cssi/SciSciGPT-SciSciNet huggingface dataset:
P2Y2 receptors mediate nucleotide-induced EGFR phosphorylation and stimulate proliferation and tumorigenesis of head and neck squamous cell carcinoma cell lines.

Abstract Objectives To assess functional expression of the P2Y2 nucleotide receptor (P2Y2R) in head and neck squamous cell carcinoma (HNSCC) cell lines and define its role in nucleotide-induced epidermal growth factor receptor (EGFR) transactivation. The use of anti-EGFR therapeutics to treat HNSCC is hindered by intrinsic and acquired drug resistance. Defining novel pathways that modulate EGFR signaling could identify additional targets to treat HNSCC. Materials and Methods In human HNSCC cell lines CAL27 and FaDu and the mouse oral cancer cell line MOC2, P2Y2R contributions to extracellular nucleotide-induced changes in intracellular free Ca2+ concentration and EGFR and extracellular signal-regulated kinase (ERK1/2) phosphorylation were determined using the ratiometric Ca2+ indicator fura-2 and immunoblot analysis, respectively. Genetic knockout of P2Y2Rs using CRISPR technology or pharmacological inhibition with P2Y2R-selective antagonist AR-C118925 defined P2Y2R contributions to in vivo tumor growth. Results P2Y2R agonists UTP and ATP increased intracellular Ca2+ levels and ERK1/2 and EGFR phosphorylation in CAL27 and FaDu cells, responses that were inhibited by AR-C118925 or P2Y2R knockout. P2Y2R-mediated EGFR phosphorylation was also attenuated by inhibition of the adamalysin family of metalloproteases or Src family kinases. P2Y2R knockout reduced UTP-induced CAL27 cell proliferation in vitro and significantly reduced CAL27 and FaDu tumor xenograft volume in vivo. In a syngeneic mouse model of oral cancer, AR-C118925 administration reduced MOC2 tumor volume. Conclusion P2Y2Rs mediate HNSCC cell responses to extracellular nucleotides and genetic or pharmacological blockade of P2Y2R signaling attenuates tumor cell proliferation and tumorigenesis, suggesting that the P2Y2R represents a novel therapeutic target in HNSCC.
The Fas/FasL Signaling Pathway: Its Role in the Metastatic Process and as a Target for Treating Osteosarcoma Lung Metastases.

Understanding how the tumor microenvironment participates in inhibiting or supporting tumor growth is critical for the development of novel therapies. Osteosarcoma (OS) metastasizes almost exclusively to the lung, an organ where Fas ligand (FasL) is constitutively expressed. This chapter focuses on our studies dedicated to the interaction of OS cells with the lung microenvironment. We will summarize our studies conducted over the past 20 years showing the importance of the Fas/FasL signaling pathway to the establishment and progression of OS metastases in the lung. We demonstrated that the FasL+ lung microenvironment eliminates Fas-positive (Fas+) OS cells that metastasize to the lungs, through apoptosis induced by Fas signaling following interaction of Fas on the tumor cell surface with FasL on the lung epithelial cells. Expression of the Fas receptor on OS cells inversely correlated with the ability of OS cells to form lung metastases. Blocking this pathway interferes with this process, allowing Fas+ cells to grow in the lung. By contrast, upregulation of Fas on Fas− OS cells inhibited their ability to metastasize to the lung. We demonstrated how the FasL+ lung microenvironment can be leveraged for therapeutic intent through the upregulation of Fas expression. To this end, we demonstrated that the histone deacetylase inhibitor entinostat upregulated Fas expression on OS cells, reduced their ability to form lung metastases, and induced regression of established micrometastases. Fas expression in OS cells is regulated epigenetically by the microRNA miR-20a. We showed that expressions of Fas and miR-20a are inversely correlated, and that delivery of anti-miR-20a in vivo to mice with established osteosarcoma lung metastases resulted in upregulation of Fas and tumor regression. Therefore, targeting the Fas signaling pathway may present therapeutic opportunities, which target the lung microenvironment for elimination of OS lung metastases. We have also shown that in addition to being critically involved in the metastatic potential, the Fas signaling pathway may also contribute to the efficacy of chemotherapy. We demonstrated that the chemotherapeutic agent gemcitabine (GCB) increased Fas expression in both human and mouse OS cells in vitro. In vivo, aerosol GCB therapy induced upregulation of Fas expression and the regression of established osteosarcoma lung metastases. The therapeutic efficacy of GCB was contingent upon a FasL+ lung microenvironment as aerosol GCB had no effect in FasL-deficient mice. Manipulation of Fas expression and the Fas pathway should be considered, as this concept may provide additional novel therapeutic approaches for treating patients with OS lung metastases.
Why major in writing? Hyperpragmatism and writing program websites

Abstract This article describes how university writing programs are represented by their institutional web pages. Presenting a content analysis of “Why major in writing” web pages that explicitly appeal to students to join a writing major, the article describes the institutional and disciplinary values those pages articulated through the series of appeals they make to recruit students to the major. Much like professional and technical writing programs, writing studies program websites focus nearly exclusively on marketable skills and job preparation, but don’t give as clear a picture of other individual, cultural, and ethical goods created by the programs. The article argues that writing programs more generally must resist the same siren call of hyperpragmatism often described in scholarship in professional and technical writing. Finally, this study offers strategies for orienting institutional web presences to productively balance economic and pragmatic ideological components with civic, social, and individual rationales for the major.
Aortic Arch Anomalies: Coarctation of the Aorta and Aortic Arch Hypoplasia

