cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5459: Regulation of IGF2 by TGF-β signaling in liver cancers and stem cell homeostasis

Development of hepatocellular carcinoma (HCC), which remains lethal, is associated with alterations in multiple factors including the transforming growth factor beta (TGF-β) signaling pathway. Previously we have uncovered a unique role for TGF-β signaling molecules, Smad3 and its adaptor β2SP, in suppressing stem cell transformation into cancer. Yet, while TGF-β plays a pleiotropic role including regulating stem cell differentiation, proliferation, and inflammation, mechanistic insight into the dichotomy of TGF-β, and its role in stem cell transformation remains poorly understood for these cancers. Here, we took an integrated approach to identify and validate effects of changes in this pathway in HCC and identify potential therapeutic targets such as IGF2. We extended our mechanistic studies associated with the regulation of insulin-like growth factor 2 (IGF2) in the context of the TGF-β-pathway, by utilizing both human liver cancer cell lines and TGF-β signaling-deficient mice (β2SP+/- and β2SP+/-/Smad3+/-) that develop liver cancers. We found the following: 1) IGF2 promotes stemness, overexpression leading to increased expression of stem cell genes that include SOX2 and ALDH1A1, and sphere formation in liver cancer cells; 2) A marked increase in IGF2 mRNA and protein in HepG2 cells and Huh7 cells with β2SP stable knockdown; 3) TGF-β signaling through β2SP/Smad3 significantly inhibits IGF2 transcription; ChIP assays validated binding of Smad3 at the human IGF2 promoter region between -859bp to -688bp upstream of the IGF2 transcriptional start site; 4) TCGA based integrated analyses identify specific HCC patient groups with altered TGF-β members and high expression of IGF2 that could be potentially targetable for IGF2; 5) TCGA analyses of 33 cancers also revealed that potentially “switching off” TGF-β-pathway (through decreased expression levels) leads to increased stemness validating findings of our TGF-β deficient mouse models that phenocopy a human cancer stem cell syndrome. In summary, TGF-β negatively regulates IGF2 transcription: loss of TGF-β signaling through β2SP/Smad3 leads to IGF2 activation, contributing to tumor progression. TGF-β-β2SP/Smad3 are important for IGF2 repression and maintaining stem cell homeostasis, which may result from TGF-β/β2SP/Smad3 and/or CTCF-dependent regulation of IGF2. Our studies provide a framework for new animal models of liver and gastrointestinal cancers and future new therapeutics. Citation Format: Shuyun Rao, Sobia Zaidi, Kazufumi Ohshiro, Jian Chen, Shoujun Gu, Wilma Jogunoori, Jon White, Bibhuti Mishra, Shulin Li, Rehan Akbani, Lopa Mishra. Regulation of IGF2 by TGF-β signaling in liver cancers and stem cell homeostasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5459.
Property/Morphology Relationships in SEBS-Compatibilized HDPE/Poly(phenylene ether) Blends

High density polyethylene suffers from poor mechanical properties at elevated temperatures (e.g., above 60 °C) due to its relatively low melting point and, particularly, low heat deflection tempera...
Role of synthetic antifreeze agents in catalyzing ice nucleation.

Abstract Nature endows antifreeze (glyco)proteins (AF(G)Ps) with the excellent capability of inhibiting ice crystal growth. Recent years have also witnessed the emergence of many potent AF(G)P mimics such as poly (vinyl alcohol) (PVA). As researchers are revealing the molecular mechanisms of inhibiting ice crystal growth by AF(G)Ps and their synthetic substitutes, there remains no agreement about their effect on ice nucleation. In this study, we report the observation of ice nucleation catalyzed by PVA of different polymerization degrees using a freeze-on-a-chip platform which allows the monitoring of freezing and melting events over hundreds of monodisperse, picoliter-sized aqueous droplets. Aqueous droplets made of 1 mg/ml PVA solution exhibit a median freezing temperature of around −36 °C, two degrees higher than the observed homogeneous nucleation temperature of water. The findings in our study bring useful insights into the different roles of synthetic antifreeze agents in controlling ice formation.
Explainable Failure Predictions with RNN Classifiers based on Time Series Data.

Given key performance indicators collected with fine granularity as time series, our aim is to predict and explain failures in storage environments. Although explainable predictive modeling based on spiky telemetry data is key in many domains, current approaches cannot tackle this problem. Deep learning methods suitable for sequence modeling and learning temporal dependencies, such as RNNs, are effective, but opaque from an explainability perspective. Our approach first extracts the anomalous spikes from time series as events and then builds an RNN classifier with attention mechanisms to embed the irregularity and frequency of these events. A preliminary evaluation on real world storage environments shows that our approach can predict failures within a 3-day prediction window with comparable accuracy as traditional RNN-based classifiers. At the same time it can explain the predictions by returning the key anomalous events which led to those failure predictions.
Athenian democracy and its critics

