cssi/SciSciGPT-SciSciNet huggingface dataset:
Alliterating Word-Pairs in Old High German: Approaching a Rhetorical Evaluation

A survey of the Old High German texts provides a number of significant finds relating to the early use, frequency, and distribution of alliterating word-pairs. In the presentation and analysis of selected data, parameters for addressing a more complete rhetorical evaluation of the phraseologisms as they appear in the texts are outlined, with consideration of issues such as transmission, source influence, genre, and dialect. Contours of the early history of the alliterating word-pair in German are presented, while perspectives for further research are sketched. An appendix lists the entire corpus of Old High German alliterating word-pairs.
Novel Anti-TM4SF1 Antibody-Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature.

Antibody–drug conjugates (ADC) represent a promising therapeutic modality for managing cancer. Here, we report a novel humanized ADC that targets the tetraspanin-like protein TM4SF1. TM4SF1 is highly expressed on the plasma membranes of many human cancer cells and also on the endothelial cells lining tumor blood vessels. TM4SF1 is internalized upon interaction with antibodies. We hypothesized that an ADC against TM4SF1 would inhibit cancer growth directly by killing cancer cells and indirectly by attacking the tumor vasculature. We generated a humanized anti-human TM4SF1 monoclonal antibody, v1.10, and armed it with an auristatin cytotoxic agent LP2 (chemical name mc-3377). v1.10-LP2 selectively killed cultured human tumor cell lines and human endothelial cells that express TM4SF1. Acting as a single agent, v1.10-LP2 induced complete regression of several TM4SF1-expressing tumor xenografts in nude mice, including non–small cell lung cancer and pancreas, prostate, and colon cancers. As v1.10 did not react with mouse TM4SF1, it could not target the mouse tumor vasculature. Therefore, we generated a surrogate anti-mouse TM4SF1 antibody, 2A7A, and conjugated it to LP2. At 3 mpk, 2A7A-LP2 regressed several tumor xenografts without noticeable toxicity. Combination therapy with v1.10-LP2 and 2A7A-LP2 together was more effective than either ADC alone. These data provide proof-of-concept that TM4SF1-targeting ADCs have potential as anticancer agents with dual action against tumor cells and the tumor vasculature. Such agents could offer exceptional therapeutic value and warrant further investigation. Mol Cancer Ther; 14(8); 1868–76. ©2015 AACR . This article is featured in Highlights of This Issue, [p. 1765][1] [1]: /lookup/volpage/14/1765?iss=8
Joint detection/estimation for modal order selection in Gaussian and nonGaussian noise

The authors present a general approach to determining the number of sinusoids present in measurements corrupted by additive white Gaussian and nonGaussian noise. The approach involves the simultaneous application of maximum a posteriori detection and nonlinear estimation using either the extended Kalman filter when the noise is Gaussian, or the extended high order filter when the noise is nonGaussian. The problem is formulated as a multiple hypothesis testing problem with assumed known a priori probabilities for each hypothesis. The advantage of the approach lies in the potential to accommodate time-varying as well as time-invariant parameters in the measurement model. Experimental evaluation of the approach demonstrates excellent performance in selecting the correct model order and estimating the system parameters even for signal-to-noise ratios as low as -5 dB. >
Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway.

During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of the alveolar epithelial barrier is required for the reabsorption of alveolar fluid. Tight junctions ...
Influence of premature birth on the health conditions, receipt of special education and sport participation of children aged 6–17 years in the USA

BACKGROUND To investigate the influence of premature birth on conditions among children aged 6-17 years. METHODS The National Survey of Children's Health in the USA added a question on premature birth for the first time in the 2011-12 wave. The influence of being born premature on different conditions while controlling for sociodemographic factors was assessed using logistic regression. A total of 6882 out of 62 078 (11.1%) of children aged 6-17 years were born premature. RESULTS Compared with children who were not born premature, those who were born premature were more likely to have cerebral palsy [odds ratio (OR) = 9.6, confidence interval (CI): 7.4-12.4], vision problems (OR = 2.3, CI: 2.0-2.6), hearing problems (OR = 1.7, CI: 1.6-2.0) and a special healthcare need (OR = 1.7, CI: 1.6-1.8). Children who were born premature had an increased likelihood of not being on a sports team or not taking sports lessons after school or on weekends during the past 12 months than those who were not born premature (OR = 1.2, CI: 1.1-1.3). CONCLUSIONS Prematurity may be associated with negative outcomes as infants transition into childhood and adolescence. Interventions within the life-course perspective are needed to alleviate the long-term consequences of prematurity.
Second-Order Lower Bounds on the Expectation of a Convex Function

We develop a class of lower bounds on the expectation of a convex function. The bounds utilize the first two moments of the underlying random variable, whose support is contained in a bounded interval or hyperrectangle. Our bounds have applications to stochastic programs whose random parameters are known only through limited-moment information. Computational results are presented for two-stage stochastic linear programs.
Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model.

