cssi/SciSciGPT-SciSciNet huggingface dataset:
Corticotropin-releasing hormone receptor antagonists: framework design and synthesis guided by ligand conformational studies.

As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation of the antagonists and to use this information to help guide preclinical optimization of the series and to develop new leads. Since receptor structural information was not available, we assumed that these small, high-affinity antagonists would tend to bind in conformations at or energetically close to their global minima and that rigid analogues that maintained the important stereoelectronic features of the bound anilinopyrimidine would also bind tightly. Conformational preferences and barriers to rotation of the anilinopyrimidines were determined by semiempirical methods, and X-ray and variable-temperature NMR spectroscopy provided experimental results that correlated well with calculated str...
Dirichlet feedback control for the stabilization of the wave equation: a numerical approach

Abstract In (J. Differential Equations 66 (1987) 340) a uniform stabilization method of the wave equation by boundary control a la Dirichlet has been discussed. In this article, we investigate the numerical implementation of the above stabilization process by a numerical scheme which mimics the energy decay properties of its continuous counterpart. The practical implementation of that scheme leads to a biharmonic problem of a new type which is solved by a method directly inspired by some related work of Glowinski and Pironneau on the solution of the Dirichlet problem for the biharmonic operator (SIAM Rev. 21(2) (1979) 167). Numerical experiments show that the decay properties of the energy are well-preserved by our numerical methodology.
Analyzing subcellular structure with optical Fourier filtering based on Gabor filters

Label-free measurement of subcellular morphology can be used to track dynamically cellular function under various conditions and has important applications in cellular monitoring and in vitro cell assays. We show that optical filtering of scattered light by two-dimensional Gabor filters allows for direct and highly sensitive measurement of sample structure. The Gabor filters, which are defined by their spatial frequency, orientation and Gaussian envelope, can be used to track locally and in situ the characteristic size and orientation of structures within the sample. Our method consists of sequentially implementing a set of Gabor filters via a spatial light modulator placed in a conjugate Fourier plane during optical imaging and identifying the filters that yield maximum signal. Using this setup, we show that Gabor filtering of light forward-scattered by spheres yields an optical response which varies linearly with diameter between 100nm and 2000nm. The optical filtering sensitivity to changes in diameter is on the order of 20nm and can be achieved at low image resolution. We use numerical simulations to demonstrate that this linear response can be predicted from scatter theory and does not vary significantly with changes in refractive index ratio. By applying this Fourier filtering method in samples consisting of diatoms and cells, we generate false-color images of the object that encode at each pixel the size of the local structures within the object. The resolution of these encoded size maps in on the order of 0.36μm. The pixel histograms of these encoded images directly provide 20nm resolved “size spectra”, depicting the size distribution of structures within the analyzed object. We use these size spectra to differentiate the morphology of apoptosis-competent and bax/bak null apoptosis-resistant cells during cell death. We also utilize the sensitivity of the Gabor filters to object orientation to track changes in organelle morphology, and detect mitochondrial fission in cells undergoing apoptosis.
Enhanced sintering rate and finer grain size in yttria-stablized zirconia (3Y-TZP) with combined DC electric field and increased heating rate

Abstract The influence of heating rate dT/dt = 2–25 °C/min on sintering of yttria-stabilized ZrO2 (3Y-TZP) powder without and with a small initial DC electric field (E0 = 13.9 V/cm) was determined. An increase in dT/dt and the application of electric field reduced both the sintering time and the grain size at a given density. Employing the master sintering curve approach it was determined that the apparent activation energy Q for sintering was 500 ± 5 kJ/mole, essentially independent of dT/dt and E. A major factor in the effects of dT/dt and E on the sintering rate is their reduction of the grain size. It is proposed that retardation of grain growth by the field results from the interaction of the field with the space charge at the grain boundaries.
Experimental Investigation of the Machinability of Polycarbonate Reinforced With Multiwalled Carbon Nanotubes

The machinability of a polycarbonate nanocomposite containing multiwalled carbon nanotubes is investigated and contrasted with its base polymer and with a conventional carbon fiber composite. The material microstructures are characterized using transmission electron and scanning electron microscopy methods. Micro-endmilling experiments are conducted on the three materials. Chip morphology, machined surface characteristics, and the nature of the cutting forces are employed as machinability measures for comparative purposes. Polycarbonate chips are seen to transition from being discontinuous to continuous as the feed-per-tooth (FPT) increases, while, at all FPT values the nanocomposite is seen to form comparatively thicker continuous chips. The nanocomposite and the carbon fiber composite are seen to have the lowest and the highest magnitudes, respectively, for both the surface roughness and cutting forces. Shearing along the nanotube-polymer interface and better thermal conductivity are speculated to be the mechanisms responsible for the observations seen in the nanocomposite.
Mastication and swallowing in patients with postirradiation xerostomia

