cssi/SciSciGPT-SciSciNet huggingface dataset:
Probability of intellectual disability is associated with soil concentrations of arsenic and lead

Abstract Background The association between metals in water and soil and adverse child neurologic outcomes has focused on the singular effect of lead (Pb), mercury (Hg), and arsenic (As). This study describes the complex association between soil concentrations of As combined with Pb and the probability of intellectual disability (ID) in children. Methods We used a retrospective cohort design with 3988 mother child pairs who were insured by Medicaid and lived during pregnancy and early childhood in South Carolina between 1/1/97 and 12/31/02. The children were followed until 6/1/08, using computerized service files, to identify the diagnosis of ID in medical records and verified by either school placement or disability service records. The soil was sampled using a uniform grid and analyzed for eight metals. The metal concentrations were interpolated using Bayesian Kriging to estimate concentration at individual residences. Results The probability of ID increased for increasing concentrations of As and Pb in the soil. The Odds Ratio for ID, for one unit change in As was 1.130 (95% confidence interval 1.048–1.218) for Pb was 1.002 (95% confidence interval 1.000–1.004). We identified effect modification for the infants based on their birth weight for gestational age status and only infants who were normal size for their gestational age had increased probability of ID based on the As and Pb soil concentrations (OR for As at normal weight for gestational age = 1.151 (95% CI: 1.061–1.249) and OR for Pb at normal for gestational age = 1.002 (95% CI: 1.002–1.004)). For normal weight for gestational age children when As = 22 mg kg−1 and Pb = 200 mg kg−1 the risk for ID was 11% and when As = 22 mg kg−1and Pb = 400 mg kg−1 the probability of ID was 65%. Conclusion The probability of ID is significantly associated with the interaction between Pb and As for normal weight for gestational age infants.
PKCβ-dependent phosphorylation of the glycine transporter 1.

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the glycine transporter 1 (GlyT1) and the clearance rate for glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the years, it has been shown that PKC tightly regulates the activity of several neurotransmitter transporters. In the present work, by stably expressing three N-terminus GlyT1 isoforms in porcine aortic endothelial cells and assaying for [(32)P]-orthophosphate metabolic labeling, we demonstrated that the isoforms GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that phosphorylation was dramatically enhanced, in a time dependent fashion, after PKC activation by phorbol ester. The phosphorylation was PKC-dependent, since pre-incubation of the cells with bisindolylmaleimide I, a selective PKC inhibitor, abolished the phorbol ester-induced phosphorylation. Blotting with specific anti-phospho-tyrosine antibodies did not yield any signal that could correspond to GlyT1 tyrosine phosphorylation, suggesting that the phosphorylation occurs at serine and/or threonine residues. In addition, a 23-40%-inhibition on V(max) was obtained by incubation with phorbol ester without a significant change on the apparent Km value. Furthermore, pre-incubation of the cells with the selective PKCα/β inhibitor Go6976 abolished the downregulation effect of phorbol ester on uptake and phosphorylation, whereas the selective PKCβ inhibitors (PKCβ inhibitor or LY333531) prevented the phosphorylation without affecting glycine uptake, defining a specific role of classical PKC on GlyT1 uptake and phosphorylation. Taken together, these data suggest that conventional PKCα/β regulates the uptake of glycine, whereas PKCβ is responsible for GlyT1 phosphorylation.
Building a working understanding of protein adsorption with model systems and serendipity.

Abstract Here we will consider a working understanding of protein adsorption to be one that is adequate for practical use. Serendipity will be considered as a resource that can be used along with model systems in order to build such a working understanding. In particular, the term refers to a preparedness on the part of the researcher to make connections between a variety of everyday inputs from sources in and outside of the main concerns of the research, and a willingness to apply those connections toward the broader utility and impact of the work. In this paper we summarize the highlights and major conclusions of our work with proteins at interfaces – gained by use of comparatively very simple experimental systems while harnessing luck as effectively as we could along the way – and its relevance to meeting challenges in biopharma and biomedical technology.
Spatial Environmental Modeling of Autoantibody Outcomes among an African American Population

In this study of autoimmunity among a population of Gullah African Americans in South Carolina, the links between environmental exposures and autoimmunity (presence of antinuclear antibodies (ANA)) have been assessed. The study population included patients with systemic lupus erythematosus (n = 10), their first degree relatives (n = 61), and unrelated controls (n = 9) where 47.5% (n = 38) were ANA positive. This paper presents the methodology used to model ANA status as a function of individual environmental influences, both self-reported and measured, while controlling for known autoimmunity risk factors. We have examined variable dimension reduction and selection methods in our approach. Following the dimension reduction and selection methods, we fit logistic spatial Bayesian models to explore the relationship between our outcome of interest and environmental exposures adjusting for personal variables. Our analysis also includes a validation “strip” where we have interpolated information from a specific geographic area for a subset of the study population that lives in that vicinity. Our results demonstrate that residential proximity to exposure site is important in this form of analysis. The use of a validation strip network demonstrated that even with small sample numbers some significant exposure-outcome relationships can be detected.
I love you but ...: Cultural differences in complexity of emotional experience during interaction with a romantic partner

