cssi/SciSciGPT-SciSciNet huggingface dataset:
Endobronchial histoplasmosis: a masquerade of primary endobronchial neoplasia—a clinical study of four cases

Abstract Background Histoplasma capsulatum is a dimorphic fungus with both hyphal and microconidial elements and is endemic in certain areas of the central United States. Most clinically recognized syndromes are self-limited, presenting in more than 80% of cases as an influenza-like acute pulmonary illness. We encountered four patients with an endobronchial presentation of histoplasmosis masquerading as a bronchogenic malignancy. Methods The patient files from one of the authors (PR) uncovered four patients diagnosed with, and treated for, endobronchial histoplasmosis; all cases were referred for a presumptive diagnosis of endobronchial neoplasia. Results The case study group comprised three women, ages 52, 68, and 81 years, respectively, and one man age 29 years, all presenting with recurrent hemoptysis. An obstructing adherent lesion was apparent on bronchoscopy in three, involving the right upper lobe bronchus in two, and right mainstem bronchus in one. In one patient, blood was observed in the bronchus intermedius; there was no gross lesion. Recurrent hemoptysis necessitated a right upper sleeve lobectomy in one, a right upper lobe lobectomy and right lower wedge resection in one, a right middle lobectomy in one, and wedge resection of the right upper lobe in one. Conclusions Endobronchial histoplasmosis may mimic primary bronchogenic carcinoma, presenting as a fixed obstructing endobronchial lesion associated with hemoptysis; the latter potentially necessitating surgical intervention. Endobronchial histoplasmosis should be considered in the differential diagnosis of obstructing endobronchial lesions associated with hemoptysis, especially when prior and(or) concurrent biopsies fail to disclose malignancy.
μ-Opioid receptor-mediated reduction of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-activated current in dorsal horn neurons

Abstract Whole-cell voltage-clamp recording was used to examine the effects of μ-opioid receptor agonists DAGO (Tyr- d -Ala-Gly-MePhe-Gly-ol-enkephalin) and PL017 (Tyr-Pro-N-MePhe- d -Pro-NH2) on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I–IV of young rats. We found that the peak and steady-state amplitude of the AMPA-induced current were depressed by μ-opioid agonists (1 nM–5 μM) in a dose-dependent manner in about 80% of the tested cells. When experiments were performed using whole-cell perforated patch technique, similar depression of AMPA current was produced by μ-opioids. The μ-opioid receptor selective antagonist CTAP (100 nM) prevented or reduced the depressant effects of DAGO and PL017. Intracellular dialysis with guanosine 5′-O-(2-thiodiphosphate) (GDP-β-S, 0.2 mM) significantly diminished the PL017-induced depression of AMPA responses. In addition, when the cells were dialyzed with guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-S, 0.1 mM) the amplitude and duration of the PL017-induced depression was significantly enhanced. Besides depressing the AMPA responses of DH cells, co-application of PL017 and kainic acid (KA) decreased the magnitude of the KA-induced current in 60% of the tested cells. These results indicate that in acutely isolated rat DH neurons, the activation of μ-opioid receptor inhibits AMPA-activated current through activation of a G-protein. This action may contribute to the regulation of the strength of the primary afferent neurotransmission including nociception.
Piezoelectric polymer films. II. Piezoelectric and pyroelectric evaluation

The concept of piezoelectric and pyroelectric effects in amorphous polymers is presented, with experimental results, details on sample preparation, and activity evaluation. Most evaluations were performed on 25–30 mol% tributyltin methacrylate/methyl methacrylate copolymers, which possessed good piezoelectric activity, antifouling properties, and paint-formulation characteristics. Solvent-induced orientation effects that lead to piezoelectric activity in amorphous, unpoled, polymers are also described.
Intrastimulus conflict in differential classical eyelid conditioning

The differential classical eyelid conditioning paradigm was used to investigate intrastimulus conflict effects. Intrastimulus conflict was manipulated within subjects by presenting the words “red” and “green” in both their respective colors and their complementary colors. Reinforcement for one group of subjects was signaled by the word itself; for the other group of subjects, it was signaled by the color of the stimulus. Contrary to the findings of an earlier study in which intrastimulus conflict was manipulated between subjects, no conflict effects were observed in the present experiment.
The food colorant erythrosine is a promiscuous protein–protein interaction inhibitor

