cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1895: The role of the IFNγ pathway in the development of vemurafenib resistance in BRAFV600E mutant thyroid carcinoma

BRAFV600E is the most common driver mutation in anaplastic thyroid cancer, and BRAF inhibitors are increasingly being used in the treatment of this disease. However, the therapeutic benefit of BRAFV600E inhibitors, such as vemurafenib, has been limited in thyroid cancer due to rapid development of drug resistance in clinical practice. Here, we characterize a targetable mechanism of vemurafenib resistance by studying vemurafenib-resistant clones derived from BRAFV600E mutant anaplastic thyroid cancer cell lines (8505C and FRO), and propose a drug combination to overcome resistance. Vemurafenib resistance in these established clones was verified by persistent activation of ERK1/2 after vemurafenib treatment by western blot analysis. RNA-sequencing and subsequent ingenuity pathway analysis (IPA) was used to identify differences in pathway activation after vemurafenib treatment in parental and vemurafenib-resistant cell lines. Treatment of parental cells with vemurafenib resulted in differential gene expression correlating with upstream activation of the IFNγ-STAT1-IRF1 pathway (All FDR Citation Format: Jessica Limberg, Katherine D. Gray, Mandeep Singh, Timothy M. Ullmann, Brian Wyrwas, Weibin Wang, Zachary Lowenstein, Steve El Eshaky, Heng Liang, Wei Li, Tuo Zhang, Jenny Xiang, Dessislava Stefanova, Rasa Zarnegar, Thomas J. Fahey, Irene M. Min. The role of the IFNγ pathway in the development of vemurafenib resistance in BRAFV600E mutant thyroid carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1895.
A Descriptive Study of Guided Tours at Mammoth Cave National Park

For most visitors, guided tours are the only way to experience a cave. Since few studies have been conducted in these settings, there is no explanation for a recent decline in attendance at many we...
A novel fish sampling system for ROVs

Abstract Mesophotic coral reefs (~30–150 m) and deeper reefs (>150 m) represent some of the least explored and poorly documented habitats in our oceans. These deep ecosystems are both high in biodiversity and ecologically distinct from shallower reefs. They are also equally threatened by natural and anthropogenic factors. Thanks to advancements in remote undersea technologies, our access to and understanding of these poorly studied environments continues to expand. With current data now suggesting more stratified populations of reef fishes and a continuous yield of new species discovered in the mesophotic zone, now under global pressures of climate change and overfishing, the need to explore these ecosystems has never been greater. Most deep-sea (>200 m) biodiversity studies rely on dredging and trawling technologies that are not selective or targeted. Here we present on the design and field demonstration of a compact, low-cost, targeted reef fish sampling system intended for use on inspection-class ROVs in the mesophotic zone. During a research expedition to the Western Province of the Solomon Islands, the system successfully collected multiple novel fish species at depths ranging from 90 to 187 m. The results obtained during this expedition highlight the utility of ROV-based collecting systems, add to the growing knowledge of mesophotic reef communities, and inspire new techniques for sampling mobile faunas at depth.
Modular Versus Conventional Construction: An Analysis of Cost and Benefits via a Case Study

This paper presents a broad analysis of the cost and benefits of the two main construction methods currently in use in North America––the conventional construction and the modular construction. The main goal is to provide a cost estimate of the implications of both construction methods for low-rise apartment buildings as well as to determine which one is more cost-effective. The methodology consists of a qualitative analysis that outlines the benefits of each construction method over the other, and a quantitative analysis that compares the cost of the finished building per square foot. Both analyses are conducted by evaluating a case study of a five-story low-rise senior residential building with similar characteristics, one built using conventional method and the other built hypothetically with modules. The benefits identified for the conventional low-rise building include later design changes, easy to understand for investors, less logistics, and easy to manage. On the other hand, the benefits for modular low-rise are higher quality control, less on-site work, and less on-site trades. The quantitative results show that the modular construction method is only marginally more cost-effective than the conventional construction method under the same circumstances. Through the proposed method, the contractors and developers can assess the cost-effectiveness of the two construction methods for low-rise residential apartment projects to make informed decisions.
Population Genomics of the Commercially Important Gulf of Mexico Pink Shrimp Farfantepenaeus duorarum (Burkenroad, 1939) Support Models of Juvenile Transport Around the Florida Peninsula