The coarctation of the aorta occurs in 7% of congenital heart defect cases with male predominance. High-quality echocardiography can reveal much information in most patients; however, it can be difficult in older/larger children. Cardiac CT angiogram is very important in delineating the extent of the aortic arch obstruction and any presence of collaterals. Prospective ECG-gated cardiac CT angiography using dual-source multidetector CT scanner has high spatial resolution and short acquisition time. Management of the obstruction depends on the severity and associated defects, but surgical repair is the most time-tested management particularly for the pediatric population.
The transcription factor code in iPSC reprogramming

Transcription factor (TF)-induced reprogramming of somatic cells across lineages and to induced pluripotent stem cells (iPSCs) has revealed a remarkable plasticity of differentiated cells and presents great opportunities for generating clinically relevant cell types for disease modeling and regenerative medicine. The understanding of iPSC reprogramming provides insights into the mechanisms that safeguard somatic cell identity, drive epigenetic reprogramming, and underlie cell fate specification in vivo. The combinatorial action of TFs has emerged as the key mechanism for the direct and indirect effects of reprogramming factors that induce the remodelling of the enhancer landscape. The interplay of TFs in iPSC reprogramming also yields trophectoderm- and extraembryonic endoderm-like cell populations, uncovering an intriguing plasticity of cell states and opening new avenues for exploring cell fate decisions during early embryogenesis.
Large Margin Training of Continuous Density Hidden Markov Models

Continuous density hidden Markov models (CD-HMMs) are an essential component of modern systems for automatic speech recognition (ASR). These models assign probabilities to the sequences of acoustic feature vectors extracted by signal processing of speech waveforms. In this chapter, we investigate a new framework for parameter estimation in CD-HMMs. Our framework is inspired by recent parallel trends in the fields of ASR and machine learning. In ASR, significant improvements in performance have been obtained by discriminative training of acoustic models. In machine learning, significant improvements in performance have been obtained by discriminative training of large margin classifiers. Building on both these lines of work, we show how to train CD-HMMs by maximizing an appropriately defined margin between correct and incorrect decodings of speech waveforms. We start by defining an objective function over a transformed parameter space for CD-HMMs, then describe how it can be optimized efficiently by simple gradient-based methods. Within this framework, we obtain highly competitive results for phonetic recognition on the TIMIT speech corpus. We also compare our framework for large margin training to other popular frameworks for discriminative training of CD-HMMs.
Julius Caesar: The Colossus of Rome

Prologue 1. Rome and Italy in the 2nd century BCE 2. Caesar's childhood: the Social War and the Sullan Civil War 3. Caesar's early manhood: the rise of Pompeius 4. Roman politics in the sixties 5. The long year 59 BCE 6. The conquest of Gaul 7. Roman politics in the fifties 8. Caesar's place in Roman literature and culture 9. The Civil Wars against Pompeius and the Optimates 10. Caesar the Dictator Epilogue
Molecular genetic analysis of purine nucleobase transport in Leishmania major

Leishmania major and all other parasitic protozoa are unable to synthesize purines de novo and are therefore reliant upon uptake of preformed purines from their hosts via nucleobase and nucleoside transporters. L. major expresses two nucleobase permeases, NT3 that is a high affinity transporter for purine nucleobases and NT4 that is a low affinity transporter for adenine. nt3((-/-)) null mutant promastigotes were unable to replicate in medium containing 10 microM hypoxanthine, guanine, or xanthine and replicated slowly in 10 microM adenine due to residual low affinity uptake of that purine. The NT3 transporter mediated the uptake of the anti-leishmanial drug allopurinol, and the nt3((-/-)) mutants were resistant to killing by this drug. Expression of the NT3 permease was profoundly downregulated at the protein but not the mRNA level in stationary phase compared with logarithmic phase promastigotes. The nt4((-/-)) null mutant was quantitatively impaired in survival within murine bone marrow-derived macrophages. Extensive efforts to generate an nt3((-/-))/nt4((-/-)) dual null mutant were not successful, suggesting that one of the two nucleobase permeases must be retained for robust growth of the parasite. The phenotypes of these null mutants underscore the importance of purine nucleobase transporters in the Leishmania life cycle and pharmacology.
Function and regulation of prostaglandin synthase 2.

