cssi/SciSciGPT-SciSciNet huggingface dataset:
Partial correction of murine β-thalassemia with a gammaretrovirus vector for human γ-globin

Abstract Several studies have demonstrated that recombinant lentivirus vectors containing extended globin gene expression cassettes and regulatory elements can ameliorate the pathogenic sequela in murine models of β-thalassemia and sickle cell disease. Similarly promising results have not yet been obtained with recombinant gammaretrovirus vectors. Of these two vector classes, only gammaretroviruses have been tested extensively in clinical trials, with a proven ability to transduce long-term reconstituting hematopoietic stem cells with an exceedingly low incidence of serious side effects. Toward the continuing goal of developing retrovirus vectors for the treatment of the β-chain hemoglobinopathies, we report here the assessment of a recombinant gammaretrovirus vector for human γ-globin in murine models of β-thalassemia. In the β-thalassemia intermedia Hbbth-3/+ model, we observed a dose-dependent but transient increase in total hemoglobin and red blood cells, with a 2.5 ± 0.2 g/dL increase in hemoglobin for transduction rates ≥ 33%. In the severe β-thalassemia major Hbbth-3/Hbbth-3 model, we observed a modest but statistically significant increase in survival, from a median of 15 days to 30 days (P = 0.001). These studies provide the first evidence that globin gene transfer vectors based on recombinant gammaretroviruses may provide a viable option for the treatment of the β-chain hemoglobinopathies.
SEXUAL SELECTION BY THE HANDICAP MECHANISM.

The handicap mechanism of sexual selection by female choice has been strongly criticized because it does not cause sexual selection to reinforce viability selection and it cannot account for the origin of mating preferences. However, several models indicate that the handicap mechanism can have important effects when operating in conjunction with Fisher's mechanism in polygynous populations. These models have been criticized because they require that fitness remains heritable indefinitely. I develop a simple haploid model of the handicap mechanism based on nonheritable variation in paternal investment, thus eliminating the problem of heritable fitness. This model produces the same evolutonary dynamics as both simple and quantitative genetic models of the handicap mechanism based on heritable fitness. If the parameters are such that Fisherian runaway selection does not occur in the null model (i.e., the polymorphic equilibria, which lie along the "Fisher line," are stable), then the handicap mechanism turns the Fisher line into an evolutionary trajectory upon which all other trajectories converge. This occurs because Fisher's mechanism generates no net selection on female preference when the population is on the Fisher line, so that any additional source of selection (direct or indirect) on female choice causes the population to evolve deterministically along the Fisher line. This change in the evolutionary dynamics has the important consequence of eliminating the potential for rapid population divergence for mating systems via genetic drift along the Fisher line.
An Examination of Internal Auditor Objectivity: In‐House versus Outsourcing

The internal audit function is evolving from its traditional oversight function to one that includes a wider spectrum of activities that add value to their organizations. In addition, economic pressures have forced many companies to consider outsourcing as an alternative. These ongoing changes have caused some concern regarding the potential lack of objectivity and independence for internal auditors. This exploratory study examines whether outsourcing of the internal audit function is susceptible to client advocacy vis‐a`‐vis in‐house auditing, which itself may be sensitive to an employer advocacy Sixty‐six practicing members of the Institute of Internal Auditors (IIA) completed a case study involving a corporate acquisition scenario. Of the 66 participants, 35 were from corporations (in‐house), while the remaining 31 were from the Big 4 accounting firms (outsource). Advocacy was manipulated by asking participants to assume the role of internal auditor for either the buyer or the seller of a target divisi...
Demonstratives without rigidity or ambiguity (penultimate draft)

Most philosophers recognize that applying the standard semantics for complex demonstratives to non-deictic instances results in truth conditions that are anomalous, at best. This fact has generated little concern, however, since most philosophers treat non-deictic demonstratives as marginal cases, and believe that they should be analyzed using a distinct semantic mechanism. In this paper, I argue that non-deictic demonstratives cannot be written off; they are widespread in English and foreign languages, and must be treated using the same semantic machinery that is applied to deictic instances.
Thermodynamic constraints from ultrasound measurements in UPt3

Abstract We show that using measurements of the longitudinal sound velocities in UPt 3 in conjunction with the results of a model for the double superconducting transition in an unconventional superconductor it is possible to derive a number of thermodynamic parameters. The values derived for these parameters differ considerably from those obtained from direct measurements. This suggests that there are possibly other factors not considered in present theory which influence the ultrasound velocity in UPt 3 .
What remains of that day: The survival of children's autobiographical memories across time