The Gulf of Mexico pink shrimp, Farfantepenaeus duorarum, supports large fisheries in the United States and Mexico, with nearly 7,000 tons harvested from the region in 2016. Given the commercial importance of this species, management is critical: in 1997, the southern Gulf of Mexico pink shrimp fishery was declared collapsed and mitigation strategies went into effect, with recovery efforts lasting over a decade. Fisheries management can be informed and improved through a better understanding of how factors associated with early life history impact genetic diversity and population structure in the recruited population. Farfantepenaeus duorarum are short-lived, but highly fecund, and display high variability in recruitment patterns. To date, modeling the impacts of ecological, physical, and behavioral factors on juvenile settlement has focused on recruitment of larval individuals of F. duorarum to nursery grounds in Florida Bay. Here, we articulate testable hypotheses stemming from a recent model of larval transport and evaluate support for each with a population genomics approach, generating reduced representation library sequencing data for F. duorarum collected from seven regions around the Florida Peninsula. Our research represents the first and most molecular data-rich study of population structure in F. duorarum in the Gulf and reveals evidence of a differentiated population in the Dry Tortugas. Our approach largely validates a model of larval transport, allowing us to make management-informative inferences about the impacts of spawning location and recruitment patterns on intraspecific genetic diversity. Such inferences improve our understanding of the roles of non-genetic factors in generating and maintaining genetic diversity in a commercially important penaeid shrimp species.
Understanding rationality in hobbes and hume

Many commentators think that Hobbes was committed to an instrumental view of rationality which foreshadows that of David Hume. The Humean conception of instrumental rationality is a conjunction of the following two claims: (a) no preferences or desires can properly be said to be irrational in themselves, and (b) the role of reason or rationality can only be confined to informing the agent with true beliefs about the world, and revealing the most effective means that could satisfy the agent’s current ends whatever they happen to be. In this paper, I argue that, unlike what many people think, a careful reading of Hobbes shows that he was committed to neither of these claims.
Short-Term, High-Dose Administration of Corticosterone by Injection Facilitates Trace Eyeblink Conditioning in Young Male Rats

Glucocorticoids released as part of the physiological response to stress are known to affect cognitive function, presumably via effects on the hippocampus. Trace classical eyeblink conditioning is an associative learning task which depends on the hippocampus and has been used to examine the development of learning processes in young mammals. Previously, we demonstrated deficits in trace eyeblink conditioning associated with postnatal administration of the glucocorticoid corticosterone by creating a sustained elevation with methods such as subcutaneous timed-release pellets and osmotic mini-pumps which were active over several days. In the present study, we examined the effects of an oscillating pattern of corticosterone elevation on subsequent trace eyeblink conditioning. Twice daily corticosterone injections (high, low, or vehicle) were administered over a 3-day period, starting at postnatal day 15. Then, on postnatal day 28, animals underwent trace classical eyeblink conditioning to examine the possible influence of earlier corticosterone elevations on the development of learning and memory. Eyeblink conditioning was affected by corticosterone treatments, but only for males, and only very early in acquisition; Males receiving the high dose of corticosterone exhibited facilitation of learning relative to controls. These data demonstrate that oscillating corticosterone elevations produce opposite effects on this associative learning task than do sustained elevations.
The Transnational Appeal Of Formalism: The Case Of Japan's Netting Law

The paper addresses the proliferation of "formalist" regulatory devices in the field of international financial regulation. It seeks to understand this transnational trend from the standpoint of a concrete case of legal reform in the global derivatives markets as they are encountered in Japan. Drawing upon five months of ethnographic fieldwork among traders and regulators, the paper offers an account of how processes identified with the expansion of the Rule of Law occur in the context of Japan's Big Bang, how they are interpreted and deployed by a variety of participants and audiences, and ultimately why formalism emerges as the solution as well as the mode or genre of deliberation in such reformist projects.
The Partial Dissociation and the Reassociation of the Pigeon Liver Fatty Acid Synthetase Complex

Abstract Enzyme activity of the pigeon liver fatty acid synthetase declines on storage in a phosphate-buffered medium containing low concentrations of mercaptoethanol. This decline in activity is accompanied by a partial dissociation of the enzyme complex into subunits which have molecular weights half that of the original complex. Reaction of the complex with carboxymethyl disulfide or dialysis against maleate also result in the loss of fatty acid synthetase activity and the dissociation of the complex to half molecular weight units. Incubation of the protein stored in mercaptoethanol or treated with carboxymethyl disulfide with the reducing agent dithiothreitol partially restores enzyme activity. This reduction also results in the reassociation of the half molecular weight units to a unit with the same molecular weight as the original complex. Dissociation of the enzyme complex with maleate is irreversible. Palmityl coenzyme A also inhibits enzyme activity for fatty acid synthesis with a concomitant dissociation of the fatty acid synthetase to half molecular weight subunits. It is concluded from the above results that noncovalent interaction exists between the two halves of the fatty acid synthetase complex. Since a modification of sulfhydryl groups weakens or eliminates this noncovalent interaction, it is evident that the maintenance of sulfhydryl groups in the reduced state is necessary for the structural organization of the fatty acid synthetase complex as well as for its catalytic activity.
On the Potential Impact of Irrigated Areas in North America on Summer Rainfall Caused by Large-Scale Systems.

