cssi/SciSciGPT-SciSciNet huggingface dataset:
One-Year Outcomes from a Disease Management Program for Chronic Obstructive Pulmonary Disease

Objective: to present the results of our 1-year, telephonic disease management interventions for 349 patients with mild to severe chronic obstructive pulmonary disease (COPD). Methods: parameters measuring utilization of medical services, days lost from work, and quality-of-life measurements (utilizing the St. George’s Questionnaire) were determined for the 12-month period prior to enrollment of patients and compared with those observed during the 12-month participation in the program. Results: there was a statistically significant reduction in all utilization measurements and a statistically significant improvement in quality of life. Emergency room (ER) visits decreased by 57% (p < 0.001), hospitalizations by 53% (p < 0.001), intensive care unit admissions by 66% (p = 0.001), unscheduled office visits by 67% (p < 0.001), and oral antibacterial bursts by 48% (p < 0.001). Of the 114 employed patients, days missed from work were reduced by 77% (p < 0.001). The total saving from reduction in hospitalizations and ER visits was $US672 000. This was against an approximate cost of the program of $US223 500 (average of $US635 per enrollee). Costs associated with medications and physician visits were not obtained. Conclusions: these outcomes suggest that, with ongoing patient support, the provision of physical rehabilitation, and improved communication between those engaged in the healing process, it is possible to reduce utilization and overall healthcare expenditures and improve the quality of life for a population of patients with moderate to severe COPD. This intervention was both cost effective and medically effective. Our experience suggests that further trials of COPD disease management are warranted.
Nonalcoholic Fatty Liver Disease: A Clinical Review

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.
Cooperative empirical failure avoidance for multithreaded programs

Concurrency errors in multithreaded programs are difficult to find and fix. We propose Aviso, a system for avoiding schedule-dependent failures. Aviso monitors events during a program's execution and, when a failure occurs, records a history of events from the failing execution. It uses this history to generate schedule constraints that perturb the order of events in the execution and thereby avoids schedules that lead to failures in future program executions. Aviso leverages scenarios where many instances of the same software run, using a statistical model of program behavior and experimentation to determine which constraints most effectively avoid failures. After implementing Aviso, we showed that it decreased failure rates for a variety of important desktop, server, and cloud applications by orders of magnitude, with an average overhead of less than 20% and, in some cases, as low as 5%.
Primitive Globalization? State and Locale in Neoliberal Global Engagement

Drawing widely from sociology, political science, and urban studies, this article introduces the term “primitive globalization” in order to address issues of state and governance for localities that globalize within a national context. Suggested by the discussion of primitive accumulation in Marx's Capital, this conceptual frame highlights the ways in which states neither circumvented by globalization nor resistant to it may facilitate neoliberal globalization by “separating” or disembedding social actors from conditions that otherwise impede short-term economic activity. This conception, which is considered primarily in relation to the United States, positions the state as both facilitator and victim of globalization, draws attention to state fragmentation and national politics, and places the role of the national state in the local state at the center of unstable linkages. It is suggested that under these conditions the national/local state may be caught between the roles of government and governance; f...
Using vibrational mode analysis for predicting the coefficient of thermal expansion of amorphous polymers

Molecular dynamics simulations and vibrational analysis on model amorphous polyethylene structures demonstrate that the main contribution to the coefficient of thermal expansion (CTE) is due to structural relaxations even at temperatures below the glass transition. The contribution due to vibrational relaxation, calculated within the Gruneissen theory of solids, accounts only for a small fraction of the CTE. Based on our findings we argue that tailoring of polymers with low CTE should focus on reduction of the relaxation processes.
Cost translation and a lifting approach to the multirate LQG problem

It is shown how to translate an instance of a multirate sampled-data LQG problem into an equivalent, modified, single-rate, shift-invariant problem via a lifting isomorphism approach. Using this approach, one can solve the multirate LQG problem without using periodic system theory or solving periodic Riccati equations and without suffering any increases in state dimension. This translation procedure shows the correct way to translate RMS noise specification to the lifted domain for a multirate Q-design computer-aided-design package. >
Critical Cysteine Residues in Both the Calcium-Sensing Receptor and the Allosteric Activator AMG 416 Underlie the Mechanism of Action

