cssi/SciSciGPT-SciSciNet huggingface dataset:
Antiproliferative and apoptotic effects of xanthohumol in cholangiocarcinoma.

// Daniel Walden 1 , Selvi Kunnimalaiyaan 1 , Kevin Sokolowski 1 , T. Clark Gamblin 1 and Muthusamy Kunnimalaiyaan 1 1 Division of Surgical Oncology, Department of Surgery, MCW Cancer Center, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA Correspondence to: Muthusamy Kunnimalaiyaan, email: mkunnima@mcw.edu Keywords: cholangiocarcinoma, xanthohumol, Notch1, apoptosis, cell cycle Received: July 06, 2017 Accepted: August 31, 2017 Published: September 30, 2017 ABSTRACT Cholangiocarcinoma remains the second most prevalent hepatic neoplasm in the United States with a 5-year survival rate of less than 10%. Currently, no systemic therapy has demonstrated efficacy. Therefore, an urgent need for the identification of molecularly targeted compound(s) remains. The Notch signaling pathway has been shown to be dysregulated in cholangiocarcinoma, exhibiting hyperactivity while also possibly mediating chemotherapeutic resistance. We analyzed the effects of xanthohumol, a prenylated chalcone, on cholangiocarcinoma proliferation utilizing human cholangiocarcinoma cell lines CCLP1, SG-231 and CC-SW-1 while gaining insight into the associated mechanism. Xanthohumol potently reduced cellular proliferation, colony formation, and cell confluency in all three cell lines. Xanthohumol induced cell cycle arrest as well as apoptosis through the reduction of cell cycle regulatory proteins as well as an increase in pro-apoptotic markers (cleaved poly ADP ribose polymerase, cleaved caspase-3) and a decrease in anti-apoptotic markers (X-linked inhibitor of apoptosis and survivin). At the molecular level, xanthohumol reduced Notch1 and AKT expression in a step-wise and time-dependent fashion, with Notch1 reductions preceding AKT. Additionally, xanthohumol reduced cholangiocarcinoma growth in both CCLP-1 and SG-231 derived mice xenografts. In summary, we show that xanthohumol significantly reduced cholangiocarcinoma growth through the Notch1/AKT signaling axis. Furthermore, known pharmacokinetics and bioavailability of XN supports continued development of treatment for cholangiocarcinoma.
Hypoxia-Inducible Factors as Essential Regulators of Inflammation

Myeloid cells provide important functions in low oxygen (O2) environments created by pathophysiological conditions, including sites of infection, inflammation, tissue injury, and solid tumors. Hypoxia-inducible factors (HIFs) are principle regulators of hypoxic adaptation, regulating gene expression involved in glycolysis, erythropoiesis, angiogenesis, proliferation, and stem cell function under low O2. Interestingly, increasing evidence accumulated over recent years suggests an additional important regulatory role for HIFs in inflammation. In macrophages, HIFs not only regulate glycolytic energy generation, but also optimize innate immunity, control pro-inflammatory gene expression, mediate bacterial killing and influence cell migration. In neutrophils, HIF-1α promotes survival under O2-deprived conditions and mediates blood vessel extravasation by modulating β 2 integrin expression. Additionally, HIFs contribute to inflammatory functions in various other components of innate immunity, such as dendritic cells, mast cells, and epithelial cells. This review will dissect the role of each HIF isoform in myeloid cell function and discuss their impact on acute and chronic inflammatory disorders. Currently, intensive studies are being conducted to illustrate the connection between inflammation and tumorigenesis. Detailed investigation revealing interaction between microenvironmental factors such as hypoxia and immune cells is needed. We will also discuss how hypoxia and HIFs control properties of tumor-associated macrophages and their relationship to tumor formation and progression.
Scale Selection and Energy Spectra of Disturbances in Southern Hemisphere Flows

Abstract The growth and nonlinear interaction of initially small-amplitude disturbances, having a complete spectrum of zonal wavenurnbers, with zonally averaged flows characteristic of January and May SouthernHemisphere situations, are studied in a multilevel primitive equation spectral model-incorporating spherical geometry and viscous dissipation. For January, the fastest growing scale has zonal wavenumberm = 9, in close agreement with linear instability theory. However, the contribution from m = 7 subsequently exceeds that of rn = 9 and is largely responsible for the general agreement between model andobserved eddy streamfunctions and fluxes. Although the individual wavenumber contributions, eg,m = 9 and m = 7 undergo vacillation cycles similar to ones found earlier with single zonal wavenumberdisturbances growing on the same zonal flows, the total eddy kinetic energy after the initial growth periodis relatively constant. This appears to be due to the interference between the larger number of waves. Fo...
MnO2-coated graphene foam micro-structures for the flame speed enhancement of a solid-propellant

