cssi/SciSciGPT-SciSciNet huggingface dataset:
Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 hACE2 transgenic mice

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the current coronavirus disease 2019 (COVID-19) pandemic. To date, it is estimated that over 113 million individuals have been infected with SARS-CoV-2 and over 2.5 million human deaths have been recorded worldwide. Currently, three vaccines have been approved by the Food and Drug Administration for emergency use only. However much of the pathogenesis observed during SARS-CoV-2 infection remains elusive. To gain insight into the contribution of individual accessory open reading frame (ORF) proteins in SARS-CoV-2 pathogenesis, we used our recently described reverse genetics system approach to successfully engineer recombinant (r)SARS-CoV-2, where we individually removed viral 3a, 6, 7a, 7b, and 8 ORF proteins, and characterized these recombinant viruses in vitro and in vivo. Our results indicate differences in plaque morphology, with ORF deficient ({Delta}ORF) viruses producing smaller plaques than those of the wild-type (rSARS-CoV-2/WT). However, growth kinetics of {Delta}ORF viruses were like those of rSARS-CoV-2/WT. Interestingly, infection of K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice with the {Delta}ORF rSARS-CoV-2 identified ORF3a and ORF6 as the major contributors of viral pathogenesis, while {Delta}ORF7a, {Delta}ORF7b and {Delta}ORF8 rSARS-CoV-2 induced comparable pathology to rSARS-CoV-2/WT. This study demonstrates the robustness of our reverse genetics system to generate rSARS-CoV-2 and the major role for ORF3a and ORF6 in viral pathogenesis, providing important information for the generation of attenuated forms of SARS-CoV-2 for their implementation as live-attenuated vaccines for the treatment of SARS-CoV-2 infection and associated COVID-19. IMPORTANCEDespite great efforts put forward worldwide to combat the current coronavirus disease 2019 (COVID-19) pandemic, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) continues to be a human health and socioeconomic threat. Insights into the pathogenesis of SARS-CoV-2 and contribution of viral proteins to disease outcome remains elusive. Our study aims to determine the contribution of SARS-CoV-2 accessory open reading frame (ORF) proteins in viral pathogenesis and disease outcome, and develop a synergistic platform combining our robust reverse genetics system to generate recombinant (r)SARS-CoV-2 with a validated rodent model of infection and disease. We demonstrated that SARS-CoV-2 ORF3a and ORF6 contribute to lung pathology and ultimately disease outcome in K18 hACE2 transgenic mice, while ORF7a, ORF7b, and ORF8 have little impact on disease outcome. Moreover, our combinatory platform serves as the foundation to generate attenuated forms of the virus to develop live-attenuated vaccines for the treatment of SARS-CoV-2.
Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging.

Importance Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease. Objective To investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition. Design, Setting, and Participants This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Aβ positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021. Main Outcomes and Measures The outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Aβ burden (as measured with a fluorine 18-labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables. Results The 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Aβ burden (β [SE] = -0.01 [0.00]; P = .005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Aβ was found between long and normal sleep duration groups (β [SE] = 0.00 [0.01]; P = .99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: β [SE] = 0.48 [0.17], P = .01; long vs normal sleep duration: β [SE] = 0.97 [0.31], P = .002), depressive symptoms (short vs normal sleep duration: β [SE] = 0.31 [0.05], P < .001; long vs normal sleep duration: β [SE] = 0.39 [0.09], P < .001), and daytime napping (short vs normal sleep duration: β [SE] = 2.66 [0.77], P = .001; long vs normal sleep duration: β [SE] = 3.62 [1.38], P = .01). Long sleep duration was associated with worse performance across multiple cognitive domains. Conclusions and Relevance In this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Aβ burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.
Integrating plant physiology and community ecology across scales through trait-based models to predict drought mortality

Forests are a critical carbon sink and widespread tree mortality resulting from climate-induced drought stress has the potential to alter forests from a carbon sink to a source, causing a positive feedback on climate change. Process-based vegetation models aim to represent the current understanding of the underlying mechanisms governing plant physiological and ecological responses to climate. Yet model accuracy varies across scales, and regional-scale model predictive skill is frequently poor when compared with observations of drought-driven mortality. I propose a framework that leverages differences in model predictive skill across spatial scales, mismatches between model predictions and observations, and differences in the mechanisms included and absent across models to advance the understanding of the physiological and ecological processes driving observed patterns drought-driven mortality.
Contamination-Defect-Fault (CDF) Simulation

As indicated in Chapter 2, the main shortcoming of the disk model was its inability to model faults starting from the actual failure mechanism, rather than from the spot defect level. It was also observed in the model validation experiment [1], [2], [3] and in the experiment described in [4] that most failures in ICs were caused by contamination which deposited on the IC during some processing step. To increase the fidelity of modeling, therefore, it is essential to begin all fault and yield model studies/simulations at the contamination level.
Indirect effects of bioinvasions in Yellowstone Lake: The response of river otters to declines in native cutthroat trout

