cssi/SciSciGPT-SciSciNet huggingface dataset:
Exploring the role of PDE10 inhibition in ovarian cancer carcinogenesis in the egg-laying hen using RNA sequencing

Objectives: Here we investigate a novel phosphodiesterase 10 (PDE10) inhibitor, MCI-030, as a drug candidate for the treatment or prevention of epithelial ovarian cancer (EOC). Prior research showed that MCI-030 decreased cancer incidence in the egg laying hen spontaneous model of EOC by a novel mechanism involving dual suppression of Wnt and MAPK signaling. This study aims to further understand the molecular pathways affected by MCI-030 in preventing EOC development. Methods: Hens were treated with MCI-030 or control feed for 6 months. Necropsy was then performed to assess tumor development. Total RNA from ovarian tissue of 8 MCI-030-treated hens (4 tumor, 4 normal) and 8 control hens (4 tumor, 4 normal) was isolated and analyzed for differential gene expression using RNA sequencing (RNAseq). RNAseq was performed by paired-end 75bp sequencing with ~35 million reads coverage using the Illumina NextSeq500 platform. Genes were mapped to the Gallus[gp1] GRCg6 reference genome. Differential gene expression analysis was performed using DESeq2; pathways were investigated in the Molecular Signatures Database of the GSEA ( www.gsea-msigdb.org ). Results: Tumors from MCI-030 treated hens had 1,412 significantly downregulated genes (fold-change≤-2.0; p Download : Download high-res image (325KB) Download : Download full-size image Conclusions: Our data show multiple gene pathways downregulated in tumors treated with MCI-030 compared to untreated controls, including pathways such as Wnt and MAPK believed to be suppressed by PDE10 inhibition. Interestingly, many of the MCI-030 downregulated pathways mirror those observed for genes whose expression was positively correlated PDE10A mRNA in ovarian tumors of The Cancer Genome Atlas (TCGA). Our data also suggest that MCI-030 might have minimum effect in normal ovaries, but in contrast ameliorates inflammation usually associated to the tumor microenvironment.
Development of Improved Stormwater Quality Models

It is not possible to derive general pollutant washoff functions, for either storm event total loadings or instantaneous fluxes, that contain a given set of independent variables and give reasonable results for most areas, even with calibration. Therefore, a methodology is outlined that facilitates the development of models that can be used with increased confidence to predict urban stormwater pollutant washoff. The methodology consists of testing several linear and linear transform multiple regression models for estimating pollutant washoff loadings as a function of storm and basin characteristics, using measured data. The best model can be chosen for each pollutant using the coefficient of determination (R²) and other criteria. This methodology eliminates the need to estimate both pollutant buildup and washoff.
Fracture and Fragmentation in British Romanticism: Broken origins: an introduction

To fill a Gap Insert the Thing that caused it – Block it up With Other – and 'twill yawn the more – You cannot solder an Abyss With Air – How do we fill gaps? Why do we want to fill them? What is the nature of fracture and fragmentation, in contrast to wholeness and plenitude, and our fascination with them? How can we get a grasp on our intrigue with the conceptual, historical, and material fissures that we use to account for ourselves? Emily Dickinson's concentrated lines, written in 1863, broach these questions of fracture and fragmentation effectively. Her poem thematises how an anxious desire to fill a ‘Gap’ only leads to replacing the fracture with its origin, which is ‘the Thing that caused it’. Any attempt to ‘Block it up’ with another substance results in the gap ‘yawn[ing] the more’. But whatever caused the fracture to begin with must repeat this break. To ‘insert’ the cause of a ‘Gap’ is endlessly to reproduce the fracture. The impossibility of ‘filling’ this gap either with itself or with emptiness – with ‘air’ – leaves the fracture unrepaired at the centre of the poem. The ‘Gap’ turns into an ‘Abyss’ that cannot be soldered, marked by the parenthesis and incompleted punctuation in the poem. The origin of our means to solder turns out to be broken.
An Analysis of Structured Content, with Application of Electronic Computer Research, in Psycholinguistics

Certain linguistic and psycholinguistic hypotheses require information readily derived only from the processing of numerous texts. The employment of electronic computers makes the testing of such hypotheses reasonably feasible; the machines also tend to relieve the researcher of the burden of compiling lists and reference indices “manually.” We have tested programming possibilities on a pilot sample. Two programmes which have proved successful are reported below: one designed to tally co-occurrences of units within frames, the other to yield-inventories of units.
Ectopic production of "pregnancy-specific" beta-1 glycoprotein in vitro: discordance with three other placental proteins.

