cssi/SciSciGPT-SciSciNet huggingface dataset:
Differential expression of microRNAs in Francisella tularensis-infected human macrophages: miR-155-dependent downregulation of MyD88 inhibits the inflammatory response.

Francisella tularensis is a Gram-negative, facultative intracellular pathogen that replicates in the cytosol of macrophages and is the causative agent of the potentially fatal disease tularemia. A characteristic feature of F. tularensis is its limited proinflammatory capacity, but the mechanisms that underlie the diminished host response to this organism are only partially defined. Recently, microRNAs have emerged as important regulators of immunity and inflammation. In the present study we investigated the microRNA response of primary human monocyte-derived macrophages (MDMs) to F. tularensis and identified 10 microRNAs that were significantly differentially expressed after infection with the live vaccine strain (LVS), as judged by Taqman Low Density Array profiling. Among the microRNAs identified, miR-155 is of particular interest as its established direct targets include components of the Toll-like receptor (TLR) pathway, which is essential for innate defense and proinflammatory cytokine production. Additional studies demonstrated that miR-155 acted by translational repression to downregulate the TLR adapter protein MyD88 and the inositol 5′-phosphatase SHIP-1 in MDMs infected with F. tularensis LVS or the fully virulent strain Schu S4. Kinetic analyses indicated that miR-155 increased progressively 3-18 hours after infection with LVS or Schu S4, and target proteins disappeared after 12–18 hours. Dynamic modulation of MyD88 and SHIP-1 was confirmed using specific pre-miRs and anti-miRs to increase and decrease miR-155 levels, respectively. Of note, miR-155 did not contribute to the attenuated cytokine response triggered by F. tularensis phagocytosis. Instead, this microRNA was required for the ability of LVS-infected cells to inhibit endotoxin-stimulated TNFα secretion 18–24 hours after infection. Thus, our data are consistent with the ability of miR-155 to act as a global negative regulator of the inflammatory response in F. tularensis-infected human macrophages.
Management of the non-toxic-appearing acutely febrile child: a 21st century approach.

Although it is clear that controversy remains about how best to manage the acutely febrile child, there are several areas about which most can agree. Infants ≤60 days of age continue to have the highest rates of SBI and pose a challenge to practitioners when determining how extensive an evaluation to perform in a non-toxic-appearing child. Urinary tract infections are the most common SBIs in all age groups. It is our opinion that assessment for UTI should be part of any evaluation for all but the lowest risk patients (circumcised boys). Technologies that can more rapidly diagnose common viral and bacterial infections and recommendations that simplify the management of these febrile infants and children are needed.
On the algebraic geometry of the output feedback pole placement map

In this paper we study the question of pole placement by output feedback. Our approach makes use of the idea that a transfer function can be thought of as a curve in a Grassmannian manifold and the pole placement problem is that of finding a special hypersurface in this manifold (defined by the gain matrix) which intersects the given curve at a prescribed set of points. This is a classical inverse problem in algebraic geometry and, fortunately, near 100 years ago Hermann Schubert considered some enumerative aspects of such problems in connection with his development of a topic in algebraic geometry now known as the Schubert calculus. In this paper we use results in this area to show, for example, that in the case where the number of output feedback gains available (i.e. the product the number of inputs m with the number of outputs p equals the number of poles of the system) there are generically ?(m, p) = 1!2!...(p-1)!1!2!...(m-1)!(mp)!/1!2!...(m+p-1)! different (in general complex) gains which yield the same set of poles. This, rather unexpectedly large number emphasizes the nonlinear nature of the pole placement problem and suggests that it is probably rather difficult to solve algorithmically. It turns out that ?(m,p) is odd if and only if either min(m,p)=1 or min(m,p)=2 and max(m,p)=2k-1 and in these cases we are able to show that typically there exists at least one real solution to the pole placement problem.
Modulation of heme/substrate binding cleft of neuronal nitric-oxide synthase (nNOS) regulates binding of Hsp90 and Hsp70 proteins and nNOS ubiquitination

Like other nitric-oxide synthase (NOS) enzymes, neuronal NOS (nNOS) turnover and activity are regulated by the Hsp90/Hsp70-based chaperone machinery, which regulates signaling proteins by modulating ligand binding clefts (Pratt, W. B., Morishima, Y., and Osawa, Y. (2008) J. Biol. Chem. 283, 22885–22889). We have previously shown that nNOS turnover is due to Hsp70/CHIP-dependent ubiquitination and proteasomal degradation. In this work, we use an intracellular cross-linking approach to study both chaperone binding and nNOS ubiquitination in intact HEK293 cells. Treatment of cells with NG-nitro-l-arginine, a slowly reversible competitive inhibitor that stabilizes nNOS, decreases both nNOS ubiquitination and binding of Hsp90, Hsp70, and CHIP. Treatment with the calcium ionophore A23187, which increases Ca2+-calmodulin binding to nNOS, increases nNOS ubiquitination and binding of Hsp90, Hsp70, and CHIP in a manner that is specific for changes in the heme/substrate binding cleft. Both Hsp90 and Hsp70 are bound to the expressed nNOS oxygenase domain, which contains the heme/substrate binding cleft, but not to the reductase domain, and binding is increased to an expressed fragment containing both the oxygenase domain and the calmodulin binding site. Overexpression of Hsp70 promotes nNOS ubiquitination and decreases nNOS protein, and overexpression of Hsp90 inhibits nNOS ubiquitination and increases nNOS protein, showing the opposing effects of the two chaperones as they participate in nNOS quality control in the cell. These observations support the notion that changes in the state of the heme/substrate binding cleft affect chaperone binding and thus nNOS ubiquitination.
Regulation of cytoplasmic polyadenylation can generate a bistable switch