Abstract Nonnative species threaten ecosystems throughout the world — including protected reserves. In Yellowstone National Park, river otters Lontra canadensis depend on native cutthroat trout as prey. However, nonnative lake trout and whirling disease have significantly reduced the abundance of these native fish in the park's largest body of water, Yellowstone Lake. We studied the demographic and behavioral responses of otters to declining cutthroat trout on Yellowstone Lake and its tributaries. From 2002-2008, we monitored otter activity at latrine (scent-marking) sites, collected scat for prey identification, and used individual genotypes from scat and hair samples to evaluate survival and abundance with capture–recapture methods. Otter activity at latrines decreased with declines in cutthroat trout, and the prevalence of these fish in otter scat declined from 73% to 53%. Cutthroat trout numbers were the best predictor of temporal variation in apparent survival, and mean annual survival for otters was low (0.72). The density of otters in our study area (1 otter per 13.4 km of shoreline) was also low, and evidence of a recent genetic bottleneck suggests that otter abundance might have declined prior to our study. River otters in and around Yellowstone Lake appear to be responding to reductions in cutthroat trout via changes in distribution, diet, and possibly survival and abundance. Our results provide a baseline estimate for monitoring the broader outcome of management efforts to conserve native cutthroat trout and emphasize the indirect ecosystem consequences of invasive species.
Stereospecificity of the Oxidation of Ethanol by Catalase

Abstract (R)-[1-3H1]ethanol and (S)-[1-3H1]ethanol were oxidized to acetaldehyde using bovine hepatic catalase. The acetaldehyde formed from the S but not the (R)-[1-3H1]ethanol contained tritium. Thus the stereospecificity of catalase for alcohol is the same as that of alcohol dehydrogenase.
The Mechanism of Action of Xanthine Oxidase

Abstract The changes in optical and EPR spectra observed during the anaerobic titration of xanthine oxidase with dithionite can be accounted for by simple oxidation-reduction equilibria involving Mo(VI) ↔ Mo(V) ↔ Mo(IV); FAD ↔ FADH. ↔ FADH2, and the 1-electron reduction of each of the two iron-sulfur centers. The equilibrium constants so obtained permit the calculation of the relative probabilities of the 36 possible states that occur on addition of a given quantity of reductant. pH jump experiments with this enzyme (Edmondson, D., Ballou, D., Van Heuvelen, A., Palmer, G., and Massey, V. (1973) J. Biol. Chem. 248, 6129–6135) show that internal electron transfer is much more rapid than turnover and we therefore assume that the distributions described by these equilibrium constants are maintained during catalysis. By adopting a model in which 3 moles of xanthine each donate a pair of electrons in a consecutive irreversible process, and using the equilibrium distributions described above, it is possible to calculate accurately the time course of reduction of both the flavin and iron-sulfur centers and to account for the increase in the rate of bleaching of deflavoenzyme observed experimentally. By invoking the existence of enzyme-xanthine complexes we can account for (a) the participation and time dependence of "very rapid" and "rapid" molybdenum and (b) the deuterium isotope effects observed during steady state and transient state kinetics (Edmondson et al.). The same equilibrium model accounts for the optical and EPR data obtained during the reaction of reduced enzyme with oxygen; the biphasic kinetics are readily explained by assuming that FADH2 is the species reacting rapidly with O2 in the fast phase. From these results we conclude that the iron-sulfur centers act as an electron reservoir functioning to maintain molybdenum as Mo(VI) (for efficient reduction) and flavin as FADH2 (for efficient oxidation).
IR studies of carbons—II: The vacuum pyrolysis of cellulose

Abstract The pyrolysis of cellulose in vacuum from 22 to 765°C was followed by IR photothermal beam deflection spectroscopy. Series of spectra recorded at various stages of pyrolysis showed that although the main decomposition occurred near 300°C, some decomposition occurred as low as 190°C with the formation or highly absorbing aromatic systems. Mixtures of predominantly aliphatic material predominate in the 300–400°C range but decline in extent to be replaced by mixtures of aromatic nature above 500°C. Further degassing causes discrete spectral features to decline and disappear near 700°C; a continuum absorption remains. Band assignments are discussed. In particular, the 1600 cm −1 band of spectra of carbons is shown by isotopic study not to be ascribed to carbonyls. but is thought to be a C = C mode made IR active by asymmetry caused by bound oxygen.
Concept generation using morphological and options matrices

The use of morphological analysis as a tool to aid concept generation is examined. Two principal limitations of the method are highlighted; (1) the lack of details generated for system concepts and (2) the explosion of combinatorial possibilities in the use of morphological matrices. The authors propose a method to support the generation of detailed conceptual ideas through functional combinations and use of options matrices, facilitating an intelligent exploration of the design space. In the options matrices, functions that are highly coupled are grouped together and idea generation is performed on the functional combinations based on identified innovation challenges. A subset of highly coupled functions are extracted from the morphological matrices and systematically integrated to form system level concepts. The resulting system concepts have greater design details compared to those generated through traditional morphological analysis techniques, allowing a designer to make informed decisions regarding their feasibility for the design purpose. An example of the proposed method is provided in the design of a seating chassis for automotive applications.
Survival of Airborne Pasteurella tularensis at Different Atmospheric Temperatures