Abstract "Pregnancy-specific" beta-1 glycoprotein (SP 1 ) was produced in vitro by nine of 32 established cell lines derived from human malignant neoplasms. The nine positive lines comprised a variety of cell types, and SP 1 production ranged from 0.36 to 35.5 pmol/mg cell protein at confluence. The highest production was by a fibrosarcoma line. SP 1 in medium and cells from this line was indistinguishable immunochemically and gel chromatographically from purified (Bohn) placental SP 1 . None of the SP 1 -positive lines produced placental lactogen, only three produced the alpha subunit of chorionic gonadotropin (CG), and only four produced the beta subunit of CG. SP 1 -positive lines that produced CG-α did not produce CG-β. Secretion of SP 1 and of CG-β by the fibrosarcoma line followed different time courses.
What theories are not

Publisher Summary The chapter discusses the “received view” on the role of theories in empirical science. It discusses those theories that are to be thought of as “partially interpreted calculi” in which only the “observation terms” are “directly interpreted”. The view divides the nonlogical vocabulary of science into two parts: observation terms and theoretical terms. This division of terms that belongs to two classes is allowed to generate a division of statements into two classes, such as observational statements and theoretical statements. A scientific theory is conceived of as an axiomatic system that may be thought of as initially uninterpreted and that gains empirical meaning as a result of a specification of meaning for the observation terms alone. It should be noted that the dichotomy under discussion in the chapter is intended as an explicative not a stipulative one. That is, the words “observational” and “theoretical” are not having arbitrary new meanings bestowed upon them; instead, pre-existing uses of these words (especially in the philosophy of science) are presumably being sharpened and made clear.
Catholic Social Thought, Political Liberalism, and the Idea of Human Rights

As the dominant moral vocabulary of modernity, the language of human rights establishes significant points of contact between the religious and the secular. Yet, the human rights movement increasingly finds itself in a contested relationship with religious ideas and communities. Even as the idea of human rights draws on the inherited moral resources of religion, the movement, at least in many of its dominant institutional and intellectual expressions, has established itself as an autonomous moral discourse. In this respect, the human rights movement, as an expression of western liberalism, presents itself as a totalizing moral theory that challenges countervailing theological accounts of human rights. This paper considers the distinctive account of human rights which has emerged out of Catholic social thought’s engagement with political and economic questions. Particular attention is given to the process by which Catholic thinking about human rights has embraced the possibilities of political liberalism while also bounding liberalism within a particularistic theologically-informed account of the human person. The distinctiveness of the Catholic account of human rights raises questions about the role of Catholicism, and religious communities more generally, in shaping the law of human rights. To what extent can secular and religious approaches to human rights law find common cause and overlapping consensus? How does a Catholic account of human rights rooted in theological anthropology relate to a regnant secular tradition which rests on theological categories shorn of religious content (and which has become its own intellectual and moral tradition that is, in important respects, a counter-theology)? While a Christian theological jurisprudence must maintain a concern with the common good, the fractured moral consensus of late modernity equally demands that the goods identified be described with reference to the internal resources of the tradition. Catholicism, in this respect, might both advance and challenge the universalistic impulses of the human rights movement.
CONSENSUS ON THE PRENATAL MANAGEMENT OF ANTENATALLY DETECTED UROLOGICAL ABNORMALITIES

Purpose: The incidence of an antenatally detected genitourinary abnormality is 0.5% of all pregnancies assessed, and rarely is antenatal intervention indicated. A survey of pediatric urologists was undertaken to evaluate current practice patterns and recommendations regarding the need to intervene in the antenatal period.Materials and Methods: A survey instrument was mailed to all members of the Society for Fetal Urology. There were 7 case scenarios that addressed critical decision points in patients with antenatally detected genitourinary abnormalities.Results: A total of 112 of 188 Society for Fetal Urology members (60%) completed the survey. Observation with serial ultrasound was recommended for a 32-week fetus with ureteropelvic junction obstruction. For a 36-week fetus with suspected posterior urethral valves without oligohydramnios most respondents elected no intervention with a minority favoring early delivery. For a 23-week fetus with suspected posterior urethral valves and oligohydramnios with no...
Colony to Nation: British Administration in Kenya, 1940-1963

