cssi/SciSciGPT-SciSciNet huggingface dataset:
Neuromagnetic high frequency spikes are a new and noninvasive biomarker for localization of epileptogenic zones.

Abstract Objective One barrier hindering high frequency brain signals (HFBS, >80 Hz) from wide clinical applications is that the brain generates both pathological and physiological HFBS. This study was to find specific biomarkers for localizing epileptogenic zones (EZs). Methods Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). High frequency oscillations (HFOs, > 4 oscillatory waveforms) and high frequency spikes (HFSs, > 1 spiky or sharp waveforms) in 80–250 Hz and 250–600 Hz bands were blindly detected with an artificial intelligence method and validated with visual inspection. The magnitude of HFOs and HFSs were quantified with spectral analyses. Sources of HFSs and HFOs were localized and compared with clinical EZs determined by invasive recordings and surgical outcomes. Results HFOs in 80–250 Hz and 250–600 Hz were identified in both epilepsy patients (18/23, 12/23, respectively) and healthy controls (6/23, 4/23, respectively). HFSs in 80–250 Hz and 250–600 Hz were detected in patients (16/23, 11/23, respectively) but not in healthy controls. A combination of HFOs and HFSs localized EZs for 22 (22/23, 96%) patients. Conclusions The results indicate, for the first time, that HFSs are a newer and more specific biomarker than HFOs for localizing EZs because HFOs appeared in both epilepsy patients and healthy controls while HFSs appeared only in epilepsy patients.
Response to the Contributors

This is a pre-publication draft of an essay in which I respond briefly to 18 articles contributed to a special Festschrift issue of the Connecticut Law Review. All but one of the contributions fall within two categories – constitutional change and constitutional interpretation. These topics have engaged me for most of my career as a legal scholar. While every one of the contributions sheds new and useful light on these subjects, I usually have some differences with the interpretations argued in them Of course, I can only treat those differences superficially here. In each case, moreover, my comments should not obscure my sincere admiration of and appreciation for the authors’ efforts.
Test-dose pharmacokinetics guided melphalan dose adjustment in reduced intensity conditioning allogeneic transplant for non-malignant disorders.

AIMS We studied melphalan pharmacokinetics (PK) and feasibility of melphalan full-dose adjustment based on test-dose PK in children and young adults with non-malignant disorders (NMD) undergoing allogeneic hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) containing alemtuzumab, fludarabine and melphalan. METHODS Patients received test-dose melphalan (10% of planned full-dose) prior to conditioning. Blood samples for PK were obtained around test and full-dose melphalan (140 mg/m2 or 4.7 mg/kg in patients <10 kg). Melphalan concentration was measured by liquid chromatography electrospray ionization tandem mass-spectrometry assay and data were analysed using a population-PK model and Bayesian estimation. Test and full-dose melphalan clearance estimates were evaluated by pairwise Wilcoxon test and Bland-Altman plot. RESULTS Twenty-four patients undergoing 25 transplants were included in the final analysis. Patients received standard full-dose melphalan in 17 transplants, with median area under the concentration-time curve (AUC) of 5.5 mg*h/L (range, 3.0-9.5 mg*h/L). Patients received test-dose melphalan in 23 transplants with a test-dose PK predicted full-dose AUC range of 2.9-16.8 mg*h/L. In seven transplants where patients had baseline organ impairment, test-dose PK predicted higher exposure for standard full-dose (median AUC 13.8 mg*h/L). Melphalan full-dose was adjusted in these patients, with achievement of desired target AUC (3.6-5.4 mg*h/L) and no excess toxicity. Mean ratio of test-dose clearance to full-dose clearance was 1.03. Twenty of 22 patients (91%) were within the 95% confidence intervals of the clearance ratio. CONCLUSION Melphalan test-dose PK reliably predicts full-dose PK and allows for accurate adjustment of full-dose melphalan in RIC-HCT for NMD. This approach can avoid excess toxicity from increased systemic exposure, especially in patients with organ impairment.
Increased occurrence of migraine in perimenopausal aged women with stroke (1161)

Objective: Compare the co-occurrence of migraine in perimenopausal female, postmenopausal female, and male patients admitted with stroke to a tertiary care hospital. Background: The relationship between migraine and stroke, especially migraine with aura, has been well-established. Emerging evidence suggests that menopausal vasomotor symptoms increase the risk of cardiovascular and cerebrovascular disease, potentially highest during the perimenopausal period. The association between migraine and stroke in perimenopausal women versus age-matched men and postmenopausal women is uncertain. Design/Methods: Patient population data at a large tertiary care medical center was analyzed using the Epic SlicerDicer function. Diagnosis of migraine was compared in male (M) and female (F) patients aged 42–65 and female patients aged 70–100 with stroke admission between 3/17/2019 and 9/17/2019 using Chi-Square test. Results: Between 3/17/2019 and 9/17/2019, 460 patients aged 42–65 (M: n=265, 57.6%; F: n=195, 42.4%), and 276 female patients aged 70–100 were admitted with stroke. Of 53 aged 42–65 with migraine and stroke, the majority were female (F: n=38, 71.7%; M: n=15, 28.3%). Eleven women with stroke aged 70–100 had a migraine diagnosis. Perimenopausal aged women with stroke were more likely to have co-occurrence of migraine diagnosis than age-matched men (19.49% vs 5.66%, p Conclusions: Perimenopausal aged female stroke patients were more likely than age matched male patients and postmenopausal aged female patients to have a diagnosis of migraine at a tertiary care hospital. This provides evidence that migraine may be a risk factor for stroke specifically in 42–65 year old women relative to male counterparts of the same age, or female counterparts of an older age. As this age range is consistent with perimenopause, additional research should be dedicated to studying this population to better understand the association of migraine, vasomotor symptoms, cardiovascular and cerebrovascular risk. Disclosure: Dr. Figurelle has nothing to disclose. Dr. Sosa has nothing to disclose. Dr. Wells has nothing to disclose. Dr. Guzik has nothing to disclose.
Friction and wear properties of black oxide surfaces in rolling/sliding contacts

