cssi/SciSciGPT-SciSciNet huggingface dataset:
Truth-Functional Conditionals and Modern vs. Traditional Syllogistic

The failure of nine traditionally valid categorical syllogisms in modern logic,2 as well as the failure of implications, contrariety and sub-contrariety among A, E, I, and 0 propositions with identical subject and predicate terms, is customarily explained by references to the modern doctrine of 'existential import'. But this is a mistake. We wish to show that the differences between what should be counted as laws of logic are due, instead, to the employment of two different conditionals, one truth-functional and one not, in the two logics. By traditional logic we shall mean the standard account given in modern textbooks of the theory of the syllogism as developed from Aristotle's time down through the Port Royale Logic, with 24 valid categorical syllogisms out of 256 possible, and the theory of immediate inference as expressed in the traditional square of opposition, including conversion of E and I, contraposition of A and 0 and obversion of A, E, I, and 0 propositions. By modern logic we mean the logic of Frege, Russell, and Whitehead through the first-order predicate calculus. For convenience we shall use Quine's formulation in giving proofs later in the paper.3
A Validation of a Satellite Cloud Retrieval during ASTEX

Abstract An algorithm using NOAA-12 AVHRR (Advanced Very High Resolution Radiometer) solar reflectance measurements for retrieving cloud droplet size and optical thickness has been applied to a boundary layer stratocumulus cloud in the vicinity of the Azores on 12 June 1992 during the Atlantic Stratocumulus Transition Experiment (ASTEX). This day was particularly advantageous for validations because of the absence of cirrus or other higher-level clouds during the satellite overpass and the existence of a large relatively uniform stratus cloud dock. Uncertainty estimates for the retrievals are presented along with a discussion of the algorithm. An in-flight absolute calibration of AVHRR channel 1, necessary for accurate optical thickness retrievals, was done concurrently with the retrievals through comparison with a visible radiometer flown on the National Aeronautics and Space Administration's ER-2 and using the stratus cloud as the common reflectance target. Results are compared with in situ microphysica...
Role of sarcolemmal-bound calcium in regulation of myocardial contractile force

A rapidly exchangeable component of cellular calcium plays a significant role in the control of force development in heart muscle. Recently completed studies indicate that a large fraction of this calcium is bound to sites on the sarcolemma: 1) The curve that relates extracellular calcium ([Ca]0)(from 501µMto 10 mM) to force development and the one that relates [Ca]0to calcium bound to a highly purified sarcolemmal fraction are superimposable. 2) The ability of a series of cations (lanthanum, cadmium, manganese, magnesium) to uncouple excitation from contraction is the same as their relative ability to displace calcium from sarcolemma. 3) Polymyxin B, a highly charged cationic amphiphilic peptidolipid, specifically competes for calcium-binding sites on anionic and zwitterionic phospholipid. It is a potent displacer of calcium from myocardial cells and purified sarcolemma and a potent uncoupler. 4) Phospholipase D cleaves the nitrogenous base from sarcolemmal phospholipid with production of anionic phosphatidic acid. Phospholipase D treatment increases calcium bound to cells and to purified sarcolemma and increases force development of ventricular tissue from both neonatal rats and adult rabbits. 5) Insertion of charged amphiphiles in the sarcolemma as phospholipid analogues modulates interaction of calcium with myocardial sarcolemma. Anionic dodecylsulfate increases calcium bound to sarcolemmal vesicles by more than 80% and increases force development in rabbit papillary muscle by 100%. Cationic dodecyltrimethylamine produces a negative effect on binding and decreases contractile force by 70%. Neutral laurylacetate produces negligible effects on binding and force development. 6) The effect of pH variation on calcium binding to phospholipid extracted from sarcolemma indicates that the latter accounts for at least 75 % of the binding. The pK (6.60 to 7.15) found to produce the best fit for dissociation of sarcolemmal groups (and calcium binding) suggests that the sites may be amino groups located on zwitterionic phospholipid. As pH increases these groups are neutralized (NH3+→ NH2+ H+) and would no longer shield, intra- or intermolecularly, the negatively charged phospholipid acidic groups which would then be available to bind calcium. The present concept is that pH sets the level of potential calcium-binding sites by control of their degree of dissociation and the level of [Ca]0then determines the extent to which these sites “fill” with calcium. The amount of calcium bound to these sites seems to play a critical role in the regulation of contractile force.
Determination of Intracellular Unbound Concentrations and Subcellular Localization of Drugs in Rat Sandwich-Cultured Hepatocytes Compared with Liver Tissue