Studies suggest that emotional complexity—the experience of positive and negative emotion in response to the same event—is unusual in Western samples. However, recent research finds that the co-occurrence of positive and negative emotion during unstructured situations is more common among East Asians than Westerners, consistent with theories emphasising the prevalence of dialectical folk epistemology in East-Asian culture. The present study builds upon previous research by examining Asian- and European-Americans' experience of a particular positive emotion—love—and a situationally appropriate negative emotion during four structured laboratory conversations with their romantic partner. Among Asian Americans, love and the experience of negative emotion were typically less negatively correlated during these conversations than was true for European Americans.
The effect of Cercospora rodmanii, a biological control for waterhyacinth, on the fish, Gambusia affinis

The effect of Cercospora rodmanii, a fungal pathogen being developed as a biological control for waterhyacinth, was evaluated on Gambusia affinis in a standard 96-hour bioassay. Testing indicated that C. rodmanii had no adverse effects on treated fish and would not be a hazard to populations of these fish in nature.
Fretting fatigue crack initiation behavior using process volume approach and finite element analysis

This study investigates crack initiation behavior by incorporating fretting fatigue process volume. Three critical plane based fretting fatigue crack initiation parameters are characterized by computing their averaged values over the process volume and then comparing with their counterparts obtained from the localized approach. Two approaches are used: first one involves the computation of parameter at several points over a rectangular region and then its average, and second approach computes the average state of stress/strain over a radial region from which the averaged parameter is calculated. Both approaches require pre-determination of a critical location at or around which the process volume needs to be placed. Effects of size and location of process volume on the averaged value of parameters are studied in detail. Two radii of cylindrical pad are analyzed to investigate the effect of severity of stress gradient on process volume approach. Effects of finite element mesh refinement are also investigated. Averaged value of parameter decreases with the increase of process volume size. This decrease is higher when the process volume is located in the region that is away from the contact zone. Further, a parameter based on normal stress on the critical plane shows more dependence on the size of process volume than that based on shear stress or on a combination of both shear and normal stresses. Orientation of crack initiation changes within a range that is well within the scatter band of experimental observations as the process volume size increases. Averaged value of parameter for a pad with higher stress gradient has a larger reduction with the increase of process volume size than that with a lower stress gradient. Process volume size has less effect on the averaged value of parameter with coarser finite element mesh. Finally, the localized approach provides a conservative value of fretting fatigue crack initiation parameter compared to its counterpart based on the process volume.
Finite temperature bosonic closed strings: Thermal duality and the Kosterlitz-Thouless transition

We elucidate the properties of a gas of free closed bosonic strings in thermal equilibrium. Our starting point is the intensive generating functional of connected one-loop closed bosonic string vacuum graphs on which we impose invariance under a timelike T-duality transformation. Invariance of the Polyakov path integral under thermal duality transformations gives a modular invariant expression for the free energy of free closed strings at finite temperature. We show that a ${Z}_{2}$ twist in Euclidean time is necessary for the absence of spurious vector bosons in the massless spectrum at finite temperature, thereby resolving an ambiguity in the Euclidean time prescription for perturbative string theory. The spurious modes have no correspondence among the propagating degrees of freedom in a finite temperature gauge theory. We find that states localized at the fixed points of the ${Z}_{2}$ orbifold contribute a constant term to the entropy but are otherwise absent from the thermodynamic potentials including both the internal energy and specific heat. We show that a Kosterlitz-Thouless continuous phase transition at the self-dual temperature results in the formation of the long string phase in a self-dual gas of free closed strings at high temperature. There is no Hagedorn phase transition in the free energy of the free bosonic string gas.
Cationic Complexes of Antimony(III) and Bismuth(III) Stabilized by Intra- or Intermolecular Coordination

Three cationic aryl−antimony and −bismuth complexes stabilized by intra- or intermolecular coordination have been prepared. Treatment of either SbAr2Cl or BiAr2Cl (Ar = 2-[(dimethylamino)methyl]phenyl, 2-(Me2NCH2)C6H4) with TlPF6 afforded [SbAr2][PF6] (1) or [BiAr2][PF6] (2), respectively. A related complex, [SbPh2{OP(NMe2)3}2][PF6] (5), stabilized by intermolecular coordination, was prepared via the reaction of SbPhCl2 with 2 equiv of TlPF6 in the presence of an excess of OP(NMe2)3. The X-ray crystal structures of compounds 1, 2, and 5 are described; the coordination geometry at the group 15 element center in each new compound was found to be distorted trigonal bipyramidal.
Molecular Cloning and Characterization of c‐erb‐A mRNA Species in Mouse Neuroblastoma Cells