Purpose To study the effects of geranylgeranylacetone (GGA) on the expression of inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal ganglion cells (RGCs) in a rat model of glaucoma. Methods Adult Wistar rats were given intraperitoneal injections of GGA at 200 mg/kg daily. Western blot analysis and immunohistochemical staining for HSP72 and HSC70 were performed after 1, 3, and 7 days of treatment with GGA. After 7 days of GGA pretreatment, intraocular pressure (IOP) was elevated unilaterally by repeated trabecular argon laser photocoagulation 5 days after intracameral injection of india ink. After the first laser photocoagulation, GGA was administered twice a week. RGC survival was evaluated after 5 weeks of elevated IOP. Immunohistochemistry and TdT-mediated biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of elevated IOP. Quercetin, an inhibitor of HSP expression, was also administered to a separate group. Results There was increased expression of HSP72 in RGCs at 3 and 7 days after administration of GGA, but HSC70 was unchanged. After 5 weeks of elevated IOP, there was a 27% +/- 6% loss of RGCs. The administration of GGA significantly reduced the loss of RGCs, lessened optic nerve damage, decreased the number of TUNEL-positive cells in the RGC layer, and increased HSP72. Quercetin abolished these protective effects. Conclusions These results demonstrate that systemic administration of GGA protects RGCs from glaucomatous damage in a rat model and suggest a novel pathway for neuroprotection in patients with glaucoma.
Spreading knowledge about Gnutella: a case study in understanding net-centric applications

The paper describes our experiences in attempting to understand the functional nature, high-level design, and implementation details of Gnut, a program that implements the Gnutella peer-to-peer Internet file system protocol. Gnutella is representative of a new breed of net-centric applications that is both qualitatively and quantitatively different than the typical legacy systems that are usually the focus of program understanding exercises. The primary motivation for this analysis is our interest in evaluating the applicability of traditional reverse engineering tools to aid in the understanding of this type of contemporary software system. A secondary motivation for the case study is an assessment of an existing framework for categorizing the capabilities of software reverse engineering environments, to further develop its capabilities. We found that the representative tool we used to examine Gnut, Source Navigator, does not adequately address the requirements of understanding net-centric applications. In particular, the emphasis on static source code analysis is no longer appropriate for this type of application. Dynamic analysis and network monitors are also needed to gain a more complete understanding of the subject system. We also found that the framework requires some alteration to be used in this new context, although the description of the tool's support for the canonical activities of reverse engineering and its quality attributes remains pertinent.
When Molecules and Morphology Clash: A Phylogenetic Analysis of the North American Ambystomatid Salamanders (Caudata: Ambystomatidae)

Extremely conflicting phylogenetic conclusions for the same taxa derived from different data sets are rare. When conflicts do occur, they may result from homoplasy as well as nonindependence of characters. We present an analysis of the phylogenetic relationships of the salamander family Ambystomatidae, based on variation at 26 allozyme loci. Our results conflict strongly with those derived from Kraus's (1988, Syst. Zool. 37:106-141) morphological analysis of the same taxa. The major conflict involves five species traditionally placed in the Ambystoma subgenus "Linguaelapsus." This group, and the clades within it, are each diagnosed by many morphological synapomorphies, providing unambiguous evidence for the monophyly of the subgenus. However, our allozyme data provide equally compelling evidence that "Linguaelap- sus" is polyphyletic. We jackknifed and bootstrapped our allozyme data in a likelihood and a cladistic parsimony framework, respectively; all analyses point to the same conclusions. Sub- dividing the allozyme data into rapidly and slowly evolving loci, and analyzing each separately by maximum likelihood, does not change our conclusions. Our results demonstrate that even apparently "well-corroborated" nodes of a cladogram may be suspect if the assumption of char-
De Facto States in International Politics (1945–2011): A New Data Set

Sovereign states remain the primary units of analysis in conflict research. Yet, the empirical record suggests that the international system includes a wider range of actors whose behavior is relevant for conflict outcomes. This article introduces De Facto States in International Politics (1945–2011), a new data set dedicated to understanding the behavior of de facto states—separatist statelike entities such as Abkhazia. I begin by explaining why de facto states deserve attention. Further, I provide a definition of the de facto state that separates it from cognate phenomena. Thereafter, I offer an overview of the data set and illustrate its utility by demonstrating how it contributes to the literatures on war and state making, civil war, and rebel governance.
Oral Vitamin A and Retinoic Acid Supplementation Stimulates Antibody Production and Splenic Stra6 Expression in Tetanus Toxoid–Immunized Mice

