cssi/SciSciGPT-SciSciNet huggingface dataset:
Dietary Cholesterol Regulates Hepatic 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Expression in Rats Primarily at the Level of Translation

Abstract The level of gene expression at which dietary cholesterol exerts feedback regulation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated using young male Sprague–Dawley rats. Previous studies suggested that this regulation might be exerted posttranscriptionally. Thus, possible regulation at the levels of catalytic efficiency, protein turnover, and translation was investigated. To examine possible regulation at the level of catalytic efficiency, rats were placed on chow diets supplemented with 2% cholesterol and the rates of decline in hepatic HMG-CoA reductase activity and immunoreactive protein levels were determined. Both decreased slowly over a 72-h period. The catalytic efficiency did not change. These observations are inconsistent with phosphorylation–dephosphorylation or thiol–disulfide interchange as possible mechanisms. The possibility that dietary cholesterol might act by increasing the rate of turnover of HMG-CoA reductase protein was examined by determining the half-life of the enzyme in livers from rats consuming chow or chow supplemented with 2% cholesterol. The half-life of HMG-CoA reductase protein was not decreased in the animals receiving cholesterol, thus ruling out this possibility. Regulation at the level of translation was investigated by measuring the rate of HMG-CoA reductase protein synthesis in liver slices using [ 35 S]methionine and [ 35 S]cysteine. It was found that the rate of synthesis was reduced by over 80% in liver slices from rats fed a diet supplemented with 2% cholesterol. Similar results were obtained with liver slices from rats given mevalonolactone, which supplies both sterol and nonsterol endproducts. These results indicate that cholesterol regulates hepatic HMG-CoA reductase gene expression in rats primarily at the level of translation.
Evolutionary and functional genomics of the Archaea

In the past two years, archaeal genomics has achieved several breakthroughs. On the evolutionary front the most exciting development was the sequencing and analysis of the genome of Nanoarchaeum equitans, a tiny parasitic organism that has only ∼540 genes. The genome of Nanoarchaeum shows signs of extreme rearrangement including the virtual absence of conserved operons and the presence of several split genes. Nanoarchaeum is distantly related to other archaea, and it has been proposed to represent a deep archaeal branch that is distinct from Euryarchaeota and Crenarchaeota. This would imply that many features of its gene repertoire and genome organization might be ancestral. However, additional genome analysis has provided a more conservative suggestion — that Nanoarchaeum is a highly derived euryarchaeon. Also there have been substantial developments in functional genomics, including the discovery of the elusive aminoacyl-tRNA synthetase that is involved in both the biosynthesis of cysteine and its incorporation into proteins in methanogens, and the first experimental validation of the predicted archaeal exosome.
IDENTIFICATION OF NONLINEAR FRACTURE PROPERTIES FROM SIZE EFFECT TESTS AND STRUCTURAL ANALYSIS BASED ON GEOMETRY-DEPENDENT R-CURVES

Abstract The size effect method, previously developed for concrete and mortar, is demonstrated for rock. Geometrically similar fracture specimens of limestone are tested and the measured maximum load values are used to obtain fracture energy, fracture toughness and effective size of the fracture process zone. Further, it is shown how to determine, from these results, other nonlinear fracture parameters including the critical effective crack-tip opening displacement. R-curves, dependent on specimen geometry, are calculated and used to predict load-deflection curves, which are found to agree very well with measurements. A modification of the R-curves for post-peak response is proposed.
Analytic Loop Shaping Methods in Quantitative Feedback Theory

Quantitative Feedback Theory (QFT), a robust control design method introduced by Horowitz, has been shown to be useful in many cases of multi-input, multi-output (MIMO) parametrically uncertain systems. Prominent is the capability for direct design to closed-loop frequency response specifications. In this paper, the theory and development of optimization-based algorithms for design of minimum-gain controllers is presented, including an illustrative example
Effect of fertilization and harvest frequency on yield and quality of tall fescue and smooth bromegrass

Abstract Fertilization and harvest frequency affect yield and quality of forages. The purposes of this experiment were to determine (i) the effects of fertilization and frequent harvesting on yield and quality of tall fescue (Festuca arundinacea Schreb.) and smooth bromegrass (Bromus inermis Leyss.) and (ii) the efficiency of N in animal waste as compared with inorganic N fertilizer for forage production of these cool season grasses. ‘Fawn’ tall fescue and ‘Southland’ smooth bromegrass were grown in the greenhouse on Pullman clay loam topsoil (fine, mixed thermic Torrertic Paleustoll) under eleven fertilizer treatments and two harvest regimes. Nitrogen fertilizer increased yields, N and K concentrations and K/(Ca + Mg) ratios and decreased P, Ca, and Mg concentrations. Phosphorus and K fertilizers did not affect yields but applied P increased P and tended to decrease N and Ca concentrations. Applied K tended to increase Ca concentrations. Recovery of N from feedlot manure ranged from 0.8 to 14%, whereas, ...
Transesophageal echocardiography in the pregnant patient.

