cssi/SciSciGPT-SciSciNet huggingface dataset:
RNA polymerase comes into focus

Understanding the mechanism and regulation of RNA synthesis is a key objective in molecular biology. In recent years a plethora of factors that regulate transcription has been identified. Most of these factors either facilitate or impair access of RNA polymerases to template DNA. Crosslinking and mutational studies have provided key information regarding the mechanism of RNA synthesis. Nonetheless, the structural basis of RNA synthesis has remained elusive. Until now, structural information for multisubunit RNA polymerases was limited to low-resolution electron crystallography of yeast and bacterial enzymes.We now enter a new era with high-resolution X-ray crystal structures for eukaryotic and bacterial RNA polymerases. Poglitsch et al.1xElectron crystal structure of an RNA polymerase II transcription elongation complex. Poglitsch, C.L. et al. Cell. 1999; 98: 791–798Abstract | Full Text | Full Text PDF | PubMed | Scopus (55)See all References1 have extended the low-resolution structure of yeast RNA polymerase II to an active transcription complex that includes template DNA and product RNA. In addition to identifying the catalytic region of the enzyme, this structure defines a novel path for the DNA template across one face of the enzyme. Furthermore, Fu et al.2xYeast RNA polymerase II at 5 A resolution. Fu, J. et al. Cell. 1999; 98: 799–810Abstract | Full Text | Full Text PDF | PubMed | Scopus (104)See all References2 have solved the X-ray structure of yeast RNA polymerase II in the absence of nucleic acid at 5 A resolution. Comparison of this structure with the transcriptionally active complex identified two flexible domains as potential DNA and RNA clamps. Zhang et al.3xCrystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution. Zhang, G. et al. Cell. 1999; 98: 811–824Abstract | Full Text | Full Text PDF | PubMed | Scopus (548)See all References3 treat us to an even clearer view of the enzyme with the crystal structure of bacterial core RNA polymerase at 3.3 A resolution. This is truly a landmark achievement that defines the overall architecture of RNA polymerase, subunit structures and interactions, and the active center of the enzyme. The results from DNA and RNA crosslinking studies could also be mapped onto this structure to define components involved in DNA and RNA binding. These X-ray structures are consistent with the earlier electron crystallographic structures and most features are conserved between the bacterial and yeast enzymes. We can now anticipate seeing more refined structures of RNA polymerases and their complexes trapped at different stages of the transcription cycle. A detailed mechanistic understanding of this most fundamental process in gene expression is rapidly coming into focus.
Imaging and etching: soft x-ray microscopy on whole wet cells

We have produced images of whole wet tissue culture cells with the Stony Brook/BNL scanning transmission x-ray microscope (STXM). For fixed cells we have taken images at theoretical resolutions of ~50-75 nm, and in practice have measured FWHM of features down to near 100 nm, without any exotic image processing. For un-fixed (i.e., initially live) cells we have imaged with 100 nm pixels and measured features down to 250 nm. In order to do this we have developed, tested, and used a wet cell for maintaining fixed or live cells on the STXM stage during imaging. Our design of the wet cell and the culture substrates that go with it make the STXM compatible with almost all standard systems for surface adherent tissue culture. We show some new images of whole wet fixed and unfixed cells, with visible sub-micron features. We also report data that helps to characterize the tissue damage due to x-ray absorption during STXM imaging.
The Horizontal Branch and the Cosmic Abundance of Helium

Stellar models deriving their luminosities from helium burning in the core and hydrogen burning in a shell are investigated for helium core masses of 0.425, 0.450, and 0.475 M/sub sub solar /, and for total masses ranging from 1.35 M/sub sub solar / down to the respective core masses. The investigated helium and heavy-element abundances lie within the ranges (0.25, 0.45) and (0.0001, 0.06) respectively. The readjustment of the hydrogen bunning shell on the horizontal branch is studied. The effect of a changing core mass as a function of the width of this hydrogen profile is used to extend the validity of previous zero-age-horlzontal-branch computations with steep profiles into the regime of broadened, typical horizontal-branch profiles. The color dispersion of stars along the horizontal branch is found to be about twice as sensitive to a core-mass spread than to an equal spread in total mass. Preliminary evidence for the existence of a core-mass spread along the blue horizontal branches of globular clusters is presented. A new method for determining the helium abundances of horizontal-branch stars is presented. The method is shown to be independent of the heavy-element abundance, of the mixing length, of small changes in the hydrogen composition profile,more » and independent of the main effects of evolution during the core-helium burning phase. Comparisons with available observations indicate that the helium abundance of the halo population of the Galaxy is greater than 0.30 plus or minus 0.04 by mass fraction. The helium abundances of seven open clusters average to 0.23, with an uncertainty of 0.10 to 0.20. This inverse correlation between the helium abundance and angular momentum of the populations in our Galaxy is supported by a preliminary study of helium abundances obtained from other methods. The cosmological implications of this inverse'' helium composition gradient suggest that either some helium enriching mechanism acted during the protogalactic collapse in regions of high density and low metal abundance or (and) the chemical inhomogeneities were created in the primeval fireball. (auth)« less
Intracellular transport of sulfated macromolecules in parotid acinar cells

