effect of disparate levels of SBP and DBP on blood pressure staging and eligibility for therapy. We examined 4962 Framingham Heart Study subjects between 1990 and 1995 and determined blood pressure stages on the basis of SBP alone, DBP alone, or both. After the exclusion of subjects on antihypertensive therapy (n=1306), 3656 subjects (mean age 58+/-13 years; 55% women) were eligible. In this sample, 64.6% of subjects had congruent stages of SBP and DBP, 31.6% were up-staged on the basis of SBP, and 3.8% on the basis of DBP; thus, SBP alone correctly classified JNC-VI stage in approximately 96% (64.6%+31.6%) of the subjects. Among subjects >60 years of age, SBP alone correctly classified 99% of subjects; in those </=60 years old, SBP alone correctly classified 95%. Of 1488 subjects with high-normal blood pressure or hypertension, who were potentially eligible for drug therapy, 13.0% had congruent elevations of SBP and DBP, 77.7% were up-staged on the basis of SBP, and 9.3% were up-staged on the basis of DBP; SBP alone correctly classified 91%, whereas DBP alone correctly classified only 22%. SBP elevation out of proportion to DBP is common in middle-aged and older persons. SBP appears to play a greater role in the determination of JNC-VI blood pressure stage and eligibility for therapy. Given these results, combined with evidence from hypertension treatment trials, future guidelines might consider a greater role for SBP than for DBP in determining the presence of hypertension, risk of cardiovascular events, eligibility for therapy, and benefits of treatment.
State of the Science for Practice to Promote Breastfeeding Success Among Young Mothers

Abstract A literature review and synthesis of qualitative and quantitative studies was conducted to evaluate the role of breastfeeding attitudes, beliefs, and support as they relate to young mothers. A search of CINAHL and PubMed was conducted for articles published from 2008–2013 using the terms breastfeeding and adolescents and duration; breastfeeding and adolescents and success; and breastfeeding and adolescents and support. Of several hundred papers identified, those articles selected for in depth review examined breastfeeding attitudes, beliefs, support, and practices. Factors contributing to breastfeeding success or failure were identified. Among them, participant descriptions reflected paradoxical factors such as: ‘breast is best’, ‘breastfeeding as not the norm’, convenience, privacy, sexuality, body image, healthcare provider support, family and peer support, and other barriers to breastfeeding. These factors were described to have both positive and negative effects on breastfeeding, at times in the same study.
Nearest neighbor search using additive binary tree

Classifying an unknown input is a fundamental problem in pattern recognition. One standard method is finding its nearest neighbors in a reference set. It would be very time consuming if computed feature by feature for all templates in the reference set; this naive method is O(nd) where n is the number of templates in the reference set and d is the number of features or dimension. For this reason, we present a technique for quickly eliminating most templates from consideration as possible neighbor. The remaining candidate templates are then evaluated feature by feature against the query vector. We utilize frequencies of features as a pre-processing to reduce query processing time burden. The most notable advantage of the new method over other existing techniques occurs where the number of features is large and the type of each feature is binary although it works for other type features. We improved our OCR system by at least a factor of 2 (without a threshold) or faster (with higher threshold value).
Micro-benchmark level performance comparison of high-speed cluster interconnects

In this paper we present a comprehensive performance evaluation of three high speed cluster interconnects: Infini-Band, Myrinet and Quadrics. We propose a set of micro-benchmarks to characterize different performance aspects of these interconnects. Our micro-benchmark suite includes not only traditional tests and performance parameters, but also those specifically tailored to the interconnects advanced features such as user-level access for performing communication and remote direct memory access. In order to explore the full communication capability of the interconnects, we have implemented the micro-benchmark suite at the low level messaging layer provided by each interconnect. Our performance results show that all three interconnects achieve low latency, high bandwidth and low host overhead. However, they show quite different performance behaviors when handling completion notification, unbalanced communication patterns and different communication buffer reuse patterns.
Differential Regulation of Homocysteine Transport in Vascular Endothelial and Smooth Muscle Cells