UNLABELLED Abstract The mouse neuroblastoma cell line is an excellent model in which to study thyroid hormone action and metabolism, particularly in neural tissue. We therefore undertook the molecular cloning and characterization in these cells of putative thyroid hormone receptors related to c-erb-A. Since rat brain tissue contains multiple cell types, and because of possible subtle differences between species (mouse and rat), we therefore screened a new cDNA library constructed from mouse neuroblastoma cell mRNA with synthetic oligonucleotide probes based on the published nucleotide sequence of the c-erb-A gene in whole rat brain. Despite the fact that this rat brain cDNA sequence is now recognized to represent a c-erb-A alpha 1 form, the cDNA clones that we isolated were all members of the newly-recognized c-erb-A alpha 2 form. This identification was made on the basis of nucleotide sequence divergence downstream of the nucleotide corresponding to amino-acid residue 370 in the predicted coding region. The two longest mouse neuroblastoma cDNA clones, clone 29 (1796 bp) and clone 32 (1410 bp), were 93% to 94% homologous with the c-erb-A alpha 2 and c-erb-A alpha 1 forms in their DNA binding and thyroid hormone binding domains (up to amino-acid residue 370 in the latter). Both clones 29 and 32 were incomplete in that they terminated at their 3'ends at an internal Eco R1 site. Fortunately this 120 bp (40 derived amino-acid) truncation was downstream of the reported thyroid hormone binding domain. The 5'untranslated end of clone 29 (446 bp) was of interest because a region of its nucleotide sequence (279 bp) revealed a high degree of homology (87%) with rat brain c-erb-A alpha 1. This highly conserved region in clone 29 appeared to be important in the regulation of translation because only clone 32, in which this region was truncated, efficiently translated protein in a cell-free system. The protein product of clone 32 did not bind thyroid hormone. Northern blot analysis of mouse neuroblastoma mRNA with site-specific synthetic oligonucleotides revealed that the c-erb-A alpha 2 species was dominant (major band of 2.4 kb), with a lesser amount of the c-erb-A alpha1 species (major band of 1.8 kb). IN CONCLUSION 1) We report the molecular cloning of c-erb-A variants in a specific neural tissue cell type, namely mouse neuroblastoma cells; 2) The cells contained predominantly the c-erb-A alpha 2 subtype; 3) This c-erb-A alpha 2 form was unique up to bp 167 at its 5'untranslated end, and was then followed, up to the ATG initiation codon, by a highly conserved region common to all c-erb-A a species; 4) The 5'untranslated region appeared to play a role in the translational efficiency of this mRNA; 5) The protein product of the c-erb-A alpha 2 mRNA in these cells did not appear to bind thyroid hormone. In view of this finding, the physiological role of the c-erb-A alpha 2 protein remained speculative and may involve a represser function at the thyroid hormone responsive element.
A SYSTEMS PERSPECTIVE ON MATERIAL REQUIREMENTS PLANNING

For many companies, the implementation of material requirements planning systems has failed to produce the expected improvements in manufacturing efficiency. This paper shows that MRP failure can occur in the common situation in which MRP is installed in a manufacturing environment that has evolved around manual methods of material control. A system dynamics simulation model is used to interrelate decision functions (policies) of a manufacturing firm. Simulation runs of the model operating with manual methods of material control show six- to seven-year fluctuations in production, ordering, and labor. A modified version of the model, changed only by the introduction of a requirements explosion to represent MRP, shows that MRP can actually cause more severe production fluctuations, resulting in lower average labor productivity and higher manufacturing costs. The major practical implication of the analysis is that the organizational environment that suits MRP (and utilizes its inherent strengths) is different from the environment that is likely to prevail at the time of implementation.
Echocardiographic detection of coronary artery disease during dobutamine infusion.

BACKGROUNDTwo-dimensional echocardiography performed during dobutamine infusion has been proposed as a potentially useful method for detecting coronary artery disease. However, the safety and diagnostic value of dobutamine stress echocardiography has not been established.METHODS AND RESULTSIn this study, echocardiograms were recorded during step-wise infusion of dobutamine to a maximum dose of 30 micrograms/kg/min in 103 patients who also underwent quantitative coronary angiography. The echocardiograms were digitally stored and displayed in a format that allowed simultaneous analysis of rest and stress images. Development of a new abnormality in regional function was used as an early end point for the dobutamine infusion. No patient had a symptomatic arrhythmia or complications from stress-induced ischemia. Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was present in 35 of 55 patients who had normal echocardiograms at rest. The sensitivity and specificity of dobutami...
The study of ciliary frequencies with an optical spectrum analysis system

Abstract The cilia of rabbit tracheal epithelial cells beat at the rate of from 6 to 21 cycles/sec at physiological temperatures. The cilia of each cell show a frequency response which fluctuates within a frequency range specific to that cell. Cells from the same area of the trachea tend to fluctuate in the same frequency range. The frequency may be constant for several seconds or it may vary second-by-second in the range appropriate to the cell being measured. The frequency range can be altered in part by temperature. At 37 °C the frequency range may fluctuate by ± 3.5 beats/sec. As the temperature is decreased ciliary beat becomes more coherent and the frequency range decreases to ± 0.5 beats/sec at 5 °C. Frequencies are obtained with a photomultiplier system attached to a phase-contrast microscope. The mixed population of frequencies produced by the cilia passing through the transmitted light are sorted by Fast Fourier Transform analysis into discrete frequencies. With this system, frequencies of individual ciliated cells can be analysed in real time and for unlimited duration.
Reliability and relationships among handgrip strength, leg extensor strength and power, and balance in older men