Prediction of clinical efficacy, toxicity, and drug-drug interactions may be improved by accounting for the intracellular unbound drug concentration (Cunbound) in vitro and in vivo. Furthermore, subcellular drug distribution may aid in predicting efficacy, toxicity, and risk assessment. The present study was designed to quantify the intracellular Cunbound and subcellular localization of drugs in rat sandwich-cultured hepatocytes (SCH) compared with rat isolated perfused liver (IPL) tissue. Probe drugs with distinct mechanisms of hepatocellular uptake and accumulation were selected for investigation. Following drug treatment, SCH and IPL tissues were homogenized and fractionated by differential centrifugation to enrich for subcellular compartments. Binding in crude lysate and cytosol was determined by equilibrium dialysis; the Cunbound and intracellular-to-extracellular Cunbound ratio (Kpu,u) were used to describe accumulation of unbound drug. Total accumulation (Kpobserved) in whole tissue was well predicted by the SCH model (within 2- to 3-fold) for the selected drugs. Ritonavir (Kpu,u ∼1) was evenly distributed among cellular compartments, but highly bound, which explained the observed accumulation within liver tissue. Rosuvastatin was recovered primarily in the cytosolic fraction, but did not exhibit extensive binding, resulting in a Kpu,u >1 in liver tissue and SCH, consistent with efficient hepatic uptake. Despite extensive binding and sequestration of furamidine within liver tissue, a significant portion of cellular accumulation was attributed to unbound drug (Kpu,u >16), as expected for a charged, hepatically derived metabolite. Data demonstrate the utility of SCH to predict quantitatively total tissue accumulation and elucidate mechanisms of hepatocellular drug accumulation such as active uptake versus binding/sequestration.
Optical Characterization of Coral Skeleton with Low-Coherence Enhanced Backscattering Spectroscopy

We have implemented Low-coherence Enhanced Backscattering (LEBS) as a tool for non-invasively measuring optical properties. We observe that coral skeletons that are susceptible to bleaching have smaller reduced scattering coefficients and fractal dimensions.
Phorbol 12-Myristate 13-Acetate Induces Epidermal Growth Factor Receptor Transactivation via Protein Kinase Cδ/c-Src Pathways in Glioblastoma Cells

Both the epidermal growth factor receptor (EGFR) and protein kinase C (PKC) play important roles in glioblastoma invasive growth; however, the interaction between the EGFR and PKC is not well characterized in glioblastomas. Treatment with EGF stimulated global phosphorylation of the EGFR at Tyr845, Tyr992, Tyr1068, and Tyr1045 in glioblastoma cell lines (U-1242 MG and U-87 MG). Interestingly, phorbol 12-myristate 13-acetate (PMA) stimulated phosphorylation of the EGFR only at Tyr1068 in the two glioblastoma cell lines. Phosphorylation of the EGFR at Tyr1068 was not detected in normal human astrocytes treated with the phorbol ester. PMA-induced phosphorylation of the EGFR at Tyr1068 was blocked by bisindolylmaleimide (BIM), a PKC inhibitor, and rottlerin, a PKCδ-specific inhibitor. In contrast, Go 6976, an inhibitor of classical PKC isozymes, had no effect on PMA-induced EGFR phosphorylation. Furthermore, gene silencing with PKCδ small interfering RNA (siRNA), siRNA against c-Src, and mutant c-Src(S12C/S48A) and treatment with a c-Src inhibitor (4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine) abrogated PMA-induced EGFR phosphorylation at Tyr1068. PMA induced serine/threonine phosphorylation of Src, which was blocked by both BIM and rottlerin. Inhibition of the EGFR with AG 1478 did not significantly alter PMA-induced EGFR Tyr1068 phosphorylation, but completely blocked EGF-induced phosphorylation of the EGFR. The effects of PMA on MAPK phosphorylation and glioblastoma cell proliferation were reduced by BIM, rottlerin, the MEK inhibitor U0126, and PKCδ and c-Src siRNAs. Taken together, our data demonstrate that PMA transactivates the EGFR and increases cell proliferation by activating the PKCδ/c-Src pathway in glioblastomas.
Physician participation in a Medicaid managed care program, the Kansas Primary Care Network

This study was designed to identify the factors that enhance and impede physician participation in a Medicaid managed care program, the Kansas Primary Care Network (PCN). The data for the study were collected in the summer of 1993 through a mail survey of primary care physicians in the PCN service area. Logistic regression and cross tabular analytic techniques were employed for data analysis. The results indicate that physicians who are not receptive to capitation-based reimbursement practices, those who practice in the higher per capita income counties, those who do not compare the PCN reimbursement rates favorably with private insurance rates, and physicians who think that untimely payment and the requirement to document patient referrals for specialty treatment pose problems for them are less likely to participate in the PCN program. Further, the study shows that institutional physicians have larger Medicaid caseloads than solo practitioners, who have larger Medicaid caseloads than single-specialty and multi-specialty group practitioners. Since most of the variables that attain statistical significance in explaining physician participation in the PCN program have to do with money, the study reaffirms the two market theory of the United States' health care delivery system.
U.S. Defense strategy after the cold war

(1992). U.S. Defense strategy after the cold war. The Washington Quarterly: Vol. 15, No. 2, pp. 57-76.
Rating ability in performance judgments: The joint influence of implicit theories and intelligence.

