cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular Weight and Volume at Position 46 in Transmembrane Domain 1 (TM1) are Important Determinants for Ethanol Sensitivity in P2X4 Receptors

Purinergic P2X receptors (P2XRs) are a family of fast acting, cation-permeable ligand-gated ion channels, which are gated by synaptically released adenosine 5′-triphosphate (ATP). Building evidence supports the notion that P2XRs play a role in mediating and/or modulating behavioral effects of ethanol. However, this work is in the early stages and the sites and mechanisms of ethanol action in P2XRs are poorly understood. Recently, we identified an amino acid located in TM1 that was conserved across P2X3 and P2X4Rs that appeared to represent an important site for the action of ethanol (i.e., Trp41 and Trp46, respectively). The current study tests the hypothesis that physical-chemical properties of the residue at position 46 play a significant role in determining ethanol sensitivity in P2X4Rs. We expressed wildtype and mutated receptors in Xenopus oocytes and determined changes in ethanol sensitivity (200mM) using an 8-channel two-electrode voltage clamp system (OpusXpress 6000; -70mV). Exchanging Trp46 residue with other aromatic residues did not significantly alter ethanol sensitivity whereas replacing Trp46 with aliphatic residues significantly reduced the action of ethanol. Correlation analysis determined that molecular weight and volume of the residue at position 46 were significantly correlated with ethanol sensitivity whereas polarity or hydrophobicity was not. The findings suggest that the size and aromaticity of the residue at position 46 in TM1 play an important role in determining ethanol sensitivity of P2X4Rs. Identifying physical-chemical properties of residues that are important for ethanol sensitivity will increase our knowledge regarding structural requirements that are necessary for ethanol to cause changes in modulation and/or transduction of agonist action in P2X4Rs. Support: NIAAA/NIH F31 AA017029, KO1 AA017243-01A1, AA013922, AA03972 and USC School of Pharmacy.
The future of access control: Attributes, automation and adaptation

Summary form only given. Access control has been and will always be one of the center pieces of cyber security. This talk will focus on three necessary characteristics of access control in future systems: attributes, automation and adaptation. Future access control policies will be built around attributes, which are properties of relevant entities, so they can apply to large numbers of entities while being fine-grained at the same time. This transition to attribute-based access control has been in process for about two decades and is approaching a major inflection point. Automation and adaptation, however, are newer concepts. Automation seeks to break away from requiring human users to configure access control policies, by delegating more of the routine tasks to smart software. Adaptation recognizes that access control must adjust as circumstances change. This talk will speculate on a future built around these three synergistic elements, and on the research and technology challenges in making this vision a reality.
Sex hormones and coronary disease: a review of the clinical studies.

PIP: A male to female ration of coronary disease of 2:1 has been a consistent finding. This differential persists event when the classic risk factors for coronary disease--hypertension, smoking, obesity, diabetes, and hyperlipidemia--are controlled for gender. The most likely ultimate cause of this phenomenon is male-female differences in sex hormone patterns. Clinical studies in this area have either compared the sex hormone profiles of men and women with and without coronary disease or computed the relative prevalence of disease in populations that differ in their sex hormone patterns. In general, research findings have disputed the hypothesis that persons with coronary disease have low levels of a protective factor such as estrogen or progesterone and high levels of testosterone. Coronary disease patients actually have elevated estrogen levels and low testosterone levels; endogenous progesterone levels are normal before infarction but show a stress-mediated increase in the immediate postinfarction period. Findings of a low prevalence of coronary disease in premenopausal women, a loss of protection after menopause, and a low prevalence of coronary disease in men with cirrhosis-related hyperestrogenemia suggest that natural estrogens are antiatherogenic. The protective effect of pregnancy against myocardial infarction, despite concomitant potentially thrombogenic levels of estrogen at the time, seems to indicate that progesterone, whose levels are also extremely high during pregnancy, plays a major anti-infarction protective effect distinct from that of estrogen. Studies of women oral contraceptive (OC) users and men taking estrogens for brief periods have found that these exogenous hormones produce coronary thrombosis but not atherosclerosis. Finally, the finding of increased coronary disease risk in long-term OC users indicates that synthetic estrogens favor coronary atherosclerosis by suppressing natural estrogen and progesterone production.
The distribution of immunoglobin allotypes in two Tlaxcaltecan populations.

SummaryThe distribution of Glm(f, z, a, and x), G3m(b0, b1, b3, b5, c3, c5, g, s, t and v), A2m(1 and 2) and Km(1) (formerly Inv(1)) allotypic determinants has been examined in specimens from the inhabitants of two transplanted Tlaxcaltecan villages (Cuanalan and Saltillo). The results indicate that Gmza;gAm1, Gmza;gAm2, Gmzax;g Am1, Gmza;bst Am1, Gmza;bst Am2, Gmf;b Am1, Gmza,b Am1, Gmza;bAm2 and Km1 are polymorphic or marginally polymorphic in both populations, while Gmza;bc3,5 Am2, Gmza;bs Am2, and Gmzax;gAm2 were detected only in Saltillo. Two related individuals from Saltillo have either a Gmf;gAm1 or Gmf;-Am1 haplotype while a third unrelated individual had either a Gmf;g Am1 or Gm-;gAm1 haplotype. The frequencies observed for “residents” of Cuanalan are similar to those for other Indian populations in Mexico.Estimation of Caucasian and African admixture within the two communities indicates significant heterogeneity among the inhabitants of Cuanalan, in that Tlaxcaltecan residents have no detectable...
Dual-Domain Hierarchical Classification of Phonetic Time Series