John Johnson, ed. Colony to Nation: British Administration in Kenya, 1940-1963. Banham, Norfolk: The Erskine Press, 2002. 300 pp. Illustrations. Map. Index. $14.95. Paper. An earlier generation of African historians, forged in the mid-twentieth century, often ignored colonial history. When it was given attention, it was frequently cast as only a period of oppression in efforts to create a paradigm of modern African history rooted in vicitimization. This perspective was strongly influenced by African independence movements of the 1950s and 1960s, and a laudable desire to give African history a rightful voice. However, this approach often overlooked the intricate threads of continuity between the colonial and postindependence eras, and the need to listen to a diversity of voices in order to achieve a fuller telling of events. In her recently published book, Twilight on the Zambezi: Late Colonialism in Central Africa (Palgrave, 2002), Eugenia W. Herbert cogently refers to recent efforts on the part of younger historians to make "colonial history an integral part of African history as one attempts to piece together the intricate patterns of continuity and change" (xxi). This closing of the historical circle between the colonial and postindependence eras is nowhere more dramatically evident than in the recent creation of the Mandela Rhodes Foundation devoted to the education of South Africa's poor. In helping to create this new foundation, former South African President Nelson Mandela has sought to bring historical continuity between his country's past and present in the interests of its future. The fusion of these two names, which would have been viewed as an oxymoron two decades ago, is a powerful symbol of the need to recognize a colonial past and to admit it into current collective consciousness. Although archival records can significantly inform an understanding of colonial-era history in sub-Saharan Africa, it is only through the voices of colonial participants themselves that one can find a fuller dimensionality to what actually occurred. Unfortunately, many of those voices have not been widely heard over the past several decades except when mustered in support of the vicitimization model of African history. However, that is rapidly changing. Works such as Anthony Kirk-Green's On Crown Service: A History of HM Colonial and Overseas Services, 18377 -1997 (I.B.Tauris, 1999), Eugenia W. Herbert's Twilight on the Zambezi, and Heather J. Sharkey's Living with Colonialism: Nationalism and Culture in the Anglo-Egyptian Sudan (California, 2003) represent an important direction in African historiography in that they demonstrate clearly the vast diversity of perspectives, attitudes, and values among both colonial administrators and colonial subjects. We now know, although we should have known all along, that the colonial administration in places such as Kenya was less a centrally controlled chain of command and more a collection of independent local decision-making processes, framed by broad parameters and heavily influenced by the views and reactions of the administered. …
BRANS--DICKE COSMOLOGY.

We discuss the implications of the Brans-Dicke scalar-tensor theory for cosmology with particular emphasis on the primordial element abundances that would obtain. Two general classes of models are found. Models of one class expand through the nuclear burning stage slightly more rapidly than the general relativistic case: models of the other class may expand at any rate whatsoever. The first class of models yeilds primordial abundances of D, He3 and He4 in agreement with their general relativistic values if the present mass density is low. High-density cosmologies, however, would produce too much He4. The second class of models yields element abundances which are far too high unless the expansion rate was quite large: in this case no He4 at all is produced. Finally, we determine the rate of change of the constant of gravitationG at the present epoch. For all but a very small class of models Ġ is negative at the present epoch. Models with positive values of Ġ at the present epoch produce no primordial He4 whatsoever, and have ages significantly lower than the corresponding general relativistic ages.
Nanos (nos) genes of the vector mosquitoes, Anopheles gambiae, Anopheles stephensi and Aedes aegypti

A number of genetics-based strategies for the control of vector-borne diseases require the development of genetic drive systems for introgressing antipathogen effector genes into wild populations of insects. Modified transposons whose mobilization is controlled by the DNA elements of developmentally regulated genes offer a potential solution for introducing effector genes into mosquitoes. Such elements could exhibit sex-, stage- and species-specific transposition, thus mitigating some of the concerns associated with autonomous transposition. Hybridizations in situ show that the transcription products of the nanos orthologous genes of Anopheles gambiae (Anga nos), An. stephensi (Anst nos) and Aedes aegypti (Aeae nos) accumulate in developing oocytes in adult females and localize to the posterior pole in early embryos. These features make nos genes promising candidates for donating control sequences to modified transposons.
Elucidation of Microstructural Interactions Between Collagen and Non-Fibrillar Matrix in Soft Tissue Using a Coupled Fiber-Matrix Model

The mechanical properties of soft connective tissues are governed by their collagen fiber network and surrounding non-fibrillar matrix (e.g., proteoglycans, cells, elastin, etc.). In order to understand how healthy tissues function, and how properties change in injury and disease, it is necessary to quantify the mechanical response of both the collagen network and the non-fibrillar matrix (NFM), as well as the nature of the interaction between these tissue constituents. Using collagen-agarose co-gels as a simple experimental tissue analog system, we have demonstrated how NFM contributes to the mechanical and organizational properties of soft tissues in indentation and tension [1–2]. Furthermore, we used a network-based microscale model to examine how specific NFM properties alter the response of fiber-matrix composites under load [3]. This model fit our experimental data well and provided insight into the role of NFM in tensile mechanics. Since it was constructed according to the conventional approach of superposition of the two constituents (collagen network and NFM), however, the model could not specifically examine local interactions between collagen fibers and the surrounding NFM, which could be critical in assessing tissue damage or cell-matrix interactions. Therefore, we developed and evaluated a fiber-matrix modeling scheme to characterize the microstructural interactions between tissue constituents, as well as to quantify the role of individual tissue components in the behavior of soft tissues under tensile load. For validation, the new model (‘coupled’) was compared to our previous model (‘parallel’) and to experimental co-gel data.Copyright © 2012 by ASME
Antiserum specific for the intact isoform-3 of metallothionein.