Abstract Black oxide chemical conversion treatment of steel surfaces was originally developed as a low-cost method to improve the corrosion resistance of the base material. Over time, this surface treatment was introduced on tribological components amid claims that it improved galling and smearing resistance. In rolling element bearings, smearing damage can occur during high transient slip events between roller bodies and raceways, and black oxide surface treatments have recently been prescribed as a solution for this mode of adhesive wear damage. Therefore, fundamental friction and wear experiments using unidirectional sliding and rolling/sliding contacts were conducted to explore the performance of black oxide surfaces in tribological contacts. From this work, it was concluded that mated black oxide surfaces yield similar or lower friction as compared to mated steel surfaces (in lubricated contacts), exhibit high wear in low λ conditions, and can mitigate adhesive wear damage as long as the oxide layer remains intact.
Base Metal Bottom Electrodes

Integrating electroceramic thin films with inexpensive base metal flexible substrates opens new possibilities for realistic mass production of functional oxide thin film technology. Not only do such substrates significantly reduce raw material costs, their flexible nature enables rapid, low-cost roll-to-roll processing. However, integrating an oxide with a base metal is a true scientific challenge. How can an oxide thin film be crystallized without oxidizing the base metal? One possibility is to imitate multilayer capacitor technology and crystallize the film using temperature and oxygen partial pressure (pO2) conditions that provide thermodynamic equilibrium between the oxide and base metal. Unfortunately, this is not possible for all desired oxide constituents (e.g. PbO, Bi2O3). In these cases, the low processing temperatures of a chemical solution deposition method provide another avenue to integration: kinetic avoidance of substrate oxidation. To maintain high quality oxide films at low processing temperatures requires an understanding of chelation chemistry and gel-to-ceramic conversion. This chapter addresses both the thermodynamic equilibrium and kinetic method for integrating chemical solution processed functional oxide films on base metal electrodes and provides the reader with insights into how this state-of-the-art technology is revolutionizing the commercializability of thin film electroceramics.
Left main revascularization: surgical and interventional perspectives.

As physicians, there are few decisions that we are asked to make that are more important than how to best manage patients with critical disease of the left main coronary artery. For such patients, effective revascularization is essential to prolong life and preserve health. Soon after its
Mathematical Aspects of Recursive Function Theory

Publisher Summary This chapter focuses on the mathematical aspects of recursive function theory. In mainstream recursion theory, the notions of computation and computability play a central role. There are several instances in mathematics in which recursion theoretic concepts arise naturally from concepts apparently having nothing to do with computability—for example, the Diophantine representability of recursively enumerable sets. Friedman has discovered a number of characterizations of recursion theoretic and logical notions in terms of concepts from mainstream mathematics. In a different direction, it has often been observed that certain structural property of recursive functions and their Godel numberings, which again apparently have nothing to do with the notion of a computation, play a central role. The enumeration theorem and s-m-n theorems are the most noticeable examples of this. This observation suggests two areas of study. The axiomatizations of recursion theory and its generalizations can be studied, in which these structural properties, rather than the notion of a computation, occupy center stage. Then, the structures (models) naturally occurring in recursion theory, in terms of traditional mathematical and logical issues—such as definability theory, isomorphisms of structures, and automorphisms of a structure—can be studied. The chapter looks at two characterizations of recursion theoretic notions and also describes some work of Friedman showing how some concepts of recursion theory arise naturally in linear algebra and analysis.
Grid Computing for the Masses: An Overview

The common goals of the Grid and peer-to-peer communities have brought them in close proximity. Both the technologies overlay a collaborative resource-sharing infrastructure on existing (public) networks. In realizing this shared goal, however, they concentrate on significantly contrasting issues. The Grid paradigm focuses on performance, control, security, specialization, and standardization. On the other hand, the peer-to-peer paradigm concentrates on fault tolerance, resilience, decentralization, and peer cooperation. In this paper, we discuss Grid usage models including traditional Grids, ad hoc Grids, and federated Grids. We compare these approaches to peer-to-peer computing and discuss the issues involved in the convergence of the two paradigms.
Atypical Presentation of Posterior Reversible Encephalopathy Syndrome (P6.031)