Phonemes are the smallest units of sound produced by a human being. Automatic classification of phonemes is a well-researched topic in linguistics due to its potential for robust speech recognition. With the recent advancement of phonetic segmentation algorithms, it is now possible to generate datasets of millions of phonemes automatically. Phoneme classification on such datasets is a challenging data mining task because of the large number of classes (over a hundred) and complexities of the existing methods. In this paper, we introduce the phoneme classification problem as a data mining task. We propose a dual-domain (time and frequency) hierarchical classification algorithm. Our method uses a Dynamic Time Warping (DTW) based classifier in the top layers and time-frequency features in the lower layer. We cross-validate our method on phonemes from three online dictionaries and achieved up to 35% improvement in classification compared to existing techniques. We provide case studies on classifying accented phonemes and speaker invariant phoneme classification.
Fast fault location in power transmission networks using transient signatures from sparsely-placed synchrophasors

This paper explores real-time fault location in a power transmission network using measurements of transients from sparsely-placed synchrophasors. The fault-location problem is abstracted to a statistical hypothesis-testing or detection problem, wherein the linearized dynamical models corresponding to different fault conditions must be distinguished in the face of fault-clearing and measurement uncertainty. A maximum a posteriori probability (MAP) detector is constructed. A strategy for real-time implementation of the fault-locator is discussed, which is based on pre-computation of detector parameters using state-estimator and contingency-analysis data, along with on-line collection of synchrophrasor data and implementation of the hypothesis test. Numerical case studies of the 11-Bus two area power system verify that the proposed fault-location algorithm can locate a faulted line accurately and quickly.
Ultrafast Dynamics of Highly Conjugated Porphyrin Arrays

The photophysical properties of a series of ethynyl-bridged (porphinato)zinc(II) oligomers have been investigated over the femtosecond and picosecond time scales using ultrafast magic angle and polarized pump−probe spectroscopy. Bis[(2,2‘,-5,10,15,20-tetraphenylporphinato)zinc(II)]ethyne, bis[(5,5‘,-10,20-diphenylporphinato)zinc(II)]ethyne, and 5,15-bis{[(5‘,-10‘,20‘-diphenylporphinato)zinc(II)]ethynyl}[10,20-diphenylporphinato]zinc(II) exhibit rapid (≤150 fs) formation of the emitting state following Soret photoexcitation, nearly an order of magnitude faster than the ∼1 ps S2 → S1 internal conversion observed for a monomeric (porphinato)zinc(II) complex that bears an ethyne moiety fused directly to its macrocycle carbon framework [(5-trimethylsilylethynyl-10,20-diphenylporphinato)zinc(II)]. The femtosecond and picosecond dynamics are strongly influenced by the porphyrin-to-porphyrin linkage topology: bis[(2,2‘,-5,10,15,20-tetraphenylporphinato)zinc(II)]ethyne, in which a β-to-β ethyne bridge links the t...
Inactivity of phosphoethanolamine, an endogenous GABA analog decreased in Alzheimer's disease, at GABA binding sites

Abstract Phosphoethanolamine (PE) is a metabolite of phospholipid metabolism which is decreased in Alzheimer's disease brain. PE shows a strong structural similarity to the inhibitory neurotransmitter, GABA, and the GABA B receptor partial agonist, 3-amino-propylphosphonic acid. The ability of PE to compete for binding to GABA A and GABA B binding sites was investigated. GABA A sites were studied using [ 3 H]SR-95531 and [ 3 H]muscimol. GABA B sites were studied using [ 3 H]GABA in the presence of isoguvacine to saturate GABA A sites. Total [ 3 H]GABA binding was also examined. PE showed little activity at any of the GABA binding sites investigated. PE was most potent at GABA B sites, but the IC 50 of 7.5 ± 0.75 mM was considerably higher than its maximal physiologic concentration of approximately 1.5 mM. The efficient exclusion of PE from GABA binding sites may be an important physiologic mechanism in the control of inhibitory neurotransmission. The structural basis for this exclusion is discussed in reference to the GABA B partial agonist 3-amino-propylphosphonic acid.
A comparison of solar total irradiance observations from spacecraft: 1985-1992

This paper presents a statistical comparison of the solar total irradiance measured from the Nimbus-7, the Solar Maximum Mission (SMM), the Earth Radiation Budget Satellite (ERBS), and the Upper Atmosphere Research Satellite (UARS) spacecraft platforms, for the period 1985 –1992. The mean irradiance, standard deviation, and the correlation among the daily irradiance remained high during periods of high solar activity. Linear regression models are established to estimate the irradiance measurements from one platform by the others. The results are consistent with the observations. However, the Nimbus-7 ERB responses show a drift during 1989–1992. The absolute irradiance observed by each instrument varies within the uncertainty associated with the corresponding radiometer.
Dissociative Electron Transfer in Donor−Peptide−Acceptor Systems: Results for Kinetic Parameters from a Density Functional/Polarizable Continuum Model

