cssi/SciSciGPT-SciSciNet huggingface dataset:
Pathologic T1 clear cell renal cell carcinoma: insulin-like growth factor-I receptor expression and disease-specific survival.

BACKGROUND A proportion of patients diagnosed with pathologic T1 (pT1) clear cell renal cell carcinoma (CC-RCC) will experience disease progression and death after surgery, whereas the majority remain disease free. The authors conducted a case–cohort investigation to examine the association of insulin-like growth factor I receptor (IGF-IR) expression and disease-specific survival in patients who underwent surgery for pT1 CC-RCC. METHODS Eligible patients included those diagnosed with solitary, nonfamilial pT1 CC-RCC who underwent radical nephrectomy at the Mayo Clinic-Rochester between 1970 and 2000 (n = 886 patients). Among this group, 136 patients died of CC-RCC (cases). Archived tumor blocks were not available for 62 patients, leaving a final study group of 74 cases. Stratified, random sampling was used to select a cohort of at least 3 year-matched controls (no CC-RCC death) for each case (n = 263 patients). Detection of IGF-IR was performed using a commercially available monoclonal antibody. Cox proportional hazards models were fit to assess the association between IGF-IR expression and disease-specific survival. RESULTS After adjustment for age, the risk of death from CC-RCC was greater for patients who had tumors that stained positive for IGF-IR compared with patients who had tumors that showed no IGF-IR expression (hazard ratio [HR], 1.5; 95% confidence interval, [95% CI], 0.9–2.4). In a stratified analysis, the risk was stronger among patients who had high-grade tumors (HR, 2.2; 95% CI, 1.1–4.3) compared with patients who had low-grade tumors (HR, 0.7; 95% CI, 0.3–1.5). Multivariate adjustment for tumor size and histologic tumor necrosis attenuated the association among all patients (HR, 1.3; 95% CI, 0.8–2.1) but strengthened the association among patients with high-grade tumors (HR, 2.7; 95% CI, 1.3–5.6). CONCLUSIONS The current data suggest that IGF-IR expression is associated with poor survival in patients who are diagnosed with early-stage CC-RCC, especially among those with high-grade disease. Cancer 2004. © 2004 American Cancer Society.
Analysis of Spawning Stock Biomass per Recruit: An Example for Georges Bank Haddock

Abstract Analysis of spawning stock biomass per recruit has been used to evaluate the effects of fishing mortality and age at first capture on the spawning potential of a stock. This technique, which is analogous to yield-per-recruit analysis, is used to analyze stock-recruitment data. It may be used to develop a long-term management strategy to maintain or enhance spawning stock biomass. We analyzed fishery data on Georges Bank haddock Melanogrammus aeglefinus by using this technique. Currently, this stock is at about 16% of the maximum possible spawning stock biomass per recruit, but it appears that this ratio must reach at least 30% to maintain the stock at its present level, if recent recruitment patterns persist.
Granules in cisternae of the rough endoplasmic reticulum (RER) of preameloblasts and ameloblasts and a possible function of the RER in preameloblasts of rat incisor.

In the secretion zone of incisor teeth of adult rats, fixed with a glutaraldehyde-OsO4 sequence, some ameloblasts (referred to as granulated ameloblasts) are filled with spherical granules up to 1.5 μ in diameter. In the electron microscope these granules are seen to be localized within the cisternae of the RER. They occur mainly in that part of the cytoplasm of granulated ameloblasts bounded by the apical and basal terminal bars. In contrast to normal ameloblasts, the Golgi apparatus of granulated ameloblasts contains only few dictyosomes, and no secretion granules were identified in these cells. However, lysosomes and other vesicles occur to about the same degree in both normal and granulated ameloblasts. The intracisternal granules of ameloblasts in the secretion zone resemble those found in preameloblasts. It is suggested that: (a) intracisternal granules in preameloblasts and granulated ameloblasts are caused by interference with transport of enamel proteins from RER to Golgi apparatus. In preameloblasts, intracisternal granules would play a role in a storage mechanism; (b) granulated ameloblasts in the secretion zone failed to establish a normal relationship between RER and Golgi apparatus when enamel secretion started. Thus, they would be abortive ameloblasts, without specialized function.
Expression of the heat shock gene hsp16.6 and promoter analysis in the cyanobacterium, Synechocystis sp. PCC 6803.

hsp16.6 and its upstream region from the cyanobacterium, Synechocystis sp. PCC 6803, have been analyzed. The hsp16.6 transcriptional start point was positioned 44 base pairs (bp) upstream of the ATG translation start codon. A reporter vector was constructed by ligating the 265 bp upstream fragment onto the upstream region of the lacZ coding sequence. β-galactosidase analysis indicated that the 265 bp region did not induce lacZ gene expression in E. coli; although expression was induced when the Synechocystis groESL promoter was used. In Synechocystis cells, lacZ was expressed when the 265 bp fragment was used as a promoter. Cold stress and ethanol did not induce lacZ expression, while heat shock, salt stress, sorbitol, hydrogen peroxide, and high light induced lacZ. A series of deletions from the 265 bp region demonstrated that a region around −35 was essential for hsp16.6 expression.
Thoracic outlet syndrome surgery causing severe brachial plexopathy