Purpose Very little objective data has been reported on mastication and swallowing in xerostomic patients, which would substantiate presumed causal relationships between xerostomia and patient complaints. The purpose was to elucidate which components of mastication and swallowing were abnormal, and most directly related to xerostomia, and which appeared unaffected. Methods and materials A retrospective analysis of timing events in mastication and swallowing was done using videofluoroscopic data for 15 cancer patients with xerostomia, and 20 normal controls. Scintigraphy was also used to determine oropharyngeal residue after a water swallow. Cancer treatment modalities included radiation therapy or chemoradiation therapy. Results For barium liquid and paste substances, timing measures were equivalent for controls and patients. Xerostomic patients took 46% longer to masticate a shortbread cookie, and timing for the initiation of swallowing was shorter, but duration of swallowing appeared unaffected. Oral and pharyngeal residues following the swallow were greater in the patient group. Conclusions Xerostomia primarily affected mastication and oral manipulation of a dry, absorbent food material. Increased oral and pharyngeal residues after a water swallow are ambiguously related to xerostomia. The initiation and duration of the pharyngeal swallow was not abnormal.
Abdominal surgery induces Fos immunoreactivity in the rat brain.

Previous neuropharmacological studies indicate that brain peptides are involved in mediating gastric stasis induced by abdominal surgery. Central pathways activated by abdominal surgery were investigated in the rat by using Fos protein as a marker of neuronal activation. Abdominal surgery (laparotomy alone or combined with cecal manipulation) was performed under brief enflurance anesthesia (7–8 minutes), and 1 hour later rats were killed and brains processed for Fos immunoreactivity. Double labeling with Fos and arginine vasopressin, oxytocin, or tyrosine hydroxylase antibodies was also performed. Abdominal surgery induced Fos staining in the nucleus tractus solitarii, paraventricular and supraoptic nuclei of the hypothalamus, locus coeruleus, and ventrolateral medulla. After abdominal surgery, 18–25% of vasopressin and 18–33% of oxytocin-labeled cells were found to be Fos positive in the paraventricular nucleus and 15% of activated cells in the nucleus tractus solitarii were positive for tyrosine hydroxylase immunoreactivity. Enflurane alone induced c-fos expression in the same brain area; however, the number of Fos-positive cells and double-labeled cells were decreased two-to fivefold and three- to eightfold, respectively, compared with the abdominal surgery groups. These data show that abdominal surgery induced activation of specific hypothalamic, pontine, and medullary neurons. These findings may have implications for the understanding of central mechanisms involved in mediating gastric ileus following abdominal surgery. © 1994 Wiley-Liss, Inc.
Towards resilient geographic routing in WSNs

In this paper, we consider the security of geographical forwarding (GF) -- a class of algorithms widely used in ad hoc and sensor networks. In GF, neighbors exchange their location information, and a node forwards packets to the destination by picking a neighbor that moves the packet closer to the destination. There are a number of attacks that are possible on geographic forwarding. One of the attacks is predicated on misbehaving nodes falsifying their location information. The first contribution of the paper is to propose a location verification algorithm that addresses this problem. The second contribution of the paper is to propose approaches for route authentication and trust-based route selection to defeat attacks on the network. We discuss the proposed approaches in detail, outlining possible attacks and defenses against them.
Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death.

The tumor suppressor protein p53 is a critical stress response transcription factor that induces the expression of genes leading to cell cycle arrest, apoptosis, and tumor suppression. We found that mammalian inositol polyphosphate multikinase (IPMK) stimulated p53-mediated transcription by binding to p53 and enhancing its acetylation by the acetyltransferase p300 independently of its inositol phosphate and lipid kinase activities. Genetic or RNA interference (RNAi)–mediated knockdown of IPMK resulted in decreased activation of p53, decreased recruitment of p53 and p300 to target gene promoters, abrogated transcription of p53 target genes, and enhanced cell viability. Additionally, blocking the IPMK-p53 interaction decreased the extent of p53-mediated transcription. These results suggest that IPMK acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death.
Practical considerations of clock-powered logic

Recovering and reusing circuit energies that would otherwise be dissipated as heat can reduce the power dissipated by a VLSI chip. To accomplish this requires a power source that can efficiently inject and extract energy, and an efficient power delivery system to connect the power source to the circuit nodes. The additional circuitry and timing required to support this process can readily exceed the power-savings benefit. Clock-powered logic is a circuit-level, energy-recovery approach that has been implemented in two generations of small-scale microprocessor experiments. The results have shown that it is possible and practical to extract useful amounts of power savings by leveraging the additional circuitry for other compatible purposes. The capabilities and limitations of clock-powered logic as a competitive low-power approach are presented and discussed in this paper.
Dynamic Object Viewers for Java

The jGRASP lightweight IDE provides object viewers that automatically generate dynamic, state-based visualizations of objects and primitive variables in Java. Multiple synchronized visualizations of an object, including complex data structures, are immediately available to users from the jGRASP debugger window or object workbench. Initial use has demonstrated the object viewers' potential as an aid to understanding and debugging
PHARMACOLOGY OF TETRODOTOXIN

Tetrodotoxin (TTX) is a potent neurotoxin originally found in the ovary and liver of puffer fish. It has now become abundantly clear that TTX is not synthesized in the puffer fish, and that it is p...
Molecular testing for transfusion medicine.