Objective: To report an atypical case of posterior reversible encephalopathy syndrome Background: Posterior reversible encephalopathy (PRES) is a reversible encephalopathy characterized by headache, altered mental status, visual symptoms, motor symptoms, and seizures. On neuroimaging, symmetric subcortical vasogenic edema mainly affecting posterior brain regions is present. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of PRES. Design/Methods: We report a case of a 50 year old Hispanic woman with bipolar disorder and substance abuse, who was brought in by paramedics after she was found unresponsive in her boarding home. She was hypothermic with shallow breathing and was intubated upon arrival. Initial neurological exam showed comatose state with intact brainstem reflexes. Initial CT head showed extensive vasogenic edema in both cerebral hemispheres with involvement of corpus callosum with 7 mm left to right midline shift with downward transtentorial herniation. MRI brain showed vasogenic edema in both occipital, parietal, temporal and frontal lobes along with foci of subacute hemorrhage and infarction in left occipital and parietal lobes. Results: Patient was treated with mannitol and hypertonic saline for 3 days. Her neurological exam improved gradually over the period of 2-3 weeks. She had residual right arm weakness. She was extubated, was able to communicate and ambulate. Repeat MRI done 2.5 weeks after the initial MRI showed resolving vasogenic edema and reversion of midline shift. She was discharged to a rehabilitation facility. Conclusions: PRES is reversible global encephalopathy, characterized by symmetrical subcortical vasogenic edema, affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging findings are regarded as a defining feature of typical PRES. Radiologic reversal lags behind clinical improvement. Atypical features include hemorrhage and infarction. Our patients had extensive vasogenic edema in both hemispheres with signs of transtentorial herniation, which is an atypical feature of PRES. Although she improved clinically, she had residual right arm weakness. Disclosure: Dr. Bhat has nothing to disclose. Dr. Hillen has nothing to disclose.
Formation Rates of the Two Ethyl Isocyanide Compounds of Liver Cytochrome P-450 at Low Temperatures

Abstract Liver cytochrome P-450 forms two spectroscopically and functionally distinct compounds with ethyl isocyanide, but the structural basis for the difference between them is unknown. We have examined the relative rates of formation of the two compounds at low temperatures. Reduced cytochrome P-450 was generated photochemically from its carbon monoxide complex at temperatures below 0°, and allowed to react with ethyl isocyanide. (a) The extent of conversion from the CO compound to the ethyl isocyanide compounds was a function of the relative concentrations of CO and ethyl isocyanide. At a concentration ratio of about 1, nearly complete conversion took place. (b) The ratio of the two ethyl isocyanide compounds formed upon irradiation with monochromatic light at 450 nm, measured by the relative heights of their Soret bands (455 and 430 nm), depended upon irradiation conditions such as temperature and time. In general, the lower the irradiation temperature, the higher the ratio of the 455-nm state to the 430-nm state. The sum of ethyl isocyanide compounds formed upon 1-min irradiation, however, decreased with decreasing temperature below -30°; no conversion occurred at or below -85°. (c) On irradiation at -30°, the 455-nm state was produced rapidly at first, then its concentration decreased gradually while that of the 430-nm state increased. Thus, the ratio of the 455-nm state to the 430-nm state decreased with increasing irradiation time. (d) A slow reversion from ethyl isocyanide compounds to CO complex occurred as a dark reaction after irradiation. During this conversion, at -30°, a rapid decrease in the ratio of the 455-nm state to the 430-nm state took place. These observations and others suggest that the following relationship exists among the cytochrome P-450 compounds studied. [see PDF for equation] where EtNC represents ethyl isocyanide.
Internet Pornography Use in the Context of External and Internal Religiosity

Past studies have demonstrated an inverse relationship between religiosity and such problem behaviors as crime, delinquency, alcoholism, and substance use. Religiosity may be a protective factor against problem behaviors. Recently, a new problematic behavior has emerged, Internet pornography. Popular Christian literature has suggested that Internet pornography use is common among Christians. However, there have been few research studies examining this issue in Christian populations. This study examined the extent of Internet pornography use among 751 males and females who were attending a conservative Christian university, perceived consequences and benefits of viewing, and the relationship between internal, external and quest religiosity and Internet pornography use. Findings suggest that the majority of males had some involvement in Internet pornography, but regular viewing was significantly lower than has been found in the general population. Internal and external religiosity showed only a weak, though statistically significant, inverse relationship with regular Internet pornography use.
A new kernel based on high-scored pairs of tri-peptides and its application in prediction of protein subcellular localization

A new kernel has been developed for vectors derived from a coding scheme of the tri-peptide composition for protein sequences. This kernel defines the sequence similarity through a mapping that transforms a tri-peptide coding vector into a new vector based on a matrix formed by the high BLOSUM scores associated with pairs of tri-peptides. In conjunction with the use of support vector machines, the effectiveness of the new kernel is evaluated against the conventional coding schemes of k-peptide (k ≤ 3) for the prediction of subcellular localizations of proteins in Gram-negative bacteria. It is demonstrated that the new method outperforms all the other methods in a 5-fold cross-validation.
Small sample performance of bias-corrected sandwich estimators for cluster-randomized trials with binary outcomes