The prostanoids (prostaglandins, prostacyclins, thromboxanes) are one subset of arachidonic-acid derived lipid mediators of inflammation. The leukotrienes constitute the second major class of arachidonic-acid derived lipid mediators. A variety of inflammatory signals (including exogenous mediators such as endotoxin/lipopoly-saccharide and endogenous mediators such as inflammatory cytokines) stimulate cellular phospholipase activities. As a result, arachidonic acid is released from phospholipid membrane stores. This free arachidonic acid is converted either (i) to leukotrienes via the lipoxygenase pathway(s), or (ii) to prostanoids. The key enzyme in prostanoid biosynthesis is prostaglandin synthase (PGS), also known as cyclooxygenase (COX). PGS/COX converts free arachidonate first to prostaglandin G2 (PGG2) by a cyclooxygenase reaction, and then -in a second enzymatic step- to prostaglandin H2 (PGH2) by a hydroperoxidase reaction. PGH2 is then converted to the various prostaglandins (PGE2, PGD2, PGF2a, etc), prostacyclin, (PGI2) or thromboxane by cell-type restricted synthetases that use PGH2 as substrate. The various prostanoids have a wide range of positive and negative immuno-modulatory effects on lymphoid, myeloid, and endothelial cells. New pharmacologic agents that modulate the activity of enzymes involved in prostanoid synthesis or the expression of the genes encoding these enzymes will provide improved directions in the management of acute and chronic inflammatory diseases.
Practical application of state-of-the-art NDE techniques: Evaluation of graphite-epoxy composite wing covers

The X-29 experimental aircraft, based at the NASA Dryden Flight Research Facility, Edwards Air Force Base, California, represents a demonstrator for several state-of-the-art aerospace technologies. The most obvious of these is the forward-swept wing configuration, made possible in this high-performance aircraft by the use of graphite fiber-reinforced epoxy composite laminate wing surfaces. During a routine inspection of the aircraft, a delamination was found in the wing on the right underside of the airplane. A NASA review board investigated the damage and recommended to repair the delamination and to closely monitor its integrity during the post-repair period. The local strain on the surface of the repaired part was measured with strain gages monitored in real time during subsequent flights and the area was periodically inspected nondestructively in a reproducible manner to test for failure of the repair or growth of the delamination. The Materials Characterization Instrumentation Section of the NASA Langley Research Center was called upon to acquire quantitative ultrasonic NDE data from the repaired delamination and to analyze it using the advanced techniques available at that facility. These measurements were in addition to more subjective conventional ultrasonic pulse-echo inspections.
Sentiment Analysis: A Survey.

Sentiment analysis (also known as opinion mining) refers to the use of natural language processing, text analysis and computational linguistics to identify and extract subjective information in source materials. Mining opinions expressed in the user generated content is a challenging yet practically very useful problem. This survey would cover various approaches and methodology used in Sentiment Analysis and Opinion Mining in general. The focus would be on Internet text like, Product review, tweets and other social media.
Bayesian Inference Based on Interval-Valued Prior Distributions and Likelihoods

Although Bayesian inference has been successful in many applications, its serious limitation is the requirement that exact prior probabilities be available. It has increasingly been recognized that this requirement is often not realistic. To overcome this limitation of classical Bayesian inference, we investigate a generalized Bayesian inference, in which prior probabilities as well as likelihoods are interval-valued. Employing the tools of interval analysis and the theory of imprecise probabilities, we develop a method for exact calculation of interval-valued posterior probabilities for given interval-valued prior probabilities and precise or interval-valued likelihoods. This method is further generalized for fuzzy likelihood and fuzzy probabilities later. The classical Bayesian inference is a special case of our method.
Neuro‐fuzzy time‐series analysis of large‐volume data

SUMMARY This paper describes a framework that utilizes an adaptive-network-based fuzzy inference system to perform user-constrained pattern recognition on time-series data. Using a customizable fuzzy logic grammar, the architecture allows an analyst to capture domain expertise in a context-relevant manner. Fuzzy logic rules constructed by the analyst are used to perform feature extraction and influence the training of a neural network to perform pattern recognition. We demonstrate that the architecture is capable of performing noise-tolerant searches across multiple features on large volumes of time-series data. The experiments presented here are from the domain of stock analysis. We are able to create simple rule sets automatically to search a data warehouse of stocks to select stocks that exhibit desirable behaviours. Copyright © 2011 John Wiley & Sons, Ltd.
Thank You and Good Night

Welcome to the Fall 2014 issue of Advances in Social Work. This issue represents the last one on my watch, as I retired from the Indiana University School of Social Work (IUSSW) last May. Since the journal moved to its current online, open-access format in the Fall of 2008, I have had the privilege of serving as its Editor, managing peer review, making final decisions, relaying both positive and negative news to authors, producing the issues, and trying to raise the profile of the journal. During that time we have seen an increase in manuscript submissions and the production of a number of excellent special, thematic issues under the guidance of exceptional guest editors. We now have nearly 1,000 registered users from all over the globe, more than 350 of whom also serve as peer reviewers. All of our archives, dating back to the very first issue in 2000, are now readily available from the Advances website.
Combining NMR Spectral Information with Associated Structural Features to form Computationally Nonintensive, Rugged, and Objective Models of Biological Activity

This article focuses on an alternative strategy for model building known as quantitative spectrometric data–activity relationships (QSDARs). Three-dimensional QSDAR modeling is a complementary technique that has widespread application to many informatics challenges. It provides computational model developers a sensitive, alternate perspective on biological and toxicological properties. Keywords: quantitative spectrometric data–activity relationships (QSDARs); computational model; model validation; NMR spectra
Genetically engineered truncated myosin in Dictyostelium: the carboxyl-terminal regulatory domain is not required for the developmental cycle.