Translation efficiency of certain mRNAs can be regulated through a cytoplasmic polyadenylation process at the pre-initiation phase. A translational regulator controls the polyadenylation process and this regulation depends on its posttranslational modifications e.g., phosphorylation. The cytoplasmic polyadenylation binding protein (CPEB1) is one such translational regulator, which regulates the translation of some mRNAs by binding to the cytoplasmic polyadenylation element (CPE). The cytoplasmic polyadenylation process can be turned on or off by the phosphorylation or dephosphorylation state of CPEB1. A specific example could be the regulation of Calcium/Calmodulin-dependent protein kinase II (αCaMKII) translation through the phosphorylation/dephosphorylation cycle of CPEB1. Here, we show that CPEB1 mediated polyadenylation of αCaMKII mRNA can result in a bistable switching mechanism. The switch for regulating the polyadenylation is based on a two state model of αCaMKII and its interaction with CPEB1. Based on elementary biochemical kinetics a high dimensional system of non-linear ordinary differential equations can describe the dynamic characteristics of the polyadenylation loop. Here, we simplified this high-dimensional system into approximate lower dimension system that can provide the understanding of dynamics and fixed points of original system. These simplified equations can be used to develop analytical bifurcation diagrams without the use of complex numerical tracking algorithm, and can further give us intuition about the parameter dependence of bistability in this system. This study provides a systematic method to simplify, approximate and analyze a translation/activation based positive feedback loop. This work shows how to extract low dimensional systems that can be used to obtain analytical solutions for the fixed points of the system and to describe the dynamics of the system. The methods used here have general applicability to the formulation and analysis of many molecular networks.
Contamination of Broilers with Chlordane and Pyrethrum

ABSTRACT Some insecticides cause off-flavors in broilers, fowl, capons and turkeys. Recently, several ready-to-cook, frozen, capons, turkeys and fryers were sent to A. and M. College with the complaint that the carcasses had a definite off-flavor. The possibility that the birds had become contaminated during processing was eliminated when complaints were also reported for birds processed in other plants. The birds were raised on a number of different farms. The contaminant imparted a strong, characteristic flavor to the meat. All birds which had the off-flavor, had been confined about one week prior to slaughter in wire judging coops with pine shavings for litter. The litter under the coops in which the birds were held during this period was periodically sprayed with sweet grass oil, a compound designed to keep down odors. Open containers filled with fly flakes, a compound with an obnoxious odor, were located at strategic spots for fly control . . .
Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD)

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.
Perforation of the common bile duct during endoscopic sphincterotomy: Recognition on computed tomography and successful percutaneous treatment

Retroperitoneal common bile duct (CBD) perforation is a rare complication of endoscopic retrograde cholangiopancreatography (ERCP). We describe such a case with delayed diagnosis made by computed tomography (CT) and successful percutaneous management of the injury.
Novel DNA polymerases offer clues to the molecular basis of mutagenesis.

An examination of available databases indicates the existence of an extended family of DinB-related proteins. These include E. coli UmuC, yeast Rev1, C. elegans F22B7.6, yeast Rad30, and the two human Rad30 homologs mentioned above. Additionally, mouse and human homologs of the E. coli dinB gene have been cloned (Gerlach et al. 1999xGerlach, V.L, Aravind, L, Gotway, G, Schultz, R.A, Koonin, E.V, and Friedberg, E.C. Proc. Natl. Acad. Sci. USA. 1999; in pressSee all ReferencesGerlach et al. 1999). All members of this superfamily share motifs with the known DNA polymerases Rad30 and DinB. These motifs contain invariant negatively charged residues that are likely involved in nucleotide polymerization, suggesting that DNA polymerase activity is common to the entire superfamily (Gerlach et al. 1999xGerlach, V.L, Aravind, L, Gotway, G, Schultz, R.A, Koonin, E.V, and Friedberg, E.C. Proc. Natl. Acad. Sci. USA. 1999; in pressSee all ReferencesGerlach et al. 1999).Clearly additional biochemical characterization lies ahead to identify similarities and differences among this class of enzymes and their role(s) in mutagenesis during replication of damaged and undamaged DNA. It will be particularly interesting to determine if different polymerases are selected to negotiate specific types of base damage in template DNA, and if so, how this selectivity is achieved to result in error-free or error-prone replication. Additionally, it will be important to address whether these polymerases operate in strict isolation, or participate in recruitment of the displaced replication machinery to the replication fork to allow continuation of normal DNA synthesis. Finally, do specialized polymerases such as pol η have absolute specificity for thymine–thymine dimers in template DNA? If so are cytosine–thymine, thymine–cytosine, and cytosine–cytosine dimers in DNA subject to error-free replicative bypass by other DNA polymerases, or must they be removed by DNA repair to avoid permanent replicative arrest? Based on the recent rapid strides in our understanding of the molecular basis of mutagenesis, one can optimistically look forward to the emergence of definitive answers to these questions in the near future.*To whom correspondence should be addressed (e-mail: friedberg.errol@pathology.swmed.edu).
Rigor crossbridge structure in tilted single filament layers and flared-X formations from insect flight muscle☆