In this study we investigated the contributions of the content and the coherence of initial event reports to the survival of autobiographical memories during part of the lifespan eventually obscured by childhood amnesia. Over 100 children reported personal experiences when they were 4, 6 or 8 years old, enabling a determination of age-related differences in two aspects of narrative coherence: Theme and chronology. Content was assessed separately through the presentation of directed memory probes. After a 1-year delay, younger children more frequently failed to report target experiences. Multilevel modelling indicated that the survivability of a memory was predicted over and above the child's age by high thematic coherence of the initial memory narrative, but not by the memory content. It is possible that memories described in a highly thematically coherent narrative are indicative of well-integrated event memories, and thus likely to be cued more often, resulting in their long-term survival. Copyright © 2009 John Wiley & Sons, Ltd.
Transient receptor potential melastatin 4 and cell death

Cell death proceeds by way of a variety of “cell death subroutines,” including several types of “apoptosis,” “regulated necrosis,” and others. “Accidental necrosis” due to profound adenosine triphosphate (ATP) depletion or oxidative stress is distinguished from regulated necrosis by the absence of death receptor signaling. However, both accidental and regulated necrosis have in common the process of “oncosis,” a physiological process characterized by Na+ influx and cell volume increase that, in necrotic cell death, is required to produce the characteristic features of membrane blebbing and membrane rupture. Here, we review emerging evidence that the monovalent cation channel, transient receptor potential melastatin 4 (TRPM4), is involved in the cell death process of oncosis. Potential involvement of TRPM4 in oncosis is suggested by the fact that the two principal regulators of TRPM4, intracellular ATP and Ca2+, are both altered during necrosis in the direction that causes TRPM4 channel opening. Under physiological conditions, activation of TRPM4 promotes Na+ influx and cell depolarization. Under pathological conditions, unchecked activation of TRPM4 leads to Na+ overload, cell volume increase, blebbing and cell membrane rupture, the latter constituting the irreversible end stage of necrosis. Emerging data indicate that TRPM4 plays a crucial role as end executioner in the accidental necrotic death of ATP-depleted or redox-challenged endothelial and epithelial cells, both in vitro and in vivo. Future studies will be needed to determine whether TRPM4 also plays a role in regulated necrosis and apoptosis.
Comments on “Turbulence Closure, Steady State, and Collapse into Waves”

Abstract Two-equation models are being increasingly used to model turbulence in geophysical flows. A salient aspect of these flows is the stable gravitational stratification, which implies that turbulent fluctuations can generate internal waves that drain energy from turbulent eddies. This energy is not available for mixing, and therefore this transfer of energy from turbulence to internal waves has strong implications to mixing in the atmospheric boundary layer and the oceanic mixed layer. How to parameterize energy leakage to internal waves in turbulence models has been the subject of many studies, most recently by Baumert and Peters. This comment is an attempt to critique their work and to explore alternative options.
Current-induced marker motion in gold wires☆

Abstract The motion of light transverse scratches, used as markers, has been observed on the surface of gold wires carrying current densities of about 104 A/cm2 for periods of several days. Clear evidence for a mass transport caused by momentum exchange with the electron current is shown by the magnitude and direction of the marker motion—several microns a day in some cases and always toward the cathode. This motion is exhibited by scratches on the central portion whose temperature varied from 850°C to 1000°C. Water cooling maintained the ends of the wires near room temperature. In agreement with a simplified theory the marker motion appears to be proportional to the current density and the self-diffusion constant. Possible applications of this technique include (1) the indirect determination of the activation energy for diffusion and (2) the investigation of the strength of interaction between the electrons and those lattice defects which constitute the activated complexes for atom jumping. In this case a value of 2μ ohm-cm/per cent was indicated for the “specific resistivity” of the diffusing atom in gold.
Evidence for heritability of biogenic amine levels in the cerebrospinal fluid of rhesus monkeys

Susceptibility to several human psychopathological disorders is under partial genetic influence, and many of these disorders have biological correlates that may form part of the basis of this vulnerability. In humans, alterations in cerebrospinal fluid (CSF) metabolite levels of the amine transmitters norepinephrine, dopamine, and serotonin have been associated with several forms of psychopathology, and altered levels of these metabolites have been found in healthy probands with a familial history of such illnesses. We report evidence for heritability of CSF levels of biogenic amine measures in rhesus monkeys, Macaca mulatta. In a pilot study of 54 monkeys with known pedigrees, significant differences among sire families were found for CSF levels of norepinephrine (p = 0.04), homovanillic acid (p = 0.02), and 5-hydroxyindoleacetic acid (p = 0.04). These data indicate that variation in bioaminergic measures is associated with pedigree, and that model systems incorporating both genetic and environmental factors can contribute to the understanding of the function of aminergic systems implicated in vulnerability to psychopathology.
Increased mean depth of earthquakes at Parkfield

