cssi/SciSciGPT-SciSciNet huggingface dataset:
Individual and Partnership Factors Associated with Heterosexual Anal Intercourse Among Attendees of Public Sexually Transmitted Disease Clinics in Los Angeles County.

Heterosexual anal intercourse (HAI) is an understudied sexual behavior and poses unique challenges to the prevention of sexually transmitted diseases (STDs). This study aimed to explore individual and partnership characteristics associated with HAI. This study used data collected from 243 young people who attended STD clinics in Los Angeles County between April 2012 and May 2014. Participants reported on sexual behaviors with their last three sexual partners. Hierarchical, mixed effects, repeated-measures analyses were used to assess partner-level (demographic) and individual-level (demographic and behavioral) factors associated with recent (past 6 months) HAI. Thirty-two percent of participants (n = 243) reported HAI with at least one recent sex partner, and 49% reported ever having anal intercourse (AI). After adjusting for demographic characteristics, HAI was more than twice as likely to occur in relationships (n = 503) lasting more than a year compared to relationships lasting less than one month. HAI was also more likely to occur in relationships where intimate partner violence (IPV) was reported either as IPV initiated by the respondent (aOR = 2.18, 95% CI 1.08–4.41) or IPV initiated by the partner (aOR = 2.38, 95% CI 1.27–4.47). Among our participants, a substantial proportion reported HAI in the recent past 6 months and nearly half reported lifetime AI. Notably, our results indicate the importance of relationship contexts for people engaging in HAI and highlight the increased risk of STD/HIV transmission in the context of relationships with intimate partner violence victimization and perpetration.
A Critical Exploration of Assumptions Underlying STEM Career Development

Significant resources have been invested by multiple entities and institutions into exposing more students and adults to science, technology, education, and mathematics (STEM) education and careers...
The Role of Customer Perceived Ethicality in Explaining the Impact of Incivility Among Employees on Customer Unethical Behavior and Customer Citizenship Behavior

Incivility among employees in frontline encounters is prevalent, but little is known about its impact on customers’ ethics-related perceptions and behaviors. Drawing upon the stimulus–organism–response paradigm, this study examines how witnessing incivility among employees can serve as a social atmospheric cue to influence customers’ perceived ethicality of an organization and their subsequent behaviors. According to our results, in response to employee-to-employee incivility witnessed during frontline encounters, customers perceive the uncivil employees’ organization to have a lower level of ethicality. In turn, customers engage more in unethical behavior (i.e., opportunistic behavior) and less in customer citizenship behavior (i.e., customer tolerance of employee-induced errors). We further demonstrate that the negative effect of uncivil employee-to-employee interactions on customers’ perception of the ethicality of an organization is amplified when customers have an a priori perception that the organization is competent. The findings hold theoretical and practical implications for the management of employee-to-employee incivility and unethical customer behavior during frontline encounters.
Targeting RNA polymerase II Mediator subunits in cancer therapy.

Human cancers undergo an extremely diverse range of DNA mutations and rearrangements to generate oncogenes and to inactivate tumor suppressors in the process of their malignant transformation. As a consequence, decades of research have focused on the genes and the molecular pathways as well as the mechanisms that promote the growth of specific tumor cell types. This in turn has motivated the discovery and development of precision drugs that can target tumor-specific mechanisms. Although notable successes have been achieved, particularly with the targeting of oncogenes that encode protein kinases, many known drivers of human cancers have remained hitherto “undruggable” (1). These include unmutated transcription factors (TFs) such as Myc, Myb, E2F, and nuclear factor κB or chimeric transcriptional regulators generated by chromosomal translocations and novel gene fusions such as those encoding E2A-PBX1 and E2A-HLF. The DNA-binding domains of such oncogenic TFs, which confer specificity to their genomic actions, have proven to be intractable surfaces for selective and potent small molecules that can be developed into drugs. The Roeder laboratory, along with other groups, has been analyzing the molecular properties and functions of the E2A-PBX1 fusion protein given its import as an oncogenic driver in 5 to 7% of pediatric acute lymphoblastic leukemias (ALLs). The chimeric protein is generated by the t(1;19)(q23;p13) chromosomal translocation and contains the DNA-binding domain (homeobox) of PBX1 and the transcriptional activation domains of E2A (2). In PNAS, Li et al. (3) provide deeper molecular insight into the mechanism by which E2A-PBX1 promotes dysregulated expression of a set of target genes, including an E2F family … [↵][1]1Email: harinder{at}pitt.edu. [1]: #xref-corresp-1-1
Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.