Abstract The purpose of this study was to approach the issue of rating ability by examining the influence of rater implicit theories and rater intelligence on rating outcomes. Using the inferential accuracy model ( Jackson, 1972 ), raters were identified as either possessing a normative or idiosyncratic implicit theory of the occupation of college instructor. In a laboratory setting, 50 normative and 50 idiosyncratic raters judged the videotaped performance of either a good or poor lecturer. Results showed that (a) intelligence was positively related to rating accuracy and to possessing a normative implicit theory, (b) rater type moderated the relationship between intelligence and rating accuracy, and (c) controlling for intelligence, normative raters committed stronger halo effects than idiosyncratic raters. These results were discussed in relation to furthering the understanding of rating ability.
Students' Basic Philosophical Assumptions in History of Psychology: A Measure and Teaching Tool.

Many psychology students initially have difficulty with the philosophical character of the typical history of psychology course. One way to introduce students to psychology's philosophical roots is to survey their assumptions on the nature of mind, emotion, and behavior. This article describes and gives examples of a 50-item Likert-scale questionnaire concerning the positions of many philosophers, biologists, and psychologists that are typically covered in the class. This article also presents data from three history of psychology classes and suggestions for using the measure as a teaching tool.
Route selection on freight networks with weight and volume constraints

This paper investigates the properties of freight networks where flow is measured with two attributes (weight and volume) and where costs are linear. Two dual variables are associated with each arc, one representing the marginal cost of increasing the weight flow on the arc and the other representing the marginal cost of increasing the volume flow. Optimal routes are determined in two steps: (1) set weight and volume prices and solve shortest path problems, and (2) adjust weight and volume prices in a way that causes the dual objective to increase. Each iteration provides a feasible solution and a bound on the maximum improvement in the objective function. The algorithm is applied to various test problems, to identify the conditions where it is most important to account for multiattribute freight flows.
A Multivariate Analysis of the Wechsler/Woodcock-Johnson Discrepancy Controversy

The Woodcock-Johnson Tests of Cognitive Ability (WJ-COG) is a relatively new measure of intellec tual ability that is being used by psychoeducational practitioners. Research comparisons suggest strong concurrent and superior predictive validity when compared with the WISC-R. However, early research reports suggested that for some children the WJ-COG produced "lower" scores than the WISC-R, a finding that produced much controver sy. The current study examined the validity of three content difference hypotheses (viz., differences in g, verbal, or achievement content) that have been advanced to explain WISC-R/WJ- COG discrepancies. A series of canonical correla tional analyses were conducted with an elemen tary school sample of 167 children to explore the redundancy between the WISC-R, WJ-COG, and achievement as measured by the Woodcock- Johnson Tests of Achievement. Inspection of the canonical variates, redundancy coefficients, and canonical loadings on the two significant variates extracted in each analysi...
Alternate industrial feedstocks from agriculture

Before the rapid development of the petrochemical industry, many feedstocks for manufacturing paints, plastics, fibers, lubricants, adhesives, and a host of other products were derived from agriculture. Good examples are linseed, castor, tung, tall, and soybean oils; natural rubber, gums, starch and cellulose, and many sources of fiber from the plant kingdom, as well as hides, bones, and fats and oils from the animal kingdom. In addition to these traditional agricultural materials, several new plant sources have been developed through new crops research. Also, new ways have been developed for converting existing agricultural products to better chemical intermediates. Availability of farm land, economics of crop production, and competition with petroleum are such that agriculture should be considered seriously as a viable alternative for at least part of our chemical feedstock requirements.
Roasting the Seeds of Law School Stress

Law school is a highly demanding experience; that is no surprise. But the toll which law school can exact on the well-being and life satisfaction of many students is a surprise. It is often much more severe than can be explained by the heavy workload alone. I discuss here the most common things that can multiply your distress as you go through law school, and suggest ways to affirmatively deal with each factor.
A rapidly convergent iterative procedure for the calculation of the temperature-pressure relation in a stellar atmosphere

Abstract The “coordinate perturbation procedure” developed in an earlier paper is extended to include scattering and radiation pressure in the calculation of the temperature pressure relation in a purely radiative atmosphere.
Competition between C−C and C−H Activation in Reactions of Neutral Yttrium Atoms with Cyclopropane and Propene

Branching ratios between C−C and C−H bond activation were measured for reactions of ground-state Y (a2D, s2d1) atoms with two C3H6 isomers (cyclopropane and propene) in crossed molecular beams. For...
Sensitivity-Enhanced Quantitative 13C NMR Spectroscopy via Cancellation of 1JCH Dependence in DEPT Polarization Transfers