Taking the Greeks to be progenitors of a legacy of ethno-national political inequality, The Spectre of Race: How Discrimination Haunts Western Democracy brings to light the endurance of the Athenia...
The plight of some of the poorest of the poor: vulnerabilities of fishing families on Kutubdia Island, Bangladesh

Globally, fisheries are important economic resources and support many coastal communities, but the people that rely on fishing experience a range of environmental hazards. This research sur...
Magnetic Resonance Imaging of the Alimentary Tube

Magnetic resonance imaging (MRI) of the alimentary tube became feasible as techniques to (a) arrest bowel motion, (b) remove competing high signal intensity of adjacent fat, (c) increase the dynamic range of intra-abdominal signal intensities, and (d) decrease susceptibility artifacts became widespread. Specifically, fat suppression, breath-hold gradient echo, single-shot echo train T2-weighted sequences, and intravenous gadolinium chelates have all contributed to this endeavor (SEMELKA et al. 1991). Controversy still exists, however, over which oral contrast agent, if any, is necessary for performing diagnostic studies.
NUP98-KDM5A Fusion Induces Hematopoietic Cell Proliferation and Alters Myelo-Erythropoietic Differentiation

Chromosomal translocations are common in acute myeloid leukemia (AML), causing gene fusions that encode oncogenic proteins. The NUP98 gene participates in chromosomal rearrangements with over 30 fusion partners and comprises 6-10% of de novo cases of pediatric AML. These fusions are associated with poor prognosis in children and adults. Among them, NUP98-KDM5A is further enriched in specific subpopulations, found in 15% of non-Down syndrome acute megakaryoblastic leukemia cases and 20% of pediatric acute erythroleukemia. Despite these associations, the direct impact of NUP98-KDM5A on the growth and differentiation of human hematopoietic cells has not been systemically studied. In this study, we transduced cord blood CD34+ hematopoietic stem and progenitor cells (HSPCs) with NUP98-KDM5A or control lentiviral vectors and examined cell proliferation and differentiation. Exposure to cytokines (SCF, TPO, IL-6, FLT3L, SR-1) selected for CD34+ cell growth, and expression of NUP98-KDM5A increased proliferation rate in liquid culture by 19.4-fold (p To further elucidate NUP98-KDM5A effects on differentiation, cytokine supplements known to drive myeloid differentiation (SCF, TPO, G-CSF, and GM-CSF) were added to culture media, which demonstrated the same disruption in myelo-erythropoiesis based on a 4.0-fold decrease (p To evaluate the leukemic potential of NUP98-KDM5A, cells were injected into NRG-SGM3 mice with NUP98-KDM5A inducing at 12 weeks a rapidly lethal myeloid disease in vivo (97.8% human CD45+ cells vs. 2.3% in control, p In conclusion, the expression of NUP98-KDM5A in HSPCs drives proliferation and alters differentiation to maintain stem cell markers while driving an erythroid phenotype in vitro. Furthermore, this fusion is sufficient to engraft in the bone marrow and spleen of NRG-SGM3 mice in vivo and cause marked splenomegaly. Taken together, these data suggest this model properly recapitulates the human disease phenotype seen in patients expressing NUP98-KDM5A and future functional assays and drug screens may provide important insights into understanding the pathophysiology and pharmacologic vulnerabilities of this fusion class. Disclosures Mullighan: Loxo Oncology: Research Funding; Amgen: Honoraria, Other: speaker, sponsored travel; Illumina: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored travel; AbbVie: Research Funding; Pfizer: Honoraria, Other: speaker, sponsored travel, Research Funding.
Effect of Titanium Induced Chemical Inhomogeneity on Crystal Structure, Electronic Structure, and Optical Properties of Wide Band Gap Ga2O3

Tailoring the optical and electronic properties of wide band gap β-Ga2O3 has been of tremendous importance to utilize the full potential of the material in current and emerging technological applic...
Event generation with normalizing flows

We present a novel integrator based on normalizing flows which can be used to improve the unweighting efficiency of Monte Carlo event generators for collider physics simulations. In contrast to machine learning approaches based on surrogate models, our method generates the correct result even if the underlying neural networks are not optimally trained. We exemplify the new strategy using the example of Drell-Yan type processes at the LHC, both at leading and partially at next-to-leading order QCD.
Alveolar size effects on nanoparticle deposition in rhythmically expanding-contracting terminal alveolar models