Hundreds of first rib resections are performed yearly in the United States to treat a controversial type of neurogenic thoracic outlet syndrome (NTOS). This surgery was thought to be devoid of serious neurological complications until 1982. However, that year Dale unearthed the rather astounding fact that the members of a single surgical society were aware of nearly 300 brachial plexus injuries resulting in motor deficits that had occurred during such operations, although almost none had been reported in the literature. In this report the features of the two main types of NTOS ("true" and "disputed") are discussed. The history of brachial plexus injury occurring during TOS surgery is traced back to the late nineteenth century. The clinical and electrophysiological features of eight patients who sustained such injuries are described in detail, the literature on this topic is reviewed, and the location and causes for these injuries are discussed.
Selective collateral elimination in early postnatal development restricts cortical distribution of rat pyramidal tract neurones.

The pyramidal tract, comprising those axons which pass from the neocortex to the medulla and spinal cord, is among the most thoroughly studied projections of the mammalian cortex. Recent studies using anterograde axon tracing techniques have provided information concerning the time course of the growth of pyramidal tract fibres1,2, yet much remains to be learned about its development. We have now begun to study the distribution of the neurones of origin of the pyramidal tract during the postnatal development of the rat neocortex using the recently introduced retrogradely transported fluorescent marker, True blue3. During the first postnatal week, injections of True blue into the pyramidal decussation result in the labelling of pyramidal tract neurones which are distributed virtually throughout the tangential extent of layer V of the neocortex, whereas after comparable injections during the fourth postnatal week the distribution of such cells is much more restricted and remains restricted into adult life. This developmental restriction is most dramatic in the occipital cortex: during the first postnatal week many pyramidal tract neurones are found throughout the visual cortex while none is seen in this area in the adult. When True blue is injected into the pyramidal decussation during the first postnatal week and the animals are allowed to survive until the fourth postnatal week, the distribution of pyramidal tract neurones is as widespread as in the immediate postnatal period and includes the entire visual cortex. This implies that many of the neurones in the occipital cortex initially send a collateral into the pyramidal tract which is later eliminated, although the neurones themselves persist. These findings, together with similar recent observations on the development of the callosal connections4,5, indicate that the elimination of axon collaterals may be a general feature of the development of cortical projection systems, and that such transitory collaterals may traverse considerable distances.
The Social Networks of Leaders in More and Less Viable Rural Communities1

The relationship between the social networks of leaders and community viability is examined in a comparative study of leaders (N = 75) in five rural communities (population range, 1,000 to 2,500). The analysis looks at leaders' connections to organizations outside of their communities and at different kinds of linkages between leaders within their respective communities. Leaders in more and less viable communities do not differ much in characteristics such as age, education, and occupations, but the presence of women in leadership positions is associated with community viability. In addition, there is some support for the expectation that leaders in more viable communities are more likely to have formal linkages to statewide and national networks. The most important finding, however, is that the way in which leaders relate to each other in instrumental tasks within their respective communities is associated with community viability.
Bioenergetics and bioremediation of contaminated soil

Abstract The microbial biodegradation of xenobiotic compounds in soil and ground water is constrained by the laws of thermodynamics. Bioremediation is being investigated in a rhizosphere environment in which higher plants provide carbon and energy to sustain the microbial population. Toluene, phenol, trichloroethylene and trichloroethane have been fed in separate experiments to a pilot scale system with alfalfa growing in sandy soil containing less than 10% of silt. It is well known that microbial populations are numerous in the root zone of healthy vegetation. Root exudates can stimulate aerobic microbial biodegradation of compounds which by themselves support growth poorly or not at all. Polynuclear aromatic compounds such as phenanthrene, anthracene, and pyrene, which are not very soluble in water, and chlorinated aliphatic hydrocarbons such as trichloroethylene are examples of compounds that can be biodegraded in the rhizosphere when root exudates are present to enhance and sustain microbial activity. Solar driven transport processes such as water and solute movements due to evapotranspiration increase the likelihood that the contaminants will come into contact with the microorganisms and be degraded. The thermodynamic and bioenergetic aspects of transport and biodegradation in the rhizosphere are examined through a review of the literature and the analysis of experimental data collected in the pilot scale system.
Bringing proteomics into the lab: Proteomics lab 101

With the increasing importance and visibility of proteomics there is a notable lack of teaching tools that can be used for “hands on” proteomic experience. Here we describe a simple lab for teaching proteomics that is based on the two-hybrid system. Using only simple modifications of a commercial system, an experiment set is described that takes the student from the identification of potential protein:protein interactors from a large set of proteins through the classification of the disruption of these interactions in response to the presence of a neurotoxin, in this case lead. The lab uses a prokaryotic two-hybrid system and two human neuronal cDNA libraries as the pool from which the initial interactors are drawn. The prokaryotic system provides increased transformation efficiencies, which translate into better cDNA library representation. The lab concludes with the identification of protein:protein interactions that are affected by increasing amounts of neurotoxin and the sequencing of the cDNA-encoded genes. Students not only gain hands on proteomic experience but also then relate their sequence to an entry in one of the burgeoning sequence databases to glean information about the identified molecular target. The experiment set is flexible and could be adapted for use with any compound that affects protein complex formation.
Effect of recombinant human inhibin on gonadotropin secretion by the male rat.