Intracellular transport of sulfated macromolecules in parotid acinar cells was investigated by electron microscopic radioautography after injection of 35S-sulfate. Ten minutes after injection radiosulfate was concentrated in the Golgi region. By 1 hr, much of the radioactive material had been transported to condensing vacuoles. These vacuoles were subsequently transformed into zymogen granules which contained almost 70% of the radioactivity 4 hrs after injection. These results indicate that, in addition to its packaging function, the Golgi apparatus in parotid acinar cells is capable of utilizing inorganic sulfate for the production of sulfated macromolecules. These molecules, following an intracellular route similar to that taken by digestive enzymes, become an integral component of zymogen granules. The possibility that sulfated macromolecules play a role in exocrine secretion by aiding in the packaging of exportable proteins is discussed.
Preparation and Characterization of an Endogenously Fluorescent Annexin for Detection of Apoptotic Cells

Abstract Annexin proteins specifically bind anionic phospholipids such as phosphatidylserine, which are normally confined to the cytoplasmic leaflet of cellular membranes. During programmed cell death, or apoptosis, this phospholipid asymmetry is lost, and anionic phospholipids are exposed on the extracellular leaflet of the plasma membrane where they are accessible to exogenously added, labeled annexins. Chemically [e.g., fluoroscein isothiocyanate (FITC)]-modified annexin V has been widely used to detect and enumerate apoptotic cells by flow cytometry. We prepared chimeric proteins containing green fluorescent protein (GFP) fused to annexin V. A chimera containing GFP fused to the C-terminus of annexin V was soluble and fluorescent, but was unable to bind phospholipids. In contrast, a chimera containing GFP fused to the N-terminus of annexin V specifically bound apoptotic cells. GFP–annexin V represents a sensitive and facile alternative to FITC–annexin V for studies of apoptosis.
Production of FeCrAlY and CoCrAlY coatings by laser surface fusion and their oxidation behavior

Abstract In this paper the results of a study aimed at coating large areas with FeCrAlY and CoCrAlY alloys by laser surface fusion are described. Metallurgical characteristics and oxidation behavior of the coatings are discussed. The results indicate that fusion of the coating materials was complete and a metallurgical bond was formed between the coatings and the type 304 stainless steel (SS) substrate as a result of laser processing. Some dilution of the coating alloys, in particular the aluminum content, was noticed due to melting of a portion of the substrate. Some small cracks, observed in the CoCrAlY coating, were formed as a result of shrinkage during solidification. Oxidation studies were performed at 1000–1185 °C in air for various times. The coatings, although diluted, showed excellent oxidation resistance and protection, while the type 304 SS substrate deteriorated rapidly. The effect of the thermal and oxidation treatment on the microstructural and chemical stabilities of the coatings are discussed.
Influence of Sodium Dodecyl Sulfate and Tween 20 on Fungal Growth and Toluene Degradation in a Vapor-Phase Bioreactor

Biofiltration, a process in which contaminated air is passed through a biologically active bed, can be used to remove volatile organic pollutants from air streams. While most biofilters rely on bacteria to degrade organic pollutants, biofilters utilizing a fungal biofilm have the potential to be an efficient and robust treatment alternative. In this study, two surfactants were evaluated for their ability to activate the spores of the fungus \IExophiala lecanii-corni\N and reduce the start-up period typically observed in fungal vapor-phase bioreactors. Sodium dodecyl sulfate, an anionic surfactant, was found to inhibit growth of \IE. lecanii-corni\N. Polyoxyethylene sorbitan monolaurate (Tween 20), a nonionic surfactant, stimulated bud formation and enhanced toluene degradation in \IE. lecanii-corni\N cultures. Tween 20 was also found to enhance inoculum development by shortening the lag period during culture growth. However, when bioreactors were presoaked in medium containing Tween 20, washout of the fungal cells occurred during inoculation, inhibiting the initial fungal biofilm development. After a seven-day start-up period, no detrimental effects on reactor performance due to residual Tween 20 were observed, and toluene elimination capacities of up to 150 g/m3h were achieved.
Sensitivity of AIRS and IASI radiometric calibration to scene temperature

High radiometric accuracy under all conditions (such as scene temperature and scan angle) is critical for establishing a climate-quality data record. In this study we compare radiances of both AIRS and IASI using the difference each instrument sees between the brightness temperature at 1231 cm-1 and that at 961 cm -1 . We collected spectra at 17 different sites distributed around the world in tropical, temperate, desert, and arctic climates. For perfectly calibrated instruments, the brightness temperature differences should closely agree, since diurnal differences caused by the differing orbits cancel to first order. We examine observed differences (indicative of calibration artifacts) as functions of scene temperature, time of day, and scan angle. AIRS is a cooled grating array spectrometer with 2378 spectral channels in the wavelength range from 3.7 to 15.4 microns. AIRS began routine operations in September 2002. IASI is a Fourier Transform spectrometer covering the range 3.6 to 15.5 microns in three bands. The spectral resolutions of AIRS and IASI are similar. IASI data have been available since July 2007.
Endoscopic fluorescence imaging of tissue selective lanthanide chelates