conclusion of TPA treatment, aspirin and heparin therapy were started to prevent further thrombosis. Several days later, her regimen of daily doses of warfarin was resumed, and the heparin therapy was discontinued. The patient tolerated thrombolysis well, with no obvious side effects, and was transferred out of the intensive care unit on day 6. She was discharged on day 16, with no detectable signs of valvular dysfunction. Follow-up examinations 3 and 6 months later revealed no further signs of valvular thrombosis. We chose a lower dose of TPA, approximately l/10 to l/20 the usual adult acute dose, in an attempt to decrease the risk of bleeding and embolization of the thrombi through the patient’s ventricular septal defect. We felt that a continuous infusion would provide the optimum activation of the thrombolyt,ic pathway because it, would allow slow dissolution of the clots’ exposed surfaces and thus would help prevent embolization of a larger piece. The combination of continuous infusion and a half-life of 3 to 10 minutes would, we believed, allow us to terminate the process rapidly if bleeding or cerebral embolism occurred or if the therapy failed and an urgent operation was necessary. The prolonged half-life of streptokinase and urokinase make them less attractive for this reason. There are potentially serious risks associated with thrombolytic agents. There is an 0.4”,’ to 1“;) incidence of intracranial bleeding and as high as a 5”~’ incidence of other organ bleeding. Also, TPA is 10 to 20 times more expensive than the other thrombolyt,ic agents. Despite the potential problems of TPA, its use should be considered for the treatment of life-threatening thrombosis when other agents have failed or have caused allergic reactions, or when an urgent operation will be necessary should medical management fail. Medical management with TPA should only be attempted, however, in institutions where alternative medical and surgical therapies are available in case of emergency.
Characterization of Sinterable Oxide Powders: I, BeO

The discovery of readily sinterable BeO powder facilitated the production of dense, high-strength BeO ceramics and created interest in the properties and preparation of sinterable BeO. BeO powders prepared by the thermal decomposition of Be(OH)/sub 2/ were studied in an effort to relate sinterability with other more basic characteristics of the oxide powder. Different BeO powders made from analyzed :hydroxides showed a wide range of sinterability. The teraperatures required for sintering the powder compacts to theoretical density ranged from 2300 deg to above 3200 deg F. Lattice paranneters, thermal decomposition, surface areas, and refractive indices were determined on these powders after calcination in air at 750 deg , 1470 deg , 1830 deg , and 2190 deg F. Although unexpected variations in these properties were observed, no simple relation with sinterability was found. Occluded and surface impurities appeared to have a critical effect on sintering behavior. (auth)
The Religious Geography of Religious Expression: Local Governments, Courts, and the First Amendment

Scholars of religion and politics have long noted the impact and influence of religion on local government policymaking. More so than state or federal politics, local politics often engage the intersection of law, politics, and religion in fundamental ways through basic functions such as public schooling, zoning, government building permits, or simple requests to use government property for meetings, rallies, or orner expressive activities. Indeed, as Richard K Morgan noted, church-state conflicts are most acute at the local level: "here are waged those intimate little community wars over religious practices in particular schools; here are the disputes over religious services and artifacts in public parks."1 As Morgan pointed out, local disputes are often triggered by demographic changes in which religious minorities come into religiously nomogenous communities.
Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been in continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.
The evolution of surface texture in automotive coatings

The curing behavior and texture development of automotive clearcoats was studied by noncontacting profilometry and dynamic viscosity measurements during solvent evaporation and thermal curing. The changing surface texture was shown to be a strong function of temperature and solvent content. Leveling occurred during the initial heating of the clearcoats, while smaller wavelength roughness was observed to appear during cooling after curing. The dynamic viscosity was shown to be a strong function of catalyst loading. Numerical simulations were conducted to calculate the apparent viscosity during the leveling process. Calculated viscosity profiles matched theoretical predictions for the behavior of these clearcoats.
Gadolinium and nephrogenic systemic fibrosis: the evidence of things not seen.