Abstract Purpose To quantify the reliability of isometric leg extension torque (LE MVC ), rate of torque development (LE RTD ), isometric handgrip force (HG MVC ) and RFD (HG RFD ), isokinetic leg extension torque and power at 1.05 rad·s − 1 and 3.14 rad·s − 1 ; and explore relationships among strength, power, and balance in older men. Methods Sixteen older men completed 3 isometric handgrips, 3 isometric leg extensions, and 3 isokinetic leg extensions at 1.05 rad·s − 1 and 3.14 rad·s − 1 during two visits. Intraclass correlation coefficients (ICCs), ICC confidence intervals (95% CI), coefficients of variation (CVs), and Pearson correlation coefficients were calculated. Results LE RTD demonstrated no reliability. The CVs for LE RTD and HG RFD were ≤ 23.26%. HG MVC wasn't related to leg extension torque or power, or balance (r = 0.14–0.47; p > 0.05). However, moderate to strong relationships were found among isokinetic leg extension torque at 1.05 rad·s − 1 and 3.14 rad·s − 1 , leg extension mean power at 1.05 rad·s − 1 , and functional reach (r = 0.51–0.95; p ≤ 0.05). Conclusions LE RTD and HG RFD weren't reliable and shouldn't be used as outcome variables in older men. Handgrip strength may not be an appropriate surrogate for lower body strength, power, or balance. Instead, perhaps handgrip strength should only be used to describe upper body strength or functionality, which may compliment isokinetic assessments of lower body strength, which were reliable and related to balance.
Identity, genetic lineages and putative hybrids of an obligate mycobiont associated with the mycoheterotrophic plant Pterospora andromedea in the south-central Rocky Mountains

Abstract Mycoheterotrophic plants are nonphotosynthetic and must form a relationship with a mutualistic fungus and an autotrophic host to acquire carbon. In this study, identity of fungal associates of Pterospora andromedea in the south-central Rocky Mountains was determined. Although P. andromedea has been found to associate with at least three Rhizopogon species groups throughout its range in North America, it was found to exclusively associate with the Rhizopogon salebrosus species group in the Rocky Mountains. In addition, the genetic structure of R. salebrosus was examined. The data support the presence of two genetic lineages within the R. salebrosus species group that exhibit strong biogeographic distribution linked to historic conifer association with Pinus contorta and Pinus ponderosa . A zone of secondary contact between the two lineages was also identified along with a number of putative hybrids.
Phencyclidine (PCP) acts at σ sites to induce c-fos gene expression

Phencyclidine (PCP) is a compound that results in abnormal human behavior and has been proposed as a chemical model for schizophrenia. It was hypothesized that PCP induction of the immediate-early gene, c-fos, should be seen in areas associated with emotional behavior, such as the cortex and limbic system. It was also proposed that PCP may induce c-fos via the sigma receptor. PCP and two sigma ligands, 1,3-di(2-tolyl)guanidine (DTG) and pentazocine, were shown to induce c-fos in similar patterns. The three compounds abundantly induced c-fos in the cingulate, parietal, and piriform cortices and the midline structures of the thalamus and hypothalamus. Neither PCP nor the sigma ligands induced c-fos in the hippocampus. This suggests that PCP binding at NMDA receptors does not result in significant c-fos induction. Rimcazole, a putative sigma2 receptor antagonist, and other sigma ligands have been shown to ameliorate PCP stereotypic behavior. Rimcazole inhibited PCP c-fos induction in the cingulate and parietal cortices and DTG c-fos induction in the cingulate cortex. DTG shows both sigma1 and sigma2 binding affinity. Rimcazole failed to inhibit pentazocine c-fos induction. Pentazocine binds only to sigma1 receptors. This suggests that PCP may produce a significant fraction of its c-fos induction via sigma2 receptors.
Characterization of an insoluble adenosine deaminase complexing protein from human kidney

Abstract Evidence for the presence of an insoluble form of adenosine deaminase complexing protein in human kidney has been obtained. An initial study demonstrated that binding of monomeric adenosine deaminase to particulate material from kidney was saturable and could be blocked by preincubating the enzyme with soluble complexing protein. Treatment of particulate material with deoxycholate, followed by immunoassay of the detergent extract, confirmed the presence of an insoluble form of complexing protein in the kidney. Several other human organs examined by this technique contained smaller amounts of insoluble complexing protein. Complexing protein isolated from the soluble and particulate fractions of kidney homogenates were found to be structurally similar. The proteins had the same subunit Mr and showed complete crossreactivity with antiserum to soluble complexing protein. Indirect immunoperoxidase staining of renal cortical tissue revealed that complexing protein was concentrated in the brush border of the proximal tubules. These results indicate that (a) the soluble and insoluble forms of complexing protein from human kidney may be products of the same gene(s) and (b) a portion of the complexing protein in human kidney is bound to the brush border membranes of cells lining the proximal tubules.
Ester interchange reactions in poly(ethylene terephthalate): observation using smallangle neutron scattering☆