Objective— We previously reported that homocysteine (Hcy) inhibits endothelial cell (EC) growth and promotes vascular smooth muscle cell (VSMC) proliferation. This study characterized and directly compared Hcy transport in cultured human aortic ECs (HAECs) and smooth muscle cells (HASMCs). Methods and Results— Hcy (10 μmol/L) was transported into both cell types in a time-dependent fashion but was approximately 4-fold greater in HASMCs, and is nonstereoenantiomer specific. Hcy transport in HAECs had a Michaelis-Menten constant ( Km ) of 39 μmol/L and a maximal transport velocity ( Vmax ) of 873 pmol/mg protein/min. In contrast, Hcy transport in HASMCs had a lower affinity ( Km =106 μmol/L) but a higher transport capacity ( Vmax =4192 pmol/mg protein/min). Competition studies revealed that the small neutral amino acids tyrosine, cysteine, glycine, serine, alanine, methionine, and leucine inhibited Hcy uptake in both cell types, but the inhibition was greater for tyrosine, serine, glycine, and alanine in HAECs. Sodium-depletion reduced Hcy transport to 16% in HAECs and 56% in HASMCs. Increases in pH from 6.5 to 8.2 or lysosomal inhibitors blocked Hcy uptake only in HAECs. In addition, Hcy shares carrier systems with cysteine, in a preferable order of alanine-serine-cysteine (ASC)>aspartate and glutamate (X AG )=large branched-chain neutral amino acids (L) transporter systems in HAECs and ASC>L>X AG in HASMCs. The sodium-dependent system ASC plays a predominant role for Hcy transport in vascular cells. Conclusions— Transport system ASC predominantly mediates Hcy transport in EC and is lysosomal dependent.
High prevalence of autoimmune Thyroid disease in pulmonary arterial hypertension

Study objectives An association between thyroid disease and pulmonary arterial hypertension (PAH) has been reported, yet the pathogenetic relationship between these conditions remains unclear. Because immune system dysfunction may underlie this association, we sought to determine the prevalence of autoimmune thyroid disease (AITD) in patients with PAH. Design and setting Prospective observational study at a single academic institution. Patients Sixty-three consecutive adults with PAH (ie, sustained pulmonary artery systolic pressure, > 25 mm Hg) were evaluated for clinical, biochemical, and serologic features of AITD. Measurements Thyroid gland dysfunction was determined by clinical examination for goiter, and by biochemical measurements of thyrotropin and free thyroxine. Immune system dysfunction was determined by serologic measurements of antibodies to thyroglobulin and thyroid peroxidase. First-degree family history of AITD also was ascertained in order to investigate for genetic clustering of autoimmunity. Results Thirty-one patients (49%; 95% confidence interval [CI], 37 to 62%) received diagnoses of AITD. Eighteen patients were newly diagnosed, and 9 patients required the initiation of pharmacologic treatment. There was no chronologic relationship between the diagnosis or treatment of PAH and that of AITD. Sixteen patients (25%; 95% CI, 15 to 36%) had 24 first-degree family members with AITD. Conclusions Approximately half of the patients with PAH have concomitant AITD. These two conditions may be linked by a common immunogenetic susceptibility, and the elucidation of this association may advance the understanding of the pathophysiology and treatment of PAH. Systematic surveillance for occult thyroid dysfunction in patients with PAH may prevent the hemodynamic exacerbation of right heart failure.
Antioxidants and Reduced Functional Capacity in the Elderly: Findings From the Nun Study

Background. This study investigated the relationship of plasma antioxidants to reduced functional capacity in the elderly. A hallmark of reduced functional capacity in the elderly is dependence in self-care (i.e., requiring assistance with bathing, walking, dressing, standing, toileting, and feeding). Methods. This relationship was assessed in a cross-sectional study of 88 Catholic sisters (nuns). These 77- to 98-yearold women lived in the same building, ate food prepared in the same kitchen, and had all nursing services provided by the same staff. In 1993, ability to perform self-care was assessed, and blood was drawn to determine plasma carotenoids (lycopene, beta carotene, alpha carotene, zeaxanthin and lutein combined, and beta cryptoxanthin) and alpha tocopherol. Results. Dependence in self-care had a strong negative association with lycopene, but was not clearly related to other carotenoids or alpha tocopherol. Results from age-adjusted least squares regression indicated that a 30 p,g/dl decrease in lycopene was associated with 2.4 additional dependencies in self-care (95% confidence interval = 1.5, 3.3; p < .001). Lycopene's relationship to dependence was modified by plasma LDL-cholesterol, the predominant carrier of lycopene in the blood. Women with low lycopene and low LDL-cholesterol had 3.6 dependencies (95% confidence interval = 3.1, 4.2; p < .001), compared to 1.0 dependency (95% confidence interval = 0.3, 1.8) in those with high lycopene and low LDL-cholesterol.
Undocumented Migration from Latin America in an Era of Rising U.S. Enforcement

Available data have consistently pointed up the failure of U.S. policies to reduce undocumented migration from Latin America. To shed light on the reasons for this failure, we estimated a series of dynamic models of undocumented entry into and exit from the United States. Our estimates suggest that undocumented migration is grounded more in mechanisms posited by social capital theory and the new economics of labor migration rather than neoclassical economics. As a result, U.S. efforts to increase the costs of undocumented entry and reduce the benefits of undocumented labor have proven unsuccessful given the widespread access of Latin Americans to migrant networks. The main effect of U.S. enforcement efforts has been to reduce the circularity of Latin American migration.
Routes to Chaos in Neural Networks with Random Weights