The main structural and electronic factors playing a role in intramolecular dissociative electron transfer of a simple donor-peptide-acceptor (D-peptide-A) model have been investigated by an integrated computational protocol based on the density functional theory, its time-dependent extension, and the polarizable continuum model. Our results allow us to elucidate the electronic states involved in the process and how they are perturbed by the orientation of the donor and the acceptor with respect to the peptide chain and by the presence of the solvent. We also report a semiquantitative estimation of the rate constant governing electron transfer obtained by a direct quantum mechanical evaluation of all the terms entering the kinetic expressions based on the Marcus theory and its extensions.
Population Dynamics and Life History Characteristics of the Blue Crabs Callinectes similis and C. sapidus in Bay Environments of the Northern Gulf of Mexico

. The population dynamics and life history characteristics of Callinectes similis and C. sapidus in the Mobile Bay-Mississippi Sound estuarine system of the northern Gulf of Mexico were studied. We report that C. similis is numerically dominant in open-bays, while C. sapidus is more abundant in shallow salt marshes. Juvenile C. similis recruit into both open-bays and salt marshes, but juvenile C. sapidus primarily recruit into shallow salt marshes. Sex ratios of C. similis and C. sapidus were generally skewed towards higher proportions of males than females. Callinectes similis appears to have a life cycle similar to that of C. sapidus. Egg-carrying C. similis migrate to higher salinity waters and presumably release larvae to nearshore shelf waters; following development, the larvae re-invade estuaries as megalopae. Juvenile C. similis grow more slowly than C. sapidus. This may be attributable to reduced feeding rates. Marked differences in fecundity and reproductive effort were found between these species. Callinectes similis and C. sapidus, respectively, produced 2.4–5.5 times 105 and 2.1–3.2 times 106 eggs and invested 24–49 and 171–372 kJ per brood. Rhizocephalan barnacle infestation by Loxothylacus texanus was encountered in C. sapidus, while sympatric C. similis were free of this rhizocephalan parasite.
776-5 Mechanism of Decrease of Angiotensin II Receptor Message Through Dual Signal Transduction Pathways in Vascular Smooth Muscle

We previously have shown that the angiotensin II receptor, type 1a (ATlaR) message transiently decreases during ang II stimulation of cultured rat aortic vascular smooth muscle cells (VSMC); and, it has been previously reported by others that the mechanism of this decrease in cultured kidney cells is through cAMP dependent pathways. In this study we examined the signal transduction pathway of this regulation in quiescent VSMC. Total cellular RNA was harvested after time course exposure to reagents, Northern blotted and probed. AT1aR message abundance decreased beginning two hours after exposure to ang II (10 nM) and reached a minimum at 4 hours after stimulation of 25% of baseline level. The protein kinase C(PKC) stimulator, PMA (50 nM), caused a decrease in AT1aR message level with the same time course and to the same extent as ang II. Downregulation of PKC with 24 hour prior exposure to PDBU (500 nM) blocked the decrease in AT1aR message caused by PMA. However, pretreatment with either PDBU orthe potent PKC inhibitor calphostin C(50 nM) did not block the decrease of AT1aR message level caused by ang II. In contrast. stimulation of cAMP with forskolin (50 mM), cholera toxin (10 ng/ml) or the soluble analog 8-bromocyclic AM P(1 mM) did not decrease AT1aR message level. whereas inhibition of PKA with H-8 pretreatment (10 mM) followed by ang II still decreased AT1aR message abundance. We conclude that the decrease of AT1aR message level in VSMC is through both PKC and non-PKC dependent pathways, but not through PKA or cAMP dependent pathways.
A Hierarchical Production Planning and Scheduling Model

A hierarchical production planning and scheduling system is developed that integrates planning decisions into a unified and consistent framework. A three-tiered approach is used to address long-term inventory control, short-term production planning, and daily scheduling tasks. A product grouping scheme introduces uniformity into the solution process and simplifies overall model complexity. Results of the model implementation are reported.
Explanation of the unusual temperature dependence of the atmospherically important OH + H2S → H2O + HS reaction and prediction of the rate constant at combustion temperatures

Rate constants for the OH + H2S → H2O + HS reaction, which is important for both atmospheric chemistry and combustion, are calculated by direct dynamics with the M06-2X density functional using the...
An analysis of the radial distribution function of SIOx