Following our observation that erythrosine B (FD&C Red No. 3) is a relatively potent inhibitor of the TNF-R-TNFα and CD40-CD154 protein-protein interactions, we investigated whether this inhibitory activity extends to any other protein-protein interactions (PPI) as well as whether any other approved food colors possess such inhibitory activity. We found erythrosine, a poly-iodinated xanthene dye, to be a non-specific promiscuous inhibitor of a number of PPIs within the tumor necrosis factor superfamily (TNF-R-TNFα, CD40-CD154, BAFF-R-BAFF, RANK-RANKL, OX40-OX40L, 4-1BB-4-1BBL) as well as outside of it (EGF-R-EGF) with a remarkably consistent median inhibitory concentration (IC(50)) in the 2-20 μM (approximately 2-20mg/L) range. In agreement with this, erythrosine also showed cellular effects including clear cytotoxic effects around this concentration range (IC₅₀≈50 μM). Among the seven FDA-approved food colorants, only erythrosine showed consistent PPI inhibitory activity in the sub-100 μM range, which might also explain (at least partially) why it also has the lowest approved acceptable daily intake (ADI) (0.1 mg/kg body weight/day). Among a number of xanthene structural analogs of erythrosine tested for activity, rose Bengal, a food colorant approved in Japan, showed similar, maybe even more pronounced, promiscuous inhibitory activity, whereas fluorescein was inactive and gallein, phloxine, and eosin were somewhat active in some of the assays.
The effect of sample preparation on the preferred orientation of polycrystalline YBa2Cu3O7

Abstract Studies using X-ray diffraction on polycrystalline YBa2Cu3O7 pellets showed that, when compressed, YBa2Cu3O7 crystals preferentially align with their {001} planes, i.e. Cu-O planes, normal to the compression axis. The extent of the preferential orientation is sensitive to the thermal history during the powder preparation, and the chemistry of the solid reactants involved. In particular, YBa2Cu3O7 pellets prepared using BaCO3 as the Ba source and relatively short calcination times, a procedure adopted in most of the earlier investigations, did not show the preferential alignment. In contrast, pellets prepared from BaO showed a distinct {001} preferential orientation normal to the compression axis, and the extent of the alignment increases with the calcination time.
Relation of vitamin D-dependent intestinal calcium-binding protein to calcium absorption during the ovulatory cycle in Japanese quail.

SummaryDuodenal CaBP levels and the efficiency of 47Ca absorption by the duodenal segment of ovulating Japanese quail were determined as a function of eggshell formation. No differences in these parameters were noted in quail in which eggs were being calcified and in quail with no egg in the calcification stage. Thus, there is a correlation between the efficiency of Ca absorption and the level of vitamin D-dependent intestinal calcium-binding protein in this physiological state in Japanese quail.
The surface acidity of hydrous CdS(s)

Abstract The surface acidity of hydrous CdS was determined by both the electrokinetic and the alkalimetric titration methods. The potential determining role of Cd 2+ ion (PDI) was also established. In aqueous solution, two types of surface functional sites can be recognized, namely, Bro¨nsted sites where H + and OH − ions are PDI and Lewis sites where Cd 2+ and S 2− are PDI. In the absence of specific adsorption, both the titration and the electrokinetic methods can be used to determine the intrinsic Bro¨nsted and Lewis acidity constants. At an ionic strength of 5 × 10 −2 M , the acidity constants (p K 's) are 6.10 and 9.02 for the Bro¨nsted acid site and 4.27 for the Lewis acid site. The points of zero charge are pH zpc = 7.5 and pCd zpc = 5.6 at pH 7.5. The total number of surface sites, i.e., the sum of the Bro¨nsted and the Lewis sites, is 20 μC/cm 2 . The ratio of the Lewis to Bro¨nsted acid site depends more on the pH than on the pCd.
AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.

Hepatitis C virus (HCV) enters its target cell via clathrin-mediated endocytosis. AP-2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) are host kinases that regulate clathrin adaptor protein (AP)-mediated trafficking in the endocytic and secretory pathways. We previously reported that AAK1 and GAK regulate HCV assembly by stimulating binding of the μ subunit of AP-2, AP2M1, to HCV core protein. We also discovered that AAK1 and GAK inhibitors, including the approved anticancer drugs sunitinib and erlotinib, could block HCV assembly. Here, we hypothesized that AAK1 and GAK regulate HCV entry independently of their effect on HCV assembly. Indeed, silencing AAK1 and GAK expression inhibited entry of pseudoparticles and cell culture grown-HCV and internalization of Dil-labeled HCV particles with no effect on HCV attachment or RNA replication. AAK1 or GAK depletion impaired epidermal growth factor (EGF)-mediated enhanced HCV entry and endocytosis of EGF receptor (EGFR), an HCV entry cofactor and erlotinib's cancer target. Moreover, either RNA interference-mediated depletion of AP2M1 or NUMB, each a substrate of AAK1 and/or GAK, or overexpression of either an AP2M1 or NUMB phosphorylation site mutant inhibited HCV entry. Last, in addition to affecting assembly, sunitinib and erlotinib inhibited HCV entry at a postbinding step, their combination was synergistic, and their antiviral effect was reversed by either AAK1 or GAK overexpression. Together, these results validate AAK1 and GAK as critical regulators of HCV entry that function in part by activating EGFR, AP2M1, and NUMB and as the molecular targets underlying the antiviral effect of sunitinib and erlotinib (in addition to EGFR), respectively. IMPORTANCE Understanding the host pathways hijacked by HCV is critical for developing host-centered anti-HCV approaches. Entry represents a potential target for antiviral strategies; however, no FDA-approved HCV entry inhibitors are currently available. We reported that two host kinases, AAK1 and GAK, regulate HCV assembly. Here, we provide evidence that AAK1 and GAK regulate HCV entry independently of their role in HCV assembly and define the mechanisms underlying AAK1- and GAK-mediated HCV entry. By regulating temporally distinct steps in the HCV life cycle, AAK1 and GAK represent “master regulators” of HCV infection and potential targets for antiviral strategies. Indeed, approved anticancer drugs that potently inhibit AAK1 or GAK inhibit HCV entry in addition to assembly. These results contribute to an understanding of the mechanisms of HCV entry and reveal attractive host targets for antiviral strategies as well as approved candidate inhibitors of these targets, with potential implications for other viruses that hijack clathrin-mediated pathways.
The Causes of the Depression in Australia in the 1930′s: A General Equilibrium Evaluation