Purpose of reviewMolecular testing methods were introduced to the blood bank and transfusion medicine community more than a decade ago after cloning of the genes made genetic testing for blood groups, that is genotyping, possible. This review summarizes the progress made in the last decade in applyi
Global Patterns of Low-Mode Internal-Wave Propagation. Part II: Group Velocity

Abstract Using a set of 80 globally distributed time series of near-inertial and semidiurnal energy E and energy flux F computed from historical moorings, the group velocity ĉg ≡ FE−1 is estimated. For a single free wave, observed group speed |ĉg| should equal that expected from linear wave theory. For comparison, the latitude dependence of perceived group speed for perfectly standing waves is also derived. The latitudinal dependence of observed semidiurnal |ĉg| closely follows that expected for free waves at all latitudes, implying that 1) low-mode internal tides obey linear theory and 2) standing internal-tidal waves are rare in the deep ocean for latitudes equatorward of about 35°. At higher latitudes, standing waves cannot be easily distinguished from free waves using this method because their expected group speeds are similar. Near-inertial waves exhibit scattered |ĉg| values consistent with the passage of events generated at various latitudes, with implied frequencies ω ≈ 1.05–1.25 × f, as typically...
Remote arteriolar dilations in response to muscle contraction under capillaries.

In hamster cremaster muscle, it has been shown previously that contraction of skeletal muscle fibers underlying small groups of capillaries (modules) induces dilations that are proportional to meta...
A scalable cache design for I-structures in multithreaded architectures

I-Structures were originally proposed to handle producer-consumer parallelism in data-driven execution models. Although they provide fine-grain synchronization and non-strict execution capability, they do not exploit data locality, usually a key factor in performance improvement. In this paper, we propose a novel cache design for I-Structures in a multithreaded multiprocessor. It can exploit both temporal and spatial locality without any of the associated cache coherence costs. A highly scalable method for storing the deferred requests is employed, which further facilitates the processing of deferred requests in a parallel and distributed fashion.
TOWARD AN INTERACTIONAL THEORY OF DELINQUENCY

Contemporary theories of delinquency are seen as limited in three respects: they tend to rely on unidirectional causal structures that represent delinquency in a static rather than dynamic fashion, they do not examine developmental progressions, and they do not adequately link processual concepts to the person's position in the social structure. The present article develops an interactional theory of delinquency that addresses each of these issues. It views delinquency as resulting from the freedom afforded by the weakening of the person's bonds to conventional society and from an interactional setting in which delinquent behavior is learned and reinforced. Moreover, the control, learning, and delinquency variables are seen as reciprocalIy interrelated, mutually affecting one another over the person's life. Thus, delinquency is viewed as part of a larger causal network, affected by social factors but also affecting the development of those social factors over time.
Cross Section for Radiative Electron Capture(REC) by 20-80 MeV CL Ions Incident on C and CU Foils

Radiative electron capture (REC) cross sections for 40-80 MeV Cl ions incident on thin C foils are reported and compared with previous results using Cu targets. We find that the measured REC cross section per K vacancy scales according to the number of "free" electrons on the target atom, i. e., those bound target electrons with a velocity much less than the incident projectile velocity. Comparison is made with the free-electron theory of Bethe and Salpeter and good agreement is obtained. Experimental and theoretical results are compared with those of Lindskog et al., and consideration is given to different ways of computing the K-shell binding energy of the projectile at the time of REC which enters into the calculation of the theoretical REC cross section in an important way.
THE PROPHAGE OF SPβc2dcitK1, A DEFECTIVE SPECIALIZED TRANSDUCING PHAGE OF BACILLUS SUBTILIS

The defective specialized transducing phage SP βc2 d citK1 carries two known bacterial genes, kauA and citK , as well as SPβ phage markers including the heat-sensitive repressor allele, c2 . Some phage genes (including essential ones) are missing. When SP βc2 d citK1 transduces SPβ-sensitive cells of Bacillus subtilis, the defective prophage is inserted into sites in the homologous bacterial DNA of the attSPβ-kauA-citK region of the recipient chromosome. During the growth of these transductants, occasional excisions occur that result in the loss of the phage genes and OI the heterogenotic state. These excisions increase greatly in frequency during growth at repressor-inactivating temperatures. The kinds of insertions and excisions seen suggest that a Campbell-type (CAMPBELL 1962) circular phage genome may occur transiently. If the transductants are superinfected by SP βc2 or by the clear-plaque mutant SP βc1 , the resulting double lysogen can be heat induced to release high-frequency of-transduction (HFT) lysates for kauA and citK .
Chemical oxygen demand fate from cottage cheese (acid) whey applied to a sodic soil