We have examined the effect of recombinant human inhibin-A on basal and GnRH-induced gonadotropin secretion by male rats or cultured anterior pituitary cells. Inhibin, administered sc 6 h before the experiment, induced doseand time-related decreases in plasma FSH, but not LH, levels in both intact and castrated male rats. Inhibin also significantly interfered with the in vivo stimulatory effect of 20-500 ng GnRH on FSH release, but had inconsistent and usually modest effects on the LH response. While exposure of cultured pituitary cells to inhibin for 72 h has been reported to interfere with GnRHinduced gonadotropin release, we examined here the effects of shorter exposure periods relevant to in vivo experiments. Exposure of the cells to inhibin (31.3-312.5 pM) for 2-6 h measurably (P S 0.01) decreased the ability of 10 nM GnRH to stimulate both FSH and LH released by cultured cells. In contrast, lower (3.1 and 9.4 pM) doses of inhibin had little or no effect. Longer exposures to inhibin (10, 24, and 72 h...
A note on the problem of pure bending for linear elastic materials with voids

This note concerns the problem of quasi-static pure bending of a beam in the context of the complete theory of linear elastic materials with voids presented in [1]. It is shown here that the solution in the context of the complete theory of [1] is coincident with the pure bending solution of classical elasticity for small time, and that the solution for large time is the bending solution given in [1], a solution which neglected the rate effect in the complete theory of [1]. In between these two limit solutions the rate effect moderates a monotonic transition.
Inert gases in a terra sample. Measurements in six grain-size fractions and two single particles from Luna 20

Review of the results of inert gas measurements performed on six grain-size fractions and two single particles from four samples of Luna 20 material. Presented and discussed data include the inert gas contents, element and isotope systematics, radiation ages, and Ar-36/Ar-40 systematics.
Influence of the turbulent diffusion boundary layer on the apparent kinetics of surface catalysed reactions in external flow systems

Abstract Steep gradients of reactant concentration in the immediate vicinity of solid catalysts in forced-flow systems cause the apparent chemical kinetics of surface catalysed reactions to differ from the true interfacial kinetics. In the present paper the magnitude of this falsification is investigated quantitatively for the case of turbulent incompressible flow within the diffusion boundary layer, using the uniform activity catalytic flat plate as an example. Corresponding results for laminar diffusion layers are included for comparison. Several distinct computational techniques are briefly discussed for diffusional Prandtl numbers Pr ≡ ν/ D of order unity as well as for the asymptotic extreme Pr → ∞. While the accuracy of predictions which completely neglect the effect of upstream reaction history on the local transfer coefficient is found to be better than in the corresponding laminar boundary layer case, their accuracy degenerates as the diffusional Prandtl number is increased (contrary to the fully laminar case). Using a rational improvement of the Frank-Kamenetskiĭ quasi-stationary approximation, results are given for all pertinent non-dimensional reaction rate coefficients over the entire range from reaction rate to diffusion-control for half-order, first-order and second-order irreversible, surface-catalysed reactions.
The future CESR–CLEO program

Abstract After the completion of this year's upgrade installation, CLEO will be able to run at luminosities in excess of 10 33 /cm 2 s with improved tracking and particle identification. Plans are underway for a future upgrade to bring CESR luminosity to the level of 3×10 34 . Such luminosities will be required for a full understanding of CP violation in B decays.
Toxin from Skin of Frogs of the Genus Atelopus: Differentiation from Dendrobatid Toxins

A potent, dialyzable toxin (atelopidtoxin) occurs in the skin of frogs of the genus Atelopus . A concentrate of atelopidtoxin from Atelopus zeteki has an LD50 in mice of 16 micrograms per kilogram. It differs from batrachotoxin, tetrodotoxin, and saxitoxin, the only known nonprotein substances of greater toxicity, as well as from all toxins previously isolated from amphibia.
DISTRESS, ELEVATED CORTISOL, COGNITIVE DEFICITS, AND ILLNESS FOLLOWING A NATURAL DISASTER☆

It was hypothesized that students who endured harm following a hurricane would show more distress and illness than students who were threatened by the storm's impact, and threatened students would be distressed more than students at two remote locations. These hypotheses were tested by obtaining measures of distress, performance, and hormones (cortisol and testosterone) from 160 students on four college campuses. The hypotheses received partial support. As hypothesized, threatened students had higher levels of illnesses than students at remote sites, but they did not report more psychological distress. Further, the highest levels of cortisol levels and lowest levels of cognitive complexity were recorded among students who had been harmed as well as threatened. These results were interpreted in terms of social stage models of behavioral inhibition.
Adaptive optimal array detection of targets of unknown spatial location