Abstract A theory is presented for the short-range order (sro) in the SiOx alloy system for 0⩽x⩽2. The parameters of the sro are taken to be fixed by the properties of amorphous Si and SiO2, except that the probability of an Si atom having (i−1) oxygen neighbors is left as a free parameter, Ci(x), for i=1 through 5. The areas of the first three peaks in the radial distribution function (RDF) of SiOx are calculated as a function of x and Ci(x). It is shown that the RDF can be used to differentiate between the two models proposed for the sro in SiOx namely the SiSiO2 mixture model and the random bonding model. In the case of SiO powder, a mixture model at the atomic level is found to be consistent with the RDF. It is suggested that accurate RDF's of SiOx films, which are not currently available, would be useful in determining the sro of the alloy system. The present theory may be extended to analyze the GeOx and SnOx alloy systems.
Creatine metabolism in the developing rat fetus

Abstract 1. 1. Guanidinoacetate-N-methyltransferase activity (GMT) of fetal rat liver was less than half that of maternal liver late in gestation. GMT was not detected in the chorioplacenta. 2. 2. A high creatine concentration was observed in fetal blood from the twentieth to the twenty-second day of gestation. Creatine levels in blood of 3-day-old neonates were not significantly different from those of the mother. 3. 3. Radioactivity found in fetal blood 30 min after the maternal injection of creatine-1-14C was higher than that in maternal blood. 4. 4. The total creatine and protein content of the fetus increased exponentially and in parallel from the thirteenth to the nineteenth day of gestation.
Exploring fit and misfit with multiple contingencies.

The author wishes to acknowledge Andy Van de Ven for his contribution to this stream of research and his permission to use the data, and Bob Drazin, Nancy Fisher, Mike Tushman, Elaine Romanelli, Blair Sheppard, the anonymous reviewers of ASQ, and especially Gerald Salancik for their insightful comments and suggestions. Bob Drazin, in particular, provided both guidance and inspiration in his role as my dissertation advisor. Portions of an earlier draft of this paper appeared in the 1987 Academy of Management Proceedings. Support during the revision stage was provided by the Fuqua School Business Associates Fund. This paper proposes a multiple-contingencies theory that simultaneously examines the effects of task and dependence on unit design and efficiency. The theory explores and predicts the conditions under which work-unit designs fail to fit their contexts. Findings from studies of one contingency factor (e.g., uncertainty or dependence) have shown that poor performance by units is related to a lack of fit with theoretically prescribed patterns of design, but because such studies do not do justice to the complexities of design, it is difficult to predict misfit. The multiple-contingency approach proposed here specifically focuses on issues such as misfit, conflicting contingencies, and equifinality. The model is tested, using data from 529 work units in 60 employment-security offices. A key finding is that units facing conflicting contingencies are more prone to design misfit and lower performance.
Stepwise oxidation of benzylamine coordinated to the [Tp'W(CO)(PhC2Me)]+ moiety

Coordination of benzylamine to the [Tp‘W(CO)(PhC2Me)]+ moiety activates the amine for stepwise oxidation by sequential hydride/proton removal steps. Each metal complex along the stepwise reaction path (amine, amido, imine, azavinylidene, and nitrile) has been isolated and characterized. The structure of the imine complex [Tp‘W(CO)(PhC2Me)(NHCHPh)][BF4] (4) has been confirmed by an X-ray diffraction study. Complex 4 crystallizes in the space group P21/c (Z = 4, a = 13.790(3) A, b = 13.225(3) A, c = 19.150(4) A, β = 108.769(1)°, R = 3.5%, Rw = 4.4%), and key geometric features include a W−N dative bond length of 2.135(6) A to the imine nitrogen and a W−N−C angle of 129.7(5)°.
Ritual Murder in a Russian Border Town

On April 22, 1823, in the small White Russian border town of Velizh, a three-year-old boy finished his lunch and went outside to play. Fedor never returned home, and several days later a neighbor found his body at the very edge of town, punctured in numerous places. Now largely forgotten, Fedor’s death resulted in the longest and one of the most comprehensive investigations of ritual murder in the modern world. Using the analytical techniques of microhistory, this essay reconstructs small-town life in the Russian Empire, exploring along the way neighborly encounters, law and daily life, and the complex motivations that led to the ritual murder charge. While scholars usually attribute the charge to antisemitism and economic rivalries, this essay offers an alternative explanation. By recreating the day-to-day world of Velizh, I argue that tales of blood sacrifice proved remarkably contagious in the towns and villages of eastern Europe because of their role in the popular belief systems of the time and their ability to express the fears and preoccupations of a population that left no other records.
DAB1 and Reelin Effects on Amyloid Precursor Protein and ApoE Receptor 2 Trafficking and Processing

Numerous cytoplasmic adaptor proteins, including JIP1, FE65, and X11α, affect amyloid precursor protein (APP) processing and Aβ production. Dab1 is another adaptor protein that interacts with APP as well as with members of the apoE receptor family. We examined the effect of Dab1 on APP and apoEr2 processing in transfected cells and primary neurons. Dab1 interacted with APP and apoEr2 and increased levels of their secreted extracellular domains and their cytoplasmic C-terminal fragments. These effects depended on the NPXY domains of APP and apoEr2 and on the phosphotyrosine binding domain of Dab1 but did not depend on phosphorylation of Dab1. Dab1 decreased the levels of APP β-C-terminal fragment and secreted Aβ. Full-length Dab1 or its phosphotyrosine binding domain alone increased surface levels of APP, as determined by surface protein biotinylation and live cell staining. A ligand for apoEr2, the extracellular matrix protein Reelin, significantly increased the interaction of apoEr2 with Dab1. Surprisingly, we also found that Reelin treatment significantly increased the interaction of APP and Dab1. Moreover, Reelin treatment increased cleavage of APP and apoEr2 and decreased production of the β-C-terminal fragment of APP and Aβ. Together, these data suggest that Dab1 alters trafficking and processing of APP and apoEr2, and this effect is influenced by extracellular ligands.
Direct Imaging and Spectroscopic Characterization of Stimulus-Responsive Microgels