Coadministration of retinoic acid (RA) and polyinosinic acid:polycytidylic acid (PIC) has been shown to cooperatively enhance the anti–tetanus toxoid (anti-TT) vaccine response in adult mice. Germinal center formation in the spleen is critical for a normal antibody response. Recent studies have identified Stimulated by Retinoic Acid-6 (Stra6) as the cell membrane receptor for retinol-binding protein (RBP) in many organs, including spleen. The objectives of the present studies were to test whether orally administered vitamin A (VA) itself, either alone or combined with RA, and/or treatment with PIC regulates Stra6 gene expression in mouse spleen and, concomitantly, antibody production. Eight-week-old C57BL/6 mice were immunized with TT. In an initial kinetic study, oral VA (6 mg/kg) increased anti-TT IgM and IgG production as well as splenic Stra6 mRNA expression. In treatment studies that were analyzed 9 d postimmunization, retinoids including VA, RA, VA and RA combined, and PIC significantly increased plasma anti-TT IgM and IgG (P 20-fold (P < 0.01). Immunohistochemistry of STRA6 protein in mouse spleen confirmed its increase after immunization and retinoid treatment. In conclusion, retinoid treatments that included VA, RA, VA and RA combined, and the combination of retinoid and PIC stimulated the expression of Stra6 in spleen, which potentially could increase the local uptake of retinol. Concomitantly, these treatments increased the systemic antigen-specific antibody response. The ability of oral retinoids to stimulate systemic immunity has implications for public health and therapeutic use of VA.
Expression of the maize GALACTINOL SYNTHASE gene family: (II) Kernel abscission, environmental stress and myo‐inositol influences accumulation of transcript in developing seeds and callus cells

Accumulation of transcript from three maize (Zea mays L. inbred line B73) GALACTINOL SYNTHASE (ZmGOLS) genes in abscised developing seeds and callus before and after stress was examined. Previous work showed that transcript from ZmGOLS3 predominates during seed development, whereas ZmGOLS2 transcript accumulates when triggered by certain stresses following imbibition. Abscission stimulated accumulation of ZmGOLS transcript in immature kernels. This accumulation was enhanced by increasing durations of dehydration stress. In callus tissue, neither ZmGOLS1 nor ZmGOLS3 was detected regardless of media composition or the nature or duration of the applied stress. Accumulation of ZmGOLS2 transcript in heat- or dehydration-stressed callus was induced by exogenously supplied myo-inositol in low amounts but not by sucrose. However, abundance of transcript was a poor indicator of activity of GOLS or amounts of galactinol/raffinose regardless of type of tissue, composition of media, or imposition of stress. Neither were amounts of galactinol/raffinose tightly associated with activity of GOLS nor amounts of myo-inositol, despite the ability of exogenously supplied raffinose to maintain the growth of dehydration-stressed callus. The abundance of ZmGOLS transcript did not increase in response to exogenously supplied abscisic acid.
Environment and Stimulation of Growth of Chicks by Antibiotics

Abstract COATES et al. (1951, 1952) have reported the influence of environment upon the response of chicks to antibiotic. Groups of day-old chicks were maintained in 2 buildings and in each, were fed a basal diet without and with procaine penicillin G. One building had been previously occupied by chicks, whereas the other one was a newly constructed building where no chicks had been reared. Antibiotic response occurred in the “old” quarters, but not so in the “new” quarters. The chicks that were fed no antibiotic in the “new” quarters grew more rapidly than those fed the antibiotic in the “old” quarters. The authors concluded that the reason for the antibiotic response in “old” quarters was the presence of an “infection” that was sensitive to the antibiotic. We reported previously that withdrawal of antibiotic from the diet of chicks at 5 or 6 weeks of age caused a temporary retardation of …
Mitochondrial proton and electron leaks

Mitochondrial proton and electron leak have a major impact on mitochondrial coupling efficiency and production of reactive oxygen species. In the first part of this chapter, we address the molecular nature of the basal and inducible proton leak pathways, and their physiological importance. The basal leak is unregulated, and a major proportion can be attributed to mitochondrial anion carriers, whereas the proton leak through the lipid bilayer appears to be minor. The basal proton leak is cell-type specific and correlates with metabolic rate. The inducible leak through the ANT (adenine nucleotide translocase) and UCPs (uncoupling proteins) can be activated by fatty acids, superoxide or lipid peroxidation products. The physiological role of inducible leak through UCP1 in mammalian brown adipose tissue is heat production, whereas the roles of non-mammalian UCP1 and its paralogous proteins, in particular UCP2 and UCP3, are not yet resolved. The second part of the chapter focuses on the electron leak that occurs in the mitochondrial electron transport chain. Exit of electrons prior to the reduction of oxygen to water at cytochrome c oxidase causes superoxide production. As the mechanisms of electron leak are crucial to understanding their physiological relevance, we summarize the mechanisms and topology of electron leak from complexes I and III in studies using isolated mitochondria. We also highlight recent progress and challenges of assessing electron leak in the living cell. Finally, we emphasize the importance of proton and electron leak as therapeutic targets in body mass regulation and insulin secretion.
Necrotizing enteritis in Crohn's disease of the small bowel.