Abstract Ester interchange reactions have been studied in poly(ethylene terephthalate) (PET) by means of small-angle neutron scattering (SANS). Cast film PET samples containing 20 wt% deuterated PET chains were prepared at low temperature. The SANS molecular weight of the as-prepared specimen agrees with the g.p.c. value and the molecular dimensions are close to the unperturbed value. Samples were then annealed at temperatures of 150°C–300°C at times from 10–600 min. If ester interchange occurs in a blend sample, block copolymer chains are formed with the blocks consisting of protonated and deuterated sequences. The SANS Mw obtained from these samples is an apparent Mw, the Mw of the blocks, and is lower than the g.p.c. value. Ester interchange is shown to be rapid in the melt and also to take place at a slower rate at temperatures 15°C below Tm, in general agreement with previous studies. An apparent clustering effect at elevated temperatures is also reported.
A Novel Gene That Bears a DnaJ Motif Influences Cyanobacterial Cell Division

Transposon Tn5-692 mutagenizes Synechococcus sp. strain PCC 7942 efficiently. The predicted product of the gene mutated in the Tn5-692-derived cell division mutant FTN2 has an N-terminal DnaJ domain, as have its cyanobacterial and plant orthologs. Anabaena sp. strain PCC 7120, when mutated in genes orthologous to ftn2 and ftn6, forms akinete-like cells.
Fingerprint patterns from laser-induced Azido photochemistry of spin-labeled photoaffinity ATP analogs in matrix-assisted laser desorption/ionization mass spectrometry

The photochemical reaction of azide derivatives induced by ultraviolet (UV) laser in matrix-assisted laser desorption/ionization mass spectrometry (MALDI) is reported. A novel synthesized class of azide aromatic derivatives, spin-labeled photoaffinity non-nucleoside adenosine triphosphate (ATP) analogs which are useful probes in study of muscle contraction mechanism, is used in this investigation. In the negative ion MALDI spectra of these ATP analogs, "fingerprint" peaks corresponding to [M - 10 - 1]-, [M - 12 - 1]-, [M - 16 - 1]-, [M - 26 - 1]-, [M - 28 - 1]-, [M - 41 - 1]-, and [M - 42 - 1]- were observed with relative intensities depending on the MALDI matrix. Only the [M - 16 - 1]- is present in the similar mass spectra of the analog in which the azido group is replaced by a hydrogen. A model is suggested for the photochemical reactions of azide derivatives under UV laser irradiation. The photoreaction fingerprint information is diagnostically useful in characterization of azido compounds, especially for spin-labeled photoaffinity non-nucleoside ATP analogs.
Using price discrimination theory to plan promotions

Serious mistakes can be made by agribusiness marketers if they ignore the potential leakages between segments when they plan price promotions. The model illustrated in this paper considers leakages along with communication spending and nonparticipation by potential buyers to find the optimal list and discount prices for a promotion. © 1997 John Wiley & Sons, Inc.
Speaker-sensitive emotion recognition via ranking: Studies on acted and spontaneous speech

We introduce a ranking approach for emotion recognition which naturally incorporates information about the general expressivity of speakers. We demonstrate that our approach leads to substantial gains in accuracy compared to conventional approaches. We train ranking SVMs for individual emotions, treating the data from each speaker as a separate query, and combine the predictions from all rankers to perform multi-class prediction. The ranking method provides two natural benefits. It captures speaker specific information even in speaker-independent training/testing conditions. It also incorporates the intuition that each utterance can express a mix of possible emotion and that considering the degree to which each emotion is expressed can be productively exploited to identify the dominant emotion. We compare the performance of the rankers and their combination to standard SVM classification approaches on two publicly available datasets of acted emotional speech, Berlin and LDC, as well as on spontaneous emotional data from the FAU Aibo dataset. On acted data, ranking approaches exhibit significantly better performance compared to SVM classification both in distinguishing a specific emotion from all others and in multi-class prediction. On the spontaneous data, which contains mostly neutral utterances with a relatively small portion of less intense emotional utterances, ranking-based classifiers again achieve much higher precision in identifying emotional utterances than conventional SVM classifiers. In addition, we discuss the complementarity of conventional SVM and ranking-based classifiers. On all three datasets we find dramatically higher accuracy for the test items on whose prediction the two methods agree compared to the accuracy of individual methods. Furthermore on the spontaneous data the ranking and standard classification are complementary and we obtain marked improvement when we combine the two classifiers by late-stage fusion.
β2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-κB-independent mechanisms