AMG 416 is a novel D-amino acid-containing peptide agonist of the calcium-sensing receptor (CaSR) that is being evaluated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients receiving hemodialysis. The principal amino acid residues and their location in the CaSR that accommodate AMG 416 binding and mode of action have not previously been reported. Herein we establish the importance of a pair of cysteine residues, one from AMG 416 and the other from the CaSR at position 482 (Cys482), and correlate the degree of disulfide bond formation between these residues with the pharmacological activity of AMG 416. KP-2067, a form of the CaSR agonist peptide, was included to establish the role of cysteine in vivo and in disulfide exchange. Studies conducted with AMG 416 in pigs showed a complete lack of pharmacodynamic effect and provided a foundation for determining the peptide agonist interaction site within the human CaSR. Inactivity of AMG 416 on the pig CaSR resulted from a naturally occurring mutation encoding tyrosine for cysteine (Cys) at position 482 in the pig CaSR. Replacing Cys482 in the human CaSR with serine or tyrosine ablated AMG 416 activity. Decidedly, a single substitution of cysteine for tyrosine at position 482 in the native pig CaSR provided a complete gain of activity by the peptide agonist. Direct evidence for this disulfide bond formation between the peptide and receptor was demonstrated using a mass spectrometry assay. The extent of disulfide bond formation was found to correlate with the extent of receptor activation. Notwithstanding the covalent basis of this disulfide bond, the observed in vivo pharmacology of AMG 416 showed readily reversible pharmacodynamics.
Assessment of Quantitative Enclosure Sampling of Larval Amphibians

Reports of the disappearance and decline of amphibians have stimulated interest in developing more accurate methods for sampling amphibian populations. Specific sampling methods are often suggested because of logistical concerns or simple tradition, but the validity of underlying assumptions for particular methods are rarely confirmed. This study examined potential problems and biases with quantitative enclosure sampling of larval amphibians. Results indicate that movement within a pond by an investigator does not reduce the number of captured tadpoles any more than does approaching a sampling station from the shore. Disturbance created in taking a sample does not appear to reduce number of tadpoles captured in subsequent samples taken 5 m or even 1 m away. Net type can be critical in how efficiently animals are removed from the enclosure, but the effect of net type on capture efficiency may vary with the amount of vegetation present. Investigators should assess the validity of assumptions for enclosure sampling before using this technique to draw inferences about populations of larval amphibians.
Animal Sentinels for Environmental and Public Health

Studies of the effects of environmental exposures on domestic and wild animals can corroborate or inform epidemiologic studies in humans. Animals may be sensitive indicators of environmental hazards and provide an early warning system for public health intervention, as exemplified by the iconic canary in the coal mine. This article illustrates the application of animal sentinel research to elucidate the effects of exposure to traditional and emerging contaminants on human health. Focusing on environmental issues at the forefront of current public health research, the article describes exposures to community air pollution, environmental tobacco smoke, and pesticides and associations with cancer, reproductive outcomes, and infectious diseases. Finally, it covers the role of marine mammals in monitoring the health of the oceans and humans.
Sheared Flow as a Stabilizing Mechanism in Astrophysical Jets

Summary form only given. It has been hypothesized that the sustained narrowness observed in the asymptotic cylindrical region of bipolar outflows from young stellar objects (YSO) suggests that an intrinsic collimating mechanism is present in these jets. The j x B force observed in z-pinch plasmas {jzldrBthetas) is a possible explanation for these observations. However, z-pinch plasmas are subject to current driven instabilities (CDI). The interest in using z-pinches for controlled nuclear fusion has lead to an extensive theory on the stability of magnetically confined plasmas. Analytical, numerical, and experimental evidence from this field suggest that sheared flow in magnetized plasmas can reduce the growth rates of the sausage and kink instabilities. Here we propose the hypothesis that sheared helical flow can exert a similar stabilizing influence on CDI in YSO jets. Experimental, analytical, and numerical analysis of sheared flow in magnetohydrodynamic plasmas with and without helical magnetic fields is presented. The results support the hypothesis that sheared flow may impart a stabilizing influence in astrophysical jets. Future laboratory experiments are proposed that will provide enhanced support for this conclusion.
Spinning with Dave: David Yphantis's contributions to ultracentrifugation.

For nearly 50 years David Yphantis has helped advance analytical ultracentrifugation, promoted rigor in the thermodynamic analysis of biochemical data and encouraged students and colleagues to look for the deepest possible understanding of science. This article, written by five of Daves's students, presents some of the impressions he has made over the years.
Recognizing recycled osmium

Understanding the behavior of noble metals like Os in Earth systems is important from both scientifi c and economic standpoints. The abundances of noble metals in the mantle have signifi cant implications for our understanding of the Earth’s evolution. The relative abundances of these strongly siderophile elements in the mantle potentially preserve a fi ngerprint of core formation, which likely scavenged much of the Earth’s budget of these elements, as well a record of the latest stages of accretion history, during which time the Earth’s mantle may have been re-enriched in these elements (e.g., Walter et al., 2000). Understanding processes that can modify these signatures in the Earth’s mantle is fundamental to such models. In addition, documenting environments under which noble metals are mobile, and those under which they become scavenged and concentrated, are critical for understanding the formation of precious metal ore deposits and developing strategies for prospecting. For example, many economic Au deposits are associated with magmatism at convergent margins, yet the source of the Au and the behaviors of other noble metals are generally not well constrained (McInnes et al., 1999). The paper by Suzuki et al. (2011, p. 999 in this issue of Geology) contributes important new results regarding the mobility of Os in subduction settings. The Re-Os isotope system, involving the decay of
Ion beam profiling of small objects using resonant nuclear reactions