Endoscopic probes have been incorporated into a fluorescent imaging system for the remote quantitation of tissue selective markers. Resolution at the level of 114 line pairs/mm allows visualization of regions that are approximately 6 mm wide. Tissue selective markers, based on polyazamacrocyclic chelates of terbium increase contrast and can be quantified in tissues at the sub-picomole level. Minimally invasive in vivo fluorescence imaging is demonstrated. The potential for application of the system to disease diagnosis and bone graft morphology quantitation is discussed.
Expectant Management of Anal Squamous Dysplasia in Patients With HIV

Anal squamous dysplasia is commonly found in patients with HIV infection. There is no satisfactory treatment that eradicates this premalignant lesion with low morbidity and low recurrence. This study reviews a series of patients with HIV and an abnormal anal examination who had squamous dysplasia and who have been followed with physical examination alone and with repeat biopsies as necessary for new or suspicious lesions. We reviewed the charts of 40 HIV-positive men who had squamous dysplasia of the anal canal and anal margin, focusing on history, physical findings, histologic diagnosis, and the occurrence of invasive squamous-cell carcinoma. Forty HIV-positive men (mean age, 39 years) were followed for anal squamous dysplasia. Biopsies revealed dysplasia, which was usually multifocal. The grade of dysplasia varied, but 28 of 40 patients had at least one area of severe dysplasia. All patients had a follow-up period greater than one year (mean, 32 months; range, 13–130 months). Three patients developed invasive carcinoma while under surveillance, and these were completely excised or cured with chemoradiation. Extensive excision for dysplasia in the context of HIV confers high morbidity and questionable benefit, and other treatments are of uncertain value. In a group of patients followed expectantly, most did not develop invasive cancer, and in those who did, early cancers could be identified and cured. Physical examination surveillance for invasive carcinoma may be acceptable for following patients with HIV and biopsy-proven squamous dysplasia.
And the Beat Goes On: Intergovernmental Mandates and Preemption in an Era of Deregulation

For state and local governments, the 101st Congress (1989-1990) compiled a mixed record of intergovernmental regulation and preemption. Costly and intrusive mandates were enacted to combat air pollution, protect the rights of disabled persons, and provide medical assistance to the poor. At the same time, new restrictions were defeated in legislation affecting oil-spill liability and child care. This article reviews the issues and politics surrounding these enactments, and places them within the broader context ofintergovernmental regulatory trends during the 1980s. The past decade was characterized by increasing regulatory burdens imposed on states and localities, punctuated by occasional examples of regulatory relief and deferral.
Effects of virus concentration and ultraviolet irradiation on the activity of corn earworm and beet armyworm (Lepidoptera: Noctuidae) nucleopolyhedroviruses.

Laboratory studies were initiated to determine the relationship between virus concentration and radiation-caused inactivation of NPVs from Helicoverpa zea (HzSNPV) and Spodoptera exigua (SeMNPV). In the laboratory, a UV-B/UV-A system was used for inactivation studies. For both viruses inactivation was dependent upon both length of UV exposure and virus concentration. At all virus concentrations HzSNPV was more sensitive to UV than SeMNPV. In the field HzSNPV was used and virus persistence was significantly affected by virus concentration (i.e., inactivation was inversely related to virus concentration).
Role of Central 5-HT2 Receptors in Fluoxetine-Induced Decreases in T Lymphocyte Activity

Previous studies have demonstrated that fluoxetine administration decreases mitogen-induced T lymphocyte proliferation. The present studies were carried out to determine which receptor subtype(s) was involved and whether these effects on lymphocyte responses were centrally or peripherally mediated. Two hours following administration of the 5-HT(1A) agonist 8-OH-DPAT (1 mg/kg), there was no change in lymphocyte proliferation responses, whereas the 5-HT(2) agonist DOI (2.5 mg/kg) significantly decreased (80%) proliferation. Similarly, pretreatment with the 5-HT(2) antagonists ritanserin (5 mg/kg, 30 min) or ketanserin (5 mg/kg, 1 h) was found to completely antagonize the effects of fluoxetine on lymphocyte proliferation. Consistent with central 5-HT(2) receptor involvement, microinjection of DOI (50 microg) resulted in a decrease in lymphocyte proliferation similar to that observed following systemic administration. Furthermore, central administration of ketanserin (20 microg) prevented the suppressive effects of systemic fluoxetine. Collectively, these results suggest that decreases in mitogen-induced lymphocyte proliferation following acute fluoxetine administration was due to indirect effects of fluoxetine following the activation of central 5-HT(2) receptors.
Development of intrinsic connections in cat somatosensory cortex.