Activation of the beta(2) adrenergic receptor (beta(2)AR) located on macrophages has been reported to possess anti-inflammatory properties, inhibiting nuclear factor kappaB (NF-kappaB) activation and cytokine production induced by pro-inflammatory stimuli. Here, we show that activation of the beta(2)AR in the absence of pro-inflammatory stimuli produced up to an 80- and 8-fold increase in IL-1beta and IL-6 transcripts, respectively, in the RAW 264.7 murine macrophage cell line. This increase in mRNA expression was accompanied by a significant increase in IL-1beta and IL-6 protein production. Pre-treatment of RAW cells with pharmacological inhibitors of protein kinase A (PKA) or NF-kappaB pathway failed to block this cytokine increase. Instead, the beta(2)AR-mediated increase in cytokines required activation of both the B-raf-ERK1/2 and p38 pathways. Treatment of RAW cells with the exchange protein directly activated by cAMP (EPAC) agonist also resulted in the up-regulation of IL-1beta and IL-6 transcripts. Examination of the main transcription factors downstream of the ERK1/2 and p38 signaling revealed that beta(2)AR activation resulted in the stimulation of CRE-, but not C/EBPbeta-, ETS-, or NF-kappaB-dependent transcription. Western blot analysis further showed that among the transcription factors which recognize the CRE-binding site, ATF-1 and ATF-2 but not CREB proteins were phosphorylated in an ERK1/2- and p38-dependent manner. Collectively, these results demonstrate that beta(2)ARs possess pro-inflammatory properties and that their activation leads to IL-1beta and IL-6 production through ERK1/2- and p38-dependent activation of ATF-1 and ATF-2 transcription factors.
Stochastic models for tracer experiments in the circulation III. The lumped catenary system

Abstract The theory of the dispersion of indicator substances injected into the blood has been analyzed in the past from two apparently different viewpoints. On one side, the distribution of transit times through the circulatory labyrinth has been discussed as a stochastic process and, on the other, by application of compartmental kinetic analysis. The frequency function for transit times P(t) possesses moments which can be expressed in terms of coefficients of a power-series expansion near λ = 0 of the Laplace transform L (λ) of P(t). By treating the compartmental case as a finite birth and death process it is shown that the infinity of stochastic states of the classical random walk can be approximated by lumping the states into a few sets of equivalent ones, yielding an approximate frequency function Pn(t A method is presented whereby, through matching of moments of Pn(t and P(t) or their transforms near λ = 0, the best approximation can be made. Results for the classical random walk and for a lumped five-compartment and a three-compartment system are compared. The similarity in the three cases explains the often observed fact that fairly good representations of physiological indicator-dilution curves can be obtained by the use of lumped hydraulic and electrical analogs. A general principle of lumping in catenary tracer-kinetic systems is established.
On Turing degrees of points in computable topology

This paper continues our study of computable point-free topological spaces and the metamathematical points in them. For us, a point is the intersection of a sequence of basic open sets with compact and nested closures. We call such a sequence a sharp filter. A function fF from points to points is generated by a function F from basic open sets to basic open sets such that sharp filters map to sharp filters. We restrict our study to functions that have at least all computable points in their domains. We follow Turing's approach in stating that a point is computable if it is the limit of a computable sharp filter; we then define the Turing degree Deg(x) of a general point x in an analogous way. Because of the vagaries of the definition, a result of J. Miller applies and we note that not all points in all our spaces have Turing degrees; but we also show a certain class of points do. We further show that in ℝn all points have Turing degrees and that these degrees are the same as the classical Turing degrees of points defined by other researchers. We also prove the following: For a point x that has a Turing degree and lies either on a computable tree T or in the domain of a computable function fF, there is a sharp filter on T or in dom(F) converging to x and with the same Turing degree as x. Furthermore, all possible Turing degrees occur among the degrees of such points for a given computable function fF or a complete, computable, binary tree T. For each x ∈ dom(fF) for which x and fF (x) have Turing degrees, Deg(fF (x)) ≤ Deg(x). Finally, the Turing degrees of the sharp filters convergent to a given x are closed upward in the partial order of all Turing degrees. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons

Voltage-gated potassium (K+) channels display a wide variety of conductances and gating properties in vivo. This diversity can be attributed not only to the presence of many K(+)-channel gene products, but also to the possibility that different K(+)-channel subunits co-assemble to form heteromultimeric channels in vivo. When expressed in Xenopus oocytes or transfected cells, K(+)-channel polypeptides assemble to form tetramers. Certain combinations of Shaker-like subunits have been shown to co-assemble, forming heteromultimeric channels with distinct properties. It is not known, however, whether K(+)-channel polypeptides form heteromultimeric channels in vivo. Here we describe the co-localization of two Shaker-like voltage-gated K(+)-channel proteins, mKv1.1 and mKv1.2, in the juxtaparanodal regions of nodes of Ranvier in myelinated axons, and in terminal fields of basket cells in mouse cerebellum. We also show that mKv1.1 and mKv1.2 can be coimmunoprecipitated with specific antibodies that recognize only one of them. These data indicate that the two polypeptides occur in subcellular regions where rapid membrane repolarization may be important and that they form heteromultimeric channels in vivo.
Synthesis and Thermal Properties of Macrocyclic Poly(2-vinylnaphthalene) Containing Single 1,4-Benzylidene or 9,10-Anthracenylidene Groups