Abstract Techniques for obtaining the shape of small solid objects (and larger periodic surfaces) using resonant nuclear reactions will be described. Both (p, γ) and (p, α) reactions prove suitable for this purpose. The computer programs required, how ambiguities may be resolved and the problem of radiation damage are treated.
Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344 rats

Larkin, Lisa, Eric R. Leiendecker, Mark Supiano, and Jeffrey Halter. Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344 rats.J. Appl. Physiol....
Interannual and Interdecadal Variations of the East Asian Summer Monsoon and Tropical Pacific SSTs. Part II: Meridional Structure of the Monsoon

Abstract The relationship between the interannual variations of the East Asian summer monsoon and that of the tropical SST shows considerable variations. In this study, rainfall in the southeastern coastal area of China (SEC) during 1951–96 is used to composite the tropical SST, 850-hPa wind, and 500-hPa height. The results relative to the May–June rainfall, which represents most of the SEC summer monsoon rainfall, are compared to the Yangtze River Valley (YRV) rainfall composites. It is shown that strong interdecadal changes in the Pacific may account for the observed variations in the meridional structure of the monsoon–SST relationship. The western Pacific 500-hPa subtropical ridge, which is influenced by the equatorial eastern Pacific SST, is crucial to these variations. During 1951–77 the SEC wet phase is produced by an anomalous anticyclone in the northern South China Sea, which tends to make the monsoon pre-Mei-yu and Mei-yu fronts quasi-stationary in the general area of both SEC and YRV, and also ...
A sarcomeric protein tongue-twister: post-translation, citrullination/deimination and elimination of arginine residues

This editorial refers to ‘Citrullination of myofilament proteins in heart failure’ by J. Fert-Bober et al. , doi:10.1093/cvr/cvv185. There is now appreciation in the research community that post-translational modification (PTM) at the level of cardiac sarcomeres is a significant element in the control of cardiac contractility down-stream of Ca-signaling.1,2 These modifications are critical in the tuning of the heart beat to impositions of altered heart rate, pre-load, afterload, and metabolic demands. The constellation of cardiac sarcomeric PTMs that occur are related to the maintenance of a homeostatic state, and as with other regulatory mechanisms, when the PTMs do not synchronize with demands on cardiac function a progressive disorder may occur. With the emergence of remarkably sophisticated aches employing mass spectrometry,3,4 there has been a deeper understanding of the diversity and potential significance of PTMs of sarcomeric proteins beyond their well-characterized state of phosphorylation and oxidation. The list includes a multitude of potential modifications, and a newly discovered modification has been reported by Fert-Bober et al. 5 This novel finding indicates that a number of critical cardiac sarcomeric proteins from control human hearts and from hearts with ischaemic disease and dilated cardiomyopathy undergo deimination or citrullination in which an Arg residue is replaced with a citrulline, resulting in an irreversible loss of a negative charge and an increase in hydrophobicity. As recently reviewed by Fert-Bober and Sokolove,6 this reaction is under the control of peptidylarginine deiminase (PAD), a Ca2+-regulated enzyme with poorly understood substrate specificity. There are a number of isoforms of PAD, several of which are expressed in myocardium. However, Fert-Bober et al. 5 report that the PAD2 is …
Simulation of Sulfur Cycle in Estuarine Sediments

A mathematical model of estuarine sediment is developed using rate coefficients and field measurements. The model has a particular emphasis on the sulfur cycle and includes specific chemical components of dissolved oxygen, soluble organic carbon, sulfates, free sulfides, total sulfides, sulfide capacity, sulfur, and pyrite. Different levels of sediment organics (OCS) and turnover rates (RST) are mathematically imposed and the subsequent levels of chemical components are determined after a 210-day period. General chemical properties are identified for a RST-OCS plane.
Effect of clutch size on incubation persistence in male Wilson's phalaropes (Phalaropus tricolor)

