cssi/SciSciGPT-SciSciNet huggingface dataset:
HEPATOPROTECTIVE EFFECTS OF VITAMIN C AGAINST METHOTREXATE INDUCED ACUTE LIVER INJURY: AN EXPERIMENTAL STUDY

Methotrexate (MTX), a synthetic antimetabolite with a wide range of therapeutic indications, although its liver toxicity induced mainly through oxidative stress limits its clinical use. Vitamin C (ascorbic acid) possesses potent antioxidant and anti-inflammatory properties, Therefore, has a possible hepatoprotective effect. This study seeks to address the hepatoprotective effects of vitamin C against MTX-induced liver injury in albino mice. MTX showed significant elevation in both serum Alanine aminotransferase (ALT) and liver tissue Malondialdehyde (MDA), indicating hepatic injury, while vitamin C pre-treatment will hold down this elevation significantly and dose-dependently, causing amelioration of the toxic effect of MTX; the histopathological findings also support this finding. Also, MTX causes consumption of liver tissue content of superoxide dismutase (SOD) and Glutathione (GSH), while vitamin C pre-treatment boosts the SOD hepatic tissue level while GSH is diminished even more. In conclusion, vitamin C has a dose-dependent amelioration effect on the toxic effect of MTX on the liver.
A Brief Illustrated Chronicle of Retroactive Copyright Term Extension

At least since the Supreme Court’s 2003 decision in Eldred v. Ashcroft, it has been widely known that whenever Congress has extended copyright term, it has done so retroactively, granting the benefit of the extension to all works still under copyright on the effective date of the extension. However, I have never found succinct, complete tables and charts detailing the periods during which works received various copyright terms given the retroactive effect of all extension legislation. It is the modest aim of this article to provide that information, and to provide some examples of the operation of retroactive term extension. The article also makes some general observations. For example, it notes that the last date on which a work obtained federal copyright protection that ended up not having its term of protection extended by later legislation was July 1, 1867.
Comparison of two finite element homogenization prediction approaches for through thickness thermal conductivity of particle embedded textile composites

Abstract A detailed three dimensional finite element model was developed to predict the through-thickness thermal conductivity of a textile composite structure consisting of a woven fabric and matrix in our previous work [1] in which conductive particles are randomly distributed in the matrix in the unit cell already containing the woven fabric and the effective thermal conductivity of this three-phase system is numerically evaluated. In this paper, results of this three-component system are compared with a two-component system in which the thermal conductivity of the matrix and particles is homogenized by a finite element approximation under the same thermal conditions. A parametric study of this comparison is conducted over different volume fractions and thermal conductivities of both textile fabric and loaded particles and its efficacy is discussed. Typically such composites could be coated with a conductive skin on the surface. Thus, the role of the skin and fiber conductivities in enhancing heat transfer is compared for this structure. The proposed approach of finite element homogenization of particle-matrix medium can be used to conduct a preliminary assessment of through-thickness thermal conductivity of such three-component composite systems with fabrics, particles and matrices with and without the presence of a skin layer.
Photocarrier relaxation in the quantum kinetics regime

Summary form only given. We present a study of carrier relaxation in bulk GaAs at room temperature in the quantum kinetics regime. We use a modified frequency-resolved pump-probe technique with pump and probe durations independently adjustable from 30-100 fs. Differential absorption spectra (DAS) for 70-fs pump and probe at low excess energy is presented.
Identification of a putative isoform of the Na,K-ATPase beta subunit. Primary structure and tissue-specific expression.

Abstract We have isolated cDNA clones from rat brain and human liver encoding a putative isoform of the Na,K-ATPase beta subunit. The rat brain cDNA contains an open reading frame of 870 nucleotides coding for a protein of 290 amino acids with a calculated molecular weight of 33,412. The corresponding amino acid sequence shows 98% identity with its human liver counterpart. The proteins encoded by the rat and human cDNAs exhibit a high degree of primary sequence and secondary structure similarity with the rat Na,K-ATPase beta subunit. We have therefore termed the polypeptides these cDNAs encode a beta 2 subunit with the previously characterized rat cDNA encoding a beta 1 subunit. Analysis of rat tissue RNA reveals that the beta 2 subunit gene encodes a 3.4-kilobase mRNA which is expressed in a tissue specific fashion distinct from that of rat beta 1 subunit mRNA. Cell lines derived from the rat central nervous system shown to lack beta 1 subunit mRNA sequences were found to express beta 2 subunit mRNA. These results suggest that different members of the Na,K-ATPase beta subunit family may have specialized functions.
Atmospheric Ionization and Clouds as Links Between Solar Activity and Climate