The averaged structure of rigor crossbridges in insect flight muscle has been studied in filtered images. Their three-dimensional structure has been deduced by relating tilt views of single filament layers in 25 nm longitudinal sections (myac layers and actin layers) to the flared-X appearance in 15 nm cross-sections showing single crossbridge levels. Tilting myac or actin layers around the filament axis makes crossbridges show one of two patterns. Beadlike densities appear either singly over thin filaments ("center-beading") or doubled and flanking thin filaments ("straddle-beading"). These express two different projections from the crossbridge-actin complexes as seen end-on in flared-X formations. Tannic acid/glutaraldehyde fixation gave improved actin preservation, showing, in 15 nm cross-sections, the long-pitch helical strands as "two-dot" profiles of consistent azimuth in the gaps between double chevrons. The azimuth in the flared-X arms was then inferred from lattice relationships, since it was not seen directly. The tangential attachment of comma-shaped crossbridges to the inferred actin dyad fits the binding geometry in recent actin-subfragment 1 complex reconstructions. However, averaged crossbridge structure differs between lead and rear members of double chevrons, unlike the uniform heads on decorated actin. In filtered images of myac layers, the lead bridges are dense and steeply angled; the rear chevron is seen as a dense bead over the thin filament with faint, less angled bars extending laterally. Actin layer images also suggest that rear and lead bridges differ in angle. Left and right flared-X arms are end-on views of lead and rear chevron bridges, respectively, and differ in shape. Improved fixation with tannic acid/glutaraldehyde allows us to distinguish three crossbridge domains in flared-X arms: (1) a dense bulb-like head merged into the thin filament; (2) a dense but thinner neck tangential to actin; and (3) a faint thin stem joining the necks to myosin filaments. Shape differences in lead and rear members between the head-neck-actin complexes are indicated by the names "L sigmoid" and "R dogleg". Within crossbridges, internal angles between the head-neck axis and the head-actin-head axis differ between sigmoid and dogleg by about 30 degrees, implying a flexible junction between bridge-head and bridge-neck. Lead and rear bridges are axially at least 13 nm apart on actin; the expected 60 degrees difference in azimuth is expressed by head-neck portions, but the head-actin-head axis rotates by only 30 degrees.(ABSTRACT TRUNCATED AT 400 WORDS)
Frame representations and Parseval duals with applications to Gabor frames

Let {x n } be a frame for a Hilbert space H. We investigate the conditions under which there exists a dual frame for {x n } which is also a Parseval (or tight) frame. We show that the existence of a Parseval dual is equivalent to the problem whether (x n ) can be dilated to an orthonormal basis (under an oblique projection). A necessary and sufficient condition for the existence of Parseval duals is obtained in terms of the frame excess. For a frame {π(g)ξ: g ∈ G} induced by a projective unitary representation π of a group G, it is possible that {π(g)ξ: g ∈ G} can have a Parseval dual, but does not have a Parseval dual of the same type. The primary aim of this paper is to present a complete characterization for all the projective unitary representations π such that every frame {π(g)ξ:g ∈ G} (with a necessary lower frame bound condition) has a Parseval dual of the same type. As an application of this characterization together with a result about lattice tiling, we prove that every Gabor frame G(g, L, K) (again with the same necessary lower frame bound condition) has a Parseval dual of the same type if and only if the volume of the fundamental domain of L × K is less than or equal to 1/2.
Cancer-related bone pain is attenuated by a systemically available δ-opioid receptor agonist