Significant differences in alveolar size exist in humans of different ages, gender, health, and among different species. The effects of alveolar sizes, as well as the accompanying breathing frequencies, on regional and local dosimetry of inhaled nanoparticles have not been sufficiently studied. Despite a well-accepted qualitative understanding of the advection-diffusion-sedimentation mechanism in the acinar region, a quantitative picture of the interactions among these factors remains inchoate. The objective of this study is to quantify the effects of alveolar size on the regional and local deposition of inhaled nanoparticles in alveolar models of varying complexities and to understand the dynamic interactions among different deposition mechanisms. Three different models were considered that retained 1, 4, and 45 alveoli, respectively. For each model, the baseline geometry was scaled by ¼, ½, 2, 4, and 8 times by volume. Temporal evolution and spatial distribution of particle deposition were tracked using a discrete-phase Lagrangian model. Lower retentions of inhaled nanoparticles were observed in the larger alveoli under the same respiration frequency, while similar retentions were found among different geometrical scales if breathing frequencies allometrically matched the alveolar size. Dimensional analysis reveals a manifold deposition mechanism with tantamount contributions from advection, diffusion, and gravitational sedimentation, each of which can become dominant depending on the location in the alveoli. Results of this study indicate that empirical correlations obtained from one sub-population cannot be directly applied to others, nor can they be simply scaled as a function of the alveolar size or respiration frequency due to the regime-transiting deposition mechanism that is both localized and dynamic.
Localizing the seizure onset zone from single pulse electrical stimulation responses using transfer function models

Surgical resection of the seizure onset zone (SOZ) could potentially lead to seizure-freedom in medically refractory epilepsy patients. However, localizing the SOZ can be a time consuming and tedious process involving visual inspection of intracranial electroencephalographic (iEEG) recordings captured during passive patient monitoring. Single pulse electrical stimulation (SPES) is currently performed on patients undergoing invasive EEG monitoring for the main purposes of mapping functional brain networks such as language and motor networks. We hypothesize that evoked responses from SPES can also be used to localize the SOZ as they may express the natural frequencies and connectivity of the iEEG network. To test our hypothesis, we construct patient specific single-input multi-output transfer function models from the evoked responses recorded from five epilepsy patients that underwent SPES evaluation and iEEG monitoring. Our preliminary results suggest that the stimulation electrodes that produced the highest gain transfer functions, as measured by the ${\mathcal{H}_\infty }$ norm, correspond to those electrodes clinically defined in the SOZ in successfully treated patients.Clinical Relevance— This study creates an innovative tool that allows clinicians to identify the seizure onset zone in medically refractory epilepsy patients using quantitative metrics thereby increasing surgical success outcomes, mitigating patient risks, and decreasing costs.
Fast and nonuniform dynamics of perisaccadic vision in the central fovea.

Humans use rapid eye movements (saccades) to inspect stimuli with the foveola, the region of the retina where receptors are most densely packed. It is well established that visual sensitivity is generally attenuated during these movements, a phenomenon known as saccadic suppression. This effect is commonly studied with large, often peripheral, stimuli presented during instructed saccades. However, little is known about how saccades modulate the foveola and how the resulting dynamics unfold during natural visual exploration. Here we measured the foveal dynamics of saccadic suppression in a naturalistic high-acuity task, a task designed after primates’ social grooming, which—like most explorations of fine patterns—primarily elicits minute saccades (microsaccades). Leveraging on recent advances in gaze-contingent display control, we were able to systematically map the perisaccadic time course of sensitivity across the foveola. We show that contrast sensitivity is not uniform across this region and that both the extent and dynamics of saccadic suppression vary within the foveola. Suppression is stronger and faster in the most central portion, where sensitivity is generally higher and selectively rebounds at the onset of a new fixation. These results shed light on the modulations experienced by foveal vision during the saccade-fixation cycle and explain some of the benefits of microsaccades.
Floral traits differentiate pollination syndromes and species but fail to predict the identity of floral visitors to Castilleja.

PREMISE Animal pollination is critical to plant reproduction and may cause convergent evolution of pollination syndromes. Pollination syndromes in Castilleja have been distinguished based on floral traits and historical observations of floral visitors. Here we addressed these questions: (1) Can pollination syndromes be distinguished using floral morphological traits or volatile organic compound emissions? (2) Is there significant variation in floral traits within a pollination syndrome at the level of populations or species? (3) Do pollination syndromes predict the most frequent floral visitor to Castilleja? METHODS Floral traits and visitation were measured for five co-occurring Castilleja species (C. applegatei, C. linariifolia, C. miniata, C. nana, and C. peirsonii), representing three pollination syndromes (bee, fly, and hummingbird), at four sites in the Sierra Nevada Mountains. We used nonmetric multidimensional scaling (NMDS) and multiple linear regressions to address key questions in the differentiation of Castilleja and floral visitors. RESULTS Our analyses revealed that both morphological traits and floral VOCs can be used to distinguish between some pollination syndromes and Castilleja species. Morphological traits defined pollination syndromes reliably, but within the hummingbird syndrome, there was also significant variation among populations and species. Pollination syndrome was a poor predictor of visitors to Castilleja. CONCLUSIONS Floral trait differentiation among Castilleja individuals reflects both taxonomy and pollination syndromes. Differentiation was generally more evident in morphological traits compared to VOCs. Furthermore, a priori notions of pollination syndromes in this system are overly simplistic and fail to predict which animals most frequently visit Castilleja in natural populations.
Lung Proteases and Protease Inhibitors