Observations of changes in cloud properties that correlate with the 11-year cycles observed in space particle fluxes are reviewed. The correlations can be understood in terms of one or both of two microphysical processes; ion mediated nucleation (IMN) and electroscavenging. IMN relies on the presence of ions to provide the condensation sites for sulfuric acid and water vapors to produce new aerosol particles, which, under certain conditions, might grow into sizes that can be activated as cloud condensation nuclei (CCN). Electroscavenging depends on the buildup of space charge at the tops and bottoms of clouds as the vertical current density (J z ) in the global electric circuit encounters the increased electrical resistivity of the clouds. Space charge is electrostatic charge density due to a difference between the concentrations of positive and negative ions. Calculations indicate that this electrostatic charge on aerosol particles can enhance the rate at which they are scavenged by cloud droplets. The aerosol particles for which scavenging is important are those that act as in-situ ice forming nuclei (IFN) and CCN. Both IMN and electroscavenging depend on the presence of atmospheric ions that are generated, in regions of the atmosphere relevant for effects on clouds, by galactic cosmic rays (GCR). The space charge depends, in addition, on the magnitude of J z . The magnitude of J z depends not only on the GCR flux, but also on the fluxes of MeV electrons from the radiation belts, and the ionospheric potentials generated by the solar wind, that can vary independently of the GCR flux.
Inclusion of turbulence effects in numerical fluid dynamics

To show this distinction, consider the flow of water past a circular cylinder. For very slow speeds, the flow development is uniquely determined by the magnitude of the Reynolds number, Re E ud/9, in which u is the input flow speed, d is the diameter of the cylinder, and 9 is the kinematic viscosity of the water. Since these are macroscopic parameters, this flow is called laminar. As the speed increases, a double vortex develops behind the cylinder, and when the Reynolds number exceeds about 40, the double vortex begins to oscillate. Except for an arbitrary phase, however, the oscillations are uniquely determined by the macroscopic parameters, u, d, and ~, and the flow is still completely laminar. As the Reynolds number continues to increase, the changing pattern maintains its laminar property until a stage is reached in which noticeable effeots are observed that do not depend upon the macroscopic parameters. These spurious features are the result of microscopic perturbations, which for lower Reynolds numbers could never amplify to significance. They depend upon the details of cylinder roughness , slight mechanical vibrations and minor fluctuations of input water speed, and signify the onset of turbulence.
Beyond knowledge and skills: Discursive construction of civic identity in the world history classroom

ABSTRACTThe research presented in this article investigates the role of classroom discussions for supporting students’ ongoing identity work during the study of global issues. Civic identity is theorized as a socially constructed process in which individuals become associated as a particular type of citizen created through social interactions in a given context. The findings revealed that classroom discussion focused on supporting identity work facilitated students to critique civic discourses and to negotiate global civic identities within the classroom relations of power that privilege certain positions. The findings suggest conceptualizing civic identity as a fundamentally unresolved process of navigating multiple ways of being a citizen that are ongoing and contingent. However, the students did not discard their national identities in favor of global ones. Instead, they made sense of diverse responsibilities by considering the moral implications of remaining loyal to the nation. Thus, rather than impo...
An iterative method to restore the performance of clipped and filtered OFDM signals

Clipping is an efficient and simple method to reduce the peak-to-average power ratio (PAPR) of OFDM signals. However, clipping causes distortion and out-of-band radiation. In this paper, a novel iterative receiver is proposed to estimate and cancel the distortion caused by clipping noise. The proposed method is applied to clipped and filtered OFDM signals. It is shown by simulation that for an 802.11a system, the PAPR can be reduced to as low as 4 dB while the system performance can be restored to within 1 dB of the non-clipped case with only moderate complexity increase and with no bandwidth expansion.
Regulation of coagulation abnormalities and temperature in organ donors

The 3 most common reasons for abnormal coagulation of blood in organ donors result from prior medications, consumption or dilution of coagulation factors and platelets during massive transfusion, and disseminated intravascular coagulation. Evaluation and treatment of these conditions are reviewed, and recommendations are provided for ordering appropriate laboratory tests and blood bank products.
Using cave deposits as geologic tiltmeters: Application to postglacial rebound of the Sierra Nevada, California

[1] Secondary calcite shelfstone deposits in caves can be used to precisely measure tilting over geologic timescales. Calcite deposited along the edges of former pools can be surveyed to within a single millimeter, and can be dated using uranium-series disequilibrium. Two caves in the southern Sierra Nevada, California, contain tilted calcite deposits of glacial age. A third cave contains a similar but untilted deposit of older interglacial age. The cave deposits record glacio-isostatic rebound of the Sierra Nevada, following melting of an ice cap ∼15,000 years ago. Models of crustal flexure beneath mapped ice thickness reproduce the observed tilting with an effective elastic thickness (Te) of approximately 5 km.
Towards efficient tracking of inertial particles with high-order multidomain methods