The mean focal depth of earthquakes in the northern and southern parts of the Parkfield segment of the San Andreas fault was greater than long term average by 1km during the last 4 years approximately. It is proposed that this is a precursor to the next characteristic Parkfield earthquake, because the same phenomenon occurred before at least three other mainshocks along the San Andreas fault. In the northern segment the increase in mean depth is mostly due to reduction of shallow activity, in the southern segment deeper than usual activity seems to have increased. Within about 8 km from the 1966 epicenter no significant increase of mean depth is observed, but seismic quiescence [Wyss et al., 1990a] and a decrease in deformation rate [Wyss et al., 1990b] was documented. These observations are interpreted to suggest that the precursory process at Parkfield varies along strike, and that the next rupture may extend further north than the last one.
The effects of the pitch difference on the load distribution of a roller chain drive

Abstract An analysis is presented to determine the effects of pitch difference, friction, and centrifugal forces on the load distribution of a roller chain. Load distribution curves for chain links and sprocket teeth as a function of the angle of rotation of the sprocket, as well as plots of the sprocket and roller chain interaction are given. Friction is shown to cause a higher tooth load on a driven sprocket than that of a driver sprocket.
Estimation of the kinetic energy dissipation in fall-arrest system and manikin during fall impact

Fall-arrest systems (FASs) have been widely applied to provide a safe stop during fall incidents for occupational activities. The mechanical interaction and kinetic energy exchange between the human body and the fall-arrest system during fall impact is one of the most important factors in FAS ergonomic design. In the current study, we developed a systematic approach to evaluate the energy dissipated in the energy absorbing lanyard (EAL) and in the harness/manikin during fall impact. The kinematics of the manikin and EAL during the impact were derived using the arrest-force time histories that were measured experimentally. We applied the proposed method to analyse the experimental data of drop tests at heights of 1.83 and 3.35 m. Our preliminary results indicate that approximately 84-92% of the kinetic energy is dissipated in the EAL system and the remainder is dissipated in the harness/manikin during fall impact. The proposed approach would be useful for the ergonomic design and performance evaluation of an FAS. STATEMENT OF RELEVANCE: Mechanical interaction, especially kinetic energy exchange, between the human body and the fall-arrest system during fall impact is one of the most important factors in the ergonomic design of a fall-arrest system. In the current study, we propose an approach to quantify the kinetic energy dissipated in the energy absorbing lanyard and in the harness/body system during fall impact.
Behavioral Evidence for Interactions between a Hallucinogenic Drug and Group II Metabotropic Glutamate Receptors

Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT2A and metabotropic glutamate2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT2A receptors induce head shakes when directly administered into the medial prefrontal cortex. The purpose of the present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT2A receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT2A receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3–10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY341495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs may be mediated in part, via increased glutamate release following activation of 5-HT2A receptors.
Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss.

Because elevated ubiquitin ligase atrogin-1/MAFbx and MuRF1 mediate skeletal muscle wasting associated with various catabolic conditions, the signaling pathways involved in the upregulation of these genes under pathological conditions are considered therapeutic targets. AKT and NF-κB have been previously shown to regulate the expression of atrogin-1/MAFbx or MuRF1, respectively. In addition, we recently found that p38 MAPK mediates TNF-α upregulation of atrogin-1/MAFbx expression, suggesting that multiple signaling pathways mediate muscle wasting in inflammatory diseases. To date, however, these advances have not resulted in a practical clinical intervention for disease-induced muscle wasting. In the present study, we tested the effect of curcumin—a non-toxic anti-inflammatory reagent that inhibits p38 and NF-κB—on lipopolysaccharide (LPS)-induced muscle wasting in mice. Daily intraperitoneal (i.p.) injection of curcumin (10–60 μg/kg) for 4 days inhibited, in a dose-dependent manner, the LPS-stimulated (1 mg/kg, i.p.) increase of atrogin-1/MAFbx expression in gastrocnemius and extensor digitorum longus (EDL) muscles, resulting in the attenuation of muscle protein loss. It should also be noted that curcumin administration did not alter the basal expression of atrogin-1/MAFbx, nor did it affect LPS-stimulated MuRF1 and polyubiquitin expression. LPS activated p38 and NF-κB, while inhibiting AKT; whereas, curcumin administration inhibited LPS-stimulated p38 activation, without altering the effect of LPS on NF-κB and AKT. These results indicate that curcumin is effective in blocking LPS-induced loss of muscle mass through the inhibition of p38-mediated upregulation of atrogin-1/MAFbx.
Implementation of nondestructive Young's modulus measurement by miniature optical sensors