Homogenates of guinea pig lung show significant protease activity at pH values from 2.2 to 9.9. Perfusion results in increased activity in both acid and alkaline ranges. Protease activity can be extracted by repeated homogenization and sonication of the pellet. Some of the neutral and alkaline proteases require a dialyzable co-factor and are inhibited by 1.2 mM Ag+and Cu++. 2-mercaptoethanol increases activity of the acid cathepsins and of an enzyme at pH 9.9, while DFP inhibits at both acid and alkaline pH. Lung is very active as shown by the „profile“ of its total protease activity over a wide pH range. Serum can inhibit protease activity of lung extracts through the whole pH range tested.
Dimensions of Elements: Their Comparative Relations

A figure may emerge or dominate because it is simply spatially larger, or occupies more of our time and attention. It can also dominate in other ways that may enhance, offset, or even nullify spatial or temporal dominance; for example, through greater brightness or saturation of color, higher level of pitch, greater loudness or intensity, unusual (for the context) timbre, and so on. The emergence we have suggested in Chapter 4, through expanse in space and duration in time, is certainly of the first importance, but other magnitudes than those of size are equally arresting and, as often as not, more so.
Hormones and Neurochemicals in the Regulation of Breathing

The sections in this article are: 1 Hormones 1.1 Progesterone 1.2 Thyroid Hormone 1.3 Estrogens and Androgens 1.4 Angiotensin 2 Neurochemicals 2.1 Monoamines 2.2 Amino Acids 2.3 Peptides
Regional resource management techniques: The case of Colorado oil shale development

Abstract Regions under stress from rapid development require comprehensive planning and management tools, capable of identifying the pace, location and magnitude of growth and assessing social, economic and environmental impacts. Northwest Colorado, endowed with massive rich deposits of oil shale, went through a boom-bust cycle of growth during the early 1980s as US interest in synthetic fuels peaked and then rapidly declined. An innovative resource information system has been developed which has assisted the region in anticipating growth and modifying its consequences. This article reviews the organization and development of the Colorado Resource Information System (CRIS) and evaluates its role and impact in the decisionmaking process. Experience shows that regions which develop and maintain planning and information tools can have significant influence on economic development.
OVEREDUCATION IN GREECE

While much has been written lately on overeducation, little is known about the effect of socioeconomic background on the incidence of overeducation and its impact on earnings. In this paper, the question of socioeconomic background is taken up and estimates of the incidence and labor market impacts of overeducation are examined with data from Greece. It is estimated that 16 percent of the university educated labor force is overeducated, varying considerably by discipline. The proportion of those overeducated from the lower classes is high (54 percent), although this varies by specialization. Overall, there is a 10 percent "penalty" in earnings associated with being overeducated for a university graduate. The negative and statistically significant effect of overeducation affects those faculties that are more general and do not correspond to particular occupations. Overeducated workers are younger than those properly matched, and more likely to work in the private sector. This suggests that overeducation is a phenomenon that affects workers as they make their way through the labor market. It may also mean that overeducation is a new phenomenon, brought about by the oversupply of graduates. Frustrated graduates are forced to take jobs in inappropriate fields. And as public sector employment decreases in size and the numbers of university graduates increase, private sector employment will necessarily increase for graduates. The question then is whether the private sector can provide jobs that are appropriate to the qualifications of university graduates.
Flexible Communication Mechanisms for Dynamic Structured Applications

Irregular scientific applications are often difficult to parallelize due to elaborate dynamic data structures with complicated communication patterns. We describe flexible data orchestration abstractions that enable the programmer to express customized communication patterns arising in an important class of irregular computations—adaptive finite difference methods for partial differential equations. These abstractions are supported by KeLP, a c++ run-time library. KeLP enables the programmer to manage spatial data dependence patterns and express data motion handlers as first-class mutable objects. Using two finite difference applications, we show that KeLP's flexible communication model effectively manages elaborate data motion arising in semi-structured adaptive methods.
Hedgehog signalling in gut development, physiology and cancer

The Hedgehog pathway is one of the most common signal transduction pathways used by mammalian cells. Most studies have focused on its role during development, primarily of the nervous system, skin, bone and pancreas. Due to the activation of this pathway during proliferation and neoplastic transformation, more recent studies have examined its role in adult tissues. Significant levels of sonic hedgehog are expressed in the gastric mucosa, which has served to direct analysis of its role during organogenesis, gastric acid secretion and neoplastic transformation. Therefore the goal of this review is to apply current knowledge of this pathway to further our understanding of gastrointestinal physiology and neoplasia, using the stomach as a prototype.
Studies on quantitative phosphopeptide analysis by matrix-assisted laser desorption/ionization mass spectrometry without label, chromatography or calibration curves.