The aerosol survival, recovery, and death rate of Pasteurella tularensis SCHU S5 disseminated in particle sizes of 1 to 5 μm were significantly affected by air temperature. The highest aerosol recovery of viable P. tularensis was observed within -7 and 3 C; the recovery decreased significantly below and above this temperature range. The death rate of airborne P. tularensis was not significantly influenced by an increase in temperature from -40 to 24 C. However, a progressive increase in atmospheric temperature from 24 to 35 C resulted in increased death rates; thus, a linear relationship appeared to be present between the temperature and death rates. At 49 C, the recoveries of viable airborne P. tularensis were significantly lower and the death rates were higher than at the other temperatures.
A Track Physics Retrospective

Many condensed matter dosimeters and detectors respond to the perspectives of track physics, a parametric model which relates their response to gamma rays to their response to heavy ions through the radial distribution of dose about a heavy ion’s path. Most dosimeters are treated as 1-hit detectors, a classification which includes emulsions, scintillators, TLDs, the Fricke dosimeter, alanine, and some biological substances: enzymes and Eschericia coli, among others. We have discovered many hit detectors. An extended model describes the killing, transformation, and mutation of biological cells after gamma and heavy ion irradiation. A detector is treated as a black box, in which the only relevant information is the nature of the incident radiation and the output response, although, at times, it is convenient to imagine some simple structure. Because the model is parametric it can be global, applying to many detectors. Once a set of numerical parameters is extracted from experimental findings, the equations of the model predict response to all radiation fields whose photon-particle energy spectrum is known. Finally, parameters of the model serve as a test of the validity of mechanistic theories, for these parameters summarize detector response to all ionizing radiations.
Application oriented networking (AON): adding intelligence to next-generation internet routers

Application Oriented Networking (AON) transforms the traditional network from pure packet-level routing to application-level processing by performing several customized computations at different nodes or routers. We study the operation of a Cisco AON system as a motivating example for our research. A multimedia transcoding application, which dynamically transforms video streams to different output patterns to satisfy the bit rate and bandwidth requirements of a variety of clients, is considered in our research. We build an active router cluster for real MPEG stream transcoding service in our laboratory; and design, implement and evaluate various scheduling algorithms for the online transcoding operation. When transcoding operation is performed by multiple processors in the cluster, it produces out-of-order departure of media units and high jitter. We quantitatively define the QoS requirements for each media stream, and design a two-step QoS aware scheduling scheme, which is tested and compared with other algorithms. Moving a packet from the network to the application level incurs large overhead due to PCI bottleneck and protocol stack in the operating system. Instead, we propose to move execution of the application to the network level by employing programmable network processors. We design and implement a web switch using Intel IXP 2400 network processor, and show its superiority compared to traditional Linux processing.
New trends in art conservation, the use of lasers to clean as well as generate an augmented reality representation of an iconic public monument in bronze: The Alma Mater

AbstractThe 3.66 m tall and over nine-ton outdoor bronze sculpture of Alma Mater, created by Lorado Taft in 1929, is an iconic symbol of the University of Illinois at Urbana-Champaign. The conservation treatment of the sculpture came with some unexpected surprises, such as the discovery of failing internal ferrous nuts and bolts which needed to be replaced. The treatment involved removing the sculpture from its granite base, dismantling major elements of the sculpture and replacing the ferrous bolts with silicon bronze bolts, laser cleaning the surface with 1064 nm Q-switch scanning lasers, application of patina, applying a protective microcrystalline wax coating, and reinstallation of the sculpture. Analysis was performed with microscopy, X-radiography, and scanning electron microscopy. The conservation treatment involved cutting edge laser technology to remove corrosion from the surface, while structured light three-dimensional (3D) scanning and digital modeling techniques were used to create a new form...
Liposome-dependent delivery of pteridine antifolates: a two-compartment growth inhibition assay for evaluating drug leakage and metabolism

Abstract We have developed a two-compartment growth inhibition assay that can provide information about leakage, metabolism and delivery of liposome-dependent drugs under cell culture conditions, and at drug concentrations that are relevant to drug delivery. Two cell lines are grown in separate compartments separated from each other by a 0.1 μm polycarbonate membrane. The membrane allows free drugs to diffuse rapidly from one compartment to another, and does not allow liposomes to diffuse through. Liposomes are added to the first compartment, which contains target cells. The extent of leakage caused by these cells is determined by the growth inhibition of non-target cells in the second compartment. We show that methotrexate and methotrexate-γ-aspartate leak rapidly and almost completely when encapsulated in phosphatidylglycerol/cholesterol (67:33) liposomes. In contrast, there is only 42% leakage when the drugs are encapsulated in distearoylphosphatidylglycerol/cholesterol (67:33) liposomes. We also demonstrate that the target cells (CV1-P) may partially degrade encapsulated methotrexate-γ-aspartate to methotrexate. Therefore, methotrexate-γ-aspartate may be a lysosomally cleaved pro-drug of methotrexate.
Two-, Three-, and Four-Atom Exchange Effects in bcc He 3