A scheme has been developed to eliminate virtually all signal intensity dependence on 1JCH in polarization transfers between 1H and 13C nuclei, reducing differences in signal intensity to only 1.5% over the entire natural 1JCH range. The scheme relies on the summation of time-domain data acquired with four suitably selected Δ delays so that the J dependence is essentially canceled in the final, signal-averaged free-induction decay. These Δ delays have been incorporated into the DEPT pulse sequence to create sensitivity-enhanced experiments for collecting quantitative 13C{1H} spectra. Four experiments, each with unique read pulse angles, give quantitative spectra with 200−300% more sensitivity than conventional 13C spectra acquired with inverse-gated 1H decoupling. The experiments are ideal for recording spectra with improved quantitative information or for substantially reducing the long acquisition times indicative of quantitative 13C experiments. The ability of the experiments to provide quantitative sp...
The Effects of Measurement and Methods Decisions on Committee Preference Outlier Results

Studies of outlying committee preferences have been conducted with different preference measures and methodological approaches and have generated conflicting results. To assess the effects of these study design differences, I use multiple methodological approaches to examine committee-floor differences with jurisdiction-specific interest group data during a longer time period than earlier studies. After comparing results across methods, I compare them to past findings using the same method but different preference measures. I find that differences in preference measures largely explain previous contradictory results. Additionally, outlying tendencies exist among all committees expected to be outliers under conditional claims of the distributive theory.
Serum Cholesterol, Fat Intake and Breakfast Consumption in the United States Adult Population

Morgan et al demonstrated that adults who consumed ready-to-eat cereals had significantly lower fat and cholesterol intakes than those who ate other foods at breakfast. Not discussed in that study was the effect of breakfast consumption habits on serum cholesterol levels. The NHANES II study of 11,864 adults was used to both verify the Morgan et al results with a different sample and to extend that research by including serum cholesterol. The analysis disclosed that serum cholesterol levels are lowest among adults eating a breakfast that includes ready-to-eat cereal and highest among breakfast skippers.
Permutations of the positive integers with specified differences

Abstract In this paper, we show that given any finite set, D = { D 1 , D 2 , … , D n }, of positive integers, with gcd ( D 1 , D 2 , … , D n ) = 1, there is a permutation of the positive integers such that the absolute value of the difference between any two consecutive values is in D . Further, it is possible to choose the permutation so that each element of D occurs infinitely often as a difference. This answers in the affirmative a conjecture of Slater and Velez (1977, 1979).
The Intentionality of Desire and the Intentions of People

In this paper I explore the peculiarly human contribution to desire-behaviour; i.e., I discuss the fact that humans can be conscious that their desires are for certain things, can reflect upon these desires, and can, apparently, decide to act contrary to what, in some sense, they are aware of wanting to do. To say that a desire is intentional is to say that, in some sense, it involves a concept of the object of desire. For my purposes I shall understand the claim that desires are intentional in whatever way it must be understood in order that it might be true to say, for example, that animals and babies have desires, even though they are not conscious that they have desires, or conscious that their desire is for a particular thing or kind of thing. Having a desire does not entail that one is conscious that one has the desire, nor does it entail that one can give an account of one's desire. When considering the relation between needs and the intentionality of desire (to introduce a topic concerning which more will be said later) it might be suggested that desires constitute the means by which a need is brought into relation with an object which will satisfy the need. This suggestion is not quite right, however. A need can be 'brought into relation' with that which will satisfy the need without there being a desire for that particular thing. Any number of physiological mechanisms in fact exist which satisfy needs by 'obtaining' the required substance in some way. A desire is a special way of bringing an object into relation with a need and involves an intentional relation to the object desiredwhat Freud would call 'cathexis of a mental representative' which represents both the need and the desired object. Wanting and desiring, then, bring needs into relation with objects by means of intentional relations to those objects, i.e., by means of conceptions of those objects. Desire-behaviour is conceptmediated behaviour. Wants and desires involve intentional relations to objects as conceived. Wants and desires, therefore, are a function of one's knowledge, beliefs and concepts concerning objects as well as a function of one's needs. We can say, then, that wants and desires bring needs into relation not just with
Long-Term Functional Outcomes After Operative Treatment for Intra-Articular Fractures of the Calcaneus

