cssi/SciSciGPT-SciSciNet huggingface dataset:
Diurnal Variability of the Marine Boundary Layer during ASTEX

The diurnal cycle of the marine boundary layer over the Atlantic Stratocumulus Transition Experiment (ASTEX) domain is examined during a two-week period of June 1992 in several fields, including: fractional low cloudiness, various parameters that enter into the heat and moisture budgets (e.g., temperature, water vapor mixing ratio, vertical motion), the budgets themselves, radiative heating, and the vertical eddy flux of moist static energy. Results show fractional low cloudiness varies over this region from a maximum of 54% in the predawn hours to a minimum of 39% in the midafternoon. These changes in low cloudiness are accompanied by an opposite trend in the boundary layer moisture, which shows a predawn drying and an afternoon moistening. Large-scale vertical motion also varies diurnally with a peak amplitude of 0.12 cm s 21 at 1.8 km, which is a ;20% variation from the mean subsidence rate. Cloud-radiative processes play an important role in determining the diurnal characteristics of the vertical eddy flux of moist static energy, with a peak amplitude in the cloud layer at 1.2 km and a variation at this level from 24 W m 22 at 1300 LST to 100 W m22 at 0400 LST. These diurnal changes suggest that the early morning peak in eddy flux results in a drying of the subcloud layer as moisture transport into the cloud layer is enhanced, leading to the observed low-cloud maximum. In contrast, during the daylight hours, solar heating within the cloud leads to a well-mixed cloud layer, a stabilizing of the subcloud layer with respect to the cloud layer, a decoupling of the cloud and subcloud layers, and ultimately, a thinning or reduction of the low clouds. Comparison of the diurnal cycle of summertime low-level divergence and vertical motion from this study with earlier published results from other regions in the North Atlantic shows a complex diurnal pattern with alternating phase in adjacent latitude belts across this region. The sense of these phase changes suggests that the northern branch of the Hadley circulation from roughly 58 Nt o 258N over the eastern Atlantic is pulsing diurnally with enhanced mass flow during the early morning hours.
Hormonal regulation and cellular localization of fatty acid synthase in human fetal lung

Fatty acid synthase (FAS; EC 2.3.1.85) supplies de novo fatty acids for pulmonary surfactant synthesis, and FAS gene expression is both developmentally and hormonally regulated in the fetal lung. T...
Suicide among young Alaska Native men: community risk factors and alcohol control.

Objectives. I examined community risk factors that explained variation in suicide rates among young rural Alaska Native men, evaluating the effectiveness of local alcohol control as a public health policy to reduce this population’s historically high vulnerability.Methods. I compiled suicide data, alcohol control status, and community-level social, cultural, and economic characteristics for Alaska Native men aged 15 to 34 years in 178 small Alaska communities from 1980 to 2007. Poisson regression equations explained variation in suicide rates as a function of endogenous alcohol control and community characteristics.Results. Suicide rates were higher in communities prohibiting alcohol importation under state law, but the effect was not significant after controlling for other community characteristics. More remote communities, those with fewer non-Natives, and those with evidence of cultural divides had higher suicide risks. Communities with higher incomes, more married couples, and traditional elders had l...
Model selection in multivariate adaptive regression splines (MARS) using information complexity as the fitness function

This paper introduces information-theoretic measure of complexity (ICOMP) criterion for model selection in multivariate adaptive regression splines (MARS) to tradeoff efficiently between how well the model fits the data and the model complexity. As is well known, MARS is a popular nonparametric regression technique used to study the nonlinear relationship between a response variable and the set of predictors with the help of piecewise linear or cubic splines as basis functions. A critical aspect in determining the form of the nonparametric regression model during the MARS strategy is the evaluation of portfolio of submodels to select the best submodel with the appropriate number of knots over subset of predictors. In the usual regression modeling, when a large number of predictor variables are present in the model, and there is no precise information about the exact functional relationships among the variables, many model selection criteria still overfit the model. In this paper, to find the simplest model that balances the overfitting and underfitting for the model, ICOMP is proposed as a powerful model selection criterion for MARS modeling. Here, the model complexity is treated with respect to the interdependency of parameter estimates, as well as the number of free parameters in the model. We develop and study the performance of ICOMP along with several most popular model selection criteria such as Akaike's information criterion, Schwarz's Bayesian information criterion and generalized cross-validation in MARS modeling to select the best subset models. We provide two Monte Carlo simulation examples and a real benchmark example to demonstrate the utility and versatility of the proposed model selection approach to determine best functional form of the predictive model. Our numerical examples show that ICOMP provides a general model selection criterion with an insight to the interdependencies and/or correlational structure between parameter estimates in the selected model. This new approach can also be applicable to many complex statistical modeling problems.
Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms

The discovery of the Janus kinase (JAK)2 V617F mutation in patients with myeloproliferative neoplasms was a major milestone in understanding the biology of those disorders. Several groups simultaneously reported on the high incidence of this mutation in patients with myeloproliferative neoplasms: almost all patients with polycythemia vera harbor the mutation and about 50% of patients with essential thrombocythemia and primary myelofibrosis have the mutation, making the development of JAK2 tyrosine kinase inhibitors an attractive therapeutic goal. In addition, inhibition of JAK2 kinase may have a therapeutic role in other hematologic malignancies, such as chronic myeloid leukemia or lymphoma. A number of molecules that inhibit JAK2 kinase have been described in the literature, and several are being evaluated in a clinical setting. Here, we summarize current clinical experience with JAK2 inhibitors.
Osh4p is needed to reduce the level of phosphatidylinositol-4-phosphate on secretory vesicles as they mature

Phosphatidylinositol-4-phosphate (PI4P) is produced on both the Golgi and the plasma membrane. Despite extensive vesicular traffic between these compartments, genetic analysis suggests that the two pools of PI4P do not efficiently mix with one another. Several lines of evidence indicate that the PI4P produced on the Golgi is normally incorporated into secretory vesicles, but the fate of that pool has been unclear. We show here that in yeast the oxysterol-binding proteins Osh1–Osh7 are collectively needed to maintain the normal distribution of PI4P and that Osh4p is critical in this function. Osh4p associates with secretory vesicles at least in part through its interaction with PI4P and is needed, together with lipid phosphatases, to reduce the level of PI4P as vesicles approach sites of exocytosis. This reduction in PI4P is necessary for a switch in the regulation of the Sec4p exchange protein, Sec2p, from an interaction with the upstream Rab, Ypt31/32, to an interaction with a downstream Sec4p effector, Sec15p. Spatial regulation of PI4P levels thereby plays an important role in vesicle maturation.
Deletion of eIF2beta suppresses testicular cancer incidence and causes recessive lethality in agouti-yellow mice

The agouti-yellow (A(y)) deletion is the only genetic modifier known to suppress testicular germ cell tumor (TGCT) susceptibility in mice or humans. The A(y) mutation deletes Raly and Eif2s2, and induces the ectopic expression of agouti, all of which are potential TGCT-modifying mutations. Here we report that the reduced TGCT incidence of heterozygous A(y) males and the recessive embryonic lethality of A(y) are caused by the deletion of Eif2s2, the beta subunit of translation initiation factor eIF2. We found that the incidence of affected males was reduced 2-fold in mice that were partially deficient for Eif2s2 and that embryonic lethality occurred near the time of implantation in mice that were fully deficient for Eif2s2. In contrast, neither reduced expression of Raly in gene-trap mice nor ectopic expression of agouti in transgenic or viable-yellow (A(vy)) mutants affected TGCT incidence or embryonic viability. In addition, we provide evidence that partial deficiency of Eif2s2 attenuated germ cell proliferation and differentiation, both of which are important to TGCT formation. These results show that germ cell development and TGCT pathogenesis are sensitive to the availability of the eIF2 translation initiation complex and to changes in the rate of translation.
Enhanced multiband excitation coding of speech at 2.4 Kb/s with discrete all-pole spectral modeling

This paper presents a high quality, low bit rate speech coder which applies an effective spectral modeling technique called discrete all-pole (DAP) modeling to efficiently represent speech spectra. The technique provides a fixed-dimension representation of the (pitch-dependent) variable dimension spectral shape vectors which arise in harmonic coders. Consequently, the spectral shapes are quantized more efficiently than with the usual linear prediction modeling, leading to better speech quality. We present a 2.4 kb/s speech coder, based on the multiband excitation (MBE) model and DAP modeling of the speech spectra, which delivers speech quality comparable to two standard higher rate coders: the 4.8 kb/s U.S. Federal Standard 1016 CELP coder and the 4.15 kb/s IMBE coder, adopted as the INMARSAT-M standard for satellite voice communications.
A functional role of prostate-specific membrane antigen in prostate cancer metastasis