Abstract The recombinant form of isoform-3 of mouse brain metallothionein (MT3) was used as an antigen to immunize rabbits and raise MT3-selective antiserum. The antiserum was essentially specific for MT3 with 100-fold greater sensitivity for MT3 compared to MT1 or MT2. Immunonblot analysis of whole mouse brain homogenates showed that MT3 was present only in the fraction retained by a 30,000-Da cut-off filter. The antiserum was used to immunoprecipitate MT3 from mouse brain extracts of Swiss Webster mice and provided evidence that MT3 was a member of a macromolecular complex of greater than 30,000 Da mass in brain. An ELISA was developed using purified, recombinant mouse brain Cd7-MT3 as the antigen and used to quantify MT3 in mouse brain extracts. The concentration of MT3 was found to be 3.0 ± 0.8 μg/ml or approximately 3.5 μg/g mouse brain (wet weight).
Electrical conductivity and creep of polycrystalline α-Al2O3 doped with titanium or iron plus titanium

Creep and conductivity were measured for polycrystalline α-Al2O3 doped with titanium or iron plus titanium. Both series of samples show a transition from acceptor domination to donor domination at the point where the concentrations of titanium and acceptors are approximately equal. Parameters in the expression for the creep rate\(\dot \varepsilon \) ∞Snd-PPrO2 exp (-QlkT) (whereS is the applied stress,d the grain size,Q an activation energy andn, p, r are constants characterizing the creep mechanism) indicate limitation by bulk diffusion in the acceptor-dominated samples and in the donor-dominated samples at low [Ti]. In the latter samples the ratelimiting species isO″i at highPO2, VA′″Al at lowPO2, with involvement of e′ at mediumPO2. At higher titanium concentrations the creep rate is limited by generation/recombination of defects at grain boundaries. Iron appears to increase the rate of these grain-boundary reactions. When second-phase particles of Al2TiO5 are present,\(\dot \varepsilon \) is decreased but ionic conductivity is increased.
Effect of sodium state on reactivity of renal juxtaglomerular cells and adrenal zona glomerulosa.

SummaryChanges in degree of granularity of juxtaglomerular cells (JGI) and width of zona glomerulosa of adrenal cortices (ZGI) of adult Wistar rats subjected to dietary restriction of sodium or salt overload was encountered only when these regimens were supplemented by peritoneal dialysis or administration of DCA, respectively. Increase in these parameters following the former and decrease after the latter both exhibited delay in onset as well as their recovery to control values following sodium repletion or cessation of salt overloading. Decrease in JGI and ZGI occurred prior to the onset of hypertension in rats receiving DCA and saline. These findings are consonant with views concerning the “endocrine” nature of JGC as well as their role as osmoreceptors.
Comparative teratogenicity of phenytoin among several inbred strains of mice

Inbred strains of mice differ in their response to the embryopathic effects of phenytoin (PHT). A/J animals, the most susceptible strain, were mated to C57BL/6J mice, the most resistant strain. The susceptibility of the F1 hybrid offspring was determined by the susceptibility of the mother. B6AF1 animals were as resistant as C57BL/6J parental mice, and AB6F1 hybrids were as susceptible as A/J mice. This was especially evident when orofacial anomalies were tallied. (B6A)F2 hybrid offspring were as resistant as their C57BL/6J grandparents.
What is truly important about information technology in higher education

THIS PAPER ADDRESSES the issues involved in using instructional technology in the classroom. How appropriate is it for an instructor to be immersed in technology as opposed to other aspects of the teaching and learning paradigm? As multimedia presentations become more ubiquitous, should instructors be cautious about turning the classroom into a theater? The tension between substance and display peak with the use of technology in higher education. How that tension is resolved is a central issue in examining the actual values and disadvantages of instructional technology. One conclusion is that technology, a more familiar construct to the student than it is to the teacher, is more apt to ameliorate learning in the future than it is to enhance teaching in the present.
The ATP ANalogue Containing a Methylene Group in Place of the 5′ Oxygen Serves as a Substrate for Bacteriophage T3 RNA Polymerase

Abstract Transcription reactions catalyzed by bacteriophage T3 RNA polymerase and using CTP, GTP, UTP and an analogue of ATP containing a methylene group in place of the 5′ oxygen yield RNA-like polymers. These products are degraded to the 5′-mononucleotides CMP, GMP, UMP, and the corresponding analogue of AMP by exposure to snake venom phosphodiesterase. By using appropriate DNA templates, a single residue of the AMP analogue can be located at the site adjacent to the cleavage position in the substrate strand of a hammerhead ribozyme. The modified substrate strand is completely resistant to cleavage by the ribozyme's catalytic strand.
Digital Image Analysis Of Cervical Biopsies