The sandwich estimator in generalized estimating equations (GEE) approach underestimates the true variance in small samples and consequently results in inflated type I error rates in hypothesis testing. This fact limits the application of the GEE in cluster-randomized trials (CRTs) with few clusters. Under various CRT scenarios with correlated binary outcomes, we evaluate the small sample properties of the GEE Wald tests using bias-corrected sandwich estimators. Our results suggest that the GEE Wald z-test should be avoided in the analyses of CRTs with few clusters even when bias-corrected sandwich estimators are used. With t-distribution approximation, the Kauermann and Carroll (KC)-correction can keep the test size to nominal levels even when the number of clusters is as low as 10 and is robust to the moderate variation of the cluster sizes. However, in cases with large variations in cluster sizes, the Fay and Graubard (FG)-correction should be used instead. Furthermore, we derive a formula to calculate the power and minimum total number of clusters one needs using the t-test and KC-correction for the CRTs with binary outcomes. The power levels as predicted by the proposed formula agree well with the empirical powers from the simulations. The proposed methods are illustrated using real CRT data. We conclude that with appropriate control of type I error rates under small sample sizes, we recommend the use of GEE approach in CRTs with binary outcomes because of fewer assumptions and robustness to the misspecification of the covariance structure.
Wires, Catheters, and More: A Primer for Residents and Fellows Entering Interventional Radiology: Resident and Fellow Education Feature

1From the Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, 601 N Caroline St, Room 4210, Baltimore, MD 21287. Presented as an education exhibit at the 2013 RSNA Annual Meeting. Received October 2, 2014; revision requested December 8 and received January 7, 2015; accepted January 19. All authors have disclosed no relevant relationships. Address correspondence to B.G.N. (e-mail: bnorthc1@ jhmi.edu). The full digital presentation is available online.
Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer

A promising agent for use in prostate cancer therapy is the Hedgehog (Hh) signaling pathway inhibitor, cyclopamine. This compound, however, has the potential for causing serious side effects in non-tumor tissues. To minimize these bystander toxicities, we have designed and synthesized two novel peptide-cyclopamine conjugates as prostate-specific antigen (PSA)-activated prodrugs for use against prostate cancer. These prodrugs were composed of cyclopamine coupled to one of two peptides (either HSSKLQ or SSKYQ) that can be selectively cleaved by PSA, converting the mature prodrug into an active Hedgehog inhibitor within the malignant cells. Of the two prodrugs, Mu-SSKYQ-Cyclopamine was rapidly hydrolyzed, with a half-life of 3.2 h, upon incubation with the PSA enzyme. Thus, modulating cyclopamine at the secondary amine with PSA-cleavable peptides is a promising strategy for developing prodrugs to target prostate cancer.
Photographic Emulsion Calibration with the Use of a Digital Computer

A computer program, written in FORTRAN IV, has been developed for the calibration of photographic emulsions using the two-step method of Churchill. Innovations in this program are: (1) the proportional weighting of all points used in the construction of the preliminary curve to their precision of determination; (2) the examination of the preliminary curve of best fit with the rejection of spurious values; and (3) an automatic increase of the degree of the equation used if a random scatter of points about the preliminary curve has not been found. A table relating relative intensities to percent transmittance is printed and a data card containing the coefficients of the emulsion calibration curve is punched.
Measurement of gestational cocaine exposure: sensitivity of infants' hair, meconium, and urine.

We studied the sensitivity of testing the newborn infant's hair, meconium, and urine in detecting gestational cocaine exposure. The infants were born to 59 women who were interviewed to determine their use of cocaine during pregnancy and whose hair was analyzed for the presence of cocaine. Regression analysis was used to evaluate the relationship between cocaine in newborn hair and in maternal hair. Radioimmunoassay of infants' hair and gas chromatography-mass spectrometry of meconium were more sensitive than immunoassay of urine ( p R = R =0.77) and explained variation (59%) improved slightly when premature infants (n=9) were excluded. We conclude that analysis of the newborn infant's hair by radioimmunoassay or of meconium by gas chromatographymass spectrometry is more sensitive than analysis by immunoassay of urine, and can detect fetal cocaine exposure that occurred during the last two trimesters of pregnancy.
Risk factors for child sexual abuse

We review the risk and protective factors for child sexual abuse. Overall, characteristics of perpetrators, victims, and families of victims were moderate to strong risk factors for child sexual abuse. However, it is difficult to distinguish between risk factors for extra-familial and intra-familial child sexual victimization because most of the studies combined these two types of child sexual abuse, although the risk factors for these two types of child sexual abuse most likely differ. Research in this area is difficult because etiological and prevention models of victimization would differ substantially from those of perpetration. Given the low yearly prevalence of child sexual victimization, very large samples would be necessary to obtain sufficient power. Thus, most studies have used lifetime prevalence, which may provide much useful information but which add substantial time confounds. Finally, child sexual victimization is probably a misnomer, as the nature, impact, and etiology of sexual victimization most likely differs over the large age span of childhood and gender. Because improved models and prevention programs require improved etiological models (based on knowledge of risk and protective factors), we hope that this review will focus stakeholders on the need for continued research in this area.
Going Out: The Rise and Fall of Public Amusements