Much has been learned, but "nephrogenic" is misleading: this fibrosing disorder is not caused by the kidneys.
Effect of pH and some reagents on the sucrose-independent non-specific sorption of the oral bacterium Streptococcus mutans to glass

Abstract The effect of hydrogen-ion concentration on the sucrose-independent attachment of various strains of Streptococcus mutans to glass was studied using overlapping phosphate and acetate buffers through a pH range of 4.0 to 8.0 at a constant molarity. Some strains of the same serotype showed nearly identical patterns of adhesion with respect to pH, and all strains of serotype a , d and g behaved similarly, showing increased sorption at low pH only. Studies with serotype g cells demonstrated that increased sorption at low pH was not a result of changes in the ionic strength of the buffer. Metal chloride salts increased adhesion at some concentrations. Cyclohexyl isocyanide, EDTA, Tween 80, and saccharides had varied effects on several strains of serotype b and g cells at pH 4.6. Pre-treatment of serotype b and g cells with proteolytic enzymes or 2-mercaptoethanol usually resulted in reduced adhesion at pH 4.6; pre-treatment with dextranase had no effect or increased adhesion. The results suggest that the pH-sensitive adhesin is a protein, and that low pH increases adhesion either by increasing hydrogen bonding between the adhesin and the substrate or by altering the conformation of the adhesin. Contraction of the diffuse double layer is also important in explaining how adhesion is increased at low pH.
Asthma During Pregnancy

Ineffectively controlled asthma during gestation must be avoided to protect the fetus from untoward effects of matenal hypoxemia and hypocarbia. With current therapy and a compliant gravida, the outcome of pregnancy can be similar to the general population. Physician confidence in antiasthma medications is important. Respiratory distress has pregnancy implications by 20-24 weeks gestation and it is important to have fetal assessment documented when the gravida is treated in the emergency room or during hospitalization for status asthmaticus.
Architecture: an emerging core competence for IT professionals

With the emergence of globalization, IT organizations have begun to shift from service organizations to solutions organizations. IT professionals must now mitigate complexity by understanding both the enterprise and IT solutions. An IT professional has to balance the business needs of the enterprise with the possibilities that technology offers.At the same time, technology itself has enabled hard IT skills jobs to become commodities that can be outsourced around the world and performed at a fraction of the cost. This shift has changed the core competencies needed by IT professionals in the developed countries. IT professionals must now have the competencies of leadership/followership, communication and collaboration, problem solving and critical thinking, creativity and innovation, global business expertise, systems thinking, and self management, in addition to the technology expertise and project management skills we expected in the past. Arising from all these competencies, architecture has emerged as an overarching core competence for IT professionals.The purpose of this paper is to provide an overview of how IT competencies have changed in the last decade and to introduce architecture as a critical component of an IT education curriculum. We will discuss the implications this might have for the SIGITE model curriculum framework.
CELL WALL CONSTITUENTS OF APHANOTHECE HALOPHYTICA (CYANOPHYTA)1

Some aspects of the cell wall and extracellular polysaccharide (ECPS) of the obligate halophile Aphanothece halophytica Fremy (Chroococcales) have been investigated. Extracellular polysaccharide concentration was found to remain constant on a per cell basis in medium containing from 1–3 M NaCl. The rate of ECPS production remained constant during mid-log growth phase and increased substantially as the culture reached stationary phase. The lipopolysaccharide of this organism was found to possess a low and unusual fatty acid content when compared to other chroococcalean forms. The cell wall appears to contain a typical gram-negative peptidoglycan. The covalently attached protein resembles the envelope protein of extremely halophilic bacteria in its possession of a similar molar percentage of amino acids with lipophilic R-groups and a high acidic amino acid fraction. The ECPS and cell wall fractions of A. halophytica were found to chemically more closely resemble those from other non-halophilic, chroococcalean bluegreen algae than those from the obligately halophilic bacteria.
Primary and long term epithelial cell cultures from human fetal normal colonic mucosa

Primary and passaged cultures of normal colon epithelial cells, derived from human fetuses (13 to 17 wk of conceptual age) have been established. These cultures have been passaged 16 times thus far. The cultures have been initiated and maintained in medium consisting of 50% Dulbecco's minimum essential medium and 50% Ham's F12 medium and supplemented with antibiotics (penicillin, 100 U/ml; streptomycin, 100 micrograms/ml); ascorbic acid, 40 micrograms/ml; L-isoleucine, 50 micrograms/ml; epidermal growth factor, 20 ng/ml; insulin, 5 micrograms/ml; cholera toxin, 5 ng/ml; transferrin, 1 microgram/ml; fetal bovine serum (10%); and HEPES, 25 mM final concentration, and incubated at 37 degrees C in humidified gas containing 5% CO2: 95% air. The cellular and subcellular characteristics of primary and passaged cultures were defined using light microscopy and scanning and transmission electron microscopy. The cells exhibited microvilli on cell surfaces and showed junctional complexes and interdigitations between cells. Indented nuclei with dense chromatin and marginated heterochromatin, numerous mitochondria, rough endoplasmic reticulum, polysomes, and extensive Golgi zones were conspicuous. Also, periodic acid Schiff's reagent-positive staining of the cells suggests the active synthesis of complex mucopolysaccharides in the cytoplasm.
Endothelium removal does not affect potentiation by neuropeptide Y in rabbit ear artery