Patients with bone cancer report severe pain and receive mu-opioids. We developed a family of peptidomimetic delta-agonists, one of which H2N-Tyr-dVal-Gly-Phe-Ala-OH ([dVal(L)2,Ala(L)5]E) binds with a 1700x affinity at the delta versus mu receptor. To examine the systemic analgesic efficacy of this delta-agonist versus morphine in osteosarcoma pain, osteosarcoma cells are injected into one femur of the anesthetized mouse. After 10-18 days, a decalcification of the injected femur occurs along with a pronounced tactile allodynia. IP morphine and [dVal(L)2,Ala(L)5]E produced a dose-dependent reversal of allodynia with the respective ED50 values being 5.3+/-1.9 mg/kg for morphine and 1.3+/-0.3 mg/kg for [dVal(L)2,Ala(L)5]E. Plotting peak effect versus area under the analgesic curve for doses of morphine and [dVal(L)2,Ala(L)5]E revealed overlapping curves suggesting that for a given effect, [dVal(L)2,Ala(L)5]E produced a similar duration of action as morphine. These effects were reversed by IP naloxone (3 mg/kg). IP naltrindole (1 mg/kg) preferentially reversed [dVal(L)2,Ala(L)5]E. The upper dose effects of morphine but not [dVal(L)2,Ala(L)5]E were limited by pronounced hyperactivity. No other effects were noted. These results show that IP [dVal(L)2,Ala(L)5]E through a delta receptor produces analgesia equal in efficacy to that of morphine but with a 4.5-fold greater potency. Over the doses examined, morphine actions were side effect limited. The delta side effects were not so limited, suggesting a favorable therapeutic ratio for delta-agonists in this pain model. These studies suggest that a systemically delivered delta-opioid agonist has pronounced analgesic properties on a preclinical cancer pain model.
Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens

Staphylococcus aureus and group A Streptococcus secrete a collection of toxins called superantigens (SAgs), so-called because they stimulate a large fraction of an individual's T cells. One consequence of this hyperactivity is massive cytokine release leading to severe tissue inflammation and, in some cases, systemic organ failure and death. The molecular basis of action involves the binding of the SAg to both a T cell receptor (TCR) on a T cell and a class II product of the major histocompatibility complex (MHC) on an antigen presenting cell. This cross-linking leads to aggregation of the TCR complex and signaling. A common feature of SAgs is that they bind with relatively low affinity to the variable region (V) of the beta chain of the TCR. Despite this low affinity binding, SAgs are very potent, as each T cell requires only a small fraction of their receptors to be bound in order to trigger cytokine release. To develop high-affinity agents that could neutralize the activity of SAgs, and facilitate the development of detection assays, soluble forms of the Vβ regions have been engineered to affinities that are up to 3 million-fold higher for the SAg. Over the past decade, six different Vβ regions against SAgs from S. aureus (SEA, SEB, SEC3, TSST-1) or S. pyogenes (SpeA and SpeC) have been engineered for high-affinity using yeast display and directed evolution. Here we review the engineering of these high-affinity Vβ proteins, structural features of the six different SAgs and the Vβ proteins, and the specific properties of the engineered Vβ regions that confer high-affinity and specificity for their SAg ligands.
Successful treatment of methicillin‐resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic fibrosis

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of pulmonary infection in patients with cystic fibrosis (CF). Because these organisms are frequently multidrug-resistant, most patients require intravenous therapy with vancomycin. We report on the first case of successful treatment of a pulmonary exacerbation due to MRSA in a CF patient with a new antimicrobial, linezolid. We demonstrated equivalence of intravenous and oral dosing in this patient, suggesting that oral linezolid may be an excellent alternative to intravenous vancomycin for CF patients infected with MRSA. Pediatr Pulmonol. 2002; 33:221–223. © 2002 Wiley-Liss, Inc.
Magnetic properties of superconducting K3C60 and Rb3C60 synthesized from large single-crystal fullerenes.

Single crystals of ${\mathrm{C}}_{60}$ were doped with alkali metal (K and Rb), characterized, and measured magnetically in fields up to 5 T. Detailed experiments show the samples to be of high quality with superconducting transition widths on the order of 1 K. Data on the field and temperature dependences of the critical current density ${J}_{C}$ and ${H}_{C1}$ are presented. We find that while the general behavior is similar to that of powder specimens, there are significant differences when comparing magnitudes. We attribute these differences to the fact that powder samples have much more surface area per volume than single crystals which can affect the determination of superconducting parameters. The critical current density also shows clear differences when compared to polycrystalline samples. In addition, comparisons between ${\mathrm{K}}_{3}$${\mathrm{C}}_{60}$ and ${\mathrm{Rb}}_{3}$${\mathrm{C}}_{60}$ indicate that defects may be more prevalent in the latter compound due to more sensitive synthesis requirements.
The FOSSology project

By its nature, the availability of FOSS has given computer scientists a large body of software and software projects to analyze. By having available source, version control system metadata, and open project communities, much can be learned about a software project, software development and collaborative project development. The goal of the FOSSology project is to create a public, open source software repository, together with tools to facilitate analysis, storage, and sharing of open source software and its metadata. FOSSology does license detection today.
PUQ: A code for non-intrusive uncertainty propagation in computer simulations