Neural networks are dense in the space of dynamical systems. We present a Monte Carlo study of the dynamic properties along the route to chaos over random dynamical system function space by randomly sampling the neural network function space. Our results show that as the dimension of the system (the number of dynamical variables) is increased, the probability of chaos approaches unity. We present theoretical and numerical results which show that as the dimension is increased, the quasiperiodic route to chaos is the dominant route. We also qualitatively analyze the dynamics along the route.
Ethylene-Vinyl Acetate Potential Problems for Photovoltaic Packaging

Photovoltaic (PV) devices are typically encapsulated using ethylene-vinyl acetate (EVA) to provide mechanical support, optical coupling, electrical isolation, and protection against environmental exposure. Under exposure to atmospheric water and/or ultraviolet radiation, EVA will decompose to produce acetic acid, lowering the pH and increasing the surface corrosion rates of embedded devices. Even though acetic acid is produced at a very slow rate, it may not take much to catalyze reactions that lead to rapid module deterioration. Another consideration is that the glass transition of EVA, as measured using dynamic mechanical analysis, begins at temperatures of about -15 degC. Temperatures lower than this can be reached for extended periods of time in some climates. Because of increased moduli below the glass transition temperature, a module may be more vulnerable to damage if a mechanical load is applied by snow or wind at low temperatures. Modules using EVA should not be rated for use at such low temperatures without additional low-temperature mechanical testing beyond the scope of UL1703
Racially and Ethnically Selective Oligoanalgesia: Is This Racism?

Abstract [Goldfrank LR, Knopp RK. Racially and ethnically selective oligoanalgesia: is this racism? Ann Emerg Med. January 2000;35:79-82.]
How Corporations Manage Industry and Consumer Expectations via the CSR Report

With increased stakeholder scrutiny, it is increasingly salient to consider how corporations make the case that their CSR activities are sufficient, appropriate, and successful. The CSR report is the vehicle by which organizations communicate the breadth of activities they engage in to make a difference in society. Using rhetorical analysis and surveys, we argue that the CSR report functions as a means by which corporations manage stakeholder expectations and seek to legitimate corporate behaviors. Our findings indicate that most reports are structured based on external guidelines but include the use of classic rhetorical strategies of ethos, pathos, and logos to establish the rightness. This study shows the value of moving past a catalog of activities, a consideration of channels, and a description of message attributes to focus on the rhetorical strategies employed by corporations.
Phase boundary of superconducting networks: A new approximation scheme.

We calculate the normal-superconducting phase boundary of a superconducting wire network in arbitrary magnetic fields using the London approximation of the linearized Ginzburg-Landau equation. Our formulation in terms of the constituent loop currents allows an iteration procedure to calculate the energy of a network, which in turn determines the mean-field transition temperature ${\mathit{T}}_{\mathit{c}}$(H). For infinite lattices, finite-order truncation in this scheme produces good agreement with other calculations and experiments.
ANDROGENS DIRECTLY STIMULATE PROLIFERATION OF BONE CELLS IN VITRO

This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.
Z-DOL and carbon overcoat: bonding mechanism

It has been postulated earlier that the bonding between Z-DOL and sputtered carbon occurs when a hydrogen atom is transferred from a hydroxyl end of Z-DOL to a dangling bond site shielded inside the sp/sup 3/ (diamondlike) granules of the carbon film, and the Z-DOL moiety is linked to the carbon as an alkoxyl group, HO-CH/sub 2/-CF/sub 2/-O-(-CF/sub 2/-CF/sub 2/-O-)/sub m/-(-CF/sub 2/-O-)/sub n/-CF/sub 2/-CH/sub 2/ -O-[carbon]. The postulated mechanism predicts that the Z-DOL bonding should occur spontaneously if freshly sputtered carbon were exposed to Z-DOL molecules without prior exposure to air, and that, for disks lubricated with Z-DOL, there would be less hydroxyl hydrogens, and there would exist the alkoxyl units depicted above. A recent reported result on vacuum deposition of Z-DOL (without prior exposure to air) clearly revealed the predicted spontaneous bonding, and analyzes by TOF-SIMS of disks lubricated with Z-DOL demonstrated the predicted decrease of the hydroxyl hydrogen and emergence of the predicted alkoxyl units as the bonding fraction of Z-DOL increases.
A control structure using an adaptive observer

The state and parameter estimates produced by a recently reported adaptive observer [3] are used to form an adaptive control scheme. For a large class of inputs, the adaptive process will converge in the sense that asymptotically the system transfer function will exhibit a set of desired poles. The rate of parameter convergence can be made arbitrarily fast by appropriate choice of the constant gain parameters in the adaptive laws. However, a limitation of the apparent closed-loop control structure is exposed.
Image intensifier distortion correction.