The coexistence of cardiovascular disease and erectile dysfunction is widespread, possibly owing to underlying endothelial dysfunction in both diseases. Millions of patients with cardiovascular disease are prescribed phosphodiesterase-5 (PDE5) inhibitors for the management of erectile dysfunction. Although the role of PDE5 inhibitors in erectile dysfunction therapy is well established, their effects on the cardiovascular system are unclear. Preclinical studies investigating the effect of PDE5 inhibitors on ischemia–reperfusion injury, pressure overload-induced hypertrophy, and chemotoxicity suggested a possible clinical role for each of these medications; however, attempts to translate these findings to the bedside have resulted in mixed outcomes. In this review, we explore the biologic preclinical effects of PDE5 inhibitors in mediating cardioprotection. We then examine clinical trials investigating PDE5 inhibition in patients with heart failure, coronary artery disease, and ventricular arrhythmias and discuss why the studies likely have yet to show positive results and efficacy with PDE5 inhibition despite no safety concerns.
Cochlear function reflected in mammalian hair cell responses

Publisher Summary Sensory receptor cells in the mammalian cochlea have fully differentiated into two distinct populations: inner and outer hair cells (IHCs and OHCs). This chapter describes the response patterns recorded in inner and outer hair cells in the apical three turns of the guinea pig cochlea. Characteristic frequencies (CF) in these regions are approximately 270 Hz in turn four, 1,000 Hz in turn three, and 4,000 Hz in turn two. Although these two receptors exhibit differences in resting membrane potentials and in response phase at low stimulus frequencies, they both produce ac and dc receptor potentials in response to sound. When measured around CF, both cell types produce a depolarizing dc response at low and moderate levels. At very low frequencies, IHCs are velocity detectors. Above several hundred Hertz, however, both IHCs and OHCs respond to basilar membrane displacement. All IHCs and OHCs recorded using the lateral approach in turns four, three, and two produce depolarizing responses when stimulated at and around CF.
Weak Theories of Nonstandard Arithmetic and Analysis

Abstract. A general method of interpreting weak higher-type theories of nonstandard arithmetic in their standard counterparts is presented. In particular, this provides natural nonstandard conservative extensions of primitive recursive arithmetic, elementary recursive arithmetic, and polynomial-time computable arithmetic. A means of formalizing basic real analysis in such theories is sketched. Introduction. Nonstandard analysis, as developed by Abraham Robinson, provides an elegant paradigm for the application of metamathematical ideas in mathematics. The idea is simple: use model-theoretic methods to build rich extensions of a mathematical structure, like second-order arithmetic or a universe of sets; reason about what is true in these enriched structures; and then transfer the results back to the ordinary mathematical universe. Robinson showed that this allows one, for example, to provide a coherent and consistent development of calculus based on the use of infinitesimals. From a foundational point of view, it is natural to try to axiomatize such nonstandard structures. By formalizing the model-theoretic arguments, one can, in general, embed standard mathematical theories is conservative, nonstandard extensions. This was done e.g. by Kreisel, for second-order arithmetic [31]; Friedman, for first-order Peano arithmetic (unpublished); Nelson, for set theory [33]; and Moerdijk and Palmgren for intuitionistic first-order Heyting arithmetic [32] (see also [7]). In recent years there has also been an interest in formalizing parts of mathematics in weak theories, at the level of primitive recursive arithmetic ( PRA ), or below. The underlying motivations vary. One may be drawn by the general philosophical goal of minimizing ontological commitments, or, less ethereally, by the sport of seeing how little one can get away with. Alternatively, one may be interested in extracting additional mathematical information from standard mathematical developments (e.g. [26, 27, 29, 30]), or narrowing the theoretical gap between abstract mathematics and concrete computation. In any event, a number of appropriate formal frameworks have been developed, including subsystems of first- and second-order arithmetic (e.g. [10, 37, 17, 19, 18, 49]), theories of finite types (e.g. [28, 30]), and versions of Feferman's theories of explicit mathematics (e.g. [41]), to name just a few.
Functional Organization of the Auditory Cortex

The properties of an acoustic signal produced by an animal can be studied by examining the output of a microphone displayed on the screen of an oscilloscope. Such an examination, however, gives us only limited information about the signal properties, so that the signal is usually analyzed with a spectrum analyzer. The spectrum analyzer has many filters tuned to different frequencies and it expresses the output of each as a function of time. Therefore, the properties of the acoustic signals are expressed by a pattern that appears in three coordinates: frequency, amplitude and time. To recognize individual acoustic patterns with an instrument, information-bearing elements (elements characterizing the signal) are first extracted and then their combinations are examined. The question next arises: how are acoustic signals analyzed and processed in the auditory system?
Activation of a heterologous promoter by human immunodeficiency virus type 1 Tat requires Sp1 and is distinct from the mode of activation by acidic transcriptional activators.