Influence of endothelial cells on the effect of neuropeptide Y (NPY) was investigated. NPY (30 nM) doubled the vasoconstriction elicited by transmural nerve stimulation (8 pulses at 8 Hz) in the perfused rabbit ear artery with or without endothelium. Conditions that increase the biophase concentration of norepinephrine, longer stimulation trains or application of yohimbine, decreased the potentiation by NPY, although in the presence of cocaine potentiation by NPY was unchanged. However, no significant differences between control and endothelium-removed arteries were revealed. Thus modulation of adrenergic neurotransmission by NPY does not depend on endothelium-derived vasoactive substances.
Revenue management for low-cost providers

Low-cost providers have emerged as important players in many service industries, the most predominant being low-cost, or the so-called discount airlines. This paper presents models and results leading toward understanding the revenue management outlook for a discount pricing firm. A framework and model is formulated specifically for the airline industry, but is generalizable to low-cost providers in similar revenue management settings. We formulate an optimal pricing control model for a firm that must underprice to capture a segment of exogenous demand. Two specific model formulations are considered: a continuous deterministic version, and a discrete stochastic version. Structural results are derived for the deterministic case, providing insight into the general form of optimal underpricing policies. The stochastic results support the structural insight from the deterministic solution, and illuminate the effect of randomness on the underpricing policies.
Unconventional Origin of Metal Ion Rescue in the Hammerhead Ribozyme Reaction: Mn2+-Assisted Redox Conversion of 2‘-Mercaptocytidine to Cytidine

A specific oxygen atom in RNA is identified as a ligand for a metal ion when sulfur substitution of that atom shifts the metal ion specificity of the RNA-mediated process to a more thiophilic metal...
Sirtuins in neurodegenerative diseases: an update on potential mechanisms.

Silent information regulator 2 proteins (sirtuins or SIRTs) are a group of deacetylases (or deacylases) whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Compelling evidence supports that sirtuins play major roles in many aspects of physiology, especially in pathways related to aging–the predominant and unifying risk factor for neurodegenerative diseases. The focus of this review is to examine the molecular mechanisms underlying the protective effects of sirtuins in neurodegenerative diseases, focusing on protein homeostasis, neural plasticity, mitochondrial function, and sustained chronic inflammation. We will also examine the potential and challenges of targeting sirtuin pathways to block these pathogenic pathways.
The practice of clinical genetics: A survey of practitioners

Purpose: A survey of clinical geneticists was undertaken to learn more about current practice. Methods: An attempt was made to survey all geneticists practicing in the United States to elicit information on a variety of issues. Results: A total of 69% of geneticists responded. Most practice at a medical school, most receive a portion of their income from salary, and many receive personal financial support from research grants. Conclusion: The specialty of medical genetics is primarily housed in tertiary care settings. Although a substantial amount of time is required to see patients, reimbursement for these services does not cover the costs to maintain such practices.
Pervanadate Mimics IFNγ-Mediated Induction of ICAM-1 Expression via Activation of STAT Proteins

Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the epidermis plays a critical role in the regulation of cutaneous inflammation, immunologic reactions, and tissue repair. Transcriptional upregulation of ICAM-1 in response to interferon- γ (IFN γ ) occurs through a palindromic response element pI γ RE, pI γ RE is homologous to IFN γ -activated sequences, which bind to tyrosine phosphorylated members of the transcription factor family known as signal transducers and activators of transcription (STAT). The importance of tyrosine phosphorylation events in the STAT pathway led us to investigate the effect of the protein tyrosine phosphatase inhibitor, pervanadate, on ICAM-1 expression. We show that treatment of A431 cells and human keratinocytes with pervanadate stimulates protein complex formation on pI γ RE in a time- and concentration-dependent manner. As demonstrated by mobility supershift assays, the pervanadate-stimulated complex is similar to the IFN γ -stimulated complex and contains Stat1. Pervanadate treatment also led to an increase in overall protein tyrosine phosphorylation and phosphorylation of Stat1, as well as the subsequent increase in ICAM-1 mRNA and cell surface protein levels. These data show that pervanadate can mimic each step in the IFN γ -mediated pathway leading to ICAM-1 expression, demonstrate the ability of a pharmacologic agent to bypass the standard cytokine–receptor interaction required for increased ICANI-1 expression, and emphasize the importance of protein tyrosine phosphatases and protein tyrosine kinases in mediating inflammatory responses in the skin.
Evaluating the development of elastic anisotropy with plastic flow