We have made mean-field calculations with a Hamiltonian obtained from two-, three-, and four-atom exchange in bcc solid $^{3}\mathrm{He}$. We are able to fit the high-temperature experiments as well as the phase diagram of Kummer et al. at low temperatures. We find two kinds of antiferromagnetic phases as suggested by Kummer's experiments.
Simulations and scaling of horizontal convection

In this paper we describe the results of various numerical simulations of sideways or horizontal convection. Specifically, a two-dimensional Boussinesq fluid is both heated and cooled from its upper surface, but the walls and the bottom of the tank are insulating and have no flux of heat through them. We perform experiments with a range of Rayleigh numbers up to 10 11 , obtained by systematically reducing the diffusivity. We also explore the effects of a nonlinear equation of state and of a mechanical force imposed on the top surface at a fixed Rayleigh number. We find that, when there is no mechanical forcing, both the energy dissipation and the strength of the circulation itself monotonically fall with decreasing diffusivity. At Rayleigh numbers greater than 10 10 the flow is unsteady; however, the eddying flow is still much weaker than the steady flow at smaller Rayleigh numbers. At high Rayleigh numbers, the stratification and the mean circulation are increasingly confined to a thin layer at the upper surface, with the layer thickness decreasing according to Ra −1/5 . There is no evidence that the flow ever enters a regime that is independent of Rayleigh number. Using a nonlinear equation of state makes little difference to the flow phenomenology at a moderate Rayleigh number. The addition of an imposed stress at the upper surface makes a significant difference in the flow. A strong, energy-dissipating circulation can be maintained even at Ra =10 9 , and the stratification extends more deeply into the fluid than in the unstressed case. Overall, our results are consistent with the notion that in the absence of mechanical forcing a fluid that is heated and cooled from above cannot maintain a deep stratification or a strong sustained flow at high Rayleigh numbers, even if the interior flow is unsteady. Keywords: horizontal convection; sideways convection; meridional overturning circulation; buoyant plume; gravity current; horizontal density gradient (Published: 14 May 2012) Citation: Tellus A 2012, 64 , 18377, http://dx.doi.org/10.3402/tellusa.v64i0.18377
Seasonal evolution of upper‐ocean horizontal structure and the remnant mixed layer

[1] We discuss the seasonal evolution of upper-ocean thermohaline structure at small horizontal scales. The upper 350 m of a 1000 km long section in the subtropical North Pacific was observed in winter, spring, and summer with 3–14 km horizontal resolution. Four vertical regions had distinct density and salinity structure: the mixed layer, remnant mixed layer, high-stratification layer, and permanent thermocline. The remnant mixed layer consists of water from the winter mixed layer left over after restratification. The remnant mixed layer was most similar to the mixed layer in winter and spring, and most similar to the high-stratification layer below in summer. The high-stratification layer had elevated stratification that varied seasonally. The permanent thermocline varied little seasonally and was horizontally and vertically uniform in comparison. In all seasons, density ratios showed that mixed-layer θ-S differences tended to compensate in density with the strongest tendency toward compensation in winter. Density ratios were temperature dominated in the remnant mixed layer consistent with salt-fingering. Salinity anomalies were largest at the surface and decayed with depth in all seasons. Spectra of isopycnal depth and θ-S anomalies along isopycnals are compared between the three seasons and four vertical layers. Isopycnal depth variance at 30–46 km wavelengths decreased from winter to spring to summer by a factor of 2–10 in stratified regions. By treating salinity anomalies as a tracer, the effective isopycnal diffusivity in the remnant mixed layer was estimated to be 1.4 m2 s−1 over 30–46 km wavelengths.
Effect of in vitro administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on DNA-binding activities of nuclear transcription factors in NIH-3T3 mouse fibroblasts.

TCDD is a very toxic environmental contaminant which is known to cause a variety of toxic symptoms in many species. Because of a myriad of biochemical changes TCDD is known to induce in many test animals, it has been difficult to pinpoint the causative event common to all those symptoms in different species. One of the research avenues we have been following is identification of the pattern of TCDD-induced changes in DNA binding characteristics of nuclear transcription factors (NTFs), each of which has the property to trigger a set of coordinated changes in many gene expressions. Since in our previous work we studied animals affected by TCDD in vivo using gel mobility shift assay approached with32P labeled oligonucleotide probes, [1] we examined in the current study the possibility whether we could establish an equivalent in vitro system in NIH-3T3 mouse fibroblast cells so as to be able to learn the similarities and the dissimilarities of TCDD-induced responses of NTFs between in vitro and in vivo. The r...
Carbon sequestration in soils: some cautions amidst optimism