Abstract The potential impact of the increase in irrigated areas in North America during the past 100 years on summer rainfall associated with medium- to large-scale precipitation systems is evaluated conceptually and by several illustrative numerical model simulations. The model results for the simulated cases suggest a tendency toward some increase in the continental-average rainfall for the present irrigation conditions compared with those of past irrigation. The maximum increase obtained for several studied cases of 6-day duration each was 1.7%. Rainfall increases typically occur in the location of existing rainfall areas, and the main effect of irrigation is to redistribute rainfall in those preexisting precipitation regions.
Adapting the SpaceCube v2.0 data processing system for mission-unique application requirements

The SpaceCube™ v2.0 system is a high performance, reconfigurable, hybrid data processing system that can be used in a multitude of applications including those that require a radiation hardened and reliable solution. This paper provides an overview of the design architecture, flexibility, and the advantages of the modular SpaceCube v2.0 high performance data processing system for space applications.
Pharmacotherapy of Alzheimer’s disease: current and future trends

Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD therapy, drug development has not met significant clinical success. Current pharmacotherapy of AD is limited to cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine. Considerable research is underway to develop newer agents for the management of AD. Since amyloid-β (Aβ) has been implicated in AD pathogenesis, the use of β secretase inhibitors as well as immunotherapy against Aβ has been investigated. A considerable effort has been spent investigating the therapeutic potential of antioxidants and anti-inflammatory agents, several of natural products and dietary origin, in AD treatment. Numerous drug targets have also been investigated for AD treatment and a modest drug pipeline is available. Despite these efforts, drug development for AD has proved extremely difficult and most clinical trials have afforded disappointing results.
Lateral or radial segregation in solidification of binary alloy with a curved liquid-solid interface

This paper deals with steady state lateral or radial segregation of solute in solidification of a binary alloy with a curved solid-liquid interface. It is an extension of the work of Coriell and Sekerka and of Coriell et al. for interface shapes that meet the crucible wall at an arbitrary angle, as is commonly found in experiments. This work is limited to the diffusion controlled growth regime in which the Peclet number Pe = Vl/D is large, and where the interface deflection is small. In the definition of Peclet number V is the growth rate, l is a characteristic length, and D is the binary diffusion coefficient of the solute in the liquid. We present analytical expressions for lateral and radial segregation which can be readily evaluated, given the material properties, growth velocity, and an interface shape obtained from experiment.
Calculation of convective heating on proposed aeroassist flight experiment vehicle

Convective heating calculations of a NASA aeroassist flight experiment (AFE) configuration consisting of a blunted, elliptic cone raked off at the base, and fitted with a skirt-type afterbody with a generous corner radius, are presented. The HALIS inviscid flowfield code is used to supply edge properties to an approximate three-dimensional boundary-layer method to calculate the surface heating. Calculations at Mach number 9.86 and approximate Reynolds number of 500,000, for angles of attack from -10 to 10 degrees, are in general good agreement with Langley 31-inch Mach 10 Tunnel experimental data. The results validate the application of the present overall AFE configuration heating pattern heating contours to aeroassist orbital transfer vehicle heating distribution determinations.
The arsenal on fire: The reader in the riot, 1943

During World War II the dissonance between American discriminatory practices and our egalitarian ideology achieved heightened visibility. Stories about the Detroit Race Riot of 1943 revealed that dissonance. Victor Turner's concept of the processual social drama frames reading of the story in Life magazine—the most important contemporary American media presence—within a context of African‐ and Euro‐American media of the period. This reading shows a repositioning of middle class white readers as liberals who supported an enlarged, technologically sophisticated federal government which could end America's racial conflict.
The mass spectra of carbon‐13 labeled 2‐hydroxynaphthoquinones

Carbon monoxide is lost from the molecular ion of 2-hydroxy-1,4-naphthoquinone (I) almost exclusively from C-2 as shown from carbon-13 labeling studies. The fragmentation scheme originally proposed by Williams for I is not a major process.
Symptom disclosure to male and female physicians: effects of sex, physical attractiveness, and symptom type.

Seventy-five subjects (50 male and 25 female) rated their willingness to disclose symptoms of a personal nature, general nature, and mental illness nature to male and female physicians whose photographs had been pretested as being either physically attractive or physically unattractive. Increased willingness to disclose was related to (1) the more physically attractive physicians, (2) general as compared to personal or mental symptoms, (3) same-sex match-ups between patient and physician, especially when (4) disclosing personal or mental illness symptoms or concerns. The sex of the physician per sehad no influence on patients' willingness to disclose symptoms. Implications are drawn concerning the patient's assignment to or choice of physician based on sex. Patient education and training in symptom disclosure as well as physician's skill building in facilitating symptom disclosure are also indicated.
Extreme Flood Response: The June 2008 Flooding in Iowa