RATIONALE Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry combined with isotope labeling methods are effective for protein and peptide quantification, but limited in their multiplexing capacity, cost-effectiveness and dynamic range. This study investigates MALDI-MS-based quantification of peptide phosphorylation without labeling, and aims to overcome the shot-to-shot variability of MALDI using a mathematical transformation and extended data acquisition times. METHODS A linear relationship between the reciprocal of phosphopeptide mole fraction and the reciprocal of phosphorylated-to-unphosphorylated signal ratio is derived, and evaluated experimentally using three separate phosphopeptide systems containing phosphorylated serine, threonine and tyrosine residues: mixtures of phosphopeptide and its des-phospho-analog with known stoichiometry measured by vacuum MALDI-linear ion trap mass spectrometry and fit to the linear model. The model is validated for quantifying in vitro phosphorylation assays with inhibition studies on Cdk2/cyclinA. RESULTS Dynamic range of picomoles to femtomoles, good accuracy (deviations of 1.5–3.0% from expected values) and reproducibility (relative standard deviation (RSD) = 4.3–6.3%) are achieved. Inhibition of cyclin-dependent kinase phosphorylation by the classical inhibitors olomoucine and r-roscovitine was evaluated and IC50 values found to be in agreement with reported literature values. These results, achieved with single-point calibration, without isotope or chromatography, compare favorably to those arrived at using isotope dilution (p >0.5 for accuracy). CONCLUSIONS The mathematical relationship derived here can be applied to a method that we term Double Reciprocal Isotope-free Phosphopeptide Quantification (DRIP-Q), as a strategy for quantification of in vitro phosphorylation assays, the first MALDI-based, isotope- and calibration curve-free method of its type. These results also pave the way for further systematic studies investigating the effect of peptide composition and experimental conditions on quantitative, label-free MALDI. Copyright © 2014 John Wiley & Sons, Ltd.
Problem Analyses and Recommendations in DRM Security Policies

We claim that the current digital rights management (DRM) technology and its related policy do not address customers' needs in the perspective of availability, which---along with confidentiality and integrity---is one of the main security properties. Our research has focused on how the current security policy in regards to DRM addresses the availability as a main security property. We study the current policies of DRM in U.S. law, the fair use doctrine, and the Digital Millennium Copyright Act. Additionally, we look at policies at the market, examining how the recording industry has used DRM in both the past and present. We analyze how much the companies and distributors place unnecessary controls on customers by considering customers' online resource usage. Finally, we suggest the market-level policy criteria as our possible solutions for the copyright owners, the distributors, and the general users.
Active files: a mechanism for integrating legacy applications into distributed systems

Despite increasingly distributed Internet information sources with diverse storage formats and access-control constraints, most of the end applications (e.g. filters and media players) that view and manipulate data from these sources operate against a traditional file-based interface. These legacy applications need to be rewritten to access remote sources, or need to rely upon ad-hoc intermediary applications that aggregate the data into a passive file before executing the legacy application. This paper presents a simple, elegant, programmable method for allowing natural integration of legacy applications into distributed system infrastructures, The approach, called "active files", enables multiple information sources to be encapsulated as a local file that serves as their logical proxy. This local file is accessed though a sentinel process, which automatically starts when the file is opened, aggregates data from multiple sources, and filters all access to and from the file. More importantly, the integration of active files into client applications is transparent: an active file is virtually indistinguishable from a regular file. Active files find a variety of applications in both distributed and non-distributed systems. We discuss active files, their semantics, their usage and their implementations in Windows NT.
Effect of metabolic inhibitors on vasopressin‐stimulated transport systems in the toad bladder

Vasopressin increases the permeability of receptor cells to water and, in tissues such as toad bladder, to solutes such as urea. While cyclic AMP appears to play a major role in mediating the effects of vasopressin, there is evidence that activation of the water permeability system and the urea permeability system involves separate pathways. In the present study, we have shown that inhibitors of oxidative metabolism (rotenone, dinitrophenol, and methylene blue) selectively inhibit either vasopressin-stimulated water flow or vasopressin-stimulated urea transport. There was no inhibition, however, when exogenous cyclic AMP was substituted for vasopressin, and little to no inhibition when the potent analogue 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) was employed. Rotenone had no effect on adenylate cyclase activity or cyclic AMP levels within the cell; dinitrophenol decreased adenylate cyclase activity minimally. Additional studies with vinblastine and nocodazole, inhibitors of microtubule assembly, demonstrated an inhibition of vasopressin and cyclic AMP-stimulated water flow but showed no effect on urea transport. We would conclude that water and urea transport, as examples of hormone-stimulated processes, have different links to cell metabolism, and that in addition to cyclic AMP, a non-nucleotide pathway may be involved in the action of vasopressin.
Estimating strategic interactions in petroleum exploration