A sink for atmospheric carbon (i.e., CO2) in soils may derive from the application of conservation tillage and the regrowth of native vegetation on abandoned agricultural land. Accumulations of soil organic matter on these lands could offset emissions of CO2 from fossil fuel combustion, in the context of the Kyoto protocol. The rate of accumulation of soil organic matter is often higher on fertilized fields, but this carries a carbon “cost” that is seldom assessed in the form of CO2 emissions during the production and application of inorganic fertilizer. Irrigation of semiarid lands may also produce a sink for carbon in plant biomass, but its contribution to a sink for carbon in soils must be discounted by CO2 that is emitted when energy is used to pump irrigation water and when CaCO3 precipitates in the soil profile. No net sink for carbon is likely to accompany the use of manure on agricultural lands.
Evaluation of the Effectiveness of DNA-Binding Drugs To Inhibit Transcription Using the c-fos Serum Response Element as a Target†

Previous work has demonstrated that sequence-selective DNA-binding drugs can inhibit transcription factors from binding to their target sites on gene promoters. In this study, the potency and effectiveness of DNA-binding drugs to inhibit transcription were assessed using the c-fos promoter's serum response element (SRE) as a target. The drugs chosen for analysis included the minor groove binding agents chromomycin A(3) and Hoechst 33342, which bind to G/C-rich and A/T-rich regions, respectively, and the intercalating agent nogalamycin, which binds G/C-rich sequences in the major groove. The transcription factors targeted, Elk-1 and serum response factor (SRF), form a ternary complex (TC) on the SRE that is necessary and sufficient for induction of c-fos by serum. The drugs' abilities to prevent TC formation on the SRE in vitro were nogalamycin > Hoechst 33342 > chromomycin. Their potencies in inhibiting cell-free transcription and endogenous c-fos expression in NIH3T3 cells, however, were chromomycin > nogalamycin > Hoechst 33342. The latter order of potency was also obtained for the drugs' cytotoxicity and inhibition of general transcription as measured by [(3)H]uridine incorporation. These systematic analyses provide insight into how drug and transcription factor binding characteristics are related to drugs' effectiveness in inhibiting gene expression.
Recent developments in Hadamard transform Raman spectrometry

ABSTRACT An introduction to Hadamard transform spectrometry in general and Hadamard transform Raman spectrometry inparticular is presented. Two generations of Hadamard encoding masks are described. Experimental details are providedfor the operation of a Hadamard transform Raman spectrometer utilizing the Hadamard encoding masks described.Near-infrared Hadamard transform Raman spectra are presented to illustrate spectral subtraction, the multiplexadvantage and a selective multiplex technique. With the second generation of Hadamard encoding masks available, theHadamard transform Raman technique is now ready to begin its testing in the analytical world. 1. INTRODUCTION Two well established methods for performing optical spectrometry are dispersive spectrometry (DS) and Fouriertransform spectrometry (FF5). A third alternative is Hadamard transform spectrometry (HTS), which is a marriageof dispersive and multiplexing techniques and possesses some of the desirable features of both DS and FTS1.
Adenosine and its receptors Multiple modulatory functions and potential therapeutic targets for neurologic disease

5′NT= : 5′-nucleotidase; AC= : adenylate cyclase; ACh= : acetylcholine; ADK= : adenosine kinase; AMP= : adenosine monophosphate; ATP= : adenosine triphosphate; CCL= : chemokine ligand; CGRP= : calcitonin gene related peptide; COX-2= : cyclooxygenase-2; EctoN= : ectonucleotidases; ENT= : equilibrative nucleoside transporters; ERK1,2= : extracellular signal regulated kinase 1,2; G= : guanine nucleotide binding protein; GABA= : γ-aminobutyric acid; GIRK= : G-protein gated inward rectifying potassium channels; IL= : interleukin; NGF= : nerve growth factor; NMDA= : N -methyl-d-aspartate; NO= : nitric oxide; PD= : Parkinson disease; PLA2= : phospholipase A2; PLC= : phospholipase C; PLD= : phospholipase D; SNc= : substantia nigra pars compacta; VLPO= : ventrolateral preoptic area. Adenosine is a ubiquitous chemical messenger that modulates cellular activity in both the CNS and peripheral organs.1–5 Adenosine levels in the brain extracellular space increase dramatically during metabolically stressful conditions, such as ischemia, seizures, or trauma. Adenosine, acting via different receptors, modulates excitability in the CNS2–4 and has a role in mechanisms of seizure susceptibility,5,6 sleep induction,7 basal ganglia function,8 pain perception,9 cerebral blood flow,10 and respiration.11 Adenosine receptors are inhibited by caffeine and other methylxanthines and provide a potential target for treatment of cerebral ischemia,12 seizures,13 pain,9 Parkinson disease (PD),8,14 and Huntington disease.15 There are several excellent reviews on recent experimental findings and insights into adenosine signaling in the CNS,1–6,8 and on adenosine as a potential therapeutic target in neurologic disorders.5–7,12–15 There is tight and dynamic regulation of adenosine levels in the nervous system.1–5 All cell types contribute to the accumulation of extracellular adenosine (figure). Extracellular concentrations of adenosine are determined by the interplay between the activity of intracellular and extracellular enzymes involved in adenosine metabolism and the transport of adenosine across the cell membrane. Metabolic stress triggers the dephosphorylation of adenosine triphosphate (ATP) and formation of adenosine monophosphate (AMP), which is converted to adenosine by 5′-nucleotidase. Adenosine is then released from cells by facilitated diffusion via nucleoside transporters, the best characterized being the equilibrative nucleoside transporters (ENT).16 Adenosine may also be produced by the extracellular metabolism of ATP via a cascade of ectonucleases.2–4 The primary route of adenosine metabolism is adenosine kinase (ADK), which is expressed primarily in astrocytes (figure). The concentration of extracellular adenosine increases dramatically in the setting of metabolic stress such as hypoxia, ischemia, trauma, or seizures.2–5,12 Transport from the astrocyte is the primary source of …
Five generations of selective breeding for ultrasonic vocalization (USV) responses in N:NIH strain rats.