This paper develops an efficient particle tracking algorithm to be used in fluid simulations approximated by a high-order multidomain discretization of the Navier-Stokes equations. We discuss how to locate a particle's host subdomain, how to interpolate the flow field to its location, and how to integrate its motion in time. A search algorithm for the nearest subdomain and quadrature point, tuned to a typical quadrilateral isoparametric spectral subdomain, takes advantage of the inverse of the linear blending equation. We show that to compute particle-laden flows, a sixth-order Lagrangian polynomial that uses points solely within a subdomain is sufficiently accurate to interpolate the carrier phase variables to the particle position. Time integration of particles with a lower-order Adams-Bashforth scheme, rather than the fourth-order Runge-Kutta scheme often used for the integration of the carrier phase, increases computational efficiency while maintaining engineering accuracy. We verify the tracking algorithm with numerical tests on a steady channel flow and an unsteady backward-facing step flow.
Myasthenia gravis and associated autoimmune diseases in children.

Myasthenia gravis has been associated with other autoimmune disorders. We report two children with myasthenia gravis and another autoimmune disease: an 18-month-old boy with ocular myasthenia gravis and Hashimoto's disease and a 14-year-old girl presenting with autoimmune polymyositis, then generalized myasthenia gravis 2 years later. The rare combinations of myasthenia gravis and Hashimoto's disease or polymyositis in children are discussed, and we also briefly review myasthenia gravis and other associated autoimmune diseases in children. (J Child Neurol 2000;15:767-769).
History education and historical remembrance in contemporary Russia: Sources of political attitudes of pro-Kremlin youth

Abstract Why during the last decade have many young Russians become politically active well beyond simply voting? Particularly striking among youth activists is their enthusiastic support for Putinism and a resounding rejection of the policies, symbols and political figures of the era of President Boris Yeltsin (1992–2000). The vast majority of youth activists are of college age (18–24), which means they were far too young to be aware of what was happening in the country in the 1990s, the period that while democratic and pro-Western, also represents a failure of the Russian state in their imagery. To what degree do the opinions and world views of politically active pro-Kremlin youth reflect the recently emerged, nearly ubiquitous interpretation of recent history as presented in the high school curriculum? To that end, we undertake a content analysis of 47 high school textbooks in Russian history, followed by open-ended interviews with 37 activists from the three most visible youth organizations, all of whom are pro-Kremlin in their orientation. Although demonstrating a causal relationship is methodologically unfeasible, we find a marked correlation between the views of both the Yeltsin and Putin eras presented in those textbooks and in the political beliefs of the youth groups.
Experimental characterization of the effect of skimmer cone design on shock formation and ion transmission efficiency in the vacuum interface of an inductively coupled plasma mass spectrometer

Abstract Laser-induced fluorescence has been used to evaluate five commercially available skimmer cone designs from inductively coupled plasma mass spectrometers in terms of shock formation at the skimmer tip and transmission efficiency. Efficiency was measured as the ratio of analyte density downstream from the skimmer tip to analyte density upstream from the skimmer tip. The strongest shock was recorded for a skimmer with a cylindrical throat, and the weakest shock was produced by the skimmer with the largest diameter and a conical throat. Transmission efficiency increased with increasing orifice diameter. Coulombic effects, revealed in a comparison between the behaviors of neutral barium atoms and barium ions, were small. Transmission efficiencies recorded for calcium ions were lower than those recorded for barium ions by more than a factor of two.
Extracellular signal-regulated protein kinase/Jun kinase cross-talk underlies vascular endothelial cell growth factor-induced endothelial cell proliferation

Ligand binding to vascular endothelial cell growth factor (VEGF) receptors activates the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK). Possible cross-communication of ERK and JNK effecting endothelial cell (EC) actions of VEGF is poorly understood. Incubation of EC with PD 98059, a specific mitogen-activated protein kinase kinase inhibitor, or transfection with Y185F, a dominant negative ERK2, strongly inhibited VEGF-activated JNK. JNK was also activated by ERK2 expression in the absence of VEGF, inhibited 82% by co-transfection with dominant negative SEK-1, indicating upstream activation of JNK by ERK. VEGF-stimulated JNK activity was also reversed by dominant negative SEK-1. Other EC growth factors exhibited similar cross-activation of JNK through ERK. VEGF stimulated the nuclear incorporation of thymidine, reversed 89% by PD 98059 and 72% by Y185F. Dominant negative SEK-1 or JNK-1 also significantly reduced VEGF-stimulated thymidine incorporation. Expression of wild type Jip-1, which prevents JNK nuclear translocation, inhibited VEGF-induced EC proliferation by 75%. VEGF stimulated both cyclin D1 synthesis and Cdk4 kinase activity, inhibited by PD 98059 and dominant negative JNK-1. Important events for VEGF-induced G1/S progression and cell proliferation are enhanced through a novel ERK to JNK cross-activation and subsequent JNK action.
MANNITOL OSMOLAR CLEARANCE IN DIABETES INSIPIDUS OF CHILDREN