A primary reason that much attention has been given to array antenna systems is their ability to perform rapid inertialess scanning.[1][2] Despite this great interest in array processing,[3]-[6] the concept of an overall Bayesian approach to the scanning-detection problem has attracted little attention.[7] Classically "beams" are pointed at discrete spatial locations and detection decisions made on a local basis. Other suggested solutions include several non-parametric approaches[8]-[10] and a generalized likelihood ratio approach.[11]
The Authoritative Medium: George Eliot, Ruin, and the Rationalized Market

This essay analyses the competing dynamics that shaped the formation of market relations in mid-nineteenth-century Britain: abstraction and rationalization, on the one hand, and embeddedness and personalism, on the other. It takes as its central case the mid-century debates over bankruptcy reform, focusing in particular on two textual representations of ‘ruin’: the system of certificates classifying bankrupts according to their culpability of character, established in 1849 and abolished in 1861; and Eliot's 1860 novel The Mill on the Floss, with its account of financial and sexual ruin. I argue that the debates surrounding the character certificates' intervention in market relations, and Eliot's explorations of abstract and embedded or sympathetic modes of knowledge were part of a larger concern to negotiate the tensions produced by the contemporary impulse toward market rationalization. Eliot's mode of omniscient narration – her construction of a simultaneously interested and disinterested, authoritative...
Effects of chronic and acute ozone exposure on lipid peroxidation and antioxidant capacity in healthy young adults.

BackgroundThere is growing evidence for the role of oxidative damage in chronic diseases. Although ozone (O3) is an oxidant pollutant to which many people are exposed, few studies have examined whe...
WHAT COGNITIVE PROCESSES ARE TRIGGERED BY INPUT ENHANCEMENT

Recently in Second Language Acquisition research much attention has been focused upon the cognitive mechanisms that underpin learner processing of input. In studies of how second language instruction has an effect on L2 learner’s subsequent processing of input, researchers have examined how external manipulation of input can affect intake and subsequent learning. In this literature review, input enhancement (an instantiation of manipulated input) will be examined in light of current cognitive psychological models of attention and memory. After reviewing current models of attention and memory as they pertain to SLA, previous input enhancement studies will be analyzed in order to see how input enhancement could affect L2 learner processing. Particular attention will be paid to the potential triggering effects of input enhancement as well as its impact upon second language learning.
Degeneracy-driven self-structuring dynamics in selective repertoires.

Numerous biological interactions, such as interactions between T cell receptors or antibodies with antigens, interactions between enzymes and substrates, or interactions between predators and prey are often not strictly specific. In such less specific, or “sloppy,” systems, referred to here as degenerate systems, a given unit of a diverse resource (antigens, enzymatic substrates, prey) is at risk of being recognized and consumed by multiple consumers (lymphocytes, enzymes, predators). In this study, we model generalized degenerate consumer-resource systems of Lotka–Volterra and Verhulst types. In the degenerate systems of Lotka–Volterra, there is a continuum of types of consumer and resource based on variation of a single trait (characteristic, or preference). The consumers experience competition for a continuum of resource types. This non-local interaction system is modeled with partial differential-integral equations and shows spontaneous self-structuring of the consumer population that depends on the degree of interaction degeneracy between resource and consumer, but does not mirror the distribution of resource. We also show that the classical Verhulst (i.e. logistic) single population model can be generalized to a degenerate model, which shows qualitative behavior similar to that in the degenerate Lotka–Volterra model. These results provide better insight into the dynamics of selective systems in biology, suggesting that adaptation of degenerate repertoires is not a simple “mirroring” of the environment by the “fittest” elements of population.
Monomorphisms between subgroups of groups of type G2

Abstract Abstract monomorphisms of a full subgroup of a group of type G 2 into another group of type G 2 are shown to have a standard decomposition into a field monomorphism and a special isogeny of algebraic groups.
“If it is too inconvenient I'm not going after it:” Convenience as a critical factor in information-seeking behaviors

Abstract In today's fast-paced world, anecdotal evidence suggests that information tends to inundate people, and users of information systems want to find information quickly and conveniently. Empirical evidence for convenience as a critical factor is explored in the data from two multi-year, user study projects funded by the Institute of Museum and Library Services. The theoretical framework for this understanding is founded in the concepts of bounded rationality and rational choice theory , with Savolainen's (2006) concept of time as a context in information seeking , as well as gratification theory , informing the emphasis on the seekers' time horizons. Convenience is a situational criterion in peoples' choices and actions during all stages of the information-seeking process. The concept of convenience can include their choice of an information source, their satisfaction with the source and its ease of use, and their time horizon in information seeking. The centrality of convenience is especially prevalent among the younger subjects (“millennials”) in both studies, but also holds across all demographic categories—age, gender, academic role, or user or non-user of virtual reference services. These two studies further indicate that convenience is a factor for making choices in a variety of situations, including both academic information seeking and everyday-life information seeking, although it plays different roles in different situations.
Value of maintenance therapy with oral tocolytics: a systematic review.