Abstract In this work, the functionalized form of a highly-conductive, porous, three-dimensional graphene foam (F-GF) was used to enhance the flame speed of a solid propellant, nitrocellulose (NC). The graphene foam (GF) micro-structures, synthesized by the chemical vapor deposition (CVD) technique, were coated with a transition metal oxide (TMO), manganese dioxide (MnO2), using a hydrothermal approach. Average flame speeds as a function of both the NC-GF and MnO2 NC loadings were studied. Overall, flame speed enhancement up to 9 times that of the bulk NC flame speed was observed. An optimum MnO2 NC loading corresponding to the maximum flame speed was obtained for each NC-GF loading, which was found to shift to the right as the NC-GF loading was decreased. In addition, thermogravimetric (TG) and differential scanning calorimetry (DSC) analysis were also conducted to determine the effect of NC-GF and MnO2 NC loadings on the activation energy (E) and peak thermal decomposition (PTD) temperatures of the propellant NC. Similar to the flame speed results, for each NC-GF loading tested, an initial decrease in both E and PTD temperatures was obtained as a function of the MnO2 NC loading but above a certain MnO2 concentration, a slight rise and a plateaued behavior was observed, respectively.
Electroporation-mediated gene delivery.

Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models.
DD56: Der Inquisitor und der Manager (Januar 2008)

Der Grosinquisitor sagte zum Manager, der beim Foltern eines Gefangenen erschauerte: „Solange die Angeklagten noch schreien, gibt es Potential. Wenn sie erst einmal schweigen, gestehen sie nichts mehr. Dann ist das Spiel fur beide Seiten unglucklich gelaufen.“ Schrille Angst erfullte die Gruft, ein Quetschen war zu horen.
Gazella leptoceros (Slender-horned gazelle)

Lymphocyte cultures, using poke week stimulant, produced above karyotypes from animals at San Diego Zoo. As in other gazelles, the X is a compound chromosome with the Y2 of males attached at the end of the long arms. Faint satellites exist at the ends of the first autosomes and Xp. The female karyotype is prepared with ASG technique. In C-banding, Xp is heterochromatic.
Unsteady, Wall-Bounded Turbulent Flows

Unsteady turbulent flows occur in a variety of engineering applications. Boundary layers on the surface of turbine blades, reciprocating engine cylinder flow, and most biological flows are but a few examples of turbulent flows in which the basic motion (mean flow) is harmonic time-dependent. A systematic investigation of the effect of unsteadiness in turbulent flows was first performed by Karlsson (1959). Experimental investigations were limited by the difficulties associated with analog processing of a velocity signal from such flows. Recently several investigators have examined the response of turbulent flows to imposed disturbances (Binder and Kueny, 1981; Binder et al., 1985; Brereton et al., 1990; Can, 1981; Cousteix, 1986; Cousteix et al., 1981; Mao and Hanratty, 1986; 1982; Ramaprian and Tu, 1983; Ronneberger and Ahrens, 1977; Shemer et al., 1985; and Tu and Ramaprian, 1983; among others.)
New attacks on RNN based healthcare learning system and their detections

Abstract Advances in machine learning (ML) in recent years have enabled a wide range of applications such as data analytics, autonomous systems, and security diagnostics. For example, recurrent neural networks (RNNs), such as long short-term memory networks (LSTMs), serve as a fundamental building block for many sequence learning tasks. Many researchers construct learning based inference and decision making models using primitive learning modules (PLMs) hosted in popular developer platforms, e.g., github. However, most of the publicly available primitive learning modules (PLMs) are maintained by third parties and lack proper checking to ensure they have not been maliciously modified by adversaries. In this paper, we articulate a particular threat to Recurrent Neural Network (RNN) based ML systems by introducing a new attack, which adjusts the weights of a RNN-based model causing it to produce wrong prediction results. Via synthetic and real world datasets, we demonstrate that such an attack is feasible. Next, we propose a detection scheme which can be used to infer if a particular PLM used in a RNN-based ML system contains such malicious behaviors. Experimental results show that our RNN based attack algorithm decreases the system performance when weights of important features are modified during training. In addition, our results also show that our detection mechanism is useful in identifying such malicious PLM.
Review Essay: Picturing Benin: Where Insiders and Outsiders Lenses Converge and Diverge

Europeans imagined Africa and its peoples long before they started plying its coasts, and centuries before Nichore Niepce invented photography in 1816. The images of Africa were positive until the early Middle Ages, then they progressively became negative, especially in the 18th and 19th centuries at the height of European imperialism, although the 16th and 17th centuries saw a combination of positive and negative images (Nederveen, 1992). In the 20th century, the advent and popularity of television and mass media, including the Internet boom certainly have provided Africans with a few opportunities to project their own images, but denigrating and distorting images continue, unabated and unstoppable. Over time, the European image of the African has evolved from that of the savage brute, demon, close to nature and pagan to the simple-minded savage and eternal childish jester who never matures. S/he is incapable of governing her/himself, is genetically or culturally corrupt, ready to kill his or her own, promiscuous, and carries diseases.
Observability of Perspective Systems a New Approach to Computer Vision