Background: Calcaneal fractures can have long-term consequences in terms of pain and disability. Comparative studies have suggested that operative treatment of these fractures may result in better outcomes than nonoperative treatment; however, to our knowledge, the long-term outcomes of operative treatment of calcaneal fractures have not been reported for a large cohort of patients. Methods: One hundred and fifty-seven patients with calcaneal fractures were managed at our institution between January 1, 1989, and April 30, 2003. Seventy-three patients who were managed operatively for eighty-one intra-articular calcaneal fractures responded to a functional questionnaire that included the adjusted American Orthopaedic Foot and Ankle Society ankle-hindfoot scale (subjective component only), the Foot Function Index, and the calcaneal fracture scoring system at a median of 12.8 years (range, 5.0 to 18.5 years) after the injury. Results: In our study population, the mean adjusted American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 65.4 (95% confidence interval, 60.6 to 70.2), the mean Foot Function Index score was 20.5 (95% confidence interval, 16.6 to 24.4), and the mean calcaneal fracture scoring system score was 69.3 (95% confidence interval, 63.6 to 74.9). Patients who had sustained the calcaneal fracture as a result of a motor-vehicle accident rather than a fall reported significantly worse outcomes on two of three scales (p = 0.04 for the adjusted American Orthopaedic Foot and Ankle Society ankle-hindfoot scale, p = 0.05 for the Foot Function Index, and p = 0.35 for the calcaneal fracture scoring system), but this analysis was limited by the exclusion of twenty-four patients because of crush injuries (two) or unavailable documentation of the mechanism of injury (twenty-two). Conclusions: The long-term outcomes of operative treatment described in the present report are comparable with the long-term outcomes previously reported among smaller patient cohorts. Additional investigation is required to determine why patients with fractures that resulted from a motor-vehicle accident reported worse outcomes than patients with fractures that resulted from a fall. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
PWROG Buried Pipe Degradation Evaluation Handbook

Buried pipe degradation is an issue of increasing importance with respect to the nuclear industry due to an increased frequency of leaks over the past 10 years. The WCAP-17465-NP Handbook [1] was commissioned by the Pressurized Water Reactor Owners Group (PWROG) to address the need for a fitness-for-service evaluation methodology with the additional goal of providing a means of reducing the amount of time and work required to perform the evaluation.The Handbook details the developed methodology, which is consistent with Revision 6 of draft Code Case N-806 for the evaluation of degradation in buried metallic pipe [2]. The developed methodology is applicable to ASME Class 2 and 3 buried metallic piping items (excluding cast iron piping items). The methodology consists of nine criteria that encompass stresses resulting from burial and surface surcharge loads, internal pressure, and external events (i.e., seismic, frost heave, etc. that generate shear, longitudinal, and bending stresses.) The methodology does not permit through-wall leakage.The majority of the evaluation procedures come from existing ASME documents with the exception of the burial and surcharge loads. The definition of these loads is new to the ASME Boiler and Pressure Vessel Code, but not new to buried piping analysis for other fields of work, which have defined standards that are used to calculate these loads. If one of the requirements defined in the Handbook is not passed, one of several steps must be taken: a check may be performed to see if further refinement of soil, loads, and corrosion profile can be made to reduce conservatism, a more detailed analysis could be performed using a structural analysis tool such as finite element analysis, or the piping section containing the metal loss region would need to be repaired or replaced.Additionally, the Handbook provides pre-calculated results for a range of piping materials, sizes, soil classifications, and surface loads, as well as a sample calculation. These results are included in the Handbook in chart and table format. The inclusion of the charts and tables changes a relatively complex, time consuming evaluation to one can be performed in a minimum amount of time by a seasoned evaluator. This attribute is very important because plant operability (or needed relief request) may be heavily dependent on appropriate but prompt fitness-for-service evaluations.Copyright © 2012 by ASME
Chondromalacia of the trochlear notch in athletes who throw

Six athletes who throw and one shot-putter, who underwent elbow arthroscopy were found to have an area of chondromalacia involving the posterolateral aspect of the olecranon. Preoperative symptoms were pain and tenderness to palpation over the lateral edge of the olecranon. On physical examination, range of motion was full or only slightly decreased (
A model for computer-based data acquisition and control

This paper describes the theory and ongoing development of a computer-based system for data acquisition and control termed theVIrtualDataAcquisition andControl (VIDAC) system. The VIDAC system has particular application to laboratory experimental research and is currently applied to the field of materials testing. A model is presented and intended to display the basic similarities of data-acquisition algorithms and forms the conceptual basis for the VIDAC system. A discussion of the implementation of this model in computer software is given and two experimental programs in materials testing are described which have used the VIDAC ideology.
A shadow-moiré method with continuously variable sensitivity

Abstract This paper presents a shadow moire method whereby the isostathmics (contours of surface depth) can be studied with continuously variable sensitivity. In the method the sensitivity is varied by simply rotating the grating in front of the object surface. Equations interpreting the isostathmics are derived, and an experimental demonstration is included.
[14C]Pentachlorophenol mineralization in the rice rhizosphere with established oxidized and reduced soil layers.