ABSTRACr.-The effect of clutch size on incubation persistence of male Wilson's Phalaropes (Phalaropus tricolor) was studied over two breeding seasons in south-central Saskatchewan. The Wilson's Phalarope is a "sex-role-reversed" shorebird in which only males incubate and provide parental care. The breeding season is long enough to allow for renesting but not for the rearing of more than one brood per male. Barring secondary mating strategies, the total annual reproduction of a male is limited by the size of its clutch. Females lay determinate clutches of four eggs. By determining the minimum clutch size necessary for male incubation persistence, we demonstrated that males alter their reproductive effort in response to clutch size, and we identified the minimum potential annual reproduction for males necessary to maintain this unusual mating system. Clutch-size reductions led to an increased frequency of abandonment inversely proportional to the number of eggs remaining in the clutch. The timing of egg loss also was critical. Among males with clutches reduced to one egg or reduced to two eggs early in the incubation cycle, all but one abandoned incubation. Among males with clutches reduced to two eggs late in incubation or three eggs early, an intermediate proportion abandoned incubation. All but one male with three eggs late in incubation or a full, four-egg clutch continued to incubate. Experimentally increasing clutch sizes by two eggs over the normal four-egg clutch led to rapid nest failure. This suggests that the determinate, four-egg clutch of females is not suboptimal for males and that nest parasitism of two eggs by females has little potential benefit as an alternative reproductive tactic. Received 24 February 1992, accepted 22 November 1992.
KURU AND MAD COW DISEASE : UNDERSTANDING THE PRION THEORY

A preponderance of evidence indicates that several neurodegenerative disorders are caused by prions: abnormally folded proteins that can induce abnormal folding in other normal protein molecules. Further, these "infections" can cross some species barriers.
Assessment of Homogeneity of Extruded Alumina-SiC Composite Rods Used in Microwave Heating Applications by Impedance Spectroscopy

Composite rods consisting of Alumina (Al 2 O 3 ) and Silicon Carbide whiskers (SiC w ) are used to fabricate microwave cooking racks because they effectively act as a microwave intensification system that allows cooking at much faster rates than conventional microwave ovens. The percolation behavior, electrical conductivity and dielectric properties of these materials have been reported previously. However, it has been observed that the electrical response of the extruded bars is a function of the rod length and that long rods show substantially different behavior than thinner disks cut from them. A percolation model has been proposed that describes the effect of the alignment of the semiconducting SiC whiskers and the quality of the interfaces present in the composite rods: SiC-SiC and SiC-Al 2 O 3 -SiC for example. This study was undertaken with the goal of testing out whether the response of the individual sections could be used to generate the response of the full length rods and to assess the importance of the homogeneous distribution of the SiC fillers on the resultant impedance response.
Section 7. Epilogue

The geochemical context that supported hydrothermal research was also maturing rapidly during the last half of the 20th century. Some observations on that progress may improve our perspective on the advances discussed in the preceding sections of this volume. Both written and verbal communication
Etiological analysis of postmenopausal vaginal bleeding among 256 patients

Objective:To analysis the etiological factors of postmenopausal vaginal bleeding.Methods: 256 patients with postmenopausal vaginal bleeding were retrospectively analyzed.Results: The etiological factors of postmenopausal vaginal bleeding in 256 patients included cervicitis(30.08%,77/256),vaginitis(20.31%,52/256),functional uterus bleeding(13.28%,34/256),endometritis(8.98%,23/256),malignant tumor(8.20%,21/256),atypical hyperplasia of endometrium(7.81%,20/256),hysteromyoma(6.25%,16/256),intrauterine contraceptive device(IUCD)(3.91%,10/256),trauma(1.17%,3/256).Conclusion: Inflammation is the prior cause for postmenopausal vaginal bleeding.The longer time from menopause to postmenopausal vaginal bleeding,the higher the rate of malignant tumour.
PSEDOCOMPOSITIONAL MODEL FOR MISCIBLE FLOODING

As a usual, compositional model is used to simulate miscible flooding. However, because of its slow calculation and much data difficult to be got, it is not very easy to use by reservoir engineers. So this paper introduces a simulation model for miscible flooding. It is a developed pseudocompositional model based on conventional black oil model, and it has good stability and fast calculation of black oil model, and also has the compositional model characteristic such as simulation of condensate gas reservoir and miscible displacement etc. In addition, the paper presented the mathematical model and the approach to deal with different physical parameters and fluid properties. The model was used to verify the SPE example, it proved to be true.
The effect of MYJ and YSU schemes on the simulation of boundary layer meteorological factors of WRF

This study analyzed the effects of two difference boundary layer schemes in the Weather Research and Forecast(WRF) model on the simulation of meteorological factors related to pollutant dispersion over Shenyang China in winter.The performance of WRF was evaluated against observation data with statistics.It was revealed that WRF underestimated the temperature and overestimated the surface wind speed which may be attributed to the outdated land use data.The Yonsei University(YSU) scheme simulated higher air temperature and weaker nocturnal surface-based inversion layer than the Mellor-Yamada-Janjic(MYJ) scheme,due to the stronger entrainment at the top of the boundary layer and vertical mixing in YSU.The duration of inversion layer was 4 hours longer in MYJ than YSU.The temperature difference between the two schemes was highest before sunrise,after which the surface heating weakened the difference.The surface wind was not sensitive to the boundary layer schemes and both MYJ and YSU simulated north wind with the highest frequency and speed,agreed with observation.The boundary layer height was also higher in YSU than MYJ,favoring the vertical dispersion of pollutant.Among the three methods determining the boundary layer height,the TKE(Turbulent Kinetic Energy) method led to the highest values,while potential temperature method led to the lowest.The bulk Richardson number method was sensitive to the critical value.
In Vivo Transfer of an R-Plasmid in a Urinary Tract Infection Model