It has been observed that many initially isotropic materials show the development of anisotropic elastic response after plastic flow. It is desirable to be able to model this change in the elastic properties as a function of the extent of plastic flow. This is particularly important when considering the traveling of waves in some glassy polymers that exhibit large differences in the wave moduli along the different directions resulting from unequal plastic flow in these directions. A thermodynamically based model of plasticity is developed and used to evaluate the elastic moduli associated with infinitesimal elastic deformations around the unloaded configuration. It is shown that for this model there are at least four independent material functions describing the elastic moduli of an initially isotropic material. These moduli are functions of the isotropic invariants of the right plastic Cauchy stretch tensor.
Nociceptin/orphanin FQ contributes to hypoxic/ischemic impairment of hypercapnic cerebrovasodilation

Previous studies in piglets show that hypercapnic pial artery dilation was blunted following cerebral ischemia. Unrelated studies show that the newly described opioid nociceptin orphanin FQ (NOC/oFQ) is released into cerebrospinal fluid and contributes to altered cerebral hemodynamics following hypoxia/ischemia. This study was designed to determine the contribution of NOC/oFQ to hypoxic/ischemic impairment of hypercapnic pial dilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased PO2 to 34 ± 3 mmHg. Topical NOC/oFQ (10−10 M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypercapnia PCO2 of (73 ± 2 mmHg)-induced pial artery dilation (28 ± 2 vs. 19 ± 2%). Hypercapnia pial artery dilation was blunted by hypoxia/ischemia but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1–13) NH2 (10−6 M), (25 ± 1, sham control; 4 ± 1, hypoxia/ischemia; and 12 ± 3%, hypoxia/ischemia + [F/G] NOC/oFQ (1–13) NH2, respectively). These data suggest that NOC/oFQ release contributes to impaired hypercapnia-induced cerebrovasodilation following hypoxia/ischemia.
Large differences in the electronic structure and spectroscopic properties of three phases of Al P O 4 from ab initio calculations

The electronic structure, interatomic bonding, and spectroscopic properties of the three known phases of $\mathrm{Al}\mathrm{P}{\mathrm{O}}_{4}$ in trigonal, orthogonal, and monoclinic structures formed at different pressures were studied using the density functional method. These three crystals have the same chemical formula and the same percentages of different atomic species but distinct local atomic coordination which offers a unique opportunity to systematically investigate their structure-properties relationship. The $\mathrm{Al}\text{\ensuremath{-}}K$, $\mathrm{Al}\text{\ensuremath{-}}{L}_{3}$, $\mathrm{P}\text{\ensuremath{-}}K$, $\mathrm{P}\text{\ensuremath{-}}{L}_{3}$, and $\mathrm{O}\text{\ensuremath{-}}K$ x-ray absorption near edge structure (XANES) edges were calculated using a supercell approach including the effects of core hole. The large differences in these properties among the three crystals are demonstrated and explained in terms of the unique structural units present in each phase. These results are in contradiction to the prevailing notion of using fingerprinting for XANES spectra interpretation.
Narrative descriptions should replace grades and numerical ratings for clinical performance in medical education in the United States.

Background: In medical education, evaluation of clinical performance is based almost universally on rating scales for defined aspects of performance and scores on examinations and checklists. Unfortunately, scores and grades do not capture progress and competence among learners in the complex tasks and roles required to practice medicine. While the literature suggests serious problems with the validity and reliability of ratings of clinical performance based on numerical scores, the critical issue is not that judgments about what is observed vary from rater to rater but that these judgments are lost when translated into numbers on a scale. As the Next Accreditation System of the Accreditation Council on Graduate Medical Education (ACGME) takes effect, medical educators have an opportunity to create new processes of evaluation to document and facilitate progress of medical learners in the required areas of competence. Proposal and initial experience: Narrative descriptions of learner performance in the clinical environment, gathered using a framework for observation that builds a shared understanding of competence among the faculty, promise to provide meaningful qualitative data closely linked to the work of physicians. With descriptions grouped in categories and matched to milestones, core faculty can place each learner along the milestones’ continua of progress. This provides the foundation for meaningful feedback to facilitate the progress of each learner as well as documentation of progress toward competence. Implications: This narrative evaluation system addresses educational needs as well as the goals of the Next Accreditation System for explicitly documented progress. Educators at other levels of education and in other professions experience similar needs for authentic assessment and, with meaningful frameworks that describe roles and tasks, may also find useful a system built on descriptions of learner performance in actual work settings. Conclusions: We must
IN SEARCH OF URANIAN DECAMETRIC EMISSION