A method is described for determining and correcting the spatial distortion affecting images acquired with image‐intensified video systems. The distortion is separated into two physically distinct components, a predominant one originating from the projection of the x‐ray image onto the curved input phosphor, and a smaller component corresponding to the mapping from the input phosphor to the output phosphor and the digital image matrix. The former is determined geometrically and the latter is modeled with four empirical parameters. A method for determining the two components from calibration images of a grid phantom is presented. The model of the image intensifier distortion was found to be in good agreement with the measured distortion in the images. The correction is applicable to arbitrary angulations of the x‐ray beam with respect to the image intensifier tube, and consequently is directly applicable to digital tomosynthesis. The correction allows one to obtain accurate positional information with fluorography and may also be useful in radiation therapytreatment planning and quantitative digital subtraction angiography.
Cloud computing for comparative genomics.

Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes.
Securities Litigation Risk for Foreign Companies Listed in the U.S.

We study securities litigation risk faced by foreign firms listed on U.S. exchanges. We find that U.S. listed foreign companies experience securities class action lawsuits at about half the rate as do U.S. firms with similar levels of ex ante litigation risk. The lower rate appears to be partly attributable to higher transaction costs in uncovering and pursuing litigation against foreign firms. However, once a lawsuit triggering event like an accounting restatement, missing management guidance, or a sharp stock price decline occurs, there is no difference in the litigation rates between a foreign and comparable U.S. firm. This evidence suggests that effective enforcement of securities laws is constrained by transaction costs, and the availability of high quality information that reveals potential misconduct is an important determinant of litigation risk for foreign firms listed in the U.S.
Slit-lamp adapted, video-correlated real-time optical coherence tomography of the anterior segment

We present a slit-lamp adapted optical coherence tomography (OCT) system capable of imaging the entire anterior segment of the eye in real time. Non-linear scan methods and automated anterior chamber dimension determination are also presented.
Precision Medicine, Cardiovascular Disease and Hunting Elephants

Precision medicine postulates improved prediction, prevention, diagnosis and treatment of disease based on patient specific factors especially DNA sequence (i.e., gene) variants. Ideas related to precision medicine stem from the much anticipated "genetic revolution in medicine" arising seamlessly from the human genome project (HGP). In this essay I deconstruct the concept of precision medicine and raise questions about the validity of the paradigm in general and its application to cardiovascular disease. Thus far precision medicine has underperformed based on the vision promulgated by enthusiasts. While niche successes for precision medicine are likely, the promises of broad based transformation should be viewed with skepticism. Open discussion and debate related to precision medicine are urgently needed to avoid misapplication of resources, hype, iatrogenic interventions, and distraction from established approaches with ongoing utility. Failure to engage in such debate will lead to negative unintended consequences from a revolution that might never come.
Severe TBI Outcome Prediction: Usefulness of FIM Scores during Inpatient Rehabilitation (P01.187)

Objective: The goal of this study is to examine possible clinical predictors related to exceptional long-term functional outcomes in severe truamatic brain injury(STBI). Background Long-standing impairments are commonplace following STBI. There is plentiful literature on clinical predictors following STBI, but cases of greater than expected recovery following STBI have not as yet been a focus for research. Design/Methods: Case report series of three female participants with STBI initially admitted to inpatient rehabilitation(IR). Participants had initial Glascow Coma Scale scores of 3, post-traumatic amnesia durations of 18-115 days, time to follow commands of 16-100 days, abnormal initial brain CT scans, and initial pupil abnormalities. Outpatient rehabilitation ranged from three to six months. All resumed major life roles (gainful employment, ability to drive, ability to live independently). Participant IR Functional Independence Measure(FIM) score improvements were compared to national normative STBI FIM data from National Data Systems (NDS) for 2010 (n = 15,808). Results: All three participants were involved in gainful employment, resumed driving, and were living independently by 12 months post-injury. Initial FIM scores ranged from 12 to 42 (χ = 28; NDS = 51.8) with discharge scores ranging from 39 to 76 (χ = 59; NDS = 79.3). Total FIM gain from IR admission to discharge ranged from 27 to 34 points (χ = 31; NDS = 27.5). Cognitive FIM rating improved an average of 13.7 points, compared to 5.9 points for NDS. Sphincter (bowel and bladder) FIM rating improved an average of 5 points, compared to 3 points for NDS. Conclusions: IR FIM score changes may be useful in long-term STBI outcome prediction All three participants demonstrated marked improvements in FIM scores during inpatient rehabilitation and subsequent resumption of major life domains. Further research is necessary to validate whether sphincter and cognitive FIM score changes may be useful in long-term STBI outcome prediction. Disclosure: Dr. Kushner has nothing to disclose. Dr. Johnson-Greene has nothing to disclose.
Task transition and pacing: The role of temporal atypicality, task complexity, and individual time orientation

We investigate experimentally how temporal perception, task characteristics, and individual differences affect pacing and task transitions. 108 individuals were asked to manage task transitioning b...
Development program for a general purpose computer and strapdown inertial measurement unit