Objective: The objective was to perform a systematic review of prospective randomized trials evaluating the efficacy of oral tocolytics in the prevention of recurrent preterm labor and its associated complications.Methods: A MEDLINE search of English language articles published since 1966 was performed to identify studies of maintenance oral tocolytic therapy. Studies were included in the review which: 1) randomized patients to an oral tocolytic after stabilization with parenteral therapy; 2) reported results for either a placebo or a control group; and 3) included patients with intact membranes only. These studies were analyzed for nine outcomes, including incidence of preterm delivery, incidence of recurrent preterm labor, latency from treatment to delivery, gestational age, birthweight, admission to an intensive care nursery (ICN), incidence of respiratory distress syndrome (RDS), incidence of intraventricular hemorrhage (IVH), and perinatal mortality.Results: Seven studies met the inclusion criteria, ...
Rewiring makes the difference.

Mol Syst Biol. 7: 463 While canonical pathways and regulatory networks provide a representation of molecular interactions in the cell that appears static and immutable, actual regulatory pathways are anything but. Rather, they appear to reconfigure dynamically as a function of the specific molecular context in which they operate. This was shown initially in yeast (Luscombe et al , 2004) and more recently in mammalian cells (Mani et al , 2008; Wang et al , 2009). Now, in an elegant study recently published in Science, Trey Ideker, Nevan Krogan, Michael‐Christopher Keogh and colleagues show that the cellular response to environmental stress is also associated with massive rewiring of genetic interaction networks (Bandyopadhyay et al , 2010). Specifically, the authors tested 80 000 genetic interactions, both under standard laboratory conditions and upon perturbation by the DNA damaging agent methyl methanesulfonate (MMS). Using the epistatic miniarray profiles technique (Schuldiner et al , 2006), strains carrying systematical pairwise deletions (for non‐essential genes) or hypomorphic alleles (for essential genes) were tested to …
Mapping Protease Inhibitor Resistance to Human Immunodeficiency Virus Type 1 Sequence Polymorphisms within Patients

Resistance genotyping provides an important resource for the clinical management of patients infected with human immunodeficiency virus type 1 (HIV-1). However, resistance to protease (PR) inhibitors (PIs) is a complex phenotype shaped by interactions among nearly half of the residues in HIV-1 PR. Previous studies of the genetic basis of PI resistance focused on fixed substitutions among populations of HIV-1, i.e., host-specific adaptations. Consequently, they are susceptible to a high false discovery rate due to founder effects. Here, we employ sequencing "mixtures" (i.e., ambiguous base calls) as a site-specific marker of genetic variation within patients that is independent of the phylogeny. We demonstrate that the transient response to selection by PIs is manifested as an excess of nonsynonymous mixtures. Using a sample of 5,651 PR sequences isolated from both PI-naive and -treated patients, we analyze the joint distribution of mixtures and eight Pis as a Bayesian network, which distinguishes residue-residue interactions from direct associations with PIs. We find that selection for resistance is associated with the emergence of nonsynonymous mixtures in two distinct groups of codon sites clustered along the substrate cleft and distal regions of PR, respectively. Within-patient evolution at several positions is independent of PIs, including those formerly postulated to be involved in resistance. These positions are under strong positive selection in the PI-naive patient population, implying that other factors can produce spurious associations with resistance, e.g., mutational escape from the immune response.
Nursing Models and Community as Client

Each of the four nursing frameworks discussed here represents worldviews that result in different meanings of the concepts of health, community, and, therefore, of community health. Orem's framework reflects a casual model of the community as an aggregate of individuals and a concept of health that is most akin to Smith's clinical and functional levels of health. Roy's model broadens to allow for consideration of the community as a system. The community as a system is perceived from the perspective of behaviors in response to stimuli. Causality is time ordered and linear, although one must consider the context of continuing time through the mechanism of feedback loops. Smith's adaptive level of health is most congruent with this perspective. King's conceptual framework views the community as a system interacting with the personal and interpersonal systems it includes. Causality is necessarily symmetrical within a systems approach. Health includes both role performance and adaptive levels of health. Finally, Rogers' model considers the community as a field in itself. That field is one of awareness, is integral with the environmental field, and is acausal in nature. Health as expanding awareness is most similar to Smith's eudaimonistic concept of health. It is proposed that these four frameworks reflect increasingly integrated conceptions of community health by which to guide public health/community health nursing practice.
Development Theory, Globalism, and the New World Order: The Need for a Postmodern, Antiracist, and Multicultural Critique

In a 1991 article, "P.C. and the Politics of Multiculturalism in Higher Education," Evelyn Hu-Dehart discusses and analyzes the ongoing ideological debate between those advocating multicultural education and their opponents. These so-called culture wars that have been waged on university campuses and in national media debates are often polemical, intense, and heated. The debate over multiculturalism forms the ideological and political context of my own analysis. I, therefore, will begin by providing some self-explanatory quotes from Hu-Dehart and from Richard Bernstein, who recently has strongly attacked diversity and multiculturalism in his book Dictatorship of Virtue: Multiculturalism and the Battle for America's Future.
H3K27 demethylation at the proviral promoter sensitizes latent HIV to the effects of vorinostat in ex-vivo cultures of resting CD4+ T cells