Abstract We have previously shown that the Tat protein of the human immunodeficiency virus type 1 (HIV-1) is a modular transcriptional activator that can be targeted upstream of either a synthetic promoter or the intact HIV promoter to activate transcription. This activation was shown to be largely dependent on the presence of consensus binding sites for the cellular transcription factor Sp1. Since the use of heterologous promoters may provide further insight into Tat-mediated transactivation, we have analyzed the transactivation of the thymidine kinase promoter of herpes simplex virus by Tat and by the acidic transcriptional transactivator VP16. The effects of mutations of defined upstream promoter elements show that Tat transactivation is dependent on Sp1 binding sites in a site-specific manner. In contrast, transactivation by the acidic transactivator VP16 is completely independent of any of the defined promoter elements upstream of the TATA box. These results suggest that Tat and the classically defined modular acidic transcriptional activators have different modes of transactivation. In addition, the substitution of the HIV-1 TATA box for the thymidine kinase TATA box substantially increases Tat transactivation, indicating that Tat transactivation may also ultimately involve TATA box-associated cellular transcription factors.
Surviving Medical Device Preemption under 21 U.S.C. 360k: Clarifying Pleading Standards for Parallel Claims in the Wake of Twombly and Iqbal

Surviving Medical Device Preemption under 21 U.S.C. 360k: Clarifying Pleading Standards for Parallel Claims in the Wake of Twombly and Iqbal Ashley Abraham Williams*
Topotecan Increases Topoisomerase IIα Levels and Sensitivity to Treatment with Etoposide in Schedule-dependent Process

To elucidate the effect of topoisomerase (Topo) I inhibitors in the modulation of Topo II levels and sensitivity to Topo II-directed drugs, athymic mice bearing SW480 human colon cancer xenografts were treated with simultaneous, subsequent, or distant doses of topotecan and etoposide. This in vivo study demonstrates that simultaneous administration of topotecan and etoposide results in an antagonistic response. In contrast, inhibition of Topo I by topotecan results in a compensatory increase in Topo IIα levels associated with increasing sensitivity of tumors to subsequent treatment with the Topo II inhibitor etoposide. Furthermore, we show that Topo IIα levels decline 5 days after the last dose of topotecan, resulting in restoration of the original response of the xenografts to etoposide. Thus, this study emphasizes the critical role of schedule dependency to optimize the effectiveness of combination chemotherapy with Topo I and Topo II inhibitors.
Isopropanol and Isopropanol Deaths—Ten Years' Experience

A population of persons who were found, at death, to have significant levels of isopropyl alcohol (isopropanol) in their blood is described. The role of isopropanol in causing death is reviewed in 57 fatal cases. The contribution of acetone, the major metabolite of isopropanol, to death is assessed. Results indicate that mixed alcohol poisoning with ethanol and isopropanol suggests decreased production of acetone. Modalities for antemortem and postmortem detection of isopropanol are presented.
Visually-Weighted Regression

Uncertainty in regression can be efficiently and effectively communicated using the visual properties of statistical objects in a regression display. Altering the "visual weight" of lines and shapes to depict the quality of information represented clearly communicates statistical confidence, even when readers are unfamiliar with the formal and abstract definitions of statistical uncertainty. Here we present examples where the color saturation, contrast of regression lines, and confidence intervals are parametrized by local measures of an estimate's variance. The results are simple, visually intuitive, and graphically compact displays of statistical uncertainty. This approach is generalizable to almost all forms of regression.
Polymerized ionic liquid block copolymers for electrochemical energy

Polymerized ionic liquid (PIL) block copolymers are an emerging class of polymers that synergistically combine the benefits of both ionic liquids (ILs) and block copolymers into one, where the former possesses a unique set of physiochemical properties and the latter self assembles into a range of nanostructures. The potential to synthesize a vast array of new block copolymers is almost limitless with numerous IL cations and anions available. In this paper, we highlight the very recent work on PIL block copolymers, specifically, synthesis and unique solid-state properties for electrochemical energy.
Managing Distributed Applications Using Gush

Deploying and controlling experiments running on a distributed set of resources is a challenging task. Software developers often spend a significant amount of time dealing with the complexities associated with resource configuration and management in these environments. Experiment control systems are designed to automate the process, and to ultimately help developers cope with the common problems that arise during the design, implementation, and evaluation of distributed systems. However, many of the existing control systems were designed with specific computing environments in mind, and thus do not provide support for heterogeneous resources in different testbeds. In this paper, we explore the functionality of Gush, an experiment control system, and discuss how it supports execution on three of the four GENI control frameworks.
Is there an indigenous knowledge in the urban north? Re/inventing local knowledge and communities in the struggles over garbage and incinerators in Campania, Italy