This article reports on early results from an ongoing selective breeding study in which rats were selected for different rates of ultrasonic vocalization (USV) in response to isolation. Using the N:NIH strain, all litters were screened at 10 (±1) days of age in a 2-min isolation test, and those males and females with the highest (or lowest) rates in each litter were selected for later breeding with like breeders from unrelated litters. A Random line (unselected control) was also bred. In the first selected generation (S1), the Low line diverged from Random line controls, and has maintained significantly lower rates over all generations since. In the S3 generation, the High line diverged significantly from Random line controls, and has shown significantly higher USV rates in each succeeding generation. No line differences were found in other behaviors measured in isolation. Data from a small sample of S5 pups tested at postnatal Days 3, 10, 14, and 18 days showed that individual pups' rates of USV from Day 10 predicted those at Day 14, consistent with findings from an unselected generation. Ambient temperature, modulated by body weight, controlled USV at Day 3, whereas at Days 10 and 14 line accounted for most of the variance in USV. This is the first instance of laboratory selection occurring on the basis of an infantile trait. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 31: 255–265, 1997
Versatile Cloning Vectors Constructed with Genes Indigenous to a Glutamic Acid-Producer, Brevibacterium lactofermentum

Versatile plasmid vectors useful for gene cloning in Brevibacterium lactofermentum, a glutamic acid-producing bacterium, have been constructed. The trimethoprim (Tp)-resistant dihydrofolate reductase gene derived from chromosomal DNA of the Tp-resistant mutant of B. lactofermentum was introduced into pAM330, a cryptic plasmid in B. lactofermentum. The constructed cloning vector pAJ228 (7.6kb) exists in 10 to 20 copies in cells of B. lactofermentum and donated Tp-resistance, which is a useful selective marker of transformants. pAJ228 was further improved to a versatile plasmid vector pAJ224 having some profitable characteristics such as smaller size (3.7 kb), higher copy number (60 ~ 80 copies), and additional useful cloning sites (Bam HI, Pst I and Sal I) equipped with two different promoters arranged at both orientations for the expression of passenger DNA without promoter. These plasmids were stably retained in B. lactofermentum even in the absence of Tp over many generations. Thus, they have been found...
Interaction of MMP-3 and sex hormones in the control of energy balance.

Matrix metalloproteinase-3 (MMP-3) is an endopeptidase important for regulating cell-to-cell interactions and remodeling the extracellular matrix, including the development of adipose tissue. We hypothesized that MMP-3 is also active in the central nervous system, specifically acting to cleave synedecan-3 and thereby regulate AgRP signaling. Because previous studies have shown sex difference in syndecan-3-mediated regulation of food intake, we also tested the hypothesis that CNS MMP-3 might mediate the sex-differences underlying syndecan-3 regulation of energy balance. We first observed that MMP-3 deficient mice are hyperphagic and gain significantly more weight on high-fat diet compared to wild-type controls. Second, MMP-3 null mice exhibit a delayed and prolonged orexigenic response to ICV NPY and AgRP, compared to wild-type controls. These findings are consistent with our hypothesis that MMP-3 regulates cleavage of cell-surface syndecan-3. To test the role of sex hormones in mice lacking MMP-3, we assessed food intake following ovariectomy (OVX). WT-ovariectomized mice exhibit hyperphagia and increased food intake and body weight compared to sham-controls. A separate cohort of MMP-3 null or WT female mice was randomized to receive OVX or sham surgery, after which we recorded daily food intake and body weights. While MMP-3 null and WT OVX mice exhibited similar amounts of hyperphagia, MMP-3 KO mice gained more weight than WT controls. Collectively, these data suggest an important role for MMP-3 in the regulation of food intake and the mediation of sex-hormones on energy balance, consistent with a potential role to regulate cleavage of hypothalamic syndecans.
Enhanced Backscattering Of Optical Waves Due To Densely Distributed Scatterers