ABSTRACT Histone methyltransferase inhibitors (HMTis) and histone deacetylase inhibitors (HDACis) are reported to synergistically induce the expression of latent human immunodeficiency virus type 1 (HIV-1), but studies have largely been performed with cell lines. As specific and potent HMTis directed at EZH1 (enhancer of zeste 2 Polycomb repressive complex 2 subunit 1)/EZH2 are now in human testing, we wished to rigorously test such an inhibitor in a primary resting T-cell model of HIV latency. We found that GSK343, a potent and selective EZH2/EZH1 inhibitor, reduced trimethylation of histone 3 at lysine 27 (H3K27) of the HIV provirus in resting cells. Remarkably, this epigenetic change was not associated with increased proviral expression in latently infected resting cells. However, following the reduction in H3K27 at the HIV long terminal repeat (LTR), subsequent exposure to the HDACi suberoylanilide hydroxamic acid or vorinostat (VOR) resulted in increases in HIV gag RNA and HIV p24 antigen production that were up to 2.5-fold greater than those induced by VOR alone. Therefore, in primary resting CD4 + T cells, true mechanistic synergy in the reversal of HIV latency may be achieved by the combination of HMTis and HDACis. Although other cellular effects of EZH2 inhibition may contribute to the sensitization of the HIV LTR to subsequent exposure to VOR, and to increase viral antigen production, this synergistic effect is directly associated with H3K27 demethylation at nucleosome 1 (Nuc-1). Based upon our findings, the combination of HMTis and HDACis should be considered for testing in animal models or clinical trials. IMPORTANCE Demethylation of H3K27 mediated by the histone methyltransferase inhibitor GSK343 in primary resting T cells is slow, occurring over 96 h, but by itself does not result in a significant upregulation of cell-associated HIV RNA expression or viral antigen production. However, following H3K27 demethylation, latent viral expression within infected primary resting CD4 + T cells is synergistically increased upon exposure to the histone deacetylase inhibitor vorinostat. Demethylation at H3K27 sensitizes the HIV promoter to the effects of an HDACi and provides a proof-of-concept for the testing of combination epigenetic approaches to disrupt latent HIV infection, a necessary step toward the eradication of HIV infection.
An Efficient Implementation of a Joint Generation Algorithm

Let \(\mathcal{C}\) be an n-dimensional integral box, and π be a monotone property defined over the elements of \(\mathcal{C}\). We consider the problems of incrementally generating jointly the families \(\mathcal{F}_{\pi}\) and \(\mathcal{G}_{\pi}\) of all minimal subsets satisfying property π and all maximal subsets not satisfying property π, when π is given by a polynomial-time satisfiability oracle. Problems of this type arise in many practical applications. It is known that the above joint generation problem can be solved in incremental quasi-polynomial time. In this paper, we present an efficient implementation of this procedure. We present experimental results to evaluate our implementation for a number of interesting monotone properties π.
Crossbridge head detachment rate constants determined from a model that explains the behavior of both weakly- and strongly-binding crossbridges.

Experimentally it is observed that the head regions of weakly-binding myosin cross-bridges (crossbridges with ATP or ADP.Pi at the nucleotide binding site) are mobile while attached to actin, while strongly-binding crossbridge heads, such as those with PPi or AMP-PNP at the nucleotide binding site, are immobile (Pate and Cooke, Biophys. J., 1988; Fajer et al., Biophys. J., 1988). I postulate that the fundamental difference between weakly-and strongly-binding crossbridges is not their difference in affinity for actin, but the difference in mobility of the myosin heads attached to actin. Because the heads of weakly-binding crossbridges are mobile while attached to actin, the heads function independently and their behavior can be described by a simple independent-head model. With strongly-binding crossbridges, when one head detaches, it cannot re-attach in a position of lesser strain while the other is attached immobile; both heads must be detached concurrently before the crossbridge can relocate to a position of less strain and relax any tension it supports. This makes the heads appear to act cooperatively. A double-headed cross-bridge model is presented which takes into account the difference between weakly-and strongly-binding crossbridges. The model is quite successful at describing the experimental data. In particular, for weakly-binding crossbridges the time constant of the response to stretch is shown to be relatively insensitive to ionic strength and for strongly-binding crossbridges, the model predicts with great accuracy the large ionic strength dependence of the rate constant for force decay. When the experimental results are interpreted according to the model, an important conclusion that emerges is that in all cases (for both weakly-and strongly-binding crossbridges) unstrained crossbridge heads in the muscle fiber detach from actin with approximately the same rate constant as myosin subfragment-1 detaches from actin in solution.
Design and analysis of the Ward converter for capacitor charging applications

A prototype capacitor charging power supply (CCPS) utilising the Ward converter circuit topology has been developed and evaluated by charging various values of energy storage capacitors and discharging them at various repetition rates. This converter topology is naturally protected against short circuit conditions. The primary side of the transformer appears as a current source to the energy storage capacitor, which is a desirable characteristic when charging a large capacitor. The operation of the CCPS is discussed, followed by the analysis and design of the CCPS. Experimental results obtained from the CCPS are given. >
Elastic properties of laminated calcium aluminosilicate/silicon carbide composites determined by resonant ultrasound spectroscopy