Acknowledgments 1. Introduction 2. Dollar Theaters, Concert Saloons, and Dime Museums 3. "Something for Everybody" at the Vaudeville Theater 4. "The Best Smelling Crowd in the World" 5. The "Indecent" Others 6. The City as Playground: The World's Fair Midways 7. "The Summer Show" 8. The National Game 9. "Laughter and Liberty Galore": Early Twentieth-Century Dance Halls, Ballrooms, and Cabarets 10. Talking and Singing Machines, Parlors, and Peep Shows 11. "The Surest Immediate Money-Maker Ever Known" 12. The First Picture Shows 13. "The Pernicious 'Moving Picture' Abomination" 14. Combination Shows, Stars, and Features 15. Waving the Flag 16. Palaces for the People 17. Decline and Fall List of Abbreviations Notes Index
Massive Gas Injection Systems for Disruption Mitigation on the DIII-D Tokamak

Injection of massive quantities of deuterium or noble gases (>1022 molecules) has proven to be very effective at mitigating the deleterious effects of disruptions in the DIII-D tokamak. Both the heat load to the divertor and the halo current forces to the first wall were reduced by more than a factor of four. Total electron densities (free and bound) of ~1021 m-3 have been achieved, close to densities required to prevent avalanche multiplication of runaway electron currents during the fast plasma current ramp down that injection produces. Two gas injection configurations used in experiments in the period 2001-2005 will be described. Both configurations use a fast operating (open/close~0.5 ms) solenoid valve with an orifice diameter of 4 mm. The maximum flow rate in helium is 5times104 Pa m3/s at a reservoir pressure of 7 MPa. A new valve with an orifice diameter of 20 mm will be tested when DIII-D resumes operation in 2006. The new valve, with a theoretical flow of 25 times the original valve, has flow capabilities that approach those required for ITER. Calculations show that a set of four such valves can reach the no-avalanche density in ITER in ~0.25 t CQ where tCQ, ~30 ms, is the 'fastest-possible' plasma current quench time. While there are still-open questions about the mechanisms whereby injected neutral gas and free and bound electrons penetrate (or are mixed) into the core of a high-temperature plasma, it is clear that massive gas injection can easily and reliably provide sufficient mass flow to minimize disruption damage in large reactor-scale tokamaks. The relatively long current decay times inherent in such devices will make it feasible for injection valves to be located external to the blanket modules, in regions of relatively low magnetic field. It will be necessary, however, to provide a relatively high-conductance 'injection tube' path from the valve to the plasma surface. Trade offs of many system design factors including gas flow rise time, neutron streaming and damage to the valve seat and actuator and valve and driver reliability and in-situ maintainability will have to be made to determine the most suitable configuration. The principal open physics question is what is the mixing mechanism which transports the impurities to the plasma interior and how fast and effective will it be in a reactor-scale plasma
A Different Approach to Lighting and Imaging: Formulas for Flux Density, Exact Lens and Mirror Equations and Caustic Surfaces in Terms of the Differential Geometry of Surfaces

A formula is derived for the flux density associated with each ray traced through an optical system. The formula involves the ratio of the products of the principal curvatures of the wave front as it approaches and leaves each refracting surface. As input to the flux equation, a new and simplified derivation of the general lens equations is given. The general lens equations yield the normal curvatures and torsion of normal curves in the refracted wave front at each surface; these in turn, are related to the corresponding quantities for the incident wave front and the refracting surface. As an application, the flux equation and the generalized lens equations are specialized to meridional rays. The flux density and the caustic surfaces, that is, the loci of wave front principal curvatures, are then computed for a singlet lens. In a second application the flux density for skew rays is calculated over a receiver plane perpendicular to the symmetry axis when light from an off axis point source is reflected from a paraboloid.
Exposure of neuronal cultures to K+ depolarization or to N-methyl-d-aspartate increases the transcription of genes encoding the α1 and α 5 GABAA receptor subunits

The transcription rates of the alpha 1, alpha 5, and alpha 6 gamma-aminobutyric acidA receptor subunit genes were analyzed in cultures maintained in low KCl (12.5 mM), in low KCl treated with NMDA (10 microM), and in high KCl (25 mM). alpha 1 and alpha 5 transcription rates were significantly increased in response to NMDA or high KCl treatment, while alpha 6 and cyclophilin transcription rates were not changed by either condition. These data suggest that following NMDA or high KCl treatment of granule cells, changes in alpha 1 and alpha 5 mRNA content are a consequence of a specific transcriptional rate increase of the corresponding subunit genes.
Monoclonal antibodies to the integrin α−4 subunit inhibit the murine contact hypersensitivity response