Proc Amer Assoc Cancer Res, Volume 47, 2006 4373 Despite the consistent finding of upregulated prostate specific membrane antigen (PSMA) with increased prostate cancer (PCa) aggressiveness, the functional role of PSMA in PCa is unknown. Recently, it was reported that suppression of PSMA expression increases invasiveness, and expression of inactivating PSMA mutants reduces invasiveness. In this study, using in vitro cell model systems and live-cell imaging methods, we characterized the role of PSMA in cell motility and adhesion. We demonstrated, using wound-healing assay, that PSMA expression reduces cell motility when compared with control PSMA-negative PCa cells. Six hours after wounding, significant numbers of PSMA-negative cells migrating into the wounded area could be observed. In contrast, limited migration was observed in cells expressing PSMA. We also found enhanced PCa cell motility in cells when the PSMA enzymatic activity was inhibited by a specific anti-PSMA antibody. When live cell motility was recorded, the number of PSMA-positive LNCaP cells migrating into the wounded area was almost 2-fold higher in the presence of the inhibitory antibody than control LNCaP cells in the absence of the antibody. No difference in the number of the PSMA-negative PC3 cell migration was observed with or without the application of the inhibitory antibody. More interestingly, we found that expression of PSMA results in morphologically better-spreading PCa cells with redistributed F-actin filaments that regulate cell adhesion and motility. Since the progression of PCa is a multi-stage process that requires repeated adhesion to and detachment from the extracellular matrix microenvironment, our results suggest that PSMA may play a role in PCa adhesion and migration during PCa metastasis.
Expert systems for software engineering

Issues that need to be addressed concerning the application of expert-system technology to software engineering are discussed. It is concluded that one should approach expert system use in software engineering with great caution, realizing that software engineering problems are ill-structured. A strong relationship abides between the specificity of software development methodology and the applicability of expert technology. If the methodology is to be very specific, no probable need for an expert system exists due to the availability of stronger methods. If the methodology is too weak, on the other hand, the problem is likely to be too ill-defined for expert system solutions. >
"Omic" approaches for unraveling signaling networks.

Signaling pathways are crucial for cell differentiation and response to cellular environments. Recently, a large number of approaches for the global analysis of genes and proteins have been described. These have provided important new insights into the components of different pathways and the molecular and cellular responses of these pathways. This review covers genomic and proteomic (collectively referred to as ‘omic’) approaches for the global analysis of cell signaling, including gene expression profiling and analysis, protein–protein interaction methods, protein microarrays, mass spectroscopy and gene-disruption and engineering approaches.
The effect of ambient humidity and metabolic rate on the gas-exchange pattern of the semi-aquatic insect Aquarius remigis

We have examined the effects of temperature on metabolic rate and respiratory pattern in the water strider Aquarius remigis. As temperature was increased from 10 to 30°C, the metabolic rate of the insects increased and the respiratory pattern transitioned from discontinuous, to cyclic, to continuous. The discontinuous gas-exchange cycle (DGC) was observed even in insects standing on water when the respirometry chamber was being perfused with humid (>95% relative humidity) air. Comparisons of insects at 20°C in humid and dry air showed no statistically significant differences in metabolic rate or respiratory pattern (P>0.05). The proportion of time that the spiracles were closed was greater at 10°C than at 20°C (P<0.01), and greater at 20°C than at 30°C (P<0.05). These results are compatible with the hypothesis that the respiratory patterns of insects are determined by the relationship between oxygen supply and oxygen demand. There was no evidence in this insect that humidity had any effect on the respiratory pattern. The results are discussed in the context of the ongoing discussion in the literature of the origin, maintenance and adaptive significance of the DGC in insects.
Toward a Psychological Theory of Accountability

Accountability is becoming an increasingly significant concept in the management literature. The traditional association of accountability with budgetary control and hence an economic perspective has been expanded to include responsibility for the worth of the individual as advocated in human resource accounting. The demand for accountable performance has also increased. Although the term accountability is becoming more visible, there has been relatively little work done in understanding the psychological processes involved. Two questions arise. First, what establishes accountability? Second, what motivates accountable behavior? This paper attempts to provide a basic groundwork for answering these questions.
A central role for RNA in the induction and biological activities of type 1 interferons

In mammals the type 1 interferon (IFN) system functions as the primary innate antiviral defense and more broadly as a stress response and regulator of diverse homeostatic mechanisms. RNA plays a central role in the induction of IFN and in its biologic activities. Cellular toll-like receptors (TLR), RIG-I-like receptors (RLR), and nucleotide organization domain-like receptors (NLR) sense pathogen- and danger-associated RNAs as nonself based on structural features and subcellular location that distinguish them from ubiquitous host RNAs. Detection of nonself RNAs activates signaling pathways to induce IFN transcription and secretion. In turn, IFN binds cell surface receptors to initiate signaling that results in the induction of IFN-stimulated genes (ISGs) that mediate its biologic activities. RNA also plays a critical role in this effector phase of the IFN system, serving as an activator of enzyme activity for protein kinase RNA-dependent (PKR) and oligoadenylate synthetase (OAS), and as a substrate for 2('), 5(') -linked oligoadenylate dependant-endoribonuclease (RNase-L). In contrast to the transcriptional response induced by RNA receptors, these key ISGs mediate their activities primarily through post transcriptional mechanisms to regulate the translation and stability of host and microbial RNAs. Together RNA-sensing and RNA-effector molecules comprise a network of coordinately regulated proteins with integrated feedback and feed-forward loops that tightly regulate the cellular response to RNA. This stringent regulation is essential to prevent deleterious effects of uncontrolled IFN expression and effector activation. In light of this extensive crosstalk, targeting key mediators of the cellular response to RNA represents a viable strategy for therapeutic modulation of immune function and treatment of diseases in which this response is dysregulated (e.g., cancer).
A 1.3 GHz SOI CMOS test chip for low-power high-speed pulse processing