The elastic properties of unidirectional and 0°/90° crossply Nicalon-SiC-fiber-reinforced calcium aluminosilicate (CAS/SiC) ceramic-matrix composites have been measured using a resonant ultrasound spectroscopy (RUS) technique. This approach has allowed the nondestructive determination of the complete set of independent second-order elastic stiffness constants of these ceramic composites. These stiffness data have been used to obtain the orientation dependence of Young's modulus and the shear modulus. The results are in reasonably good agreement with the limited experimental data obtained from mechanical testing. The RUS measurements reveal that the unidirectional CAS/SiC composite is well modeled by transverse isotropic symmetry, indicating relatively isotropic fiber spacing in the transverse plane. The analysis indicates that the overall elastic anisotropy is also small for unidirectional and 0°/90° laminated CAS ceramic-matrix composites, a result that can be attributed to the relatively low modulus ratio of the Nicalon SiC fiber to the CAS matrix and to the moderate fiber volume fraction.
The interaction of internal waves with an unsteady non-uniform current

On the assumptions of incompressibility, and negligible thermal conduction, salinity diffusion and viscosity, simple expressions are derived for the conservation equations of mass, momentum and energy when internal waves encounter an unsteady non-uniform current. These expressions of conservation equations are valid for all kinds of internal waves without regard to their different characteristics. From the dynamical conservation equations, we find that a stress-like term, the ‘excess momentum flux tensor’, plays an important role in the interaction between internal waves and an unsteady non-uniform current. Furthermore, it is deduced from the energy balance equation that, in the encounter of interfacial waves with a steady non-uniform current in a two-liquid system, the waves are amplified in an adverse current but suppressed in an advancing current as a result of interaction of the waves with the current. This conclusion may explain the large amplitudes sometimes observed in internal waves near the confluence of currents and near fronts at the thermocline, the region in the ocean where the density gradient is a maximum.
Projection pursuit in high dimensional data reduction: initial conditions, feature selection and the assumption of normality

Supervised classification techniques use labeled samples to train the classifier. Often the number of such samples is limited, thus limiting the precision with which class characteristics can be estimated. As the number of spectral bands becomes large, the limitation on performance imposed by the limited number of training samples can become severe. Such consequences suggest the value of reducing the dimensionality by a pre-processing method that takes advantage of the asymptotic normality of projected data. Using a technique called projection pursuit, a pre-processing dimensional reduction method has been developed based on the optimization of a projection index. A method to estimate an initial value that can more quickly lead to the global maximum is presented for projection pursuit using the Bhattacharyya distance as the projection index.
Ubicorder: A Mobile Device for Situated Interactions With Sensor Networks

The Ubicorder is a mobile, location and orientation aware device for browsing and interacting with real-time sensor network data. In addition to browsing data, the Ubicorder also provides a graphical user interface (GUI) that users can use to define inference rules. These inference rules detect sensor data patterns, and translate them to higher order events. Rules can also be recursively combined to form an expressive and robust vocabulary for detecting real-world phenomena, thus enabling users to script higher level and relevant responses to distributed sensor stimuli. The Ubicorder's mobile, handheld form-factor enables users to easily bring the device to the phenomena of interest, hence simultaneously observe or cause real-world stimuli and manipulate in-situ the event detection rules easily using its graphical interface. In a first-use user study, participants without any prior sensor network experience rated the Ubicorder highly for its usefulness and usability when interacting with a sensor network.
Differential effects on natural reward processing in rats after repeated heroin

Rationale Heroin users report reward deficits as well as reward enhancements (to drug stimuli). To better understand the causal relation between chronic heroin and alterations in natural reward processing, we used experimental techniques in animal models.
’Marketing in the 1970s: A Symposium’ Revisited and a Trepidations Peek at the 1990s

In the January, 1970 issue of the Journal of Marketing, then-editor Eugene J. Kelley ran a special lead section entitled "Marketing in the 1970s: A Symposium." Solicited articles from eight pre-eminent scholars comprised this collection. The following paper steps back two decades in time and reviews the predictions made and their accuracy. Some of the more momentous missed calls are also addressed and some qualified prognostications are made with respect to this concluding decade of the twentieth century.
Functional significance of human trp1 and trp3 in store-operated Ca2+ entry in HEK-293 cells

The Drosophila trp (transient receptor potential) gene appears to encode the Drosophilastore-operated channel (SOC), and some mammalian trp homologues have been proposed to encode mammalian SOCs. T...
Genetic disruption of Ano5 in mice does not recapitulate human ANO5 -deficient muscular dystrophy