ABSTRACTDigital image analysis techniques and statistical discriminant analysis are used to identify mitotic cells in the biopsies of cervical dysplasia. This dysplasia is a preinvasive stage of cervical cancer. Parameters extracted from each cell include areal and geometrical measures, opticaldensity statistics, bending energy, and various statistical texture features. The discriminant analysis attempts to classify mitotic cells from those in interphase on the basis of the imageanalysis output data vectors using pre- scored classifications. The first comprehensive trial of the imaging technique for a dataset of 32 cervical cells showed that 88% of the cells could be properly identified automatically. A fast, accurate and robust expert imaging system is ultimately desired for the classification of cervical cancer and other types of malignancy. INTRODUCTIONMitotic activity corresponds to the rate of proliferation. This activity is usedextensively in the classification and prognostication of human cancers.
The X-ray structure and substitution reactions of the amido bridged IrII dimer Ir2(I)2[μ-NH(p-tolyl)]2(CO)4

Abstract The addition of I 2 to Ir 2 [μ-NH( p -tolyl)] 2 (CO) 4 ( 1 ) produces the Ir II -Ir II dimer Ir 2 (I) 2 [μ-NH( p -tolyl)] 2 (CO) 4 ( 2 ), where the two iridium centres are connected by a metal-metal single bond of length 2.591 (1)A˚. The complex 2 undergoes substitution of only one CO with phosphines (PPh 3 and PPh 2 Me), even when an excess of the phosphines is used. NMR and IR data of all the complexes are presented, along with an X-ray structure of 2 .
Nonresonant absorption of shear AlfvÉn waves

Resonant absorption of shear Alfven waves is thought to be a likely candidate to explain heating of the solar corona and acceleration of the solar wind. A difficulty with the theory is that the absorption process is slow. Moreover, heating occurs in a very thin layer. A faster absorption mechanism is nonresonant absorption by compressional viscosity, in a curved magnetic field. Heating is nonresonant and is not localized to a narrow layer. The effect could be quite important where the solar coronal magnetic field is strongly curved, in the chromosphere. It could also be important on open field lines in the upper corona, where the compressional viscosity is large. It might imply that a significant part of outgoing Alfven waves are absorbed in the corona.
Helium chronometry of apatite and titanite using Nd-YAG laser heating

We developed a technique for extracting ^4He from apatite and titanite using laser heating that permits measurement of U and Th and, hence, (U–Th)/He ages, on a single sample aliquot. Unlike direct laser heating, quantitative He extraction and U, Th retention can be achieved when samples are indirectly laser heated to temperatures below their melting point. Resulting He ages are consistent with those obtained from conventional furnace heating of larger samples. The major advantages of this technique include faster analysis and far lower, more reproducible He blanks that permit single crystal analyses. Single crystal dating opens a variety of new avenues for (U–Th)/He chronometry.
Post-Soviet Placebos: Epistemology and Authority in Russian Treatments for Alcoholism

The dominant modalities of treatment for alcoholism in Russia are suggestion-based methods developed by narcology—the subspecialty of Russian psychiatry which deals with addiction. A particularly popular method is the use of disulfiram—an alcohol antagonist—for which narcologists commonly substitute neutral substances. Drawing on 14 months of fieldwork at narcological clinics in St. Petersburg, this article examines the epistemological and institutional conditions which facilitate this practice of “placebo therapy.” I argue that narcologists’ embrace of such treatments has been shaped by a clinical style of reasoning specific to a Soviet and post-Soviet psychiatry, itself the product of contested Soviet politics over the knowledge of the mind and brain. This style of reasoning has facilitated narcologists’ understanding of disulfiram as a behavioral, rather than a pharmacological, treatment and has disposed them to amplify patients’ responses through attention to the performative aspects of the clinical encounter and through management of the treatment’s broader reputation as an effective therapy. Moreover, such therapies have generally depended upon, and helped to reinforce, clinical encounters premised on a steeply hierarchical physician–patient relationship.
Relevance of immature tuber periderm to high commercial peeling losses

Cell wall composition and histological distinctions between immature and mature periderm are reviewed. The structural characteristics of the periderm of immature tubers vitiate economic peeling. Continuous sloughing and replacement of periderm, occurring with rapid enlargement of Russet Burbank tubers, creates large unsuberized surface areas particularly susceptible to deep penetration of hot caustic and consequent pitting of tubers. The fully developed russetted net of mature periderm is well suberized and holds the caustic so it does not deeply penetrate. Improved crop management and harvest practices could eliminate excessive peel loss due to immature periderm.
Neural network approach to digital control

This paper starts with an overview of a classical PID controller design. An account of how Neural Networks may be incorporated to provide control is such a setup. The example used in this paper is the problem of controlling a High Frequency Acoustics Platform (HFAP) in-flight. The HFAP is towed by a ship and flown in the water behind the ship to acquire acoustic data reflected from the sea floor. The stability of such a platform is of prime importance to the accuracy of data collected. Using fight data from previous runs of the platform, a Neural Network is trained. The trained network is then used to predict the behavior of the platform. These predictions may then be directly translated to control signals minimizing the platform's spatial deviations. In this paper results form the trained Neural Network on predicting the behavior of the platform are displayed. Network prediction results illustrating the ability of the network to operate with partial input are displayed. Displaying these results in contrast with conventional controller results given the same input parameters emphasizes the importance of such a feature. Finally the use of different network architectures and the cost of using these network, in terms of computing power is investigated.
Conversion of cholesterol to testosterone and androstanediol in testicular homogenates of immature and mature rats.