Scanning transmission X-ray microscopy has been employed to visualize pH-responsive acid-swellable microgel particles directly in their swollen state in aqueous acidic solution. Moreover, NEXAFS studies confirm that the nitrogen atoms of these cationic microgel particles are completely protonated at low pH.
Non-depleting anti-CD4, but not anti-CD8, antibody induces long-term survival of xenogeneic and allogeneic hearts in α1,3-galactosyltransferase knockout (GT-Ko) mice

The anti-galactose-alpha1,3-galactose (Gal) antibody (Ab) response following pig-to-human transplantation is vigorous and largely resistant to currently available immunosuppression. The recent generation of GT-Ko mice provides a unique opportunity to study the immunological basis of xenograft-elicited anti-Gal Ab response in vivo, and to test the efficacy of various strategies at controlling this Ab response [1]. In this study, we compared the ability of non-depleting anti-CD4 and anti-CD8 to control rejection and antibody production in GT-Ko mice following xenograft and allograft transplantation. Hearts from baby Lewis rat or C3H mice were transplanted heterotopically into GT-Ko. Non-depleting anti-CD4 (YTS177) and anti-CD8 (YTS105) Abs were used at 1 mg/mouse, and given as four doses daily from day -2 to 1 then q.o.d. till day 21. Xenograft rejection occurred at 3 to 5 days post-transplantation in untreated GT-Ko recipients, and was histologically characterized as vascular rejection. Anti-CD4, but not anti-CD8, Ab treatment prolonged xenograft survival to 68 to 74 days and inhibited anti-Gal Ab as well as xeno-Ab production. In four of the five hearts from anti-CD4 mAbs-treated GT-Ko mice, we observed classic signs of chronic rejection, namely, thickened intima in the lumen of vessels, significant IgM deposition, fibrosis and modest mononuclear cell infiltrate of Mac-1+ macrophages and scattered T cells (CD8>CD4). Xenograft rejection in untreated, as well as anti-CD4- and anti-CD8-treated, recipients was associated with increased intragraft IL-6, IFN-gamma and IL-10 mRNA. C3H allografts were rejected in 7 to 9 days by untreated GT-Ko mice and were histologically characterized as cellular rejection. Treatment with anti-CD4 and anti-CD8 mAb resulted in graft survivals of >94.8 and 11.8 days, respectively. Anti-CD4 mAb treatment resulted in a transient inhibition of alloreactive and anti-Gal Ab production. The presence of circulating alloreactive and anti-Gal Abs at >50 days post-transplant was associated with significant IgM and IgG deposition in the graft. Yet, in the anti-CD4 mAb-treated group, the allografts showed no signs of rejection at the time of sacrifice (>100 days post-transplantation). All rejected allografts had elevated levels of intragraft IL-6, IFN-gamma and IL-10 mRNA, while the long-surviving anti-CD4-treated allografts had reduced mRNA levels of these cytokines. Collectively, our studies suggest that the elicited xeno-antibody production and anti-Gal Ab production in GT-Ko mice are CD4+ T-cell dependent. The majority of xenografts succumbed to chronic rejection, while allografts survived with minimal histological change, despite elevated levels of circulating alloAbs. Thus, immunosuppression with anti-CD4 mAb therapy induces long-term survival of allografts more effectively than to xenografts.
PHOTOREACTIVATION OF KILLING IN STREPTOMYCES-III. ACTION SPECTRA FOR PHOTOLYSIS OF PYRIMIDINE DIMERS AND ADDUCTS IN S. GRISEUS AND S. GRISEUS PHR-l*

Abstract— Photolysis of tritium-labelled thymine-derived photoproducts by 254-nm ultraviolet radiation (u.v.) in conidia of Streptomyces griseus was measured by chromatography of cell hydrolysates. The relative photolysis cross-sections of uracilthymine dimer (UT○) at various wavelengths are the same as those of thymine-thymine dimer (TT○), and their ratios at 313, 365, 405 and 436 nm are 2:1:2:3. Except at 436 nm, these relative values agree very well with cross-sections previously reported for photoreactivation of u.v. killing in this organism, leading to the conclusion that photoreactivation in the wild type is due to repair of cyclobutane-type pyrimidine dimers. In a mutant showing restricted photoreactivation (S. griseus PHR-1), post-u.v. treatments at the above wavelengths did not affect UT○ and TT○ in the conidia, supporting the earlier suggestion that this organism does not contain active PR enzyme. Another u.v. photoproduct, the precursor of a pyrimidine adduct (PO-T) that appears in cell hydrolysates, was removed from both wild-type and mutant cells very efficiently at 313 nm. This is presumably a direct photochemical reaction. In addition, in wild-type cells, the precursor of PO-T appeared to be inefficiently removed photoenzymatically at all wavelengths. Removal of the precursor of PO-T appears to be biologically significant, however, only in the mutant.
Federalism, Courts and Legal Systems: The Emerging Constitution of the European Community