The first synthesis of well-defined narrow molecular weight (MW) distribution macrocyclic poly(2-vinylnaphthalene) (P2VN) containing a single 1,4-benzylidene or 9,10-anthracenylidene unit is reported. The synthesis involves the potassium naphthalide (K-Naph) or potassium 1,1,4,4,7,7,10,10-octamethyl-1,2,3,4,7,8,9,10-octahydronaphthacene (K-OMOHN) initiated polymerization of 2-vinylnaphthalene (2VN) in THF at -78 °C, followed by end-to-end coupling of the resulting P2VN dianions under high dilution conditions (10 -6 -10 -4 M). Narrow MW distribution (1.11-1.26) P2VN macrocycles with MW's between 740 and 13 200 have hydrodynamic volumes that are between 5% and 29% smaller than those of the matching linear chains. The glass transition temperatures of macrocyclic P2VN do not deviate from the limiting value (151 °C) ofthe high MW P2VN, decreasing only below a DP n of about 20. Compared to the linear analogues, macrocyclic P2VN shows higher nonoxidative thermal decomposition stability.
Effect of Load Eccentricity on the Behavior of a Bolted Joint With a Yielded Fastener

A nonlinear model is proposed for studying the effect of the eccentricity of applied tensile forces on the clamp load loss in bolted joints that were initially tightened beyond the bolt elastic limit. The joint may not have been yielded at initial assembly, however. A closed form solution is obtained for the amount of clamp load loss due to a cyclic separating force. The proposed model takes into account two sources of nonlinearity; namely, the strain hardening behavior of the yielded bolt material as well as the nonlinear deformation behavior of the clamped plates under an external separating load. After the initial tightening of the fastener past its elastic limit, the subsequent application of a tensile separating force on the joint tends to increase the fastener tension in a nonlinear fashion, and simultaneously reduce the clamping force in the bolted joint from its initial value. Upon the removal of the cyclic tensile load, the bolted joint system reaches a new equilibrium point between the residual fastener tension, and the joint clamping force. At the new equilibrium point, the fastener tension is reduced from its preload due to its plastic elongation; simultaneously, a partial-yet permanent-loss in the clamp load level takes place. Excessive clamp load loss may lead to joint leakage, fastener loosening, or fatigue failure. For a known amplitude of the external cyclic tensile load, the increase in bolt tension and corresponding reduction in the joint clamp load are highly sensitive to the eccentricity of the tensile load (from the bolt center). Variables studied include the eccentricity value of the separating load, the rate of strain hardening of the bolt material, compressive and tensile stiffnesses of the clamped plates, bolt stiffness, bolt preload, and the magnitude of the separating tensile load.Copyright © 2009 by ASME
Mathematical Programming Methods of Pattern Classification

This survey examines eight mathematical programming models of pattern classification. The paper determines the range of applicability and computational merits of each model. The flexibility and large sample properties of the models are also discussed. We find that six of the models produce decision rules that maximize a function we call the quality of a decision rule. The remaining two models minimize a weighted sum of errors.
SCALE AND EQUITY IN WATER RESOURCE DEVELOPMENT: A NASH BARGAINING MODEL

. This paper presents an application of the Nash model to a combined problem of optimal development of a joint facility and related cost-benefit allocation considerations. Two alternative modifications and a diagrammatic procedure are developed. The conditions for an optimal Nash solution are derived. The procedure is illustrated using an example from a regional water development project that includes determination of the optimal capacity and allocation of costs and water among participants.
Cultural kinship as a computational system: from bottom-up to top-down forms of social organization

A key change in the evolution of our species from a common ancestor with the chimpanzees was the shift to a field of social interaction no longer dependent upon face-to-face interaction for the maintenance of social coherency. Our hunter-gatherers ancestors made a radical shift to social relations based on a culturally constructed system of kinship relations. Unlike biological kinship that reflects the facts of biological reproduction, cultural kinship is a constructed, computational system that enables symbolic computation of kinship relations that are expressed through the kin terms of a kinship terminology. The system of kin terms is analogous to arithmetic as a computational system for computing quantities with symbols instantiated by the counting numbers. The internal logic of a kinship terminology ensures consistency both in kinship relation computations and translation of kin term computations to the perspective of each person who culturally shares the same kinship terminology. The constraint of internal and external consistency does not lead to a single kinship terminology computational system, hence there are a variety of kinship terminology systems across human societies. In this paper I outline a theory for the generative structure of kinship terminology systems and briefly discuss the implications this for explaining structural differences between kinship terminologies and how structure relates to social organization.
Addressing the essential difficulties of software engineering

Abstract The central concept of Brooks' classic paper, “No Silver Bullet,” is that the hard part of building software is the specification, design, and testing of the conceptual construct that comprises the essence of software. The purpose of this article is fourfold: (1) to develop a formal conceptual framework for representing all aspects of a client organization, including those that have traditionally not been addressed formally, such as “culture,” “values,” “concepts,” and perspective; (2) to use this framework to gain a more detailed understanding of Brooks' essential difficulty, including a better understanding of the sources of conceptual errors, particularly in the requirements definition phase; (3) to show that Brooks' essential difficulty is inextricably involved with a second essential difficulty, namely, that the computer system is built by one group of people, for another group of people, who differ from them in at least one, usually very important, way, including their work activities, language, the fundamental concpets that define their work and what it is about, and the principles that form the basis for their choices in their work; and (4) to present Outside-In Development, a methodology for addressing these intertwined essential difficulties.
Contamination of commercially available quisqualic acid by glutamate-like and aspartate-like substances