Accurate real time nondestructive modulus measurement is one of the principal requirements in service life monitoring of smart structures. However, most current measurement methods, such as tension and/or compression testing are inappropriate for such applications. For one thing, the force load may damage the casting. For another, the test process is not trivial and inconvenient for real-time modulus monitoring. This paper describes an acoustic-based measurement mechanism using two separated miniature optical sensors. The sensor features miniature size (<500μm), high resolution and accuracy, high temperature and pressure survivability, electromagnetic interference immunity (EMI), electrically non- conductivity, and chemical erosion inertness. This technique offers future potential for real-time measurement for in-service monitoring, particularly in applications involving such environments as high temperatures or high pressure.
Advances in Electromagnetic Modelling through High Performance Computing

Under the DOE SciDAC project on Accelerator Science and Technology, a suite of electromagnetic codes has been under development at SLAC that are based on unstructured grids for higher accuracy, and use parallel processing to enable large-scale simulation. The new modeling capability is supported by SciDAC collaborations on meshing, solvers, refinement, optimization and visualization. These advances in computational science are described and the application of the parallel eigensolver Omega3P to the cavity design for the International Linear Collider is discussed.
Reinventing germanium avalanche photodetector for nanophotonic on-chip optical interconnects

A key element in the integration of microprocessor chips with optical communications circuits is a photodetector to mediate the optical and electronic signals. Germanium photodetectors are very attractive in this regard because they are compatible with conventional silicon circuitry, but they suffer from noise that limits their performance. Assefa et al. now show how the poor intrinsic noise characteristics of germanium can be overcome through the careful engineering of optical and electrical fields at the nanometre scale. The result is a compact and efficient photodetector that could enable a range of optoelectronic applications. To integrate microchips with optical communications a photodetector is required to mediate the optical and electronic signals. Although germanium photodetectors are compatible with silicon their performance is impaired by poor intrinsic noise. Here the noise is reduced by nanometre engineering of optical and electrical fields to produce a compact and efficient photodetector. Integration of optical communication circuits directly into high-performance microprocessor chips can enable extremely powerful computer systems1. A germanium photodetector that can be monolithically integrated with silicon transistor technology2,3,4,5,6,7,8 is viewed as a key element in connecting chip components with infrared optical signals. Such a device should have the capability to detect very-low-power optical signals at very high speed. Although germanium avalanche photodetectors9,10 (APD) using charge amplification close to avalanche breakdown can achieve high gain and thus detect low-power optical signals, they are universally considered to suffer from an intolerably high amplification noise characteristic of germanium11. High gain with low excess noise has been demonstrated using a germanium layer only for detection of light signals, with amplification taking place in a separate silicon layer12. However, the relatively thick semiconductor layers that are required in such structures limit APD speeds to about 10 GHz, and require excessively high bias voltages of around 25 V (ref. 12). Here we show how nanophotonic and nanoelectronic engineering aimed at shaping optical and electrical fields on the nanometre scale within a germanium amplification layer can overcome the otherwise intrinsically poor noise characteristics, achieving a dramatic reduction of amplification noise by over 70 per cent. By generating strongly non-uniform electric fields, the region of impact ionization in germanium is reduced to just 30 nm, allowing the device to benefit from the noise reduction effects13,14,15 that arise at these small distances. Furthermore, the smallness of the APDs means that a bias voltage of only 1.5 V is required to achieve an avalanche gain of over 10 dB with operational speeds exceeding 30 GHz. Monolithic integration of such a device into computer chips might enable applications beyond computer optical interconnects1—in telecommunications16, secure quantum key distribution17, and subthreshold ultralow-power transistors18.
Effect of tetrodotoxin on adrenaline secretion in the perfused rat adrenal medulla.