Abstract A comparison of the metabolism of cholesterol-7α-3H in immature and mature rat testis has been carried out in homogenate preparations. Androstanediol was formed in large amounts but relatively little testosterone accumulated in 3 hour incubations of immature testis. In the mature testis there was an increase in testosterone accumulation paralleled by a decrease in androstanediol formation. Androstenedione did not accumulate to any greater extent in the immature testis indicating there was no block in its conversion to testosterone. These studies are in agreement with earlier studies of progesterone metabolism in rat testicular homogenates, and indicate that this change in testicular reductase activities may play a role in the process of sexual maturation.
Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention.

Abstract Research indicates that vulnerability to oxidative stress (OSV) may increase in aging, suggesting that age-related neurodegenerative diseases such as Alzheimer’s disease (AD) or vascular dementia (VAD) may be superimposed upon a vulnerable neuronal environment. Determinations in cell models have suggested that the enhanced OSV may be the result of, (a) increases in membrane lipids, especially sphingomyelin and the sphingomyelin metabolite, sphingosine-1-phosphate, (b) decreases in glutathione, and (c) CNS distribution of OS-sensitive neuronal muscarinic receptor subtypes (e.g. M1, M2 and M4). These changes appear to enhance, (a) decrements in cellular calcium buffering following KCl-induced depolarization, and (b) cell death under OS conditions. Among the most effective agents that antagonized cellular OSV were the combination of polyphenolics found in fruits (e.g. blueberry extract) with high antioxidant activity. Subsequent experiments using dietary supplementation with fruit (strawberry) or vegetable (spinach) extracts have shown that such extracts are also effective in forestalling and reversing the deleterious effects of behavioral aging in F344 rats. Thus, it appears that the beneficial effects of the polyphenolics found in fruits and vegetables in neuronal aging and behavior may be similar to those seen with respect to carcinogenesis and cardiovascular disease.
Lipopolysaccharide can trigger a cathepsin B-dependent programmed death response in human endothelial cells.

In this study, we examined the mechanisms that contribute to lipopolysaccharide (LPS)-induced death responses in cultured human umbilical vein endothelial cells (HUVECs). In the presence of the protein synthesis inhibitor cycloheximide, LPS primarily induces caspase-dependent apoptotic cell death of HUVECs, which is blocked by siRNA-mediated knockdown of myeloid differentiation factor 88 adaptor protein but not of Toll-like receptor-associated interferon-inducing factor. Knockdown of Fas-associated death domain protein (FADD) by either siRNA or overexpression of a truncated version of FADD that lacks the N-terminal death effector domain (FADD DN ) increases the sensitivity of HUVECs to LPS plus cycloheximide-mediated death. However, based on the use of proteinase inhibitors, cell death changes from being principally caspase-dependent to being principally cathepsin B (Cat B)-dependent. Knockdown of cellular FLICE inhibitory protein potentiates the caspase-dependent pathway but does not activate the Cat B-dependent death response. Knockdown of either myeloid differentiation factor 88 or Toll-like receptor-associated interferon-inducing factor expression does not affect the LPS-triggered Cat B death response in FADD-deficient HUVECs. Finally, in the presence of either the phosphatidylinositol 3 kinase inhibitor LY294002 or the inflammatory cytokine interferon-γ, LPS activates both caspase- and Cat B-dependent death pathways. We conclude that LPS can activate a Cat-B-dependent programmed death response in human endothelial cells that is independent of both myeloid differentiation factor 88 and Toll-like receptor-associated interferon-inducing factor, is blocked by both FADD and phosphatidylinositol 3 kinase, and is potentiated by interferon-γ.
Improving low-temperature performance of Li-alloy anodes by optimization of the electrolyte–electrode interface

Abstract The −20 °C performance of nano-tin-(lithium emeraldine base), i.e. nano-tin-(lithium hemi-oxidized polyaniline), abbreviated as nano-Sn-PAni, anodes was investigated. The rate-limiting process is slow charge-transfer kinetics, rather than poor electrolyte conductivity or a high solid electrolyte interface (SEI) film resistance. Two ionic conductors, i.e. Li + -doped polyethylene oxide (PEO) and 14Li 2 O–9Al 2 O 3 –38TiO 2 –39P 2 O 5 ((LiAlTiP) x O y ) ceramic powders were incorporated into the anode material to accelerate the interfacial charge-transfer process. The (LiAlTiP) x O y ceramic proved to be much better than doped PEO in improving the low-temperature performance. One nano-Sn-PAni anode material containing 15 wt.% (LiAlTiP) x O y gave particularly high initial charge and discharge capacities (795 and 545 mAh g −1 , respectively) at −20 °C.
Nutritive value and display-life attributes of selenium-enriched beef-muscle foods