The problem of computer vision that we consider in this paper may be sumMarized as follows. We have a rigid body which rotates and Translates with constant angular and linear velocities respectively. The velocities are assumed to be unknown. The vision problem is to identify these unknown parameters (hereafter referred to as motion parameters) by observing the perspective projections of the moving object on a screen. Typically however, the motion parameters are identified not from the projection of the entire object but possibly from the projections of certain features on the object. In this paper, such a feature is considered to be a straight line or a planar polynomial curve of degree 2. Other possibilities can be treated analogously.
Platelet-Neutrophil Aggregates Promote Pulmonary Arteriole Microembolism in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects ~100,000 Americans and millions of people worldwide. The acute chest syndrome (ACS), a form of acute lung injury, is a major cause of morbidity among SCD patients. The current treatment for ACS is primarily supportive and the molecular mechanism remains largely unknown. SCD patients hospitalized with vaso-occlusive pain crisis (VOC) often develop ACS within the ensuing days, suggesting a role for pulmonary vaso-occlusion in the onset of ACS. However, the cellular and molecular mechanism and the anatomical site of pulmonary vaso-occlusion are still elusive. Materials and Methods: Intravenous (IV) bacterial lipopolysaccharide (LPS) was used to induce VOC in SCD mice. Intravital multiphoton excitation (MPE) fluorescence microscopy was used to study the blood cell trafficking within the pulmonary microcirculation of live SCD or control mice. Fluorochrome-conjugated anti-mouse Ly-6G, Ter-119, and CD49b antibodies were administered IV for in vivo staining of circulating neutrophils, red blood cells and platelets, respectively. Cellular trafficking was recorded at baseline and 2 hours after IV challenge with LPS. Image sequences were analyzed to identify vaso-occlusion, which was defined as cellular aggregation and stasis of blood flow within the pulmonary blood vessels. Results and Discussion: Preliminary data using MPE imaging in transgenic SCD mice revealed that vaso-occlusion was absent at baseline in unchallenged SCD mice and the cellular trafficking within the pulmonary microcirculation was comparable in SCD and control mice. Doses of IV LPS (0.01-5 mg/kg of body weight), which were innocuous to control mice were found to be lethal to SCD mice. Remarkably, MPE imaging of the lung microcirculation revealed that IV LPS led to microembolism of the pre-capillary pulmonary arterioles by platelet-neutrophil aggregates in SCD but not control mice. The microembolism involved either entrapment of circulating platelet-neutrophil aggregates or in situ aggregation through sequential steps of neutrophil arrest on the arteriolar endothelium, followed by platelet nucleation on arrested neutrophils and microthrombus formation. Conclusions: Initial findings demonstrate that pulmonary vaso-occlusion in SCD mice involves microembolism of the pre-capillary pulmonary arterioles by platelet-neutrophil aggregates. Future studies will determine the molecular interactions responsible for pulmonary arteriolar microembolism. Acknowledgements: This study is supported by the 11SDG7340005 from the American Heart Association (P.S.) and the VMI startup account (P.S.). M.F.B is supported by the NIH NHLBI VMI T32 training grant T32HL110849. Disclosures No relevant conflicts of interest to declare.
The economics of geriatric mental health care

Abstract This chapter provides an overview of the current funding mechanisms that support the provision of mental health care for older adults, the ongoing systemic economic and service delivery challenges in the provision of mental health care for older adults, and recent innovations in payment mechanisms and service delivery that offer promise for improving mental health care in our rapidly aging population. These innovations will be viewed through the lens of the Affordable Care Act (ACA) as well as the rise of risk-based payment mechanisms, underscoring recent advances in high-value care delivery processes targeting mental health care in this population.
Human colon cancer cells deficient in DCC produce abnormal transcripts in progression of carcinogenesis.

Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may be superior to lymph node status in predicting patient survival for intermediate stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting DCC would be ideal as a prognostic indicator. DCC is an alternatively spliced molecule; thus, reliability of a PCR test for DCC will depend on amplifying only those regions of the molecule that are lost in the progression of colon cancer. For this reason, we studied a colon cancer cell line model at different stages of tumor progression to determine the alternative splice pattern for DCC. A commercially available colon cancer cell line system at different stages of tumor progression was used to identify which DCC exons are lost by western blot analysis, PCR, and RT-PCR techniques. Colon cancers express abnormal DCC transcripts. The proximal and distal exons are present (exons 2 and 28–29). Exons located in the center of the molecule are absent (6–7 and 18–23). This correlated to DCC protein loss in the cell lines. For clinical utility as a disease marker, exons in the middle portion of the DCC molecule that are spliced out should be utilized. Amplification of the proximal and distal regions will result in falsely concluding that DCC is present when its protein product is not expressed.
Preservice Teachers' Understanding of 'Real world': Developing a Typology

This study examines the beliefs of 33 preservice teachers (PSTs) from the U.S. have about using different types of real-world contexts in the mathematics classroom. Qualitative data about the participants' reactions to specially designed word problems that varied in contexts from 'neutral' to controversial were collected. A thematic analysis of the responses indicated that they could be arranged into three typologies on a continuum based on their openness towards the use of controversial issues in the mathematics classroom. Drawing on the analysis of PSTs' responses and the literature, a fourth typology was inferred. The typologies can be useful to teacher educators and education programs as they seek to prepare PSTs to work with increasingly diverse students in their future mathematics classes. The study also highlights the potential of using word problems as a tool to understand PSTs' beliefs.
Accumulation of HIV-1 Drug Resistance Mutations and Methamphetamine Use.

Background Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutation accumulation is less studied. Objective We assessed factors associated with drug resistance mutation accumulation. Methods We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the prior 30 days. Results One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses. Conclusions We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutation accumulation. Research cohort patients may have been more engaged in care and treatment adherence than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.
Four-port Spatiotemporally Modulated Circulator with Low Modulation Frequency

Spatiotemporal modulation has gained significant attention recently for allowing the design of magnetless nonreciprocal components. However, most of the approaches presented to date require relatively large modulation frequencies, which creates significant challenges in their implementation at high frequencies. In this paper, we present a four-port magnetless circulator which overcomes this problem and works with a modulation frequency almost 100 times smaller than the operation frequency. The circuit is based on four Wheatstone bridges of varactors, connected to each other through inductors and modulated with a 90 deg phase difference, which, in addition to allowing operation with a low modulation frequency, is generally easier to realize than other phase differences. The design procedure of the proposed circuit is presented, together with simulation and measurement results, with a good agreement between them. For an operation frequency around 1 GHz and a modulation frequency of only 15 MHz, the proposed circulator can be designed to have high isolation (IX) (>30 dB) and relatively low insertion loss (IL) (<3 dB). The proposed approach can have important applications in high-frequency systems, where fast modulation is generally challenging.
The Frequency and Activity of Single Helper T Cells

We have investigated the activities of T cell populations able to cooperate in the humoral immune response to TNP coupled to the carriers SRBC or KLH. We used Poisson analyses in which small numbers of carrier-primed spleen cells were added to cultures containing an excess of B cells and antigen. We have demonstrated that we could a) detect the activity of a single helper T cell; b) calculate its frequency in a given spleen cell suspension; and c) calculate its relative activity in stimulating the humoral immune response.
LERS-A System for Learning from Examples Based on Rough Sets

The paper presents the system LERS for rule induction. The system handles inconsistencies in the input data due to its usage of rough set theory principle. Rough set theory is especially well suited to deal with inconsistencies. In this approach, inconsistencies are not corrected. Instead, system LERS computes lower and upper approximations of each concept. Then it induces certain rules and possible rules. The user has the choice to use the machine learning approach or the knowledge acquisition approach. In the first case, the system induces a single minimal discriminant description for each concept. In the second case, the system induces all rules, each in the minimal form, that can be induced from the input data. In both cases, the user has a choice between the local or global approach.
Digital government: new tools to define terroirs and viticultural areas in the northern great plains

Terroir embodies a defined geographic place, integrating soils, geology, climate, the cultivar (variety), and the role of cultivation, culture, and history in producing wine (White, 2003). It captures the concept of "genotype x environment", integrates the human dimensions of vineyard management, and builds a "sense of place" from landscape and climate characteristics. The understated topographic changes, broad thick mantles of loess, subtle changes in large agronomic fields, diffuse climatic and ecological boundaries, and brief viticulture history contribute to a misperception that terroir may not be applicable or that niche microclimates for vineyards may not exist in the Northern Great Plains. Compared to New York and the Great Lakes vineyard traditions, our history is brief and our knowledge of growing environments is only now evolving. The lack of viticulture history in the Northern Great Plains is a real constraint to new growers, wineries, crop insurance companies, USDA, and the Alcohol and Tobacco Tax and Trade Bureau (TTB; formerly ATF). Although the growing season characteristics of the Northern Great Plains are very suitable to producing high quality winegrapes, it is the dormancy period and the inherent extreme temperature variability that challenges the sustainability of the vineyards.
Expression profiling upon Nex1/MATH‐2‐mediated neuritogenesis in PC12 cells and its implication in regeneration