When individual petroleum-producing firms make their exploration decisions, information externalities and extraction externalities may lead them to interact strategically with their neighbors. If they do occur, strategic interactions in exploration would lead to a loss in both firm profit and government royalty revenue. Since these strategic interactions would be inefficient, changes in the government offshore leasing policy would need to be considered. The possibility of strategic interactions thus poses a concern to policy-makers and affects the optimal government policy. This paper examines whether these inefficient strategic interactions take place in U.S. federal lands in the Gulf of Mexico. In particular, it analyzes whether a firm's exploration decisions depend on the decisions of firms owning neighboring tracts of land. A discrete response model of a firm's exploration timing decision that uses variables based on the timing of a neighbor's lease term as instruments for the neighbor's decision is employed. The results suggest that strategic interactions do not actually take place, at least not in exploration, and therefore that the current parameters of the government offshore leasing policy do not lead to inefficient petroleum exploration.
F-pili dynamics by live-cell imaging

Bacteria have evolved numerous mechanisms for cell–cell communication, many of which have important consequences for human health. Among these is conjugation, the direct transfer of DNA from one cell to another. For Gram-negative bacteria, conjugation requires thin, flexible filaments (conjugative pili) that are elaborated by DNA donor cells. The structure, function, and especially the dynamics of conjugative pili are poorly understood. Here, we have applied live-cell imaging to characterize the dynamics of F-pili (conjugative pili encoded by the F plasmid of Escherichia coli). We establish that F-pili normally undergo cycles of extension and retraction in the absence of any obvious triggering event, such as contact with a recipient cell. When made, such contacts are able to survive the shear forces felt by bacteria in liquid media. Our data emphasize the role of F-pilus flexibility both in efficiently sampling a large volume surrounding donor cells in liquid culture and in establishing and maintaining cell–cell contact. Additionally and unexpectedly, we infer that extension and retraction are accompanied by rotation about the long axis of the filament.
A queueing system with queue length dependent service times, with applications to cell discarding in ATM networks

A queueing system (M/G1,G2/1/K) is considered in which the service time of a customer entering service depends on whether the queue length, N(t), is above or below a threshold L. The arrival process is Poisson, and the general service times S1 and S2 depend on whether the queue length at the time service is initiated is &#60;L or &#8805;L, respectively. Balance equations are given for the stationary probabilities of the Markov process (N(t),X(t)), where X(t) is the remaining service time of the customer currently in service. Exact solutions for the stationary probabilities are constructed for both infinite and finite capacity systems. Asymptotic approximations of the solutions are given, which yield simple formulas for performance measures such as loss rates and tail probabilities. The numerical accuracy of the asymptotic results is tested.
The use of conditioning to probe for CNS pathways that regulate fever and NK cell activity.

Immune and central nervous system (CNS) interactions are complicated because afferent signals from the immune system to the CNS in response to antigens or infections may elicit an immediate efferent response to the immune system. This communication loop is required for the homeostatic regulation of the immune system. Conditioning can be used as a tool to take the communication loop apart. In conditioned animals, the conditioned stimulus can be employed later to trigger the site of the association memory located within CNS, and set off the efferent pathway. Conditioning therefore allows one to isolate and identify the potential circuits in the brain that becomes conditioned. We have conditioned a pathway in the brain which can be used to modulate core body temperature (Tc) and natural killer (NK) cell activity. The Tc and NK cell activity are used as readouts to detect the expression of the conditioned response which is taking place in the brain. Since various cytokines (IFN, IL-1 etc.) that are produced b...
HYPOXIA SIGNALS FOR MORE MUSCLE CELLS

![Figure][1] Adult phenotypes are the result of both genetic and environmental factors acting to program the form and function of embryonic tissues during development. Skeletal muscle development is known to be plastic for many vertebrate species and is affected by a variety of environmental
Energy Dependence of Defect Production in Displacement Cascades in Silver

Proton damage rates in Ag measured below 10 K show good agreement with calculated defect-production cross sections for low-energy recoils. A substantial decrease in damage efficiency (from $\overline{\ensuremath{\xi}}=1$ to $\overline{\ensuremath{\xi}}\ensuremath{\approx}0.6$) occurs as the energy and/or mass of the incident particle increases and displacement cascades are produced. Preliminary results are consistent with cascade efficiencies near $\ensuremath{\xi}=0.3$ and an effective transition from $\ensuremath{\xi}=1$ to $\ensuremath{\xi}=0.3$ centered near recoil energies between 1 and 3 keV.
Finite sample properties of estimators for autoregressive moving average models

Abstract We analyze by simulation the properties of three estimators frequently used in the analysis of autoregressive moving average time series models for both nonseasonal and seasonal data. The estimators considered are exact maximum likelihood, exact least squares and conditional least squares. For samples of the size commonly found in economic applications, the estimators are compared in terms of bias, mean squared error, and predictive ability. The reliability of the usually calculated confidence intervals is assessed for the maximum likelihood estimator.
How Often does a Source Code Unit Change within a Release Window

To form a training set for a source-code change prediction model, e.g., using the association rule mining or machine learning techniques, commits from the source code history are needed. The traceability between releases and commits would facilitate a systematic choice of history in units of the project evolution scale (i.e., commits that constitute a software release). For example, the major release 25.0 in Chrome is mapped to the earliest revision 157687 and latest revision 165096 in the trunk. Using this traceability, an empirical study is reported on the frequency distribution of file changes for different release windows. In Chrome, the majority (50%) of the committed files change only once between a pair of consecutive releases. This trend is reversed after expanding the window size to at least 10. That is, the majority (50%) of the files change multiple times when commits constituting 10 or greater releases are considered. These results suggest that a training set of at least 10 releases is needed to provide a prediction coverage for majority of the files.
An Overview of the Scholarship in Law and Religion of Judge John T. Noonan, Jr.