We explored the development of clustered connections in cat somatosensory cortex by using intracortical injections of biocytin and carbocyanine dye (DiI). Biocytin injections in adults revealed clusters of retrogradely labeled cells, affirming earlier reports of the patchy nature of corticocortical connectivity in the adult cat somatosensory cortex. On postnatal days (PNDs) 1 and 3, a diffuse distribution of axons and labeled cells were found after DiI injections. A dramatic rearrangement of connections had taken place by PND 6. Well-defined clusters of labeled cells surrounded the injection site. Intercluster zones were relatively free of labeled cells and contained few labeled axons. At later ages (PNDs 12 and 15), a clear patchy distribution of intrinsic connections was seen. We analyzed neuronal clustering by using spatial point process analysis, which corroborated our qualitative observations. The density of labeled neurons was significantly higher in clusters than in the intercluster zones on PND 6. Autocorrelations run on profile plots of optical density values, along paths parallel to the edge of the injection sites (reflecting axonal distributions), revealed significant periodicity (P < .05; center-to-center ∼ 750 μm) by PND 6. These data demonstrate that corticocortical connections in cat somatosensory cortex develop from a diffuse network at birth, which transforms into a patchy network by the end of the 1st postnatal week. This is substantially earlier than the development of local circuits in the cat visual cortex and may reflect fundamental differences in the organization of the two cortices. J. Comp. Neurol. 384:501–516, 1997. Published 1997 Wiley-Liss, Inc.
Laser desorption Fourier transform mass spectra and mass measurement accuracy for bradykinins

Abstract Laser desorption Fourier transform mass spectrometry (LD/FTMS) was used to obtain mass spectra of bradykinin, Lys-bradykinin, and Met-Lys-bradykinin. With poly(ethylene glycol) as an external mass standard, absolute errors for mass measurement accuracy averaging 2–7 ppm were obtained for the major ions of the bradykinins. Similar absolute errors for mass measurement accuracy were obtained when poly(ethylene glycol) was used as an internal standard. Mass measurement accuracy was investigated and applicability of the measurements to elemental composition assignments examined. Present results are compared with previous field desorption, secondary ion mass spectrometry, and fast atom bombardment spectra of bradykinins.
Heterotopic ossification: A case report and immunohistochemical observations

This report describes the case of a 69-year-old man with adenocarcinoma of the transverse colon who developed heterotopic ossification in a metastatic axillary lymph node. The areas of pathologic bone formation were characterized by the appearance of osteoblast-like cells at the surfaces of the mineral deposits. Immunostaining for alkaline phosphatase revealed a significant concentration of this enzyme in these cells and, to a lesser degree, on the apical membrane of the glandular cells of the adenocarcinoma adjacent to the ossification centers. Proliferating mesenchymal cells in close proximity to the areas of osteogenesis also showed significant immunolabeling. We conclude that metastatic colonic carcinoma can promote heterotopic ossification, and that alkaline phosphatase is intimately associated with bone formation under these pathologic conditions.
The Pride and Prejudice of the Western World: Canonic Memory, Great Books and Archive Fever

The article examines controversies arising from the perception of the instruments of cultural memory and the logic of their transmissibility. On the one hand we have a carefully selected, temporally and geographically orchestrated body of texts, the Great Books, which are an enduring testament to the authority of Western intellectual artifacts. On the other hand, Jacques Derrida’s Archive Fever locates a furtive transformation of collective memory in the informal practices exemplified by oral narrative and public discourse. Not only do both models rely on archives as a functional instrument of collective identity, but they also value them as institutions circumscribing social and cultural conventions. However, when synchronizing the traces embedded in oral discourse and written documents, the repositories are frequently subject to manipulation by interpretive communities. Recognizing the processes underlying archives and artifacts is essential to comprehending how canons and canonic practices impact Western cultural memory.
Make secondary education universal

The time is right to push global learning beyond primary-school level, says Joel E. Cohen. The benefits could include a dramatically smaller increase in world population by 2050. One of the UN Millennium Development Goals is universal primary education for all children — boys and girls — by 2015. Population biologist Joel Cohen argues that it is time to look to the next step. Universal secondary education is achievable within 25 years, he says. Secondary education motivates people to reduce their own fertility, improve the survival of their children, and care for family health. It can help counter population increase and benefit the environment. Visit Nature Network to discuss the topic further.
Volatility relationship between stock performance and real output

This paper investigates the interaction between stock index returns and the real output growth for five countries. This study focuses on the second moment relationship using various forms of the bivariate generalized autoregressive conditional heteroscedastic models (BGARCH). This study shows that interactivity between stock returns and growth rates are robust at the second order. The results imply that high volatility in the stock market is likely to be followed by increased volatility in the output sector and periods of high volatility in real output is likely to be followed by increased volatility in the stock market.
Sex Hormone Binding Globulin and Sex Steroids Among Premenopausal Women in the Diabetes Prevention Program