A modified technique of amnnitol-induced diuresis is described, in order to assess renal concentrating ability in infants and children. The infusion of 10% mannitol in 0.9% saline avoided the hypertonic saline overload and the fluid restriction period, both badly tolerated by infants and small children. In a control group of children aged from two months to seven years, the values of T(H2O) plotted against C(OSM) allowed to calculate the adjustment curve y=0.80x0.75, r=0.98 (p is less than 0.0001). In six patients with pituitary diabetes insipidus (PDI), the test was used in order to quantify the degree of ADH deficiency and evaluate the carbamazepine and clofibrate effect, in the renal concentrating mechanism. The test was tolerated perfectly in every case, obtaining qualitative and quantitative data and avoiding the hyponatremia and hypokalemia produced by the mannitol.
Atomic force and optical force microscopy: applications to interfacial microhydrodynamics

Abstract Atomic force microscopes (AFM) and related scanning probe microscopes are most commonly used for imaging interfaces and measuring surfaces and colloidal forces. More recently, their use in probing mechanical and viscoelastic properties of macromolecules and fluids near interfaces has begun to receive attention. Here, we examine the dissipative responses of an AFM cantilever and of a spherical particle used as a probe in an optical force microscope (OFM), as a first step in the eventual development of AFMs and OFMs for microrheological measurements near interfaces. We focus specifically on measurements of probe motions normal to the substrate in viscous fluids in order to examine the accuracy of simple models for the oscillations of the cantilever in the case of AFMs and for testing the accuracy of measurements in the case of OFMs. The advantages and disadvantages of the two techniques and some of the outstanding issues are also discussed.
Copolymers derived from phenol functional telechelic oligofluorenes

A series of phenol-capped, oligofluorenes having 2,3,5 and 7 fluorene units and a statistical oligomer with an average of about 10 fluorene units was prepared. In a similar fashion, phenol-capped oligomers having various charge-transporting moieties incorporated into the oligomeric structures were prepared. Polymers were prepared from the oligomers by various linking reactions involving the phenol groups. Trends in the optical and electrical properties as a function of oligomer length will be reported. Device data for this family of emissive copolymers indicates that charge mobility increases with conjugation length, and can be as good as or better than that of an analogous fluorene homopolymer.
Temperature effects in the modal phase shift of a weakly guiding fiber

Temperature may be determined by monitoring the modal phase shift of an optical fiber. We present the results of a numerical model that has been developed to calculate the phase shift of a weakly guiding optical fiber due to thermal strain. Whenever an optical fiber is subjected to temperature changes, the optical path length, the index of refraction and the propagation constants of each fiber mode change. In consequence, the modal phase term, beta(ln)L, of the fields is also modified. A relationship for the modal phase shift is presented. This relation is applied to both single mode and two-mode fibers in order to determine the sensitivity characteristics of fibers that are subjected to temperature changes.
The binding of inhibitors to carbonic anhydrase in vivo: drugs as markers for enzyme.

Abstract Units of activity of carbonic anhydrase in tissues or solutions may be converted to molar terms, as a result of an analysis of inhibition kinetics 1 . In vitro , lens suspensions and, under certain conditions red cells, bind potent carbonic anhydrase inhibitors in concentrations equivalent to original enzyme 2 . The present study shows that acetazolamide, an inhibitor of K I = 6.4 × 10 −8 , binds stoichiometrically to carbonic anhydrase — containing tissues in vivo . If conditions are properly selected, (EI), the bound form of enzyme, might be used as a marker for (E o ), enzyme orginally present.
No risky shift effect with real groups and real risks

Five discussion sections of an introductory psychology course (containing 16-18 students each) were asked to select an examination schedule from a set of eight alternatives. The choices had been scaled by students in a previous course on a risk-safety continuum and were selected for maximum dispersion on the continuum as well as for consistency in placement on the continuum. Individual preferences for schedule were obtained both before and after the group decision. Four of five groups shifted in a conservative direction from the average of initial individual choices. A significant proportion (.9) of those Ss who changed their individual preferences after discussion shifted in a conservative direction. The results suggest that the “risky-shift” effect is an artifact of the laboratory conditions under which it has been obtained.
Distal Interleukin-1β (IL-1β) Response Element of Human Matrix Metalloproteinase-13 (MMP-13) Binds Activator Protein 1 (AP-1) Transcription Factors and Regulates Gene Expression