A comparison between strapdown and gimbal navigation systems suggests t h a t platforms have been prefer red for h i s t o r i c a l r a t h e r than t echn ica l reasons. The r e s u l t s from van tests i n d i c a t e t h e feasi b i l i t y of a strapdown system using a s u i t a b l e general-purpose computer, provided t h e bandwidth and dynamic range of t h e algorithms match those of t h e instruments. The development program f o r i n t eg ra t ing t h e MIT/IL GIMU with t h e Raytheon Aerospace Computer (RAC-230) i n t o a s t rapdown system i s descr ibed, including informa t ion flow, computer hardware, and s o f t ware design. Software compensations f o r accelerometer and gyro e r r o r s pecu l i a r t o t h e strapdown mechanization and algorithms e f f e c t i v e i n e l imina t ing a n a l y t i c e r r o r s of t runca t ion , non-commutativity, non-orthogonality, and non-normality were mechanized. A descr ip t ion of t h e van tests a r e presented. Data i s included showing a t t i t u d e re ference performance better than 0.1 degrees per hour f o r road tests l a s t i n g up t o s i x hours covering d i s t ances of 100 m i l e s . I n e r t i a l navigat i o n performance da ta a r e a l s o presented.
The Measure of Recognizable Sets of Real Numbers

The sets of real numbers which can be recognized by certain finite state automata are (Lebesgue) measurable. A necessary and sufficient condition for such sets to have measure 0 is that from each s...
In large-vessel ischemic stroke, adding endovascular thrombectomy to usual care reduced 90-day disability.

Source Citation Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five rand...
The responsiveness of airway smooth muscle in vitro from dogs with airway hyper-responsiveness in vivo.

To determine whether smooth muscle from airways made hyper-responsive by ozone exposure is hyper-responsive in vitro, tracheal smooth muscle strips taken from five dogs with airway hyper-responsiveness induced by ozone exposure were compared with strips from five control animals. On 1 day, airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance. On a second day, five dogs were exposed to ozone (3.0 p.p.m. for 2 h) and five were exposed to filtered air. Then airway responsiveness to acetylcholine was reassessed. All dogs were then killed, the trachea was rapidly removed and strips of smooth muscle were prepared from the central one-third of the trachea. The responsiveness of each strip to electrical field stimulation (contractions inhibitable by atropine and tetrodotoxin) and exogenous acetylcholine was assessed after 2 and 6 h of incubation and washing. Ozone caused a marked increase in responsiveness in vivo to acetylcholine with a fall in mean provocation concentration from 0.15 g % to 0.026 g % (P less than 0.001) while sham exposure had no effect. The responsiveness of muscle strips to electrical field stimulation in ozone-exposed dogs after 2 h of incubation and washing was increased when compared with 6 h of incubation and washing and with the control dogs (P less than 0.05 for EF50, the frequency of stimulation giving 50% maximum contraction). However, responsiveness to exogenous acetylcholine was similar in all strips from both ozone-exposed and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Monetary Relations between Europe and America

The monetary history of the past century can be conveniently divided into three periods : the sterling-dominated gold standard prior to the First World War, the dollar-dominated gold standard following the Second World War, and the transition period in between (1914 to 1945). The transition period saw the attempt to restore sterling in 1925, the separation of sterling from gold in 1931, and the rise of the dollar to international status after devaluation in 1934. The post-war system has been dominated by the United States. The monetary order established at Bretton Woods in 1944 created a code of conduct for the adjustable peg system in addition to a multilateral credit facility, but it was the interaction of national power rather than the International Monetary Fund that dominated the form into which the post-war system evolved.
Constitutive Activation of p38 MAPK in Myeloma Cells Contributes to Myeloma-Induced Osteolytic Bone Lesions.