Abstract The study of engineered Dictyostelium mutants with altered or missing myosin has revealed the molecule to be essential both for cytokinesis and for completion of the complex Dictyostelium developmental cycle. To explore the biological role of the carboxyl-terminal portion of the myosin tail, we have created a Dictyostelium cell line bearing a mutation designated my delta C34 in the myosin (mhcA) locus. This cell line produces a truncated myosin protein lacking the 34-kDa carboxyl terminus of the wild-type tail. Southern blots of the mutant cells show that the myosin gene was disrupted by homologous recombination of the transforming plasmid into the myosin locus. Based on in vitro studies of myosin functional domains, the 200-kDa truncated myosin was designed to include a domain important for assembly but to eliminate a domain important for threonine phosphorylation. The mutant cells are defective in cytokinesis, similar to those mutants that are either devoid of myosin (null cells) or contain a truncated 140-kDa myosin (hmm cells). However, unlike previous mutants, the cells carrying the my delta C34 mutation are able to complete the Dictyostelium developmental cycle to form fruiting bodies. Thus a truncated 200-kDa myosin can substitute for native myosin to function in developing cells. These results demonstrate that the 34-kDa carboxyl terminus of myosin, which contributes regulated phosphorylation sites and 20% of the total length of the rod, is not required for the developmental cycle of Dictyostelium.
Self-Assembled Cobalt−Diisocyanobenzene Multilayer Thin Films

Novel coordination chemistry-based multilayers can be self-assembled by alternate immersion of amine-functionalized substrates in CoCl2 and 1,4-diisocyanobenzene (DiCNB) solutions. Resulting multilayers show uniform film growth with increasing number of Co−DiCNB layers. This system provides alternative chemistry to silane-based, carboxylate or metal−bis(phosphonate) multilayer self-assembly, expanding the potential properties and applications of multilayer thin films.
QUANTUM SATURATION AND CONDENSATION OF EXCITONS IN CU2O : A THEORETICAL STUDY

Recent experiments on high density excitons in ${\mathrm{Cu}}_{2}$O provide evidence for degenerate quantum statistics and Bose-Einstein condensation of this nearly ideal gas. We model the time dependence of this bosonic system including exciton decay mechanisms, energy exchange with phonons, and interconversion between ortho (triplet-state) and para (singlet-state) excitons, using parameters for the excitonic decay, the coupling to acoustic and low-lying optical phonons, Auger recombination, and ortho-para interconversion derived from experiment. The single adjustable parameter in our model is the optical-phonon cooling rate for Auger and laser-produced hot excitons. We show that the ortho excitons move along the phase boundary without crossing it (i.e., they exhibit a ``quantum saturation''), as a consequence of the balance of entropy changes due to cooling of excitons by phonons and heating by the nonradiative Auger two-exciton recombination process. The Auger annihilation rate for para-para collisions is much smaller than that for ortho-para and ortho-ortho collisions, explaining why, under the given experimental conditions, the para excitons condense while the ortho excitons fail to do so. \textcopyright{} 1996 The American Physical Society.
A naturalistic experiment investigating the effects of hypnotic induction upon creative imagination scale performance in a clinical setting

Abstract A novel experimental design compared performances on the Creative Imagination Scale (CIS) of Wilson and Barber (1978) under hypnotic induction and control conditions. The Ss were 42 paying clients who participated in the study as an implicit part of their first clinical session. Results in this clinical context replicated previous laboratory studies which found that a conventional hypnotic induction procedure did not enhance scores on CIS. The present study suggests that the implicit clinical investigation, where appropriate, permits scientifically sound hypnosis research in natural field settings.
A study of sound transmission in curved duct bends by the Galerkin method

A computational procedure based on the Galerkin method is developed to study the sound transmission and reflection characteristics of circularly curved bends of rectangular ducts. This procedure is adaptable to routine computer calculation. An important component of the computer program consists of a QR iterative algorithm which solves the matrix eigenvalue problem generated by the Galerkin method. The present procedure produced very satisfactory convergent results when applied even to cases where the incident wave has high frequency and high wave mode numbers. Some properties of the Galerkin solution are investigated. Its relationship to the classical solution by the method of separation of variables is discussed.
The extraction chromatography of californium, einsteinium, and fermium with di(2-ethylhexyl)orthophosphoric acid

Abstract The extraction chromatography of Cf(III), Es(III), and Fm(III) was studied using di(2-ethylhexyl)orthophosphoric acid (HDEHP) adsorbed on hydrophobic diatomaceous earth. Dilute nitric and hydrochloric acid solutions were used as the elutriants. Column performance was studied as a function of particle size, capacity, flow rate, and temperature by measuring the number of theoretical plates obtained for Cf(III) and Es(III) elutions. The distribution coefficients of Cf(III), Es(III), and Fm(III) and the separation factors, Es/Cf and Fm/Es, were studied as a function of temperature with HDEHP adsorbed on Celite, pure undiluted HDEHP, and HDEHP in heptane. The extraction chromatography method was applied to the separation of Es(III) and Fm(III).
Marketing electricity—A military approach