Abstract This paper examines the causes of the depression in Australia in the 1930′s using the computable general equilibrium approach. A nine-sector general equilibrium model of the Australian economy in the 1930′s is formulated and some counterfactual simulations are carried out using the model. The results tend to suggest that the evaporation of the capital inflow, which reduced domestic investment, and the fall in export prices, which worsened the terms of trade, are the leading factors in the Australian depression. These findings square with Boehm′s assertion that the depression was an uncommon economic experience imposed on Australia′s usual business cycle by the collapse of the international economy.
CD11a/CD18 (LFA-1) Integrin Engagement Enhances Biosynthesis of Early Cytokines by Activated T Cells

To study the signaling role of CD11a/CD18 in the early events of T cell activation we have examined the induction of transcription of two important cytokines, namely TNF alpha and IL-2. Human peripheral blood T cells were stimulated with PMA/ionophore or immobilized anti-CD3 mAb (OKT3) with or without CD11a/CD18 engagement. Induced cytokine production by immobilized OKT3 was enhanced (3- to 10-fold) in cells adhering to OKT3 and ICAM-1 coimmobilized surfaces and anti-CD11a mAb abolished this enhancement effect. Similarly, inhibition of the PMA/ionophore-induced CD11a/CD18-mediated homotypic aggregations of T cells by mAbs specific for either CD11a or ICAM-1 reduced the induced cytokine production by more than 70%. We have also observed that greatly enhanced cytokine production resulted from cellular interactions between activated T cells and monolayers of endothelial cells. This enhancement was inhibited by a combination of CD11a-, CD18-, and ICAM-1-specific mAbs implicating a role of CD11a/CD18 in leukocyte adhesion to endothelium and diapedesis as part of the inflammatory process. By Northern analyses induced TNF alpha mRNA expression was significantly enhanced by the engagement of CD11a/CD18 in all the conditions mentioned above. These results, together with our previous studies on monocytes, lead to the conclusion that engagement of the CD11/CD18 family of receptors results in the transduction of cellular signals that quantitatively enhance the expression of important leukocyte-mediated immune and inflammatory responses.
Identification and immunocharacterization of a 25K structural protein in Autographa californica nuclear polyhedrosis virus (AcMNPV)

A 25K protein was a major component of the Triton X-100 solubilized fraction prepared for the isolation of nuclear matrices from Spodoptera frugiperda cells infected with Autographa californica nuclear polyhedrosis virus (AcMNPV). Polyclonal antisera to p25 were produced in rabbits and used in the characterization of p25. Western blots of proteins probed with the p25 antiserum demonstrated the presence of the p25 in both the polyhedral-derived and extracellular viral phenotypes. Using an indirect fluorescent antibody assay, p25 was detected within the infected host cell as early as 6 h p.i. and throughout the time course examined. The intensity in fluorescence increased from the periphery of the infected cells to within the nucleus at late times post-infection. On electron micrographs, the p25 was observed as dense gold particles in localized pockets and around virions in the nucleus at 16 and 36 h p.i., respectively. By 48 h p.i., p25 was concentrated over the surface of nucleocapsids in the intranuclear region and within polyhedra. p25 was not associated with any infected cell structures and did not appear to be involved in polyhedron formation. These studies demonstrated that p25 was a structural protein which was expressed very early during infection and displayed characteristics similar to In major capsid proteins of the baculoviruses.
Gaining That “Near-Perfect” Teaching Schedule

(1998). Gaining That “Near-Perfect” Teaching Schedule. Strategies: Vol. 11, No. 3, pp. 34-36.
Stabilization of photically evoked after-discharge activity: control procedures and effects of classical trace conditioning.