An experiment to detect decametric radiation from Uranus is described. It is argued that in light of recent discoveries of a magnetic field on Uranus, it may be possible to detect low-frequency radio emission similar to the decametric emission from Jupiter. The experiment consisted of 106 hours of monitoring using the 26.3 MHz array of the University of Florida Dixie County Radio Observatory. No radiation from Uranus was detected. An upper flux density limit of 400 Jy was obtained.
JML: Expressive Contracts, Specification Inheritance, and Behavioral Subtyping

JML, the Java Modeling Language, is a formal specification language tailored to the specification of sequential Java classes and interfaces. It features contracts in the style of design by contract (as in Eiffel), as well as more sophisticated features that allow it to be used with a variety of tools from dynamic assertion checking to static verification. The talk will explain JML using some small examples.JML also features a notion of "specification inheritance," which forces all subtypes to be "behavioral subtypes." Behavioral subtyping allows client code to validly reason about objects using "supertype abstraction"; for example, when calling a method on an object, the specification for that method in the object's static type can be used, even though the method call may dynamically dispatch to an overriding method in some subtype. Specification inheritance makes this valid by forcing each such overriding method to obey the specification of that method given in each of its supertypes. Specification inheritance, and thus supertype abstraction, also apply to JML's invariants, history constraints, and initially clauses. These features make reasoning about object-oriented programs modular.Work on JML has been supported in part by NSF grants CCF0916350, CCF0916715, CCF1017262, and CNS1228695.
Advances in shotgun proteomics and the analysis of membrane proteomes

The emergence of shotgun proteomics has facilitated the numerous biological discoveries made by proteomic studies. However, comprehensive proteomic analysis remains challenging and shotgun proteomics is a continually changing field. This review details the recent developments in shotgun proteomics and describes emerging technologies that will influence shotgun proteomics going forward. In addition, proteomic studies of integral membrane proteins remain challenging due to the hydrophobic nature in integral membrane proteins and their general low abundance levels. However, there have been many strategies developed for enriching, isolating and separating membrane proteins for proteomic analysis that have moved this field forward. In summary, while shotgun proteomics is a widely used and mature technology, the continued pace of improvements in mass spectrometry and proteomic technology and methods indicate that future studies will have an even greater impact on biological discovery.
The Membrane-Active Tri-Block Copolymer Pluronic F-68 Profoundly Rescues Rat Hippocampal Neurons from Oxygen–Glucose Deprivation-Induced Death through Early Inhibition of Apoptosis

Pluronic F-68, an 80% hydrophilic member of the Pluronic family of polyethylene-polypropylene-polyethylene tri-block copolymers, protects non-neuronal cells from traumatic injuries and rescues hippocampal neurons from excitotoxic and oxidative insults. F-68 interacts directly with lipid membranes and restores membrane function after direct membrane damage. Here, we demonstrate the efficacy of Pluronic F-68 in rescuing rat hippocampal neurons from apoptosis after oxygen–glucose deprivation (OGD). OGD progressively decreased neuronal survival over 48 h in a severity-dependent manner, the majority of cell death occurring after 12 h after OGD. Administration of F-68 for 48 h after OGD rescued neurons from death in a dose-dependent manner. At its optimal concentration (30 μm), F-68 rescued all neurons that would have died after the first hour after OGD. This level of rescue persisted when F-68 administration was delayed 12 h after OGD. F-68 did not alter electrophysiological parameters controlling excitability, NMDA receptor-activated currents, or NMDA-induced increases in cytosolic calcium concentrations. However, F-68 treatment prevented phosphatidylserine externalization, caspase activation, loss of mitochondrial membrane potential, and BAX translocation to mitochondria, indicating that F-68 alters apoptotic mechanisms early in the intrinsic pathway of apoptosis. The profound neuronal rescue provided by F-68 after OGD and the high level of efficacy with delayed administration indicate that Pluronic copolymers may provide a novel, membrane-targeted approach to rescuing neurons after brain ischemia. The ability of membrane-active agents to block apoptosis suggests that membranes or their lipid components play prominent roles in injury-induced apoptosis.
Relationships for Green's function spectral dyadics involving anisotropic imperfect conductors embedded in layered anisotropic media

The Green's function spectral dyadic that characterizes a perfectly conducting patch antenna or propagating line can be modified to account for noninfinite conductivity. This is done through a relationship for a single planar interface imbedded in an anisotropic medium. A relationship for an arbitrary number of planar interfaces imbedded in an anisotropic medium is also derived. The imperfect conductor is represented by an anisotropic impedance. >
Solitary and Collaborative Pretense Play in Early Childhood: Sources of Individual Variation in the Development of Representational Competence