Lymphocyte-endothelial cell recognition is an active multistep process central to the pathophysiology of inflammation. In vitro models of lymphocyte adhesion predict that the beta 1 integrin very late antigen-4 (VLA-4), an activation-dependent adhesion receptor, can mediate the firm sustained attachment required for the extravasation of memory lymphocytes. We have used murine contact hypersensitivity as an in vivo model in which to evaluate the role of alpha-4 integrins in an evolving inflammatory response. We demonstrate that the intravenous administration of 75 micrograms of the anti-alpha-4 specific monoclonal antibodies R1-2 or PS/2 4-6 h prior to challenge significantly inhibits the efferent response of 2,4 dinitrofluorobenzene, or oxazolone-sensitized mice. The disease-modifying effect of anti-alpha 4 treatment was evident as a 50-60% reduction in the ear swelling response. By histological analysis treated animals scored lower for edema, number of epidermal lesions and degree of leukocyte infiltration. Antibody-treated animals have elevated numbers of circulating mononuclear leukocytes present in the same relative ratio as untreated control animals, suggesting that the inhibitory effect was not due to antibody-dependent cellular depletion of effector lymphocytes. These data are consistent with a central role for VLA-4 in the pathophysiologic process of inflammation.
Wounding increases intracellular encapsulation (melanization) of developing Brugia malayi (Nematoda: Filarioidea) larvae in thoracic muscles of Anopheles quadrimaculatus

Wounding of females of the refractory strain of Brugia malayi-infected Anopheles quadrimaculatus by an injection of saline solution resulted in a significant increase in encapsulation and melanization of intracellularly located first stage (L1) larvae of B. malayi in their thoracic muscles 24 and 48 hr after the injection, when compared to uninjected infected females. This increased encapsulation and melanization response was inhibited by injecting saline solution containing prophenoloxidase and phenoloxidase inhibitors and competitors (benzamidine HCl, p-nitrophenyl-p′guanidinobenzoate HCl, soybean trypsin inhibitor, diethyldithiocarbamic acid-sodium salt, 1-phenyl-2-thiourea, and reduced glutathione) into B. malayi-infected An. quadrimaculatus females. These results demonstrate for the first time that wounding of the cuticle by injecting saline solution into the hemocoel of the infected females activated the prophenoloxidase cascade that increased encapsulation and melanization of intracellularly located L1 of B. malayi in infected thoracic muscles of An. quadrimaculatus.
Speaker normalization and adaptation using second-order connectionist networks

A method for speaker normalization and adaption using connectionist networks is developed. A speaker-specific linear transformation of observations of the speech signal is computed using second-order network units. Classification is accomplished by a multilayer feedforward network that operates on the normalized speech data. The network is adapted for a new talker by modifying the transformation parameters while leaving the classifier fixed. This is accomplished by backpropagating classification error through the classifier to the second-order transformation units. This method was evaluated for the classification of ten vowels for 76 speakers using the first two formant values of the Peterson-Barney data. The results suggest that rapid speaker adaptation resulting in high classification accuracy can be accomplished by this method. >
Metal toxicity and opportunistic binding of Pb2 + in proteins

Lead toxicity is associated with various human diseases. While Ca(2+) binding proteins such as calmodulin (CaM) are often reported to be molecular targets for Pb(2+)-binding and lead toxicity, the effect of Pb(2+) on the Ca(2+)/CaM regulated biological activities cannot be described by the primary mechanism of ionic displacement (e.g., ionic mimicry). The focus of this study was to investigate the mechanism of lead toxicity through binding differences between Ca(2+) and Pb(2+) for CaM, an essential intracellular trigger protein with two EF-Hand Ca(2+)-binding sites in each of its two domains that regulates many molecular targets via Ca(2+)-induced conformational change. Fluorescence changes in phenylalanine indicated that Pb(2+) binds with 8-fold higher affinity than Ca(2+) in the N-terminal domain. Additionally, NMR chemical shift changes and an unusual biphasic response observed in tyrosine fluorescence associated with C-terminal domain sites EF-III and EF-IV suggest a single higher affinity Pb(2+)-binding site with a 3-fold higher affinity than Ca(2+), coupled with a second site exhibiting affinity nearly equivalent to that of the N-terminal domain sites. Our results further indicate that Pb(2+) displaces Ca(2+) only in the N-terminal domain, with minimal perturbation of the C-terminal domain, however significant structural/dynamic changes are observed in the trans-domain linker region which appear to be due to Pb(2+)-binding outside of the known calcium-binding sites. These data suggest that opportunistic Pb(2+)-binding in Ca(2+)/CaM has a profound impact on the conformation and dynamics of the essential molecular recognition sites of the central helix, and provides insight into the molecular toxicity of non-essential metal ions.
Lava-dome growth and explosive volcanism in the Jemez Mountains, New Mexico: Evidence from the plio-pleistocene puye alluvial fan