Abstract Cottage cheese (acid) whey is an effective amendment in sodic soil reclamation, but the high chemical oxygen demand (COD) of whey is of concern in land application. The objective of this research was to determine the fate of COD from cottage cheese whey applied to a sodic soil. Treatments of 0, 25, 50, and 100 mm (0, 20, 40, and 80 Mg COD ha‐1) of whey were applied to dry‐unacclimated Freedom silt loam (fine‐silty, mixed, mesic, Xerollic Calciorthids) in greenhouse lysimeters. The COD from lysimeter leachate at 1 m depth was monitored. Ninety days after whey application, total accumulative leachate COD for 0‐, 25‐, and 50‐mm whey applications was not significantly different. Leachate COD concentrations from the 100‐mm application reached 37% (29 400 mg COD L‐1) of the applied whey COD. Twenty‐eight days after whey treatment, infiltration was reduced in all whey‐treated lysimeters, probably as a result of increased microbial activity. Barley (Hordeum vulgare L. cv. Ludd) grain yield was 0.0, 0.0, ...
The relationship between limb morphology, kinematics, and force during running: the evolution of locomotor dynamics in lizards

Terrestrial locomotion occurs via the hierarchical links between morphology, kinematics, force, and center-of-mass mechanics. In a phylogenetically broad sample of seven lizard species, we show that morphological variation drives kinematic variation, which, in turn, drives force variation. Species with short limbs use a short stride–high frequency strategy when running at steady-speed and to change speeds. This link between morphology and kinematics results in relatively small vertical forces during the support phase of the stride cycle. Conversely, species with long limbs use a long stride–low frequency strategy, resulting in large vertical forces during the support phase. In view of these findings, we suggest that limb length may predict locomotor energetics in lizards because energetics are largely determined by vertical forces and stride frequency. Additionally, we propose an energetic trade-off with both long- and short-limbed species paying the most energy to move, whereas intermediate-limbed species move using less energy. Finally, when these traits are mapped onto a lizard phylogeny, we show that locomotor functional morphology exhibits both deep phylogenetic effects and contemporary patterns of evolutionary convergence. Overall, the present study provides a foundation for testing hypotheses regarding the integration and evolution of functional traits in lizards and animals in general. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 634–651.
The development of attachment in new relationships: single subject analyses for 10 foster infants.

This paper presents single-subject analyses of newly developing attachment relationships in 10 foster infant‐caregiver dyads. Using a diary methodology, at least 2 months of daily data were provided by foster parents on infants’ attachment behaviors. Foster infant attachment was also assessed using the Strange Situation. Foster mother state of mind regarding attachment was measured using the Adult Attachment Interview. For eight infants, diary data revealed predominant patterns of attachment behavior emerging within 2 months of placement. In most cases, diary data predicted Strange Situation classifications. Both Strange Situation and diary data indicated that the three children placed in foster care before 12 months of age with foster parents having primary or secondary autonomous states of mind were classified as having secure attachments. The five children placed after 12 months of age showed predominantly insecure attachment behavior in the diary and were classified as insecure in the Strange Situation. Contingency analyses of behavioral sequences reported in the diary revealed that foster parents tended to complement their foster childrens’ attachment behaviors.
Laparoscopic Partial Kidney Ablation With High Intensity Focused Ultrasound

Purpose: High intensity focused ultrasound has been performed for transrectal and extracorporeal thermal ablation of tissues. We developed and tested a laparoscopic probe that allows real-time ultrasound imaging during partial renal ablation using high intensity focused ultrasound.Methods: A Sonablate 200 (Focus Surgery, Indianapolis, Indiana) high intensity focused ultrasound system with a modified 18 mm. laparoscopic probe was used in all experiments. In 13 Yucatan mini-pigs a 5Fr ureteral catheter was inserted into the renal pelvis and 10 cc air were instilled into the collecting system. The kidney was laparoscopically dissected, the high intensity focused ultrasound probe was inserted through a 33 mm. laparoscopic port and the targeted renal pole was treated.Results: Renal lesions were created in 12 of 13 treated kidneys under real-time ultrasound visualization. Median operative time was 180 minutes, average high intensity focused ultrasound activation time was 18.3 minutes and lesion size was 23 × 17...
Basic leucine zipper transcription factor Hac1 binds DNA in two distinct modes as revealed by microfluidic analyses

A quantitative understanding of how transcription factors interact with genomic target sites is crucial for reconstructing transcriptional networks in vivo. Here, we use Hac1, a well-characterized basic leucine zipper (bZIP) transcription factor involved in the unfolded protein response (UPR) as a model to investigate interactions between bZIP transcription factors and their target sites. During the UPR, the accumulation of unfolded proteins leads to unconventional splicing and subsequent translation of HAC1 mRNA, followed by transcription of UPR target genes. Initial candidate-based approaches identified a canonical cis-acting unfolded protein response element (UPRE-1) within target gene promoters; however, subsequent studies identified a large set of Hac1 target genes lacking this UPRE-1 and containing a different motif (UPRE-2). Using a combination of unbiased and directed microfluidic DNA binding assays, we established that Hac1 binds in two distinct modes: (i) to short (6–7 bp) UPRE-2-like motifs and (ii) to significantly longer (11–13 bp) extended UPRE-1-like motifs. Using a genetic screen, we demonstrate that a region of extended homology N-terminal to the basic DNA binding domain is required for this dual site recognition. These results establish Hac1 as the first bZIP transcription factor known to adopt more than one binding mode and unify previously conflicting and discrepant observations of Hac1 function into a cohesive model of UPR target gene activation. Our results also suggest that even structurally simple transcription factors can recognize multiple divergent target sites of very different lengths, potentially enriching their downstream target repertoire.
Motivated About Motivated Reasoning