Acute free perforation of the small bowel in regional enteritis occurred in 6 cases. In 3 cases, the clinical course was that of fulminating necrotizing enteritis ( enteritis necroticans ) characterized by "showers" of perforations, patchy necrosis of the bowel in areas not involved with regional enteritis, and fatal outcome. The roles of intestinal bacteria and corticosteroids in relation to this necrotizing process are discussed.
Reinforcer Efficacy, Response Persistence, and Delay of Reinforcement

In an evaluation of the effects of delayed reinforcement on response persistence, two pigeons were exposed to a series of conditions in which reinforcement that either immediately followed or was delayed from the response that produced it alternated across blocks of sessions. Responding was maintained by a progressive-ratio schedule in which the response requirements incremented for successive reinforcers. The effects of signaled and unsignaled delay values of 1, 5, 10, and 20 s were investigated. In general, responding was more persistent, as measured as the point at which responding ceased for 300 s, with shorter delays, regardless of whether the delays were correlated with a distinct stimulus (that is signaled) or not. The results complement earlier findings showing that reinforcement delays affect reinforcer efficacy or response persistence by showing similar effects using an index of response strength that is independent of response rate. They also extend the general effects of delay of reinforcement to a schedule in which they previously have not been demonstrated.
Asynchronous Learning Networks

Asynchronous Learning Networks ( ALNs) use computer-mediated communication to support online courses of study, in which anytime, anywhere access to interactions among the students and the teacher/facilitator is a key element. In addition to class discussions, other elements frequently incorporated are use of the World Wide Web and of web-based tutorials or simulations. A number of contingencies determine the extent to which ALN's are successful learning environments, including characteristics of the software used, whether the pedagogical techniques employed fit the medium, and characteristics of the individual learners.We have selected three papers which represent some of the basic objectives of research on Asynchronous Learning Networks. Our first paper by Catherine Middleton compares two asynchronous conferencing systems; the results are very interesting. The second paper by Urban Nulden discusses an educational philosophy for structuring asynchronous courses. The third paper, by Jane Leuthold discussed whether computer-based learning is right for everyone
The Ecology of Diversity in Organizational Settings: Lessons from a Case Study

This paper advances a social ecological perspective on the resources necessary to support workplace diversity. It is based on observations from an ongoing organizational case study which used a collaborative inquiry process. We worked with insiders to establish a project steering team, conducted 36 confidential interviews, and met with work units to assess diversity-related concerns. The complex case portrait that emerged illuminates four lessons about the ecology of workplace diversity: (1) the influential role of organizational history and tradition in shaping current diversity dynamics, (2) the importance of understanding how participants' experiences of events may differ, (3) the power of informal organizational processes, and (4) the connections between individual, organizational, and broader cultural values. We discuss these lessons in the context of a three-part definition of support for effective diversity which includes representational, interactional, and cultural components. The goal is to furt...
Physical and chemical properties of radionuclide therapy

As more radionuclide therapies move from laboratory feasibility studies into clinical reality, it becomes increasingly important for the labeling chemistry to produce consistently a stable radiopharmaceutical that remains intact under the challenge of human catabolism. Similarly, once proof of principle is established to bring a radionuclide conjugate into clinical therapy trials, dosimetric estimates should be made to select the appropriate radionuclide properties, which are based on animal-specific or patient-specific pharmacokinetics and match a set of specific clinical endpoints. These properties may include the radionuclide physical half-life, radiolabeled conjugate biological uptake and clearance, product-specific activity, range and type of emissions, and resultant effects on tumor and normal tissue cellular survival. The immunologist and labeling, chemist have now produced a variety of strategies that have potential to increase the therapeutic ratio (tumor-to-normal tissue dose ratio). The advent of normal tissue clearing agents, fragmented or chimerized carriers to improve targeting, and the method of bispecific or two-step and three-step targeting agents has increased the need for realistic modeling of the carrier in vivo to guide prospectively the competitive development of these radiopharmaceuticals. In this article, examples have been taken from the literature to elucidate the benchmark of success that careful experimental design has fostered to bring these agents into clinical practice by creative and logical methodologies.
Quantitative Determination of Chromium Valence in Environmental Samples Using Xafs Spectroscopy