EXTRACELLULAR Ca ions are required for the secretion of many hormones1. In the adrenal medulla catecholamine secretion evoked by acetylcholine (ACh) is completely blocked by omitting Ca from the medium2,3. The mechanism for Ca entry has been studied in a phaeochromocytoma cell line (PC12) which originated from a rat adrenal medullary tumour4,5. Two alternative ways of Ca entry were considered, voltage-dependent Ca channels and ACh channels. By analysing dopamine secretion4 and radioactive Ca influx5 in various ionic environments it was concluded that more than 80% of the Ca ions enter through the voltage-dependent Ca channels during stimulation by cholinergic agonists. Action potentials mediated by Na6,7 and Ca7 have been demonstrated in primary cultures of rat adrenal chromaffin cells. Furthermore, extracellular recording techniques can detect spontaneous action potentials in these cells. The frequency of these action potentials is modified in a dose-dependent manner by ACh (3×10−7M to 10−4M)7, and the same range of ACh concentrations stimulates adrenaline secretion in the perfused rat adrenal medulla3,8. Thus modulation of action potential frequency by ACh may be a mechanism for controlling the amount of Ca entry. The potential change during a Na action potential may activate voltage-dependent Ca channels, thereby increasing Ca influx. Also, spontaneous action potentials are blocked by 6 µM tetrodotoxin (TTX)7, a specific inhibitor of Na channels9. Therefore, if the Na action potential is involved in secretion, TTX should reduce Ca entry which in turn should decrease catecholamine secretion. We tested this hypothesis in the perfused rat adrenal medulla and report here that TTX decreases a portion of the adrenaline secretion evoked by either high KCl or ACh. Thus, Na action potentials, by facilitating the activation of Ca channels, may be involved in the regulation of adrenaline secretion from adrenal chromaffin cells.
Synergism and Multiple Mechanical Relaxations Observed in Ternary Systems Based on Benzoxazine, Epoxy, and Phenolic Resins

The synergism in the glass-transition temperature (Tg) of ternary systems based on benzoxazine (B), epoxy (E), and phenolic (P) resins is reported. The systems show the maximum Tg up to about 180 °C in BEP541 (B/E/P 5 5/4/1). Adding a small fraction of phenolic resin enhances the crosslink density and, therefore, the Tg in the copolymers of benzoxazine and epoxy resins. To obtain the ultimate Tg in the ternary systems, 6 -10 wt % phenolic resin is needed. The molecular rigidity from benzoxazine and the improved crosslink density from epoxy contribute to the synergistic behavior. The mechanical relaxation spectra of the fully cured ternary systems in a temperature range of 2140 to 350 °C show four types of relaxation transitions: g transition at 280 to 260 °C, b transition at 60 - 80 °C, a1 transition at 135-190 °C, and a2 transition at 290 -300 °C. The partially cured specimens show an additional loss peak that is frequency-independent as a result of the further curing process of the materials. The ternary systems have a potential use as electronic packaging molding compounds as well as other highly filled systems. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1687-1698, 2000
Non-WKB Models of the First Ionization Potential Effect: The Role of Slow Mode Waves

A model for element abundance fractionation between the solar chromosphere and corona is further developed. The ponderomotive force due to Alfven waves propagating through or reflecting from the chromosphere in solar conditions generally accelerates chromospheric ions, but not neutrals, into the corona. This gives rise to what has become known as the first ionization potential effect. We incorporate new physical processes into the model. The chromospheric ionization balance is improved and the effect of different approximations is discussed. We also treat the parametric generation of slow mode waves by the parallel propagating Alfven waves. This is also an effect of the ponderomotive force, arising from the periodic variation of the magnetic pressure driving an acoustic mode, which adds to the background longitudinal pressure. This can have subtle effects on the fractionation, rendering it quasi-mass independent in the lower regions of the chromosphere. We also briefly discuss the change in the fractionation with Alfven wave frequency, relative to the frequency of the overlying coronal loop resonance.
Theory of nucleon-nucleon scattering in the strip approximation to the mandelstam representation

Abstract The nucleon-nucleon scattering amplitude is discussed within the framework of the strip approximation. Asymptotic bounds to the behavior of the amplitudes are derived, and are applied to limit the number of “allowed” single spectral functions to six and correspondingly to limit the types of dynamically independent one-particle states. In particular, it is found that the pion is in this sense allowed, whilst the deuteron is not. The unitarity equations, in which only two-particle intercalated states are retained, are explicitly derived in both the N-N and N - N channels. The N - N equations express a portion of the double spectral functions in terms of the π-N amplitudes; the N-N equations express another portion of these functions through coupled integral equations.
Description of a new tracheline spider, Trachelas mombachensis sp. n., in the T. bispinosus species group from the Mombacho Volcano in Nicaragua (Araneae: Trachelidae)

Trachelas L. Koch, 1872 is a large and diverse genus of sac spiders, originally placed in the family Drassidae Koch. Simon (1897) transferred Trachelas to the family Clubionidae Wagner, 1887 in the Tracheleae group Karsch, 1880, under the subfamily Corinninae Karsch, 1880. Corinninae was elevated to family rank by Lehtinen (1967). Lehtinen (1967) did not refer to the Trachelineae group in that publication; however, in a later publication he refers to the family Trachelidae, without justification for family elevation (Lehtinen 1996). Therefore, Trachelinae remained a subfamily of Corinnidae Karsch, 1880 until 2014 when it was elevated to family rank by Ramirez (2014).
Short CommunicationEvaluating a ‘service elective’ in clinical teaching for medical students