AbstractWith the increased use of antibiotics in urinary tract infections, the appearance of resistant organisms. We demonstrated transfer of an R-factor in vitro at a transfer frequency rate of 0.5 to 1.0 × 10−7 and in vivo rate of 5 × 10−2. When urine was used instead of nutrient broth as the medium for in vitro transfer, recombinants were not recovered. Transfer of R-plasmids between place in the intestine and possibly elsewhere, depending on a number of factors. This mechanism is thought to be responsible for hospital and community outbreaks of infections with resistant organisms. We demonstrated transfer of an R-factor in vitro at a transfer frequency rate of 0.5 to 1.0 × 10−7 and in vivo rate of 5 × 10−2. When urine was used instead of nutrient broth as the medium for in vitro transfer, recombinants were not recovered. Transfer of R-plasmids between bacterial strains is thought to be the primary mechanism by which antibiotic resistance has flourished in bacterial populations and the finding of trans...
Effects of pH on Ca2+i, Na+i, and pHi of MDCK cells: Na(+)-Ca2+ and Na(+)-H+ antiporter interactions.

The effects of high and low extracellular pH (8.0 and 6.8) on the intracellular concentration of Ca2+, Na+, and H+ were measured in perfused Madin-Darby canine kidney (MDCK) cells cast in agarose gel threads. Cytosolic free Ca2+ (Ca2+i) was measured with aequorin, while intracellular Na+ (Na+i) and H+ (Hi+ or pHi) were determined with the fluorescent indicators SBFI and BCECF, respectively. In addition, H+ secretion was assayed by the pH-stat method, and Na+ or Ca2+ fluxes were measured with 22Na or 45Ca, respectively. H+ secretion was significantly depressed by several experimental conditions that are known to inhibit the Na(+)-H+ antiporter: H+ secretion decreased 44% in the presence of 10(-5) M ethylisopropylamiloride, 49% in Na+o-free media, 44% in the presence of 10(-4) M ouabain, and 32% in the presence of 10(-4) M 8-bromoadenosine 3',5'-cyclic monophosphate. In addition, pHi decreased by 0.2 pH units in Na+o-free media. Finally, recovery from an intracellular acidosis evoked by 20 mM NH4Cl pulse required the presence of extracellular Na+. When the extracellular pH (pHo) was increased from 7.4 to 8.0, H+ secretion increased 58% from 17.5 to 27.7 nmol.min-1.mg protein-1 and Na+ influx increased 48%. As a result, pHi rose from 7.43 to 7.71 and Na+i increased from 15.6 to 19.7 mM. Finally, Ca2+i rose from 120 to 268 nM. These results suggest that the high pHo stimulated the Na(+)-H+ antiporter, and the subsequent rise in Na+i decreased the Na+ electrochemical potential, thereby activating the reverse mode of Na(+)-Ca2+ exchange (Ca2+ influx vs. Na+ efflux) which led to the rise in Ca2+i.(ABSTRACT TRUNCATED AT 250 WORDS)
DOE SMART Mobility: Systems and Modeling for Accelerated Research in Transportation

New paradigms emerging in transportation and information and communication technology create opportunities to better understand and leverage the interactions between travelers, vehicles, and the built environment to reduce greenhouse gas emissions and save energy. The U.S. Department of Energy’s SMART (Systems and Modeling for Accelerated Research in Transportation) Mobility Initiative recognizes and harnesses these megatrends by elevating DOE’s traditional transportation energy focus beyond the vehicle component technology level to transportation-as-a-system analysis, modeling and simulation, and applied research and development in 5 interrelated topics: connected and automated vehicles, mobility decision science, urban science, vehicles and infrastructure, and multi-modal.
The Effect of Insulin-Like Growth Factor 1 on Waldenstrom Macroglobulinemia