Three experiments were carried out in unanesthetized awake rats to (1) quantify control procedures for the stabilization of photically evoked after-discharge (PhAD) occurrence at maximized levels, (2) compare the PhAD response with other components of the visually evoked response (VER), and (3) document the effects of habituation and classical trace conditioning on stabilized PhAD activity. Results indicate that at least 3 days of exposure to experimental conditions were necessary for the development of stabilized PhAD bursting. Stabilized PhAD responding was found to be associated with a stabilization in other VER components. The principal findings of the habituation and classical conditioning experiments were as follows: (A) Preconditioning habituation and postconditioning habituation procedures (massed-trial extinction) resulted in an increase followed by a decrease in PhAD amplitude as a function of time, and (B) with trace conditioning of a tail-flip response, PhAD amplitude was stabilized over conditioning trials but decreased with extinction. These results were interpreted to suggest there is an optimal level of arousal for the evocation of PhAD, with marked activation or relaxation precluding its occurrence.
Engineered herpes simplex viruses efficiently infect and kill CD133+ human glioma xenograft cells that express CD111

Oncolytic herpes simplex viruses (HSV) hold promise for therapy of glioblastoma multiforme (GBM) resistant to traditional therapies. We examined the ability of genetically engineered HSV to infect and kill cells that express CD133, a putative marker of glioma progenitor cells (GPC), to determine if GPC have an inherent therapeutic resistance to HSV. Expression of CD133 and CD111 (nectin-1), the major entry molecule for HSV, was variable in six human glioma xenografts, at initial disaggregation and after tissue culture. Importantly, both CD133+ and CD133− populations of glioma cells expressed CD111 in similar relative proportions in five xenografts, and CD133+ and CD133− glioma cell subpopulations were equally sensitive to killing in vitro by graded dilutions of wild-type HSV-1(F) or several different γ134.5-deleted viruses. GPC did not display an inherent resistance to HSV. While CD111 expression was an important factor for determining sensitivity of glioma cells to HSV oncolysis, it was not the only factor. Our findings support the notion that HSV will not be able to effectively enter, infect, and kill cells in tumors that have low CD111 expression (<20%). However, virotherapy with HSV may be very effective against CD111+ GPC resistant to traditional therapies.
To dream, perchance to remember: individual differences in dream recall

Each day for 14 weeks, 193 college students indicated whether or not they remembered a dream from the previous evening; they also recorded their sleep schedules and noted whether they had (1) exercised and (2) consumed alcohol and caffeine. In addition, the students completed measures of dissociation, schizotypy, sleep-related experiences, and the five-factor model of personality (N=169). Analyses of these data indicated that individual differences in dream recall were strongly stable over a 2-month interval. Dream recall was specifically associated with openness and was unrelated to the other Big Five traits. Subsequent analyses indicated that individuals who are prone to absorption, imagination and fantasy are particularly likely to remember their dreams and to report other vivid nocturnal experiences. These results are consistent with a salience model of dream recall and a continuity model of human consciousness.
ON THE SOLUTION OF ESTIMATING EQUATIONS FOR TRUNCATED AND CENSORED SAMPLES FROM NORMAL POPULATIONS

To calculate maximum-likelihood estimates of the mean and standard deviation of a normally distributed population from doubly truncated or from doubly censored samples, it is necessary to solve simultaneously a pair of rather complex non-linear estimating equations. Although solutions can be approximated by straightforward iterative procedures, the calculations often become tedious and time-consuming. This paper is concerned with reducing computational labour required in obtaining these solutions. For use in the doubly truncated case, a chart which permits direct reading of the standardized terminals with an accuracy of from three to five units in the second decimal is included. For use in both the doubly truncated and doubly censored cases, an iterative procedure is devised, which, for a specified degree of accuracy, appears to require less computational effort than similar procedures previously proposed. For use in singly censored cases, where only one estimating equation is involved, a chart which permits direct reading of estimates of the standardized terminal with a degree of accuracy comparable to that possible in the doubly truncated case is presented. Since tables recently published by Cohen & Woodward (1953) reduce the calculation of estimates from singly truncated norinal samples to the simple task of interpolating between table entries, that case is considered here only by reference.
Optimization of THz wave coupling into samples in DNP/NMR spectroscopy

High power millimeter wave and terahertz sources are used in DNP/NMR spectroscopy to greatly enhance the NMR signal. A key issue is the efficient coupling of the source power to the sample. We present HFSS calculations showing that the MIT 250 GHz DNP/NMR system provides a B 1 value of 13 µT/W1/2. The simulation shows the importance of the diffraction of radiation passing through the RF coil, leading to non-uniform illumination of the sample. A simple single pass model yields insight into the origin of the observed B 1 value. Methods of optimizing the B 1 value are described.
Raman/CHAMP Instrument for Lunar In-situ Resource Prospecting I - Imager Design

Lunar ISRU precursor prospecting missions are being considered in order to characterize the lunar surface environment and to determine volatile and mineral content as well as mechanical and thermal properties of the lunar regolith for purposes of designing future excavation and In-Situ Resource Utilization (ISRU) processing equipment. The Raman/CHAMP instrument (RCI) is being developed as part of an instrument/experiment suite development project known as Regolith and Environment Science and Oxygen and Lunar Volatile Extraction (RESOLVE) being developed and sponsored under the NASA ISRU Project. The RCI supports the lunar surface characterization measurements by providing crucial field macroscopic and microscopic images coupled with Raman spectroscopy. The RCI provides the ability to collect high resolution, hand lens to field microscopy images and spectroscopic measurements from a robotic arm with the ability to resolve, characterize, and chemically differentiate >90% of lunar Apollo fines. The entire measurement process is highly adaptive and does not necessarily require any type of active sampling. In this paper we provide an overview of the RCI. We discuss the optical design optimization and analysis process for this particular type of instrument. We discuss recent results of integration tests of the Mars Microbeam Raman Spectrometer (MMRS) with the MIDP CHAMP instrument, fluorescence analysis, and individual glass fluorescence tests. Finally, we conclude with a summary of anticipated instrument measurement performance based on Zemax optical modeling of an RCI engineering model that is currently in development.
Tight binding of folate substrates and inhibitors to recombinant mouse glycinamide ribonucleotide formyltransferase.