Many medical students wish to begin developing clinical teaching skills before residency. Faculty at the University of California, Irvine developed a 60-hour, longitudinal ‘service elective’ in teaching skills, which 50 third-year and fourth-year students have completed since 2001. Students learned to enact and rate eight stations of an objective structured teaching examination (OSTE) for generalist resident physicians, broadening this practical training with in-class exercises. To evaluate the elective, structured, written questionnaires were administered. Participating students gave the elective a mean rating of 5.24 on a seven-point Likert-type scale, which fell between ‘very good’ (5) and ‘excellent’ (6). Narrative comments showed that students believed the elective—and in particular the OSTE training—prepared them well for teaching as residents.
Laser capture microdissection (LCM) and expression analyses of Glycine max (soybean) syncytium containing root regions formed by the plant pathogen Heterodera glycines (soybean cyst nematode).

Roots of soybean, Glycine max cv. Kent L. Merr., plants susceptible to the soybean cyst nematode (SCN), Heterodera glycines Ichinohe, were inoculated and allowed to develop feeding sites (syncytia) for 8 days. Root samples enriched in syncytial cells were collected using laser capture microdissection (LCM). RNA was extracted and used to make a cDNA library and expressed sequence tags (ESTs) were produced and used for a Gene Ontology (GO) analysis. RT-PCR results indicated enhanced expression of an aquaporin (GmPIP2,2), α-tubulin (GmTubA1), β-tubulin (GmTubB4) and several other genes in syncytium-enriched samples as compared to samples extracted from whole roots. While RT-PCR data showed increased transcript levels of GmPIP2,2 from LCM tissue enriched in syncytial cells, in situ hybridization showed prominent GmPIP2,2 hybridization to RNA in the parenchymal cells tightly juxtaposed to the syncytium. Immunolocalization indicated stronger α-tubulin signal within the syncytium as compared to surrounding tissue. However, α-tubulin labeling appeared diffuse or clumped. Thus, LCM allowed for the isolation of tissue enriched for syncytial cells, providing material suitable for a variety of molecular analyses.
Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells

Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation.
The use of vitamin B complex in the treatment of infantile eczema

Abstract 1.1. From a small series of twenty cases it would, of course, be imposible to draw definite conclusions. 2.2. While we were unable to obtain the uniformly excellent results obtained by other workers, we feel that vitamin B complex in some cases is a valuable adjunct in the treatment of eczema.
The stability of superspheres

The stability of superspheres containing a few tens of particles, formed by the aggregation of weakly charged spherical colloidal crystalites, can be explained by the existence of two opposing forces of different range within the superspheres: long-range electrostatic repulsion and shortrange attractive dispersion. A condition of stability is found that is in quantitative agreement with observation. The superspheres are a manifestation of frustration, analogous to frustration in spin glasses. The generality of the phenomenon is discussed.
Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha.

Adipocyte differentiation is regulated by at least two major transcription factors, CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). Expression of PPARγ in fibroblasts converts them to fat-laden cells with an adipocyte-like morphology. Here, we investigate the ability of PPARγ to confer insulin-sensitive glucose transport to a variety of murine fibroblast cell lines. When cultured in the presence of a PPARγ ligand, Swiss-3T3 and BALB/c-3T3 cells ectopically expressing PPARγ accumulate lipid droplets, express C/EBPα, aP2, insulin-responsive aminopeptidase, and glucose transporter isoform 4 (GLUT4), and exhibit highly insulin-responsive 2-deoxyglucose uptake. In contrast, PPARγ-expressing NIH-3T3 cells, despite similar lipid accumulation, adipocyte morphology, and aP2 expression, do not express C/EBPα or GLUT4 and fail to acquire insulin sensitivity. In cells ectopically expressing PPARγ, the development of insulin-responsive glucose uptake correlates with C/EBPα expression. Furthermore, ectopic expression of C/EBPα in NIH-3T3 cells converts them to the adipocyte phenotype and restores insulin-sensitive glucose uptake. We propose that the pathway(s) leading to fat accumulation and morphological changes are distinct from that leading to insulin-dependent glucose transport. Our results suggest that although PPARγ is sufficient to trigger the adipogenic program, C/EBPα is required for establishment of insulin-sensitive glucose transport.
Evidence for Clostridium Septicum as a Primary Cause of Cellulitis in Commercial Turkeys

Etiology and methods of immunoprophylaxis against common field cellulitis in commercial turkeys were evaluated. It was determined that intravenous administration (∼108 cells/ml) of 1 of 4 isolates ...
Games and immersive participatory simulations for science education: An emerging type of curricula