A test chip has been fabricated in a fully depleted SOI CMOS process with 0.25-/spl mu/m drawn gate length, It successfully demonstrates the types of circuits required to perform digital filtering, detection, and data thinning functions at high clock speeds. The test chip contains over 5000 transistors and was clocked at speeds up to 1.3 GHz. A target application for these circuits is a very wideband compressive receiver for real-time spectral analysis, which requires digital signal processing to be performed on a 20-Gb/s data stream formed by digitizing a stream of fast analog pulses. Adjustable high-speed on-chip clocks, input and output registers, and large decoupling capacitors allowed testing of the chip to be performed using an inexpensive, low-speed probe card and a standard wafer prober.
Medium term functional results of single-lung transplantation for endstage obstructive lung disease

Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to th...
Abstract T P365: Does Stroke Contribute to Racial Differences in Cognition?

Objective: Although dementia prevalence is higher in blacks than whites, it is unknown whether blacks’ elevated risk of dementia is due to racial differences in acute stroke, the impact of stroke on cognitive health, or other factors. We determined whether racial differences in cognitive function are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition. Methods: The study population was a prospective cohort of 5,126 white or black adults aged ≥65 years responding to the Health and Retirement Study in 1998 and followed through 2006. Cognitive function was assessed at 2-year intervals with a modified version of the Telephone Interview for Cognitive Status (TICS-m). Acute strokes were identified using linked Medicare claims. Adults with cognitive impairment (TICS-m<7) in 1998 were excluded. We examined changes in cognitive function over time by race, before and after adjusting for time-dependent acute stroke using linear mixed effects models that also included baseline values of age, sex, education, self-reported history of stroke, depressive symptoms, TICS-m, and random effects for intercept and slope. We then added a race-by-stroke interaction in the model. Results: There were 5,126 adults with ≥1 follow-up TICS-m measure, of whom 490 had acute stroke (466 whites and 24 blacks; P=0.39). Blacks had lower adjusted TICS-m scores than whites (mean difference, -1.41 points; 95% CI, -1.67 to -1.16 points; P<0.001), and this racial difference persisted after adjusting for acute stroke (Table). Acute stroke was associated with average acute decreases in TICS-m scores of about 1.17 points. The association of acute stroke with change in cognition did not differ by race (P for race-by-stroke interaction=0.62). Conclusions: In this nationally representative cohort of older adults, acute stroke did not explain black-white differences in cognition or impact cognition differently by race. ![][1] [1]: /embed/graphic-1.gif
Surgical management of isolated popliteus tendon injuries in paediatric patients

Isolated popliteus avulsion injuries are a rare occurrence, especially in the skeletally immature population. Two cases of isolated popliteus tendon avulsion injuries in paediatric patients were identified and successfully managed with suture anchor reattachment of the avulsed fragment in the anatomic position. The objective of this case report is to raise awareness of orthopaedic surgeons to the rarely encountered isolated popliteus tendon injury that can occur in paediatric patients. Level of evidence Expert opinion, Level V.
Asian Lobbies in Washington, D.C.: The Rise and Fall and Rise of the China Lobby

The famed China Lobby died in the early 1970s, but was revived in a Taiwan Lobby that has proven to be quite successful in certain types of issues crucial to the island nation. But it is the power and success of the New China Lobby (PRC) that has brought attention once again to powerful foreign lobbies in the United States other than the Israel Lobby that has been in the news so much recently. This paper will examine the New China Lobby in the context of the theories developed by political science regarding the power of ethnic lobbies in Washington and what they need to be successful. The paper argues that the best comparison for the New China Lobby is not with Israel, but with its emerging rival, India.
Modeling stochasticity in biochemical reaction networks

Small biomolecular systems are inherently stochastic. Indeed, fluctuations of molecular species are substantial in living organisms and may result in significant variation in cellular phenotypes. The chemical master equation (CME) is the most detailed mathematical model that can describe stochastic behaviors. However, because of its complexity the CME has been solved for only few, very small reaction networks. As a result, the contribution of CME-based approaches to biology has been very limited. In this review we discuss the approach of solving CME by a set of differential equations of probability moments, called moment equations. We present different approaches to produce and to solve these equations, emphasizing the use of factorial moments and the zero information entropy closure scheme. We also provide information on the stability analysis of stochastic systems. Finally, we speculate on the utility of CME-based modeling formalisms, especially in the context of synthetic biology efforts.
Culture-independent diagnosis of Chlamydia trachomatis using monoclonal antibodies