Abstract Marketing offers electric utilities an effective method for combating increased competition in end-use markets. Based on concentration, manoeuvre and speed, utilities can mount a strategic offensive. Such a campaign may involve one or more of the following elements: (1) become customer- and competitor-oriented throughout the organization; (2) set a command structure to integrate demand-side and supply-side options into a unified business plan; (3) seize the initiative from the competition by exploiting the unique attributes of electricity in a few, strategically selected market segments and conducting penetration attacks; (4) develop new uses of electricity to compensate for the saturation and efficiency of existing uses, and conducting flank attacks and guerilla attacks; (5) offer a menu of pricing options based on the differing needs of customers in separate market segments; and (6) in markets where electric use is dominant, conduct 'attack yourself' strategies to improve efficiency.
Ethnic Mobility and the Lower-Income Negro: A Socio-Historical Perspective

The plight of the lower-income Negro is interpreted in ethnic rather than racial terms. The problems confronting the black American result primarily from his lower-class positioning rather than from his "racial" characteristics. Historically he constitutes the most recent ethnic group to encounter the paradoxes of the city, and like all previous groups he faces the predicament of upward mobility. Historically, the ethnic minorities utilized three core routes of upward mobility—labor, ethnic crime, and ethnic politics. Present economic and socio-political developments, however, have increased the difficulty of advancement by these routes. The atrophy of these modes thus generates much of the frustration and violence observed in the urban centers. The solutions to these frustrations lie not in “racial” understanding but rather in the economic restructuring of American life.
Dystrophin-deficient myofibers are vulnerable to mast cell granule-induced necrosis

Duchenne muscular dystrophy is the most common inherited lethal X-linked disorder of mankind and is caused by dystrophin deficiency. The steps involved in the dystrophin-deficiency-induced cascade which lead to myofiber necrosis, progressive muscle wasting in humans and dogs and prominent muscle hypertrophy in mice and cats are obscure. Dystrophin is an intracellular component of the membrane cytoskeleton and its absence would be expected to cause necrosis of isolated myofibers (cell autonomous defect). However, all dystrophin-deficient muscles characteristically show simultaneous degeneration of large groups of muscle fibers (grouped necrosis). This implies that cell death may be mediated by extracellular, non-cell autonomous factors which occur as a secondary consequence of dystrophin deficiency. We have proposed a model where tissue pathology may be mediated by infiltrating mast cells (Gorospe et al., J Neurol Sci 1994). Here we show that intramuscular injections of purified mast cell granules induce widespread myofiber necrosis in dystrophin-deficient mdx mice, but not in normal mice. These data support the hypothesis that dystrophin acts as a plasma membrane stabilizer and that its deficiency renders myofibers more susceptible to damage from mast cell proteases. Moreover, our results support the hypothesis that mast cell degranulation may be a trigger for myofiber death in dystrophin-deficient muscle.
Market Power and Efficiency in Card Payment Systems: A Comment

In this short comment, I provide my views on "Market Power and Efficiency in Card Payment Systems" (published in this issue) that was presented at the Antitrust Activity in Card-Based Payment Systems: Causes and Consequences conference, and more generally on the ideas introduced by Rochet and Tirole's work on payment systems.
Analyses of serum levels of type 1, type 2 and type 3 cytokines reveal multiple abnormalities in lupus‐prone (NZB × NZW) F1 mice

Aim: Inherent in vivo cytokine milieu may help protect normal subjects from developing clinical autoimmunity, whereas changes in cytokine milieu may contribute to the development of lupus-like autoimmunity. Method: Here, we measured circulating levels of the three prototypic cytokines, type 1 (IFN-γ and IL-2), type 2 (IL-4) and type 3 (TGFβ) in the NZB/NZW F1 model of lupus and MHC-matched nonautoimmune mice. Results: Our results demonstrate that circulating IFN-γ and IL-4 levels were higher and active TGFβ levels were lower in lupus-prone animals than in nonautoimmune mice. Conclusion: Such an in vivo cytokine milieu may contribute to the development of lupus in NZB/NZW F1 mice and to the nonautoimmune phenotype in normal animals.
Intercellular adhesion molecule expression in ductal carcinoma of the breast: correlation of immunohistochemical staining with cytologic smear pattern.

Recent studies suggest that altered expression of intercellular adhesion molecules (ICAM) in ductal carcinoma of the breast is associated with a higher incidence of metastases and decreased patient survival. In addition, the presence of significant cellular dyscohesion in cytologic smear preparations has been found to correlate with the presence of regional and distant metastases in a subset of patients. In this study, we correlate the smear pattern in preparations taken directly from surgically excised breast tumors with their immunohistochemical staining pattern, using antibodies directed against a panel of ICAM. We found excellent correlation, as all three tumors with an extremely high degree of tumor cell cohesion showed strong staining with all ICAM antibodies in the vast majority (>/=90%) of tumor cells in corresponding tissue sections. In contrast, five tumors displaying a largely dyscohesive smear pattern demonstrated decreased staining (</=70% of tumor cells) with at least one of the ICAM antibodies used. Tumors with intermediate degrees of cellular cohesion in smear preparations showed varied patterns of ICAM staining. These findings support the theory that loss of ICAM expression represents the physiologic basis for patterns observed in cytologic smears of ductal carcinoma of the breast.
Variation-Conscious Formal Timing Verification in RTL