The expression of Nex1 peaks during brain development when neurite outgrowth and synaptogenesis are highly active. We previously showed that Nex1 is a critical effector of the nerve growth factor (NGF) pathway and its overexpression results in spontaneous neuritogenesis. Furthermore, the PC12-Nex1 cells exhibit accelerated neurite extension upon NGF exposure, and have the capacity to regenerate neurites in the absence of NGF. In this study, we identify the repertoire of genes targeted by Nex1 to unravel the molecular mechanisms by which Nex1 promotes differentiation and regeneration. Our transcriptional analysis reveals that Nex1 modulates a wide spectrum of genes with diverse functions, many of them being key downstream regulators of the NGF pathway, and critical to neuritogenesis, such as microtubules, microtubule-associated proteins (MAPs) and intermediate filaments. We also provide the first evidence that a basic helix-loop-helix (bHLH) protein stimulates the expression of the cyclin-dependent kinase (CDK) inhibitors belonging to the INK4 family, which plays a role in promoting cell-cycle arrest. Finally, we show a dramatic synergistic effect between Nex1 and cAMP, resulting in an impressive regeneration of an elaborate and dense neurite network. Thus, Nex1 has endowed the PC12-Nex1 cells with a distinct combination of gene products that takes part in the complex regulation of neuritogenesis and regeneration.
Diadenosine tetraphosphate (Ap4A) produced by lysyl-tRNA synthetase may play a role in inhibiting the function of the HINT1 tumor suppressor in human colon cancer cells

1782 HINT1 is a member of the highly conserved histidine triad nucleotide binding protein family. Previously we demonstrated that HINT1 is a haplo-insufficient tumor suppressor in mice, and overexpression of HINT1 in human cancer cells causes growth inhibition. However, analysis of cellular levels of HINT1 in various human cancer cell lines indicated that many cancer cells continue to express considerable amounts of the HINT1 protein. Therefore, mechanisms other than repressing gene expression of HINT1 may contribute to inactivation of HINT1 in these cells. In this study we examined the effects of changes in cellular Ap 4 A level on the tumor suppressing function of HINT1 in human colon cancer cells. One of the ligands of HINT1, Ap 4 A, is an exotic nucleotide produced by lysyl-tRNA synthetase (LysRS). In mast cells, an increased cellular level of Ap 4 A attenuated the inhibitory effect of HINT1 on MITF transcription activity. To evaluate whether similar effect of Ap 4 A may contribute to inactivation of HINT1 in human colon cancer cells, we first determined the expression levels of LysRS in these cells. We found that there was a positive correlation between the protein levels of HINT1 and LysRS in a series of human colon cancer cells. HCT116 and SW834 cells expressed high levels of both proteins, and SW480 cells expressed low levels of both proteins. The normalized LysRS/HINT1 ratio was similar in the three cancer cell lines. On the other hand, a normal colon cell line, CCD841, had a significantly lower LysRS/HINT1 ratio, compared with the colon cancer cell lines. Since overexpression of LysRS increases the cellular level of Ap 4 A, this result suggested that HINT1 might be inactivated by high level of cellular Ap 4 A in human colon cancer cells. Because of the importance of TCF/β-catenin signaling in the growth of human colon cancer cells, and HINT1 inhibits the activity of β-catenin through interacting with Pontin and Reptin, which form complex with and regulate the activity of β-catenin, we next conducted GST-pull down assay to examine the effect of Ap 4 A on the association of HINT1 and Pontin. Using recombinant GST-tagged HINT1 and non-tagged Pontin, we found that Ap 4 A caused dissociation of these two proteins in a dose-dependent manner, and that 100 μM of Ap 4 A completely abolished the association of HINT1 and Pontin. Co-immunoprecipitation assays indicated that Pontin formed a complex with LysRS, and overexpression of LysRS inhibited the interaction between HINT1 and Pontin, as well as HINT1 and β-catenin. Consistent with the above findings, overexpression of HINT1 inhibited TCF/β-catenin-mediated gene transcription, and co-overexpression of LysRS reversed this inhibitory effect. Taken together, our results suggest that overexpression of LysRS might contribute to functional inactivation of the tumor suppressor HINT1.
TQM implementation factors for software development: an empirical study

There is a need for methodologies which can enhance the quality of software and improve software developmental efficiencies. One such approach commonly used by software development enterprises is Total Quality Management (TQM). To assess the effectiveness of a TQM program, a key question that is often posed is: What are the salient underlying constructs (factors) essential to a successful TQM program? This study examines these issues in the domain of software development. An analysis of the data gathered from 247 software development sites shows 8 factors pertinent to an effective TQM program in software development. Also, this study compares and contrasts these factors with the Malcolm Baldrige Award criteria and other published results.
Heritable Disorders of Connective Tissue