Abstract The Plio-Pleistocene Puye Formation, north-central New Mexico, is a 200-km2 volcanogenic alluvial fan shed eastward from the Tschicoma volcanic center, part of the Jemez Mountains volcanic field. The fan contains > 15km3 of volcaniclastic material derived from closely spaced lava domes in the northeastern portion of the Tschicoma center. Interbedded in the fan sediments are at least 25 primary pyroclastic units from explosive eruptions of dacitic and rhyolitic lava domes. Tephra occur mainly as pumice falls but include several pumiceous ignimbrites and two thick proximal block-and-ash pyroclastic flows. The upper part of the fan also contains rhyolitic plinian deposits erupted from sources in the central portion of the Jemez field and basaltic ash derived from the central Rio Grande rift. Fanglomeratic (pyroclastic and epiclastic) facies exhibit considerable lateral variation. Primary tephra deposits, however, provide a stratigraphic framework for reconstruction of the growth of individual lava domes. While only volcanic domes and lava flows are exposed in the Tschicoma center, Puye tephra layers show that vulcanian, subplinian and plinian activity, and block-and-ash pyroclastic flows accompanied many dome-forming events. Degradation of these lava domes produced coarse-grained debris flows dominated by lava and dome carapace clasts. From these epiclasts it is possible to identify lithologies of lavas that are either currently buried or have been obliterated by erosion or by collapse of the Valles calderas. The preservation of Puye deposits reflects very high rates of aggradation and gradual down-faulting in the Espanola basin of the central Rio Grande rift. This record of pyroclastic and epiclastic deposition allows detailed interpretation of the evolution of a volcanic center from its pyroclastic and erosion products, and is the first example of a volcanogenic alluvial fan in an intracontinental rift setting to be described in detail. This study emphasizes that interpretation of any ancient volcanic terrain based solely upon data derived from mapping, radiometric dating, and chemical analysis of lavas or existing denuded edifices is likely to greatly underestimate both the role of explosive volcanism in the build-up of volcanic centers and subsequent estimates of the volumes of material produced.
Terrestrial biogeochemistry in the community climate system model (CCSM)

Described here is the formulation of the CASA' biogeochemistry model of Fung, et al., which has recently been coupled to the Community Land Model Version 3 (CLM3) and the Community Climate System Model Version 3 (CCSM3). This model is presently being used for Coupled Climate/Carbon Cycle Model Intercomparison Project (C4MIP) Phase 1 experiments. In addition, CASA' is one of three models – in addition to CN (Thornton, et al.) and IBIS (Thompson, et al.) – that are being run within CCSM to investigate their suitability for use in climate change predictions in a future version of CCSM. All of these biogeochemistry experiments are being performed on the Computational Climate Science End Station (Dr. Warren Washington, Principle Investigator) at the National Center for Computational Sciences at Oak Ridge National Laboratory.
A perturbative correction to restricted open shell configuration interaction with single substitutions for excited states of radicals

Abstract A perturbative correction, termed RCIS(D), to restricted open shell single excitation configuration interaction (ROCIS) is formulated and implemented for excited states of radicals. RCIS(D) gives spin-pure energies (but not wavefunctions), is size-consistent, and has computational complexity scaling with the fifth power of molecular size. All these properties are analogous to second order restricted Moller-Plesset theory for the ground state. Comparison of calculated vertical excitation energies against experiment for a diverse series of small radicals, BeH, BeF, CH, CH 3 , CN, CO + , NO and OH, suggests that RCIS(D) constitutes a useful improvement over ROCIS.
Time dependent direct and inverse electromagnetic scattering for the dispersive cylinder

Abstract Direct and inverse scattering problems for the inhomogeneous dispersive cylinder for electromagnetic wave propagation in the time domain are considered. Emphasis is placed on the inverse problem in which the reconstruction of the susceptibility kernel, a time dependent function characterizing the dispersive nature of the medium, is accomplished by using reflection data. The technique consists of splitting the electromagnetic field into cylindrical waves that would be radially incoming and outgoing in a homogeneous medium, and relating the internal field components to the applied field at the surface by means of a Green's function operator. Numerical implementation of the algorithm is described, and several examples are presented. Although the formulation becomes singular at one round trip time (corresponding to a caustic when the radially incoming wave reaches the axis of the cylinder), recovery of the susceptibility kernel can be extended beyond one round trip time by fitting the obtainable data to an assumed model by nonlinear least squares.
INTERFACIAL MODIFICATION IN METAL MATRIX COMPOSITES BY THE SOL-GEL PROCESS

ABSTRACT Detailed examination of thermodynamic and kinetic data suggest that it should be possible to develop an interfacial barrier coating which promotes wetting of metal matrix composite reinforcements, while simultaneously reducing deleterious interfacial chemical interactions. The current study has examined the feasibility of developing a procedure to coat graphite reinforcements with a thin, crack-free, protective oxide layer. Emphasis in this investigation being placed on sol-gel, TiO2, coated PAN 650/42 graphite for inclusion in an aluminum metal matrix. Initially, the effect of the sol-gel composition and coating procedure on the coating uniformity, structure, and thickness were investigated. These procedures were then utilized for graphite fiber coating, with the coated fiber preforms being subsequently infiltrated by pure liquid aluminum. Energy dispersive x-ray analysis, optical and transmission electron microscopy confirmed that no reaction occurred at the TiO2 -C interface, while chemical we...
A role for lysyl oxidase regulation in the control of normal collagen deposition in differentiating osteoblast cultures