Abstract This paper deals with the narratives about environmental struggles over garbage facilities in Campania, Italy, a region which, in the last decades, has become the worldwide icon of the failure in the management of its own metabolism. In particular I analyze the narratives about the activists involved in the struggles and their creative interaction with scientific knowledge. My thesis is that ecological conflicts--at least in this specific case--have been producers of communities and knowledges. Instead of reinforcing the narrative about “natural” communities living in a space of radically otherness and oppressed by global villains, I would like to explore the interstitial South, mixed with the North and its science and contradictions. Using a collection of interviews and some grassroots documentaries about the crisis and the mobilization, I analyze the rising of a collective knowledge and the making of communities through the very experience of resistance to the governmentality plan of waste disposal. Keywords Environnemental justice. Garbage. Knowledge. Napoles (Italy) Resumo Este artigo lida com as narrativas sobre as lutas ambientais contra as facilidades de lixo em Campania (Italia), uma regiao que, nas ultimas decadas, tornou-se o icone mundial da falha na gestao do seu proprio metabolismo. Em particular, serao analisadas as narrativas dos ativistas envolvidos nas lutas e sua interacao criativa com o conhecimento cientifico. Minha tese e que os conflitos ecologicos - pelo menos neste caso especifico - foram o que produziu as comunidades e seus saberes. Em vez de reforcar a narrativa sobre as comunidades "naturais" que vivem em um espaco de alteridade radical e oprimidas pelos viloes globais, busco explorar a situacao do Sul intersticial, misturado com o Norte e sua ciencia e contradicoes. Usando uma colecao de entrevistas e alguns documentarios produzidos por movimentos sociais sobre a crise e a mobilizacao, analisarei o surgimento de um conhecimento coletivo e a fabricacao de comunidades atraves da propria experiencia de resistencia ao plano governamental de eliminacao de residuos. Palavras-chave Justica ambiental. Lixo. Conhecimento. Napoles (Italia).
Rheology of foams and highly concentrated emulsions

Abstract Expressions are derived for certain rheological properties, such as the stress vs strain relationship, yield stress, and shear modulus, of monodisperse foams and highly concentrated emulsions for the model of infinitely long cylindrical drops (or bubbles). The variables considered are the volume fraction of the dispersed phase, the drop radius, the interfacial tension, the thickness of the films separating adjacent drops, and the films' associated contact angle. Both the yield stress and the shear modulus are proportional to the interfacial tension and inversely proportional to the drop radius. The yield stress increases sharply with increasing volume fraction, while the shear modulus varies as its square root. The effect of a finite contact angle, θ, is to decrease the shear modulus and, in most cases, to increase the yield stress. Finally, the effect of a finite film thickness is to always increase both the yield stress and the shear modulus. The implications of these results to real emulsions and foams are discussed.
Tobacco Promotion to Military Personnel: “The Plums Are Here to Be Plucked”

Smoking rates among military personnel are high, damaging health, decreasing short- and long-term troop readiness, and costing the Department of Defense (DOD). The military is an important market for the tobacco industry, which long targeted the military with cigarette promotions. Internal tobacco industry documents were examined to explore tobacco sponsorship of events targeted to military personnel. Evidence was found of more than 1,400 events held between 1980 and 1997. In 1986, the DOD issued a directive forbidding such special promotions; however, with the frequently eager cooperation of military personnel, they continued for more than a decade, apparently ceasing only because of the restrictions of the Master Settlement Agreement. The U.S. military collaborated with the tobacco industry for decades, creating a military culture of smoking. Reversing that process will require strong policy establishing tobacco use as unmilitary.
Glycaemic thresholds for hypoglycaemic symptoms, impairment of cognitive function, and release of counterregulatory hormones in subjects with functional hypoglycaemia

Nine patients with food-relieved hypoglycaemic symptoms, in whom insulinoma and other organic diseases presenting with hypoglycaemia had been ruled out, and nine matched controls, participated in the study. Subjects were studied during a 5-h controlled (Biostator) insulin-induced (1-2 mU kg-1 min-1) hypoglycaemic clamp. After 1 h of euglycaemia, we aimed to lower the glucose level in arterialized venous blood in a stepwise manner at 30-min intervals to 3.5, 3.0, and 2.0 mmol l-1, and to withhold these levels for a further 30 min. At euglycaemia and at the end of the latter steps, the visual reaction time and cognitive function (digit span, letter cancellation and trail making) were tested, together with recording symptoms and signs of hypoglycaemia. Counter-regulatory hormones were measured at 20-min intervals. In the patients, clinical signs and symptoms of hypoglycaemia developed at median blood glucose levels of 2.6-2.8 and 2.8-3.1 mmol l-1, respectively. By contrast, the blood glucose levels were 0.4-0.8 mmol l-1 lower in control subjects (P less than 0.05). Similarly, the median threshold for deterioration of visual reaction time was 2.8 mmol l-1 in patients and 2.1 mmol l-1 in controls (P less than 0.01). A similar trend was observed for the results of the neuropsychological tests. Visual reaction time deteriorated in all subjects, whereas the cognitive function of some of the subjects in each group remained unchanged during hypoglycaemia. The glycaemic thresholds for release of cortisol, glucagon and growth hormone were significantly higher in patients (P less than 0.05), whereas the thresholds for catecholamine release showed no significant difference from controls. Despite the comparable glucose infusion rates required to sustain each of the hypoglycaemic levels in the two groups, the control subjects achieved lower glucose levels, suggesting that there is resistance to insulin or glucose in functional hypoglycaemia. In conclusion, the present study suggests that the existence of a higher threshold for symptoms and signs, as well as for deterioration of brain function, may explain every-day hypoglycaemic symptoms, despite normal glucose levels, in subjects with functional hypoglycaemia. However, the hypothesis should be tested further using a blinded approach, including euglycaemic control studies.
Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K‐12