The manuscripts that comprise this special issue are focused on understanding how games and immersive participatory simulations, with their focus on doing science (not receiving science), are becoming an emerging type of curricula for supporting science education. The environments discussed here build on theoretical frameworks positing that ‘‘knowing’’ is a contextual and participatory act, and that the context in which one learns any particular content shapes the resultant understandings of that content (Barab et al., 1999). Central to this perspective is that, rather than simply telling students about science facts or even socio-scientific issues, knowledge and skills in science should be situated as an inquiry process and that new technologies and design methodologies can facilitate this process. The various articles that comprise this special issue are inquiry-based, leverage multiple media, and integrate game-design principles and scenarios to establish rich inquiry-based contexts for engaging scientific issues. Over the last two decades, a growing movement
C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight *

CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance.
PThomas: an adaptive information retrieval system on the connection machine

Abstract This paper reports the state of development of PThomas , a network based document retrieval system implemented on a massively parallel fine-grained computer, the Connection Machine. The program is written in C ∗ , an enhancement of the C programming language which exploits the parallelism of the Connection Machine. The system is based on Oddy's original Thomas program, which was highly parallel in concept, and makes use of the Connection Machine's single instruction multiple data (SIMD) processing capabilities. After an introduction to systems like Thomas , and their relationship to spreading activation and neural network models, the current state of PThomas is described, including details about the network representation and the parallel operations that are executed during a typical PThomas session.
Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis.

Abstract Nongenotoxic carcinogens are chemicals that induce neoplasia without it or its metabolites reacting directly with DNA. Chemicals classified as nongenotoxic carcinogens have been assumed to act as tumor promoters and exhibit threshold tumor dose-responses. This is in contrast to genotoxic carcinogens that are DNA reactive, act as tumor initiators, and are assumed to exhibit proportional responses at low doses. In this perspective, we examine the basic tenets and utility of this classification for evaluating human cancer risk. Two classes of so-called nongenotoxic chemical carcinogens selected for review include cytotoxic agents that induce regenerative hyperplasia (trihalomethanes and inducers of alpha 2-microglobulin nephropathy) and agents that act via receptor-mediated mechanisms (peroxisome proliferators and dioxin). Major conclusions of this review include: a) many chemicals considered to be nongenotoxic carcinogens actually possess certain genotoxic activities, and limiting evaluations of carcinogenicity to their nongenotoxic effects can be misleading; b) some nongenotoxic activities may cause oxidative DNA damage and thereby initiate carcinogenesis; c) although cell replication is involved in tumor development, cytotoxicity and mitogenesis do not reliably predict carcinogenesis; d) a threshold tumor response is not an inevitable result of a receptor-mediated mechanism. There are insufficient data on the chemicals reviewed here to justify treating their carcinogenic effects in animals as irrelevant for evaluating human risk. Research findings that characterize the multiple mechanisms of chemical carcinogenesis should be used quantitatively to clarify human dose-response relationships, leading to improved scientifically based public health decisions. Excessive reliance on oversimplified classification schemes that do not consider all potential contributing effects of a toxicant can obscure the actual causal relationships between exposure and cancer outcome.
Contextualizing the power of social media: Technology, communication and the Libya Crisis

At the beginning of 2011, revolution across the MENA region threw into question the potential power of new media to bring about large-scale revolutionary pursuits. In Libya, the correlation between social media usage and social upheavals seemed, at most, tenuous in light of low levels of Internet penetration generally and in light of the state-sponsored Internet blackout following the nation-wide protests there. This qualitative research intends, through content analysis and semi-structured interviewing of key communicators, to decode the realities of how and why people were communicating through the crisis in Libya from its inception and to overcome misconceptions about social media as a stand alone or predominant factor in liberation across the region. What emerged from this case study was a confluence of actions and tools responsible for communication through the crisis, of which social media featured significantly. This paper will further discuss the significance of the convivial relationships of the Internet-based campaigners working towards a ‘democratic’ outcome in Libya and working beyond the limitations of national Internet connectedness. I conclude that there is a great potential for Internet-based networks to support widespread social upheaval within ripe socio-political settings.
Characterization of an Abundant COL9A1 Transcript in the Cochlea with a Novel 3′ UTR: Expression Studies and Detection of miRNA Target Sequence