The European Community' is not a federation, though it may one day become one. It nevertheless possesses a number of distinctly federal elements, a fact which has led writers to coin the neologism "supranational" to describe it. This paper is concerned with a comparative analysis of these elements in so far as they relate to the courts and legal system of the Community. The United States and Canada, both mature federations, will be used as a "control group" to provide an example of what true federalism requires.2 By concentrating on these features (clearly the most interesting) the impression might be given that the European Community is more developed, and more nearly federal, than is the case. This is particularly so in view of the fact that it is precisely those parts of the Community constitution which are concerned with the legal and judicial system that are most federal; the parts concerned with the political system, on the other hand, are still firmly rooted in the pre-federal
DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.
A pushdown automation or a context-free grammar—which is more economical?☆☆☆

Abstract For every pair of positive integers n and p, there is a language accepted by a real-time deterministic pushdown automaton with n states and p stack symbols and size O(np), for which every context-free grammar needs at least n2p+1 nonterminals if n>1 (or p non-terminals if n = 1). It follows that there are context-free languages which can be recognized by pushdown automata of size O(np), but which cannot be generated by context-free grammars of size smaller than O(n2p); and that the standard construction for converting a pushdown automaton to a context-free grammar is optimal in the sense that it infinitely often produces grammars with the fewest number of nonterminals possible.
Spatial distribution of electron densities during optical excitation of C60.

We calculate the spatial distribution of the oscillating electron density for the low energy optical excitations in C60, using ab initio time-dependent density functional theory. We contrast this with the unscreened free response of the Kohn–Sham eigenfunctions, in which the charge transfer is between hemispheres and the simple density oscillation patterns are very similar for electrons outside and inside the C60 radius. In the screened case, the oscillation patterns involve charge transfer on the scale of interatomic distances. The exterior and interior densities play different roles in the oscillator strength and screening. Almost all of the dipole oscillation for optical absorption strength is from exterior electrons, a consequence of the superposition of π and σ electron oscillations. The lowest transition with appreciable strength is dominated by screening from π electrons.
Distinct neurite outgrowth signaling pathways converge on ERK activation.

Several distinct classes of proteins positively regulate axonal growth; some of these are known to activate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling cascade, at least in nonneuronal cells. We have found that N-cadherin, as well as laminin (LN) and basic fibroblast growth factor (bFGF), can activate ERK in embryonic chick retinal neurons. Additionally, adhesion of retinal neurons to LN or N-cadherin substrates induced a redistribution of ERK from the cytoplasm toward the plasma membrane. Neurite outgrowth induced by bFGF, LN, or N-cadherin was strongly inhibited by treatment with inhibitors of ERK kinase activation, but not by an inhibitor of p38 MAPK. We conclude (1) that N-cadherin and LN can activate ERK in retinal neurons and (2) that activation of ERK is required for full neurite outgrowth induced by these proteins. Our results suggest that ERK activation is one point of convergence for signaling pathways generated by a variety of axon growth inducers.
Fetal surgery for lung lesions, congenital diaphragmatic hernia, and sacrococcygeal teratoma.

Abstract After more than 2 decades of experimental and clinical work, fetal surgery is an accepted treatment option for highly selected fetuses with life-threatening anomalies. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunt placement may be effective in the setting of a single large cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with associated liver herniation and a low right lung to head circumference ratio have a relatively poor prognosis with conventional therapy after birth, but in utero therapeutic approaches have yet to show a comparative survival benefit. A prospective randomized trial is required to critically evaluate the efficacy of fetal tracheal occlusion for severe diaphragmatic hernia. Fetal sacrococcygeal teratoma complicated with progressive high output cardiac failure may benefit from in utero resection of the tumor.
Guidelines for planning and evaluating school psychology service delivery systems

Abstract Contemporary standards of professional practice (e.g., American Psychological Association, 1977) and recent educational compliance legislation (e.g., PL 94–142) emphasize the delivery of appropriate school psychological services geared to a range of school-age children with special needs. Thus, school psychologists must pay increased attention to the development of school psychology service delivery systems. Toward this end, guidelines are presented for planning and evaluating school psychology service delivery systems. The guidelines are set forth in order that school psychologists might consider them and adapt them to local circumstances. The eight principles which comprise the guidelines have been used by the author in planning and evaluating school psychology service delivery systems in several public school districts. One particular school district will serve to illustrate the utilization of the guidelines.
Analysis of the human adult hemoglobin "core".