Abstract Our objective was to assess the nutritive value and display-life attributes of selenium-enriched beef-muscle foods. Samples of foreshank and short-loin subprimals were excised from chilled carcasses ( n =20) of beef steers that were individually finished (120 days) on either supranutritional selenium (selenium-enriched; 68.1 μg Se/kg body weight/day; n =9) or adequate selenium (non-enriched; 9.1 μg Se/kg body weight/day; n =11) diets. High-selenium wheat grain was included in the diet of supranutritional selenium-fed steers to achieve selenium-enrichment. Selenium-enriched foreshank had 3.8 times more (1085 vs. 283 ng/g wet weight, P P P =0.16–0.89) moisture, ash, crude protein, and lipid contents, and expressible moisture, or short-loin ( P =0.11–0.41) drip-loss percentage or color change throughout the display-life evaluation. The results indicate that, compared to non-enriched, selenium-enriched beef-muscle foods have a much higher amount of selenium and similar display-life attributes.
Immunological Studies of the Follicle-Stimulating Hormone. I. Identification of the HCG Augmenting Principle

Rabbit antiserum to NIH ovine follicle-stimulating hormone (FSH) completely absorbed with sheep serum and tissue extract reacted with ovine FSH to form 2 precipitin bands. In agarose immunoelectrophoresis, one of these lines was entirely on the anodal side and appeared to be homogeneous, and it was short and well defined. Another line, more toward the cathodal side, was heterogeneous and longer. The component of FSH responsible for this cathodal line was quantitatively richer and immunogenically weaker and was demonstrable also in porcine FSH and in luteinizing hormone (LH) and thyroid stimulating hormone (TSH) preparations which did not have measurable FSH activity. The antibodies directed against this component were responsible for the cross reaction with LH and TSH of ovine and bovine origin and porcine FSH as far as serologically demonstrable elements were concerned. The 2 components coexisted in ovine FSH and LH preparations with measurable FSH activity as revealed by the human chorionic gonadotropin...
Salicylic Acid Blocks Indomethacin-Induced Cyclooxygenase Inhibition and Lesion Formation in Rat Gastric Mucosa

Salicylic acid has been shown to decrease gastric mucosal lesions induced by indomethacin in the rat. In vitro, it has also been shown to counteract the inhibitory effect of indomethacin and aspirin on the cyclooxygenase enzyme system in seminal vesicle microsomes and in platelets and vascular tissue. The hypothesis that the mechanism of salicylic acid "protection" against indomethacin-induced gastric lesions involves interference with indomethacin-induced mucosal cyclooxygenase inhibition was tested. Male, fasted rats were treated with intragastric salicylic acid in doses of 50, 100, 200, 300, or 400 mg/kg concomitantly with a sc injection of 20 mg/kg of indomethacin. Gastric mucosal lesions and mucosal cyclooxygenase activity (as measured by ex vivo prostaglandin F2 alpha synthesis) were examined 3 hr later. Intragastric salicylic acid, 200-400 mg/kg, significantly reduced indomethacin-induced lesion formation, while counteracting significantly indomethacin inhibition of prostaglandin synthesis. Salicylic acid alone did not significantly change cyclooxygenase activity. It is concluded that topical salicylic acid can decrease indomethacin-induced gastric mucosal lesion in the rat, in part, by counteracting the inhibitory effect of indomethacin at the cyclooxygenase level.
Fabrication of sub-20 nm nanopore arrays in membranes with embedded metal electrodes at wafer scales

We introduce a method to fabricate solid-state nanopores with sub-20 nm diameter in membranes with embedded metal electrodes across a 200 mm wafer using CMOS compatible semiconductor processes. Multi-layer (metal–dielectric) structures embedded in membranes were demonstrated to have high uniformity (±0.5 nm) across the wafer. Arrays of nanopores were fabricated with an average size of 18 ± 2 nm in diameter using a Reactive Ion Etching (RIE) method in lieu of TEM drilling. Shorts between the membrane-embedded metals were occasionally created after pore formation, but the RIE based pores had a much better yield (99%) of unshorted electrodes compared to TEM drilled pores (<10%). A double-stranded DNA of length 1 kbp was translocated through the multi-layer structure RIE-based nanopore demonstrating that the pores were open. The ionic current through the pore can be modulated with a gain of 3 using embedded electrodes functioning as a gate in 0.1 mM KCl aqueous solution. This fabrication approach can potentially pave the way to manufacturable nanopore arrays with the ability to electrically control the movement of single or double-stranded DNA inside the pore with embedded electrodes.
Ethanol-induced conformational changes in rat brain microsomal membranes.