Abstract We present a software package for the non-intrusive propagation of uncertainties in input parameters through computer simulation codes or mathematical models and associated analysis; we demonstrate its use to drive micromechanical simulations using a phase field approach to dislocation dynamics. The PRISM uncertainty quantification framework (PUQ) offers several methods to sample the distribution of input variables and to obtain surrogate models (or response functions) that relate the uncertain inputs with the quantities of interest (QoIs); the surrogate models are ultimately used to propagate uncertainties. PUQ requires minimal changes in the simulation code, just those required to annotate the QoI(s) for its analysis. Collocation methods include Monte Carlo, Latin Hypercube and Smolyak sparse grids and surrogate models can be obtained in terms of radial basis functions and via generalized polynomial chaos. PUQ uses the method of elementary effects for sensitivity analysis in Smolyak runs. The code is available for download and also available for cloud computing in nanoHUB. PUQ orchestrates runs of the nanoPLASTICITY tool at nanoHUB where users can propagate uncertainties in dislocation dynamics simulations using simply a web browser, without downloading or installing any software. Program summary Program title: PUQ Catalogue identifier: AEWP_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEWP_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: MIT license No. of lines in distributed program, including test data, etc.: 45075 No. of bytes in distributed program, including test data, etc.: 3318862 Distribution format: tar.gz Programming language: Python, C. Computer: Workstations. Operating system: Linux, Mac OSX. Classification: 4.11, 4.12, 4.13. External routines: SciPy, Matplotlib, h5py Nature of problem: Uncertainty propagation and creation of response surfaces. Solution method: Generalized Polynomial Chaos (gPC) using Smolyak sparse grids. Running time: PUQ performs uncertainty quantification and sensitivity analysis by running a simulation multiple times using different values for input parameters. Its run time will be the product of the run time of the chosen simulation code and the number of runs required to achieve the desired accuracy.
Organic thin-film transistors of pentacene films fabricated from a supersonic molecular beam source

Top-contact organic thin-film transistors (OTFTs) of pentacene have been fabricated on bare SiO2 and SiO2 modified with hexamethyldisilazane (HMDS) and octadecyltrichlorosilane (OTS). The pentacene films were deposited from a supersonic molecular beam source with kinetic energy of incident molecules ranging from 1.5 to 6.7 eV. The field-effect mobility of OTFTs was found to increase systematically with increasing kinetic energy of the molecular beam. The improvements are more important on HMDS- and OTS-treated surfaces than on bare SiO2. Tapping mode atomic force microscopy images reveal that pentacene thin films deposited at high kinetic energy form with significantly larger grains—independent of surface treatment—than films deposited using low-energy beams.
Who cares about development outcomes? : market failures and the role of the evaluation function

Development agencies expend large amounts of money and manpower ostensibly to achieve development outcomes that improve living conditions in developing countries. If development agencies cared only about development outcomes and these were easily observable in a timely manner, development agencies would ‘buy’ the best outcomes they could get for their money. And if someone else could get it for them at a lower cost, they would transfer the funds to this other agency. Unfortunately, outcomes are not easily observable, they often take years to appear, and frequently the ‘shopper’ cares more about being seen shopping than about what ends up in the cart. So how do we go about creating a functioning market for development outcomes? What role can the evaluation function play in helping the process of internalising development outcomes into the development agencies’ objective functions and thereby aligning incentives with the ultimate goal of improving lives? We present the development business through the lense...
Towards Data and Sensor Planning Service for Coupling Earth Science Models and Earth Observations

How to obtain sensor observation data easily and quickly is one of the challenging research areas in the Earth science community. Data and Sensor Planning Service aims to generate requirements on Earth observations data from which the geophysical products needed by Earth science models can derive. Then, the service discovers relevant data sources which meet these requirements, schedules data acquisition by ordering and retrieving data from these sources, and processes and returns the customized data which will be used in the Earth science models. In this general framework, Sensor Web Enablement specifications of Open Geospatial Consortium are implemented and integrated with other open Web geospatial data services seamlessly to access real or virtual Earth observation sensors. Additionally, an Ajax-enabled browser client is built to facilitate the standard sensor Web operations, user account management along with data acquisition. The prototype system is demonstrated to retrieve near real-time satellite observation data from Comprehensive Large Array-data Stewardship System through standard Web services, and also is applied in the bird migration model which uses climate data, vegetation data, as well as other remotely sensed and in-situ observation data to determine the bird migration routes and identify the possible resting areas.
Central nervous system and peripheral nerve growth factor provide trophic support critical to mature sensory neuronal survival

Primary sensory neurones in cranial and dorsal root ganglia (DRG) of adult animals are generally thought to be maintained through connections with their peripheral (but not central) targets by trophic factor(s) other than nerve growth factor (NGF). Damage to the peripheral process of sensory neurones results in a dramatic response or even death of the neurones, whereas axotomy (cutting) of the central process does not initiate profound reaction in these neurones. The development and maintenance of neurones are highly dependent on a supply of trophic agents produced by targets and retrogradely transported via the peripheral process to the cell body. NGF deprivation in fetal rodents produced either by exogenously administered antibodies or by those of maternal origin, results in death of DRG and of some cranial sensory neurones. However, as chronic NGF deprivation in neonatal or adult rodents produces little or no cell death, it has been assumed that some other trophic factor(s) derived from the peripheral target sustains sensory neurones in postnatal life. By inducing NGF deprivation by autoimmunizing guinea pigs with mouse NGF and/or by cutting the central root (process) of a DRG, we demonstrate here that under certain conditions DRG neurones require NGF and centrally derived trophic support. Our results indicate that sensory neurones are maintained by the trophic support provided by both peripheral and central targets. This support is mediated by NGF and other as yet unidentified trophic factors. The relative importance of the two target fields and NGF compared with other trophic factors changes during development.
Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 by menthofuran, β-nicotyrine and menthol