The molecular composition and organization of connective tissue, known as the extracellular matrix, are extraordinarily complex. Much remains unknown about the number, structure, map location, and regulation of genes that control synthesis, organization, and metabolism of this ubiquitous tissue. However, the genes that specify several hundred proteins involved in connective tissue metabolism and skeletal development have been mapped (1). Mutations in the genes for these proteins cause a variety of disorders. The heritable disorders of connective tissue (HDCT) follow Mendel’s laws, but like many such disorders, show both considerable variability within and among families and genetic heterogeneity (2,3).
Analysis of intangible factors in waste minimization projects

Continual population growth and rising standards of living that accelerate the consumption of limited resources, are forcing society to encourage conservation of these resources. These resources not only include raw material, but also the areas to dispose of the wastes. As a result, communities are driving industries towards waste minimization by limiting waste generation and landfill availability. Firms' environmentally friendly strategies can gain competitive advantage by leading in environmental practices. This advantage emanates from the reduction of risk of environmental regulatory overreaction, as well as improved asset utilization and landfill utilization. However, these intangible benefits are difficult to identify and evaluate particularly with tools that were developed when intangibles were less critical. Many firms simply institute policies that force the tactical decision-makers to make environmentally friendly decisions. However, these policies can commit the firm to act in ways that are not in their best interest, since actions that absorb too many of the firm's resources without sufficient beneficial impact, can generate competitive disadvantages. This paper surveys the available analytical tools that are available to support effective decision-making dealing with intangible costs and benefits. It provides ways to identify some of the intangible benefits and address the value they generate. This paper looks at a case study, where there was an opportunity to reuse a large volume of oven bricks, showing how two companies addressed this opportunity.
An Earned Insurgency: Quality Education as a Constitutional Right

In the following pages, Robert Moses tells the history of the early civil rights movement in Mississippi, focusing on the individuals, alliances, and strategies that brought about fundamental change in the United States and ultimately made possible the election of Barack Obama to the presidency. Moses describes how the efforts of Justice Department officials working from the "top" of society combined with the day-to-day work of sharecroppers and organizers at the "bottom" to challenge Jim Crow. His story takes us from the front lines of the movement in Mississippi to his contemporary efforts to ensure that all children in this country receive a quality education. While working from the bottom of today's movement for educational equality, he calls on Obama to provide the leadership needed at the top to ensure lasting change. In this "illuminated story" he infuses his narration (in sans serif) with his own reflections and insights about the lessons this story offers.
Efficacy of dietary antioxidants to prevent oxidative damage and inhibit chronic disease.

Many in vitro studies have shown that dietary antioxidants, such as vitamin C (ascorbic acid), vitamin E ( tocopherol), s-carotene, and flavonoids, act as effective antioxidants in biological systems such as plasma, lipoproteins, and cultured cells (1–3). For example, vitamin C effectively inhibits lipid and protein oxidation in human plasma exposed to various (patho)physiologically relevant types of oxidative stress, such as activated polymorphonuclear leukocytes, reagent or myeloperoxidase-derived hypochlorous acid, cigarette smoke, or redox-active iron or copper ions (1,3). Vitamin E is the most abundant lipid-soluble antioxidant in human lipoproteins and tissues and acts as a chain-breaking antioxidant against lipid peroxidation (3). scarotene, lycopene, lutein, and other carotenoids and oxy-carotenoids are efficient singlet oxygen quenchers and, thus, may be important in protecting the eye and skin against UV-induced oxidative damage (2,5). These small-molecule dietary antioxidants interact with each other in an "antioxidant network" and complement antioxidant enzymes and metal-binding proteins present in cells and extracellular fluids.
Centrosome Overduplication in Canine Hemangioma and Hemangiosarcoma

Centrosome overduplication (more than 2; >2C) is commonly associated with aneuploidy in many human cancers and is theorized to contribute to malignant transformation via increased chromosomal instability. >2C is not been described in endothelial cell (EC) tumors such as hemangioma (HA) and hemangiosarcoma (HSA). HAs are common, benign canine tumors that may undergo malignant transformation to HSA through unknown cellular mechanisms. To characterize the possible contribution of >2C to the development of HSA, archived formalin-fixed paraffin-embedded canine tissue (5-8 uM thick) with a previous diagnosis of HA (n=4) or HSA (n=6) from the subcutis, spleen or liver were labeled with EC (isolectin) and centrosome (gamma-tubulin) markers by immunofluorescence. Samples were imaged via confocal microscopy and quantified as % of neoplastic EC with >2C. HSAs had significantly greater >2C compared with HAs (20.1+/- 1.4% vs 4.4 +/- 2.3%; p 2C (control...
Determination of transistor infant failure probability in InGaP/GaAs heterojunction bipolar technology