Mining the emerging abundance of microbial genome sequences for hypotheses is an exciting prospect of "functional genomics". At the forefront of this effort, we compared the predictions of the complete Escherichia coli genomic sequence with the observed gene products by assessing 381 proteins for their mature N-termini, in vivo abundances, isoelectric points, molecular masses, and cellular locations. Two-dimensional gel electrophoresis (2-DE) and Edman sequencing were combined to sequence Coomassie-stained 2-DE spots representing the abundant proteins of wild-type E. coli K-12 strains. Greater than 90% of the abundant proteins in the E. coli proteome lie in a small isoelectric point and molecular mass window of 4-7 and 10-100 kDa, respectively. We identified several highly abundant proteins, YjbJ, YjbP, YggX, HdeA, and AhpC, which would not have been predicted from the genomic sequence alone. Of the 223 uniquely identified loci, 60% of the encoded proteins are proteolytically processed. As previously reported, the initiator methionine was efficiently cleaved when the penultimate amino acid was serine or alanine. In contrast, when the penultimate amino acid was threonine, glycine, or proline, cleavage was variable, and valine did not signal cleavage. Although signal peptide cleavage sites tended to follow predicted rules, the length of the putative signal sequence was occassionally greater than the consensus. For proteins predicted to be in the cytoplasm or inner membrane, the N-terminal amino acids were highly constrained compared to proteins localized to the periplasm or outer membrane. Although cytoplasmic proteins follow the N-end rule for protein stability, proteins in the periplasm or outer membrane do not follow this rule; several have N-terminal amino acids predicted to destabilize the proteins. Surprisingly, 18% of the identified 2-DE spots represent isoforms in which protein products of the same gene have different observed pI and M(r), suggesting they are post-translationally processed. Although most of the predicted and observed values for isoelectric point and molecular mass show reasonable concordance, for several proteins the observed values significantly deviate from the expected values. Such discrepancies may represent either highly processed proteins or misinterpretations of the genomic sequence. Our data suggest that AhpC, CspC, and HdeA exist as covalent homomultimers, and that IcdA exists as at least three isoforms even under conditions in which covalent modification is not predicted. We enriched for proteins based on subcellular location and found several proteins in unexpected subcellular locations.
Dual-tapered piston (DTP) module cooling for IBM Enterprise System/9000 system

The water-cooled thermal conduction modules (TCMs) in the IBM Enterprise System/9000™ (ES/9000™) systems require a fourfold thermal improvement over TCMs in the 3090™ system. An examination of the thermal/mechanical tolerance relationships among the chips, substrate, and cooling hardware showed that a cylindrical piston would not meet this requirement. The piston was redesigned with a cylindrical center section and a taper on each end. This shape minimizes the gap between the piston and “hat” while retaining intimate contact between the piston face and chip surface during all assembly conditions. Numerical and analytical models demonstrate that this new piston shape, coupled with improved conductivity of the cooling hardware materials, exceeds ES/9000 system needs. These models were verified by tests conducted on single-site and full-scale modules in the laboratory and by tests on actual ES/9000 systems.
Studies of silica-supported metal chloride catalysts for the vapor-phase hydrochlorination of acetylene

Abstract The first phase of a systematic examination of heterogeneously catalyzed vaporphase reactions of acetylene with acids of the HQ type has involved infrared and reaction studies of silica-supported metal chloride catalysts. Examination of the infrared spectra of acetylene and propyne adsorbed on these catalysts has yielded information on the mode of adsorption. On all surfaces studied a species of the type is observed, where R is H and CH 3 and M(II) is Ca(II), Mn(II), Cu(II), and Zn(II). Shifts of propyne CC as well as propyne and acetylene CH vibrations to lower frequencies on adsorption in this configuration are related to the electron affinities of the metal ions. Studies of the catalytic activities of silica-supported Hg(II), Bi(III), Ni(II), Zn(II), Cd(II), Cu(II), Mn(II), and Ca(II) chlorides for the vapor-phase hydrochlorination of acetylene have supplemented literature information and provided some basis for interpretation of the infrared results. After a rapid decline from a higher initial activity, a nearly steady activity is attained yielding the order Hg(II) > Bi(III) > Ni(II) > Zn(II) > Cd(II) > Cu(II) > Mn(II) > Ca(II). It is possible to rationalize spectroscopic data obtained so far with the observed order of catalyst activity in terms of the adsorbed species .
Effective Treatment of Established GL261 Murine Gliomas through Picornavirus Vaccination-Enhanced Tumor Antigen-Specific CD8+ T Cell Responses.