AbstractThe authors examine the hydroclimatology, hydrometeorology, and hydrology of extreme floods through analyses that center on the June 2008 flooding in Iowa. The most striking feature of the June 2008 flooding was the flood peak of the Cedar River at Cedar Rapids (3964 m3 s−1), which was almost twice the previous maximum from a record of 110 years. The spatial extent of extreme flooding was exceptional, with more U.S. Geological Survey stream gauging stations reporting record flood peaks than in any other year. The 2008 flooding was produced by a sequence of organized thunderstorm systems over a period of two weeks. The authors examine clustering and seasonality of flooding in the Iowa study region and link these properties to features of the June 2008 flood event. They examine the environment of heavy rainfall in Iowa during June 2008 through analyses of composite rainfall fields (15-min time interval and 1-km spatial resolution) developed with the Hydro-NEXRAD system and simulations using the Weat...
Informal Learning and Identity Formation in Online Social Networks

All students today are increasingly expected to develop technological fluency, digital citizenship, and other twenty‐first century competencies despite wide variability in the quality of learning opportunities schools provide. Social network sites (SNSs) available via the internet may provide promising contexts for learning to supplement school‐based experiences. This qualitative study examines how high school students from low‐income families in the USA use the SNS, MySpace, for identity formation and informal learning. The analysis revealed that SNSs used outside of school allowed students to formulate and explore various dimensions of their identity and demonstrate twenty‐first century skills; however, students did not perceive a connection between their online activities and learning in classrooms. We discuss how learning with such technologies might be incorporated into the students’ overall learning ecology to reduce educational inequities and how current institutionalized approaches might shift to ...
Correlation between β-defensin expression and induction profiles in gingival keratinocytes

Abstract Human β-defensins are antimicrobial peptides produced by epithelial cells. To date, 28 β-defensins have been described and the expression of a select few has been classified as constitutive or inducible. Most studies have evaluated expression and regulation using a limited number of primary cell cultures or immortalized cell lines. The goal of this study was to quantitatively assess the in vitro expression and inducibility profiles of human β-defensins, HBD-1, HBD-2, and HBD-3 across a number of primary gingival keratinocyte cultures. Cultured cells from 14 human subjects were stimulated with interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ) or Escherichia coli lipopolysaccharide (LPS) and analyzed by reverse transcription (RT)-PCR. A subset of cultures were quantitatively assessed by real-time PCR. HBD-1 presented the highest and most heterogeneous expression at the basal level (non-stimulated) as compared to expression of HBD-2 and HBD-3, which was significantly lower and homogeneous. IFN-γ was a primary inducer for HBD-1 and HBD-3, while IL-1β and TNF-α were primary inducers for HBD-2. Sporadic induction was seen for IL-2, IL-6 and LPS. Synergistic expression was seen when various cytokines were combined. Interestingly, the induction potential of each β-defensin was directly correlated to its basal expression. An inhibitor of JAK2 kinase (Janus kinase), down-regulated IFN-γ-induced HBD-1 and HBD-3 expression, suggesting a role for the JAK/signal transducer and activator of transcription (STAT) signaling pathway in their expression. HBD-2 protein expression of supernatants and cell lysates paralleled mRNA expression. The results suggest that β-defensin expression and induction in gingival keratinocytes is similar to that seen in other tissue. However, the novel finding of considerable variation among induction levels and the correlation of the induction with basal expression suggests that these innate response elements may play a key role in susceptibility or resistance to disease in the oral cavity.
Analysing the effects of serially-correlated demands on costs and service levels: a lost-sale case inventory system

This paper studies a stochastic inventory system exposed to demands that exhibit serial-correlation components. The relationship between different levels of serial-correlation and inventory cost components as well as reorder points and order quantities are analysed in this study. Understanding these relationships provides opportunities for managers to leverage logistic and cross-functional supply chain levers which may be used to inform managerial risk mitigation plans. We consider a lost-sale inventory system with continuous monitoring while applying an enhanced version of simulated annealing that incorporates pattern search, ranking and selection to generate sub-optimal solutions to this problem. We employ an experimental design methodology to quantify the magnitude and significance of main effects and interactions. The analysis of the variance demonstrates that holding costs and the order quantity become substantial and significant as the auto-correlation increases in the studied setting. Total costs and service levels are compared between solutions that ignore autocorrelation factors and those that account for these dependencies.
Reactivity and transformation of antibacterial N-oxides in the presence of manganese oxide.

Organic N-oxides are an important structural class in many pharmaceutical and industrial chemicals. Little is known about the potential transformation of organic N-oxides at the sediment−water interface. Veterinary antibacterial agents carbadox and olaquindox are examples of commonly used heterocyclic N-oxides. Investigation with various N-oxides including carbadox, olaquindox, quinoline N-oxide, and quindoxin revealed surprisingly high reactivity toward MnO2 for all of the compounds except olaquindox. Desoxycarbadox and quinoxaline, two structurally related compounds that lack an N-oxide functional group, showed much lower or no reactivity toward MnO2. Comparisons among the previous compounds indicate that N-oxide moiety is the primary reactive site to MnO2, and substitution at the α-C adjacent to the N-oxide group is critical in determining the overall reactivity. Reactions of N-oxides with MnO2 appeared to be oxidation, with generation of Mn2+ parallel to degradation of the parent organics. Product cha...
Reply to “Comment on ‘Isotope effect in high- T c superconductors’ ”