Abstract The “core” of human adult hemoglobin has been isolated from the tryptic digest of heat-denatured hemoglobin and of the purified hemoglobin peptide chains. The “core” has been digested with chymotrypsin and the digest analyzed by fingerprinting. The α chain “core” is digested effectively and the resulting peptides have been separated and analyzed. The β chain “core” is resistant to chymotryptic digestion.
Depacon in the acute treatment of mania

Study objectives: Anticonvulsants are a first-line treatment for acute mania and offer a safer and more efficacious treatment than lithium. Oral loading with valproic acid is US Food and Drug Administration approved. Valproate, the intravenous form of valproic acid, reaches peak serum concentration 4 times faster than valproic acid but is primarily used for acute seizure treatment. There is minimal literature on intravenous valproate in treating acute mania. Methods: We describe a pilot study designed to test the safety and efficacy of intravenous valproate in treating manic patients presenting to the emergency department (ED). Five subjects, aged 21 to 50 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for mania, were enrolled between May 1999 and April 2002. On admission to the ED, consent, blood tests, and physical examination were obtained. Psychiatric testing, including the clinical global impression score (CGI), brief psychotic rating scale (BPRS), and Young's mania rating scale (YMRS), were administered before and 1, 2, and 24 hours after valproate infusion. A loading dose of 1,200 mg valproate was given over a 1-hour period at initial testing. Results: No adverse effects were noted. Mean scores before infusion were consistent with moderate to severe mania (CGI=4.8, BPRS=32.6, and YMRS=21.2). One hour after infusion, scores were reduced 12.5%, 7.4%, and 15.1%, respectively. The 2-hour interval showed further improvement from baseline of 29.2%, 16.6%, and 21.7%. Twenty-four hour follow-up for 4 of 5 patients showed a 37.5%, 17.2%, and 30.2% decrease from baseline. Two of the 5 patients were treated as outpatients, with transition to oral valproate. Conclusion: Notable decreases in illness severity rapidly occurred in all manic subjects receiving intravenous valproic acid. However, because of low enrollment, no statistical significance can be inferred. Also, we must caution that decreased symptomology could be due to sedation rather than reduction of the manic episode. Typically, manic patients require hospitalization; intravenous loading of valproate may decrease hospital stay or possibly alleviate the need for admission. This pilot study would suggest that further inquiry is warranted.
A cohort-based indicator of housing progress

Measuring housing quality has continued to be an elusive task. This article proposes a new social indicator of housing quality that builds on three conceptual decisions. The first step is to define an indicator that measures quality with reference to a standard that households are striving to attain. Single-family homeownership is a standard of housing sought by nine-tenths of Americans under age 45. A second decision is to measure quality not according to absolute attainment of this standard, but rather with reference to the aggregate experience of progress toward attaining the standard. Under this experiential definition, quality is assumed to be high when the average individual moves quickly toward homeownership. The third conceptual decision is to aggregate individuals' progress toward homeownership by measuring the trajectory of cohorts into homeownership. The indicator of housing progress is thus a vector of age-specific ownership rates. Twentieth-century cohorts are compared on this indicator and the implication of differences among them are discussed.
Jitter in H/sup -/ beam position at Neutral Particle Beam Test Stand

Measurements of the time variation of beam position (jitter) during a single pulse and from pulse to pulse were made at various locations in the Neutral Particle Beam Test Stand using five directional coupler (stripline) beam position monitors developed by Los Alamos National Laboratory. The average measured beam jitter at the linac exit during a 100- mu s long pulse was 130 mu m in X and 50 mu m in Y, and the pulse-to-pulse jitter was 30-50 mu m in X and 30-40 mu m in Y. At the entrance to the telescope, the beam jitter during a pulse was from 70 mu m in X and 160 mu m in Y for high current to less than 20 mu m for X and Y for low current. The jitter from pulse to pulse varied from 150 to 160 mu m in X and 70 to 80 mu m in Y for high current and 60 to 70 mu m in X and Y for low current. >
Communicating (St)ageism: Exploring Stereotypes of Age and Sexuality in the Workplace

Older adults are often plagued with the stereotype that they have outgrown any semblance of sexual identity. This stereotype is prominent in the workplace, as older coworkers are assumed to be past the stage in their lives where sexuality is an aspect of one’s identity. The present study explored how age was a central factor in describing sexuality in the workplace. More specifically, active interviews unearthed age of organization members as a prominent rationale for why sexual discussion is prohibited in the workplace. Results indicated a discursive divide separating older workers from their younger counterparts, reifying the notion that older coworkers are largely asexual. Implications are provided and include an opportunity to see age at the intersection of sexuality as a discursive dividing line in the workplace.
Chronic cerebral effects of alcohol and drug abuse.