The binding of the prototypical folate inhibitor of de novo purine synthesis, 5,10-dideazatetrahydrofolate (DDATHF), and its hexaglutamate to recombinant trifunctional mouse glycinamide ribonucleotide formyltransferase (rmGARFT) was studied by equilibrium dialysis and by steady-state kinetics using sensitive assays that allowed initial rate calculations. rmGARFT was expressed in insect cells infected with a recombinant baculovirus and purified by a two-step procedure that allowed production of about 25 mg of pure protein/L of culture. The binding of DDATHF to GARFT was ≈50-fold tighter than previously reported, with Kd and Ki values of 2−9 nM, making the parent form of this antifolate a tight-binding inhibitor. The binding of the hexaglutamate of DDATHF to rmGARFT had Kd and Ki values of 0.1−0.3 nM, consistent with the view that polyglutamation enhances binding of antifolates to GARFT. Kinetic analyses using either mono- or hexaglutamate substrate did not yield different values for the Ki for the hexaglut...
Isomer shifts of the octupole doublet in muonic 207Pb

Abstract Isomer shifts in the doublet 5 2 + , 7 2 + levels in muonic 207 Pb have been measured. The shifts are essentially the same as in the core 3 − collective state. They support the hypothesis that the octupole vibration does not conserve volume.
Iron-limited diatom growth and Si:N uptake ratios in a coastal upwelling regime

There is compelling evidence that phytoplankton growth is limited by iron availability in the subarctic Pacific1, and equatorial Pacific2 and Southern oceans3. A lack of iron prevents the complete biological utilization of the ambient nitrate and influences phytoplankton species composition in these open-ocean ‘high-nitrate, low-chlorophyll’ (HNLC) regimes4. But the effects of iron availability on coastal primary productivity and nutrient biogeochemistry are unknown. Here we present the results of shipboard seawater incubation experiments which demonstrate that phytoplankton are iron-limited in parts of the California coastal upwelling region. As in offshore HNLC regimes, the addition of iron to these nearshore HNLC waters promotes blooms of large chain-forming diatoms. The silicic acid:nitrate (Si:N) uptake ratios in control incubations are two to three times higher than those in iron incubations. Diatoms stressed by a lack of iron should therefore deplete surface waters of silicic acid before nitrate, leading to a secondary silicic acid limitation of the phytoplankton community. Higher Si:cell, Si:C and Si:pigment ratios in diatoms in the control incubations suggest that iron limitation leads to more silicified, faster-sinking diatom biomass. These results raise fundamental questions about the nature of nutrient-limitation interactions in marine ecosystems, palaeoproductivity estimates based on the sedimentary accumulation of biogenic opal, and the controls on carbon export from some of the world's most productive surface waters.
Influence of the timing of nutritional insult on alterations of cell-mediated immunity in guinea pigs infected with Mycobacterium bovis BCG by the respiratory route

Abstract Alterations of cell-mediated immunity in nutrient-deficient humans and animals are influenced by the severity and chronicity of the nutritional insult. Previously we have shown that initiation of deficient diets at the time of vaccination with Mycobacterium bovis BCG alters the immunologic status of guinea pigs several weeks later. In the present study, guinea pigs were infected by the respiratory route with M. bovis BCG simultaneously with, or two weeks or four weeks prior to placing groups on either low protein (LP), low zinc (LZ) or control (C) diets. Six weeks post-infection, all guinea pigs were skin tested with tuberculin and sacrificed. Splenocyte suspensions were stimulated in vitro with three doses each of two polyclonal T cell mitogens, phytohemagglutinin (PHA) and concanavalin A (Con A). Tuberculin reactions were completely suppressed in both LP and LZ groups maintained for the entire vaccination interval (6 weeks) and partially impaired in the protein-deficient animals after 4 weeks or 2 weeks on the LP diet. Reduced lymphoproliferative responses to both PHA and Con A were seen in acutely malnourished LP and LZ guinea pigs after 2 weeks on the diet. After 6 weeks on the deficient diets, lymphocytes from LZ animals were hyporesponsive to low concentrations of both mitogens.
Development of T2-relaxation values in regional brain sites during adolescence