Our paper on the isotope effect in high-temperature superconductors with cation substitutions presents a comprehensive analysis rooted completely in the experimental evidence. In this Reply we show that pair-breaking disorder, isotope effects, doping-induced variations in ${T}_{c}$ and in the magnetic penetration depth, Coulomb's law, and Anderson's theorem are treated with correct physical and mathematical fundamentals. In contrast, the theory fostered in the Comment by Alexandrov and Zhao contradicts several specific experimental facts, eight of which are briefly discussed. Their Comment also uncritically repeats a previously discredited assertion of an isotope effect in the superconducting carrier mass, incorrectly assumes that cation doping continuously varies intrinsic superconducting parameters, unjustifiably assigns importance to data from samples with serious quality problems, and renders a false estimate of the pair-breaking strength.
Interaction of a mantle plume and a segmented mid-ocean ridge: Results from numerical modeling

Abstract Previous investigations have proposed that changes in lithospheric thickness across a transform fault, due to the juxtaposition of seafloor of different ages, can impede lateral dispersion of an on-ridge mantle plume. The application of this “transform damming” mechanism has been considered for several plume–ridge systems, including the Reunion hotspot and the Central Indian Ridge, the Amsterdam–St. Paul hotspot and the Southeast Indian Ridge, the Cobb hotspot and the Juan de Fuca Ridge, the Iceland hotspot and the Kolbeinsey Ridge, the Afar plume and the ridges of the Gulf of Aden, and the Marion/Crozet hotspot and the Southwest Indian Ridge. This study explores the geodynamics of the transform damming mechanism using a three-dimensional finite element numerical model. The model solves the coupled steady-state equations for conservation of mass, momentum, and energy, including thermal buoyancy and viscosity that is dependent on pressure and temperature. The plume is introduced as a circular thermal anomaly on the bottom boundary of the numerical domain. The center of the plume conduit is located directly beneath a spreading segment, at a distance of 200 km (measured in the along-axis direction) from a transform offset with length 100 km. Half-spreading rate is 0.5 cm/yr. In a series of numerical experiments, the buoyancy flux of the modeled plume is progressively increased to investigate the effects on the temperature and velocity structure of the upper mantle in the vicinity of the transform. Unlike earlier studies, which suggest that a transform always acts to decrease the along-axis extent of plume signature, these models imply that the effect of a transform on plume dispersion may be complex. Under certain ranges of plume flux modeled in this study, the region of the upper mantle undergoing along-axis flow directed away from the plume could be enhanced by the three-dimensional velocity and temperature structure associated with ridge–transform–ridge geometry. It is suggested that, for a setting where a plume–ridge system has one or more transforms, a location-specific model with appropriate plate boundary geometry be used to assess the importance of ridge offsets on upper mantle geodynamics
Modification of the competitive protein-binding assay for corticosterone: Serial measurements in the rat

Abstract An ultramicro method for plasma corticosterone based on a competitive protein-binding technique is described and evaluated. The method proved highly satisfactory for the serial assay of plasma corticosterone in 20 μl of rat plasma. A chronic indwelling catheter placed in the jugular vein was used for continuous infusion of heparinized saline and withdrawal of blood samples for corticosterone measurement at appropriate intervals in undisturbed rats.
Responses to failed humor

Abstract Although research on the pragmatics of humor has increased, the study of failed humor has continued to be neglected. The purpose of the present paper is to open the discussion of this phenomenon through the examination of a corpus of 186 responses to failed humor. These responses, which were elicited through the telling of a joke found to be lacking in humor for most hearers, were classified by type and affective sense (positive, negative, and neutral). The data were also categorized by the sociolinguistic variables of age, gender, and social relationship. The findings indicate that responses to failed humor go well beyond the typical groans or fake laughter that are often asserted as prototypical reactions in the literature, with laughter, metalinguistic comments, and interjections as the most common responses. In addition, no significant differences were found in response types according to age or gender; however, very strong effects were found for social relationship, with negative reactions more common among intimates and neutral reactions preferred by acquaintances and strangers.
P66 Characterization of wild type and patient-described mutant forms of Human Persulfide Dioxygenase, ETHE1