Eileen Braman’s Law, Politics & Perception: How Policy Preferences Influence Legal Reasoning invokes the cognitive psychology theory of “motivated reasoning” to explain not only how judges might sincerely believe that their rulings are based on legal authorities even as they choose outcomes consistent with their attitudinal preferences but also how precedent can unconsciously constrain attitude-consistent behavior when judges are unable reasonably to reconcile the two. The book makes a substantial contribution to the literature by taking seriously widely shared and deeply held norms and operative assumptions of bench and bar. And Braman’s inventive and careful experimental studies offer partial support for her theory. But neither of those studies nor her analysis of recent Supreme Court Commerce Clause opinions provide convincing support for her key claim that judges’ “perception” of precedent is unconsciously influenced by ideological preferences, as opposed to the attitudinalists’ and rational choice theorists’ assertion that judges consciously choose to characterize precedent to suit their preferred outcomes. The book’s limits, however, including its inability to refute the deliberate-manipulation view, do not negate its utility but instead point the way toward more focused study.
State-Space Models and the Kalman Recursions

In recent years, state-space representations and the associated Kalman recursions have had a profound impact on time series analysis and many related areas. The techniques were originally developed in connection with the control of linear systems (for accounts of this subject, see the books of Davis and Vinter (1985) and Hannan and Deistler (1988)). The general form of the state-space model needed for the applications in this chapter is defined in Section 12.1, where some illustrative examples are also given. The Kalman recursions are developed in Section 12.2 and applied in Section 12.3 to the analysis of ARMA and ARIMA processes with missing values. In Section 12.4 we examine the fundamental concepts of controllability and observability and their relevance to the determination of the minimal dimension of a state-space representation. Section 12.5 deals with recursive Bayesian state estimation, which can be used (at least in principle) to compute conditional expectations for a large class of not necessarily Gaussian processes. Further applications of the Bayesian approach can be found in the papers of Sorenson and Alspach (1971), Kitagawa (1987) and Grunwald, Raftery and Guttorp (1989).
Axisymmetric rotational stagnation point flow impinging on a radially stretching sheet

Abstract The normal impingement of the rotational stagnation-point flow of Agrawal (1957) [8] on a sheet radially stretching at non-dimensional stretch rate β is studied. A similarity reduction of the Navier–Stokes equations yields an ordinary differential equation which is solved numerically over a range of β. A unique solution exists at the turning point β = β t and dual solutions are found in the region β > β t where β t = − 0.657 is the turning point in the parametric shear stress curve separating upper from lower branch solutions. An analysis of solutions near the Agrawal point β = 0 is provided, and the large-β asymptotic behavior of solutions is determined. Sample velocity profiles along both solution branches are presented. A linear temporal stability analysis reveals that solutions along the upper branch are stable while those on the lower branch are unstable.
2-D Magnetic Recording: Progress and Evolution

Two-dimensional magnetic recording (TDMR) was proposed in 2008 as a means of pushing beyond 1 Tbit/in $^{2}$ areal-density yet staying with relatively conventional magnetic components. A density of approximately 1 Tbit/in $^{2}$ is considered to be the limit for conventional perpendicular magnetic recording. The original concept for TDMR has evolved greatly since it was originally proposed. This evolution has occurred as more information has become available about the characteristics of shingled tracks and 2-D read-back signals and as constraints have become apparent in the implementation of recording components and electronics. With today’s technology, the projected gains are smaller than originally envisioned. As a very practical first step that introduces TDMR and provides modest gains without incurring undue complexity or cost, this paper focuses on the idea of a stacked two-element reader operating on shingled magnetic recording tracks and a two-input equalizer feeding a standard data detector. The dual-reader gains are assessed based on combining waveforms captured from a single reader at many off-track positions, track-pitches, and radii.
Development of a simple model to predict spatial distribution of cycle-averaged wall heat flux using artificial neural networks