Recently, an interesting phenomenon has been reported as a result of a series of optical backscattering experiments conducted using collimated light sources (lasers). A locally high intensity maximum has been observed in the range of π-e<θ<π + e where e is of the order of milliradians and 0 = πit is the backscattering direction. Albeit similar phenomena found in backscattering from various random media, e.g., Anderson localization, light scattering from random rough surfaces, this is the first observation of enhanced backscattering from suspensions.
RESONANT AND NON-RESONANT THIRD-ORDER OPTICAL PROPERTIES OF METALLOPHTHALOCYANINES

Abstract Non-resonant third-harmonic generation and resonant saturable absorption measurements of liquid solutions of silicon naphthalocyanine are discussed. The results provide further insight into the non-linear optical properties previously reported for random glassy polymers containing silicon naphthalocyanine.
Identification and potential biological effects of the major components in the seawater extract of a bunker fuel.

The composition of the seawater extract of a bunker fuel similar to that spilled in San Francisco Bay in 1971 is reported. Previous methodology for obtaining the seawater-soluble fraction of bunker fuels as well as the possible significance of the dissolved oil to a local crab species are discussed. (JTE)
Carotene as a molecular wire: Conducting atomic force microscopy

A conducting atomic force microscope was used to measure the electrical properties of carotenoid molecules attached to a gold electrode. The thiolated carotene molecules were embedded in insulating n-alkanethiol self-assembled monolayers. At a contact force of a few nanoNewtons, a carotenoid molecule behaves ohmically with a resistance of approximately 4.2 ± 0.7 GΩ, over a million times more conductive than an alkane chain of similar length. Modes of electron transport are discussed.
Polarization and Albedo

SCHWERDTFEGER1 has recently directed attention to the mechanism underlying the dependence of short-wave or optical albedo on solar elevation and the presence or absence of cloud cover. He cites as one of the major causes of this dependence the polarization of incident radiation (solar) on reflexion at terrestrial surfaces. The few comments made here are intended to bring out the rather involved interrelation between polarization and albedo, which plays a very prominent part in the solution of radiant -energy transfer problems in the Earth's atmosphere.
Directional atherectomy of coronary and saphenous vein graft ostial stenoses

Directional coronary atherectomy (DCA) has been proposed as an alternative to balloon dilatation for treating coronary ostial stenoses, but the long-term efficacy of this procedure has not been well studied. To determine the procedural success and long-term efficacy of DCA for ostial stenoses, clinical data from 1 large registry database and from 2 single centers were retrospectively reviewed. Patients included in the study underwent DCA of aortocoronary (left main or right coronary artery), non-aortocoronary (left anterior descending or circumflex), or vein graft ostial stenoses. In 158 patients undergoing DCA of 160 lesions (30 left main or right coronary, 73 left anterior descending or circumflex, and 57 vein graft stenoses), overall procedural success, defined as 50% diameter stenosis at the site of DCA, was 48% (de novo lesions 40% and restenotic lesions 61%). Restenosis rates for de novo and restenotic lesions were: aortocoronary (33%/50%), native coronary (38%/35%), and vein graft (47%/93%), respectively. We conclude that DCA of ostial stenoses is an effective revascularization strategy associated with a high procedural success rate and a low incidence of major complications.(ABSTRACT TRUNCATED AT 250 WORDS)
HIV testing among U.S. women during prenatal care: findings from the 2002 National Survey of Family Growth.

Objectives: To measure progress toward the US Public Health Service recommended goal that HIV screening be part of the routine battery of prenatal tests for all pregnant women, using data from a nationally-representative reproductive health survey. Methods: Data from the 2002 National Survey of Family Growth (NSFG) measure self-reported prenatal HIV testing for all women who had a completed pregnancy in the 12 months before interview. We estimated the percentage with a prenatal test for categories defined by major socio-economic groups, HIV risk, knowledge of HIV treatment, and access to health care. Results: Sixty-nine percent of 748 recently pregnant women reported receiving a prenatal HIV test. The percentage tested was significantly higher for women with incomes below 300% of the poverty level (76%) and women who reported some degree of HIV risk (82%), suggesting that prenatal care providers offer and encourage testing based on perceived risk, even though universal HIV screening is recommended. Testing was also higher among women with knowledge of interventions to prevent perinatal HIV transmission (74%), suggesting that more public information on these treatments might be helpful. Conclusions: A national estimate indicates that nearly one in 3 recently pregnant women reported they were not tested for HIV during prenatal care. Studies showing that prenatal testing for other infectious diseases can approach 100% suggest that a similar level of testing is attainable for perinatal HIV screening, particularly if it is incorporated into the routine package of prenatal tests and procedures offered to all pregnant women.
Self-directed behavior change in children: Is it self-directed?