Hydrogen sulfide (H 2 S) is an endogenously produced gaseous signaling molecule with beneficial effects in various cellular processes in the central nervous system, cardiovascular system and gastrointestinal tract. The biogenesis of H 2 S involves the enzymes of the transsulfuration pathway cystathionine b-synthase and g-cystathionase. H 2 S oxidation and removal occurs in the mitochondria and the electrons from this oxidation are used in electron transfer chain to generate energy. Steady-state levels of H 2 S are controlled by its biogenesis in the transsulfuration pathway and its efficient oxygen-dependent catabolism in the mitochondria by a 3-enzyme pathway including sulfide quinone oxidoreductase, persulfide dioxygenase (ETHE1) and a sulfur transferase. Mutations in the persulfide dioxgenase, ETHE1, result in ethylmalonic encephalopathy, an inborn error of metabolism. In this study, we report the biochemical characterization and kinetic properties of human persulfide dioxygenase and describe the biochemical penalties associated with two patient mutations, T152I and D196N. Steady-state kinetic analysis reveals that the T152I mutation results in a 3-fold lower activity, which is correlated with a 3-fold lower iron content compared to the wild-type enzyme. The D196N mutation results in a 2-fold higher K M for the substrate, glutathione persulfide (GSSH).
Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross-presenting function

Ability to cross-present exogenous antigens in the human leukocyte antigen class I pathway is key to the antigen presenting function of mature tumor cell-loaded dendritic cells (DC). Conditions of DC maturation have been shown to be important for DCs ability to produce proinflammatory cytokines and induce T cell effector functions. However, it remains unknown if the different pathways of maturation are associated with modulation of the ability of mature DCs to cross-present tumor antigens (TA). Here, we compare DC matured with 3 clinically relevant cytokine combinations including interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6 (termed DC-0), DC-0 cells incubated with prostaglandin-2 (termed DC-0+prostaglandin-2), or DC treated with interferon-gamma, interferon-alpha, tumor necrosis factor-alpha, Poly I:C, and IL1-beta (termed DC-1). We found that these DC vary in their ability to cross-present TA to cytotoxic T lymphocytes (CTL), with the DC-1 cytokine combination being significantly more effective than the other 2. TA cross presentation and CTL priming were strongly correlated with level of expression of the antigen processing machinery components, TAP1 and TAP2, indicating that these components could be used as biomarkers to standardize DC preparations for optimal function. However, the up-regulation of TAP1/TAP2 was not sufficient to explain the enhanced cross-presentation ability of DC-1 cells, as the use of IFN-gamma alone to up-regulate TAP1/TAP2 did not generate DC as effective at cross-presentation as the full DC-1 maturation cytokine combination. These data indicate for the first time that the pathways of DC maturation modulate antigen processing machinery component expression to different extents and that differently matured DC vary in the ability to cross-present TA to human leukocyte antigen class I-restricted CTL.
Activation of peroxisome proliferator activated receptor-gamma results in an atheroprotective apolipoprotein profile in HepG2 cells

Background: Insulin resistance is linked to dyslipidemia, characterized by a decrease in high density lipo-proteins and an increase in low density lipoproteins. Thiazolidinediones (TZDs) are insulin-sensitizing agents used to improve glycemic control in patients with type 2 diabetes. Recently, the safety of certain TZD regimens has been questioned because of associated adverse effects on the plasma lipid profile. We examined the effect of a TZD, Ciglitazone, on apolipoprotein synthesis and secretion in human liver HepG2 cells. Methods and Results: The effect of Ciglitazone treatment on apolipoprotein synthesis was addressed at the level of transcription, translation and secretion. RT-PCR showed that Ciglitazone increased the transcription of apoE and apoAI but reduced the levels of apoCI and apoB mRNA. Western blot analysis showed an increase in apoAI and apoE secreted in the cell culture media, whereas the amounts of apoB100 and apoCI were reduced. To confirm that Ciglitazone regulates apolipoprotein translation, its effect on de novo protein synthesis was evaluated by metabolic labeling with [35S]-methionine/cysteine, and a similar pattern of regulation was observed. The change in apolipoprotein levels was not secondary to cholesterol biosynthesis or clearance, since Ciglita-zone did not regulate the transcription of HMGCoA reductase, or the LDL receptor. However, mRNA levels for both PPAR-γ and LXRα were induced, suggesting a role for either or both receptors in modulating the hepatic apolipoprotein profile. The involvement of these nuclear receptor transcription factors was confirmed since direct activation of these receptors by endogenous PPAR-γ ligand, 15d-prostaglandin J2, or LXRα ligand, 22(R)hydroxycholesterol, similarly upregulated apoAI and apoE, but down-regulated apoB100 protein synthesis. Conclusion: Our results suggest that Ciglita-zone treatment results in an atheroprotective lipoprotein profile in liver cells. Thus, while the adipose and muscle tissues may be primary targets in TZD-mediated glucose homeostasis, liver PPAR-γ contributes significantly to the regulation of plasma lipoprotein profile.
A study of software management: the state of practice in the United States and Japan

Abstract The purpose of the study reported here was to increase our understanding of the problems in managing software development and the situations in which these problems occurred — all from the perspective of software managers. The qualitative research method used during this study was based on grounded theory, a user-based approach from the social sciences that facilitates the discovery and definition of generalizations and themes about a complex subject, such as software development. Thirty-two managers from 14 companies in the United States and Japan were interviewed. The results of the analysis of the data collected suggest that many interacting technical and nontechnical factors come into play. Two major differences between the development contexts of the managers in the United States and Japan were related to development personnel and constraints placed on the projects. Similar hardware, software tools, and software processes were applied to their development efforts. Examination of the technological aspects of software development showed few distinguishing characteristics between the practices of the two countries. In contrast, examination of management and sociological issues provides insight into the differences, specifically those related to roles managers played with their people, subcontractors, and customers.
Remanent Magnetism of Intrusive Rocks from the Idaho Batholith