Abstract Flooded soils with rooted aquatic macrophytes have adjacent aerobic and anaerobic zones at the soil–water interface and rhizosphere where many common soil constituents undergo sequential oxidation and reduction reactions. To investigate whether pentachlorophenol (PCP) mineralization would also be enhanced under these conditions, a laboratory study was conducted to determine the conversion of [ 14 C]PCP to 14 CO 2 , 14 CH 4 and [ 14 C]humic substances in soil microcosms with established aerobic–anaerobic zones at the soil–water interface and rice ( Oryza sativa ) rhizosphere. Contrary to what was expected, PCP was least rapidly degraded in rhizosphere-soil microcosms that contained the most extensive amounts of aerobic–anaerobic interfaces (63% PCP loss in 82 d) and was most rapidly degraded in soil microcosms that lacked redox interfaces in the soil profile (94% PCP loss in 82 d). Decreased PCP mineralization in the presence of aerobic–anaerobic interfaces was explained by (i) lack of sufficient O 2 for aerobic PCP mineralization, due to the oxidation of other soil constituents in aerobic zones, and (ii) lack of an adequate supply of electron equivalents for reductive dechlorination of PCP, due to the reduction of other alternate electron acceptors in anaerobic zones. It was concluded that PCP mineralization is inhibited in flooded soils that contain extensive amounts of aerobic-anaerobic interfaces, due to redox cycling of other soil constituents that occur in these zones.
Computational evidence for the ligand selectivity to the α4β2 and α3β4 nicotinic acetylcholine receptors

The homology models of the α4β2 and α3β4 nicotinic acetylcholine receptors (nAChRs) suggest that the two nAChR subtypes are different in their ligand-binding pockets due to the non-conserved residues in the β-subunits. The docking of nicotine, epibatidine, A-84543, and the two analogs of A-84543 ligands 1 and 2 to the homology models of α4β2 and α3β4 is presented. It is found that the protonated amino groups of these ligands bind to the α-subunits, whereas the remaining parts of the ligands bind to the β-subunits. The two non-conserved amino acids Lys77 and Phe117 in the β2-subunit corresponding to Ile77 and Gln117 in the β4-subunit are identified to be the key players determining the binding modes of the ligands. We demonstrate how the increase in the number of the atoms connecting the pyrrolidine and pyridine rings in A-84543, 1, and 2, and an introduction of the alkynyl substituent in the pyridine ring affect the binding and shift the selectivity of these ligands toward the β2-containing receptors. Further improvement in affinity and selectivity in this and other series of the ligands may be achieved by designing molecules that would specifically target the non-conserved regions in nAChRs.
Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.
Injury requirement for initiation of regeneration of newt limbs which have whole skin grafts

THERE are three known requirements for salamander limb regeneration—injury, nerves, and wound epidermis1,2. During the past few years we have examined cellular events in amputated, regenerating limbs and compared these with non-regenerating limbs after either denervation3,4 or after whole skin grafts over the amputation surface5. Results of these experiments led to the formulation of an hypothesis6 which suggests unique roles for injury, nerves, and the wound epidermis during the initiation of regeneration : injury is important to cause dedifferentiation of limb stump tissue cells, entry of these cells into G1 of the cell cycle and DNA replication; nerves are important for one or more G2 events and thus indirectly for mitosis; and the wound epidermis maintains these cells in the cell cycle so that significant outgrowth (blastema formation) can occur. In the present study we have examined the extent and kinds of injury necessary to initiate regeneration in newt limbs which have had skin grafts for 5 weeks and externally show no regeneration. The results suggest that non-cycling dedifferentiated cells are present in 5-week skin graft limbs which immediately begin cycling when a wound epidermis forms after re-injury.
Cardioprotective effects of diltiazem when given before, during or delayed after infusion of norepinephrine in anesthetized dogs☆

Abstract Catecholamine excess has been shown to produce 2 distinct forms of irreversible myocardial necrosis termed contraction band lesions. Calcium channel blocking agents provided a variable protective effect from these contraction band lesions. The purpose of this study was to determine the temporal responses of the most effective of these blocking agents, diltiazem, when given before, simultaneous with or after an initial exposure to a necrogenic infusion of norepinephrine (NE). Forty-one adult mongrel dogs were anesthetized with sodium pentobarbital (32 mg/kg) and infused with saline solution or NE (4 μg/kg/min) for 60 minutes or diltiazem at a rate of 20 μg/kg/min for the first 5 minutes and 10 μg/kg/min for the remaining 70 minutes. Diltiazem was infused as pretreatment 15 minutes before continued infusion with NE for 60 minutes, simultaneously infused with NE for 60 minutes or delayed 30 minutes after the start of NE infusion. Diltiazem alone exhibited no significant effect on hemodynamics, but pretreatment with diltiazem was able to moderate the rapid NE-induced increases in heart rate. NE infusion produced significant numbers of the 2 forms of contraction band lesions: (1) paradiscal contraction band lesions involving a small portion of the cell adjacent to the disc, and (2) holocytic contraction band lesions involving the entire cell. Diltiazem reduced the number of contraction band lesions, particularly the holocytic contraction band lesions, provided diltiazem was available before the insult and massive influx of calcium with a pharmacologic dose of NE. Although the exact mechanism of diltiazem's cardio-protective properties is not known, the timing of drug administration does appear to affect the degree of protection.
Use and satisfaction with key functions of a common commercial electronic health record: a survey of primary care providers