Brain tissue changes accompany multiple neurodegenerative and developmental conditions in adolescents. Complex processes that occur in the developing brain with disease can be evaluated accurately only against normal aging processes. Normal developmental changes in different brain areas alter tissue water content, which can be assessed by magnetic resonance (MR) T2 relaxometry. We acquired proton-density (PD) and T2-weighted images from 31 subjects (mean age±S.D., 17.4±4.9 years; 18 male), using a 3.0-T MR imaging scanner. Voxel-by-voxel T2-relaxation values were calculated, and whole-brain T2-relaxation maps constructed and normalized to a common space template. We created a set of regions of interest (ROIs) over cortical gray and white matter, basal ganglia, amygdala, thalamic, hypothalamic, pontine and cerebellar sites, with sizes of ROIs varying from 12 to 243 mm(3); regional T2-relaxation values were determined from these ROIs and normalized T2-relaxation maps. Correlations between R2 (1/T2) values in these sites and age were assessed with Pearson's correlation procedures, and gender differences in regional T2-relaxation values were evaluated with independent-samples t tests. Several brain regions, but not all, showed principally positive correlations between R2 values and age; negative correlations emerged in the cerebellar peduncles. No significant differences in T2-relaxation values emerged between males and females for those areas, except for the mid pons and left occipital white matter; males showed higher T2-relaxation values over females. The findings indicate that T2-relaxation values vary with development between brain structures, and emphasize the need to correct for such age-related effects during any determination of potential changes from control values.
Pro region C-terminus:protease active site interactions are critical in catalyzing the folding of alpha-lytic protease.

α-Lytic protease is encoded with a large (166 amino acid) N-terminal pro region that is required transiently both in vivo and in vitro for the correct folding of the protease domain [Silen, J. L., and Agard, D. A. (1989) Nature 341, 462−464; Baker, D., et al. (1992) Nature 356, 263−265]. The pro region also acts as a potent inhibitor of the mature enzyme [Baker, D., et al. (1992) Proteins: Struct., Funct., Genet. 12, 339−344]. This inhibition is mediated through direct steric occlusion of the active site by the C-terminal residues of the pro region [Sohl, J. L., et al. (1997) Biochemistry 36, 3894−3904]. Through mutagenesis and structure−function analyses we have begun to investigate the mechanism by which the pro region acts as a single turnover catalyst to facilitate folding of the mature protease. Of central interest has been mapping the interface between the pro region and the protease and identifying interactions critical for stabilizing the rate-limiting folding transition state. Progressive C-term...
RNA SHAPE Chemistry Reveals Nonhierarchical Interactions Dominate Equilibrium Structural Transitions in tRNAAsp Transcripts

Current models assume that RNA folding is strongly hierarchical such that the base-paired secondary structure is more stable than and forms independently of the tertiary structure. This model has been difficult to test due to the experimental inability to interrogate the local environment at every nucleotide as a comprehensive function of the RNA folding state. Reaction of an RNA 2‘-hydroxyl group with N-methylisatoic anhydride to form a nucleotide 2‘-ester is governed by the extent to which the nucleotide forms base pairing or tertiary interactions. Selective 2‘-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) is shown to be an RNA analogue of the protein hydrogen exchange experiment. Single nucleotide resolution SHAPE analysis emphasizes a complexity for the unfolding of tRNAAsp transcripts that is not anticipated by current models for RNA folding. We quantify six well-defined transitions for tRNAAsp transcripts between 35 and >75 °C, including asymmetric unfolding of the two strands in a single ...
Functional enhancement of skeletal muscle by gene transfer.

This article considers the development of gene therapies as a potentially viable means of enhancing skeletal muscle function for the treatment of dystrophin-related muscular dystrophies. As has been discussed, however, a clearer understanding of the causative mechanisms of muscle weakness in a given disease model and identification of the precise mechanisms of action associated with promising interventions may enable the rational design of gene therapies for many additional conditions characterized by impaired muscle function. The authors anticipate that these developments also would benefit from continuing improvements in vector design that enhance gene transfer efficiency and intervention safety. Assessing technical improvements in animal disease models of varying size and physiology would be crucial for verifying their efficacy and safety and should provide solid platforms from which to identify promising intervention strategies that warrant translation to clinical application. As with all experimental approaches being devised for life-threatening conditions for which no cure currently exists, thorough but sympathetic oversight of the development process by responsible regulatory agencies will prove invaluable for the ultimate realization of what it is hoped will be the next generation of therapies for serious neuromuscular disorders. © 2005 Elsevier Inc. All rights reserved.
Auditory orienting: automatic detection of auditory change over brief intervals of time: a neural net model of evoked brain potentials

The human auditory system has a neurophysiological component, mismatch negativity (MMN), that automatically registers change over time of a variety of simple auditory features, e.g., loudness, pitch, duration, and spatial location. A neural network automatic auditory orienting (AAO-MMN) model which simulates the MMN response is described. The main assumption of the proposed AAO-MMN model is that the broad range characteristic of MMN is achieved by local inhibition of the nonlocal thalamic sources of distributed neural activation. The model represents this activation source by a single thalamic (T) unit that is always fully active. The second assumption is that the buildup of MMN over several repetitions of the standard stimulus is accomplished by a local cumulative activation function. All the local accumulator neurons inhibit the nonlocal, steady-state, thalamic activation represented by T. >
Safety and economic impacts of photo radar program.