Synchrotron x-ray absorption fine structure (XAFS) spectroscopy provides quantitative information on the speciation of Cr in complex oxide samples, including the Cr(VI):Cr(III) ratio, without any sample pretreatment. The authors discuss several XAFS methods that can be used for this purpose, including: (1) measurement of the height of the pre-edge peak of Cr K-edge spectra which is caused by 1s {r_arrow} 3d electronic transitions occurring predominantly in the Cr(VI)O{sub 4} tetrahedron; (2) fitting observed XANES spectra using combinations of experimental spectra from Cr(III)- and Cr(VI)-containing model compounds; (3) fitting observed EXAFS spectra using combinations of experimental spectra from Cr(III)- and Cr(VI)-containing model compounds; and (4) ab-initio modeling of observed Cr K-EXAFS spectra using theoretical phase-shift and amplitude parameters for Cr(III)O{sub 6} and Cr(VI)O{sub 4} models. The first method is shown to be the simplest and most accurate. The samples examined using these methods include highly pure model compounds, Cr{sub 2}{sup 3+}O{sub 3} and Na{sub 2}Cr{sup 6+}O{sub 4}:4H{sub 2}O, as well as more complex soil samples taken from Cr-contaminated industrial sites and Cr waste disposal pits. The authors present XAFS evidence for the reduction of Cr(VI) to Cr(III) after reaction with the Fe(II)-bearing oxide magnetite, Fe{sub 3}O{sub 4}, and show that Crmore » associated with magnetite in soils is reduced, whereas that associated with non-Fe(II)-bearing silicate minerals is not. Also presented are ab-initio multiple-scattering calculations of XANES spectra of an Cr(VI)O{sub 4} tetrahedron, which help explains the XANES features of this Cr species in solids and aqueous solutions.« less
A dynamic reduced order model for simulating entrained flow gasifiers: Part I: Model development and description

Abstract The development of accurate, flexible and robust dynamic reduced order models (ROMs) is an important step towards greater commercialization of entrained flow gasifiers (EFGs). This two-part series of papers describes the development of such a ROM. Part I, below, describes the model, while Part II presents its validation for four EFG designs and sensitivity analysis. The ROM employs a reactor network model (RNM) that approximates fluid mixing and recirculation using a series of idealized chemical reactors; well-stirred reactors and 1-D plug flow reactors. The RNM is constructed such that the ROM is capable of simulating the operation of a range of commercial or research gasifiers and syngas cooler configurations. The ROM incorporates submodels for multiple feedstocks, mixing and recirculation, particle properties, drying and devolatilization, chemical kinetics, fluid dynamics, heat transfer, pollutant formation, slag behavior and syngas cooling. It is the first experimentally-validated gasifier simulator to incorporate all of the above submodels as well as possess dynamic capability. Modifications to some of the submodels from their original form to improve ROM accuracy, flexibility and robustness are also discussed. The ROM performs the steady-state simulations presented in Part II of this series in 1–5 min on a desktop personal computer, compared to multiple days on multiple processors for more detailed CFD-based simulations.
Do Increasing Cormorant Populations Threaten Sportfishes in the Great Lakes? A Case Study in Lake Huron

After near extirpation earlier this century in the Great Lakes, double-crested cormorant (Phalacrocorax auritus) populations reached all-time highs, raising concerns among sport anglers and fisheries managers, who see cormorants as a significant source of mortality for yellow perch (Perca flavescens), whose populations are perceived to have declined in concert with cormorant increases. We partitioned age-specific perch mortality for 1995 into that caused by (1) cormorant predation, (2) angler harvest, and (3) other sources. Cormorant consumption of perch was calculated by simultaneously estimating diet composition (using stomach analysis and number of foraging cormorants from aerial and ground surveys), and daily consumption (using energetic values from the literature). Consumption of perch by cormorants was heaviest during April and May (48% of the diet by weight) when perch spawn, but yellow perch was not an important prey species overall (11%). Primary prey groups were alewife (47%) and sticklebacks (15%). Cormorants consumed 11,400 kg of perch, mostly young fish (ages 1–3), but mortality caused by cormorant predation was estimated at ≤ 6.3% of mortality for all ages of perch. Neither cormorants nor anglers contributed more than one-fourth of the total annual mortality of any age class of perch. Although cormorants were highly visible predators of perch in Les Cheneaux Islands area, they did not represent a major source of mortality in 1995. Impact of cormorants on perch may vary from year to year, and may relate to fluctuations in timing of the birds’ migration relative to perch spawning. However, we conclude that overall impact is not significant, and control measures to limit their populations were not warranted at the time of this study.
A Study of the Pathological Findings and Treatment in Soft-Tissue Injury of the Thumb Metacarpophalangeal Joint

1. The normal thumb metacarpophalangeal joint varies greatly in range of motion and stability as evidenced by a clinical study of one thousand hands. Arthrodesis of the joint should be avoided if possible; but if necessary, the absence of motion does not limit thumb function greatly. 2. One hundred and forty-five cases of soft-tissue injury of the thumb metacarpophalangeal joint have been reviewed. These included twenty-six dorsal dislocations, twenty-seven radial or ulnar injuries with complete medial or lateral instability, and ninety-two sprains with slight instability. 3. The pathological findings in the totally unstable joints were variable. Plaster immobilization when maintained for four weeks produced satisfactory results in many of these injuries. Immediate or early surgery is not indicated until the results of a trial with immobilization in a plaster cast have been carefully evaluated. Surgical treatment should then be considered if there is pain and functional impairment. 4. Dorsal dislocation of the thumb metacarpophalangeal joint seldom results in instability. This observation suggests that the collateral ligaments are relaxed in extension and are stretched or partially torn and not avulsed in most instances. 5. Stability of the thumb metacarpophalangeal joint can be determined by clinical and roentgenographic stress testing when both thumbs are compared.
Incidence of Clinically Significant Prostate Cancer After a Diagnosis of Atypical Small Acinar Proliferation, High-grade Prostatic Intraepithelial Neoplasia, or Benign Tissue.