Abstract A novel circuit for measuring the infant mortality rate in InGaP/GaAs HBT Technology is presented. The circuit allows reliability stressing to be performed on as many as 100,000 transistors per wafer and is necessary in order to predict the infant circuit failure rate in circuits with >500 transistors without costly burn-in screens. This new circuit allows for the rapid identification of failed transistors and subsequent failure analysis to allow for process improvements. A variation of the same circuit has also been used to estimate the activation energy, Ea, of the infant failure mechanism. Rough estimates of Ea indicate that the infant failure mechanism is ∼0.5 eV, and that there may be two distinct failure mechanisms responsible for infant failures. Process defects have not been found on the vast majority of failed transistors, and there is good correlation between the substrate dislocation density and the infant failure rate. We have concluded that substrate dislocations are the leading cause of infant mortality in our HBT process.
Unraveling the Social Construction of Homelessness

This article provides a historical and critical analysis of homelessness in the United States. It argues that societal understanding of homelessness stems from a process of social construction in which, over time, differing groups have framed the definition and debate. The main groups influencing interpretations of homelessness are those ascribing to individual and the structural interpretations of social problems. Individual interpretations suggest that homelessness is the result of personal deficiencies, such as substance abuse and social disaffiliation, whereas structural interpretations suggest that it is the result of systemic factors, such as lack of affordable housing and employment opportunities. Social construction has influenced scholarship as well by dictating which questions researchers ask and which evidence gets disseminated. The article concludes by encouraging scholars to reframe the policy debate in a way that more accurately reflects the empirical reality of homelessness.
Latex allergy in patients with myelomeningocele presenting for imaging studies of the urinary tract.

Objective. We prospectively surveyed patients with myelomeningocele who presented in our department over a 3-month period to determine the frequency of latex allergy in this population.Materials and methods. A questionnaire assessed history of allergy to latex and attitudes toward and use or avoidance of latex-containing products in both medical and non-medical environments.
Comparative View of Prenatal Care between the United States and Cuba: Lessons for the United States?

Infant mortality is an indication of a country’s health. The United States has struggled to lower its infant mortality rates. Cuba, a small island with notably fewer resources, has been successful in maintaining a lower infant mortality rate than the United States. The two neighboring countries vary greatly in political systems, economies, and available resources. How can the difference in mortality rate be explained? What can the United States learn from Cuba? This article explores these differences and provides suggestions for change within the United States’ system of health care.
Species specificity of ribosomal proteins in eucaryotic and procaryotic organisms.

Abstract Immunological analysis of ribosomal proteins from E. coli , rat liver, yeast ( S. Cerevisiae ) and plant (mung bean cotyledon) show no cross reactions. Electrophoresis by the split-gel technique in polyacrylamide also indicates that the proteins from eucaryotic (80S) and procaryotic (70S) ribosomes are unique for each species.
Tumor necrosis factor is required for RANTES-induced astrocyte monocyte chemoattractant protein-1 production.

Astrocytes respond to stimulation with the chemokine RANTES (regulated on activation, normal T cell expressed) by production of a series of cytokines and chemokines, including tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). In the present study we demonstrate that RANTES induces TNF, which in turn stimulates subsequent production of MCP-1. TNF-R1 (p55) serves as the principal receptor responsible for MCP-1 synthesis. The results define an astrocyte proinflammatory cascade that amplifies synthesis of proinflammatory mediators. The implications of these findings to inflammatory diseases of the central nervous system are discussed. © 2003 Wiley-Liss, Inc.
Optimization of selective hyperthermia

Selective hyperthermia can be a feasible treatment modality for deep tissue abnormalities. It is accomplished by using a laser or ultrasound noninvasively to transfer energy to a desired target causing tissue damage. This process has two potential benefits to medical professionals: simplicity of procedure and safety to patient. However, optimizing these selective interactions is difficult due to the number of variables. We propose an optimization coefficient relating the dynamic and geometric parameters of selective hyperthermia, and proceed to measure it in an experimental setup consisting of a near-infrared laser and laser-absorbing dye. To simulate tissue, gelatin phantoms are created using a combination of water, intralipid, and gelatin. Our experiments use a 1.00-cm-diam spherical phantom that is homogeneously enhanced with an indocyanine green (ICG) solution and placed inside a nontarget phantom and irradiated by an 805-nm diode laser. Temperature measurements taken at different locations are analyzed so optimization coefficients can be calculated for different parameters. This optimization coefficient compares the difference in temperatures from inside and outside the target. Analysis of the values after thermal equilibrium provides information about the best parameter selection. Our findings indicate that the optimal ICG concentration and power combination for our tested parameters are 0.083% and 0.97 W, respectively. Based on our analysis, optimization can be obtained by using this coefficient to compare the selectivity of several parameter combinations.
Phosphorylation of Pyrimidine Deoxynucleoside Analog Diphosphates SELECTIVE PHOSPHORYLATION OF l-NUCLEOSIDE ANALOG DIPHOSPHATES BY 3-PHOSPHOGLYCERATE KINASE