Nicotine is the primary addictive agent in tobacco products and is metabolized in humans by CYP2A6. Decreased CYP2A6 activity has been associated with decreased smoking. The extrahepatic enzyme, CYP2A13 (94% identical to CYP2A6) also catalyzes the metabolism of nicotine, but is most noted for its role in the metabolic activation of the tobacco specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, the inhibition and potential inactivation of CYP2A6 and CYP2A13 by two tobacco constituents, 1-methyl-4-(3-pyridinyl) pyrrole (β-nicotyrine) and (-)-menthol were characterized and compared to the potent mechanism based inactivator of CYP2A6, menthofuran. The effect of these compounds on CYP2A6 and CYP2A13 activity was significantly different. (-)-Menthol was a more efficient inhibitor of CYP2A13 than of CYP2A6 (KI, 8.2 μM and 110 μM, respectively). β-Nicotyrine was a potent inhibitor of CYP2A13 (KI, 0.17 μM). Neither menthol nor β-nicotyrine was an inactivator of CYP2A13. Whereas, β-nicotyrine was a mechanism based inactivator of CYP2A6 (KI(inact), 106 μM, kinact was 0.61 min(-1)). Similarly, menthofuran, a potent mechanism based inactivator of CYP2A6 did not inactivate CYP2A13. Menthofuran was an inhibitor of CYPA13 (KI, 1.24 μM). The inactivation of CYP2A6 by either β-nicotyrine or menthofuran was not due to modification of the heme and was likely due to modification of the apo-protein. These studies suggest that β-nicotyrine, but not menthol may influence nicotine and NNK metabolism in smokers.
Energy loss of slow, highly charged ions in solids

The loss of kinetic energy of highly charged, heavy ions (Ar{sup 18+}, Xe{sup 44+}, and Au{sup 69+}) in thin carbon foils has been measured as a function projectile velocity in the range from 6{times}10{sup 5} to 11{times}10{sup 5}m/s. Evidence for strong pre-equilibrium energy-loss enhancements is observed for highly charged xenon and gold ions. {copyright} {ital 1997} {ital The American Physical Society}
Mibefradil: A New Selective T-Channel Calcium Antagonist for Hypertension and Angina Pectoris.

Calcium antagonists are an established therapy for patients with hypertension and angina pectoris, but their current usage is often limited by their pharmacologic profiles and side effects. Mibefradil is a recently developed calcium antagonist with a unique chemical struc ture, site of action, and set of pharmacologic effects. Unlike currently available calcium antagonists, which block only L-type calcium channels, mibefradil selectively blocks T-type channels as well as L-type channels. It is further distinguished from other calcium antago nists in that it is the first member of a new class of calcium antagonists, the tetralol deriva tives. With chronic oral dosing, mibefradil attains steady-state plasma concentrations within 3-4 days, has a bioavailability of approximately 90%, and a plasma half-life of 17-25 hours. It has a gradual onset of action and can be administered once daily without regard to food intake. It increases coronary blood flow and lowers peripheral vascular resistance. The vasodilator...
Are pretreatment simulation estimates predictive of actual rectal and bladder doses delivered during radiation for prostate cancer

Materials/Methods: 15 patients (pts) with localized prostate (pros) cancer were enrolled on a pilot study. Each pt was scanned 25 times during the course of RT (once at simulation with a full bladder and empty rectum and 24/42 tmt days) for a total of 369 evaluated CTs. On each scan the bladder (bld), seminal vesicles, pros, rectum and rectal wall were contoured. An IMRT plan was generated for each pt on the initial simulation (sim) CT. This plan was then superimposed on each of the 24 treatment (tmt) CT scans. Isocentric fiducials were used to align tmt plans after which the clinically utilized BAT shift was applied. DVHs were generated for rectal anatomic volume (rav), rectal wall (rw), bld, prostate and seminal vesicles (prsv). For the purposes of this evaluation we looked in detail at 3 pts (75 CTs). The choice of pts was as follows: the pt with the largest variation in pros center of volume (COV) over the RT course, the pt with the least variation, and one with average daily pros COV change.
Fatty acid turnover rates in the adipose tissues of the growing chicken (Gallus domesticus).

