cssi/SciSciGPT-SciSciNet huggingface dataset:
Use of tanezumab for patients with hip and knee osteoarthritis with reference to a randomised clinical trial by Berenbaum and colleagues.

Publication spin, in the context of randomised clinical trials, is defined as ‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results’ (p. 2059).1 In our view, a secondary but clinically important alternative type of publication spin is reliance on statistically significant findings without regard to potential clinical implications of the estimated effects. The American Statistical Association (ASA) has commented on this issue, stating a statistically significant effect does not inform its size or importance.2 A later editorial more explicitly states that conclusions not be based solely on statistical significance.3 We believe the recently published trial by Berenbaum and colleagues4 meets our secondary definition of publication spin and does not meet the recommendation endorsed by the ASA. Berenbaum and colleagues conducted a three-arm phase III randomised …
A Critical View of the Evolution of the Accounting Professoriate

The first two-thirds of this paper is a review and analysis of the evolution of the accounting research and education environments, primarily in the United States but also with respect to Canada, from the 1960s to the present time. The final third of the paper consists of a critique of contemporary approaches to both accounting research and education.
Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN -amplified neuroblastoma.

MYCN-amplified neuroblastoma is a lethal subset of pediatric cancer. MYCN drives numerous effects in the cell, including metabolic changes that are critical for oncogenesis. The understanding that both compensatory pathways and intrinsic redundancy in cell systems exists implies that the use of combination therapies for effective and durable responses is necessary. Additionally, the most effective targeted therapies exploit an "Achilles' heel" and are tailored to the genetics of the cancer under study. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified neuroblastoma is hypersensitive to the combination of an inhibitor of the lactate transporter MCT1, AZD3965, and complex I of the mitochondrion, phenformin. Our data demonstrate that MCT4 is highly correlated with resistance to the combination in the screen and lowly expressed in MYCN-amplified neuroblastoma. Low MCT4 combines with high expression of the MCT2 and MCT1 chaperone CD147 in MYCN-amplified neuroblastoma, altogether conferring sensitivity to the AZD3965 and phenformin combination. The result is simultaneous disruption of glycolysis and oxidative phosphorylation, resulting in dramatic disruption of adenosine triphosphate (ATP) production, endoplasmic reticulum stress, and cell death. In mouse models of MYCN-amplified neuroblastoma, the combination was tolerable at concentrations where it shrank tumors and did not increase white-blood-cell toxicity compared to single drugs. Therefore, we demonstrate that a metabolic combination screen can identify vulnerabilities in subsets of cancer and put forth a metabolic combination therapy tailored for MYCN-amplified neuroblastoma that demonstrates efficacy and tolerability in vivo.
The Fisher and Neyman-Pearson Theories of Statistical Inference

This chapter explores how Fisher, and then Neyman and Pearson, tried to build a theory of statistical inference from the frequency definition of probability. Fisher, despite his rejection of Laplacean inverse probability, remained with the epistemic tradition, and the fundamental tension in his theory was never resolved. Neyman and Pearson developed a more consistent theory, but Neyman’s commitment to the frequency theory led him inexorably to a theory of inductive behavior, to a theory of statistical decision-making. This approach found paradigmatic application to problems of quality control in manufacturing but had little relevance for basic research in psychology.
Protein Modifications and Mitochondrial Import of Yeast Cytochrome c: An Overview

In addition to transcription and translation, the biosynthesis of mitochondrial cytochrome c involves the following co-translational and post-translational steps for formation and localization of the final product: excision of the amino-terminal methionine residue and amino-terminal acetylation of certain cytochromes c; trimethylation of specific lysine residues in fungal and plant cytochromes c; and the covalent attachment of protoheme to two cysteinyl residues, concomitant with transport into the mitochondrial membrane. Subsequently, mature cytochrome c interacts with a variety of other heme proteins to carry out various redox reactions. These processes, schematically outlined in Fig. 1, have been systematically investigated with the yeast Saccharomyces cerevisiae.
Is Greed Good? Learning Business Ethics from King Leopold II, Mass Murderer

Adam Smith demonstrated how self-interest and the “invisible hand” of the marketplace allocated scarce resources efficiently and promoted social welfare. Unfortunately, the invisible hand argument led to the belief that regulation is unnecessary and that “greed is good.” This paper uses the life of one of the greatest mass murderers of history, King Leopold II, who caused the death of 10 million people, to show how greed can actually result in great harm. Greed should not be confused with self-interest. In the long run, greed can destroy an organization or country.
Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones.

Depolarization-induced suppression of excitation and inhibition (DSE and DSI) appear to be important forms of short-term retrograde neuronal plasticity involving endocannabinoids (eCB) and the activation of presynaptic cannabinoid CB1 receptors. We report here that CB1-dependent DSE can be elicited from autaptic cultures of excitatory mouse hippocampal neurones. DSE in autaptic cultures is both more robust and elicited with a more physiologically relevant stimulus than has been thus far reported for conventional hippocampal cultures. An additional requirement for autaptic DSE is filled internal calcium stores. Pharmacological experiments favour a role for 2-arachidonyl glycerol (2-AG) rather than arachidonyl ethanolamide (AEA) or noladin ether as the relevant endocannabinoid to elicit DSE. In particular, the latter two compounds fail to reversibly inhibit EPSCs, a quality inconsistent with the role of bona fide eCB mediating DSE. Δ9-Tetrahydrocannabinol (Δ9-THC) fails to inhibit EPSCs, yet readily occludes both DSE and EPSC inhibition by a synthetic CB1 agonist, WIN 55212-2. With long-term exposure (∼18 h), Δ9-THC also desensitizes CB1 receptors. Lastly, a functional endocannabinoid transporter is necessary for the expression of DSE.
Cubegrades: Generalizing Association Rules

Cubegrades are a generalization of association rules which represent how a set of measures (aggregates) is affected by modifying a cube through specialization (rolldown), generalization (rollup) and mutation (which is a change in one of the cube's dimensions). Cubegrades are significantly more expressive than association rules in capturing trends and patterns in data because they can use other standard aggregate measures, in addition to COUNT. Cubegrades are atoms which can support sophisticated “what if” analysis tasks dealing with behavior of arbitrary aggregates over different database segments. As such, cubegrades can be useful in marketing, sales analysis, and other typical data mining applications in business. In this paper we introduce the concept of cubegrades. We define them and give examples of their usage. We then describe in detail an important task for computing cubegrades: generation of significant cubes which is analogous to generating frequent sets. A novel Grid Based Pruning (GBP) method is employed for this purpose. We experimentally demonstrate the practicality of the method. We conclude with a number of open questions and possible extensions of the work.
On the Need for Negotiation in Policy-based Interaction with Autonomic Computing Systems

Large organizations develop guidelines, processes, and tools to help them implement and manage IT. In many cases, these encode policies, the central means of control for autonomic computing systems. Policies consist of goals, scope, constraints, and tradeoffs in system management, and define the boundaries of delegation of work between people and systems. Yet little is known about policy-based interaction among people and between people and systems. Are policies created once and used routinely over long periods? Or do policies change frequently? How do policies work in the real world? Our field observations suggest that policies are continually negotiated and re-interpreted as they are applied to specific instances. This implies several design points, including the need to make policy application transparent and flexible, enabling lightweight, rapid, incremental, and reversible interactions with policy-based systems
Psychosomatic Medicine in the 21st Century: Understanding Mechanisms and Barriers to Utilization

The psychosomatic approach arose in antiquity as mankind looked for explanations for illness and death. With the rise of modern medicine, the links between emotions and medical conditions, such as cardiac disease and diabetes, were described by astute clinical observers, but the mechanisms for these conditions were based on correlation from observations rather than on experimental design. Psychoanalytic theory was often utilized to explain many common diseases. For example, peptic ulcer disease was blamed upon anger and stress, but scientific methodology discovered Helicobacter pylori to be the significant causal factor of this disease and resulted in the development of more effective treatments. Nevertheless emotional factors are still linked to disease states and morbidity; for example, depression is a risk factor for mortality following myocardial infarction. Advances in neuroscience demonstrate that the reduction of telomere length by anxiety and stress leads to more rapid aging and potential disease vulnerability. Thus, neuroscientific probes may allow for the elucidation of psychosomatic mechanisms. Sadly, clinical barriers, in terms of time pressure upon physicians and the current separation of mental health services from primary care settings, continue the dualistic treatment of many conditions where psychological factors are important. It is not clear whether a mandate for the integration of behavioral health into primary care will remedy this partition and finally maximize a psychosomatic approach to medical care.
The X Files--One Step Closer to Closure

There may be drugs and a useful vaccine available to combat the hepatitis B virus, but one aspect of this pathogen remains a puzzle: the function of its HBx protein. As [Ganem][1] reveals in his Perspective, new findings ([ Bouchard et al .][2]) show that this versatile viral protein is an activator of calcium-dependent Ras signaling, an observation that may explain many of its biological effects. [1]: http://www.sciencemag.org/cgi/content/full/294/5550/2299 [2]: http://www.sciencemag.org/cgi/content/short/294/5550/2376
Modal Logic of Concurrent Nondeterministic Programs

This paper describes a logic, L, for reasoning about concurrent programs. Programs are similar to those of dynamic logic, with a shuffle operator included. L is a modal logic including the modalities [], meaning "throughout the future," and +, meaning "sometime in the future." These modalities are extended by constraints, so that they can be used to express assertions such as "p holds as long as q does." Programs contain labels. Using labels, it is possible to isolate the behavior of a single process or segment of a process, while at the same time keeping the segment in the context of the whole parallel system. A certain subset of the propositional case of L is known to be decidable.
A Longitudinal Investigation of Speaking Rate in Preschool Children Who Stutter

Both clinical and theoretical interest in stuttering as a disorder of speech motor control has led to numerous investigations of speaking rate in people who stutter. The majority of these studies, ...
Influence of hydrogen on the crack resistance of 10Kh15N27T3V2MR steel

In high ranges of pressure and temperature, hydrogen reduces the thresholds Δ Kth , cyclic fracture toughness Kfc , and short-term static crack resistance Kc of 10Kh15N27T3V2MR austenitic dispersion-hardened steel. Conditions of plane deformation and, correspondingly, conditions of determination of the characteristic K Ic are maintained in testing in the range 293 – 483 K of compact specimens 20 mm thick after their preliminary hydrogenation to a hydrogen content of 8 ppm. Low-cycle fatigue and sizes of the plastic zone under static crack resistance are most sensitive to hydrogen (and decrease by 80 and 70%, respectively, against those in helium), and the cyclic crack resistance parameters Δ K th and K fc (decrease by 25%) are least sensitive to hydrogen. The static crack resistance K c and the percentage reduction in the cross-sectional area ψ in short-term tension are reduced by 50%.
Conservation and the Lure of the Garden

: Among the conservation voices today who seek a sensible “middle ground” in remedying land-use problems are those who propose a tend-the-garden ethic in which humans would merely need to view the earth as a garden and labor to make it productive and beautiful in order to solve conservation challenges. This line of reasoning is exemplified by Michael Pollan's highly praised book, Second Nature, which supports conservation values but harshly criticizes contemporary environmental efforts, including the work of such organizations as The Nature Conservancy. Pollan's portrayal of the gardener as model conservationist is usefully compared with an important essay by Aldo Leopold from a half-century ago, “The Farmer as a Conservationist,” which similarly uses a model land tender as exemplar of where conservation needs to head. Comparing the two writings reveals profound flaws in the contemporary tend-the-garden line of thought. In doing so, it usefully reveals to scientists why their efforts are so often misunderstood and resisted. The popularity of tend-the-garden reasoning illustrates how successful the environmental backlash has been in misportraying the motives and aims of serious conservationists, particularly those who seek to protect wildlife and natural habitat. In doing so, it highlights the need for conservationists to take their own ideas more seriously and to do a far better job of presenting those ideas, in coherent form, to broad audiences. Resumen: Entre las actuales voces conservacionistas que buscan un sensato “punto intermedio” en la remediacion de problemas de uso del suelo se encuentran las que proponen una etica de cuidar-el-jardin en la que los humanos tendrian que ver a la Tierra meramente como un jardin, trabajar para hacerlo productivo y embellecerlo para resolver los retos de la conservacion. Esta linea de razonamiento esta ejemplificada por el muy elogiado libro de Michael Pollan, Segunda Naturaleza, que mantiene valores conservacionistas pero critica severamente los esfuerzos ambientalistas contemporaneos., incluyendo el trabajo de organizaciones como The Nature Conservancy. Es util comparar la representacion de Pollan del jardinero como conservacionista modelo con un importante ensayo de Aldo Leopold de hace medio siglo, “El Campesino como Conservacionista,” que similarmente utiliza un cuidador modelo como el ideal de hacia donde debe ir la conservacion. La comparacion de ambos escritos revela profundos defectos en la linea contemporanea de pensamiento de cuidar-el-jardin. Al hacerlo, revela a los cientificos porque sus esfuerzos son mal entendidos y rechazados tan a menudo. La popularidad del razonamiento cuidar-el-jardin ilustra el exito que ha tenido la repercusion ambiental negativa en la interpretacion incorrecta de los motivos y las metas de conservacionistas serios, particularmente los que buscan proteger la vida silvestre y el habitat natural. En ello, resalta la necesidad de que los conservacionistas tomen sus ideas mas seriamente y hagan mucho mejor trabajo en la presentacion de esas ideas, de manera coherente, al publico en general.
The roles of photoreceptor systems and the COP1-targeted destabilization of HY5 in light control of Arabidopsis seedling development

Arabidopsis seedlings display contrasting developmental patterns depending on the light environment, e.g. photomorphogenesis in the light and skotomorphogenesis (etiolation) in darkness. Recent studies have implicated protein degradation as a means of regulating this developmental switch ([Osterlund
Model For The Molecular Origins Of The Polarization In Ferroelectric Liquid Crystals

A ferroelectric polarization P (permanent, spontaneous electric dipole moment) is predicted for certain non-racemic liquid crystals based upon simple symmetry arguments. The magnitude of this polarization is a major factor in determining the eletro-optic response times achievable in ferroelectric liquid crystal (FLC) spatial light modulators. While the symmetry arguments are compelling, insight into the actual molecular origins of P is necessary if new materials with high polarization and fast electro-optic response are to be designed in a directed way. Based upon the concept that ferroelectricity in FLCs is a manifestation of a novel form of molecular recognition occurring in the FLC phase, we have developed a simple stereochemical model for P in principle allowing prediction of the sign (handedness) and magnitude of the polarization for specific compounds. The design, synthesis and ferroelectric properties of new materials will be described in the context of this model.
The contextual components of ecotoxicology

* Thought processes are contextual, so humans assimilate new information and ideas best when they can be associated with familiar contexts. In graduate school I studied freshwater protozoans, and my first professional position (summer 1948) in the Department of Limnology at the Academy of Natural Sciences in Philadelphia required that I gather information on pollution effects in aquatic communities in the Conestoga River basin ecosystem. Two river survey teams studied everything from bacteria to fish, plus water chemistry. Sampling areas were both above and below point source water discharges so that effects upon aquatic life could be compared. Occasionally, both teams would sample the same area at different times during the same day so that variability (e.g., splitters vs lumpers) could be determined. In fall 1948, a single permanent river survey team was formed, and I continued studies of freshwater protozoan communities in North America and other parts of the world (e.g., headwaters of the Amazon River). Consequently, early in my career I viewed pollutional effects in a systems context. Freshwater protozoan samples are highly perishable (also bacterial and water chemistry samples), but
The particularity of jesus and the time of the kingdom: philosophy and theology in yoder

John Howard Yoder's work, while appreciated in many respects, is not generally read in a philosophical register. This essay attempts to alter this situation by proposing a relation between his theology and a philosophy of particularity. The project articulates a logic of Jesus that is independent from and antagonistic towards the Powers. This logic is resolutely secular, revolutionary, and creative. I contend that Jesus' “equality with God” amounts to a radical affirmation of history and temporality. Yoder's work is presented as a zone of interference, a particular vantage from which a simultaneous practice of philosophy and theology becomes possible.
Effects of α-adrenoceptor agents on norepinephrine release from vas deferens of several species including man

Abstract Unlike the situation with the vas deferens of rats, guinea-pigs, rabbits an dogs, neither phentolamine nor yohimbine enhanced electrically-evoked release of [3H]norepinephrine from the in vitro human vas deferens. However, clonidine produced, by a phentolamine-sensitive mechanism, a concentration-related inhibition of release inthe human vas deferens. The results indicate that, even though presynaptic α-adrenoceptors exist, a negative feedback regulation of release by norepinephrine, which occurs in the vas deferens of the other species, may not be functionally important in the vas deferens of the human.
SOLVING PLATE BENDING PROBLEMS USING FINITE STRIPS ON NETWORKED WORKSTATIONS

Abstract In this paper, we present two parallelization schemes for solving a particular class of plate-bending problems using the finite strip method on a network of workstations equipped with the well-known software package PVM (parallel virtual machine). The first scheme is based on the master-slave model and the second is a multilevel master-slave approach. The finite strip method, first developed in the context of thin plate bending analysis, is a semi-analytical finite element process. It takes advantage of the orthogonality properties of harmonic functions in the stiffness matrix formulation to yield a block diagonal stiffness matrix and, thus, decomposes a single problem in two dimensions into several independent subproblems, each corresponding to a problem in one dimension. The method not only reduces the bandwidth of the system stiffness matrix, but offers obvious advantages for solving the problem on either shared-memory machines or distributed-memory multiprocessors. Our parallelization strategies are implemented on a network of SUN workstations interconnected by the Ethernet. Numerical experiments and the performance of the implementations are presented. Our results clearly indicate that the multilevel master-slave model is better than the master-slave scheme on the networked system using PVM.
Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers.

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux [Jno] in picoliters per second) produced in the large airways is due to an enzyme overexpression, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in the peripheral lungs (ie, alveolar NO concentration [Calv] in parts per billion [ppb]) or on the diffusing capacity of NO (Dno) [in picoliters per second−1 per ppb−1) in the airways. Aminoguanidine administration resulted in a significant reduction in Jno compared with administration of the saline solution control in eight healthy subjects and in eight patients with asthma but caused no significant changes in Calv or in Dno in either group. No rise in BP, fall in FEV1, or adverse effects were observed in either group. These results indicate that iNOS from larger airways is the predominant source of elevated large airway-derived NO in patients with asthma, and that exhaled NO from peripheral lungs is not affected by a nebulized iNOS inhibitor and, therefore, is more likely to be derived form constitutive forms of NO synthase.
Actualism and possible worlds

THE IDEA of possible worlds has both promised and, I believe, delivered understanding and insight in a wide range of topics. Pre-eminent here, I think, is the topic of broadly logical possibility, both de t the function of proper names and definite descriptions; the nature of counterfactuals; time and temporal relations; causal determinism; in philosophical theology, the ontological argument, theological determinism, and the problem of evil (see [7], chapters IV-X). In one respect, however, the idea of possible worlds may seem to have contributed less to clarity than to confusion; for if we take this idea seriously, we may find outselves committed to the dubious notion that there are or could have been things that do not exist. Let me explain.
Surrace and Volume Phenomena in Dielectric Breakdown of Polyethylene

This is a progress report on the authors' studies of the mechanism of longterm dielectric breakdown in polyethylene; the report wus first given in 1948. Testing has been accelerated by using higher than power frequencies. Earlier testing concerned the effects of surface ionization on life; current studies include solid breakdown. To date the authors have been unable to produce solid breakdown in polyethylene which was not preceded and caused by surface ionization.
Variable Structure Digital Repetitive Controller

Repetitive controllers as a new type of servo mechanism have been successfully applied to mechanical systems such as robot and disk drive track following. Many research in this field have been devoted to stability and robustness considerations of adding a repetitive signal generator in the feedback loop. In this paper, a variable-structure digital repetitive controller, which can adapt a slow varying period, is proposed. For accurately identified plant, it is shown that computations involved in identifying a period can be substantially reduced. Furthermore, an FIR filter is added to the period identifiers in order to cope with model uncertainties. It is shown that for small perturbations, unbiased estimate of period can be achieved by adding a low-order FIR filter.
Characterization of carbon nanotubes by scanning probe microscopy

Abstract Carbon nanotubes, fabricated by the Ebbesen-Ajayan method, were imaged using scanning tunneling microscopy (STM) and atomic force microscopy (AFM) in air and were compared to images obtained with high-resolution transmission electron microscopy (HRTEM). The HRTEM images revealed an abundance of elongated structures ranging in diameter from 3.0 to 30 nm, and with lengths of up to 0.8 μm. Many of the structures possessed several graphitic shells as if the tubes were nested one in the other. Reproducible images of the tubular structures, typically 20 nm in diameter and with a large variation in length, were obtained with both STM and AFM when the nanotubes were deposited on hydrogen-terminated Si(111), confirming that the nested structures observed with HRTEM do indeed have a tubular morphology. No single-walled, bare nanotubes or spherical fullerenes (typical of the Kratschmer-Huffman process) were observed.
Transglutaminase reactions associated with the rat semen clotting system: Modulation by macromolecular polyanions

Abstract The coagulation of rodent semen after ejaculation involves the establishment of ϵ-(γ-glutamyl)lysyl cross linkages between seminal vesicle secretion proteins as catalyzed by Ca ++ -dependent transglutaminases secreted by the coagulating (anterior prostate) gland. During enzymic clotting of rat vesicular secretion proteins, low molecular weight amines such as putrescine are incorporated into covalent linkage with proteins of both the coagulum and the clot liquor. Bulbourethral gland secretions and certain macromolecular polyanions (notably poly-L-glutamate) enhance the enzymic coagulation of rat vesicular secretion proteins and putrescine incorporation therein. The stimulatory macromolecular polyanions appear to exert their effects by facilitating the ability of vesicular secretion proteins to serve as transglutaminase amine acceptor substrates.
The Influence of Habitat Structure On a Nolis Foraging Behavior

1. A series of seven species of Anolis lizards was studied at two sites in southwest Haiti (Ducis, 350 m, and Les Platons, 750 m). Data consisted primarily of continuous observations of individuals. 2. Species differed in their structural microhabitats by the heights and diameters of their perches. Species occupying larger perches and perches higher above the ground tended to confine their movements to a perch surface rather than jumping between surfaces. 3. A series of six "foraging zones" was recognized. These were specific configurations of surfaces which were believed to influence the scanning and movement patterns of hunting lizards. 4. Comparisons of the distributions of distances between scanning locations and waiting times between moves for all species showed patterns consistent with the size and complexity of the area scanned. 5. Differences in orientation in space and with respect to the perch surface were consistent with predicted movement and scanning patterns of particular foraging zones. 6. Plots of waiting time versus distance moved were used to distinguish species with different search strategies but similar rates of progression through the habitat. 7. A stylized diagram of foraging zones as they are connected in a typical habitat was used to compare the niche breadths of the seven species. Species which used a wider array of foraging zones were most widely distributed in southwest Haiti. 8. Although all the species could be classed as sit-and-wait predators, the various analyses revealed consistent site-specific foraging patterns which can be functionally related to the structural configuration of foraging zones. 9. It is suggested that optimal choice of patch types (structural microhabitats) is influenced by the locomotion costs associated with hunting in each patch type. Selection should act to enhance adaptation for site-specific foraging which will reinforce the predictions of the niche compression hypothesis.
Fabrication and characterization of THUNDER actuators—pre-stress-induced nonlinearity in the actuation response

This paper documents an experimental and theoretical investigation into characterizing the mechanical configurations and performances of THUNDER actuators, a type of piezoelectric actuator known for their large actuation displacements, through fabrication, measurements and finite element analysis. Five groups of such actuators with different dimensions were fabricated using identical fabrication parameters. The as-fabricated arched configurations, resulting from the thermo-mechanical mismatch among the constituent layers, and their actuation performances were characterized using an experimental set-up based on a laser displacement sensor and through numerical simulations with ANSYS, a widely used commercial software program for finite element analysis. This investigation shows that the presence of large residual stresses within the piezoelectric ceramic layer, built up during the fabrication process, leads to significant nonlinear electromechanical coupling in the actuator response to the driving electric voltage, and it is this nonlinear coupling that is responsible for the large actuation displacements. Furthermore, the severity of the residual stresses, and thus the nonlinearity, increases with increasing substrate/piezoelectric thickness ratio and, to a lesser extent, with decreasing in-plane dimensions of the piezoelectric layer.
Mass transfer with chemical reaction from spherical one or two component bubbles or drops

Abstract Unsteady state mass transfer between a one or two component bubble (or drop) and the continuous phase with a chemical reaction occuring either in the continuous or in the dispersed phase is examined. The main assumption for binary bubbles is that the rate determining step is diffusion in the continuous phase. Two limiting velocity fields. Hadamard flow ( Re ⪡:1) and potential flow ( Re ⪡:1) are used in the calculations. For the single component bubble the solution obtained previously by Ruckenstein for mass transfer without chemical reaction is generalized to include chemical reaction by using Danckwerts' transformation and the Duhamel theorem and relatively simple analytical expressions are deduced for transient and steady state average Sherwood numbers. For binary bubbles the concentration of the continuous phase depends on the dispersed phase concentration which is a function of time. Consequently the same procedure used for the single component case, together with a material balance on the bubble, generates an integral equations which is solved by an iterative technique for the concentration inside the bubble. To determine the accuracy of simplified models of the type suggested by Higbie an extended penetration model is proposed and used for the situation in which a chemical reaction occurs in the continuous phase. The results of the simplified model are compared with the exact solutions for one and two component systems, and the range of parameters for which it is accurate is determined. The accuracy of the quasi-steady state assumption, based on the steady state equations for the mass transfer coefficient and on an unsteady mass balance for the bubble, is also examined and it is shown that this assumption may introduce significant errors under certain conditions. Criteria giving the conditions under which the quasi-steady state assumption may be used are established.
Abstract IA18: Early but promising data: PD-1 inhibitors in non-small cell lung cancer.

Blockade of the programmed death (PD-1) checkpoint has emerged as a promising approach for immunotherapies in the treatment of non-small cell lung cancer (NSCLC). Immune checkpoints, such as PD-1, an inhibitory T-cell immunoreceptor, and the receptor9s ligands, PD-L1 and PD-L2, assist in hindering autoimmunity and protecting peripheral tissues to minimize damage (1). However, in cancers, the interaction between PD-1 and its ligands also can result in the promotion of an immunosuppressive tumor microenvironment (1). Several agents targeting PD-1 are currently undergoing clinical development. Clinical trials of anti-PD-1 antibodies nivolumab (BMS-936558) and MK-3475 have produced encouraging results in non-small cell lung cancer patients with regards to objective response rates (ORR) and progression free survival (PFS) (2,3). In a pretreated advanced NSCLC population, nivolumab produced durable responses, particularly at 3 and 10 mg/kg doses (2). For 38 previously-treated NSCLC patients, MK-3475, administered at 10 mg/kg every three weeks, led to an ORR of 24 percent based on irRC (21 percent based on RECIST 1.1) (3). Median overall survival was 51 weeks with a PFS, which had not been reached at a time when the minimum PFS would be 62 weeks among the responders (3). ORR was 67% in patients with tumors having PD-L1 expression above a cutpoint versus 4% in those below the cutpoint (3). Based on the favorable response rates relative to historical controls, and the durability of responses in clinical trials, the development of PD-1 inhibitors in lung cancer is proceeding rapidly. Future trials utilizing anti PD-1 antibodies will explore further biomarkers, and combination with other therapies. Citation Format: Edward B. Garon, Brian R. Wolf, Deborah JL Wong, Jonathan W. Goldman. Early but promising data: PD-1 inhibitors in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA18.
Behaviour of inverted propane-hydrogen sulphide flames at the blow-off limits

Abstract Blow-off studies with inverted propane-hydrogen sulphide flames show that at the lean limit propane appears to contribute its proportionate share to the stability of the mixed fuel, whereas the burning of hydrogen sulphide is inhibited in the presence of propane. At rich blow-off, hydrogen sulphide appears to inhibit the burning of propane in all mixtures, and when the fuel mixture contains more than 50 volume per cent hydrogen sulphide the component fuels are mutually inhibiting.
The Malthus-Godwin debate, then and now

The famous opposition between Malthus and Godwin began early in their respective careers and has continued not only throughout their lives but, in the words of their supporters, still today. This seemingly forthright statement represents several paradoxes. Starting from quite divergent views of man and society, both moved much closer to what can be taken to be the ethical and political norm of their time; but as they approached agreement on fundamentals, their debate became more vituperative. From our point of view, their similarities are often more significant than their differences, for both represented variations on a common theme of Benthamite liberalism. To continue the debate in 19th-century terms is inappropriate, especially since in many recent analyses the views of both men are distorted. By our measures of politics, Godwin was more often the reactionary, Malthus more often the progressive.
Quantitative Analysis of the EEG - General Concepts and Animal Studies

Quantification of the EEG using digital computers is based on complex subjective processes of data reduction and feature extraction. In this paper, the signal characteristics of the EEG are identifred and major developments in the field of computerized electroencephalography (such as spectral analysis, compressed spectral arrays, etc.) are surveyed. Particular attention is given to signal analysis techniques used to characterize 1) background (stationary) EEG activity, and 2) interrelated multichannel EEG activity. The fast Fourier transform (FFT) has dominated approaches used to study background activity while cross-spectrum and coherence analysis have extended frequency or spectrum analysis into frequency-limited relationships between channels. In the realm of applications, the use of the digital computer-analyzed EEG to quantify 1) vigilance state dependent EEG changes, 2) the central effect of pharmacological agents, and 3) the normal ontogeny of the cortical and hippocampal EEG is described.
A non-negative Wigner-type distribution☆

Abstract The Wigner function, which is commonly used as a joint distribution for non-commuting observables, is shown to be non-negative in all quantum states when smoothed with a gaussian whose variances are greater than or equal to those of the minimum uncertainty wave packet.
Charge and Energy Information from Heavy Ion Tracks in ‘Lexan’

ENERGETIC heavy ions (Z≳6, E>10 MeV/a.m.u.) can be identified with high resolution by measurements of etched tracks in ‘Lexan’ and other plastic detectors1. Much of our knowledge of trans-iron nuclei in the cosmic radiation has come from studies of etched plastics2 and important advances are being made in our understanding of energetic solar particles with plastic detectors3,4. Here we describe a new technique that permits heavy ions of extremely low energy to be identified, thus extending the scope of plastic particle identifiers to include nuclear chemistry as well as making possible the study of low energy interplanetary particles.
The collision of heritage and economy at Uxbenká, Belize

The relationship between the Mopan Maya community of Santa Cruz and the Classic period Maya site of Uxbenka in southern Belize has had a lasting impact on archaeological investigation and conservation at the site over the last generation. Community members, long the ‘stewards’ of Uxbenka, believe they have an economic right to the ruins that translates loosely into ‘ownership’. Although they seek to maintain the relationship between Santa Cruz and Uxbenka, archaeologists with the Uxbenka Archaeological Project (UAP) challenge the legitimacy of the community’s claim via the power vested in them by the state to conduct scholarly investigations at the site. For both the UAP and the state‐affiliated Institute of Archaeology, Uxbenka belongs not to one village but to all Belizeans. This paper is a data‐driven analysis of the interactions and expectations of community members, archaeologists, and the state as they interact within the archaeoscape of Uxbenka.
Traumatic brain injury-induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis.

Proper CNS function depends on concerted expression of thousands of genes in a controlled and timely manner. Traumatic brain injury (TBI) in mammals results in neuronal death and neurological dysfunction, which might be mediated by altered expression of several genes. By employing a CNS-specific GeneChip and real-time polymerase chain reaction (PCR), the present study analyzed the gene expression changes in adult rat cerebral cortex in the first 24 hr after a controlled cortical impact injury. Many functional families of genes not previously implicated in TBI-induced brain damage are altered in the injured cortex. These include up-regulated transcription factors (SOCS-3, JAK-2, STAT-3, CREM, IRF-1, SMN, silencer factor-B, ANIA-3, ANIA-4, and HES-1) and signal transduction pathways (cpg21, Narp, and CRBP) and down-regulated transmitter release mechanisms (CITRON, synaptojanin II, ras-related rab3, neurexin-1, and SNAP25A and -B), kinases (IP-3-kinase, Pak1, Ca 2 / CaM-dependent protein kinases), and ion channels (K channels TWIK, RK5, X62839, and Na channel I). In addition, several genes previously shown to play a role in TBI pathophysiology, including proinflammatory genes, proapoptotic genes, heat shock proteins, immediate early genes, neuropeptides, and glutamate receptor subunits, were also observed to be altered in the injured cortex. Real-time PCR analysis confirmed the GeneChip data for many of these transcripts. The novel physiologically relevant gene expression changes observed here might explain some of the molecular mechanisms of TBI-induced neuronal damage. © 2002 Wiley-Liss, Inc.
The Neural Correlates of Consciousness An Update

This review examines recent advances in the study of brain correlates of consciousness. First, we briefly discuss some useful distinctions between consciousness and other brain functions. We then examine what has been learned by studying global changes in the level of consciousness, such as sleep, anesthesia, and seizures. Next we consider some of the most common paradigms used to study the neural correlates for specific conscious percepts and examine what recent findings say about the role of different brain regions in giving rise to consciousness for that percept. Then we discuss dynamic aspects of neural activity, such as sustained versus phasic activity, feedforward versus reentrant activity, and the role of neural synchronization. Finally, we briefly consider how a theoretical analysis of the fundamental properties of consciousness can usefully complement neurobiological studies.
Anticomplementary activity in unaggregated ‘purified’ macroglobulin paraprotiens

Abstract Deficiencies in whole serum complement (C) activity as well as that of individual components studied (c1, C2, C3) have been found in the sera of several patients with Waldenstroms Macroglobulinemia. To test whether such deficiencies were related to anticomplementary activity of the IgM paraprotiens, macroglobulins were purified from the sera of 11 patients macroglobulinemia. Although, the paraproteins were pure by imunnoprecipitin techniques, trace contaminants, containing anticomplementary activity, were found. Such anticomplementary activity was isolated in the 7S region sucrose density gradients ultracentrifugation. Both Cl hemolytic activity and the ability to fix partially purified guinea pig C2 was present in the anticomplementary material. The anticomplementary activity was completely blocked by the C1 esterase inhibitor. This indicated that the anticomplementary activity was due to C1S, either alone or complexed with C1R. If marked differences in complement binding affinities were present among different subclasses of macroglobulin paraproteins, such an effect might have been manifested by differences in the anticomplementary activity of such paraprotiens. However, the unaggregated IgM paraprotiens could not be separated into subclasses according to their quantitative anticomplementary activity.
Rebalancing Quality Education in a Democratic Society

The integrity of democracy and quality education in the United States has been jeopardized by a market-based school reform agenda. The last twenty years of federal policy and legislation has resulted in privatizing public education, vilifying the voices of teachers and narrowing the curriculum to easily quantified skills in reading and math. The curriculum taught in U.S. public schools has been reduced to corporate terms of achievement and measurement. Within this paper, I explored the question, “What does quality education look like in a democracy?” A critique of recent educational reforms in the United States and influential international benchmarks are presented, and a curricular scope for quality education is proposed incorporating the missing democratic fundamentals. This paper hopes to encourage a global dialogue among policy makers, educators and other stakeholders who value a quality public education and see it as necessary to pursue a democratic vision.
Systolic opportunities for multidimensional data streams

Portable image processing applications require an efficient, scalable platform with localized computing regions. This paper presents a new class of area I/O systolic architecture to exploit the physical data locality of planar data streams by processing data where it falls. A synthesis technique using dependence graphs, data partitioning, and computation mapping is developed to handle planar data streams and to systematically design arrays with area I/O. Simulation results show that the use of area I/O provides a 16 times speedup over systems with perimeter I/O. Performance comparisons for a set of signal processing algorithms show that systolic arrays that consider planar data streams in the design process are up to three times faster than traditional arrays.
Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression.

Abstract Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: COX-1 encoded by a 2.8-kb mRNA, and a mitogen-inducible COX-2 encoded by a 4-kb mRNA. We have cloned the COX-1 and COX-2 cDNAs from the cDNA library constructed from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages. The deduced amino acid sequence showed that COX- I contained 602 amino acids, whereas COX-2 contained 604 amino acids. There is 95% conservation of the nucleotide sequence in the open reading frame of COX-1 between the rat and the mouse, while the homology of the 3′ untranslated region is 68% except for a 150 bp segment adjacent to the stop codon which is nonhomologous with the mouse. Transfection of both COX cDNAs into Cos-7 cells resulted in increased COX activity. In rat vascular smooth muscle cells, interleukin-1β selectively increased the expression of COX-2, but not that of COX-1, as assessed by enzyme activity, immunoprecipitation of COX proteins, and mRNA analysis. Only the brain among tissues tested exhibits basal expression of COX-2 as the major form of the enzyme. However, COX-2 mRNA was expressed in vivo in the lung and kidney, but not in the heart, after systemic administration of LPS, suggesting that COX-2 but not COX-1 plays a major role in producing COX-derived products of arachidonic acid during endotoxic shock. Thus, the two COX isoforms were differentially expressed, and COX-2 was selectively induced in response to inflammatory stimuli in rats.
Quantization as analysis in partial differential varieties

Replacing positive-energy considerations by considerations of invariance under theS-operator, and applying Paneitz' extension of the stability theory of the school of M. G. Krein, a long-sought canonical positive symplectic complex structure in the stable phase space of infinite-dimensional classical field-theoretic systems can be mathematically determined. This almost-Kahlerization of the phase space then yields a (positive-definite) infinite-dimensional Riemannian structure that serves to specify formally, and convergently in finite-mode approximation, the physical vacuum measure for functional integrals involved in the associated quantized field. The method applies to a general class of nonlinear wave equations including that of Yang-Mills.