The KIVA 3V code has been applied to predict combustion chamber heat flux in an air-cooled utility engine. The KIVA heat flux predictions were compared with experimentally measured data in the same engine over a wide range of operating conditions. The measured data were found to be approximately two times larger than the predicted results, which is attributed to the omission of chemical heat release in the near-wall region for the heat transfer model applied. Modifying the model with a simple scaling factor provided a good comparison with the measured data for the full range of engine load, heat flux sensor location, air-fuel ratio and spark timings tested. The detailed spatially resolved results of the KIVA predictions were then used to develop a simplified model of the combustion chamber temporally integrated heat flux using an artificial neural network (ANN). The input parameters of the ANN model are engine load, air-to-fuel ratio, spark timing and zonal engine wall temperature distribution; and the outputs of the model are the temporally averaged heat flux to each zone. This simplified model provides a coupling between thermal structural finite element analysis and detailed in-cylinder processes with low computational overhead.
189: Differences in cytokine responses during infection with high and low pathogenic Ebola viruses

To date five Ebolavirus species have been identified, differing in pathogenicity. The highly pathogenic Zaire ebolavirus (EBOV) causes a hemorrhagic disease in humans with case fatality rates up to 90%. A hallmark of EBOV infection is a dysregulated immune response, including high levels of cytokines. In contrast, Reston ebolavirus (RESTV) seems to be nonpathogenic in humans, as only asymptomatic cases of RESTV infection in humans have been reported. The mechanisms of protection against RESTV in humans are not yet understood. As cytokines might play a role in the pathogenesis of EBOV infection, we analyzed the cytokine response in EBOV- and RESTV-infected human macrophages and dendritic cells. These cells not only orchestrate innate and adaptive immune responses but are also early targets of Ebolaviruses. We observed degradation of I κ Bα and nuclear translocation of p65 in EBOV-infected macrophages, indicating activation of NFκB signaling. qRT-PCR and Luminex assays revealed induction of selected cytokines in EBOV-infected macrophages. Most analyzed cytokines and chemokines were upregulated in EBOV infection at 6 hpi or later, whereas others, including IL10, did not show increased secretion levels. In contrast, p65 was not translocated into the nucleus in RESTV-infected macrophages and no significant changes in cytokine mRNA levels or secreted protein levels were observed. To investigate if this effect is due to inhibition of pro-inflammatory signaling pathways, RESTV-infected macrophages were treated with LPS at 1 dpi and cytokine production was determined. Similar levels of pro-inflammatory cytokines, including IL6 and TNFα, were detected in RESTV-infected and LPS-treated macrophages compared to non-infected LPS-treated cells, suggesting that RESTV is not able to inhibit LPS-mediated cytokine induction. Our data support the hypothesis that high pathogenicity correlates with high cytokine levels in Ebolavirus infection. Currently we are investigating which cellular signaling pathways are involved in the observed differential cytokine induction in EBOV versus RESTV infection.
Sanction and Obligation

H. L. A. Hart's criticism of Austin's theory of law is that it is essential ly false to the facts. Austin asserts that "Every positive law simply and strictly so called, is set by a sovereign person, or sovereign body of persons, to a . . . person or persons in a state of subjection to its author."1 Laws get their force from the threat of sanction. This view, which we may call "the gunman theory of law," is what Hart criticizes.2 Too many laws, he argues, do not look like commands backed by sanctions for us to find this theory compelling. I wish to defend Austin's theory against Hart's objections. In large part the defense will be that Austin would accept virtually all of Hart's views on the structure of actual laws and would fit them easily to the gun man theory. As Kelsen wittily remarked of his own dispute with Hart, Austin might find his dispute with Hart "of a wholly novel kind" because, though Austin would agree with Hart, Hart does not agree with Austin.3 My central thesis is that categories of law that, it is often argued, do not fit the gunman theory are either necessary to the exercise of law under that theory or are parasitic upon it. Those that are necessary are necessary for essentially either formal or strategic reasons. For example, laws that em power judges to act are formally necessary. Laws such as those under which judges declare contracts and other promises null are generally required for strategic reasons: they are necessary for giving judges and other actors under the law a clear sense of when the law applies and when it does not. One way to put the case for Austin is to say that his theory is motivated by concern with explanation of how the law works. Therefore he writes of the "province of jurisprudence." Hart's later concern is with definition. Therefore he writes of the "concept of law." Since Austin does not explicit ly avow his purpose as one of giving an explanatory theory, one may sup pose that I tendentiously wish to do something with his project that is not his purpose. But I think that an effort to see how Austin's categories are related to distinctions that fit his apparent explanation of how the law works clarifies Hart's debate with him and suggests that much of the debate is a matter of definitional quibbles that do not cut to the central features of Austin's theory. In particular, in an explanatory theory we would need to be centrally concerned with the strategic nature of many aspects of the law. It is a striking feature of Austin's work that he seems generally alert to
Orthomnion wui (Mniaceae, Musci), a new species from Hubei Province, China

A new moss species, Orthomnion wui T.J. Kop. (Mniaceae) is described. It differs from its morphologically nearest relative O. yunnanense T.J. Kop., X.J. Li & M. Zang in being synoicous and lacking decurrent leaf bases, and from most of the other congeners by its stereidal cells in costa and serrate leaf margin. It is known only from the type specimens collected in the Hubei Province of China.
Seed set and seed mass in Ipomopsis aggregata: variance partitioning and inferences about postpollination selection.