A minority of alcohol abusers develop severe cerebral dysfunction in the form of Wernicke-Korsakoff syndrome. There is also evidence to suggest that cerebral dysfunction, particularly impaired abstracting ability, occurs in that larger population of heavy drinkers who do not go on to develop the Wernicke-Korsakoff syndrome. There is no consistent evidence that long-term marijuana, hallucinogen, or sedative use causes lasting neuropsychological disturbance. The deficits in abstract thinking reported by some LSD studies are similar to deficits others have reported among alcoholics. Since the LSD studies were not controlled for alcohol use, their interpretation is difficult. It appears that cerebrovascular accidents occur more frequently and at a younger age among amphetamine abusers. There is no reliable information about possible other long-term effects of stimulants on the brain per se (i.e., nonvascular complications). Abuse of intravenous narcotics has been associated with case reports of transverse mye...
Estimation of Total Cholesterol in Serum by a Micro Method

A method has been described for the estimation of total cholesterol in 0.02ml. of serum without the need for micro apparatus. It involves the measurement of the fluorescence developed after the addition of sulfuric acid to a solution of cholesterol in a mixture of 1,1,2-trichloroethane and acetic anhydride(1). The results obtained with both human and rat sera have been in good agreement with those obtained with a standard colorimetric method(2), and the standard deviation for an estimation carried through in duplicate, owing to error within the method, has been ±4-5 mg. per 100 ml. under routine conditions.
AMP kinase activation improves angiogenesis in pulmonary artery endothelial cells with in utero pulmonary hypertension.

Pulmonary artery endothelial cells (PAEC) isolated from fetal lambs with in utero pulmonary hypertension (IPH) have phenotypical changes that lead to increased reactive oxygen species (ROS) formati...
Inhibitors of renin: present and future.

Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogen and peptides that are related to the amino-terminal sequence of renin's precursor (Prorenin). With the purification of renin, specific polyclonal or monoclonal antibodies have become available. The former have already been used extensively in physiologic studies in intact animals. Pepstatin is an inhibitor of many acid proteases. Its in vivo application has been retarded by its relative insolubility, but recent chemical modifications, particularly the addition of charged amino acids at the carboxy-terminus have rendered it more useful. The minimal substrate for renin is an octapeptide segment of the protein substrate: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have resulted in competitive inhibitors that are useful in vivo. Recently, remarkably active inhibitors have been synthesized by reducing the peptide bond...
Independent sampling vs interitem dependencies in whole report processing: contributions of processing architecture and variable attention

All current models of visual whole report processing assume perceptual independence among the displayed items in which the perceptual processing of individual items is not affected by other items in the display. However, models proposed by Townsend (1981, Acta Psychologica 47, 149-173), Shibuya and Bundesen (1988, Journal of Experimental Psychology: Human Perception and Performance 14, 591-600), and Bundesen (1990, Psychological Review 97, 523-547) contain postperceptual buffers that must predict negative dependencies. The perceptual-independence assumption forms what we term the modal model class. A recent example of a model that assumes perceptual independence is the Independent Sampling Model of Loftus, Busey, and Senders (1993, Perception and Psychophysics 54, 535-554). The fundamental independence assumption has only been directly tested once before, where tests revealed no dependencies except those produced by guessing. The present study tests the independence assumption using several different statistics and, contrary to most extant models of whole report, finds significant positive dependence. Poisson models do predict a positive dependence and we develop a succinctly parameterized version, the Weighted Path Poisson Model, which allows the finishing order to be a weighted probabilistic mechanism. However, it does not predict the data quite as well as a new model, the Variable Attention Model, which allows independence within trials (unlike the Poisson models). This model assumes that attention (or, potentially, other aspects such as signal quality) varies widely across trials, thus predicting an overall positive dependence. Intuitions for and against the competing models are discussed. In addition, we show, through mimicking formulae, that models which contain the proper qualitative type of dependence structure can be cast in either serial or parallel form. Copyright 2001 Academic Press.
Efficient Free-Space Coupling to LMA-PCF by Aberration Correction

A scheme is presented here to lower the free-space coupling loss to large mode area (LMA) photonic crystal fiber (PCF). A numerical study (using optics software for layout and optimization/beam propagation method) has been performed which demonstrates that the major source of coupling loss is due to the aberrations present in the optical system (using bulk optics) creating a source beam with appropriate size to couple into the LMA-35. We show that by carefully choosing a single or multiple aspheric lenses the wavefront aberrations can be minimized and the coupling loss into the LMA-PCF can be reduced to only 0.5 dB.
Novel patterns of interstitial lung disease

Abstract The 2002 ATS/ERS Idiopathic Interstitial Pneumonia Classification provided diagnostic criteria for seven well-known entities. Since then, new information has enriched our knowledge about these conditions and rare new entities have been proposed by different authors. Among these, pleuroparenchymal fibroelastosis has been recognized as a distinct clinicopathologic entity characterized by pleura and subpleural parenchymal fibrosis, predominantly composed of elastic fibres. Moreover, unusual histologic patterns, including acute fibrinous and organizing pneumonia and airway-centred interstitial fibrotic diseases, have also been described. The former is characterized by intra-alveolar fibrin deposition and associated organizing pneumonia in the absence classical hyaline membranes, while the latter includes a group of patterns remarkable for inflammation and fibrosis centred around the bronchioles. Whether these latter two patterns represent distinct entities or variants of existing idiopathic lung diseases requires further study. Since the practicing pathologists should to be aware these rare entities and patterns, this paper highlights the current knowledge about these conditions.