Abstract The conformation of membrane-bound proteins was monitored by the reaction of sulfhydryl (SH) groups with N -ethyl maleimide (NEM) and 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB). Brain microsomes isolated from rats chronically imbibing a 10% (v/v) ethanol solution were found to contain 12–16 per cent more DTNB-reactive SH groups than similarly isolated controls. [ 3 H]NEM reacted with 32 per cent more SH groups in the microsomes obtained from ethanol-treated rats than controls. Since no change in the protein composition was evident from disc electrophoresis, and no significant differences in the total number of SH groups was present between the two samples, these findings suggest a conformational change in the microsomal membrane. Microsomes isolated from ethanol-naive animals, when treated with ethanol in vitro , showed a dose-dependent decrease in DTNB-reactive SH groups. The results indicate that the neural membrane may exist in different morphological states during acute and chronic exposure to ethanol.
Writing desire in Nepali love letters

Abstract This article examines the ways in which romantic love was experienced, discussed, and written about by Nepali villagers in the 1990s. Love letters written by young village residents illustrate how love came to be reconceptualized during this time period as a desirable rather than an embarrassing emotion, one linked up with other achievements perceived as admirable, such as education, development and success. Because love letter correspondences were only made possible by increased female literacy rates in the village, the article also explores some of the socioculturally and historically specific impacts of the acquisition of literacy skills on gender hierarchies and intimate relationships.
Effect of alamethicin, gramicidin S and melittin uppn the particulate guanylate cyclase from rat lung

The channel-forming antibiotic alamethicin activated rat lung particulate guanylate cyclase (GTP pyrophosphate-lyase (cyclizing) EC 4.6.1.2), and the activated enzyme was further stimulated by sodium nitroprusside when a thiol such as 2-mercaptoethanol was present. Similar effects were seen with the antibiotic gramicidin S and with melittin, a polypeptide purified from bee venom. All of these agents are amphiphilic polypeptides. Nitroprusside was not able to stimulate both particulate and soluble enzyme treated with the nonionic amphiphile, Lubrol PX, suggesting that the membrane-active polypeptides had a different mechanism of action. These polypeptides are known to alter the membrane matrix by binding to phospholipid, and we suggest that this alteration allowed greater access of substrate and of nitroprusside to the enzyme. Lubrol PX, however, may interact preferentially with the enzyme, and thus block nitroprusside activation. The most potent of these agents was melittin, which stimulated nitroprusside activation at a concentration which had little effect by itself (7 microns), and at which others have demonstrated lytic effects on cells.
Marketing Gets Personal: Promoting Reference Staff to Reach Users

ABSTRACT With a growing population of part-time and distance education students, changing technologies, and evolving user expectations, it is becoming increasingly challenging to reach users through traditional marketing approaches. This article will review previous trends in library marketing and promotion and explore new initiatives, including partnering with marketing courses, roving reference, and highlighting staff expertise to raise awareness among users.
Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population.

Circadian Rhythms in Pediatric De. brillator Discharges.Introduction: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. Methods and Results: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. Conclusion: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors.
Evolution of latex and its constituent defensive chemistry in milkweeds (Asclepias) : a phylogenetic test of plant defense escalation

A tremendous diversity of plants exude sticky and toxic latex upon tissue damage, and its production has been widely studied as a defensive adaptation against insect herbivores. Here, we address variation in latex production and its constituent chemical properties (cardenolides and cysteine proteases) in 53 milkweeds [ Asclepias spp. (Apocynaceae)], employing a phylogenetic approach to test macroevolutionary hypotheses of defense evolution. Species were highly variable for all three traits, and they showed little evidence for strong phylogenetic conservatism. Latex production and the constituent chemical defenses are thus evolutionarily labile and may evolve rapidly. Nonetheless, in phylogenetically independent analyses, we show that the three traits show some correlations (and thus share a correlated evolutionary history), including a positive correlation between latex exudation and cysteine protease activity. Conversely, latex exudation and cysteine protease activity both showed a trade-off with cardenolide concentrations in latex. We also tested whether these traits have increased in their phenotypic values as the milkweeds diversified, as predicted by plant defense escalation theory. Alternative methods of testing this prediction gave conflicting results ‐ there was an overall negative correlation between amount of evolutionary change and amount of latex exudation; however, ancestral state reconstructions indicated that most speciation events were associated with increases in latex. We conclude by (i) summarizing the evidence of milkweed latex itself as a multivariate defense including the amount exuded and toxin concentrations within, (ii) assessing the coordinated evolution of latex traits and how this fits with our previous notion of ‘plant defense syndromes’, and finally, (iii) proposing a novel hypothesis that includes an ‘evolving community of herbivores’ that may promote the escalation or decline of particular defensive strategies as plant lineages diversify.