Despite considerable financial incentives for adoption, there is little evidence available about providers’ use and satisfaction with key functions of electronic health records (EHRs) that meet “meaningful use” criteria. We surveyed primary care providers (PCPs) in 11 general internal medicine and family medicine practices affiliated with 3 health systems in Texas about their use and satisfaction with performing common tasks (documentation, medication prescribing, preventive services, problem list) in the Epic EHR, a common commercial system. Most practices had greater than 5 years of experience with the Epic EHR. We used multivariate logistic regression to model predictors of being a structured documenter, defined as using electronic templates or prepopulated dot phrases to document at least two of the three note sections (history, physical, assessment and plan). 146 PCPs responded (70%). The majority used free text to document the history (51%) and assessment and plan (54%) and electronic templates to document the physical exam (57%). Half of PCPs were structured documenters (55%) with family medicine specialty (adjusted OR 3.3, 95% CI, 1.4-7.8) and years since graduation (nonlinear relationship with youngest and oldest having lowest probabilities) being significant predictors. Nearly half (43%) reported spending at least one extra hour beyond each scheduled half-day clinic completing EHR documentation. Three-quarters were satisfied with documenting completion of pneumococcal vaccinations and half were satisfied with documenting cancer screening (57% for breast, 45% for colorectal, and 46% for cervical). Fewer were satisfied with reminders for overdue pneumococcal vaccination (48%) and cancer screening (38% for breast, 37% for colorectal, and 31% for cervical). While most believed the problem list was helpful (70%) and kept an up-to-date list for their patients (68%), half thought they were unreliable and inaccurate (51%). Dissatisfaction with and suboptimal use of key functions of the EHR may mitigate the potential for EHR use to improve preventive health and chronic disease management. Future work should optimize use of key functions and improve providers’ time efficiency.
(18)F-FDG PET and vascular inflammation: time to refine the paradigm?

The recognition of the significance of atherosclerotic plaque biology and more specifically, inflammation in determining the propensity of plaque to rupture has led to efforts aimed at detecting vessel wall inflammation through molecular imaging 1. Given their high sensitivity and non-invasive nature, nuclear imaging modalities are particularly suitable for vascular molecular imaging. This is especially true when they are combined with CT or MRI to localize the target vessel. Following several reports on incidental observations of 18F-FDG uptake in large arteries on PET studies performed for cancer staging and other applications 2, a landmark study by Rudd et al more than a decade ago linked carotid artery 18F-FDG signal to symptomatic carotid artery disease 3. Since then a large number of studies have been performed to evaluate 18F-FDG PET as a tool for vessel wall characterization. To date, arterial 18F-FDG PET signal has been linked to age 4, gender 5, diabetes 6, metabolic syndrome 7, history of coronary artery disease 5, Framingham risk score 8, symptomatic carotid disease 3, 9, distal microembolization 10, atherosclerotic plaque structure and morphology 5, 11, 12, systemic inflammatory disease 13, and risk of future cardiovascular events, as reported by several groups of investigators, including Blomberg et al in an earlier issue of the journal 14, 15. The proposed applications of vascular 18F-FDG PET include retrospective identification of culprit lesions after transient ischemic attack 9, tracking the effect of therapeutic interventions on plaque biology 16–18 and cardiovascular risk stratification 14, 15.
Adaptive regularized canonical correlations in clustering sensor data

A regularized canonical correlations scheme is proposed for adaptive clustering of sensor measurements according to their information content. A novel framework utilizing sparsity-inducing regularization and exponential weighing is designed to deal with nonstationary settings. Distributed recursions to minimize the proposed formulation are put forth by utilizing coordinate descent techniques combined with the alternating direction method of multipliers. Numerical tests demonstrate that the novel adaptive clustering framework is capable to deal with nonstationary settings while outperforming existing alternatives.
Abrasion resistant casts for removable partial dentures.

Stone casts used for fabrication of cast frameworks for removable partial dentures can be distorted or mechanically abraded in the duplication process. As a result the framework produced may not accurately fit the cast and the patient’s mouth, and it may require major adjustment. Surface trealment of gypsum casts with cyanoacrylate resins significantly increases abrasion resistance without loss of surface detail.‘bz The dimensional increase in size of the casts has been found to be in the range of 2 to 4 pm, which is not a clinically significant amount. To reduce the mechanical abrasion and/or distortion of casts made for the fabrication of removable prostheses, the following procedure is recommended. 1. Make a slone cast, trim, and thoroughly dry it. 2. Apply cyanoacrylate resin (Aron Alpha adhesive, Howmedica, Inc., Clifton, N.J.; or Permabond 910 Adhesive, Permabond Int,ernational Corp., Inglewood, N. J.) liberally to the cast with a cotton-tipped applicator. Excess resin is
The value of automated data mining.