The purpose of this study was to investigate the mobility of fatty acids in adipose tissue of the chicken and to determine whether adipose tissue dynamics are altered by dietary repartitioning agents. To this end, the turnover rates of fatty acids and triglycerides were estimated in adipose tissue of growing chicks by using isopentadecanoic acid (IPDA) and elaidic acid (EA) as marker dietary fatty acids. The half-life of IPDA in abdominal and sartorial adipose tissues of birds over 6 to 10 wk of age were 20±4 and 23±6 d, respectively. The half-life for the remaining total carcass lipids was 23±3 d. The corresponding half-life for EA in abdominal fat tissue of birds over 2 to 7 wk of age was 18±3 d, a half-life not significantly different from the IPDA half-lives. On the other hand, a thyromimetic repartitioning agent (L-94901) fed to birds at the 2 ppm level from 2 to 7 wk of age significantly decreased the half-life of EA in abdominal fat tissue to 6±2 d. The data suggest that fatty acids were released from a more labile adipose site and subsequently reincorporated into abdominal and sartorial tissues and that fat mobilization occurred at the same time as did adipose tissue deposition in the growing chicken.
Using Mathematical Models of the Learning Curve in Training System Design

This paper reviews and synthesizes some of the literature on the mathematical modeling of the learning curve that has been developed by many diverse technical disciplines. These disciplines include the behavioral sciences, manufacturing engineering, and accounting. The paper discusses the relationships among the models and the potential uses of the models in the design, development, and control of training systems.
A data acquisition and processing system for the ultraviolet optical ultracentrifuge.

Abstract Detector signals from the ultraviolet optical scanner of an analytical ultracentrifuge have been recorded on magnetic tape, converted to computer-compatible digital form, and processed using a digital computer program designed to compute molecular weight from sedimentation equilibrium concentration distributions. The system when tested with well characterized protein and nucleic acid solutions enabled molecular weight determinations conforming to theoretical or literature values with precision equivalent to or greater than conventional manual methods. Since the interface system electronically measures concentrations and distances from the rotational axis, and print-punches these values, it is also feasible to utilize it for sedimentation velocity analyses.
Effect of bacterial polysaccharide on artificial activation in the frog egg.

THE viscosity of dividing cells goes through definite changes, increasing during prophase, dropping abruptly at metaphase, and increasing sharply just prior to division1. These changes are believed essential for mitosis. Heilbrunn2 has pointed out many similarities between the protoplasmic gelation which precedes the appearance of the mitotic spindle and blood clotting.
Internucleotide Scalar Couplings Across Hydrogen Bonds in Watson−Crick and Hoogsteen Base Pairs of a DNA Triplex

An extensive analysis of trans-hydrogen bond 2hJNN and 1hJHN scalar couplings, the covalent 1JHN couplings, and the imino proton chemical shifts is presented for Hoogsteen−Watson−Crick T•A−T and C+•G−C triplets of an intramolecular DNA triplex. The 2hJNN coupling constants for the Watson−Crick base pairs have values ranging from 6 to 8 Hz, while the Hoogsteen base paired thymines and protonated cytidines have values of approximately 7 and 10 Hz, respectively. Distinct decreases of 2hJNN are observed at the triplex strand ends. Trans-hydrogen bond J correlations (1hJHN) between the donor 1H nucleus and the acceptor 15N nucleus are observed for this triplex by a novel, simple quantitative J-correlation experiment. These one-bond 1hJHN couplings range between 1 and 3 Hz. A strong correlation is found between the chemical shift of the imino proton and the size of 2hJNN, with stronger J couplings corresponding to downfield chemical shifts. A similar, but inverse correlation is found between the proton chemical...
Simulation for risk management: risk management of a P/C insurance company scenario generation, simulation and optimization

A large conglomerate such as a property/casualty insurance firm in this case, can be divided along business boundaries. This division might be along commercial lines, homeowner lines and perhaps across countries. An insurance firm's capital can be interpreted as a buffer that protects the company from insolvency and its inability to pay policyholder losses. Rare events have been simulated over the two divisions of an insurance firm. Different risk measures like conditional value at risk (CVaR) have been implemented into the optimization model. Decomposition methods will be applied in the context of decentralized decision making of a multi-divisional firm.
General Anosmia Caused by a Targeted Disruption of the Mouse Olfactory Cyclic Nucleotide–Gated Cation Channel

Olfactory neurons transduce the binding of odorants into membrane depolarization. Two intracellular messengers, cyclic AMP (cAMP) and inositol trisphosphate (IP3), are thought to mediate this process, with cAMP generating responses to some odorants and IP3 mediating responses to others. cAMP causes membrane depolarization by activating a cation-selective cyclic nucleotide-gated (CNG) channel. We created a mutant "knockout" mouse lacking functional olfactory CNG channels to assess the roles of different second messenger pathways in olfactory transduction. Using an electrophysiological assay, we find that excitatory responses to both cAMP- and IP3-producing odorants are undetectable in knockout mice. Our results provide direct evidence that the CNG channel subserves excitatory olfactory signal transduction, and further suggest that cAMP is the sole second messenger mediating this process.
Numerical simulation of electromagnetic wave attenuation in nonequilibrium chemically reacting flows