Objective To assess the incidence of clinically significant and insignificant prostate cancer after an initial biopsy that revealed either atypical small acinar proliferation (ASAP), high-grade prostatic intraepithelial neoplasia (HGPIN), or benign tissue. Materials and Methods We retrospectively identified patients diagnosed with ASAP, HGPIN, or benign tissue who had a repeat prostate biopsy within 1 year of diagnosis during 1987-2015. We compared the incidence of any prostate cancer and clinically significant prostate cancer (based on Gleason score, prostate-specific antigen (PSA), number of positive cores, and core volume) for each diagnostic group. Results A total of 17,016 biopsies were performed in 12,817 patients during 1987-2015. Among the 615 patients who had a repeat biopsy within 1 year of their first, 261 (42.4%), 208 (33.8%), and 146 (23.8%) had ASAP, HGPIN, or benign tissue on the initial biopsy, respectively. The second biopsy demonstrated significant differences in prostate cancer detection rates between these 3 groups (34.1%, 20.2%, and 15.8%, respectively; P P P = .001 vs HGPIN). The rates of clinically significant prostate cancer did not differ between groups (8.0%, 6.7%, and 4.1%, respectively, P = .31). Conclusion On repeat biopsy, rates of clinically significant prostate cancer did not differ between patients initially diagnosed with ASAP, HGPIN, or benign tissue. Elevated rates of prostate cancer after a diagnosis of ASAP appear to be largely due to differences in the rate of clinically insignificant disease.
Effect of starvation on contractile response of isolated rat atria to citrate and bicarbonate-free medium.

SummaryIsolated atria from 24-hr starved rats show a smaller rate of decline of contractility with time, when incubated in the absence of exogenous substrate than atria from fed rats. During starvation, endogenous substrate apparently accumulates and can be used by the heart to maintain contractility in vitro. The nature of this endogenous substrate was elucidated by the use of bicarbonate-free medium and 1.5 mM citrate. These agents apparently depress contractility by an inhibition of the phosphofructokinase (PFK) reaction in the glycolytic cycle. Both inhibitors produced marked, but not complete, contractile depression of atria from starved or fed rats incubated in the absence of exogenous substrate. This depression is likely due to an interference with the utilization of endogenous substrate, probably glycogen, normally metabolized via PFK. The maintenance of some degree of contractility in the presence of these inhibitors indicates that endogenous substrates, not metabolized via PFK, are utilized. Add...
Monte Carlo solution convergence analysis via COMET in a stylized integral inherently safe LWR benchmark problem

Abstract In this paper, the coarse mesh radiation transport (COMET) method is used to study the convergence of the Monte Carlo solution in a stylized benchmark problem based on the beginning of the equilibrium cycle of the Integral Inherently Safe Light Water Reactor concept (I 2 S-LWR) with silicide U 3 Si 2 fuel. The benchmark problem is comprised of 121 fuel assemblies with radial, top and bottom reflectors. COMET consists of a stochastic local solver (response function generator) for generating a library of incident flux response expansion coefficients for the unique coarse meshes (e.g., all fuel assembly types and reflector/non-fuel blocks) and a deterministic iterative solver for whole-core calculations using this response library. The Monte Carlo method is regarded as the gold standard for benchmarking other numerical transport methods. However, for eigenvalue problems, Monte Carlo results require careful analysis to ensure the convergence of the fission source distribution. It is known that this issue can be of concern, particularly for large eigenvalue problems typical of realistic (i.e., operating) reactors. This became evident when the radially-integrated axial fission density distributions predicted by 50 independent MCNP runs in the I 2 S-LWR benchmark problem were compared to each other and were found to be significantly different, with the difference ranging from −9% to +9%. However, the average of the fission density distributions from these 50 runs agreed very well with that predicted by COMET, with a relative difference varying from −0.18% to 0.13%, being within one standard deviation of the average. This agreement confirms that the averaged Monte Carlo solution is converged.
Abstract 1193: Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody

Although initially responsive to hormone therapy and chemotherapy, many patients with metastatic breast cancer develop resistant and potentially fatal disease. One of the mechanisms of resistance is the emergence of post-treatment survival of a small number of breast cancer stem cells (CSC), which are relatively resistant to chemotherapy, have self-renewal capacity, and can repopulate the tumor and spread to distal sites. New therapies are required to eliminate breast CSC that could be used alone or in combination with standard therapy to mitigate the risk of developing relapsed disease. In this study, treatment of immune-deficient mice bearing breast-cancer patient-derived xenografts (PDX) with paclitaxel reduced tumor volumes, but enhanced the proportion of tumor cells that expressed ROR1, an RTK-like orphan receptor that is ordinarily expressed during embryogenesis. We found that breast cancer tumors with high levels of ROR1 expression were enriched for stem-cell gene-expression signatures. Moreover, cells isolated from breast cancer PDX that were positive for CSC markers such as aldehyde dehydrogenase 1 (ALDH1) were enriched for ROR1 expression, and ROR1+-cells isolated from breast cancer PDX had a greater capacity to form spheroids in vitro or re-engraft immune-deficient mice, than did ROR1-negative (ROR1Neg) cells isolated from the same tumor population. Treatment of breast cancer cells with a humanized anti-ROR1 mAb, UC-961, suppressed expression of the polycomb-ring-finger oncogene Bmi-1, and genes encoding proteins implicated in the epithelial-mesenchymal transition. UC-961 also impaired the capacity of breast-cancer cells to form spheroids or to re-engraft immune-deficient mice. Finally, combined therapy with UC-961 and paclitaxel appeared more effective in reducing re-engraftment potential than either agent alone (Table1). Collectively, this study implies that patients with advanced breast cancer may benefit from anti-CSC therapy, either alone or in combination with conventional anti-cancer drugs. Citation Format: Suping Zhang, Grace Liu, Sam H. Lai, Han Zhang, Emanuela M. Ghia, Bing Cui, Rongrong Wu, George Widhopf, Jian Yu, Richard Schwab, Karen Messer, Barbara Parker, Thomas J. Kipps. Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1193.
Early Pubertal Timing and Childhood Family Adversity Interact to Predict Newlywed Women’s Anxiety Symptoms

The contextual amplification hypothesis posits that girls' early pubertal timing will predict anxiety and depression symptoms most strongly when early puberty occurs under adverse conditions. Research supporting this hypothesis has consistently linked early pubertal timing occurring in adverse contexts to symptoms during adolescence, but little is known about the link to adult symptoms. The present study examined the extent to which women's reports of early pubertal timing and childhood family adversity interact to predict symptoms of anxiety and depression during the first two years of marriage. Married women (N = 226) completed questionnaires within 7 months into their first marriage (Time 1) and approximately 19 months later (Time 2). Analyses indicated that at both Time 1 and 2, women's reports of earlier pubertal timing predicted anxiety symptoms only when women reported a history of greater childhood family adversity. Additional analyses indicated that the interaction of earlier pubertal timing and greater childhood family adversity predicted symptoms of traumatic intrusions and panic, but not social anxiety, at Time 1, and panic symptoms at Times 1 and 2. These findings expand our understanding of the relation of early pubertal timing to adult emotional health and the family conditions that moderate this relation.
Abstract B07: Differential roles for AKT isoforms in BRAF mutant melanoma

Despite recent advances, melanoma remains the deadliest form of skin cancer, and new therapeutic strategies are urgently needed. The MAP kinase (MAPK) and PI3K/AKT pathways are central to both disease progression and chemoresistance in melanoma, with dual targeting approaches yielding promising results that would benefit from increased target specificity and selectivity. The AKT family of serine/threonine kinases comprises three highly homologous and functionally distinct isoforms (AKT1, AKT2, and AKT3) that play unique roles in melanoma but have not yet been leveraged for isoform-specific targeting. Our lab has engineered a unique mouse model of melanoma, in which mutant BRAFV600E is constitutively targeted to mouse melanocytes, resulting in spontaneous malignant disease upon additional loss of tumor suppressor genes, and faithfully recapitulates the human disease. We have identified differential and dynamic activation of AKT isoforms in our mouse melanoma model, which supports the hypothesis that AKT isoforms may play both non-redundant and compensatory roles in melanoma progression. To systematically address this question, we have genetically ablated each AKT isoform individually in melanoma-prone mice in order to elucidate the individual and unique contribution of each isoform to melanoma progression. In parallel, we performed in vitro studies using shRNA mediated conditional knockdown of AKTs in a wide variety of human melanoma cell lines. Our results support an isoform-specific role for AKT1 in promoting melanoma cell proliferation, while AKT2 stimulates cell migration. Further studies utilizing the precision genome editing technology CRISPR/Cas9 allows us to interrogate the effects of AKT isoform specific knockout (KO) on in vivo tumor formation. This work moves toward establishing the contribution of AKT isoforms to tumor progression in melanoma, using both human melanoma cell lines and mouse models, to advance our understanding of the role of AKT in melanomagenesis. With AKT inhibitors in clinical trials for melanoma, our findings could yield novel therapeutic strategies and increase the efficiency of existing therapies to improve treatment options and outcome for this devastating disease. Citation Format: Siobhan K. McRee, Jodie R. Pietruska, Elisabeth Dignan, Philip W. Hinds. Differential roles for AKT isoforms in BRAF mutant melanoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B07.
Containment Venting During Severe Accident: Reasons and Consequences