BECAUSE of the anomalous position of the Idaho batholith within the pattern of Cordilleran intrusive rocks (Fig. 1) it figures in several schemes for the tectonic evolution of west-central North America1–3. In undertaking a palaeomagnetic study of the Idaho batholith we reasoned that, if the batholith always had reacted to tectonic stresses as a coherent mass, directions of remanent magnetization within it could be used to reconstruct its tectonic history. Such an approach has proved useful in the southern Cascades of Washington4,5 and earlier work in the Sierra Nevada batholith of California6–8 was also encouraging. A similar study9, partially completed, of an early phase of the Southern California batholith also indicates internal consistency of remanent magnetization directions over a wide area.
Pattern Dystrophy of the Retinal Pigment Epithelium and Geographic Atrophy of the Macula

Purpose Little information is available on the long-term course of pattern dystrophies, although some older individuals have been observed with macular atrophy. We sought to evaluate the evolution of symptoms, fundus changes, and physiologic findings by reexamining a family with pattern dystrophy after 20 years. Methods Four patients of seven initially examined were reevaluated 20 years later; two additional affected family members over age 60 were studied for the first time. Patients' current ages ranged from 38 to 73 years. Comprehensive ophthalmic examinations were supplemented with fluorescein angiography, dark adaptometry, color vision, electroretinography, and electrooculography. Results During the 20-year interval, visual acuity remained stable and 20/40 or better in all patients. One 62-year-old patient developed paracentral scotomas. All fundi showed evolution of pigmentary changes and increasing atrophy of pigment epithelium and choriocapillaris in the macula. Electro-oculograms were originally subnormal in all patients and changed very little. Electroretinograms, initially normal in two patients, became borderline or mildly subnormal and slightly reduced in the two patients first examined after age 60. Conclusions Pattern dystrophy in this family was associated with minimal diminution of visual function during a 20-year interval. However, there was electroretinographic evidence of mild diffuse photoreceptor damage in the older patients, and geographic macular atrophy was prominent (suggesting a risk of vision loss in old age). Some cases of atrophie, age-related macular degeneration may represent an evolution of pattern dystrophy.
E-nabled for E-Learning? The Moderating Role of Personality in Determining the Optimal Degree of Learner Control in an E-Learning Environment

This paper investigates the moderating role of specific Big Five personality traits on the relationship between learner control and training performance in an e-learning environment. Specifically, we examined the role of openness to experience, conscientiousness, and extraversion. Participants completed a video-based e-learning program with either a high or low level of learner control. Results demonstrated that the personality traits of openness to experience and extraversion moderated the relationship between learner control and training performance. Specifically, training performance was higher for trainees higher in openness and extraversion when they were in an environment with high learner control versus low learner control. Conversely, for trainees lower in these traits, performance was higher with low learner control versus high learner control. Future research and practical applications are discussed.
Effects of Ascorbic Acid Applied by Two Hydrocooling Methods on Physical and Chemical Properties of Green Leaf Lettuce Stored at 5°C

The effect of ascorbic acid applied by 2 hydrocooling methods on chemical and physical properties of‘Waldmann's’dark green leaf lettuce (Lactuca sativa L.) during cold storage was evaluated. Lettuce was immersed (in 1% ascorbic acid or tap water) or sprayed (with 1% ascorbic acid or tap water) or left untreated (control). Treatment solutions for immersion or spraying were applied at 5°C for 2 min. Afterward, lettuce was packaged in moisture impermeable plastic bags and stored at 5°C for up to 21 d. Analytical assays included total ascorbate content, 2,2′-azinobis (3-ethylbenz-thiazoline-6-sulphonic acid) (ABTS˙+) Trolox equivalent antioxidant capacity, total phenolic content, relative water content and instrumental color. Lettuce was analyzed at 5 time intervals: before treatment application and at days 1, 7, 14, and 21 of storage time. Hydrocooling of leaf lettuce by immersion or spraying using 1% ascorbic acid solution increased total ascorbate content for up to 7 d, with an increase of more than 300% in total ascorbate content on day 1 compared with its initial value before treatments. However, the ABTS antioxidant capacity of leaf lettuce did not increase in ascorbic acid treated lettuce even though total ascorbate content increased. Ascorbic acid immersion was the only treatment that maintained the relative water content of leaf lettuce for 21 d. Further experimentation with the application of ascorbic acid during hydrocooling is needed to assess its usefulness as a processing treatment.
Calculation of quantum activation free energies for proton transfer reactions in polar solvents

Abstract The quantum activation free energy for proton transfer in polar solvents is calculated with path integral activated rate theory. The specific studied is a model intramolecular proton transfer reaction in water. The path integral method is used to differentiate between the contribution to the activation free energy from the intramolecular and from the solvent modes. The water solvent is found to contribute around 5.5 kcal/mol to the total quantum activation free energy. Since the tunneling of the proton is treated in an explicit quantum mechanical fashion, the total activation free energy can be calculated and hence the overall reaction probability estimated.
Sodium and potassium fluxes across the dialyzed giant axon of Myxicola.