The collagenase matrix metalloproteinase-13 (MMP-13) plays an important role in the destruction of cartilage in arthritic joints. MMP-13 expression is strongly up-regulated in arthritis, largely because of stimulation by inflammatory cytokines such as IL-1β. Treatment of chondrocytes with IL-1β induces transcription of MMP-13 in vitro. IL-1β signaling converges upon the activator protein-1 transcription factors, which have been shown to be required for IL-1β-induced MMP-13 gene expression. Using chromatin immunoprecipitation (ChIP), we detected activator protein-1 binding within an evolutionarily conserved DNA sequence ∼20 kb 5′ relative to the MMP-13 transcription start site (TSS). Also using ChIP, we detected histone modifications and binding of RNA polymerase II within this conserved region, all of which are consistent with transcriptional activation. Chromosome conformation capture indicates that chromosome looping brings this region in close proximity with the MMP-13 TSS. Finally, a luciferase reporter construct driven by a component of the conserved region demonstrated an expression pattern similar to that of endogenous MMP-13. These data suggest that a conserved region at 20 kb upstream from the MMP-13 TSS includes a distal transcriptional response element of MMP-13, which contributes to MMP-13 gene expression.
Effects of increasing dietary polyunsaturated fatty acids within the guidelines of the AHA step 1 diet on plasma lipid and lipoprotein levels in normal males.

We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.
Finite Element Modeling of Entangled Collagen Fiber Gels With Randomly Oriented Fibers

Collagen is an important structural protein in the human body, and its molecules form structural aggregates at multiple length scales (i.e., microfibrils, fibrils, fibers, and bundles of different sizes) in biological tissues and organs [1]. The mechanical properties of most tissues are dependent on the underlying network of collagen fibers, proteoglycans, and other extracellular matrix components [2]. Similarly, the properties of in vitro tissue analogs, often created from collagen or fibrin gels, are also dependent on the organization of the biopolymers [3]. The overall mechanical response is intrinsically multi-scale and dynamic in both materials. As a result, a satisfactory description of the microstructure is important for exploring the essential physics of the tissue.Copyright © 2009 by ASME
Modification of Human Parotid Saliva Proteins by Oral Streptococcus sanguis

Polyacrylamide gel electrophoresis was used to analyze the effect of Streptococcus sanguis on the anionic proteins in human parotid gland saliva. Cell-free culture supernatants and washed-cell preparations from 23 strains of S. sanguis caused marked modification of various salivary proteins. Control studies showed that the alterations in protein profiles by the bacteria were not due to attachment of protein to the cells. Protease inhibitors were used to confirm that proteolysis by distinct enzymatic activities was responsible for most of the modifications. There was no discernible relationship between the degradation patterns and the various immunologic or genetic groups of S. sanguis. Proteins which contained high concentrations of proline were extensively degraded by S. sanguis. This effect could be blocked with the protease inhibitor phenylmethylsulphonyl fluoride.
Estimating the Health Impact of Climate Change With Calibrated Climate Model Output

Studies on the health impacts of climate change routinely use climate model output as future exposure projection. Uncertainty quantification, usually in the form of sensitivity analysis, has focused predominantly on the variability arise from different emission scenarios or multi-model ensembles. This paper describes a Bayesian spatial quantile regression approach to calibrate climate model output for examining to the risks of future temperature on adverse health outcomes. Specifically, we first estimate the spatial quantile process for climate model output using nonlinear monotonic regression during a historical period. The quantile process is then calibrated using the quantile functions estimated from the observed monitoring data. Our model also down-scales the gridded climate model output to the point-level for projecting future exposure over a specific geographical region. The quantile regression approach is motivated by the need to better characterize the tails of future temperature distribution where the greatest health impacts are likely to occur. We applied the methodology to calibrate temperature projections from a regional climate model for the period 2041 to 2050. Accounting for calibration uncertainty, we calculated the number of of excess deaths attributed to future temperature for three cities in the US state of Alabama.
Targeting Apo2L/TRAIL receptors by soluble Apo2L/TRAIL

The early observation that Apo2L/TRAIL preferentially triggers apoptosis in tumor cells over normal cells highlighted its potential as a candidate therapeutic in cancer. Since its identification in the mid-1990s, our increased understanding of Apo2L/TRAIL and Apo2L/TRAIL receptor signaling has led to the development of several agonists designed to promote tumor cell apoptosis through death receptor engagement. Recombinant human Apo2L/TRAIL/dulanermin is unique in that it is the only agonist which binds both Apo2L/TRAIL death receptors. In pre-clinical studies dulanermin demonstrates broad spectrum anti-tumor activity and the ability to cooperate with multiple conventional and targeted therapies. Results from early stage clinical trials indicate that dulanermin is well tolerated and shows some evidence of clinical activity. Not all tumors are likely to be equally sensitive to apoptosis induction by Apo2L/TRAIL. Therefore, an increased understanding of the regulation of Apo2L/TRAIL signaling should aid in the identification of molecular signatures that define a patient population likely to respond. In this review, current knowledge and new insights about Apo2L/TRAIL signaling is discussed with the focus on the development of Apo2L/TRAIL as a cancer therapeutic.
DETECTION OF HETEROGENEOUS GROWTH HORMONE (GH) GENE SPLICING BY DNA ANALYSIS OF DRIED BLOOD SPOTS FROM GH DEFICIENT SUBJECTS