Abstract Abstract 740 Bone destruction is common in osteolytic tumors such as multiple myeloma. Myeloma cells that reside in the bone cause osteolysis, which is characterized by severe bone pain, multiple fractures, and hypercalcemia in patients and thereby, compromises patient quality of life. While myeloma cells have been proposed to activate osteoclasts and/or inhibit osteoblasts leading to bone resorption, the mechanism underlying myeloma-induced osteolytic bone lesions is still poorly elucidated. As p38 mitogen-activated protein kinase (MAPK) is constitutively activated in myeloma, we hypothesized that p38 MAPK activation in myeloma cells might be responsible for myeloma-induced osteolytic bone lesions. Human myeloma cell lines ARP-1 and MM.1S caused bone lesions in SCID mice after intravenous injection. However, once p38 MAPK was knocked down by small hairpin RNAs (shRNAs) in these cell lines, myeloma was established but failed to cause bone lesions in SCID mice, whereas the wild-type or vector control myeloma cells established myeloma (with similar tumor burdens as myeloma cells with knocked-down p38 MAPK) and caused bone lesions in tibial bones, as measured by radiograph and peripheral quantitative m-computed tomography and further confirmed by histological examination. In vivo examination revealed that the number of bone surface-covering osteoclasts, osteoclast size, cellular nuclear numbers in per osteoclast, and levels of circulating collagen type I (bone resorption marker) and TRAP5b (active osteoclast marker) were all reduced in mice injected with myeloma cells with knocked-down p38 MAPK as compared with controls. Consistently, we found that tumor p38 MAPK had active effects on in vitro osteoclast differentiation and bone resorption, and inhibited osteoblast differentiation and function, suggesting that constitutive activation of p38 MAPK in myeloma cells induces osteoclastogenesis. By functional studies and protein array analysis, we showed that monocyte chemotactic protein-1 (MCP-1) and dickkopf-1 (DKK-1) are upregulated downstream of p38 MAPK activation in myeloma cells and are responsible for enhanced osteoclastogenesis. Our results showed that p38 MAPK activation in myeloma cells upregulate MCP-1 and DKK-1 expression and production, which are released into the microenvironment. MCP-1 enhanced RANK expression on osteoclast precursors and DKK-1 increased RANKL secretion from stromal cells, all of which led to activation of NF-kB and MAPK signaling pathways in osteoclasts. In vivo blockade of MCP-1 and DKK-1 by specific antibodies significantly abrogated tumor p38 MAPK-induced osteoclast activation and bone lesions in established myeloma-SCID mice. Thus, our results have elucidated a novel mechanism that p38 MAPK activity in myeloma cells contributes to myeloma-induced osteolytic bone lesions. This study indicates that disruption of tumor p38 MAPK may be a new therapeutic approach to treat osteolytic bone lesions in myeloma. Disclosures: No relevant conflicts of interest to declare.
Effects of Inflammation on Multiscale Biomechanical Properties of Cartilaginous Cells and Tissues

Cells within cartilaginous tissues are mechanosensitive and thus require mechanical loading for regulation of tissue homeostasis and metabolism. Mechanical loading plays critical roles in cell differentiation, proliferation, biosynthesis, and homeostasis. Inflammation is an important event occurring during multiple processes, such as aging, injury, and disease. Inflammation has significant effects on biological processes as well as mechanical function of cells and tissues. These effects are highly dependent on cell/tissue type, timing, and magnitude. In this review, we summarize key findings pertaining to effects of inflammation on multiscale mechanical properties at subcellular, cellular, and tissue level in cartilaginous tissues, including alterations in mechanotransduction and mechanosensitivity. The emphasis is on articular cartilage and the intervertebral disc, which are impacted by inflammatory insults during degenerative conditions such as osteoarthritis, joint pain, and back pain. To recapitulate ...
El impacto del sistema tributario y el gasto social en la distribución del ingreso y la pobreza en América Latina: Argentina, Bolivia, Brasil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, México, Nicaragua, Perú, República Dominicana, Uruguay y Venezuela Una aplicación del marco metodológico del proyecto Compromiso con la Equidad (CEQ)

Este articulo presenta resultados sobre el impacto de la politica fiscal en la desigualdad y la pobreza en dieciseis paises de America Latina para alrededor del ano 2010. Los paises que mas redistribuyen son Argentina, Brasil, Costa Rica y Uruguay, y los que menos, Guatemala, Honduras y Peru. A mayor gasto social, mayor redistribucion pero paises con un nivel de gasto social similar muestran diferentes niveles de redistribucion lo cual sugiere que otros factores tales como la composicion y focalizacion del gasto intervienen en determinar el efecto redistributivo mas alla del tamano. La politica fiscal reduce la pobreza extrema en doce paises.. Sin embargo, la incidencia de la pobreza despues de impuestos, subsidios y transferencias monetarias es mayor que la incidencia para el ingreso de mercado en Bolivia, Guatemala, Honduras y Nicaragua, aun cuando la politica fiscal reduce la desigualdad. Ademas, aun cuando la incidencia de la pobreza y la desigualdad se reducen, con la nueva medida de Empobrecimiento Fiscal se puede observar que en Brasil y Mexico un tercio de la poblacion pobre medida con el ingreso consumible fue empobrecida: es decir, paso de pobre a ser mas pobre o de no pobre a ser pobre. El gasto en educacion pre-escolar y primaria es igualador y pro-pobre en todos los paises. El gasto en educacion secundaria es igualador en todos los paises y tambien pro-pobre en algunos pero no en todos. El gasto en educacion terciaria nunca es pro-pobre pero es igualador a excepcion de Guatemala, donde es regresivo y desigualador y en Venezuela, donde su efecto redistributivo es cero. El gasto en salud siempre es igualador pero es pro-pobre solamente en Argentina, Brasil, Chile, Costa Rica, Ecuador, Republica Dominicana, Uruguay y Venezuela.
Speaking of Evidence: An Empirical Study of the Reporting of Forensic Conclusions in US Criminal Trials