I first met John Noonan at a Law Review dinner when I was a year or so out of law school and he was a third year student. Chance placed us at the same table, and the conversation—naturally—proved to be more interesting than the speeches. When I came home and reported on the occasion to my wife, it developed that she was already acquainted with John Noonan. When they were teenagers, he had been a particularly suave and glamorous summer inhabitant of a beach resort where one of her friends also spent summers.Not long after the Law Review dinner, John graduated and went to Washington, and we left Boston, first for New Jersey and then for Notre Dame. I heard nothing more of John until one day when Joe O'Meara, the formidable dean of the Notre Dame Law School, showed me an article from the 1955 volume of the Journal of Legal Education called Value References in the Teaching of Negligence. The author had looked at all the Torts casebooks he could find, and earlier editions of many of them; at all the relevant case write-ups from the Harvard Law Review and the Yale Law Journal; at a number of law school examinations; and at all the issue sheets used by Harvard's Board of Student Advisors in supervising their moot court, the Ames Competition. He had found the value concerns in great disarray, and not much relied on anyhow. It was clear that teaching about negligence involved analysis of rules and not much else. The author (of course, it was John) admitted reluctantly that neither philosophy nor theology nor social science provided any principles that would be of much use in deciding negligence cases, but he expressed a rather wistful hope that more facts might lead to a more effective application of values to these cases. “More facts” was to be a major distinguishing quality in the rest of his work.
Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts.

Rationale Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase alpha-smooth muscle actin (alpha-SMA) and collagen III synthesis by human lung fibroblasts (HLFs). Methods Transforming growth factor (TGF)-beta1, TGF-beta2, IL-4 and IL-13 levels were measured in BAL fluid from 10 asthmatics and 9 non-asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF-beta1, TGF-beta2, IL-4 or IL-13 (concentration range 0.01-10 ng/mL) over 48 h. Collagen III was measured in culture supernates and alpha-SMA in cell lysates by Western blot. Results At baseline, there was no difference in BAL fluid concentrations of TGF-beta1, IL-4 and IL-13 between asthmatics and controls; however, non-asthmatics had higher concentrations of total TGF-beta2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF-beta1, TGF-beta2 and IL-13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL-4 concentration remained elevated for at least 2 weeks. TGF-beta1, TGF-beta2 and IL-4 significantly increased alpha-SMA in fibroblasts, but only IL-4 caused corresponding increases in collagen III synthesis. IL-13 had no direct effects on collagen III synthesis and alpha-SMA expression. Conclusions Because IL-4 caused a dose-dependent increase in alpha-SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF-beta1 and TGF-beta2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines.
Recovery of Renal Function After Open and Laparoscopic Partial Nephrectomy

Abstract Background Although oncologic outcomes appear to be similar after laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN), data on renal function are lacking. Objective To evaluate the change over time in renal function after LPN and OPN. Design, setting, and participants We identified 987 patients with a single sporadic tumor and a normal contralateral kidney who were treated by LPN ( n =182) and OPN ( n =805) between January 2002 and July 2009. Intervention All patients underwent LPN or OPN at Memorial Sloan-Kettering Cancer Center. Measurements Estimated glomerular filtration rate (GFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula. We created a multivariable generalized estimating equations linear model that predicted GFR based on the time from surgery, preoperative GFR, tumor size, American Society of Anesthesiologists score, and ischemia time. Results and limitations Mean patient age, tumor size, and ASA score were similar between LPN and OPN patients. The baseline preoperative GFR was lower in the laparoscopic group (67ml/min per 1.73m 2 vs 73ml/min per 1.73m 2 ; p p p =0.045), indicating that there was a differential effect on recovery of renal function over time by approach. Laparoscopically treated patients maintained a slightly higher renal function than those treated via an open approach. The 2-mo and 6-mo predicted GFR for a typical patient increased slightly from 65ml/min per 1.73m 2 to 67ml/min per 1.73m 2 , respectively, for those treated laparoscopically but remained constant at 62ml/min per 1.73m 2 after OPN. Conclusions Our data suggest that the surgical approach has a small effect on the recovery of renal function after partial nephrectomy. Laparoscopically treated patients maintained slightly higher renal function.
Playing the Changes on the Jazz Metaphor: An Expanded Conceptualization of Music-, Management-, and Marketing-Related Themes

Playing the Changes on the Jazz Metaphor: An Expanded Conceptualization of Music-, Management-, and Marketing-Related Themes
Parathyroid hormone-receptor interactions identified directly by photocross-linking and molecular modeling studies.