The molecular basis of familial isolated GH deficiency (IGHD) is heterogeneous. We have previously found a G → A transition in codon 20 of the GH gene that produces a stop codon and two donor splice site mutations (a T → C transition in the sixth base of IVSIII and G→ C transversion in the first base of IVS IV). The G→ C transversion, which destroys an HphI (GGTGA) restriction site at the exon IV/intron IV boundary (G/GTGA → G/CTGA), was found in a Saudi family with IGHD. To determine the frequency of this mutation among Saudi IGHD subjects, dried blood spots were analyzed from 12 additional Saudi cases from different families. The methodology involved a one-step PCR amplification of DNA obtained from 2 mm2 portions of dried blood spots which were collected on filter paper. These amplification products were then digested with HphI and analyzed on agarose gels. One subject was homozygous and the single, parental sample obtained was heterozygous for loss of this HphI site. Interestingly a simple repeat polymorphism adjacent to the GH gene differed between the two non-related Saudi subjects, who lacked the HphI site, suggesting that the GH mutaiions were independent. To determine if the GH mutations causing loss of the HphI site differed between the two Saudi IGHD cases, direct sequencing of the PCR products obtained from the filler paper samples was performed. In contrast 10 the firsi Saudi case which had a G→C transversion in the first base of IVS IV (G/CTGA) the second had a G→T transversion (G/TTGA). Analysis of the transcription products of the G→C mutation documented aberrant splicing and transcript analysis of the G→T mutation is being done for comparison. Our findings demonstrate 1) detection of GH splicing defects by restriction analysis and sequencing of DNA from dried blood spots and 2) 2/13 (15%) of Saudi IGHD subjects have IVS 3V donor splice site defects. These findings suggest that heterogeneous mutations which lead to transcript splicing errors may constitute a significant proportion of IGHD cases.
Ultrasonic bone assessment: "The time has come"

Bone is unique in its ability to maintain its strength in the presence of constant turnover. It has been established that there is gradual and relatively complete removal and replacement with new bone several times in a lifetime. The reparative pattern is constantly changing in order to maintain strength and is influenced by changes in general health, the presence of disease, and the degree of physical activity. To date, no method has been developed to measure the nature of lifetime changes in patterns during childhood and throughout older age [1]. Often the first indication that a problem exists is the occurrence of a fragility fracture, which is often associated with a high degree of morbidity and mortality. Fracture risk is dependent on the strength of bone as well as other factors including tendency to fall. This latter aspect may be related to poor balance and eyesight, or to environmental obstacles like stray wires, defective pavements, and edges on carpeting [2]. Inherent strength of bone depends upon a host of multi-factorial components. Dual-energy X-ray absorptiometry (DXA), which measures the mass of the mineralized matrix at a given site (e.g., hip, spine, forearm) is currently the accepted indicator used to assess bone strength. It has been shown that bone mass has about the same predictive value for fracture as blood pressure has for stroke [3]. Stages of bone turnover have been studied by analysis of biochemical markers as bone is removed and reformed [4]. But there is as yet no reliable clinical method to assess the status of the internal trabecular structure of bone which normally contributes significantly to strength. Notwithstanding the fact that X-ray densitometry is reasonably effective in bone mass assessment, osteoporosis remains one of the most prevalent undiagnosed and under-diagnosed diseases in the world today [5]. Among the reasons for this is that densitometry (i.e., DXA) is not a standard tool in a primary care physician's office. It does not lend itself to routine screening because of expense, inconvenience, and reticence concerning X-ray exposure, particularly in young adults and children. It is estimated that approximately 20% of women with osteoporosis have unrecognized or untreated conditions that are capable of causing absorption of bone (“secondary osteoporosis”) [6]. These may include thyroid, parathyroid, gastrointestinal disease, may be drug related or associated with a whole host of other possibilities [6]. Similarly for example, in adolescents and children, bone loss may be associated with metabolic conditions including hypogonadism, malnutrition, bulimia, and medication [7]. The ability to screen the quality of bone at any age would be expected to serve as preventive medicine by uncovering unrecognized causes and permit treatment of these conditions as well as to institute early appropriate therapy for osteoporosis.
How do you diagnose latex allergy

The diagnosis of latex allergy is a clinical challenge that practitioners are confronting with increasing frequency. Distinguishing the causes of delayed-type reactions requires careful patch testing. For patients with immediate-type symptoms, currently available tests are imperfect. This review by four national experts presents practical approaches to a dermatologic dilemma.
Problem-based Learning in the Teaching of Hospitality Law