The present paper examines whether children can learn to effectively manage their own behavior. Focusing on self-reinforcement strategies, studies in which children were reported to be successful and unsuccessful in their attempts to alter their own responding are examined. Special attention is given to the role played by external treatment, mediator-imposed contingencies on the effectiveness of self-management programs. Conclusions regarding the necessary conditions for successful self-control in children are presented.
Decarboxylation of p-Aminosalicylic Acid in the Solid State

The decarboxylation reaction of p -aminosalicylic acid in the solid state has been demonstrated to be dependent on temperature, moisture, pressure, and particle size. Typical curves are given which indicate environmental influence on the degradation reaction. A possible gross mechanism is offered which analyzes the sigmoidal-type per cent decomposition versus time curve obtained with dry, atmospheric, thermal degradation of p -aminosalicylic acid. A set of equations which describes the kinetic data is given. Using these equations, the various rate constants have been determined.
Transition probabilities and branching ratios for electric-dipole transitions between arbitrary levels of hydrogen-like atoms

Branching ratios in hydrogen-like atoms due to electric-dipole transitions are tabulated for the initial principal and angular momentum quantum number n, lambda, and final principal and angular momentum quantum numbers n, lambda. In table 1, transition probabilities are given for transitions n, lambda, yields n, where sums have been made with respect to lambda. In this table, 2 or = n' or = 10, o or = lambda' or = n'-1, and 1 or = n or = n'-1. In addition, averages with respect to lambda' and sums with respect to n, and lifetimes are given. In table 2, branching ratios are given for transitions n' lambda' yields ni, where sums have been made with respect to lambda. In these tables, 2 or = n' or = 10, 0 or = lambda', n'-1, and 1 or = n or = n'-1. Averages with respect to lambda' are also given. In table 3, branching ratios are given for transitions n' lambda' yields in lambda, where 1 or = n or = 5, 0 or = lambda or = n-1, n n' or = 15, and 0 or = lambda' or = n(s), where n(s), is the smaller of the two numbers n'-1 and 6. Averages with respect to lambda' are given.
Deviance as a Situated Phenomenon: Variations in the Social Interpretation of Marijuana and Alcohol Use

Recent sociological theories of deviance argue that social interpretations of deviant acts depend heavily on the situational circumstances surrounding the act. Questionnaires administered to 925 students presented descriptions of marijuana use or alcohol use in eight different situations. These descriptions were varied systematically according to (1) the social goals of the drug-using situation, (2) the situational stability of use, and (3) the user's motivational orientation toward the drug-using situation. Half of the respondents rated the acceptability of marijuana use in these situations, while the other half rated alcohol use. Variations in the situational context of both of these acts produced marked changes in respondents' interpretations of them as deviant. However, differences between ratings of marijuana use and alcohol use also indicate that interpretations of deviance may depend on generalized social meanings of the act per se , as well as on situational circumstances.
Simultaneous Flavor Transformation of Neutrinos and Antineutrinos with Dominant Potentials from Neutrino-Neutrino Forward Scattering

Author(s): Fuller, GM; Qian, YZ | Abstract: In astrophysical environments with intense neutrino fluxes, neutrino-neutrino forward scattering contributes both diagonal and off-diagonal potentials to the flavor-basis Hamiltonian that governs neutrino flavor evolution. We examine a special case where adiabatic flavor evolution can produce an off-diagonal potential from neutrino-neutrino forward scattering that dominates over both the corresponding diagonal term and the potential from neutrino-matter forward scattering. In this case, we find a solution that, unlike the ordinary Mikeyhev-Smirnov-Wolfenstein scenario, has both neutrinos and antineutrinos maximally mixed in medium over appreciable ranges of neutrino and antineutrino energy. Employing the measured solar and atmospheric neutrino mass-squared differences, we identify the conditions on neutrino fluxes that are required for this solution to exist deep in the supernova environment, where it could affect the neutrino signal, heavy-element nucleosynthesis, and even the revival of the supernova shock. We speculate on how this solution might or might not be attained in realistic supernova evolution. Though this solution is ephemeral in time and/or space in supernovae, it may signal the onset of subsequent appreciable flavor mixing for both neutrinos and antineutrinos. © 2006 The American Physical Society.
Standardizing vitamin D assays: the way forward

For a number of years it has been widely assumed that measurement of serum 25-hydroxyvitamin D [25(OH)D] concentration is the best approach to assessing an individual's vitamin D status. However, it has also been recognized that there is substantial within-assay variation in 25(OH)D measurement and even greater between-assay variability. Such assay variation clearly confounds attempts to define what constitutes the diagnosis of hypovitaminosis D. Importantly, assay variability makes pooling of 25(OH)D results from different studies in systematic reviews for the specific purpose of determining dose-response and/or clinical cut points at best problematic. Therefore, to develop and implement evidence-based clinical guidelines, it is essential that 25(OH)D measurement be standardized in both clinical and research laboratories. In this Perspective we outline a way forward toward achieving this goal-the Vitamin D Standardization Program (VDSP).