Glioblastoma (GBM) is among the most invasive and lethal of cancers, frequently infiltrating surrounding healthy tissue and giving rise to rapid recurrence. It is therefore critical to establish experimental model systems and develop therapeutic approaches that enhance anti-tumor immunity. In the current study, we have employed a newly developed murine glioma model to assess the efficacy of a novel picornavirus vaccination approach for the treatment of established tumors. The GL261-Quad system is a variation of the GL261 syngeneic glioma that has been engineered to expresses model T cell epitopes including OVA257–264. MRI revealed that both GL261 and GL261-Quad tumors display characteristic features of human gliomas such as heterogeneous gadolinium leakage and larger T2 weighted volumes. Analysis of brain-infiltrating immune cells demonstrated that GL261-Quad gliomas generate detectable CD8+ T cell responses toward the tumor-specific Kb:OVA257–264 antigen. Enhancing this response via a single intracranial or peripheral vaccination with picornavirus expressing the OVA257–264 antigen increased anti-tumor CD8+ T cells infiltrating the brain, attenuated progression of established tumors, and extended survival of treated mice. Importantly, the efficacy of the picornavirus vaccination is dependent on functional cytotoxic activity of CD8+ T cells, as the beneficial response was completely abrogated in mice lacking perforin expression. Therefore, we have developed a novel system for evaluating mechanisms of anti-tumor immunity in vivo, incorporating the GL261-Quad model, 3D volumetric MRI, and picornavirus vaccination to enhance tumor-specific cytotoxic CD8+ T cell responses and track their effectiveness at eradicating established gliomas in vivo.
Evaluation of expert criteria for preoperative magnetic resonance imaging of newly diagnosed breast cancer

Abstract Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women ( n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57–5.91 ( p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence.
The Proposed Continuous Polar Exploration

YOUR excellent summary of the proposed continuous Polar exploration (November 2, p. 18) conveys a wrong impression in its closing sentence. The system may in the future assume large proportions; but the beginning, to be made next year, will be very small. It will consist merely in the establishment of the principal station at the south-east angle of Ellesmere Land, and 80 days' exploration along the west coast of that land. At most, an advanced depot, erected some 100 miles farther west, may be so fitted out as to serve at once as a secondary station. It is not easy to see why this work should be postponed till Peary and Nansen have returned. Their fields are far from ours, and their results can shed no light on the area west of Ellesmere Land. As well might you say that the exploration of the Mediterranean should not be begun until that of the Baltic was completed.
Biliary Secretion of α-Tocopherol and the Role of the mdr2 P-Glycoprotein in Rats and Mice

Abstract The mechanism by which α-tocopherol (α-T) is secreted into the bile is not known; however, we have previously demonstrated that treatment with piperonyl butoxide (PIP, 1 g/kg) results in increased biliary output of both α-T and phosphatidylcholine within 3 h of ip injection in rats and that the biliary output of both substances was prevented by chemicals that disrupt microtubules ( Toxicol. Appl. Pharmacol. 139, 411–417 (1996)). The P-glycoprotein (Pgp) encoded by the mdr2 gene has been shown to transport phosphatidylcholine into the bile; therefore, in the current study, we utilized the Pgp inhibitor verapamil to investigate the possible involvement of Pgps in the biliary secretion of α-T. When rats were iv injected with verapamil (4 mg/kg) 10 min prior to PIP treatment, verapamil prevented the PIP-induced increases in biliary α-T and phosphatidylcholine output and resulted in biliary α-T outputs that were significantly less than controls. Also, we determined that the biliary α-T levels in mdr2 knockout mice were 25% of those in wildtype mice; furthermore, mdr2 liver, lung, and kidney levels of α-T and glutathione differed from those of wildtype. To investigate the fate of biliary α-T, we injected 14 C-labeled α-T into the bile duct cannulae of rats and determined that approximately 60% of the radioactivity was reabsorbed within 1 h. Our results indicate that α-T undergoes enterohepatic circulation and that the biliary secretion of α-T, basally and following chemical treatment, is dependent on the presence of a functioning mdr2 Pgp in rats and mice.
Watershed liming and pit and mound topography effects on seed banks in the Adirondacks, New York, USA

Abstract Seed bank species composition, density, and frequency were evaluated as seedling emergence relative to differences in substrate chemistry associated with watershed liming and pit and mound topography (microsites) on the Woods Lake watershed, western Adirondack Mountains, NY. Liming was expected to affect calcicole and calcifuge species richness and density, while species that form persistent versus transient seed banks were expected to vary with microsite. Two of five subcatchments were limed in October, 1989 with 6.89 t ha−1 of pelletized CaCO3. Forest floor samples were collected in May 1991 and 1992 from pit, mound, and undisturbed microsites in limed and reference (untreated) subcatchments. Water soluble calcium concentrations in forest floor samples collected in May 1992 from limed subcatchments were almost ten times greater than forest floor samples from reference subcatchments, but there were no differences in soluble calcium concentration among microsites within a subcatchment. Species richness and abundance varied among microsites, but the magnitude depended on year and lime treatment. Relative frequencies of Betula alleghaniensis (yellow birch) and Oxalis acetosella (wood sorrel) exceeded 80% in both years, with a slightly greater frequency from limed than reference subcatchments. Differences in relative frequency for several species between subcatchments were not consistent between years. The relative frequency of all species by microsite was generally greater from limed than reference subcatchments. Total density and the density of individual species by microsite varied between treatments within subcatchments and between years, although some patterns exist. Seed bank patterns vary appreciably between years and among microsites. Differences in seedling emergence from pit versus mound microsites varied between years and depended on whether the microsites were in limed or reference subcatchments. These data suggest that there are no detrimental short-term effects of watershed liming on seed banks of upland deciduous forests. Microsites may affect plant community composition most through germination and survical of propagules.
Urban air pollution, health, and equity