Events that follow pollination, such as pollen-tube growth and seed maturation, comprise an important phase of angiosperm reproduction. Differential success during this "postpollination" phase may represent phenotypic selection, including sexual selection, or interaction between parents caused, for example, by their genetic similarity. By providing a detailed partitioning of variance in success, diallel crossing designs offer great potential to determine which processes are occurring and their relative magnitudes. We performed three partial diallels with the montane herb Ipomopsis aggregata, using a large sample of parental plants (69 total). Embedded in the designs were crossing-distance treatments of 1 m, 10 m, and 100 m, reflecting a range of parental genetic similarity. We partitioned phenotypic variance in seed set per fruit into six components using restricted maximum-likelihood (REML) analysis. For one diallel, we also partitioned variance in seed mass into five components, and estimated two components of covariance between seed set and mass. Variance caused by maternal effects (Vmat ) comprised 12%-35% of total variance in seed set and 62% of variance in seed mass, and there was a significant negative environmental covariance between seed set and seed mass. Parental interaction made no detectable contribution to phenotypic variance in either of our measures of postpollination success, although crossing distance did contribute slightly but significantly to fit of the model in some cases. Finally, there was no detectable paternal variance (Vpat ) in seed set or seed mass. These results are in keeping with reports from other studies of natural plant populations. The finding of little or no paternal variance in particular suggests little scope for postpollination sexual selection through the male function of cosexual plants such as I. aggregata.
Abstract 4782: The NEDD8-activating enzyme inhibitor, MLN4924, cooperates with TRAIL to augment apoptosis through JNK-dependent downregulation of c-FLIP in head and neck cancer cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a tumor-selective cytokines with potential anticancer activity and is currently being tested in clinical trials. Like other types of cancers, head and neck squamous cell carcinoma (HNSCC) cells posses varied sensitivity to TRAIL. MLN4924 is a newly developed small molecule inhibitor of NEDD8-activating enzyme with potent anticancer activity. Elevated NEDD8 conjugation has been reported in HNSCC cells. However, the effects of MLN4924 on the growth of HNSCC cells and on TRAIL-induced apoptosis in HNSCC cells have not been evaluated. In this study, we showed that MLN4924 effectively inhibited the growth of HNSCC cells (IC50s < 0.4 μM) with potent apoptosis-inducing activity. Moreover, MLN4924 synergized with TRAIL to decrease the survival and to induce apoptosis of HNSCC cells. Interestingly, MLN4924 decreased c-FLIP levels with minimal effects on DR4 and DR5 expression. Enforced expression of c-FLIP substantially attenuated MLN4924/TRAIL-induced apoptosis. These data indicate that c-FLIP reduction plays an important role in mediating cooperative induction of apoptosis by the MLN4924 and TRAIL combination. Furthermore we found that MLN4924 decreased c-FLIP stability, increased c-FLIP ubiqutination and facilitated c-FLIP degradation, suggesting that MLN4924 decreases c-FLIP levels through promoting its degradation via an ubiqutination and proteasome-dependent mechanism. Additionally, MLN4924 potently activated JNK signaling evidenced by increased levels of phospho-c-Jun in MLN4924-treated cells. Blockage of the JNK activation with the JNK inhibitor SP600125 not only prevented MLN4924-induced c-FLIP reduction, but also inhibited MLN4924/TRAIL-induced apoptosis. These results suggest that JNK activation mediates c-FLIP downregulation and subsequent enhancement of TRAIL-induced apoptosis induced by MLN4924. Our findings thus warrant further evaluation of the efficacy of MLN4924 or its combination with TRAIL against the HNSCC in vivo and highlight a novel mechanism by which MLN4924 modulates apoptosis. (This study was supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award, Department of Defense VITAL W81XWH-04-1-0142 and NIH/NCI Head and Neck Cancer SPORE CA128613 awards. FR Khuri and SY Sun are Georgia Cancer Coalition Distinguished Cancer Scholars) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4782. doi:10.1158/1538-7445.AM2011-4782
Diurnal Nectar-Feeding of Salt Marsh Tabanidae (Diptera)

Chrysops fuliginosus Wiedemann adults visited Rosa palustris Marsh. and Achillea millefolium L. flowers primarily during the morning (0700–1100 h), but following a mid-day lull in their attraction to these plants, a small number of males and females resumed feeding on flowers between 1800 and 2000 h. Chrysops atlanticus Pechuman adults were sighted on these nectar sources sporadically throughout the diurnal period. Anthrone tests showed that C. fuliginosus , C. atlanticus and Tabanus nigrovittatus Macquart females contained fructose throughout daylight h. Thin-layer chromatography detected glucose alone or a combination of glucose and fructose in more than 90% of the deer flies tested, whereas a mixture of glucose, fructose, and sucrose was found in 51.6% of the T. nigrovittatus females analyzed. Compositae, Rosaceae, Gramineae, Acer, Quercus , and/or Salix pollen grains were recovered from digestive tracts in 28% of the 150 flies examined. The presence of common nectar sugars and pollen grains in tabanids suggests an important association between these salt marsh insects and host plants. In addition to carbohydrates, proteins and amino acids (derived from pollen and nectar) may be important dietary components for adults.
Determining formaldehyde in beer by AHMT-spectrophotometry