Abstract The effects of various gasdynamic phenomena on the attenuation of an electromagnetic (EM) wave propagating through the hypervelocity flow field generated by an aerodynamic body, are numerically investigated. The reacting flow field around a blunt wedge—consisting of nitric oxide ions, free electrons, and other species—is simulated using a computational fluid dynamics computer code. The computer code solves the Navier–Stokes equations including a nonequilibrium air kinetics model consisting of seven species and ten reactions, using a time-marching, explicit Runge–Kutta scheme. An EM wave, originating from within the wedge, is attenuated by the free electrons (plasma) in the chemically reacting flow. Attenuation analysis is performed separately (uncoupled) from the gasdynamic analysis using a series solution of Maxwell's equations valid for a long-wavelength plane wave and a thin (i.e. in comparison to wavelength) inhomogeneous plasma layer. The results of this computational study systematically demonstrate the importance of chemical kinetics, viscosity, mass diffusion and wall boundary conditions (adiabatic, isothermal, catalytic) for computer modeling of EM wave attenuation due to an aerodynamic plasma. Comparison is made with experimental data.
4,11-Epoxy-cis-eudesmane, soldier cephalic secretion of the Nearctic desert termite,Amitermes minimus Light (Termitidae: Termitinae)

The soldier cephalic secretion of the Nearctic desert termite,Amitermes minimus, consists almost entirely of 4,11-epoxy-cis-eudesmane which was previously identified from soldiers of 2 AfricanAmitermes species. Soldiers ofA. minimus each store circa 61 μg of the secretion. Bioassays with the ant,Crematogaster californica, indicate a repellent role for the eudesmane compound in termite defense.
Insulated Railroad Joint Design Evaluation by Coordinated Test and Finite Element Analysis

The railroad industry faces challenges with bonded insulated joint designs in the present practice. A program initiated by Virginia Tech and the Transportation Technology Center Incorporated (TTCI) has been in progress to analyze and test a class of insulated joint designs featuring non-adhesive bolted connections. A hierarchical approach to finite element modeling with a parametric model maintaining essential mechanics of the joints has been applied to develop a bolted insulated joint design.The current paper reports on the recent phase of the program including development of experimental tests along with finite element analyses on scaled simplified insulated rail joint models. Two baseline rail joint configurations with simplified sections were considered for studying dominant mechanics under the AREMA (American Railway Engineering and Maintenance-of-Way Association) rail joint acceptance standard test loading and boundary conditions. The finite element models developed based on three-dimensional continuum elements incorporated bolt preloads and full-contact analysis. In the experimental tests, the strain analyses on 1/4 scaled polycarbonate rail joint specimens were performed by means of an array of strain gauge transducers mounted on the joint bars and a photoelasticity technique. The results of the experimental stress analyses were employed to validate the finite element models quantitatively and qualitatively in terms of load transfer mechanics and stress distribution.The validated models serve as baseline insulated joint configurations for developing fracture-mechanics-based fatigue-failure analysis. To investigate the role of cracks on the performance and reliability of joint bars, a damage tolerant analysis is performed on the rail joints utilizing linear elastic fracture mechanics. The locations of most critical type defects are estimated based on high stress/strain regions from stress analyses along with past experiences on failure of rail joints. To characterize the severity of theses defects under alternating loading conditions, stress intensity factors are computed as a function of crack length. Cracks of different lengths are introduced in the vicinity of the most fatigue-prone locations of the joint bar in a parametric modeling fashion. The fatigue-crack-growth-rate properties in terms of Paris Law scaling constants are selected from a survey of available material data. The number of loading cycles to failure is obtained by employing the computed stress-intensity factors as well as initial and final crack sizes. Predicted lifetimes as a function of pre-existing crack sizes and geometry of joint configuration can be used as a fracture-mechanics-based function for more accurate design of the rail joints.Copyright © 2013 by ASME
Suppressed cytokine expression immediatey following traumatic brain injury in neonatal rats indicates an expeditious endogenous anti-inflammatory response

The timing of therapeutic intervention in traumatic brain injury (TBI) is critical. Although immediate cell death cascades have become established in adult TBI, the pathophysiology underlying neonatal TBI is poorly understood. The objective of the present study was to determine the role of cytokine regulation following TBI in neonatal rats. Seven-day-old Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Age-matched littermates that did not receive TBI served as the controls. Immediately following TBI, rats were euthanized, and the brains were divided into the ipsilateral and contralateral hemispheres then flash frozen. A BioRad 23-Plex panel was used to measure cytokine levels. Surprisingly, the data revealed that 18 of the 23 cytokines analyzed were significantly downregulated in the hemisphere contralateral to the TBI impacted hemisphere. IL-5, IL-6 and MIP-3a were significantly suppressed in both ipsilateral and contralateral hemispheres of neonatal TBI rats compared to the control rats. A parallel study processing the plasma of the same cohort of neonatal rats revealed no difference in the same cytokines analyzed in the brain tissue, suggesting highly localized cytokine suppression in the brain during early injury. In stark contrast to the reported early pro-inflammatory response exhibited in adult TBI, the present neonatal TBI study demonstrated a reversed cytokine profile of downregulation. These results suggest a robust, immediate anti-inflammatory response mounted by the contralateral hemisphere of the young brain.