Differentiation of phenotypically normal osteoblast cultures leads to formation of a bone-like extracellular matrix in vitro. Maximum collagen synthesis occurs early in the life of these cultures, whereas insoluble collagen deposition occurs later and is accompanied by a diminished rate of collagen synthesis. The mechanisms that control collagen deposition seem likely to include regulation of extracellular collagen biosynthetic enzymes, but expression patterns of these enzymes in differentiating osteoblasts has received little attention. The present study determined the regulation of lysyl oxidase as a function of differentiation of phenotypically normal murine MC3T3-E1 cells at the level of RNA and protein expression and enzyme activity. In addition, the regulation of BMP-1/mTLD mRNA levels that encodes procollagen C-proteinases was assayed. The role of lysyl oxidase in controlling insoluble collagen accumulation was further investigated in inhibition studies utilizing β-aminopropionitrile, a specific inhibitor of lysyl oxidase enzyme activity. Results indicate that lysyl oxidase is regulated as a function of differentiation of MC3T3-E1 cells, and that the maximum increase in lysyl oxidase activity precedes the most efficient phase of insoluble collagen accumulation. By contrast BMP-1/mTLD is more constitutively expressed. Inhibition of lysyl oxidase in these cultures increases the accumulation of abnormal collagen fibrils, as determined by solubility studies and by electron microscopy. Taken together, these data support that regulation of lysyl oxidase activity plays a key role in the control of collagen deposition by osteoblast cultures. Copyright © 2004 Wiley-Liss, Inc.
Degree centrality for semantic abstraction summarization of therapeutic studies

Automatic summarization has been proposed to help manage the results of biomedical information retrieval systems. Semantic MEDLINE, for example, summarizes semantic predications representing assertions in MEDLINE citations. Results are presented as a graph which maintains links to the original citations. Graphs summarizing more than 500 citations are hard to read and navigate, however. We exploit graph theory for focusing these large graphs. The method is based on degree centrality, which measures connectedness in a graph. Four categories of clinical concepts related to treatment of disease were identified and presented as a summary of input text. A baseline was created using term frequency of occurrence. The system was evaluated on summaries for treatment of five diseases compared to a reference standard produced manually by two physicians. The results showed that recall for system results was 72%, precision was 73%, and F-score was 0.72. The system F-score was considerably higher than that for the baseline (0.47).
On the Hypothetico-Deductive Nature of Science—Darwin’s Finches

Allchin (2006) has misinterpreted a classic case of hypothetico-deductive (HD) science in terms of his preferred ‘let’s-gather-some-data-and-see-what-emerges’ view. The misrepresentation concerns the research program of Peter and Rosemary Grant on Darwin’s finches. The present essay argues that the Grants’ research is HD in nature and includes a statement by Peter Grant to that effect.
Sickle cell crisis and sensorineural hearing loss: case report and discussion

Patients in sickle cell crisis may complain of unilateral or bilateral hearing loss which is typically a mild to moderate high-frequency sensorineural hearing loss in the affected ear(s). Auditory acuity can return to precrisis levels. A literature review suggests that the etiology is cochlear ischemia. A review of the literature, case study, and discussion will be presented.
Extent of lymph node resection does not increase perioperative morbidity and mortality after surgery for stage I lung cancer in the elderly.

Abstract Background & objectives Pathologic evaluation of >10 lymph nodes (LNs) is considered necessary for accurate lung cancer staging. However, physicians have concerns about increased risk in perioperative mortality (POM) and morbidity with more extensive LN sampling, particularly in the elderly. In this study, we compared the outcomes in elderly patients with stage I non-small cell lung cancer (NSCLC) undergoing extensive (>10 nodes) and limited (≤10 nodes) LN resections. Methods Using data from the Surveillance, Epidemiology and End Results registry linked to Medicare records, we identified 4975 patients ≥65 years of age with stage I NSCLC who underwent a lobectomy between 1992 and 2002. Risk of perioperative morbidity and POM after the evaluation of ≤10 vs. >10 LNs was compared among patients after adjusting for propensity scores. Results Multiple regression analysis showed similar POM between the two groups (OR, 1,01; 95% CI, 0,71–1,44). Other postoperative complications were similar across groups except for thromboembolic events, which were more common among patients undergoing resection of >10 LNs (OR, 1,72; 95% CI, 1,12–2,63). Conclusions These data suggest that evaluation of >10 LNs, which allows for more accurate staging, appears to be safe in the elderly patients undergoing lobectomy for stage I NSCLC without compromising postoperative recovery.
Regular Article: A Solution-Adaptive Upwind Scheme for Ideal Magnetohydrodynamics

This paper presents a computational scheme for compressible magnetohydrodynamics (MHD). The scheme is based on the same elements that make up many modern compressible gas dynamics codes: a high-resolution upwinding based on an approximate Riemann solver for MHD and limited reconstruction; an optimally smoothing multi-stage time-stepping scheme; and solution-adaptive refinement and coarsening. In addition, a method for increasing the accuracy of the scheme by subtracting off an embedded steady magnetic field is presented. Each of the pieces of the scheme is described, and the scheme is validated and its accuracy assessed by comparison with exact solutions. Results are presented for two three-dimensional calculations representative of the interaction of the solar wind with a magenetized planet.
Phase Detection Electromagnetic Flowmeter-Design and Use

Two types of gated sine-wave electromagnetic flowmeter are examined critically, and found to be sensitive to phase shift in the transducer signal. This phase shift is always found in a sine-wave flow transducer because of imperfection in construction, particularly in those used for physiology and medicine. A flowmeter design that discards amplitude modulation and is sensitive to phase change only is described. Advantages over other types of electromagnetic flowmeter are discussed. Results obtained with the phase detection flowmeter are illustrated.