Abstract Direct mapping of the interface between parathyroid hormone (PTH) and its receptor (hPTH1-Rc) was carried out by photoaffinity scanning studies. Photoreactive analogs of PTH singularly substituted with a p-benzoylphenylalanine (Bpa) at each of the first six N-terminal positions have been prepared. Among these, the analog [Bpa1,Nle8,18,Arg13,26,27,l-2-Nal23,Tyr34]bPTH-(1–34)NH2(Bpa1-PTH-(1–34)) displayed in vitroactivity with potency similar to that of PTH-(1–34). The radioiodinated analog 125I-Bpa1-PTH-(1–34) cross-linked specifically to the hPTH1-Rc stably expressed in human embryonic kidney cells. A series of chemical and enzymatic digestions of the hPTH1-Rc–125I-Bpa1-PTH-(1–34) conjugate suggested that a methionine residue (either Met414 or Met425) within the contact domain hPTH1-Rc-(409–437), which includes the transmembrane helix 6 and part of the third extracellular loop, as the putative contact point. Site-directed mutagenesis (M414L or M425L) identified Met425 as the putative contact point. Molecular modeling of the hPTH1-Rc together with the NMR-derived high resolution structure of hPTH-(1–34), guided by the cross-linking data, strongly supports Met425, at the extracellular end of transmembrane helix 6, as the residue interacting with the N-terminal residue of the hPTH-(1–34). The photocross-linking and molecular modeling studies provide insight into the topologic arrangement of the receptor-ligand complex.
Investigation of possible associations between partial fertility restoration and agronomic traits in Triticum aestivum L.

Many conventional hard red spring wheat (Triticum aestivum L. em Thell) lines, including several North Dakota cultivars, carry a gene (or genes) which restore partial male fertility to male sterile plants with Triticum timopheeviZhuk. cytoplasm. Since this gene has no fertility restoration function in T. aestivum cytoplasm, the postulation can be made that it is being retained in conventional lines because of pleiotropic effects, favorable linkages or chance. The research reported in this paper examined these possibilities. Forty F6 lines, derived from a single F2 plant which was heterozygous for a gene (or genes) for partial fertility restoration, were evaluated for two years in a yield trial planted at Fargo, North Dakota. The 40 lines were testcrossed to a male sterile line having T. timopheevi cytoplasm, and the mean seed set of testcrosses was used as a measure of a line's fertility restoration potential. Twenty-seven lines had the gene for partial fertility, and 13 lines apparently lacked this gene. The 40 lines differed for heading date, anther extrusion, plant height, grain yield, 200-kernel weight, test weight, and grain protein percentage. However, comparisons of lines having the restorer gene with those lacking the gene did not provide any obvious explanation for the retention of the partial fertility restorer gene in the breeding stocks of the North Dakota conventional hard red spring wheat breeding program. The possibility that the restorer gene was linked with genes for resistance to stem rust or leaf rust also was evaluated by testing lines for their reaction to several races of rust. No conclusive association was found.
Diffusional effect of pores on the densification in microgravity liquid phase sintered FE-CU alloys

OLiPSE-02 Fe-Cu samples, which were liquid phase sintered under 10 m 5 torr in microgravity for 20, 30, 60, and 330 min for each composition, were analyzed in this article. The compositions of the samples are 80% Fe/Cu, 70% Fe/Cu, 60% Fe/Cu, and 50% Fe/Cu by volume. The experimental results of distortion and densification were presented. During the microgravity processing, liquid ejection occured for the long duration samples with compositions 70% Fe/Cu and 60% Fe/Cu. Measurements of the weights and dimensions of all the beads were made and their distributions were presented. One of the beads that are about the average weight and size from the 70% Fe/Cu long duration sample was chosen to be mounted, polished, etched, and analyzed under an optical microscope. The iron in the bead appeared as iron grains and its grain size was smaller than that in the mother sample with the same composition. Discussions of the bead and its iron grain formations are provided.
Metasurfaces for phase and polarization control

An optical metasurface providing isotropic beam refraction is reported. The metasurface consists of cascaded metallic layers which allows for complete phase control while maintaining high transmission of the co-polarized field. The efficiency of the metasurface was measured to be 3 times larger than state of the art metasurfaces consisting of a single metallic layer. Future work will consider anisotropic metasurfaces that allow both wavefront and polarization control.
A systematic review of the association between obstructive sleep apnea and ventricular arrhythmias.

Introduction:Obstructive sleep apnea (OSA) is an independent risk factor for sudden cardiac death. The aim of this review was to study the relationship between OSA and ventricular arrhythmias.Metho...