ariations in timing can occur due to multiple sources on a chip. Many circuit level statistical techniques are used to analyze timing in the presence of these sources of variation. It is desirable to have “variation awareness” at the Register Transfer Level (RTL), and estimate block level delay distributions early in the design cycle, to evaluate design choices quickly and minimize post-synthesis simulation costs. We introduce SHARPE, a rigorous, systematic methodology to verify design correctness in RTL in the presence of variations. In this paper, we describe SHARPE in the context of computing statistical delay invariants in the presence of input variations. We treat the RTL source code as a program and use static program analysis techniques to compute probabilities. We model the probabilistic RTL modules as Discrete Time Markov Chains (DTMCs) that are then checked formally for probabilistic invariants using PRISM, a probabilistic model checker. Our technique is illustrated on the RTL description of the data path of OR1200, an open source embedded processor. We demonstrate the enhanced scalability of SHARPE by applying compositional reasoning for probabilistic model checking.
From the ER to the golgi: insights from the study of combined factors V and VIII deficiency.

The unexpected identification of ERGIC-53 as the gene responsible for combined FV/FVIII deficiency clearly establishes ERGIC-53 as a component of the ER-Golgi transport machinery that is required for the efficient export of coagulation factors V and VIII. This is the first demonstration of a cargo-specific pathway for protein export from the ER in mammalian cells. However, the apparently normal levels observed in these patients for most other plasma proteins demonstrate that ERGIC-53 is not essential for the integrity of the intermediate compartment or the more general process of protein export. The identification of the genetic defect in the subset of patients with FV/VIII deficiency but with intact ERGIC-53 may unmask additional critical components of this unique transport pathway.
Sc3+-Triggered Oxoiron(IV) Formation from O2 and its Non-Heme Iron(II) Precursor via a Sc3+-Peroxo-Fe3+ Intermediate

We report that redox-inactive Sc3+ can trigger O2 activation by the FeII(TMC) center (TMC = tetramethylcyclam) to generate the corresponding oxoiron(IV) complex in the presence of BPh4– as an electron donor. To model a possible intermediate in the above reaction, we generated an unprecedented Sc3+ adduct of [FeIII(η2-O2)(TMC)]+ by an alternative route, which was found to have an Fe3+–(μ-η2:η2-peroxo)–Sc3+ core and to convert to the oxoiron(IV) complex. These results have important implications for the role a Lewis acid can play in facilitating O–O bond cleavage during the course of O2 activation at non-heme iron centers.
GLUINO AXION, NEUTRINO SEESAW, DYNAMICAL GAUGINO MASS, AND A≃0 SUPERSYMMETRY

In the axionic solution of the strong CP problem, fermions which transform under quantum chromodynamics (QCD) are required. In supersymmetry, by equating U(1)PQ with U(1)R, the natural candidates are the gluinos, as pointed out some years ago. A new specific implementation of this idea is proposed, linking the gluino axion scale to that of the canonical seesaw mechanism for neutrinos. Gaugino masses are generated dynamically and the A term is predicted to be very small.
Molecular genetic analysis of transposase-end DNA sequence recognition: cooperativity of three adjacent base-pairs in specific interaction with a mutant Tn5 transposase

Transposition of Tn5 and IS50 requires the specific binding of transposase (Tnp) to the end inverted repeats, the outside end (OE) and the inside end (IE). OE and IE have 12 identical base-pairs and seven non-identical base-pairs. Previously we described the isolation of a Tnp mutant, EK54, that shows an altered preference for OE versus IE compared to wild-type (wt) Tnp. EK54 enhances OE recognition and decreases IE recognition both in DNA binding and in overall transposition. Here we report that base-pairs 10, 11 and 12 of the OE are critical for the specific recognition by EK54 Tnp. These three adjacent base-pairs act cooperatively; all three must be present in order for EK54 Tnp to interact very favorably with the end DNA. The existence of only one or two of these three base-pairs decreases binding of EK54 Tnp. The combined use of EK54 Tnp and a new OE/IE mosaic end sequence containing the OE base-pairs 10, 11 and 12 gives rise to an extraordinarily high transposition frequency. Just as the Tnp is a multifunctional protein, the nucleotides in the 19 bp Tn5 ends also affect other functions besides Tnp binding. Furthermore, the fact that we were able to isolate end sequence variants that transpose at a higher frequency than the natural ends (OE and IE) with wt Tnp reveals yet another way in which the wt transposition frequency is depressed, i.e. by keeping the end sequences suboptimal.
Reconsidering the Compatibility Thesis and Eclecticism: Five Proposed Guidelines for Method Use

This essay examines calls for methodological eclecticism based on the “compatibility thesis,” arguing that they fail to take seriously the assumptions of method and, in so doing, fail to provide a methodological perspective that adequately incorporates the centrally important task of critically examining the theoretical background of methods and conceptual frameworks for research. The authors offer an alternative view of method use and a set of guidelines that emphasize the importance of contextual sensitivity, creativity, conceptual awareness, coherence, and critical reflection in research and evaluation practices.
Protecting against DNS cache poisoning attacks