Problem-based learning (PBL) has emerged as an important alternative or supplement to traditional lecture methods of teaching. In a PBL setting, student teams face challenging situations or cases, and the teams are expected to develop and recommend solutions. This article discusses the application of PBL to a class of 100 students enrolled in a required course in hospitality law. The case that was used involved a resort housekeeper being sexually harassed by a maintenance worker. The article reports on the experience with PBL, including problems, student evaluations, and recommendations for future PBL endeavors. Times change, and what were effective teaching methods may no longer be as effective with today's college students. The lecture method has been fundamental to higher education in the United States. The method is particularly helpful in delivering information to large numbers of students. From an efficiency standpoint, what could be better than one professor teaching a hundred or more students in o...
Amplification and rearrangement of integrated SV40 DNA sequences accompany the selection of anchorage-independent transformed mouse cells

Abstract Clones of SV40 tsA mutant-transformed mouse embryo cells with a temperature-independent transformed growth phenotype were derived from a parental line with a temperature-dependent growth phenotype, using the selective pressure of anchorage independent growth in agar at 40°C. The parental J78 clone contained a complex tandem structure of integrated SV40 DNA within two cellular DNA fragments of 10 and 14 kb, generated by Bgl II digestion. The new clonal derivatives, in addition to an altered growth phenotype, displayed additional high molecular weight sites of SV40 DNA integration. A marked structural similarity among integration sites suggested that the new sites may have arisen by duplication and translocation of an original integration structure, or via an unequal cross-over event. The rearrangement of viral DNA sequences appears to be specifically associated with the emergence of temperature-independent clones, since the isolation of new clones under nonselective conditions, that is, growth in semi-solid medium at 33°C, was not accompanied by modifications in cellular sequences containing SV40 DNA.
Resisting whiteness' rhetorical silence

This essay explores the rhetorical dimensions of whiteness in public political discourse from an ideological perspective. It analyzes a debate between Carolyn Moseley Braun and Jesse Helms over a patent extension for the United Daughters of the Confederacy insignia containing a Confederate flag. In this essay I argue that rhetoricians must do the critical and self‐reflexive ideological work necessary to make whiteness visible and overturn its silences for the purpose of resisting racism. To do this, scholars must locate interactions that implicate unspoken issues of race, discursive spaces where the power of whiteness is invoked but its explicit terminology is not, and investigate how these racialized constructions intersect with gender and class.
Loss of Na+ channel β2 subunits is neuroprotective in a mouse model of Multiple Sclerosis

Abstract Multiple sclerosis (MS) is a CNS disease that includes demyelination and axonal degeneration. Voltage-gated Na+ channels are abnormally expressed and distributed in MS and its animal model, Experimental Allergic Encephalomyelitis (EAE). Up-regulation of Na+ channels along demyelinated axons is proposed to lead to axonal loss in MS/EAE. We hypothesized that Na+ channel β2 subunits (encoded by Scn2b) are involved in MS/EAE pathogenesis, as β2 is responsible for regulating levels of channel cell surface expression in neurons. We induced non-relapsing EAE in Scn2b+/+ and Scn2b−/− mice on the C57BL/6 background. Scn2b−/− mice display a dramatic reduction in EAE symptom severity and lethality as compared to wildtype, with significant decreases in axonal degeneration and axonal loss. Scn2b−/− mice show normal peripheral immune cell populations, T cell proliferation, cytokine release, and immune cell infiltration into the CNS in response to EAE, suggesting that Scn2b inactivation does not compromise immune function. Our data suggest that loss of β2 is neuroprotective in EAE by prevention of Na+ channel up-regulation in response to demyelination.
Natural History, Evaluation, and Management of Intracranial Vascular Malformations

Intracranial vascular malformations are seen increasingly in clinical practice, primarily because of advances in cross-sectional brain and spinal cord imaging. Commonly encountered lesion types include arteriovenous malformations, cavernous malformations, venous malformations, dural arteriovenous fistulas, and capillary telangiectasias. Patients can experience various symptoms and signs at presentation. The natural history of vascular malformations depends on lesion type, location, size, and overall hemodynamics. The natural history for each lesion subtype is reviewed, with special consideration of the risk of hemorrhage or other adverse outcomes after the lesion is detected and any known predictors of hemorrhage or other outcomes. In practice, these data are compared with the risk of available treatment options as the optimal management is clarified. A multidisciplinary approach including neurosurgery, radiosurgery, interventional neuroradiology, and vascular neurology is most useful in determining the best management strategy.
Primary Care Physicians’ Access to Genetic Specialists – An Impediment to the Routine Use of Genomic Medicine?