Anoctamin 5 (ANO5) is a member of a conserved gene family (TMEM16), which codes for proteins predicted to have eight transmembrane domains and putative Ca2+-activated chloride channel (CaCC) activity. It was recently reported that mutations in this gene result in the development of limb girdle muscular dystrophy type 2L (LGMD2L), Miyoshi myopathy type 3 (MMD3), or gnathodiaphyseal dysplasia 1 (GDD1). Currently, there is a lack of animal models for the study of the physiological function of Ano5 and the disease pathology in its absence. Here, we report the generation and characterization of the first Ano5-knockout (KO) mice. Our data demonstrate that the KO mice did not present overt skeletal or cardiac muscle pathology at rest conditions from birth up to 18 months of age. There were no significant differences in force production or force deficit following repeated eccentric contractions between wild type (WT) and KO mice. Although cardiac hypertrophy developed similarly in both KO and WT mice after daily isoproterenol (ISO, 100 mg/kg) treatment via intraperitoneal injection for 2 weeks, they were functionally indiscernible. However, microarray analysis identified the genes involved in lipid metabolism, and complement pathways were altered in the KO skeletal muscle. Taken together, these data provide the evidence to show that genetic ablation of Ano5 in C57BL/6J mice does not cause overt pathology in skeletal and cardiac muscles, but Ano5 deficiency may lead to altered lipid metabolism and inflammation signaling.
Ovine fetal and adult atrial natriuretic factor metabolism

Studies were conducted to quantify ovine fetal and adult atrial natriuretic factor (ANF) metabolism. A total of 14 pregnant ewes with singleton fetuses were prepared with vascular catheters. In protocol 1, six fetuses (mean gestation, 131 +/- 1 days) received intravenous infusions of synthetic human ANF (hANF, 100 ng.min-1.kg-1) for 60 min. Mean basal fetal plasma ANF levels increased from 180 +/- 44 pg/ml to a steady-state level of 1,233 +/- 192 pg/ml. In protocol 2, five fetuses (mean gestation, 130 +/- 1 days) received successive 40-min infusions of hANF at 5, 25, and 100 ng.min-1.kg-1. Although basal fetal plasma ANF levels (522 +/- 135 pg/ml) were greater than those observed in protocol 1, fetal plasma ANF levels increased to 1,580 +/- 295 pg/ml at the highest infusion rate. In both protocols 1 and 2, basal fetal plasma ANF levels were three- to fourfold greater than maternal levels. The fetal plasma ANF clearance rates calculated from protocol 1 and from the 25- and 100-ng.min-1.kg-1 infusions from protocol 2 were similar (89 +/- 10, 120 +/- 31, and 116 +/- 38 ml.min-1.kg-1, respectively) and were combined to yield a mean estimated fetal plasma ANF clearance rate of 102 +/- 11 ml.min-1.kg-1. In protocol 3, adult plasma ANF levels increased from 137 +/- 36 to 4,142 +/- 776 pg/ml in response to ANF infusion at 200 ng.min-1.kg-1. The mean plasma ANF clearance rate calculated for the adult animals was 59 +/- 12 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
The volume and compressibility change for the formation of the LaSO 4 + ion pair at 25°C

The apparent molal volumes (φv) and adiabatic compressibilities [φK(S)] of La2(SO4)3 solutions have been determined from density and sound speed data at 25°C. The large positive deviations of φv and φK(S) of La2(SO4)3 from the limiting law have been attributed to the formation of the ion pair LaSO 4 + . The observed values of φv and φK(S) have been used to estimate the change in the apparent molal volume and adiabatic compressibility for the formation of LaSO 4 + from $$\Delta \phi (LaSO_4^ + ) = [\phi (obs.) - \phi (2La^{3 + } ,3SO_4^{2 - } )]/\alpha$$ where ϕ(2La3+, 3SO 4 2− ) is the apparent molal volume or adiabatic compressibility of the free ions, and α is the degree of association. The value of $$\Delta \phi _v^o (LaSO_4^ + ) = \Delta \bar V^o (LaSO_4^ + ) = 22.8 \pm 1cm^3 - mole^{ - 1}$$ and $$\Delta \phi _{K(S)}^o (LaSO_4^ + ) = \Delta \bar K_S^o (LaSO_4^ + ) = 85 \pm 20 \times 10^{ - 4} cm^3 - mole^{ - 1} - bar^{ - 1}$$ at infinite dilution are in reasonable agreement with the values determined from the high-pressure conductance data of Fisher and Davis. The number of hydrated water molecules (ca. 11) associated with the formation of LaSO 4 + determined from the volume and compressibility data are in good agreement.
Simultaneous administration of adrenal cortical extract and desoxycorticosterone; effects on blood pressure of hypertensive patients.

ConclusionsIn patients with hypertensive vascular disease, the simultaneous administration of an adrenal cortical extract appears to block the pressor effect of deoxycorticosterone acetate when used alone.
Higher Order Squeezing of Thermal Radiation through Parametric Amplification

A few years back Hong and Mandel1 introduced the notion of higher order squeezing and showed that it occured in a number of non-linear optical processes. Higher order squeezing is an attractive idea because it allows, in principle, a much larger fractional noise reduction than ordinary (or second order) squeezing. In their original work Hong and Mandel considered only the squeezing of vacuum fluctuations. Here we show that thermal and Fock states, which have a high intrinsic phase noise, can also be made to undergo higher order squeezing. The process we use to illustrate and discuss higher order squeezing is ideal parametric amplification. This provides us with an analytically tractable model within which we can examine many of the features of this squeezing in detail.