Abstract Background: Waldenstrom's Macroglobulinemia (WM) is an incurable lymphoplasmacytic lymphoma with limited options of therapy. Insulin-like growth factor 1 (IGF1) is a polypeptide hormone that has been shown to have a proactive role in many cancer cell types, including multiple myeloma and solid tumor cells. We evaluated the role of IGF1 in WM. Methods: WM cell lines (BCWM1 and WSU-WM) and IgM secreting low-grade lymphoma cell lines (MEC1, RL) were used. Bone marrow-derived primary CD19+ cells and bone marrow stromal cells (BMSC) were obtained from patients with WM after informed consent. The small molecule IGF-1R inhibitor II (Calbiochem) and the inhibitory antibody αIR3 (Calbiochem) were used. Cytotoxicity and DNA synthesis were measured by MTT assay and thymidine uptake assay, respectively. Cell signaling and apoptotic pathways were determined by Western Blot. Cell cycle and receptor analysis was obtained through flow cytometry. IGF1 levels were measured by ELISA. Receptor tyrosine kinase activity was evaluated in WM cell lines using the Luminex-microbeads-based assay. Results: We demonstrated that the IGF1 receptor (IGF1R) was expressed on WM primary patients and normal CD19+ control B cells, while IGF1 levels of serum and bone marrow samples in both patient and healthy donor samples were similar, suggesting a possible constitutive activation of the pathway downstream of IGF1R in WM and independent of receptor activity or cytokine levels. Surface IGF1R was expressed on BCWM1 cells, in serum-starved conditions, while, it was internalized with the addition of FBS that includes IGF-1. Finally, we also showed that IGF1 induces the activation of IGF1R as demonstrated by the induction of related tyrosine kinase activity. To demonstrate the protective effect of IGF1 on WM cells, IGF1 was added to serum starved BCWM1 cells, and we found it rescued nearly 100% of the cells from apoptosis in concentrations as low as 25ng/ml. The effect of IGF1R inhibitor on WM cells has been investigated and found that it blocked migration, induced cytotoxicity and decreased cell proliferation; without any effect on healthy donor peripheral blood mononuclear cells. Furthermore, the inhibitor decreased the tyrosine kinase activity of IGF1R, overcoming its initial activation in the presence of IGF1. Conclusion: IGF1 plays a complex role in WM cells with no evidence of constitutive activation of the receptor itself or higher levels of cytokine in WM marrow samples, indicating that activation of this pathway is downstream of IGF1R. Inhibition of IGF1R by a specific small molecule or antibody inhibitor led to a significant decrease in proliferation, survival, and migration in WM cells, but not in control mononuclear cells. These studies provide the framework to investigate the role of IGF1R inhibitors in clinical trials in WM.
Transparency and Trust — Online Patient Reviews of Physicians

With Yelp forcing the issue of publicly available patient ratings of doctors, health care organizations need to consider the goals of transparency efforts, how they can best be achieved, whose responsibility it is, and the best venues for such data sharing.
Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality.

OBJECTIVE We investigated temporal and spatial characteristics of ictal gamma and beta activity on scalp EEG during spasms in patients with West syndrome (WS) to evaluate potential focal cortical onset. METHODS A total of 1,033 spasms from 34 patients with WS of various etiologies were analyzed on video-electroencephalography (EEG) using time-frequency analysis. Ictal gamma (35-90 Hz) and beta (15-30 Hz) activities were correlated with visual symmetry of spasms, objective EMG (electromyography) analysis, and etiology of WS. RESULTS Prior to the ictal motor manifestation, focal ictal gamma activity emerged from one hemisphere (71%, 24/34) or from midline (26%, 9/34), and was rarely simultaneously bilateral (3%, 1/34). Focal ictal beta activity emerged from either one hemisphere (68%, 23/34) or from midline (32%, 11/34). Onsets of focal ictal gamma and beta activity were most commonly observed around the parietal areas. Focal ictal gamma activity propagated faster than ictal beta activity to adjacent electrodes (median: 65 vs. 170 msec, p < 0.01), and to contralateral hemisphere (median: 100 vs. 170 msec, p = 0.01). Asymmetric peak amplitude of ictal gamma activity in the centroparietal areas (C3-P3 vs. C4-P4) correlated with asymmetric semiology. On the other hand, most of the visually symmetric spasms showed asymmetry in peak amplitude and interhemispheric onset latency difference in both ictal gamma and beta activity. SIGNIFICANCE Spasms may be a seizure with focal electrographic onset regardless of visual symmetry. Asymmetric involvement of ictal gamma activity to the centroparietal areas may determine the motor manifestations in WS. Scalp EEG ictal gamma and beta activity may be useful to demonstrate localized seizure onset in infants with WS.
Low-profile endfire radiating wideband antenna for Ka band applications

This paper analyzes the performance characteristics of a coupled microstrip resonator antenna when scaled to operate in the Ka band. The antenna is low-profile, vertically polarized, radiates in the endfire direction, and is mountable on large metallic surfaces. It is comprised of a coaxial fed trapezoidal launcher along with six rows of coupled microstrip resonators. The base antenna design is modeled, simulated, fabricated, and measured. Validation of the accuracy of this model is achieved through good agreement between the measured and simulated results. The antenna model is then scaled, simulated, and compared against the performance of the base model. A bandwidth of 5.5–10.8GHz for VSWR 0 (where λ 0 is the center frequency wavelength in free space) and a radiation efficiency greater than 97%.
Cognitive Control, the Anterior Cingulate, and Nicotinic Receptors: A Case of Heterozygote Advantage.