It’s the late ’70s. A couple of things are heavy on the minds of biomed managers: how to live without disco and how to figure out trends with medical equipment based on information inside file cabinet equipment history folders. Decisions were likely made by gut feelings, and asking peers what they thought should be done regarding equipment replacement and department budgets. Now it’s the ’80s. Along comes the computer, with its 8-inch floppy disk drives. The first computerized maintenance management system (CMMS) programs are written and implemented. These applications stored basic equipment inventory information, would possibly queue up scheduled inspection tasks, and kept some very basic service and inspection history. At least it was easier to print hospital medical device inventories on that rockin’ dot matrix printer. The ’90s come bounding in, and CMMS applications have become a bit more elaborate, utilizing coding to flag important service history entries, such as use errors and certain types of failures. Asset records were coded for key information management, such as service coverage methods. With this coding, more functional reports could be written to focus in on service issues and asset management planning. But this still required printing reports (on that blazin’ laser printer), and then paging through to mark up the reports with action items. Asset records lacking key information reduced the value of the database for benchmarking cost of service or replacement planning. In order to identify asset records that needed data completion, one would have to print reports, page through them, and hand them to others to gather and input these key data such as acquisition cost and purchase date. The year 2000 comes and goes. Society did not collapse. CMMS applications introduce scheduled alerts that can be configured to mine data from equipment history and asset records. These scheduled alerts can deliver well-written reports via e-mail directly to the staff members that need information to act on. Automated data mining can release biomed managers and technical staff members from the tedious review of asset inventories and histories that was once required to make effective equipment management decisions. Well-written queries can be used to key in on records that need action. These queries can be launched close to real-time so action may be taken to correct data issues or to provide communication to technical staff and their customers. Data queries may be utilized in stand-alone reports, built within reporting modules now common in CMMS applications, or sometimes written as TransactSQL language and scheduled for automated execution within the database. A very simple example of a T-SQL query that will identify active asset records missing purchase cost is shown below:
Moving Past Collusion in Major League Baseball: Healing Old Wounds, and Preventing New Ones

This article presents a plan for Major League Baseball to move past its history of collusion, and into a new era marked by more collegial labor-management relations. Part I of this Article provides an historical analysis of Baseball's reserve system, free agency system, and anti-collusion requirements. Part II discusses the three 1980s arbitration decisions that each found Major League Baseball club owners to have illegally colluded in violation of the Major League Basic Agreement ("Collective Bargaining Agreement" or "CBA"). Part III discusses more recent allegations of collusion pertaining to the 2002 and 2007 Baseball off-seasons. Part IV explains how Baseball's history of collusion continues haunt the game's integrity in terms of both its labor-management relationship and its relationship with fans. Part V suggests a series of best practices that Major League Baseball should adopt to move past its dark history of collusion and toward a new period of labor-management cooperation.
Direct demonstration that the vitamin k-dependent bone gla protein is incompletely γ-carboxylated in humans

Incomplete vitamin K-dependent gamma-carboxylation has been found in bone Gla protein (BGP) isolated from each of 20 different human bone samples. Using N-terminal protein sequencing of the methyl-esterified protein (Anal Biochem 1991;199:93-97), a method that directly measures the percentage of gamma-carboxylation at each target glutamate residue, the extent of incomplete BGP gamma-carboxylation was found to depend strongly on sequence position, with (chi +/- SD) 67 +/- 14% gamma-carboxylation at residue 17.88 +/- 9% gamma-carboxylation at residue 21, and 93 +/- 4% gamma-carboxylation at residue 24. There is a strong correlation between the incomplete gamma-carboxylation at glutamate residues 17 and 21 for BGP purified from the 20 bone samples (p < 0.001), which suggests that individual differences in the efficiency of BGP gamma-carboxylation during synthesis probably cause the observed differences in percentage BGP gamma-carboxylation between bone samples. These results have been interpreted using a kinetic treatment of gamma-carboxylation. This treatment predicts the existence of differences in the extent of gamma-carboxylation between glutamate residues in BGP, as well as the correlation between percentage carboxylation at Glu17 and Glu21. Although the molecular basis of incomplete BGP gamma-carboxylation is at present unknown, if incomplete BGP gamma-carboxylation were caused only by differences in the availability of vitamin K in bone cells, this kinetic treatment predicts that the range in BGP gamma-carboxylation observed in the 20 human bone samples studied here could be explained by a relatively modest fivefold range in the vitamin K levels of these individuals.
Molecular Pathways: Targeting MALT1 paracaspase activity in lymphoma

MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling.