cssi/SciSciGPT-SciSciNet huggingface dataset:
Progress in analgesic development: How to assess its real merits?

BACKGROUND Assessing analgesic drugs developed over preceding 50 years demonstrated that very intensive efforts directed at diverse molecular pain targets produced thousands of PubMed articles and the introduction of more than 50 new analgesics. Nevertheless, these analgesics did not have a sufficiently broad spectrum of action and level of effectiveness to demonstrably affect the use of opioids or nonsteroidal anti-inflammatory drugs for the treatment of pain. Analgesics in current are only modestly effective in chronic pain (at least with respect to neuropathic pain), and the widespread application of mu opioid receptor agonists for this purpose culminated in the global "opioid crisis". The introduction of every new drug is regarded as an important success, at least initially. Assessing the merit of a new analgesic is extremely complicated. OBJECTIVE The aim of this article is to describe an approach that combines very different categories of drug evaluation - multifactorial approach to assessment of new analgesics. It is based on conclusiveness of clinical trials, novelty of a drug's molecular target, a drug's commercial appeal, and the interest in a drug reflected by scientometric indices. RESULTS This approach was applied to analgesics developed in 1982-2016. It shows that although several new agents have completely novel mechanisms of action, all newly approved drugs, and drug candidates, demonstrated the same persistent problems: relatively low therapeutic advantage over previous treatment and narrow spectrum of use in different types of pain, compared to opioids or NSAIDs. CONCLUSION The use of the suggested multifactorial approach to drug assessment may provide a better view of the whole spectrum of analgesics advantages and disadvantages.
Dimethyl Fumarate (DF) Suppresses GMCSF-producing Th1 cells in EAE and human CD4 T cells. (P2.2-071)

Objective: Dimethyl Fumarate(DF) acts directly on CD4 T cells and suppresses GMCSF producing Th1 cells in EAE and human PBMCs. Background: DF is an oral therapy for multiple sclerosis. DF treatment decreases the relapse rate and development of new, active brain lesions in patients, which suggests immuno-regulatory mechanism in inflammation besides its neuroprotective effects. However, DF induces IL-10 producing type II DCs, its direct role of DF on T cells is still unknown. Design/Methods: We collected splenocytes from C57BL/6 wild-type (WT) mice, and purified CD4 cells by milteny biotech microbeads. Cells were cultured with Anti CD3/CD28 in the presence/absence of DF. IFNg, IL-17 and GMCSF were measured by ELISA. Cells were analyzed by flow-cytometry. WT mice were immunized with MOG35–55 for EAE induction and treated with oral DF or vehicle daily. For experiments on human PBMCs, venous blood were collected from nine normal individuals and PBMCs were collected by percol gradient method, cultured and treated with DF/vehicle with Anti CD3/CD28 Ab for 5 days. Results: DF treatment reduced GMCSF and IFNg but not IL-17 in the supernatant of CD4 cells. DF significantly reduced GMCSF+/ IFNg +/CD4 T cells. In In-vivo experiments, DF subsides clinical EAE. Splenocytes from treated mice produced a smaller amount of GMCSF (430 vs 100 pg) and IFNg (820 vs 250pg) compared to control in culture. In addition, the number of infiltrating GMCSF+/Th1 cells in the CNS of control mice was four times more than treated mice. Furthermore, Inhuman PBMCs culture, DF decreased IFNg (3000 vs 870 pg), measured by ELISA, in the supernatant, and FACS analysis demonstrated 56% reduction of GMCSF+/ Th1 cells in DF-treated cells. Conclusions: DF acts directly on CD4 T cells and suppresses GMCSF production in Th1 cells. Above findings expand our understanding about direct immuno-regulatory mechanism of DF in CD4 T cells leading to reduction of immuno-pathogenicity of these cells. Disclosure: Dr. Safavi has nothing to disclose. Dr. Li has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Rostami has nothing to disclose.
A Database Analysis of Pediatric Tibia Fracture Surgical Fixation Rates Between 2000-2012

Background: Pediatric tibial shaft fractures are a common orthopedic injury. Traditionally, the majority of these injuries have been treated with closed management. There has been a trend in the literature, however, towards operative management without commensurate studies analyzing the overall frequency of operative fixation for pediatric tibial shaft fractures in the United States. The purpose of this study …
Corrective Osteotomy—Metacarpal

Arthroplasty has not been refined sufficiently to achieve a predictably good result in the distal interphalangeal joint of the fingers. Furthermore, distal interphalangeal motion plays a relatively small role in the overall function of a reconstructed hand. Arthrodesis has been predictable and effective for salvaging those situations with instability, destruction, or deformity of the distal interphalangeal joint (Figs. 54-1 A Figs. 54-1 B Figs. 54-1 C Figs. 54-1 D-E).
Structure studies on human serum gamma-globulins and myeloma proteins. 3. Oxidative sulfitolysis of myeloma globulins and reconstitution of the macromolecules.

Abstract Individual specimens of myeloma globulins were cleaved by sulfite and cuprammonium ion, and the fragments were separated by gel filtration in acetic acid. Molecular weight determination indicated that both the H and L chains, after separation, recovery, and redissolution in a weakly alkaline solvent, appeared as dimers. When the cleaved globulins were treated with mercaptoethanol, the disulfide bonds were reformed. The reconstituted globulins appeared similar to the original native material in molecular weight and immunodiffusion tests. Slight differences were found in the optical rotatory dispersion behavior of the native and the reconstituted globulins. Individual specimens of the globulins differed among themselves and from normal γ-globulin with respect to the H L ratio, quantity of free N-terminal amino acids, and ease of reconstitution; but their chain conformations were similar. Significant differences were found in amino acid composition and peptide patterns between the H and L chains, and between individual L chains. The L chains showed similarity to Bence-Jones proteins in redissolving on boiling, conformation, immunodiffusion, and electrophoretic mobility in gels.
HAIR ANALYSIS FOR DRUGS OF ABUSE

Hair analysis for drugs of abuse by radioimmunoassay and gas chromatography/mass spectrometry (GC/MS) is an effective means for identifying drug abusers. Hair can be collected under close supervision without embarrassment and is not subject to evasive maneuvers (false negatives) such as temporary abstention, excessive fluid intake, and substitution or adulteration of specimens. Hair analysis has a wide window of detection ranging from months to years and provides information concerning the severity and pattern of an individual's drug use. Hair analysis is also not subject to evidential false positives, such as those caused by poppy seed ingestion, spiking of drinks or food, and mix-up or contamination of specimens. In part, these problems can be avoided because hair analysis can always be repeated with a newly collected specimen. The results of animal experiments and of various clinical, forensic, and criminal justice applications are described.
Formation of molecules and dust

The theory of formation of various molecules, both on surfaces of interstellar dust-grains and in gas-phase reactions, is reviewed. Destruction of molecules, the special problems of very dark clouds and the life-history of dust-grains are also reviewed briefly.
Improving Decisions Using Nontraditional, Nonfinancial Accounting Information: Evaluation Mode Considerations When Benchmark Data Give Unclear Signals

How are decisions influenced by the presentation of nontraditional and nonfinancial accounting information, such as environmental measurements, when benchmark data provide vague signals for analysis? Generally, alternatives are analyzed either jointly (called joint evaluation mode, or JE) or separately (SE). Prior research suggests more focus on difficult-to-evaluate data, such as unfamiliar accounting information, in JE than SE (Hsee, 1996). Also, analyses involving benchmark data showing all alternatives performing better than a benchmark (a vague signal) receive higher evaluations in SE, yet higher evaluations in JE occur when all alternatives perform worse than benchmarks (Hsee & Leclerc, 1998). Two reported experiments use a 2X2 mixed factorial design; evaluation mode was manipulated as a between-subjects variable, i.e., either JE or SE, while benchmark data indicating alternatives’ performances were manipulated as a within-subjects variable, i.e., better or worse performance than the benchmarks. In Study 1 (n = 80), participants evaluated two equally weighted environmental accounting metrics with benchmark data for two factories and indicated how much they would invest in each based on success in achieving environmental objectives; one factory outperformed the other. Results indicate higher investment levels as well as more desirable investments in JE than SE when the benchmark data indicate worse-than-average alternatives (but not better-than-average alternatives). Study 2 (n = 53) was similar to Study 1, except 1) benchmark data were available for only one of the two metrics, and 2) the two factories were equally attractive. Investment levels were higher in JE than SE mode when alternatives performed worse than average (but not better-than-average alternatives). These results showcase cognitive consequences to evaluating nontraditional, nonfinancial accounting information in different evaluation modes. This awareness should inform designers of information systems, particularly those designing systems with environmental accounting attributes.
TSC_ATP: A two-stage classifier for predicting protein-ATP binding sites from protein sequence

It is well known that adenine triphosphate (ATP) binds with proteins to play important roles in metabolism, cell signaling, and as cofactor. Therefore it is crucial to identify ATP-binding sites on proteins to understand these mechanisms. In this paper, we present a computational method that can accurately predict ATP-binding sites on proteins using sequence-derived information. The algorithm is organized in a two-layered structure. The method first makes prediction by a K-Nearest Neighbors (K-NN) method using evolutionary profile information of each residue. The output of the first-layer classifier serves as an input feature together with other 11 features to a second-layer classifier. The final method achieved an AUC (area under the ROC curve) of 0.829 and 0.860 respectively on two benchmark datasets.
Protecting internal state variables from subclasses

The use of child packages to encapsulate derived tagged types and their operations should protect the state variables of the parent type that are to be manipulated by the parent operations alone. This protection can be achieved through the declaration of a data component of a limited record type, previously declared with no attributes and an access type discriminant that visibly points to an incomplete definition. The details of the data component (either scalar or composite, depending on application), whose full type declaration is in the parent package body, is accessible only through the discriminant from within the package body. This mechanism provides full information hiding of the details and maximum protection of the contents of those instance variables.
Embryonic wound healing by apical contraction and ingression in Xenopus laevis.

We have characterized excisional wounds in the animal cap of early embryos of the frog Xenopus laevis and found that these wounds close accompanied by three distinct processes: (1) the assembly of an actin purse-string in the epithelial cells at the wound margin, (2) contraction and ingression of exposed deep cells, and (3) protrusive activity of epithelial cells at the margin. Microsurgical manipulation allowing fine control over the area and depth of the wound combined with videomicroscopy and confocal analysis enabled us to describe the kinematics and challenge the mechanics of the closing wound. Full closure typically occurs only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in contrast, when deep cells are removed along with the superficial, epithelial cell-layer of the ectoderm, wounds do not close. Actin localizes to the superficial epithelial cell-layer at the wound margin immediately after wounding and forms a contiguous “purse-string” in those cells within 15 min. However, manipulation and closure kinematics of shaped wounds and microsurgical cuts made through the purse-string rule out a major force-generating role for the purse-string. Further analysis of the cell behaviors within the wound show that deep, mesenchymal cells contract their apical surfaces and ingress from the exposed surface. High resolution time-lapse sequences of cells at the leading edge of the wound show that these cells undergo protrusive activity only during the final phases of wound closure as the ectoderm reseals. We propose that assembly of the actin purse-string works to organize and maintain the epithelial sheet at the wound margin, that contraction and ingression of deep cells pulls the wound margins together, and that protrusive activity of epithelial cells at the wound margin reseals the ectoderm and re-establishes tissue integrity during wound healing in the Xenopus embryonic ectoderm. Cell Motil. Cytoskeleton 53:163–176, 2002. © 2002 Wiley-Liss, Inc.
Contraceptive security: incomplete without long-acting and permanent methods of family planning.

This commentary reviews the importance of long-acting and permanent methods (LA/PMs) and considers why they are neglected in many national contraceptive security strategies and family planning programs. It also proposes recommendations for broadening method choice to include LA/PMs more fully and thereby increasing the ability of women and men to achieve their reproductive intentions.
Preparation and evaluation of new bifunctional chelating agents: a preliminary report.

Abstract A scheme has been designed to synthesize a homologous series of new bifunctional chelating agents (BFCAs), which may increase the thermodynamic stability of metal chelates and conjugate at the specific sites on the monoclonal antibody molecule (MoAb) permitting us to analyze the structure-activity relationships of the series of compounds. Four such compounds have been prepared and chacterized by FT-i.r. and NMR spectroscopy. One of them has been used to label an antibody with 111 In, the stability and distribution of which has been examined in tumor-bearing mice and compared to that of the 111 In-MoAb prepared using cyclic anhydride of DTPA. Enhanced tumor/blood ratios (9 vs 6.5), tumour to muscle ratios (7 vs 3), and decreased liver uptake (4 vs 12%) have been obtained.
Search for sub-TeV gamma rays in coincidence with gamma ray bursts

Project GRAND is a 100m x 100m air shower array of proportional wire chambers (PWCs). There are 64 stations each with eight 1.29 m^2 PWC planes arranged in four orthogonal pairs placed vertically above one another to geometrically measure the angles of charged secondaries. A steel plate above the bottom pair of PWCs differentiates muons (which pass undeflected through the steel) from non-penetrating particles. FLUKA Monte Carlo studies show that a TeV gamma ray striking the atmosphere at normal incidence produces 0.23 muons which reach ground level where their angles and identities are measured. Thus, paradoxically, secondary muons are used as a signature for gamma ray primaries. The data are examined for possible angular and time coincidences with eight gamma ray bursts (GRBs) detected by BATSE. Seven of the GRBs were selected because of their good acceptance by GRAND and high BATSE Fluence. The eighth GRB was added due to its possible coincident detection by Milagrito. For each of the eight candidate GRBs, the number of excess counts during the BATSE T90 time interval and within plus or minus five degrees of BATSE's direction was obtained. The highest statistical significance reported in this paper (2.7 sigma) is for the event that was predicted to be the most likely to be observed (GRB 971110).
Growth Factor Regulation of Neuronal Development

Recent experimental investigations have redefined the spectrum of growth factors and developmental signalling pathways that are necessary to orchestrate the growth and differentiation of regional neuronal subpopulations. Gene knockout studies of the classic neurotrophins and their high-affinity tyrosine kinase (Trk) receptors have refined our definition of the cellular mechanisms and target populations of these neuronotrophic factors. Recognition of the significant parallels that exist between neuropoiesis and hematolymphopoiesis has fostered our study of the range and cellular actions of these hemopoietins in neuronal development. In addition, by activating receptor subunits that possess serine/threonine activity, bone morphogenetic proteins of the transforming growth factor-beta superfamily exhibit complex spatiotemporal regulation of regional neuronal subpopulations. These collective observations suggest that a complex hierarchy of epigenetic signals is required for the growth and maturation of regional neuronal lineage species in the central and peripheral mammalian nervous system.
Modeling studies of impacts from the Guinea Highlands in relation to tropical cyclogenesis along the West African coast

Numerical simulations of three separate events of tropical cyclogenesis (TC-genesis) off the West African coast between the years of 2006 and 2008 were performed. The purpose of this study was to investigate the processes that take place during the transition of an African easterly wave (AEW) and any associated mesoscale convective systems (MCSs) as they progress from continental West Africa into the maritime environment of the eastern Atlantic Ocean. Three tropical cyclones that were associated with AEWs and related MCSs over continental West Africa that progressed off the coast, later achieving at least tropical storm (TS) strength, were selected to be investigated. The three tropical cyclones were: TS Debby (2006), Hurricane Helene (2006), and TS Josephine (2008). The Weather Research and Forecasting (WRF) model was utilized to conduct numerical model simulations beginning 72 h prior to each system’s AEW being classified as a tropical depression (TD). Results demonstrated that the model was able to recapture the evolution of each MCS in association with AEWs during all three events. The sensitivity experiments of the impact of topography (i.e., Guinea Highlands) suggested that the elevation of the Guinea Highlands plays a significant role in relation to TC-genesis, even though the highest peaks of the Guinea Highlands are only approximately 1,300 m. Simulation results supported that topographical blocking and northwest deflection of strong southwest winds from the Atlantic played an important role in the enhancement of low-level cyclonic circulation. Without the presence of the Highlands, wind speeds associated with each circulation by simulation’s end were either weaker or the simulation failed to generate a circulation completely. As the MCSs developed along the coast, they became phaselocked in the downstream flow of an AEW as it exited the West African coast. The MCS in each event acted as a catalyst for TC-genesis with the associated AEW. Without the Guinea Highlands, the MCS features were either weakened or failed to develop, thus hindering TC-genesis for these three cases.
Using a sales incentive technique in a first course in software engineering

The best structure for a first course in software engineering is unclear. First, because what should be taught has not been firmly established to the general satisfaction of those involved. Second, providing a realistic environment to motivate belief in the utility of the practices involved is difficult.A strategy which provides the motivation to understand and develop the tools of software engineering is presented. The strategy also effectively requires a form of peer review. The motivating mechanism is the “sale” of software modules between class participants.
Discrepant Affinities in Caribbean Poetry: Tradition and Demotic Modernism

To properly situate the contributions of Lee Jenkins's The Language of Caribbean Poetry: Boundaries of Expression, one must first turn an eye onto three earlier books in the field of Caribbean studies. These books recognize a commonality in poetry across the region but give different accounts as to what it is based upon, and how it might be specified. J. Edward Chamberlin's Come Back to Me My Language (1993) places Caribbean verbal art within the history of black slavery and its colonial aftermath; his is a comprehensive effort to demonstrate the achievement of the poetry, as it shapes and participates in a social movement out of "four hundred years of colonial conditioning" toward the "spirit of liberation and independence."' This movement fundamentally involves a struggle with language to win possession of it from colonial dictates-a decolonization of English that links Caribbean poetry to that of other parts of the Anglophone world such as, conspicuously, Ireland and Australia. Following up on Chamberlin's thunderclap, Laurence Breiner submitted a more systematic study of the ideas that shaped literary culture in the West Indies through the early 1990s: An Introduction to West Indian Poetry (1998) provides a
Seeking more than health: Using medicine for enhancement

The purpose of this essay is to examine some of the ethical concerns raised regarding the use of neuroenhancers. Authors such as Fukuyama and Sandel argue that medical intervention should be limited to treatment of disease, and that enhancement should be outside of the scope of medicine. This commentary will examine the distinction between treatment and enhancement. I shall conclude that it is not a well-drawn distinction and should not be used to provide guidance with regards to the use of psychopharmacological agents for the purpose of cognitive enhancement. I shall further examine whether concepts such as disability and normality could provide a criterion for determining whether enhancement is a permissible use of medical intervention. I conclude that as those concepts are contextually defined, they cannot be used to make principled arguments against enhancement. Finally, I shall review the charge that medicalization of cognitive performance enhancers is not morally permissible. I shall argue that medicalization might have both negative and positive consequences, and decisions about the moral permissibility of medicalization should be made on a case-by-case basis. [Projekat Ministarstva nauke Republike Srbije, br. 41004: Retke bolesti: molekularna patofiziologija, dijagnosticki i terapijski modaliteti i socijalni, eticki i pravni aspekti, potprojekat Instituta za filozofiju i drustvenu teoriju Univerziteta u Beogradu: Bioeticki aspekti: moralno prihvatljivo u biotehnoloski i drustveno mogucem]
Adenylyl cyclase gene transfer in heart failure.

The rationale for gene transfer of adenylyl cyclase type VI (AC VI ) for clinical congestive heart failure (CHF) is based on recent experimental studies that have extended from cultured cardiac myocytes to preclinical studies in animal models of CHF. Over the past several years substantial data have indicated an unexpected and pronounced favorable effect of AC VI expression in cardiovascular disease. Preclinical studies have shown that increased cardiac AC content improves left ventricular function and attenuates deleterious remodeling in the failing heart, and reduces mortality in heart failure and in acute myocardial infarction. A brief review of the preclinical studies that have examined changes associated with increased AC expression in the heart is presented here.
Sleeping patterns in female guinea pigs; effects of sex hormones.

Abstract Daily cortical and subcortical EEG records of 8 hours duration were taken from ovariectomized guinea pigs with and without exogenous sex steroids. The individual episodes of EEG arousal, slow wave sleep, and paradoxical sleep were recorded and analyzed statistically to determine the sleeping patterns. Paradoxical sleep was characterized by a pronounced hippocampal theta rhythm (6–9 cycle/sec) accompanied by low amplitude cortical records and the behavioral manifestations of sleep. Most of the paradoxical sleep episodes lasted less than 3 min and were always preceded by a period of slow wave sleep variable in length. Each hour of recording contained approximately one and one-half paradoxical sleep episodes occupying about 4% of the total time and 10–12% of the total sleeping time. Hormone-induced estrous behavior was accompanied by a significant reduction in the amounts of both paradoxical and slow wave sleep. On the day of estrus, each hour of recording averaged less than one paradoxical sleep episode and paradoxical sleep time occupied only 2.3% of the total time and 6.7% of the sleeping time.
Electronic Transport in Alloys: Coherent-Potential Approximation

The coherent-potential approximation, which has been successfully used to describe the electronic structure of a nondilute binary alloy ${A}_{x}{B}_{1\ensuremath{-}x}$, is reformulated in a diagrammatic way suitable for the calculation of more complicated transport coefficients. This approach is applied to the calculation of three elementary transport coefficients: the conductivity $\ensuremath{\sigma}$, the thermoelectric power $Q$, and the low-field Hall coefficient ${R}_{H}$. The appropriate response functions are evaluated for a simple cubic tight-binding model. The rigid-band limit is considered in detail, with emphasis on the role of critical points. As the random alloy potential increases, deviations from rigid-band behavior --- for example, Nordheim's rule --- become more pronounced for unexpectedly small scattering strengths. However, the usual relations among the transport coefficients, e.g., Mott's equation between $Q$ and $\ensuremath{\sigma}$, are maintained. The conductivity is no longer symmetrical with respect to electron and hole concentrations. Furthermore, the change in sign of $Q$ and ${R}_{H}$ may not occur when the band is half-full. Therefore, the identification of the carrier sign becomes ambiguous. For the model treated, numerical calculations are quite tractable. Examples are given which illustrate the behavior for a wide range of alloy parameters.
Deploying comb and tunable lasers to enable precision radial velocity surveys

We describe recent progress toward developing optical frequency laser combs and tunable laser to the problem of more precise calibration of high dispersion astronomical spectra, thus permitting radial velocity determinations in the few cm/sec regime. We describe two programs in progress to calibrate both a cross dispersed echelle spectrograph with a laser comb and to calibrate a multiobject echelle spectrograph with a tunable laser.
Direct Analysis of Water Content and Movement in Single Dormant Bacterial Spores Using Confocal Raman Microspectroscopy and Raman Imaging

Heavy water (D2O) has a distinct molecular vibration spectrum, and this has been used to analyze the water content, distribution, and movement in single dormant Bacillus cereus spores using confocal Raman microspectroscopy and Raman imaging. These methods have been used to measure the kinetics of D2O release from spores suspended in H2O, the spatial distribution of D2O in spores, and the kinetics of D2O release from spores during dehydration in air at room temperature. The results obtained were as follows. (1) The Raman spectrum of single D2O-loaded dormant spores suggests that D2O in spores is in a relatively weak hydrogen-bonded mode, compared to the strong hydrogen-bonded mode in pure D2O. (2) The D2O content of individual spores in a population was somewhat heterogeneous. (3) The spatial distribution of D2O in single dormant spores is uneven, and is less dense in the central core region. Raman images of different molecular components indicate that the water distribution is somewhat different from thos...
Clinical Trial Report: Endoscopic Treatment of Postoperative Bile Duct Strictures Using Multiple Stents: Long-Term Results

Introduction: Post-laparoscopic cholecystectomy biliary strictures present a difficult management problem. Standard percutaneous radiologic and surgical treatments carry significant morbidity. Endoscopic dilation of postoperative biliary strictures with increasing numbers of stents was first described by Costamagna et al. in 2001 [1], with promising results after a long-term follow-up (mean 4 years). Prior to that, the standard endoscopic approach was serial dilation and stenting using single or double stents, with often disappointing results.
Nonhelical, fibronectin-binding basement-membrane collagen from endodermal cell culture

Abstract A novel method of affinity chromatography on insolubilized collagen-binding fragments of fibronectin was utilized to isolate a random-coil collagenous protein from culture media of mouse teratocarcinoma-derived endodermal cells. These cells also produced another collagenous protein, which did not bind to fibronectin but could be isolated by differential salt precipitation. The affinity-purified collagen differs from its conventionally isolated counterpart in that it is not triple-helical in structure, its polypeptides are not disulfide-crosslinked and it has affinity for fibronectin in its native state. Both collagens resemble previously characterized type IV basement-membrane collagens with respect to their amino acid composition, cyanogen bromide peptides, chain size, immunological reactivity and tissue localization. The random-coil collagen is directly active in promoting the attachment of some lines of cells, but for attachment of the endodermal cells addition of fibronectin is required. This suggests that the presence of nonhelical, fibronectinbinding collagen may have biological significance in the interaction of cells with the extracellular matrix.
Theories of priming. II: Types of primes

In 4 lexical-decision experiments, words were primed by associatively related words, unrelated words, neutral primes, or nonwords. The associative relations between the critical targets and the targets on preceding trials were also manipulated. The speed and the accuracy of responses were virtually identical in the unrelated-word, neutral, and nonword prime conditions. Between-trials semantic priming was the same size in all of these conditions. These results cause problems For non-spreading-activation (e.g., compound-cue) models of associative priming. These models predict either that neutral and nonword primes should facilitate or inhibit lexical decisions on the targets (with the direction of the effect dependent on specific assumptions) or that more between-trials priming should occur in these conditions relative to the unrelated-word prime condition. In contrast, the results are easily explained by spreading activation models
Bounds on the complex permittivity of a multicomponent material

Abstract Recently D. Bergman introduced a method for obtaining bounds on the effective dielectric constant (or conductivity) of a two-component medium. This method does not rely on a variational principle but instead exploits the properties of the effective parameter as an analytic function of the ratio of the component parameters. Here the method is extended to multicomponent media using techniques of several complex variables. We propose for the first time a series of bounds on the complex dielectric constant of a material of three or more components, as well as rederive the Wiener and Hashin-Shtrikman bounds for real parameters. In addition, we obtain in a simple manner a known infinite sequence of bounds for two-component media.
Assessment of Kidney Function for Drug Dosing

The effort to improve the identification and management of patients with chronic kidney disease (CKD)1 is based on implementing more precise means of assessing kidney function and kidney damage in the clinical setting. Over the past decade, the clinical chemistry community has adopted routine reporting of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease (MDRD) Study equation and is implementing a creatinine standardization program to enable the manufacturers of laboratory methods to establish calibration traceability to an isotope-dilution mass spectrometry (IDMS) reference measurement procedure. As a result, routine reporting of eGFR for adults based on an IDMS-traceable creatinine is becoming the clinical standard for patient care (1)(2). As with all changes in clinical practice, the implementation of eGFR reporting and creatinine standardization has created some uncertainty and confusion among health care providers. A focus of concern is the assessment of kidney function for drug dosing adjustment. Standardizing creatinine calibration to an IDMS reference produces a lowering of creatinine values by 10%–20% for most methods. Pharmaceutical manufacturers have used the Cockcroft–Gault (CG) equation to estimate creatinine clearance as the basis for drug dose adjustment recommendations, and there is no modified equation available for use with the IDMS-traceable creatinine results. Consequently, creatinine clearance estimated from the CG equation will be erroneously high. Because eGFR using the MDRD Study equation is relatively new, eGFR data is not part of drug safety information or package inserts approved by the US Food and Drug Administration (FDA). Clinicians are most concerned about dosing highly toxic drugs with narrow therapeutic indices, particularly carboplatin, an antineoplastic agent. Some clinical chemists have experienced resistance to creatinine standardization from clinicians in their facilities based on their uncertainty about how standardization would affect their ability to dose …
Interracial Politics: Asian Americans and Other Communities of Color

The Los Angeles rebellion of 1992 was a flashpoint in which the struggles of blacks, Latinos, and Asian Americans converged with explosive consequences. Dubbed the nation's first “multiracial” riot, it drove home the point that racial dynamics in the United States cannot be understood through a simple black–white framework. The events in L.A. were only the most dramatic example of interminority conflicts that have emerged in many American cities during the post-1965 era, as economic restructuring and immigration have brought racial/ethnic groups into more extensive contact with one another, reshaping their identities and relationships and creating new pressure points for conflict. Rapid economic and demographic change has also opened up new possibilities for coalition and cooperation among racial/ethnic groups, from electoral politics to grassroots community activism. Asian Americans, often depicted as an “interstitial” group and a potential “swing vote,” have played and will continue to play a key role in interracial conflicts and coalitions in American politics.Although we focus on the post-1965 period in this article, conflict and cooperation between Asian Americans and other communities of color date back into the 1800s.
Immunoproteasome expression in a nonimmune tissue, the ocular lens.

Abstract Interferon γ (IFNγ) induces the expression of three catalytic subunits of the 20S proteasome that can replace their constitutive homologues to form the “immunoproteasome,” named to reflect its antigen presentation function. However, immunoproteasome levels and their modulation in nonimmune tissues remain unknown. A disrupted lens differentiation program observed in transgenic mice that constitutively express IFNγ in the immune-privileged lens tissue suggests a role for this cytokine in differentiation. We have developed a competitive RT-PCR assay that demonstrates substantially increased levels of immuno subunits and unchanged levels of constitutive subunits in transgenic compared to wild-type lenses. Similar results were observed with IFNγ treated αTN4-1 lens epithelial cells. A comparison of these subunits in different immune and nonimmune mouse tissues revealed unique expression patterns. The presence of immuno subunits in nonimmune tissues such as lens suggests that the immunoproteasome may also have nonimmune functions, such as that in lens differentiation.
Copepods of the Acanthocyclops Vernalis-Group From the Otztal Alps, Tirol 1)

[In den Otztaler Alpen fing ich Copepoden der Acanthocyclops vernalis-robustus-Gruppe in 27 Kleingewassern, dessen Oberflachen 3 bis 17.000 m2 betrugen. Die Wasserkorper liegen 1770 bis 2750 m, die meisten mehr als 2200 m, uber dem Meeresspiegel. Achtundsechzig Mannchen und 103 Weibchen wurden prapariert und die Dornen an der Aussenseite der Schwimmfuss-Aussenaste gezahlt. Siebenundzwanzig verschiedene Dornenformeln wurden in sechs Kategorien eingeteilt. Funf Populationen enthielten nur Individuen mit 22,33,33,33, der sogenannten A. vernalis-Formel; zwei weitere Populationen hatten Individuen dieser Formel neben anormalen. In funf Populationen kam nur die 33,44,44,44 Formel (die sogenannte A. robustus-Formel) vor; sechs weitere enthielten Vertreter dieser Formel neben anormalen Tieren. Sieben Populationen wiesen beide normalen Formeln neben anormalen Formeln auf. Dreiundvierzig Individuen besassen anormale Formeln; sie waren nicht nach der Zufallskurve auf verteilt. Eine einzige Population enthielt fast ein Drittel der anormalen Individuen. Wasserkorper die Copepoden besassen mit derselben Dornenformel, waren okologisch nicht einheitlich. Die physikalischen Faktoren (Wassertemperatur, Licht, u.s.w.) der Kleingewasser veranderten sich taglich und unperiodisch. Die verschiedenen Dornenformeln reprasentieren wahrscheinlich deutlich voneinander verschiedenen gen-pools, die unabhangig von den Milieufaktoren existieren., In den Otztaler Alpen fing ich Copepoden der Acanthocyclops vernalis-robustus-Gruppe in 27 Kleingewassern, dessen Oberflachen 3 bis 17.000 m2 betrugen. Die Wasserkorper liegen 1770 bis 2750 m, die meisten mehr als 2200 m, uber dem Meeresspiegel. Achtundsechzig Mannchen und 103 Weibchen wurden prapariert und die Dornen an der Aussenseite der Schwimmfuss-Aussenaste gezahlt. Siebenundzwanzig verschiedene Dornenformeln wurden in sechs Kategorien eingeteilt. Funf Populationen enthielten nur Individuen mit 22,33,33,33, der sogenannten A. vernalis-Formel; zwei weitere Populationen hatten Individuen dieser Formel neben anormalen. In funf Populationen kam nur die 33,44,44,44 Formel (die sogenannte A. robustus-Formel) vor; sechs weitere enthielten Vertreter dieser Formel neben anormalen Tieren. Sieben Populationen wiesen beide normalen Formeln neben anormalen Formeln auf. Dreiundvierzig Individuen besassen anormale Formeln; sie waren nicht nach der Zufallskurve auf verteilt. Eine einzige Population enthielt fast ein Drittel der anormalen Individuen. Wasserkorper die Copepoden besassen mit derselben Dornenformel, waren okologisch nicht einheitlich. Die physikalischen Faktoren (Wassertemperatur, Licht, u.s.w.) der Kleingewasser veranderten sich taglich und unperiodisch. Die verschiedenen Dornenformeln reprasentieren wahrscheinlich deutlich voneinander verschiedenen gen-pools, die unabhangig von den Milieufaktoren existieren.]
Characterization of a model of osteoarthritis in the rabbit knee

Summary A new computerized method of histomorphometry was used to assess the development of osteoarthritis (OA) in a rabbit model. Three groups of 10 New Zealand White rabbits with closed epiphyses underwent unilateral anterior cruciate ligament transection (ACLT) and contralateral arthrotomy (sham). Groups were killed at 4, 8 and 12 weeks. At the time of death the femoral condyles were assessed grossly following the application of India ink using the following grading scale. Grade 1: intact surface; grade 2: minimal fibrillation; grade 3: overt fibrillation; grade 4: erosion. All histological sections were assessed using a color image analysis system. The mean thickness and area were measured for a defined cartilage region. The root mean square surface roughness (based on deviations from an idealized smooth surface) was calculated to assess the surface profile of the articular cartilage. The results were as follows. After ACLT, no full-thickness ulceration was noted at 4 weeks. Four of the medial femoral condyles at 8 weeks and six at 12 weeks showed full-thickness ulceration of the articular cartilage. The per cent cartilage area and cartilage thickness (ACLT divided by sham) in almost all regions showed decreases with time, indicating progressive erosion. The surface of the ACLT knees was much rougher than that of sham of the knees. These results demonstrate the usefulness of a quantitative methodology using a computerized video analysis system to assess the articular cartilage following ACLT in a rabbit model for the development of OA.
Nuclear Factor-κB Is a Critical Mediator of Ste20-Like Proline-/Alanine-Rich Kinase Regulation in Intestinal Inflammation

Inflammatory bowel disease (IBD) is thought to result from commensal flora, aberrant cellular stress, and genetic factors. Here we show that the expression of colonic Ste20-like proline-/alanine-rich kinase (SPAK) that lacks a PAPA box and an F-α helix loop is increased in patients with IBD. The same effects were observed in a mouse model of dextran sodium sulfate-induced colitis and in Caco2-BBE cells treated with the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The 5′-flanking region of the SPAK gene contains two transcriptional start sites, three transcription factor Sp1-binding sites, and one transcription factor nuclear factor (NF)-κB-binding site, but no TATA elements. The NF-κB-binding site was essential for stimulated SPAK promoter activity by TNF-α, whereas the Sp1-binding sites were important for basal promoter activity. siRNA-induced knockdown of NF-κB, but not of Sp1, reduced TNF-α-induced SPAK expression. Nuclear run-on and mRNA decay assays demonstrated that TNF-α directly increased SPAK mRNA transcription without affecting SPAK mRNA stability. Furthermore, up-regulation of NF-κB expression and demethylation of the CpG islands induced by TNF-α also played roles in the up-regulation of SPAK expression. In conclusion, our data indicate that during inflammatory conditions, TNF-α is a key regulator of SPAK expression. The development of compounds that can either modulate or disrupt the activity of SPAK-mediated pathways is therefore important for the control and attenuation of downstream pathological responses, particularly in IBD.
Modeling soil solute release into runoff with infiltration

Summary Despite empirical evidence that infiltration plays an important role in controlling the transfer of chemicals from soil to surface runoff, few mechanistic models have been tested under both infiltrating and non-infiltrating conditions. We used previously published experimental data to test a physically-based, solute transport model. The model’s underlying conceptual basis is that near-surface soil chemicals are ejected into runoff by raindrop impact and chemicals deeper in the soil diffuse into this near-surface raindrop “exchange-layer.” The experiments consisted of three soil types (clay, loam, and fine sandy loam) subjected to three infiltration conditions (none, full drainage, and reduced infiltration). Model parameters that could not be directly determined from the descriptions of the experiments were determined from previously published information or otherwise internally constrained. The model’s governing equations were solved numerically and the results agreed well with measured solute concentrations in both runoff and soil-water for all the experiments. The results emphasize the potentially important role of saturated, poorly draining parts of the landscape in contributing solutes to streams and lakes via overland flow.
On the microeconomics of specialization

Abstract We consider individual consumer–producers who operate within a perfectly competitive market economy with transaction costs, presenting several propositions that characterize the optimal production and consumption plans of such a consumer–producer. First, we show that under rather sparse conditions on production technologies and consumer preferences, there exists a solution to the consumer–producer optimization problem if transaction costs are asymptotically high. Second, under strengthened properties on consumer preferences, there exists such a solution, even in the absence of transaction costs. Third, we discuss the conditions under which a consumer–producer specializes to different degrees. These results generalize the existing results in the literature.
Effects of nitrogen and phosphorus on yields and tissue analyses of chili peppers

Abstract Nitrogen applications affected plant growth characteristics, color, nutrient content of leaves and yield of chili peppers as shown by results in this two‐year study. Moderate rates of N (100–150 kg/ha) tended to produce a more desirable type of plant and highest yields. Phosphorus treatments did not affect yields under these conditions. Analysis of stem‐petiole samples for nitrate appeared to be a good indicator of the N status of the plant. A heavy fruit set in August accompanied with NO3‐N values below 8,000 to 10,000 ppm resulted in harvest time N deficiencies and lower yields.
Trajectories of Research in Translation Studies

The article sums up the principle trajectories of research in translation studies that are likely to be productive in the coming decades. I focus on six broad areas. The first encompasses attempts to define translation: this includes research as diverse as examinations of particular linguistic facets of translation, corpus studies of translation, descriptive historical studies, and analysis of think-aloud protocols. The second area of research pertains to the internationalization of translation, which challenges basic Western assumptions about the nature of translation and generates new case studies that shake the foundations of translation theory and practice as they are known at present. Changes in translation theory and practice associated with emerging technologies and globalization constitute the third research area to be discussed. The fourth strand is the application to translation of various interpretive perspectives based on frames from other disciplines. The last two branches of research have to do with the relationship of translation studies to cognitive science and neurophysiology. The article closes with some general observations about the implications for translation research as a whole and the structure of translation studies entailed by the six areas discussed.
Relating axial motion of optical elements to focal shift

In this paper, simple relationships are presented to determine the amount of focal shift that will result from the axial motion of a single element or group of elements in a system. These equations can simplify first-order optomechanical analysis of a system. Examples of how these equations are applied are shown for lenses, mirrors, and groups of optical elements. Limitations of these relationships are discussed and the accuracy is shown in relation to modeled systems.
Private education in a poor country: The case of urban Bolivia

Abstract Investment in education is critical for economic growth and poverty alleviation. Such investment is typically being financed by the state. Yet in many countries families contribute privately to the education of their children. In an era of stagnating public budgets for education (and practically anything else), the private financing of education gains importance for a country's investment in human resources to be maintained. It is often claimed that private education is highly selective and afforded only by the rich. In this paper we examine the extent of private expenditure on education in a country that is among the poorest—Bolivia. In the empirical analysis we use data from both the 1990 and 1992 household surveys (Encuesta Intergrada de Hogares). The results show that there is a remarkable willingness of households in Bolivia to pay for private education for their children.