Abstract To simplify the diagnosis of chlamydial genital infection, we used a fluorescein-conjugated monoclonal antibody in immunofluorescence tests on smears prepared from urethral or cervical secretions obtained directly from patients. This direct test, requiring less than 30 minutes to perform, was based on the detection of extracellular chlamydial elementary bodies. A comparison of the direct test with cultures stained with iodine on specimens from 926 patients demonstrated a sensitivity of 93 per cent and a specificity of 96 per cent. The direct test provides a rapid, simple, and sensitive method for the diagnosis of chlamydial infection, which can be performed in laboratories that do not have tissue-culture capability. (N Engl J Med 1984; 310:1146–50.)
Development of Logistics for Building Radiation Storm Shelters and Their Operational Evaluation

Over the past three years NASA has been studying the operational effectiveness and astronaut protection efficacy of numerous radiation protection shelters for use in space exploration activities outside of earth's magnetosphere. The work presented was part of NASA's Advanced Exploration Systems (AES) RadWorks Storm Shelter project. This paper is a summary of the concept development activities of this third year. Fabricated items were integrated into mock up deep space habitat vehicle sections for operational evaluations. Two full scale human-in-loop simulations were designed, fabricated, and implemented through an Institutional Review Board approved solicited participant assessment process. Fabricated items are described, along with usage scenarios of two protection approaches. Existing ISS type logistics along with proposed variations of those logistics were used. Preliminary Discrete Event Simulation (DES) work is noted to be useful in quantifying and documenting operational performance measures for the two primary shelter methods, including some characterization of radiation dose accumulation over a mission timeline. The project also performed correlation analyses between effective radiation dose and the Risk of Exposure Induced Death (REID) to show that concept level work may be able to include such a performance metric in early stages of mission scenario habitat design trade space investigation.
Social support for African American low-income parents: The influence of preadolescents' risk behavior and support role on parental monitoring and child outcomes

Summary Urban parents, particularly single mothers living within inner-city communities, often struggle to obtain sufficient social support for themselves and for parenting. Support for these parents is particularly important given the prevalence of risk-taking behaviors among youth in these communities, which necessitates vigilant monitoring of these youth. The current study explored from whom low-income mothers obtain social support, the influence of child externalizing on source of social support, and how social support and child behavior interrelate with parental monitoring and supervision. Contrary to expectations, parental monitoring at time 1 did not predict child externalizing at time 2, but, as expected, a significant negative association was noted at time 1 between these constructs. Higher time 1 child externalizing did predict lower time 2 maternal monitoring, suggesting frustrated efforts by mothers to monitor high externalizing children. Mothers reporting strong support networks, however, sho...
Tire shops fire safety problems and countermeasures

According to the tire combustion characteristics.this paper analyzes the existing tire shops fire safety problems.propose countermeasures of a reasonable location.set the necessary fire-fighting facilities.horizontal stacking tires and enhance fire control.
Investigation and control of cockroaches in hospital

Objective To discuss the degree of cockroaches invasion in hospital,and formulate the control measures.Methods Investigating cockroaches invasion situation by eye and using insecticide trap method,using glue trap to determine the density of cockroaches.Results The invasion rate of cockroaches adult and nymph was 10.27% which was three times more than the national standard.73% departments exceeded the provided standard,neurosurgery and general surgery department reached nearly 7 times.The positive density index was 12.02 pieces per room.The egg positive rate was 2.74% which exceeded the national standards.Two kinds of cockroaches were investigated,they were Blattella germanica(55.3%) and Periplaneta japonica(44.7%).Conclusion The invasion situation of cockroaches is serious in hospitals.It is necessary to control cockroaches and eliminate breeding ground combined with environmental features.
Concept on Configurable Three-dimensional Network Security Operation Management System

A mass of research and statistics show that most of the network security issues come from its inside,but only bound to rely on system management or internal staff behavior restriction is not enough,only the organic combination of various types of network security technologies and hardware devices,forming an effective three-dimensional structure of the security operation and maintenance management system,making the network security technically capable of monitoring,prevention and tracking,can really shock the internal insecurity staff and behavior,to ensure network security.This article mainly concerns on how to use a variety of sophisticated network security software,hardware technologies and equipment to form three-dimensional structure of the operation and maintenance of network security management system.
Lipochondria and the Golgi substance in epithelial cells of the epididymis.

BOTH J. R. Baker1 and O. L. Thomas2 have expressed the view that ‘lipochondria’ (discrete sudanophilic droplets supravitally stainable with methylene blue and neutral red) are transformed into the classical Golgi network during the processes of fixation and impregnation with silver and osmic acid techniques. Thomas3 also considers that mitochondria are involved in the development of the classical Golgi network during fixation.
Modeling membrane transport.

Many substrates cross cell membranes by processes other than passive diffusion. When the transport is carrier-mediated, e.g., facilitated diffusion, active transport, and exchange diffusion, the carrier modifies the conductance of the membrane and may either increase or decrease the flux of the substrate across the membrane. A common characteristic of all carrier-mediated transport is its saturability, as only a finite amount of carrier is available to bind with the substrate; even the simplest one-site carrier model exhibits saturation. Inclusion of carrier-mediated transport adds additional model parameters that describe the transporter. In addition, the model must account for both labeled (tracer) and unlabeled (mother) substrate, but this introduces no new parameters. There are many possible models for a membrane carrier. The applicability of these models must be examined for the specific substrate of interest. Many experiments aimed at measuring carrier parameters are carried out on isolated cells or cell fragments. Experiments in intact organs (either in vivo and in vitro) are also possible. Of particular note is the "bolus sweep" method described by Rickaby et al. (1981) and Malcorps et al. (1984). The increasing sophistication of experimental procedures, data collection techniques, and computers available to investigators continues to extend the depth to which we can probe biological systems. With this increased sophistication comes increased costs in time and equipment. It behooves us then to extract the maximum amount of information from each experimental procedure. Mathematical models assist in doing so, and sophistication in model analysis should parallel that in other phases of the experiment. Increased realism brings several advantages. Simplification of a model to increase its ease of usage and speed in routine data analysis is a desirable goal, and comparing a simplified model against a more realistic model under the conditions specific to a given experiment is one way to test the simplifying assumptions. Additionally, increased model realism can bring new insight into unknown aspects of the system. All models, no matter how realistic, are always "wrong" in that they are less complex than the real system. Failure of the model to explain observed results forces us to further refine the model and teaches us something more about the system.
An effect of magnesium adenosine 5′-triphosphate on the structure of azoferredoxin from Clostridiumpasteurianum

Azoferredoxin from Clostridiumpasteurianum has been treated anaerobically with 65 fold excess of α,α′-dipyridyl in the presence and absence of various nucleotides. Under reduced conditions 1% of the iron of AzoFd is chelated by α,α′-dipyridyl between 1 minute and 1 hour. However, when ATP is added in the presence of Mg2+, 80% of the iron in azoferredoxin is chelated within an hour. This effect is reproducible and nonenzymatic. The lack of this effect with other purine and pyrimidine nucleotides demonstrates that it is specific for magnesium ATP. Treatment of azoferredoxin with 4 M urea or oxygen in the presence of α,α′-dipyridyl induces a similar effect. An ATP-induced change in the availability of the iron in azoferredoxin to the chelator, α,α′-dipyridyl, is evidence that a conformational change has occurred.
The Surgical Management of Obesity

The obesity epidemic among adults in the USA is well established. National data reveals significant growth of clinically severe obesity over the past several decades. Given the complexity of obesity as a disease, a multidisciplinary team approach to evaluation and treatment to include dietary, behavioral, medical, and surgical components is considered mandatory, as is the long-term postoperative follow-up and evaluation of the patient to ensure safety and provide ongoing support. There are several standard and well-studied metabolic surgery procedures currently performed in the USA. These include the adjustable gastric band, Roux-en-Y gastric bypass, sleeve gastrectomy, and duodenal switch. There are also several novel procedures that are early in their development in other countries. Future research will determine which will become standard techniques in years to come.
Abstract 3747: Identification of NSCLC biomarkers underlying quantifiable drug-induced clonal fitness

Lung cancer accounts for nearly 20% of all cancer-related deaths worldwide. Subsets of non-small-cell lung cancer (NSCLC; >80% of all lung cancers) harboring activating epidermal growth factor receptor (EGFR) mutations are highly sensitive to erlotinib, a small-molecule EGFR tyrosine kinase inhibitor. However, clinical responses to erlotinib are variable and limited in duration as all tumors eventually relapse. Clonal heterogeneity is thought to be a major cause of relapse, but it has been difficult to quantify in drug-sensitive cancer cell populations. To overcome this obstacle, we quantify clonal fitness via live-cell imaging as a drug-induced proliferation (DIP) rate that incorporates cell division, death, and quiescence into a single metric. This fitness rate varies across cell types from positive (division prevails) to negative (death prevails) and, unlike traditional IC50 measurements, can effectively discriminate intricate degrees of drug sensitivity. Moreover, in monoclonal sublines isolated naive-to-drug from NSCLC parental cell lines, erlotinib-treated DIP rates calculated in vitro predict the long-term growth rates (250+ days) of in vivo tumor xenografts. Using global proteomics across a panel of monoclonal sublines, we have characterized networks of biomarkers that act as molecular determinants of phenotypic drug fitness. We have identified unsuspected molecular correlates in the EGFR and AKT pathways and are currently investigating whether they can act as lead targets for small molecule inhibition in combination therapies. Our data indicate that a multi-scale systems approach integrating molecular subtyping with quantifiable clonal fitness can yield insights into clonal heterogeneity and lead to novel strategies to overcome tumor relapse. Note: This abstract was not presented at the meeting. Citation Format: Katherine L. Jameson, Peter L. Frick, Darren R. Tyson, Thomas E. Yankeelov, Vito Quaranta. Identification of NSCLC biomarkers underlying quantifiable drug-induced clonal fitness. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2015-3747
Abstract 3094: Sprouty and cell proliferation in colorectal cancer