This study evaluates sources of individual variation in child pretense play as an expression of emerging mental representation. Family sociodemographic characteristics, maternal personological characteristics, and maternal affective and cognitive play behaviors, as well as children's gender, language competence, and play, were examined simultaneously. Naturalistic child solitary play and child collaborative play with mother were videorecorded in 141 20-month-olds. Child solitary play, child-initiated and mother-initiated collaborative play with mother, and maternal demonstrations and solicitations of play were then coded into nonsymbolic and symbolic acts. Zero-order relations obtained between child play and, respectively, child gender and language, family SES, and maternal verbal intelligence, personality, physical affection, and play demonstrations and solicitations. Structural equation modeling supported the following unique predictive relations: Child language and mothers' symbolic play positively influenced child collaborative play, and child gender and mothers' verbal intelligence predicted child solitary play. Child gender and mothers' verbal intelligence and physical affection influenced mothers' play and so influenced child collaborative play indirectly. The cognitive advantages of child play and maternal influences on child play are placed in an adaptive parenting framework.
Endocytosis of follicle-stimulating hormone by ovarian granulosa cells: analysis of hormone processing and receptor dynamics.

Suspensions of freshly isolated rat granulosa cells were used to study endocytosis and processing of radioiodinated ovine follicle-stimulating hormone (I-oFSH) and to analyze the dynamics of its receptor. Ovine FSH was iodinated to a specific activity of 26 microCi/micrograms as determined by radioreceptor self-displacement assays with maximum specific binding to excess membrane receptors of 46%. Radiolabeled oFSH was judged biologically equivalent to the unlabeled hormone since I-oFSH shows saturation-binding kinetics and stimulates steroidogenesis in a similar dose-related manner to unlabeled oFSH. Experiments designed to study the extent and time course of degradation involved continuous exposure of isolated granulosa cells to I-oFSH. Saturation of membrane receptors was achieved within 1.5 h of incubation, and internalization of FSH occurred in a linear manner for up to 6 h. The rate of internalization was equivalent to 2,780 FSH molecules/cell/h. Degradation of FSH became apparent after 6 h of incubation and increased to 86% of total cellular-associated radioactivity at 22 h. FSH degradation was inhibited by 100 microM chloroquine or 0.45 mM leupeptin. The measurement of cell surface I-oFSH binding in the combined presence of 100 microM chloroquine and 0.5 mM cycloheximide was unchanged for up to 22 h of incubation. This and other receptor binding data suggest that there is no reutilization of FSH receptors. Scatchard analyses of 4 degrees C binding assays on intact cells indicated that a two-site model best fit the data with association constants of K11 = 1.44 (+/- .42) X 10(10) and K12 = 4.35 (+/- .91) X 10(8). Receptor binding and activation studies for progesterone production yielded ED50s of 270 pM and 7.7 pM, respectively, and also indicated that 20% receptor occupancy is sufficient to stimulate maximal progesterone production. We conclude that after the initial binding event, FSH is endocytosed very slowly and is subsequently shuttled to the lysosomal compartment for degradation. The retarded rate of endocytosis may relate to novel pathways of hormone processing.
On the injectivity of a class of Wiener-Hopf integral operators in a Hilbert space

A class of Wiener-Hopf integral operators, with kernels vanishing along the positive real axis, is obtained from considering weighted transaxial line-integrals of rotationally symmetric functions defined on ℝ2. An analysis of these operators is given when acting in, the Hilbert space L2(ℝ+). A necessary and sufficient condition for injectivity is established and inversion formulas are provided in some cases. A specific operator falling into this class, the so-called incomplete Abel transform., is presented and an inversion formula is given. This inversion formula makes precise a formal result previously established in Dallaset al. [J. Opt. Soc. Am. A4, 2039 (1987)] and it is also shown to be consistent with an inversion formula derived by Hansen [J. Opt. Soc. Am. A9, 2126 (1992)].
The Effects of Gravitational Uncertainties on the Errors of Inertial Navigation Systems

The benefits in reduced inertial navigation errors to be gained by implementating a gradiometer to measure and compensate for the gravitational vector is studied. A limit to this improvement is obtained through a parametric study that was made to compare the magnitude of the geodetic error, due to incorrect compensation, with error due to the instruments comprising the inertial system. This was done for three levels of system accuracy; “production” systems, characteristic of equipment used today; state-of-the-art systems; and a future class of systems. It was found that geodetically induced position errors generally make up a rather small proportion of total system error, less than 30% even for the future class. However, its contribution to the velocity error is quite high, approximately 50% for production, 70% for state-of-the-art, and 94% for future systems. The error behavior of a gradiometer compensated system was then investigated. When the gradiometer uncertainties are modelled as white noise, their level of accuracy must be within 1.7 and 0.93 Eotvos units to reduce, respectively, the geodetic induced velocity and position error below that value which a system with no gradiometer already exhibits. When gradiometer uncertainties are modeled as random biases, their level of accuracy must be within approximately 1.7 and .1 Eotvos units to reduce geodetic induced velocity and position error respectively.
Gravity versus manual external rotation stress view in evaluating ankle stability: a prospective study