EST N66408 represents one of several large unique clusters expressed in the Morton human fetal cochlear cDNA library. N66408 is 575 bp in size and initial BLAST analysis of this sequence showed no homology to any known genes or expressed sequence tags (ESTs) from other organs or tissues. Sequence of the original cochlear clone from which N66408 was derived revealed that the corresponding cDNA was about 700 bp in size, including 125 bp at its 5′ end with homology to the 3′ end of COL9A1 in addition to 575 bp of novel sequence. RT-PCR analysis using primers specific to COL9A1 isoforms 1 and 2 detected expression of both isoforms in human fetal cochlea. Tissue in situ hybridization using the novel 3′ UTR sequence as probe showed abundant expression in spiral limbus and spiral ligament, and a moderate level of expression in the organ of Corti. dbEST analysis of ESTs specific to the 3′ UTR of COL9A1 showed 19 ESTs derived from various tissues; three polyadenylation sites were identified and the majority of these ESTs were derived from overlapping polyadenylation signals at the second site (position 749–758). Comparison of the 3′ UTR of human COL9A1 with its orthologs as well as with dbEST uncovered a highly conserved region around the overlapping polyadenylation signals at position 749–758 in mammals. A search of the microRNA database revealed a highly conserved target sequence for miR-9 immediately preceding the overlapping polyadenylation signals in the novel 3′ UTR of COL9A1, suggesting its role in posttranscriptional regulation of COL9A1.
Density Functional Theory Calculation of Indirect Nuclear Magnetic Resonance Spin−Spin Coupling Constants in C70

We calculate NMR spin−spin coupling constants in the C70 fullerene by means of density functional theory. We show that using a hybrid density functional (B3LYP) and an adequate basis set (cc-pCVDZ-sd), excellent agreement with experimental values can be achieved for one-bond couplings. These benchmark calculations suggest that theoretical predictions of NMR spin−spin couplings can be extremely valuable for discerning structural information of fullerenes.
The effects of space closure of the mandibular first molar area in adults

There is little information regarding the orthodontic closure of remodeled, edentulous spaces in the posterior area of the mandible. The present study was undertaken to determine the dental and periodontal changes that occur when mandibular first molar areas are closed in adults. Fourteen adult patients were selected from private orthodontic practices. Pre- and posttreatment study models were used to measure the mesiodistal length of the edentulous space and the buccolingual width of the alveolar ridge. The amount of crown and root movement of the second molar and premolar was measured from lateral cephalometric radiographs. From pre- and posttreatment panoramic or periapical radiographs, the anatomic changes of the second molar and adjacent periodontium were also measured. Every case showed significant space closure (x = 6.2 mm) ranging from 2.7 to 11.5 mm. There was crestal bone loss (x = 1.3 mm) mesial to the second molar in all but five cases. These latter cases showed bone addition. As the molar moved mesially , the alveolar ridge increased in width an average of 1.2 mm. The adult patient who showed the greatest amount of space closure and the least amount of molar bone loss had (1) mesiodistal space of 6.0 mm, (2) buccolingual ridge width of 7.0 mm, and (3) mesial molar bone level 1.0 mm apical to the cementoenamel junction. The results of this study indicate that space closure is not only possible but may aid the treatment of certain cases. Space closure should be considered as a potential solution to the absence of mandibular first permanent molars.
Ultrafast Condensed-Phase Emission from Energetic Composites of Teflon and Nanoaluminum

Time and wavelength-resolved spectroscopy was used to monitor optical emission from picosecond flash-heated nanoenergetic materials consisting of 50 nm diameter Al/Al(2)O(3) core-shell nanoparticles in a matrix of Teflon(AF) oxidizer. The Al/Teflon was confined between optical windows to emphasize condensed-phase emission rather than emission from gas-phase reaction products. The Al/Teflon emission is compared to control samples of bare Al nanoparticles or nanoparticles in a nominally inert polybutadiene matrix (Al/PB). In all three materials just two types of emission were observed, a broadband (BB) emission peaked at 320 nm stretching out past 700 nm, and a narrowband (NB) emission with approximately 30 nm wide bands at 310 and 400 nm, coincident with the most intense Al atomic emission lines. The BB emission is attributed to a laser-generated Al plasma and the NB emission to excited-state Al atoms in a dense medium. Compared to Al/PB, the plasma in Al/Teflon emits with higher intensity and longer duration. The Al/Teflon excited-state NB emission was also more intense. The energy release characterizing ignition in Al/Teflon could be monitored via the increased emission intensity of the BB and NB species. We find the ignition process can be described with a global time constant of 100 ps, about twice the approximately 50 ps time constant for the initiation process seen in earlier work (Zamkov, M. A.; Conner, R. W.; Dlott, D. D., J. Phys. Chem. C 2007, 111, 10278), where infrared spectroscopy was used to monitor the disappearance of C-F stretch transitions.