Air pollution and equity Over the past decade, an ever increasing number of epidemiological studies have linked urban air pollution, particularly particulate matter, to increased risk for morbidity and mortality.1,2 These new findings have led to revised air pollution standards for the United States and they will probably have similar consequences in other countries around the world. This new evidence on adverse health effects of air pollution has also motivated research to identify those groups within the population who may be at increased risk from exposure, for example: infants, persons with chronic heart and lung disease, and the elderly population.3 This issue of the journal includes three papers that address socioeconomic status and vulnerability to air pollution. This is not a new topic for scientific investigation or for public health concern. The environmental justice movement began more than two decades ago in the United States, originally related to the locating of toxic waste landfills in minority communities.4 More recently, urban air pollution has surfaced as a significant international environmental justice concern because of the large concentration of minority and low income residents living in urban environments with unhealthful air quality.5 These persons often have unhealthy housing and significant exposures to indoor air pollution as well. Adding to the public health concern regarding the disproportionate exposure of minority and low income populations to high levels of urban air pollution is the recognition that these groups often …
Residents' Attitudes to Tourism in Central British Columbia, Canada

Abstract Traditionally dependent on extractive resource industries, communities located in peripheral regions of British Columbia are searching for economic diversification opportunities. Valemount, a small mountain community in central British Columbia, has recently attracted two large-scale resort development proposals. Based on a survey of local residents in Valemount, this paper examines residents' attitudes to tourism-induced socio-economic and recreational opportunities, and the future of tourism development. Linkages are explored between community attachment, community satisfaction, community concerns and tourism-related attitudes. Results indicate that the majority of residents are positive about tourism development. While resident satisfaction with current opportunities is low, and some residents are concerned about the negative impacts of tourism development, residents perceive that the potential benefits of tourism development outweigh its negative impacts. The positive reactions to tourism dev...
Is hormonal treatment efficacious in the management of ovarian cysts in women with histories of endometriosis

In a controlled, randomized study, we evaluated the effectiveness of various hormonal regimens in treating 70 women (mean age 34.7 ± 5.7 years) who had unilateral or bilateral ovarian cysts presumed to be physiological (functional) and a history of endometriosis . The patients were assigned randomly to one of the following groups: group I (control), no treatment; group n, oral contraceptives (35 ug ethinyl oestradiol and 1 mg norethindrone); group III, oral contraceptives (50 ug ethinyl oestradiol and 1 mg norethindrone); group IV, danazol 800 mg/day. Serum CA-125 concentrations were measured in 32 women. All medications were taken continuously for 6 weeks. Subjects were re-evaluated by pelvic examination and transvaginal ultrasound. Those with persistent cysts were offered diagnostic and possible operative laparoscopy. As 11 patients did not complete the study and five did not follow-up, the final study population comprised 54 women. At 6 weeks follow-up, complete resolution of cysts was found in: group I, 12 out of 18 (66.7%); group n, five out of nine (55.6%); group III, eight out of 14 (57.1%); and group IV, seven out of 13 (53.9%). Two of the 22 women with persistent cysts opted for 6 weeks further medical therapy and achieved complete resolution; 19 underwent laparoscopy, and one was lost to follow-up. All laparoscopic findings revealed benign masses. We found no statistically significant effect when hormonal treatment was compared with expectant management There was no correlation between serum CA-125 concentrations and the persistence or resolution of cysts.
Protein Arginine Methyltransferase 1-directed Methylation of Kaposi Sarcoma-associated Herpesvirus Latency-associated Nuclear Antigen

The Kaposi sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a multifunctional protein with roles in gene regulation and maintenance of viral latency. Post-translational modification of LANA is important for functional diversification. Here, we report that LANA is subject to arginine methylation by protein arginine methyltransferase 1 in vitro and in vivo. The major arginine methylation site in LANA was mapped to arginine 20. This site was mutated to either phenylalanine (bulky hydrophobic, constitutive methylated mimetic) or lysine (positively charged, non-arginine methylatable) residues. The significance of the methylation in LANA function was examined in both the isolated form and in the context of the viral genome through the generation of recombinant KSHV. In addition, authentic LANA binding sites on the KSHV episome in naturally infected cells were identified using a whole genome KSHV tiling array. Although mutation of the methylation site resulted in no significant difference in KSHV LANA subcellular localization, we found that the methylation mimetic mutation resulted in augmented histone binding in vitro and increased LANA occupancy at identified LANA target promoters in vivo. Moreover, a cell line carrying the methylation mimetic mutant KSHV showed reduced viral gene expression relative to controls both in latency and in the course of reactivation. These results suggest that residue 20 is important for modulation of a subset of LANA functions and properties of this residue, including the hydrophobic character induced by arginine methylation, may contribute to the observed effects.
A descriptive theory of information