Background. The purpose of this prospective study was to determine whether gravity versus manual external rotation stress testing effectively detects widening of the medial clear space in isolated ankle fractures when compared with the uninjured contralateral side. Methods. Manual external rotation stress and gravity stress tests were performed on injured and uninjured ankles of ankle fracture patients in a clinic setting. Medial clear space measurements were recorded and differences between gravity and manual stress views were determined. Results. Twenty consecutive patients with ankle injury were enrolled in the study. When compared with the uninjured side, gravity stress views showed a statistically significant (P = .017) increase in medial clear space widening (1.85 ± 1.07 mm) compared with manual stress view widening (1.35 ± 1.04 mm). Conclusions. This study suggests that gravity stress views are as effective as manual external rotation stress views in detecting medial clear space widening in isolated fibular fractures.
DISTRIBUTION OF THROMBOEMBOLISM IN VALVULAR COMPARED TO NON-VALVULAR ATRIAL FIBRILLATION

To compare the rate and vascular destination of thromboembolic events (TE) in patients with “valvular” (VAF) and “nonvalvular” (NVAF) atrial fibrillation. Patients, categorized as “valvular” (VAF, n=2099) vs. “non-valvular” (NVAF, n=44551), were analyzed for the rate and vascular
Copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) Pharmacokinetics in FaDu Xenograft Tumors and Correlation With Microscopic Markers of Hypoxia

Purpose The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) ( 64 Cu-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. Methods and Materials 64 Cu-ATSM was administered during dynamic PET imaging, and temporal changes in 64 Cu-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conducted by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). Results Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K i ) constant was 12-fold that of muscle, whereas the distribution volume (V d ) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in 64 Cu-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of 64 Cu-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was 64 Cu-ATSM and Hoechst-33342. Conclusions The oxygen partial pressures at which 64 Cu-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown 64 Cu-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer.
Pattern formation during polymerization of acrylamide in the presence of sulfide ions

When polyacrylamide gel is prepared from a mixture of acrylamide, N,N′-methylene-bisacrylamide and triethanolamine with a peroxodisulfate initiator in the presence of sulfide, spatial pattern formation occurs in the gel if water is spread on top of the gel after it solidifies. These patterns, typically arrays of spots or stripes, persist for many hours. Analysis of the effects of temperature, composition, stirring, and other factors suggests that the pattern formation occurs during polymerization due to convection driven by the highly exothermic polymerization reaction. The role of sulfide ion, which is essential for the pattern formation, appears to be to terminate the polymer chain elongation while maintaining the overall exothermic chain reaction.
Spatially disjunct effects of co‐occurring competition and facilitation

Little is known of the co-occurrence and implications of competitive and facilitative interactions within sites. Here we show spatially disjunct competition and facilitation at forest edges, with beneficial influences of trees on seedling growth via increased ectomycorrhizal infection apparent from 12 to 20 m while closer to trees seedling growth is negatively correlated with canopy closure. As a result, seedling growth is maximized at intermediate distances. Facilitative interactions were nonlinear: being within 15.7 m of a tree maximized seedling mycorrhizal infection; while competitive effects were correlated with canopy closure, which was related to distance and generally scales with density. These patterns result in a positive correlation of tree density and seedling growth at low densities of trees, and negative correlation at higher densities because of competition. A spatial model suggests that plant communities are a mosaic of positive and negative interactions, which may contribute to population homeostasis and plant diversity.
Rifaprim in urinary tract infection: A comparison with co-trimoxazole

Two regimes of rifaprim (RPM), a 3.75 to 1 combination of rifampicin (RIF) and trimethoprim (TMP), were compared with co-trimoxazole (CO-T) for the treatment of urinary tract infection in 60 patients. Dosages were: A, 450 mg RIF + 120 mg TMP twice daily; B, 600 mg RIF + 160 mg TMP at bedtime and C, 800 mg sulphamethoxazole (SMZ) + 160 mg TMP twice daily. Clinical results were similar but CO-T treatment was accompanied by a greater number of late bacteriological failures. In none of 40 patients receiving RPM did resistance to any of the components develop, while in three of 20 patients receiving CO-T resistance to TMP or SMZ emerged during treatment. There were no side effects in the patients receiving RPM, but three patients developed transient laboratory abnormalities. One patient receiving CO-T had a rash and one further transient laboratory abnormalities. Satisfactory concentrations of RIF and TMP were measured in urine up to 24 h after a dose of 600 mg RIF + 160 mg TMP. RIF may be a better companion to TMP than the sulphonamides for the treatment of urinary tract infection.