BACKGROUND & AIMS: Sprouty (SPRY) proteins are evolutionarily conserved modulators of mitogen-activated protein kinase pathway. SPRY2 appears to function as a tumor suppressor in other cancers, whereas we reported that SPRY2 functions as an oncogene in colorectal cancer (CRC). To further understand the oncogenic potential of SPRY1 and SPRY2 in CRC, we investigated the mechanisms by which these proteins regulate cell proliferation in CRC. MATERIALS & METHODS: Human CRC cDNA arrays were employed to assess mRNA levels of SPRY1, SPRY2 and p21. SPRY1 and SPRY2 were knocked-down in CaCo2 colon cancer cells by siRNA. Effects of SPRY were assessed by immunoblotting, real time PCR, luciferase reporter assay, and confocal microscopy. Mouse embryonic fibroblasts (MEFs) derived from SPRY mutant mice were utilized to dissect SPRY functions in mesenchymal cells. RESULTS: In this study, surprisingly, we present evidence to suggest that concomitant activation of ERK, p-38 and AKT signaling cascades is insufficient to drive cancer cell proliferation in SPRY modulated cells. Suppression of SPRY in colon cancer cells upregulates p21, a cell cycle inhibitor. SPRY2 dependent p21 promoter activation may account for upregulation of p21 expression and inhibition of cancer cell proliferation. Underscoring the biological relevance of these findings, recombination of floxed SPRY1 and SPRY2 alleles in mouse embryonic fibroblasts (MEFs) resulted in increased expression of p21. Finally, in a human CRC cDNA array we established an inverse correlation of SPRY1 and SPRY2 with p21 mRNA expression. CONCLUSIONS: Together, this study indicates that SPRY is a target of therapeutic intervention in CRC. Citation Format: Qiong Zhang, Katherine Shim, Kevin Wright, Alexander Jurkevich, Sharad Khare. Sprouty and cell proliferation in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3094. doi:10.1158/1538-7445.AM2015-3094
Factors and Costs Associated With Delay in Treatment Initiation and Prolonged Length of Stay With Inpatient EPOCH Chemotherapy in Patients With Hematologic Malignancies

ABSTRACTReducing delays related to inpatient chemotherapy may reduce healthcare costs. Using a national database, we identified patients with lymphoma/leukemia with ≥1 etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy claim and evaluated chemotherapy initiation delay (ID), >1 day from admission. Standard tests/procedures prior to initiation were evaluated. Among 4453 inpatient cycles, 19.7% had ID, odds ratio 2.28 (95% confidence interval: 1.83–2.85) with cycle 1 compared to cycle 2, and mean costs were higher in patients with ID than without ID (p < .0001). Prior to cycle 1, patients were more likely to undergo routine diagnostic procedures compared to subsequent cycles. Efforts to perform routine procedures prior to admission may reduce hospital length of stay and costs.
Properties of Receding Horizon Controllers for Some Hybrid Systems with Event Uncertainties

Abstract We consider optimal control problems for a class of hybrid systems with switches dependent on an external event process. In the case where all event times in this process are fully known, the solution to such problems was obtained in prior work. When event times are uncertain or unknown, we have proposed in prior work a Receding Horizon (RH) control scheme in which only some future event information is available within a time window of length T and have obtained several properties of this scheme. In this paper, we derive additional properties, including the fact that the error due to lack of future event information is monotonically decreasing under certain conditions and may be zero for segments of the sample path, depending on the window length T .
High Compliance with Scheduled Nimodipine Is Associated with Better Outcome in Aneurysmal Subarachnoid Hemorrhage Patients Cotreated with Heparin Infusion.