Primary-care physicians’ access to genetic specialists: an impediment to the routine use of genomic medicine?
Who are we? Remembering and forgetting in the reparation of communal identity:

This article offers a review of Kierkegaard’s inverse dialectic of forgiveness. It interprets his use of remembering and forgetting in the inverse dialectic as an ethical axiom, shifting the dialec...
Sites of action of testosterone in the brain of the female primate.

Thaw-mount autoradiography was used to map target neurons for tritiated steroids in the brains of ovariectomized rhesus monkeys. In five females, studies were performed 60 min after the administration of 3H-estradiol. Of these, two females were pretreated for five days with daily injections of 2 mg testosterone propionate, one female was pretreated with daily injections of 2 mg dihydrotestosterone propionate, and two females were pretreated with oil vehicle. For comparison, two additional females were administered 3H-testosterone and were killed 30 min later. Following 3H-estradiol administration in females pretreated with oil, there were numerous labeled neurons in the medial preoptic nucleus (n.), anterior hypothalamic area, ventromedial hypothalamic n., arcuate n., bed n. of stria terminalis, lateral septal n., and regions of the amygdala. In females pretreated with testosterone propionate, labeling was virtually abolished in all these areas with the exceptions of the lateral septal n. and arcuate n., presumably because estradiol formed from testosterone competed with 3H-estradiol for estrogen-binding sites. Pretreatment with dihydrotestosterone propionate had no effect on the labeling following the administration of 3H-estradiol. Areas where labeling was blocked, therefore, represent regions where testosterone acted as an estrogen, and it would appear that regional differences in the activity of aromatizing enzymes determine which estrogen target sites in the brain can interact with estrogenic metabolites of testoterone in female primates.
A Discontinuous Phase-Space Finite Element Discretization of the Linear Boltzmann-Vlasov Equation for Charged Particle Transport.

We examine the modeling of charged-particle transport when both collision processes with background media and electromagnetic effects are important using the Boltzmann-Vlasov equation. We derive and transform the Boltzmann-Vlasov equation into a form very similar to the standard linear Boltzmann equation with additional operators. We apply the discontinuous finite element methods for discretization in the spatial, energy, and angular variables. An implementation of these methods demonstrates correct transport behavior for fixed electric and magnetic fields. We also demonstrate coupling to Maxwell's equations with a simple electromagnetic solver to generate self-consistent fields.
Identification of the viscoelastic characteristics of an artificial neck

Abstract This paper is devoted to the identification of the viscoelastic characteristics of an artificial neck employed to conduct experiments on dummies in automobile crash simulation tests. The neck is assumed to be a linear viscoelastic cantilever beam subject to a bending moment and a shear force at the head-neck junction. Time histories of these forces and the associated rotation obtained in a calibration test simulating an automobile crash condition are available and furnished by the manufacturer of the neck. Using these data, an identification procedure in the Laplace transform space is developed. The analytical relationships between forces and displacements at the head-neck junction are presented in Sec. 2, and the viscoelastic model is introduced in Sec. 3. In Sec. 4, the identification problem is formulated, and in Sec. 5 an example displaying experimental versus predicted results is presented. Finally in Sec. 6 an extension to consider higher dimensional representations is outlined.
Renal metabolism of formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide

Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide (FNT) is a potent renal carcinogen in the rat. This study assessed the metabolism of FNT by the isolated perfused rat kidney and whole rat. The glomerular filtration rate and the fractional excretion of sodium for the isolated perfused kidney indicated that under the conditions of these experiments FNT did not alter these renal parameters. The half-life (t1/2) for FNT in the isolated perfused kidney was 67 +/- 8 min. Using HPLC, a metabolite of FNT was observed in urine from the isolated perfused kidney. This metabolite had absorbance at 385 nm but not 254 nm and could not be detected electrochemically at +500 mV. While the excretion of FNT decreased with time of perfusion, the metabolite excretion increased. Whole animal studies demonstrated that FNT is rapidly cleared from blood within the first 5 min of administration. The FNT metabolite was excreted at approximately the same rate from 0-30 and 30-60 min after FNT administration. The metabolite was not observed in media from FNT perfused kidneys or plasma from animals administered FNT. Analysis of purified metabolite by liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) determined the structure to be 5-nitro-2-furonitrile. This structure assignment was verified by chemical synthesis. Results demonstrate target organ metabolism of carcinogen.
The first amendment at the crossroads: Free expression and new media technology

A century and a half after it became part of the Constitution, the First Amendment finally began to fulfill its promise of protecting freedom of speech and press. Only in recent decades have courts extended that protection to a broad range of expressive activity. In an era of emerging media technology, courts will be called on to establish new constitutional principles to deal with the changing communications landscape. Once unleashed, the “new”; First Amendment standards will be available to change the legacy of landmark cases that some consider to be overly‐solicitous of freedom of speech and press. Protecting the First Amendment in the cyberspace era is best accomplished not by creating new standards, but by applying and thus preserving established First Amendment principles.