Objective. Unsafe speed is one of the major traffic safety challenges facing motorized nations. In 2003, unsafe speed contributed to 31 percent of all fatal collisions, causing a loss of 13,380 lives in the United States alone. The economic impact of speeding is tremendous. According to NHTSA, the cost of unsafe speed related collisions to the American society exceeds $40 billion per year. In response, automated photo radar speed enforcement programs have been implemented in many countries. This study assesses the economic impacts of a large-scale photo radar program in British Columbia. The knowledge generated from this study could inform policy makers and project managers in making informed decisions with regard to this highly effective and efficient, yet very controversial program. Methods. This study establishes speed and safety effects of photo radar programs by summarizing two physical impact investigations in British Columbia. It then conducts a cost-benefit analysis to assess the program's economi...
3D Spatio-Temporal face recognition using dynamic range model sequences

Research on 3D face recognition has been intensified in recent years. However, most research has focused on the 3D static data analysis. In this paper, we investigate the face recognition problem using dynamic 3D face model sequences. Based on our newly created 3D dynamic face database, we propose to use a spatio-temporal hidden Markov model (HMM) which incorporates 3D surface feature characterization to learn the spatial and temporal information of faces. The advantage of using 3D dynamic data for face recognition has been evaluated by comparing our approach to three conventional approaches: 2D video based temporal HMM model, conventional 2D-texture based approach (e.g., Gabor wavelet based approach), and static 3D-model-based approaches.
Primary care physicians' knowledge and attitudes towards genetic testing for breast-ovarian cancer predisposition

Primary health care providers are expected to be directly involved in the genetic testing for cancer susceptibility. This study assessed physicians' knowledge, attitude and perception of their role towards testing for hereditary breast ovarian cancer.
Kinetic studies of Fos.Jun.DNA complex formation: DNA binding prior to dimerization.

The bZIP proteins Fos and Jun bind DNA rapidly and with high affinity, forming a heteromeric complex that mediates activated transcription. Here we use stopped-flow fluorescence resonance energy tr...
Hierarchies for 3-orbifolds

We generalize to the category of orbifolds (topological spaces locally modelled on Euclidean space modulo a finite group) some fundamental theorems in the study of 3-manifolds, including the fact that compact $‘-irreducible 3-manifolds with nonempty boundary have incompressible surfaces and can be decomposed into balls by repeated cutting along such surfaces.
Morphology and Dioptrics of Some Ostracod Eyespots: ABSTRACT

On the Gulf Coast, as in other areas, ostracods have been much used in interpreting paleoenvironments. Such use may be enhanced by study of the ocular structures, including eyespots. Eyespot morphology appears to relate to light levels, which in turn are related to water depths. Thus, a new means of reconstructing water depths may be available. Eyespots from two species of Echinocythereis from modern sediments along the Gulf Coast were studied using polished sections and electron and light microscopy. The inner surface of an eyespot is undulating and has a central convex portion and posterior concavities, each with a small radius of curvature compared to the convex outer surface. Light is converged most strongly by the central area and is focused in the underlying eye space. Astigmatism occurs as light passes through the areas away from the center, in which case the focus is beyond the eye cavity in the absence of a tapetal layer. Comparison of a modern and an extinct (Eocene) species of Echinocythereis indicates similar morphology and presumably similar functioning. A potential exists for discerning modern morphology as rel ted to water depth and applying such knowledge to fossil forms and their environments. End_of_Article - Last_Page 1214------------
Resistance to extinction as a function of level of discriminative training and the presence or absence of an irrelevant cue

The hypothesis that behavior becomes increasingly independent of irrelevant cues as a result of overtraining was tested by partially replicating, a study of D’Amato, Schiff, & Jagoda (1962). The hypothesis was not confirmed; behavior was found to become more under the influence of irrelevant cues with prolonged training as measured by resistance to extinction.
Monolithic Sensors for Charged-Particle Imaging using Per-Pixel Correlated Double Sampling

Monolithic CMOS cameras for direct imaging in electron microscopy and other radiation imaging applications have been developed, including complete cameras of up to 1 M-pixels, and have been used to capture images with superior resolution to that of commercial CCD-based systems. Optimizations for these sensors have been made via simulation and experiment, including studies of the impact of epitaxial silicon ionization region thickness, pixel pitch and diode size optimizations, and per-pixel correlated double sampling (CDS) technology. The per-pixel CDS scheme has demonstrated reductions in kT/C noise by a factor of four. It requires only one read instead of two reads plus pre- and post-integration subtraction, and is hence faster than alternate schemes. In addition, observation of Random Telegraph Signal noise (RTS) in small-capacitance pixels is demonstrated.
Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle

RP-A is a single-stranded DNA-binding protein, which has been shown to be required for DNA replication using an SV40 model system. The protein has also been shown to be phosphorylated at the G1-S phase transition. Using Xenopus cell-free extracts we have investigated the role of RP-A in nuclear replication and characterized the kinases and conditions that lead to phosphorylation of RP-A during the cell cycle. By immunodepleting RP-A from Xenopus extracts we have shown that RP-A is essential for replication of chromosomal DNA. Our results show that, during S phase, only that RP-A which is associated with nuclei is phosphorylated. Furthermore our results indicate that during S phase RP-A is only phosphorylated when associated with single-stranded DNA. By immunodepleting cdk2 kinase we show that cdk2 kinase is required for the observed phosphorylation of RP-A in nuclei during S phase. However, using purified cdk2 kinase and RP-A we are unable to detect a direct phosphorylation of RP-A by cdk2 kinase. This observation suggests that phosphorylation of DNA-bound RP-A at S phase is carried out by a kinase distinct from cdk2. Consistent with this we find that when single-stranded DNA is added to S phase extracts depleted of cdk2 kinase, RP-A is phosphorylated. Together these results suggest that cdk2 kinase participates in the activation of DNA replication at a stage prior to the binding of RP-A to the initiation complex. In addition to RP-A phosphorylation in S phase, we have also found that at the onset of mitosis RP-A is quantitatively phosphorylated and that phosphorylation is directly mediated by cdc2 kinase. However, at this time during the cell cycle, cdc2-dependent phosphorylation of RP-A is independent of DNA binding. These observations further demonstrate the distinctions between cdk2 and cdc2 kinases.
Establishing Global Service Learning Courses

Global service-learning courses have the potential to help political scientists achieve multiple teaching goals and there is a strong desire among institutions to develop such programs. What might prevent a political scientist from developing a global service-learning course? This paper examines the challenges that a political scientist might find when working with a foreign local population in establishing a global service learning course on politics. The paper (and presentation) first turns to the literature on global service-learning to see if there is an extant prescription for immersing American students in a foreign environment for the purposes of service-learning. Next, it draws on the dual experiences of the author in establishing global service-learning courses since 2005—one successful, the other replete with failures but ultimately salvaged. The paper concludes that (1) there are unusual challenges for politics-specific global service-learning courses and (2) such undertakings require broad and deep local cooperation, which is sometimes difficult to cultivate under the best of conditions.
Molecular Determinants of Neissserial Opa Protein Interactions with CEACAM Receptors

Neisseria gonorrhoeae is a unique pathogen in that it not only colonizes human tissue by interactions with host receptors, but these interactions can trigger engulfment of the bacteria even by typically non-phagocytic cells. N. gonorrhoeae possess a family of opacity-associated (Opa) proteins, which are 8-stranded β-barrel outer membrane proteins that bind to human host cell receptors. The majority of Opa proteins engage select human CEACAM receptors (carcino-embryonic antigen-like cellular adhesion molecules), and this interaction can trigger phagocytosis of the bacterium. To date, there are 345 distinct opa alleles sequenced; the most prominent differences are in the second and third extracellular loops (hypervariable regions, HV1 and HV2). In addition to contributing to the bacteria's ability to evade the human immune system, these HV regions determine receptor specificity. While the Opa protein family has conserved structural elements, the molecular determinants of receptor recognition and engagement remain unclear. We aim to compare the interactions of various Opa proteins in vitro (reconstituted into liposomes) in order to define how differences in Opa sequence and structure inform receptor binding. To investigate structural motifs involved in Opa-receptor interactions, we are conducting binding assays and protein footprinting experiments to determine how differences in sequence affect receptor engagement. Affinities for a selection of Opa proteins with a variety of CEACAM receptors were determined using biolayer interferometry, with KD values in the low nM range. Protease protection assays are currently being performed to determine which amino acid residues in the HV regions are involved in receptor recognition and engagement. Together, the results of these experiments provide insight into the molecular determinants of the Opa-CEACAM interaction, and provide a clearer understanding of the bacterial mechanism for engulfment into human host cells.
Design of a cavity backed 15:1 bandwidth two arm spiral helix antenna

A design of a 15:1 bandwidth single-mode two-arm spiral helix antenna is presented. In order to achieve unidirectional and efficient radiation, the spiral is cavity backed and resistively loaded. A trapezoidal pyramid cavity is implemented for higher gain at the turn on frequency and smoother gain variation at higher frequencies. Numerical simulations are conducted to assess the gain and axial ratio of the spiral helix for different trapezoidal pyramid heights and diameters. By choosing proper cavity parameters, a wideband spiral with VSWR 0 dBic at the turn-on frequency are realized.
Study on the role of inflammatory factors in the cardiovascular toxicity of PM_(2.5).

The purpose of this study is to explore the potential role of inflammatory factors in the mechanism of cardiovascular toxicity of PM2.5. The cardiovascular endothelium cells were treated by PM2.5 collected from urban area of Shanghai, with doses of 0.01mg/mL,0.05mg/mL and 0.2mg/mL. The relative concentrations of IL-4 and extaxin mRNA was measured by the method of RT-PCR and compared by t-test. Results showed that the relative concentrations of IL-4 and extaxin mRNA in 0.05mg/mL and 0.2mg/mL groups were significantly higher than the control. This result meant that the ?-type allergy related inflammatory factors such as IL-4 and extaxin might play an important role on the cardiovascular toxicity of PM2.5.