The cholinergic neurotransmitter system, via diffuse projections emanating from the basal forebrain and synapsing onto numerous cortical targets, modulates several neurocognitive functions, including attention, working memory, and cognitive control ([Picciotto et al., 2012][1]). Concordantly, loss-
A simulation-based optimization framework for integrating scheduling and model predictive control, and its application to air separation units

Abstract The integration of dynamic process models in scheduling calculations has recently received significant attention as a mean to improve operational performance in increasingly dynamic markets. In this work, we propose a novel framework for the integration of scheduling and model predictive control (MPC), which is applicable to industrial size problems involving fast changing market conditions. The framework consists on identifying scheduling-relevant process variables, building low-order dynamic models to capture their evolution, and integrating scheduling and MPC by, (i) solving a simulation-optimization problem to define the optimal schedule and, (ii) tracking the schedule in closed-loop using the MPC controller. The efficacy of the framework is demonstrated via a case study that considers an air separation unit operating under real-time electricity pricing. The study shows that significant cost reductions can be achieved with reasonable computational times.
FDA Approval Summary: Niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy

The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence interval (CI), 0.17-0.41; P 20% and higher incidence in the niraparib arm) with niraparib included thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. There were five cases of myelodysplastic syndrome and acute myeloid leukemia (1.4%) in patients treated with niraparib compared with two cases (1.1%) on placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer, with improvement in PFS, regardless of gBRCAm status. Clin Cancer Res; 24(17); 4066-71. ©2018 AACRSee related commentary by Konstantinopoulos and Matulonis, p. 4062.
EPR studies on the kinetics of quenching singlet oxygen

The specific reaction between singlet oxygen (1O2) and 2,2,6,6-tetra-methyl-piperidine (TEMP) was utilized to investigate the kinetics of singlet oxygen quenching. Rose bengal was used for the generation of singlet oxygen (1O2). The deuterium isotope effect (rho) was found to be 22.1. The rate constant (kT) of the reaction of TEMP with 1O2 in H2O, D2O and ethanol were found to be 9.0 x 10(5) M-1s-1, 1.5 x 10(6) M-1s-1 and 7.3 x 10(5) M-1s-1, respectively. The intercept of the plot of [TEMPO]-1 at different H2O/D2O ratios was found to be constant, indicating the lifetime of 3Sens is independent of solvent deuteration. The quenching of 1O2 by azide and the sensitizer itself were confirmed by the constant intercept on the kinetic plots. Thus, the quenching rate constants for azide anion in ethanol solution (96%) and for ground state rose bengal in 0.05 M phosphate buffer (pH 7.4), were found to be 8.36 x 10(8) M-1s-1 and 1.72 x 10(4) M-1s-1, respectively. These studies not only verify the specificity of the reaction between TEMP and 1O2 but also provide a sensitive and specific assay for 1O2.
Investigating Text–Reader Interactions in the Context of Supported etext

We describe the empirical and theoretical roots of the Reading to Learn program of research, which was designed to investigate the metacognition and learning of upper elementary students in supportive etext environments. The results of study one, a think-aloud study in which children responded to narrative and informational texts, were used to inform the design of supports that were investigated in study two. Study two was an intervention study in which children read and responded to one of three etext versions: A static version, an interactive diagram version in which students could animate the graphic that corresponded with information presented in the prose and could manipulate the diagrams to explore ideas that were presented in the prose, or an interactive diagram/coaching version, which included two animated pedagogical agents, who provided both procedural and conceptual support. We critique the methods used in the intervention study and propose further research suggested by its findings.
Social Science Contributions to Multiple Objective Decision Making within Watersheds

Practically all natural resources development programmes have been implemented at the watershed level in recent years because it has been repeatedly observed that watersheds are integrated socio-environmental units whose component parts are interdependent. The well-being of the components is dependent on the viability of the whole. To achieve improvement in environmental quality in specific components of a watershed requires a holistic planning and programme implementation approach.
Transduction of physical force by the vascular wall Role of phospholipase C and cytochrome P450 metabolites of arachidonic acid.

Abstract The blood vessel wall responds actively to an elevation in transmural pressure. This pressure-induced myogenic response is thought to set the basal level of vascular tone upon which metabolic and neural influences operate in concert to regulate organ blood flow. The cellular mechanisms that mediate the vascular muscle response to mechanical deformation via a changing transmural pressure include membrane depolarization, activation of phospholipase C, and a rise in intracellular [Ca 2+ ] i , which appear to be nonadapting—remaining active as long as the pressure stimulus is applied. This brief review addresses some of the cellular events mediating transduction of transmural pressure by the vessel wall. Two possible mechanisms that are responsible for the nonadapting nature of pressure-induced myogenic tone are also explored, namely, formation of a P450 metabolite of arachidonic acid, which acts to buffer activation of K + channels as intracellular Ca 2+ rises, and direct activation of Ca 2+ channels by diacylglycerol. Evidence is provided suggesting that activation of phospholipase C is responsible for both the release of the arachidonic acid substrate for P450 enzymes and for the formation of diacylglycerol via its action on membrane-bound phospholipids.
Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use.