Objective: To establish a determination method of formaldehyde in beer by spectrophotometry.Methods:In the alkaline condition,formaldehyde in beer reacted with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole(AHMT) to purplish red compound 6-mercapto-S-triazole-S-tetrazole,which could be measured at wavelength 550 nm by spectrophotometry.Results:The linearity ranged between 0.02~0.60 mg/L.The recovery rate 95%~105%.Conclusion:The method is rapid,exact and reliable.So it adapts to determining formaldehyde content in beer.
Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis.

The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-methoxy-2,3,4,13-tetrahydro-1H-indolo[2′,3′:3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. P18 treatment results in downregulation of mesenchymal markers and concurrent upregulation of epithelial markers as well as inhibition of migration and invasion. Experimental epithelial–mesenchymal-transition (EMT) induced by exposure to TGFβ/TNFα is also completely reversed by P18. Importantly, P18 also inhibits mammosphere-formation along with a reduction in the expression of stemness factors, Oct4, Nanog and Sox2. We show that P18 induces expression, phosphorylation and accumulation of p53 in cancer cells. P18-mediated induction of p53 leads to increased nuclear localization and elevated expression of p53 target genes. Using isogenic cancer cells differing only in p53 status, we show that p53 plays an important role in P18-mediated alteration of mesenchymal and epithelial genes, inhibition of migration and invasion of cancer cells. Furthermore, P18 increases miR-34a expression in p53-dependent manner and miR-34a is integral for P18-mediated inhibition of growth, invasion and mammosphere-formation. miR-34a mimics potentiate P18 efficacy while miR-34a antagomirs antagonize P18. Collectively, these data provide evidence that P18 may represent a promising therapeutic strategy for the inhibition of growth and progression of breast cancer and p53-miR-34a axis is important for P18 function.
Biomass Hydropyrolysis in a Fluidized Bed Reactor

Catalytic hydropyrolysis of loblolly pine was studied in a high-pressure fluidized bed reactor using a NiMo hydrotreating catalyst. Hydropyrolysis temperature (375–475 °C) influenced the product distribution, product composition, H2 consumption, and process carbon efficiency. The material balances ranged from 84% to 106% with an average of 91%. The organic liquid yields including C4–C6 gases ranged from 20 wt % to 24 wt %, and the gas yields were between 11 and 27 wt %. The yield of the solids varied from 8 wt % to 26 wt %. Catalyst stability was studied at 450 °C and 20.68 bar (300 psig) total pressure with 40 vol % H2 for 10 days. The organic liquid product yield (22.5 ± 1.35 wt %) and quality (2.8 ± 1 wt % O) were consistent over 10 days of experiments with the same catalyst exposed to daily hydropyrolysis, regeneration, and reduction cycles indicating stable and steady-state catalyst performance over this time period.
Mechanical properties of calcium-substituted yttrium chromite

The interconnect in a solid oxide fuel cell (SOFC) is an electrical conductor that connects the individual cells in series. Therefore, the interconnect must be able to operate at high temperatures (800 to 1000 8C) in a large chemical potential gradient resulting from air (P(O2) 0:2 atm) on the cathode side and fuel, typically reformed natural gas (P(O2) 10 ˇ16 atm), on the anode surface. Due to the large chemical potential gradient, the interconnect must meet stringent electrical, environmental and thermo-mechanical requirements, and all properties must be stable in both reducing and oxidizing environments. Currently, only acceptor (calcium and strontium)substituted lanthanum and calcium-substituted yttrium chromite function adequately under these operating conditions, with lanthanum chromite receiving most of the attention as a potential
Reconceptualizing Organizational Support and its Effect on Information Technology Usage: Evidence from the Health Care Sector

This study examines the role of organizational support in motivating organizational members' usage of information technology (IT). We postulate two organizational support factors, namely infrastruc...
The Empirical Character of Evidence

We philosophers of science have long debated the issue of what counts as evidence for a scientific theory or hypothesis. Today there is as much disagreement as ever. We argue about whether evidence or confirmation should be understood by reference to probability, whether it is quantitative, whether it is inductive, hypothetico-deductive, or neither, whether predictions of new phenomena provide stronger evidence than explanations of old one, whether there are universal standards of evidence or whether such standards vary from one person or community to the next, and even over whether scientists believe hypotheses on the basis of evidence or solely because of interactions with peers.
Weibull analysis and area scaling for infrared windows

This tutorial paper explains the maximum likelihood method for Weibull analysis of mechanical strength of ceramic materials and how strength scales with area under stress. Weibull parameters for a variety of infrared window materials are presented. Calculation of the Weibull static probability of survival is illustrated.