Introduction. We sought to determine whether compliance with scheduled nimodipine in subarachnoid hemorrhage patients impacted patient outcomes, with the intent of guiding future nimodipine management in patients who experience nimodipine-induced hypotension. Methods. We performed a retrospective analysis of 118 consecutive aneurysmal subarachnoid hemorrhage patients treated with the Maryland Low-Dose IV Heparin Infusion Protocol. Patients were categorized into three independent nimodipine compliance groups: ≥ 1 dose held, ≥ 1 dose split, and no missed or split-doses. A split-dose was defined as 30 mg of nimodipine administered every 2 hours. Our primary outcome was discharge to home. Bivariate and multivariable logistic regression analyses were used to assess predictors of discharge disposition as a function of nimodipine compliance. Results. Of the 118 patients, 20 (17%) received all nimodipine doses, 6 (5%) received split-doses but never had a full dose held, and 92 (78%) had ≥ 1 dose held. Forty five percent of patients were discharged to home, including 75% who received all doses, 67% who received 1 split-doses, and 37% with 1 missed doses (p=0.003). Multivariable analysis showed that, along with age and WFNS grade, nimodipine compliance was an independent predictor of clinical outcome; compared to missing one or more nimodipine doses, full dosing compliance was associated with increased odds of discharge to home (OR 5.20; 95% CI 1.46-18.56)). Conclusions. In aneurysmal subarachnoid hemorrhage patients with modified Fisher scores 2 through 4 who are co-treated with a low-dose heparin infusion, full compliance with nimodipine dosing was associated with increased odds of discharge to home.
Two Concerns Regarding Subjectively Perceived Self-Estrangement

Investigating the subjective character of experiences perceived by patients who undergo deep brain stimulation (DBS) is an important contribution to the neuroethical literature surrounding this int...
President Trump's Proposed Budget Changes Would Increase Greenhouse Gas Emissions by More than 5 Million Metric Tons CO 2 e

The 2016 election of Donald J. Trump as the 45th President of the United States promised to usher in sweeping changes to the federal government’s policy priorities, largely at the expense of environmental and social safety. Climate change mitigation efforts will likely slow as a result of renewed federal support and an enabling regulatory environment for the fossil fuel industry, as well as diminished international cooperation. Yet the scientific community has yet to explicitly assess the direct and indirect greenhouse gas emissions impacts of the Trump Administration’s proposals to increase defense and homeland security spending by $90 billion and cut other non-defense spending by $63 billion over fiscal years 2017 and 2018. This paper uses environmentally extended input-output analysis to estimate how these budget changes would result in changes in emissions if implemented exactly as described in official documents from the executive branch of the U.S. government. Our results suggest an increase of more than 5 million metric tons of carbon dioxide-equivalent emissions over two years relative to a counterfactual scenario without the new budget proposals. We argue that our analysis grossly underestimates the complete, long-term climate impacts of the analyzed expenditure shifts because of several methodological limitations. Regardless, the federal government budget changes proposed by the Trump Administration represent a momentous stride in a dangerous direction with respect to the future functioning of the global climate system.
Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Summary Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked ( eas ), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca 2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.
Hypnosis: A 50-Year Perspective

In preparing my remarks, I took into account the fact that I would be addressing colleagues who might be exhausted after a day of listening to scientific papers. Some of you might have neutralized the exhaustion by imbibing a highball or two before sitting down to the presidential banquet, a hearty meal augmented by copious quantities of wine. These are conditions that encourage members of any audience to fall asleep. Originally I had planned a review of significant developments in hypnosis in the last half-century, but this might have added another sleep-inducing element. So, instead of presenting a formal address, I will tell a story. It is mostly autobiographical. As I construct the narrative from a number of vignettes, you will discern a plot with a beginning, a middle, and an ending. As in most stories, there are other actors, some central, some peripheral. Without these co-actors, there would be no story. In this sense, I am a co-author, involved in an enforced collaboration with other actors. The plotline of my story depicts the development of the theory of hypnosis with which I have been associated for many years. I hasten to add that the kinds of experiences reported in these vignettes are not unique to me. Any of you with an interest in theory-building can tell a story that would follow the same narrative pattern, although the content would be different.
Imaging the ordering of a weakly adsorbed two-dimensional condensate: ambient-pressure microscopy and spectroscopy of CO2 molecules on rutile TiO2(110).

Disorder–Order transitions in a weakly adsorbed two-dimensional film have been identified for the first time using ambient-pressure scanning tunneling microscopy (AP-STM) and X-ray photoelectron spectroscopy (AP-XPS). As of late, great effort has been devoted to the capture, activation and conversion of carbon dioxide (CO2), a ubiquitous greenhouse gas and by-product of many chemical processes. The high stability and non-polar nature of CO2 leads to weak bonding with well-defined surfaces of metals and oxides. CO2 adsorbs molecularly on the rutile TiO2(110) surface with a low adsorption energy of ∼10 kcal mol−1. In spite of this weak binding, images of AP-STM show that a substantial amount of CO2 can reside on a TiO2(110) surface at room temperature forming two-dimensionally ordered films. We have employed microscopic imaging under in situ conditions, soft X-ray spectroscopy and theory to decipher the unique ordering behavior seen for CO2 on TiO2(110).