OBJECTIVE Because multiple observational studies and large, randomized controlled trials indicate that NSAIDs strongly reduce the risk of colorectal neoplasms, we investigated whether NSAID use masks associations of various other risk factors with colorectal neoplasms. MATERIALS AND METHODS Using pooled data from three case-control studies of incident, sporadic colorectal adenoma (pooled n=789 cases, 2035 polyp-free controls), using multivariable logistic regression, we investigated various risk factor-colorectal adenoma associations stratified by NSAID use. RESULTS Example multivariable-adjusted odds ratios [95% confidence intervals (CI)] for those in the highest relative to the lowest quartiles of exposure, by regular nonaspirin NSAID nonuse/use, respectively, were 1.57 (95% CI: 0.96-2.55) versus 1.14 (95% CI: 0.37, 3.49) for total fat, 1.37 (95% CI: 0.86-2.18) versus 0.70 (95% CI: 0.23-2.25) for saturated fat, 0.93 (95% CI: 0.68-1.28) versus 1.30 (95% CI: 0.61-2.75) for calcium, 0.89 (95% CI: 0.64-1.23) versus 1.38 (95% CI: 0.65-2.94) for total fruits and vegetables, and 0.85 (95% CI: 0.65-1.11) versus 0.94 (95% CI: 0.52-1.71) for physical activity. For current versus never smokers, the odds ratios (95% CIs) among regular non-NSAID users/nonusers were 2.91 (95% CI: 2.22-3.82) versus 1.75 (95% CI: 0.90-3.41), respectively, and for those who were obese versus those who were normal weight, they were 1.67 (95% CI: 1.28-2.17) versus 1.19 (95% CI: 0.69-2.04), respectively. CONCLUSION Our findings suggest that regular nonaspirin NSAID use may mask, beyond simple confounding, associations of major risk factors with colorectal adenoma, and support routinely assessing such associations stratified by regular nonaspirin NSAID use.
Time-aware location sequence recommendation for cold-start mobile users

In this paper, we study the problem of recommending time-sensitive location sequence for mobile users using their check-in data on location-based social networks. Most of the existing studies on Point of Interest (POI) recommendation and prediction fail to address the following two key challenges: (1) how to handle the scenario where the user-location matrix is very sparse (i.e., each user has a very limited number of check-ins, or to say, cold-start users), and (2) how to recommend an optimal time-sensitive visit sequence where each venue matches a time slot specified by users, based on their check-in histories. Motivated by the two challenges above, we propose a predictive framework that enables time-sensitive location sequence recommendation leveraging both the users' semantic and spatial similarities, especially for cold-start users. Our novel framework consists of three modules: semantic similarity modeling, spatial similarity modeling, and on-line sequence recommendation. In semantic modeling, we calculate users' similarity scores by comparing users' temporal hierarchical semantic trees. In spatial modeling, we use Gaussian Mixture Model (GMM) to compute users' similarity scores with respect to their geographical movement paterns. Aferwards, we combine the check-in data of the target user with those of her top-k most similar users in terms of both semantic and spatial similarities to train a personalized Hidden Markov Model (HMM) to predict the most probable venue category for each specified time slot. At last, we recommend location sequence based on the predicted venue category sequence for the target user using geographical mapping.
Sustainable development and research and development intensity in U.S. manufacturing firms

Across manufacturing sectors, mounting regulatory pressures motivate the adoption of innovative sustainable practices to help address and improve environmental performance. Sustainable practices, however, face many challenges to minimize negative environmental impacts while conserving energy and natural resources. This study seeks to understand the effect of research and development intensity on dimensions of environmental performance in manufacturing firms. Using data from U.S. corporations over the period from 1991 through 2015, we find that sustainable practices are associated with a higher level of negative environmental ratings. In addition, the level of environmental concerns tends to decrease with firm investments in research and development intensity over time. These findings suggest that bigger firms are likely to report a higher level of environmental concerns due to their experimentation with sustainable practices. These firms are also likely to reduce negative environmental ratings over time and realize economies of scale with sustainable manufacturing.
Function and Regulation of the Carbonic Anhydrases in the Vertebrate Neural Retina

Carbonic anhydrase (CA) (EC 4.2.1.1.) is highly concentrated in the vertebrate retina; e.g., in birds CA is 3% of the total tissue protein in the retina.10,21 The retinas of most major groups of vertebrates have high CA activity20 with amphibians having the lowest, while birds and reptiles have 25 times as much CA.20 Most mammals are intermediate. No relationship was found between high CA activity and degree and type of vascularization.