This paper uses trial transcript data to try to determine the empirical reality of expert testimony in actual US criminal trials about a variety of forensic techniques, including latent prints, firearms and toolmarks, forensic document analyses, and forensic DNA profiling.
Downtown Art Gallery Jacket

The Downtown Art Gallery Jacket, was created as a piece in a continuing series to demonstrate research conducted into effective hybrid presentation techniques for the transitions from two-dimensional shapes to three-dimensional wearable forms. The aim of this project was to use 2D/3D textile design technologies to create pieces that function as metaphors for our relationship with the world and the impact that we, as individuals, have on our immediate environment. The printed imagery directly relates to the structural forms in the environment and includes visual interplays between the perception of two and three dimensions. This work involves the viewer in the process of conceptualizing the transitions from 2D shapes to 3D objects by asking them to physically interact/try on the piece as it remains connected to the gallery wall.
DNA binding activity of vesicles produced by competence deficient mutants of Haemophilus.

Abstract Membrane vesicles 40–70NM in diameter have been observed in the supernatant of cultures of a mutant strain of Haemophilus parainfluenzae (C-10) defective in transformation. Electron microscopy of thin sections of H. parainfluenzae (C-10) demonstrate that the vesicles are produced by budding off the outer membrane. Vesicles purified by differential centrifugation possess a DNase resistant DNA binding activity, and the membrane-DNA complex has been analyzed on CsCl gradients and shown to band at a density of 1.35g/cc. Mutants of H. influenzae having similiar properties have also been isolated. We report the method of isolation and some of the biochemical properties of vesicles from H. parainfluenzae and H. influenzae .
De Re/De Dicto Ambiguity and Presupposition Projection

The purpose of this paper is to compare three existing theories of de re/de dicto ambiguity: (i) the scope theory, (ii) the intensional variable theory and (iii) the presupposition projection theory. We will conclude that the presupposition projection theory is the conceptually most desirable among these, although all three are expressive enough to describe the data. In particular, we will present novel data suggesting that the intensional variable theory is too expressive and hence lacks explanatory power.
Immunity to Leukemia, Lymphoma, and Fibrosarcoma in Cats: A Case for Immunosurveillance

Central to the discipline of tumor immunology is the hypothesis of immunosurveillance. Does the immune response act to eliminate developing clones of cancer cells in the same manner that it eliminates injurious microorganisms or grafted tissues from unrelated individuals? A great amount of work has been done in response to this question using either virus-induced tumors or transplantable tumors in inbred mice, but very few studies have been done with spontaneous tumors of outbred animals. Evidence that immunosuppressed people have a greater risk of developing certain types of tumors (Gatti and Good, 1971; Penn, 1974, 1975; Wilson and Penn, 1975) is compatible with, but not conclusive proof of, the immunosurveillance hypothesis. Further proof requires not only the demonstration of a depressed immune response to specific tumor cell membrane antigens in outbred individuals prior to tumor development but also the reciprocal—evidence of an enhanced immune response in individuals who remain free of tumors following exposure to the same oncogenic agents. Our general lack of information concerning either the etiological agents of spontaneous tumors or the existence of tumor cell membrane antigens on such tumors probably represents the major roadblock against the design of such experiments for application to outbred individuals with spontaneous tumors.
Eicosanoids and Related Compounds from Marine Algae

One of the more surprising groups of natural products to find wide distribution in the marine environment are the eicosanoids and related fatty acids. In mammalian systems, this assemblage of diverse structures is of seminal importance to the maintenance of normal physiology. Furthermore, enhanced or aberrant production of metabolites in this structural class underlies a number of diseases related to inflammation. In the late 1960s and throughout the 1970s, occasional discoveries were made of metabolites generally describable as “eicosanoid-like” from diverse marine life. However, in the 1980s there has been an enormous increase in the number of eicosanoid-like metabolites discovered from these creatures, particularly in the red algae (Rhodophyta) and corals. Despite the widespread occurrence of eicosanoids among marine life forms and their central importance to mammalian physiology and biochemistry, very little is known about what role these compounds play in the ecology or physiology of the producing organisms. Further, in only a few cases have investigators sought to probe the biosynthetic origins of these fat-derived substances, a feature of their mammalian occurrence which has been of extreme interest to mechanistic chemists and central importance in medicinal considerations. Finally, to the extent that marine-derived eicosanoid-like substances have been evaluated for useful pharmacological properties, they are, as is expected, a potently active class.
Imaging to Diagnose Myocarditis, Cardiomyopathy, Tumor and Thrombus