D-Nucleoside analogs, which are in the natural configuration, as well as the L-nucleoside analogs, are clinically relevant antiviral and anticancer agents. Metabolism of L-nucleoside analog diphosphates to the triphosphates, however, remains unexplored. Studies with recombinant nm23-H1 and -H2 isoforms indicated that L-nucleoside analog diphosphates were not phosphorylated by their nucleoside diphosphate kinase (NDPK) activity. Therefore, roles of creatine kinase, 3-phosphoglycerate kinase, and pyruvate kinase were evaluated using preparations from commercial sources and human HepG2 cells. Phosphorylation of L-OddC, L-SddC, L-Fd4C, L-FMAU, and L-ddC were compared with D-deoxynucleoside analogs, AraC, dFdC, and D-FMAU, and D-dideoxynucleoside analogs, ddC and d4T. Results based on preparations from HepG2 cells showed that L-nucleoside analog diphosphates were selectively phosphorylated by 3-phosphoglycerate kinase, whereas, D-deoxynucleoside analog diphosphates were phosphorylated by NDPK. Interestingly, ddCDP and d4TDP were substrates for creatine kinase, but were not phosphorylated by NDPK. In conclusion, it is proposed that specificity of the phosphorylating enzymes toward the nucleoside analog diphosphates is dependent on the configuration of the analog (L or D) and the presence or absence of 3'-hydroxyl group in the sugar moiety. The enzymatic process of phosphorylation of L- and D-nucleoside analog diphosphates is different in cells.
Scattering lengths and effective ranges for He-He and spin-polarized H-H and D-D scattering

The modifications of effective-range theory, necessitated by the long-range nature of interatomic dispersion and relativistic retardation forces, are discussed. A numerical comparison is given of parameters describing $^{3}\mathrm{\ensuremath{-}}^{3}$He, $^{3}\mathrm{\ensuremath{-}}^{4}$He, and $^{4}\mathrm{\ensuremath{-}}^{4}$He scattering at very low energies calculated with several recently published interaction potentials. The effect of relativistic retardation on these parameters and on the calculated binding energies of the $^{4}\mathrm{\ensuremath{-}}^{4}$He dimer is shown. It is demonstrated that all of these quantities are extremely sensitive to the potential. Scattering lengths and effective ranges for the lowest triplet interactions of H-H and D-D are also reported.
Memristor-based unit cell for a detector readout circuit

This paper presents a memristor based unit cell design for a readout integrated circuit (ROIC). The memristor is a non-volatile nanoscale circuit component that has dynamic resistance dependent on the total charge applied between the positive and negative terminals. In the circuit presented, the memristor acts as the integrator in the unit cell. This eliminates the need for a large integrating capacitor. Simula tions demonstrate the functionality of the unit cell, where the memristor is accurately modeled according to previously pub lished device characterization data. The results show that memristors can potentially be used to reduce the unit cell area, which could increase the fill factor of the photodetector in single chip detector and readout designs. Keywords: Memristor, Photodetector, ROIC, simulation, SPICE
A Prefetching Scheme Exploiting both Data Layout and Access History on Disk

Prefetching is an important technique for improving effective hard disk performance. A prefetcher seeks to accurately predict which data will be requested and load it ahead of the arrival of the corresponding requests. Current disk prefetch policies in major operating systems track access patterns at the level of file abstraction. While this is useful for exploiting application-level access patterns, for two reasons file-level prefetching cannot realize the full performance improvements achievable by prefetching. First, certain prefetch opportunities can only be detected by knowing the data layout on disk, such as the contiguous layout of file metadata or data from multiple files. Second, nonsequential access of disk data (requiring disk head movement) is much slower than sequential access, and the performance penalty for mis-prefetching a randomly located block, relative to that of a sequential block, is correspondingly greater.To overcome the inherent limitations of prefetching at logical file level, we propose to perform prefetching directly at the level of disk layout, and in a portable way. Our technique, called DiskSeen, is intended to be supplementary to, and to work synergistically with, any present file-level prefetch policies. DiskSeen tracks the locations and access times of disk blocks and, based on analysis of their temporal and spatial relationships, seeks to improve the sequentiality of disk accesses and overall prefetching performance. It also implements a mechanism to minimize mis-prefetching, on a per-application basis, to mitigate the corresponding performance penalty.Our implementation of the DiskSeen scheme in the Linux 2.6 kernel shows that it can significantly improve the effectiveness of prefetching, reducing execution times by 20p--60p for microbenchmarks and real applications such as grep, CVS, and TPC-H. Even for workloads specifically designed to expose its weaknesses, DiskSeen incurs only minor performance loss.