Originally the mathematical theory of information was developed in the context of “selective information;” that is, information was assumed to have been transmitted when the uncertainty (as to which of a number of possible messages was sent) was reduced by the receipt of a message. This theory, eminently suitable as the basis of telecommunication technology, runs into conceptual difficulties when applied to the content of the message received. A descriptive theory of information deals with the problem of specifying quantitatively the amount of information about something.
A nurse practitioner model of practice in the neonatal intensive care unit.

Purpose: The purpose of this study was to describe the practice of the nurse practitioner (NP) in the neonatal intensive care unit (NICU) in an attempt to define an advanced practice nursing model that is unique to NP practice in the NICU. Design: This qualitative research used an ethnographic case study design to answer the research question: 'What is the practice model of nurse practitioners working in the NICU?' Methods: Seven nurse practitioners working in five level II/III NICUs in Massachusetts and Rhode Island were interviewed and observed in practice. Audiotaped interviews using open-ended questions and field notes from participant observations were analyzed for patterns of behavior. Results: These nurse practitioners practiced within a model of advanced practice nursing that emphasized health, holism, and caring within the highly technological and medical NICU environment. Clinical Implications: A model of NP practice in the NICU is emerging and needs further development and testing. Nurse educators and administrators must find ways to support the nursing model in the advanced practice nursing role in the NICU. Nurse practitioners need to be more active in promoting a clearer understanding of their practice and contributions to the NICU care delivery team.
Cyclophosphamide and abrogation of tumor-induced suppressor T cell activity.

Previously we have demonstrated that the in vitro generation of P815-specific anti-tumor cytotoxic T lymphocytes (CTL) was suppressed by splenic suppressor T cells from late tumor-bearing hosts (TBH). Suppression is not caused by in vitro growth of P815 from splenic metastases, since suppression was also seen with spleen cells from late TBH mice bearing a hypoxanthine/aminopterin/thymidine-sensitive subline (PHS-5) of P815 in the presence of HAT. Cyclophosphamide has been shown to inhibit theinduction of suppressor cells selectively in a number of immune responses, but evidence that it can inhibit active tumor-induced suppressor T cells is limited. We have found that suppressor T cells already induced by P815 in syngeneic late TBH are sensitive to low doses of cyclophosphamide (50 mg/kg) given 1 day before spleen harvest, but the in vitro CTL response of late TBH spleen cells could not be restored by pretreating the mice with cyclophosphamide, even when exogenous interleukin-2 was added to the cultures. Although 50 mg/kg cyclophosphamide did not inhibit the CTL response of spleen cells from mice immunized with P815 +Corynebacterium parvum, the same dose of cyclophosphamide eliminated the CTL response of spleen cells from early TBH. Interleukin-2 (IL-2) did not overcome this effect of cyclophosphamide, suggesting a direct effect on CTL. “Ultra-low”-dose cyclophosphamide (10 mg/kg) did not adversely effect early TBH CTL but was still able to eliminate suppressor T cell activity from late TBH. Nevertheless, late TBH CTL remained unresponsive after pretreatment of mice with ultra-low-dose cyclophosphamide, even when exogenous IL-2 was added in vitro. CTL precursor frequency analyses demonstrated that cyclophosphamide pretreatment had little or no effect on the numbers of CTL precursors from early TBH. Late TBH CTL precursor cells were not detectable in these studies, with or without suppressor T cell inhibition by cyclophosphamide pretreatment. Thus, it appears that most CTL precursor cells may be lost or irretrievably inactivated in the spleens of late TBH mice.
Parallel-burn options for dual-fuel single-stage orbital transports

A parallel-burn version of a single-stage vehicle for transport from the earth to low-earth orbit using two fuels and rocket propulsion is considered. New engine results were incorporated in vehicle performance and design studies. The results indicate that a hydrogen-cooled gas generator cycle engine provides attractive vehicle performance and that there is little incentive for increasing the chamber pressure beyond 27 MPa.
Improved synthesis of 2,5-anhydro-d-allononitrile

Abstract Two types of mixed ester of β- d -ribofuranose were synthesized. The first had the same groups attached to O-1, 2, and 3, and the second had the same groups attached to O-2, 3, and 5. The three esters obtained in the highest yields, starting from d -ribose, were then converted into the halides and nitriles. Of the esters studied, the best suited for conversion into the nitrile was 1- O -acetyl-2,3,5-tri- O-p -toluyl-β- d -ribofuranose, which afforded 2,5-anhydro-3,4,6-tri- O-p -toluyl- d -allononitrile in 60% yield.