Six different batches of the glutamic acid analogue quisqualic acid were analyzed with high-pressure liquid chromatography (HPLC). All batches examined showed contaminant peaks. Different batches had different contaminant peaks and differing amounts of each contaminant. Every batch of quisqualic acid tested demonstrated a contaminant peak which co-eluted with exogenously added glutamic acid. Certain batches possessed a contaminant which co-eluted with aspartic acid. The levels of glutamate-like contamination ranged from 0.08 to 0.60%, and the levels of aspartate-like contamination ranged from undetectable amounts to 0.80%. The amount of combined glutamate- and aspartate-like contamination of each batch of quisqualate correlated very highly with the ability of that batch to interact with non-quisqualate receptors in an autoradiographic binding assay. These non-quisqualate receptors are likely N-methyl-D-aspartate (NMDA) receptors. Thus, when high concentrations of quisqualate are used experimentally, contamination is likely to produce spurious effects at non-quisqualate glutamate receptors. Quisqualate itself may be a more specific agonist than assumed previously.
Dynamics of the constrained polymer collapse

The dynamics of polymer collapse with a fixed distance between endpoints is studied analytically and numerically by the Nose-Hoover algorithm. We find that at the pearling stage of the collapse the number of pearls decays as t−1/2 leading to anomalously long collapse time. To understand the effect of Stokes drag we reduced the problem of long-polymer-chain collapse to the one-dimensional diffusion-limited coalescence of particles with the mass-dependent mobility. In this case the number of pearls decays slower, as t−3/7.
Abstract C83: SiRNA screen identifies a G2-M signaling node as a novel therapeutic target in medulloblastoma.

Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although cisplatin chemotherapy and radiation have been the cornerstones of medulloblastoma intervention for over 20 years, the outcomes of these highly cytotoxic treatments are far from optimal, and there is increasing evidence that they cause long-term problems such as neurocognitive deficits and secondary tumors, even in patients with a good initial response. Thus, there is a critical need for more effective therapies to combat this disease. To approach this problem we investigated protein kinase function in medulloblastoma using RNAi combined with genomic methods. First, we performed a kinome-wide siRNA screen and identified a cohort of genes that mediates medulloblastoma cell viability. These include a signaling node of kinases that are key components of the G2-M transition including, Aurora Kinase A, Aurora Kinase B, Plk1, Wee1, Nek2 and Mps1. Clearly the G2-M transition is critical for medulloblastoma cells, so kinases required for the process are potentially important therapeutic targets. We subsequently validated PLK1 and WEE 1 as bona fide therapeutic targets. Small molecule inhibitors of WEE 1 and PLK1 potently inhibited medulloblastoma cell growth and sensitized cells to radiation. In conclusion, using siRNA screens we identified novel therapeutic targets for medulloblastoma therapy Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C83.
Rundown of the Hyperpolarization-Activated KAT1 Channel Involves Slowing of the Opening Transitions Regulated by Phosphorylation

Disappearance of the functional activity or rundown of ion channels upon patch excision in many cells involves a decrease in the number of channels available to open. A variety of cellular and biophysical mechanisms have been shown to be involved in the rundown of different ion channels. We examined the rundown process of the plant hyperpolarization-activated KAT1 K+ channel expressed in Xenopus oocytes. The decrease in the KAT1 channel activity on patch excision was accompanied by progressive slowing of the activation time course, and it was caused by a shift in the voltage dependence of the channel without any change in the single-channel amplitude. The single-channel analysis showed that patch excision alters only the transitions leading up to the burst states of the channel. Patch cramming or concurrent application of protein kinase A (PKA) and ATP restored the channel activity. In contrast, nonspecific alkaline phosphatase (ALP) accelerated the rundown time course. Low internal pH, which inhibits ALP activity, slowed the KAT1 rundown time course. The results show that the opening transitions of the KAT1 channel are enhanced not only by hyperpolarization but also by PKA-mediated phosphorylation.
Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence.

Abstract Acute kidney injury (AKI) is a frequent complication in the intensive care unit with limited therapeutic modalities. Although survival from isolated AKI has improved with recent advancements in renal replacement therapy, mortality from AKI complicated by multiorgan dysfunction has remained unchanged and is estimated to be approximately 50%. Hence, defining and better understanding the pathophysiology of distant organ dysfunction associated with AKI is clinically important because it may lead to new treatment strategies. In animal models, it has become increasingly clear that AKI is not an isolated event but results in remote organ dysfunction involving the heart, lungs, liver, intestines, and brain through an inflammatory mechanism that involves neutrophil migration, cytokine expression, and increased oxidative stress. The purpose of this brief review is to summarize the human and basic science evidence for AKI and its detrimental effects on distant organs.