Context: It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). Objectives: We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. Participants: A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). Interventions: Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. Results: Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (∼11%) compared to decreases of 1.1 nmol/L in...
Identification of gene expression profiles associated with prognostic groups of patients with Merkel cell carcinoma

Background Merkel cell carcinoma (MCC) is an aggressive form of skin cancer mostly caused by the Merkel cell polyomavirus [1]. MCC although rare in incidence is associated with poor prognosis. Gene expression studies (GES) have identified a number of genes that are associated with risk of developing MCC. However, their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. There is a need to better understand the biology of MCC and to develop potential new targets with regard to cancer risk and prognostic value [2]. Gene expression profiling and pathway association analysis on GES data can elucidate relevant biological processes, and identify new candidate target genes. Materials and methods We sought to identify differential gene expression and functional associations in MCC. Differentially expressed genes with a P value ≤ 0.05 and a fold change ≥ 2.5 between prognostic groups were identified and pathway association analysis was done for a total of 38 differentially expressed genes from a gene expression profiling study [3] with prognostic groups of MCC patients. The over representation of gene-based associations in each pathway was calculated using Fisher’s exact test. Results Pathways involved in neuropathic pain signaling, glutamate receptor signaling and synaptic long term potentiation were found to be highly enriched with associations. These results suggest that gene expressions associated with these pathways may contribute to MCC development and prognosis.
Cancer: whispering sweet somethings.

That genetic mutations contribute to cancer is undisputed. What now emerges is that a cancer cell's microenvironment has a much stronger hand in the course a cancer takes than previously thought.
Influence of microcompositional gradients on stress corrosion crack propagation

Abstract Stress corrosion cracking in compositionally non-uniform systems is addressed. Of special interest is the preferred direction of crack propagation in stress-corroded weld metal. Solidified structures of a cast austenitic stainless steel designed to simulate a solidified weld structure were homogenized to various degrees which caused changes in their microcompositional profiles, resulting in subsequent changes in cracking susceptibility and rates. A K ISCC expression was modified using Cahn-Hilliard non-uniform thermodynamic concepts to explain the change in cracking behavior.
Math on the Internet

Engineering math may have changed little since slide rules were traded in for computers, but math software continues to evolve, driven by the rapid progress of computers and by competition among software vendors. Perhaps the most interesting developments have been the emergence of new ways to publish documents containing math on the World Wide Web and the changes in math programs that have resulted. The paper considers how the evolving mathematical markup language plus add-ons to leading software are spurring computational sharing on the World Wide Web.
The solution structure of small peptides: An IR CD study of aqueous solutions of (L‐Ala)n [n = 3, 4, 5, 6] at different temperatures and ionic strengths

The solution conformation of a number of small, linear alanine oligomers was investigated via ir (or vibrational) CD (VCD). We find that these oligopeptides assume distinct solution conformations that depend primarily on chain lengths, and to a lesser degree on temperature, ionic strength, and pH. As expected, the longer chain oligomers exhibit more distinct VCD features and, presumably, more stable solution structures. At the level of the hexamer, however, aggregation of the peptide occurs. The fast time scale of VCD allows solution structures to be detected that may not be observable using slower techniques such as various forms of nmr spectroscopy. The VCD results reported here confirm that it is generally possible to obtain conformational information for small, linear homo- and heterooligopeptides via VCD spectroscopy. In this respect, the sensitivity of VCD is similar to that of electronic CD. Furthermore, the temperature dependence of the VCD results indicate that at elevated temperatures, the increasing number of conformational states results in a loss of discernible conformers, and consequently, a broadening and weakening of the VCD features. © 1998 John Wiley & Sons, Inc. Biopoly 46: 455–463, 1998
Ultrashort pulse propagation in KrF laser amplifiers

We consider the propagation of picosecond and subpicosecond pulses in KrF amplifiers. For pulses of ≈1-psec duration, the Frantz–Nodvik model provides an excellent fit to the experimentally measured gains as well as to the predictions of a more general coherent-propagation model. For 0.1-psec pulses, however, the Frantz–Nodvik and coherent-propagation theories predict different pulse shapes, although the predicted output fluences are in excellent agreement. We discuss the question of how short an input pulse can be without incurring substantial temporal broadening as well as the effective lower-level decay rate and line shape, the saturation fluence, and the effect of nonsaturable absorbers in the amplifying medium.
Comparison of the classical and the global solutions of the Ideal Resonance Problem

The Ideal Resonance Problem is defined by the Hamiltonian $$F = B(y) + 2\varepsilon A(y) \sin ^2 x,\varepsilon \ll 1.$$ The classical solution of the Problem, expanded in powers of e, carries the derivativeB′ as a divisor and is, therefore, singular at the zero ofB′, associated with resonance.
SU‐E‐T‐435: 4D MIMVista Workflow Vs 4D Dose Calculations Based On a Monte Carlo Method