In case of a core melt accident, the reactor containment might suffer damage resulting from overpressure caused by the decay heat generated inside the containment over a long period. Moreover, a core melt accident causes strong activity release in the containment. The challenge is keeping the containment tight and preventing significant off-site long-term dose issues. Special attention should be paid to consequences caused by organic iodine and noble gases. AREVA develops systems which allow a mitigation of severe accident impact: Filtered Containment Venting System (FCVS) for containment pressure release PEGASUS for monitoring of released activity Central Radiological Computer System (CRCS) for assessment of radiological consequences during and after severe accident CRAFT to protect the protect rooms designated for prolonged occupancy throughout the duration of accidents (control rooms and emergency response centers) from radioactive releases.
Heart rate-based window segmentation improves accuracy of classifying posttraumatic stress disorder using heart rate variability measures.

Objective. Heart rate variability (HRV) characterizes changes in autonomic nervous system function and varies with posttraumatic stress disorder (PTSD). In this study we developed a classifier based on heart rate (HR) and HRV measures, and improved classifier performance using a novel HR-based window segmentation. Approach. Single-channel ECG data were collected from 23 subjects with current PTSD, and 25 control subjects with no history of PTSD over 24 h. RR intervals were derived from these data, cleaned, and used to calculate HR and HRV metrics. These metrics were used as features in a logistic regression classifier. Performance was assessed via repeated random sub-sampling validation. To reduce noise and activity-related effects, we calculated features from five non-overlapping ten-minute quiescent segments of RR intervals defined by lowest HR, as well as random ten-minute segments as a control. Main Results. Using a combination of the four most predictive features derived from quiescent segments we achieved a median area under the receiver operating curve (AUC) of 0.86 on out-of-sample test set data. This was significantly higher than the AUC using 24 h of data (0.72) or random segments (0.67). Significance. These results demonstrate our segmentation approach improves the classification of PTSD from HR and HRV measures, and suggest the potential for tracking PTSD illness severity via objective physiological monitoring. Future studies should prospectively evaluate if classifier output changes significantly with worsening or effective treatment of PTSD.
Patient Perceptions on Facilitating Follow-Up After Heart Failure Hospitalization.

Background— Timely follow-up after hospitalization for heart failure (HF) is recommended. However, follow-up is suboptimal, especially in lower socioeconomic groups. Patient-centered solutions for facilitating follow-up post-HF hospitalization have not been extensively evaluated. Methods and Results— Face-to-face surveys were conducted between 2015 and 2016 among 83 racially diverse adult patients (61% African American, 34% Caucasian, and 5% Other) hospitalized for HF at a university hospital centered in a low-income area of Columbus, Ohio. Patient perceptions of methods to facilitate follow-up post-HF hospitalization and likelihood of using interventions were investigated using a Likert scale: 1=very much to 5=not at all. Results were analyzed by Wilcoxon signed-rank test with Bonferroni correction. The response rate was 82%. The annual household income was P =0.001) in high-ranking interventions related to location (appointment near home, transportation, home appointment) and reminder for visit compared with low-ranking interventions related to time (weekend appointment, appointment after 5 pm) and telemedicine. Conclusions— Among this cohort of racially diverse low-income patients hospitalized with HF, an appointment near the patient’s home and a reminder message were the most desired interventions to facilitate follow-up. Further study of similar populations nationwide is warranted.
On Learning and Assessment.

The challenge of educational assessments – assessments that advance the purposes of learning and instruction – is to provide useful information regarding students’ progress towards the goals of ins...
Top 50 cited journal articles on overhead throwing athletes: a bibliographic analysis

Background The frequency of citations for a journal article is a reflection of its academic impact. The purpose of this study was to identify and characterize the top 50 cited journal articles related to overhead throwing athletes in the published literature. Methods The Web of Science database was searched on January 18, 2016, using the terms "throwing athlete," "baseball," and "pitcher" to identify the top 50 cited articles related to overhead throwing athletes using the all-database function. The type of study, country of origin, publishing journal, and year published were reviewed for each article. Results The top 50 articles identified were cited between 95 and 471 times and were published in 13 journals between 1969 and 2011. Most of the articles were small case series or nonsystematic literature reviews. The shoulder was the most common body region studied in the top 50 articles (33 of 50 [66%]). Among original studies (n = 43), there was a good representation of surgical management of shoulder and elbow pathology in overhead athletes (9 of 43 [20.9%]); however, most of the articles reported on shoulder and elbow kinematics (19 of 43 [44.2%]) and pathoanatomy (15 of 43 [34.9%]). Conclusion The greater prevalence of nonsurgical articles may reflect a continued effort to better understand the different pathologies specific to overhead throwing athletes. An understanding of the variable content and quality of frequently cited articles on overhead throwing athletes may serve as a stepping stone for future studies to advance the diagnosis and management of complex elbow and shoulder injuries in these high functional individuals.