DNS is vulnerable to cache poisoning attacks, whereby an attacker sends a spoofed reply to its own query. Historically, an attacker only needed to guess a predictable, or more recently, a 16 bit pseudorandom ID in order to be successful. The Kaminsky attack [7] demonstrated successful poisoning attacks that required only 6 seconds on typical networks. Since then, source port randomization (spr) has been used for additional protection. Nevetheless, E. Polyakov demonstrated successful poisoning attacks against spr given a Gigabit network, on the order of 10 hours. Even with slower network speeds, an attack is likely to be successful in a moderate time period. DNSSEC [3] will provide a strong countermeasure to poisoning as well as other attacks against the DNS. However, until DNSSEC is actually deployed, there is a need for additional countermeasures that can be deployed in the near term. In this paper, we describe a new approach that is based on detecting a poisoning attack, then sending an additional request for the same DNS Resource Record. Since the defense is only activated when attacks occur, we expect the performance impact to be minimal. The countermeasure requires no changes to the DNS standards, and only requires modifications to the caching server. Thus it can be deployed incrementally in order to obtain immediate security benefits. We show that our proposed defense makes poisoning attacks substantially more difficult. We have implemented the countermeasure using a local proxy for the BIND caching server, and our tests show that the performance impact is minimal.
Ore Principal Subresultant Coefficients in Solutions

The principal subresultant coefficients of polynomials play a fundamental role in elimination theory and computer algebra. Recently they have been extended to Ore polynomials. They are defined by an expression in the coefficients of Ore polynomials. In this paper, we provide another expression for them. This expression is written in terms of the “solutions” of Ore polynomials (in “generic” case). It can be viewed as a generalization of the well known expression for resultants of two commutative polynomials: the product of the pair-wise differences of their roots.
In vivo structure of the E. coli FtsZ-ring revealed by photoactivated localization microscopy (PALM).

The FtsZ protein, a tubulin-like GTPase, plays a pivotal role in prokaryotic cell division. In vivo it localizes to the midcell and assembles into a ring-like structure-the Z-ring. The Z-ring serves as an essential scaffold to recruit all other division proteins and generates contractile force for cytokinesis, but its supramolecular structure remains unknown. Electron microscopy (EM) has been unsuccessful in detecting the Z-ring due to the dense cytoplasm of bacterial cells, and conventional fluorescence light microscopy (FLM) has only provided images with limited spatial resolution (200–300 nm) due to the diffraction of light. Hence, given the small sizes of bacteria cells, identifying the in vivo structure of the Z-ring presents a substantial challenge. Here, we used photoactivated localization microscopy (PALM), a single molecule-based super-resolution imaging technique, to characterize the in vivo structure of the Z-ring in E. coli. We achieved a spatial resolution of ∼35 nm and discovered that in addition to the expected ring-like conformation, the Z-ring of E. coli adopts a novel compressed helical conformation with variable helical length and pitch. We measured the thickness of the Z-ring to be ∼110 nm and the packing density of FtsZ molecules inside the Z-ring to be greater than what is expected for a single-layered flat ribbon configuration. Our results strongly suggest that the Z-ring is composed of a loose bundle of FtsZ protofilaments that randomly overlap with each other in both longitudinal and radial directions of the cell. Our results provide significant insight into the spatial organization of the Z-ring and open the door for further investigations of structure-function relationships and cell cycle-dependent regulation of the Z-ring.
Multivariate matching polynomials of cyclically labelled graphs

We consider the matching polynomials of graphs whose edges have been cyclically labelled with the ordered set of t labels {x"1,...,x"t}. We first work with the cyclically labelled path, with first edge label x"i, followed by N full cycles of labels {x"1,...,x"t}, and last edge label x"j. Let @F"i","N"t"+"j denote the matching polynomial of this path. It satisfies the (@t,@D)-recurrence: @F"i","N"t"+"j=@t@F"i","("N"-"1")"t"+"j-@D@F"i","("N"-"2")"t"+"j, where @t is the sum of all non-consecutive cyclic monomials in the variables {x"1,...,x"t} and @D=(-1)^tx"1...x"t. A combinatorial/algebraic proof and a matrix proof of this fact are given. Let G"N denote the first fundamental solution to the (@t,@D)-recurrence. We express G"N (i) as a cyclic binomial using the symmetric representation of a matrix, (ii) in terms of Chebyshev polynomials of the second kind in the variables @t and @D, and (iii) as a quotient of two matching polynomials. We extend our results from paths to cycles and rooted trees.
Characteristics of a capillary-generated particle beam