Resting and stimulated fluxes of sodium and potassium across the giant axon of the marine annelid,Myxicola infundibulum, have been characterized using the technique of internal dialysis. In most respects the ion movements were found to be similar to those in squid axons. Sodium efflux and potassium influx were found to be active, cardiac glycoside-sensitive fluxes, with a variable coupling ratio. However, when [ATP]i was lowered to less than 20 μM by treatment with cyanide and continuous dialysis, or to less than 2 μm by dialysis with glucose following injection of hexokinase, Na efflux and K influx were unaltered. The maintained fluxes were not accounted for by an increased passive permeability of the axolemma, although 30–60% of the Na efflux appeared to be due to Na−Na exchange. An altered form of Na pump operation at low [ATP]i is a more likely explanation than an alternate energy source, or an ATP source proximate to the axolemma. The transient response of22Na efflux to a change in [22Na]i was found to be much slower than in squid, τ=360 sec. The efflux delay could only be accounted for by an extra-axonal diffusion barrier, which is probably the basement membrane surrounding the ventral nerve cord.
Influence of Fe2O3 Nanofiller Shape on the Conductivity and Thermal Properties of Solid Polymer Electrolytes: Nanorods versus Nanospheres

The influence of nanofiller shape on the ionic conductivity and thermal properties of solid polymer electrolytes is investigated. Electrolytes of polyethylene oxide (PEO) and LiClO4 filled with 1–20 wt % spherical Fe2O3 nanoparticles and 0.5–10 wt % Fe2O3 nanorods are measured at an ether oxygen to Li ratio of 10:1. Nanorods improve the ionic conductivity to a similar extent as spherical nanoparticles, except at concentrations 10–20 times lower. The maximum conductivity improvement occurs at a spherical metal oxide nanoparticle loading of 10 wt %; however, an equivalent nanorod loading decreases the conductivity below that of the unfilled electrolyte. This result suggests that the long-range morphology of the two nanocomposites differs widely, where high concentrations of nanorods will inhibit instead of enhance Li transport. The shape of the nanofiller also affects the crystallization rate and resulting crystal structure. Differential scanning calorimetry measurements show that samples containing nanorod...
Decisions to Be Made When Initiating Enteral Nutrition

Enteral nutrition support is preferred to parenteral or no nutritional support, but many patients who could benefit receive inadequate enteral feeding. Many decisions must be made before initiating enteral nutrition support; including if and when enteral nutrition should be started, which formula should be used, and how enteral nutrition support should be monitored. The gastroenterologist should be able to understand and evaluate these decisions in all patients potentially requiring nutritional support.
De novo CpG Island Methylation in Human Cancer Cells

A major obstacle toward understanding how patterns of abnormal mammalian cytosine DNA methylation are established is the difficulty in quantitating the de novo methylation activities of DNA methyltransferases (DNMT) thought to catalyze these reactions. Here, we describe a novel method, using native human CpG island substrates from genes that frequently become hypermethylated in cancer, which generates robust activity for measuring de novo CpG methylation. We then survey colon cancer cells with genetically engineered deficiencies in different DNMTs and find that the major activity against these substrates in extracts of these cells is DNMT1, with minor contribution from DNMT 3b and none from DNMT3a, the only known bona fide de novo methyltransferases. The activity of DNMT1 against unmethylated CpG rich DNA was further tested by introducing CpG island substrates and DNMT1 into Drosophila melanogaster cells. The exogenous DNMT1 methylates the integrated mammalian CpG islands but not the Drosophila DNA. Additionally, in human cancer cells lacking DNMT1 and DNMT3b and having nearly absent genomic methylation, gene-specific de novo methylation can be initiated by reintroduction of DNMT1. Our studies provide a new assay for de novo activity of DNMTs and data suggesting a potential role for DNMT1 in the initiation of promoter CpG island hypermethylation in human cancer cells.
Expectation value constraints for the N -representability problem

It has long been known that reduced density matrices (RDM) can be used to obtain the exact ground state energy of many-particle Hamiltonians by performing a constrained minimization over the set of all N-representable reduced density matrices. In this paper, we present a set of N-representability constraints for both bosons and fermions based on expectation values. These expectation value constraints are derived from a simple yet nontrivial recursive formula, and can easily be included in RDM-based variational schemes. The expectation value constraints are shown to provide additional N-representability information when compared to existing N-representability constraints.