Patients with cancer and concomitant cardiovascular disease frequently need various imaging investigations to arrive at a correct diagnosis.
Abstract 113: Gemcitabine treatment induces immunosuppressive microenvironment in pancreatic cancer by promoting the infiltration, growth, and polarization of macrophages

Resistance to chemotherapeutic drugs remains a major cause of therapeutic failure in pancreatic cancer (PC) patients. Efficacy of chemotherapy is further limited by its debilitating effects on immune system. Apart from genetic abnormalities in tumor cells, the tumor immune- microenvironment plays a crucial role in PC chemoresistance. However, it is unclear how chemotherapy affects the cancer immunity or how it affects the tumor microenvironment (TME). In the present study, we demonstrate gemcitabine induces an increased infiltration of CD68+ M2 macrophages in pancreatic tumors isolated from an orthotopic xenograft murine model. Moreover, the conditioned media from PC cell lines cultured with gemcitabine (Gem-CM) promotes migration, invasion, and growth of RAW264.7 macrophage. Interestingly, Gem-CM induces an upregulation of tumor-associated or M2-polarized macrophage markers, arginase-1 and TGF-β1. Additionally, gemcitabine treatment of PC cell lines induces the expression of M2-polarization associated cytokines, growth factors and chemokines, including IL-8. IL-8 exhibits the greatest upregulation after culture with Gemcitabine. Further, IL-8 neutralization in Gem-CM diminished its ability to induce growth, migration, and invasion of RAW264.7 macrophages. Together, these findings suggest an indirect effect of gemcitabine on increasing macrophage trafficking and M2-polarization that potentially supports a pro-tumor microenvironment. These actions may contribute to the chemoresistance of PC. Prevention of gemcitabine-induced macrophage infiltration, growth and M2-polarization will offer a better strategy to counter chemotherapy-induced immunosuppression in PC. Citation Format: Sachin Kumar Deshmukh, Arun Bhardwaj, Nikhil Tyagi, Mohammad Aslam Khan, Sanjeev K. Srivastava, Ahmed AL-Ghadhban, Kari Dugger, James E. Carter, Ajay P. Singh, Seema Singh. Gemcitabine treatment induces immunosuppressive microenvironment in pancreatic cancer by promoting the infiltration, growth, and polarization of macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 113.
Students’ Self-Regulated Learning Deficiencies During the Capstone Design Course

Engineering design is an iterative problem-solving activity that utilizes basic science, mathematics, and engineering science. It is a challenging and complex process, especially during the Capstone design course, where students usually engage in a complete design process for the first time. In this course, they need to use, oversee, and adjust their design, communication, and managerial skills to accomplish the design goals. In other words, self-regulated learning (SRL or self-regulation) skills are crucial during such period. Studies suggest that a good self-regulated student tends to perform better and produce higher quality design compared to their counterparts. By reflecting on our five-year research project, students' self-regulation deficiencies while engaged in a design process are explicated, and methods to overcome them are discussed.
Acoustic bianisotropy in effective fluids of finite domain

Recent research has shown that subwavelength asymmetry and/or nonlocal effects in heterogeneous acoustic media can be described as a dynamic effective fluid displaying acoustic bianisotropic properties. Theoretical homogenization schemes have demonstrated emergent acoustic bianisotropy for an infinite array of subwavelength inhomogeneities in a fluid matrix, and experimental studies have demonstrated individual asymmetric microstructures and single layer metasurfaces exhibiting bianisotropy. However, metamaterials research has shown that a finite domain effective fluid behaves unlike an infinite domain or a surface, and the effective properties of the domain tend to depend on the chosen boundaries and on the position within the domain, even when the microstructure is periodic. This work presents the use of multiple scattering homogenization to discuss the dependence of bianisotropic properties of finite effective fluids on the choice of boundaries and domain size in order to inform future experimental studies on acoustic bianisotropy. [Work supported by the Office of Naval Research and the NRC Research Associateship Program.]
Development of indicators for the social dimension of sustainability in a U.S. business context

Abstract Businesses are being increasingly scrutinized regarding their social impacts. In order for businesses to make decisions that support all three pillars of sustainability, i.e., the social, environmental, and economic dimensions, tools and methods are needed that link their decisions to sustainability impacts – including societal effects. However, before such methods can be established, measures of social sustainability are needed. Based on Maslow's hierarchy of individual needs, a novel framework for social indicators has been developed by evaluating the needs of social entities with which a company interacts, e.g., employees and customers. A group of sustainability experts was surveyed using an iterative Delphi technique to converge on a suite of social sustainability indicators that should be addressed by a U.S. business. Statistical methods (i.e., Friedman test and t-distribution comparisons) were used to identify the “best fit” social indicators for the various entities with which businesses interact. The resulting indicators can be used to evaluate social performance for a business enterprise. As examples, some indicators identified for the employee social group include the percentage of employees below the cost-of-living adjusted poverty line and the percentage of employees that believe their contribution to a company is valued.