Abstract The characteristics of a particle beam produced by expanding monodisperse aerosols through a capillary nozzle into a vacuum were studied. The particle beam generator consists of a capillary, 100 μm diameter × 5 mm length, which produced the particle beam, and a skimmer with a 350-μ aperture. The vacuum chambers upstream and downstream of the skimmer were at 0.5 Torr (67 Pa) and 0.2 Torr (27 Pa), respectively. The efficiency of particle transmission through the capillary-skimmer system, defined as the ratio of number of particles collected downstream of the skimmer to the number of particles that enter the capillary during times of collection, was measured at variable capillary-skimmer separations, ranging from 2.0 to 14.7 mm. The angular spread of the particle beam was also measured at these same capillary-skimmer separations. At the minimum separation, transmission efficiencies were greater than 90% for particles 1.52 μm or smaller. For larger particles, the efficiency decreased with increasing particle size and was 71% for 5.48-μm particles. As the capillary-skimmer distance increased, the transmission efficiency decreased primarily because the skimmer acted as a limiting aperture. The solid angle of the particle beam deposit also showed a dependence on particle size. A minimum in the solid angle was observed for particles of 0.5 μm diameter. This focusing effect is explained by the variation of particle trajectories with aerodynamic particle diameter at the entrance to the capillary.
APLASMOMYCIN C : STRUCTURAL STUDIES OF A MARINE ANTIBIOTIC

Abstract The solid and solution state structures of aplasmomycin C, a boroncontaining antibiotic, were studied by single crystal X-ray diffraction and NMR techniques. This unusual antibiotic was shown to have a complex and as yet imperfectly understood series of conformations.
Chemoradiation enhances response in stage IIIB lung cancer

Upon workup, the vast majority of non-small cell lung cancer patients are unresectable. Classically these patients undergo external beam radiation alone to 6,000 cGy which results in a disappointing 8.9 month median survival and high local failure rate. To enhance response, radiation dose was escalated and combined with multiagent chemotherapy for patients with stage IIIB non-small cell lung carcinoma. Eight patients (ages 54–75 years, mean 63 years) were initiated on CT guided radiation therapy to the primary tumor, mediastinum, and ipsilateral supraclavicular fossa to 5,400 cGy in 200 cGy/day fractions. The primary tumor bed was then boosted to 7,400 cGy at 200 cGy/day. Concomitant with the radiation boost 4–6 monthly cycles of Cisplatinum and VP16 were initiated in an outpatient setting. Diflucan and Carafate were dispensed to minimize mucositis during radiation therapy. All eight patients completed the prescribed treatment course without interruption. No patient was hospitalized due to treatment-related toxicity and mucositis was minimal. At 12 month follow-up each patient was alive without pulmonary complaint and radiographically none had disease progression at the primary site. Four patients developed evidence of metastatic disease: one at 4 months (brain), the second at 9 months (brain), the third at 12 months (bone), and the fourth at 18 months (contralateral lung). Overall, median survival was 24 months (range 15–40 months). In conclusion, dose escalation of radiation with concomitant chemotherapy offers excellent pulmonary palliation without undue morbidity. Local control and survival appear to be increased compared to radiation alone but further evaluation is required in larger trials. Radiat Oncol Invest 1996;4:171–175. © 1996 Wiley-Liss, Inc.
Dependent Development and the Division of Labor by Sex: Venezuela

Because the values associated with sex roles are particularly tenacious, women's emancipation is likely to be one of the last frontiers of any social movement, and thus serves as a crude index of social change. More importantly, a focus on women's role in development reflects a great deal about the internal or invisible workings of a society that underlie the more visible formal structures. Researchers have observed a positive relationship between women's participation in economic activities and higher levels of economic development (Wilensky, 1968), with the result that female labor force participation rates have occasionally been used as indicators of development. In the same way as such linear schemes as Rostow's (1971) "stage theory," these assumptions are based on the "Western'i capitalist model and ignore the crucial relationships with the rest of the world. Recent studies question the belief that economic development enhances the status of women in the work force. Even in the highly-developed U.S. economy, Knudsen (1969:183) demonstrates a "gradual but persistent decline in women's occupational economic and educational achievements, compared to those of men." Changes in economic systems may actually decrease women's participation in economic activities in underdeveloped countries, especially where traditional activities which were in the hands of women come to be replaced by modern male-dominated activities (Boserup, 'The development of many of the ideas in this paper took place during the Social Science Research Council-sponsored Inter-American Training Seminar on "Feminine Perspectives in Social Science Research in Latin America," summer of 1974. I am grateful to all the other participants in the seminar who showed their willingness to exchange ideas, especially to Carmen Diana Deere and Heleieth Saffioti - whose stimulation is most responsible for the ideas expressed in this paper. A special thanks also goes to Charles Wood, who made invaluable suggestions throughout the development of this analysis, and to Harley Browning for first sparking my interest in the labor
Component-based track inspection using machine-vision technology

In this paper, we present our latest research engagement with a railroad company to apply machine vision technologies to automate the inspection and condition monitoring of railroad tracks. Specifically, we have proposed a complete architecture including imaging setup for capturing multiple video streams, important rail component detection such as tie plate, spike, anchor and joint bar bolt, defect identification such as raised spikes, defect severity analysis and temporal condition analysis, and long-term predictive assessment. This paper will particularly present various video analytics that we have developed to detect rail components, which form the building block of the entire framework. Our preliminary performance study has achieved an average of 98.2% detection rate, 1.57% false positive rate and 1.78% false negative rate on the component detection. Finally, with the lack of sufficient representative data and annotations to evaluate system performance on exception detection at both sequence and compliance levels, we proposed a mathematical modeling approach to calculate the probabilities of detecting such exceptions. Such analysis shows that there is still big room for us to improve our approaches in order to achieve desired false positive rate and miss detection rate at the sequence level.