Purpose: We investigated the accuracy of a commercially‐available software algorithm for 4D dose accumulation that consists of rigidly projecting the 3D dose calculated in the reference respiratory phase onto the remaining phases, followed by deformable registration, versus 4D dose calculation involving Monte Carlo recalculations of the original treatment plan applied to each of the phases. Methods: Radiotherapy plans for stage I–IIlung cancer were created for 8 patients who had respiratory‐correlated computed tomography (4D‐CT) performed as part of an IRB‐approved research protocol. Plans were generated and evaluated using the dose calculated by a Monte Carlo algorithm on the end‐exhale 4D‐CT phase. 3D doses for all other phases and the 4D dose were calculated using a rigid dose‐projection workflow as part of a commercially‐available software package. The resulting DVHs were compared with those obtained using Monte Carlo calculations after the initial plans were recalculated on each of the respiratory phases. In both cases the final dose accumulation was performed using the same commercially available deformable registration algorithm. The calculated dose distributions were compared according to the principal dosimetric indices used in our clinic to evaluate gross tumor volume (GTV) coverage: dose received by 99% of the gross tumor volume (D99(GTV)), minimum dose received by the GTV (Dmin(GTV)), and mean dose received by the GTV (Dmean(GTV)). Results: Mean differences between the commercial dose projection and the Monte Carlo recalculation algorithms were 0.1 Gy, 0.3 Gy, and 0.2 Gy for D99(GTV), Dmin(GTV) and Dmean(GTV). Maximum differences were 2.1 Gy, 2.9 Gy, and 2.2 Gy, respectively, between the two methods. Conclusion: The commercial dose accumulation workflow using rigid dose projection is much faster than 4D accumulation with Monte Carlo dose recalculation, and no large dosimetric differences were found between the methods. This study lends support to its use in a clinical setting.
National service and the ideal of community: a commentary on What You Can Do for Your Country

When faced with any of a number of societal problems, 20th‐century American intellectuals and public officials have found a ready answer in the ideal of community. Whatever the difficulty, these thinkers argue, the solution hinges on restoring a sense of community to American society. In this essay, the most recent example of this inclination in the report of the Commission on National and Community Service, What You Can Do for Your Country, is explored. As the Commission sees it, the best vehicle for establishing this sense of community is the introduction of programmes of national and community services in schools and in society at large. The essay examines the recommendations of the Commission and employs a case study of community building in a middle school in Indiana to consider the difficulties involved in such efforts.
Inhibition of protocadherin-α function results in neuronal death in the developing zebrafish

Abstract The pcdhα/CNR gene comprises a diverse array of neuronal cell-surface proteins of the cadherin superfamily, although very little is known about their role in neural development. Here we provide the first in-depth characterization of pcdh1α in zebrafish. Whole-mount immunocytochemistry demonstrates that a large proportion of endogenous cytoplasmic domain immunoreactivity is present in the nucleus, suggesting that endoproteolytic cleavage and nuclear translocation of the intracellular domain are important aspects of pcdh1α activity in vivo. Using whole-mount immunocytochemistry and BAC-based expression of Pcdh1α-GFP fusion proteins, we find that Pcdh1α does not appear to form stable, synaptic puncta at early stages of synaptogenesis. We also demonstrate that the presence of the Pcdh1α cytoplasmic domain is essential for normal function. Truncation of Pcdh1α proteins, using splice-blocking antisense morpholinos to prevent the addition of the common intracellular domain to the entire pcdh1α cluster, results in neuronal apoptosis throughout the developing brain and spinal cord, demonstrating an essential role for pcdh1α in early neural development. This cell death phenotype can be attenuated by the expression of a soluble Pcdh1α cytoplasmic domain.
Integrating the practical use of a database product into a theoretical curriculum

Integrating the practical use of a database product into the theoretical curriculum of a database management course is a challenge. The approach described minimizes the amount of class time that is allocated to teaching students the use of a database product, while providing guidance to the students in the use of the tool. Introduction of the database product is accomplished through cooperative learning, where students help each other learn the intricacies of the system. To facilitate this process, the students are provided with a complete database implementation example. Using this example, students gradually advance from a tutorial exercise, to a step-by-step extension of the example, and finally to more difficult extensions. These self-paced assignments provide a solid foundation for the students' knowledge in the implementation of their own cooperative group project.
Lower cytokine release by fetal porcine platelets: A possible explanation for reduced inflammation after fetal wounding

Abstract Fetal dermal wound healing is unique because of its rapidity, minimal inflammation, and lack of scarring. Cytokines such as transforming growth factor beta (TGF-β) and platelet-derived growth factor (PDGF) evoke an inflammatory response and scarring when applied to fetal wounds. Because adult and fetal platelet counts are comparable, the aim of this study was to test the hypothesis that the minimal inflammatory response seen in the fetus is attributable to differences in the serum content of cytokines released by fetal platelets. Using Yorkshire swine, blood was collected from 10 adults and 10 fetuses at day 60 of gestation (fullterm, 114 days). Platelets were isolated from anticoagulated blood and examined by transmission electron microscopy. Serum was analyzed for PDGF-AB and TGF-β2 by enzyme-linked immunosorbent assay (ELISA), and TGF-β1 by 125 I radioimmunonoassay. TGF-β samples were assayed with and without prior acid activation to determine the total TGF-β and the biologically active form of the cytokine. Electron microscopy of adult and fetal platelets showed no gross structural differences. Alpha granules, which contain cytokines as well as procoagulant factors, were present in similar quantities and with the same degree of homogeneity. The cytokines analyzed were present in all the adult and fetal sera tested. However, PDGF-AB was present in significantly lower concentrations in the fetus (383 ± 72 pg/mL v 972 ± 185 pg/mL in the adult; P v 29,864 ± 5,050 pg/mL; P v 13,407 ± 1,395 pg/mL; P v 7.69). The authors conclude that although no gross differences in platelet ultrastructure were noted, fetal porcine platelets release lower quantities of cytokines into serum. This lower serum cytokine content and the relative concentrations of TGF-β1 and TGF-β2 may explain, in part, the minimal inflammation and sparse fibrosis characteristic of fetal wounds. These observations provide further insight into the unique fetal response to wounding and may offer alternative avenues to modulate the postnatal wound healing response.
Recreational Portage Trails as Corridors Facilitating Non-Native Plant Invasions of the Boundary Waters Canoe Area Wilderness (U.S.A.)

Wilderness areas are protected and valued in part for recreation; recreational use, however, can negatively impact these areas. In particular, recreational use can facilitate transport of non-native propagules and create open sites for establishment of non-native species. We examined the role of recreational portage trails in the introduction and establishment of non-native plants into the Boundary Waters Canoe Area Wilderness of northern Minnesota (U.S.A.). On 20 portages, we sampled non-native plant richness and cover at four distances (0, 10, 25, and 50 m) from trails. Non-native richness and cover were not related to distance from wilderness entry point. Non-native richness and cover were, however, negatively related to distance from trails. All six non- native species we observed were either directly on or within 1 m of trails. These results suggest that recreational trails act as corridors facilitating invasions of non-native plants into wilderness areas. It remains unclear, however, whether these effects are caused by dispersal of propagules, creation of bare ground, or changes in the native plant community.
Heinz Body Formation in Calf Erythrocytes

Heinz body formation was induced in calf erythrocytes by a daily dose of 8 mg phenylhydrazine/kg body weight. Body weights and feed intakes were not affected, the glutathione content of erythrocytes was reduced, but the hemolysis rate of erythrocytes was not changed. Morphological changes in erythrocytes were shown by light and high resolution scanning microscopy. The appearance of Heinz bodies may have value as an indicator of oxidative stress under conditions such as copper toxicity or deficiency of selenium-vitamin E.
Chemotherapy-induced hand-foot syndrome and nail changes: A review of clinical presentation, etiology, pathogenesis, and management

Chemotherapy-induced hand-foot syndrome and nail changes are common complications of many classic chemotherapeutic agents and the newer molecular targeted therapies. They significantly impact patient quality of life, and frequently necessitate chemotherapy dose intensity modification or reduction. We aim to describe the epidemiology, pathogenesis, clinical presentation, and current evidence-based treatment options for these entities.
A Kantian critique of neoclassical law and economics

Abstract This paper outlines a critique of neoclassical law and economics based on the ethics of Immanuel Kant, focusing on four central topics: efficiency as the sole evaluative criterion for policy-making, hypothetical compensation in Kaldor–Hicks efficiency, the instrumental nature of rights and the assumption of reciprocal causation, and the role of punishment to both society and the individual. This overview addresses issues of concern not just to Kantians, but to anyone dissatisfied with the utilitarian foundations of law and economics and the amoral view of law upon which it is based.
Arbitrarily slow approach to limiting behavior

Let f(k,t):R N ×[0,∞)→R be jointly continuous in k and t, with lim t→ ∞f(k,t)=F(k) discontinuous for a dense set of k's. It is proven that there exists a dense set Γ of k's such that, for k∈Γ, |f(k,t)−F(k)| approaches 0 arbitrarily slowly, i.e., more slowly than any expressible function g(t)→0. The result is applied to diffusion and conduction in quasiperiodic media and yields arbitrarily slow approaches to limiting behavior as time or volume becomes infinite. Such a slow approach is in marked contrast to the power laws widely found for random media
Community Partnership for Level III Neonatal Intensive Care Unit Skills

Implementation, Outcomes, and Evaluation The chief nursing officers from the North Texas Division were responsible for presenting the idea of a residency to the North Texas Division. Once the internship/residency was approved, the human resources departments at each facility were responsible for posting the positions and screening the applicants. The nurse managers at each facility hired the interns/residents. The response to the residency was met with approval and great enthusiasm. Hundreds of applications were received, allowing each facility to choose exceptional candidates. In the future, we will measure overall satisfaction of the residents as well as retention rates.
ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia

ROR1 is a receptor tyrosine kinase expressed during embryogenesis, on chronic lymphocytic leukemia (CLL) and in other malignancies. Hematogones (non-neoplastic B-lymphocyte precursors) express surface ROR1 at an intermediate stage of maturation that lacks CD34 or TdT. The neoplastic counterpart to hematogones is precursor-B acute lymphoblastic leukemia (B-ALL), but less than 10% of B-ALL express surface ROR1, and these ROR1+ B-ALL cases have an unusually high frequency of lacking CD34 and/or having t(1;19), a chromosomal translocation that defines a specific subtype of B-ALL.
Spark ignition energies for dust-air mixtures: Temperature and concentration dependences

Energy requirements for the spark ignition in air of polyethylene powder, lycopodium spores, and Pittsburgh seam bituminous coal dust were measured in a 1.2-L furnace and a 20-L chamber. Dust concentrations and initial temperatures were carefully controlled (at ambient pressure) so that the mixtures were above their lean limits of flammability and below their spontaneous autoignition temperatures. Electrical ignition energy requirements are given in terms of both effective spark gap energies, eeff, and stored capacitor energies, 1/2 CE2. At ambient temperature and pressure, the average minimum eeff-values for the three dusts were: 40 mJ for lycopodium, 50 mJ for polyethylene, and 160 mJ for the coal dust. The concentrations at which those minima were observed were 300, 500, and 750 g/m3, respectively. The measured electrical ignitability ranking is consistent with the data of other researchers but the measured values are systematically higher, probably because of the higher flow and turbulence levels used here. For lycopodium, its ease of ignition allowed its lean limit to be approached readily with spark sources, and measurements of its temperature dependence confirm the validity of the modified Burgess-Wheeler law for a dust. While the concept of a minimum electrical ignition energy for homogeneous gas mixtures is well established, the data reported here, and their analysis, suggest that the concept may not be particularly useful for heterogeneous dust-air mixtures. So many contradictory requirements are involved in experimental conditions, and such extraordinary difficulties and complexities are encountered for dusts, that a reliable determination of a minimum ignition energy that reflects intrinsic flammability behavior is dubious.
Measurement of Vasoactive Intestinal Peptide using a Competitive Fluorescent Microsphere Immunoassay or ELISA in human blood samples

Abstract The concentration of Vasoactive Intestinal Peptide (VIP) as measured by recycling immunoaffinity chromatography (RIC) has been reported to be elevated in the blood of patients with autism as compared with normal subjects. In this study, we have developed a “Competitive Fluorescent Microsphere Immunoassay” (cFMI) in which VIP competes with biotinylated VIP in binding to polyclonal antibodies on microspheres. The results were obtained using the Luminex100 system. We measured VIP in serum, plasma, and material eluted from dried blood spots on filter paper with both the cFMI and an ELISA procedure. We found that a purification procedure was necessary for obtaining useful results from plasma and serum, however, a preincubation step was required with the blood eluates. This newly developed cFMI was more sensitive (2.5 vs. 20.0 pg/ml), and more reproducible than the ELISA. To get accurate measurements of VIP in eluted material high sensitivity is especially important. Thus, the cFMI using the Luminex system has definite advantages over a conventional ELISA including the possibility that samples can be assayed at higher dilutions. We have determined that the VIP concentrations of serum, plasma, and dried blood spot eluate specimens as measured with the cFMI assay system were similar to those measured with ELISA. Thus, the new cFMI using Luminex system may be useful for detection of VIP in human blood samples.
Terminal depth of penetration of spherical projectiles in transparent granular media

A series of 80 penetration tests were performed to study the terminal depth of penetration into dry and saturated transparent synthetic sand. The transparent sand was made by matching the refractive index of granulated fused quartz with a pore fluid made of either sucrose or mineral oil. Tests were conducted by shooting spherical projectiles at speeds of up to 200 m/s into the transparent soil and recording the depth of penetration non-intrusively, when possible. Analysis using existing physical and empirical models was conducted to see how well these models describe the penetration event into fused quartz and to provide best fit parameters. Adjustments to published models have also been derived which result in adequate correlations to the experimental data.
The Processing of Subject-Object Ambiguities in Native and Near-Native Mexican Spanish.

This self-paced reading study first tested the prediction that the garden path effect previously observed during the processing of subject–object ambiguities in native English would not obtain in a null subject language like Spanish. The investigation then further explored whether the effect would be evident among near-native readers of Spanish whose native language was a non-null subject language like English. Twenty-three near-native and 33 native readers of Mexican Spanish read sentences like Cuando el escultor acabo/volvio la obra tenia tres metros de altura “When the sculptor finished/came back the piece was three meters in height”. The results suggest that (i) Spanish differs from English for this type of processing and (ii) native and near-native processing can be guided by largely similar principles, at least where lexical information like verb transitivity is concerned.