cssi/SciSciGPT-SciSciNet huggingface dataset:
Quercetin inhibits the akt pathway, leading to suppression of survival and induction of apoptosis in cancer cells

Proc Amer Assoc Cancer Res, Volume 46, 2005 2281 The tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene maps to chromosome 10q23.3 and encodes dual specificity phosphatase. The PTEN gene is mutated in 40-50% of patients with brain tumors, especially glioblastomas. PTEN exerts its effects, in part, via inhibition of the antiapoptotic protein kinase B(Akt). The Akt pathway is a cell survival pathway. We evaluated the effects of quercetin (3,3’,4’,5,7-pentahydroxyflavone), a bioflavonoid found in apples, red wine, and tea, on the Akt pathway. We treated BRCA1 mutant HCC1937 breast cancer cells, which have a homozygous deletion of the PTEN gene and an activated Akt pathway, with quercetin (25 μM). The vehicle-treated control had activated levels of Akt at the Ser473 site. Treatment with quercetin for 0.5, 1, and 3 hr completely suppressed Akt phosphorylation at Ser473. The PI3K/Akt inhibitor, LY 294002 ([2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one];10 μM), also suppressed the Akt pathway as evidenced by a reduction of Akt phosphorylation at Ser473, after treatment of the HCC1937 cells for 0.5, 1, and 3 hr. Chemical structural analysis revealed that both quercetin and LY 294002 are members of the benzopyranone class of compounds. To investigate the specificity of quercetin, we used the T47D breast cancer cell line, with an intact PTEN gene. Treatment of the T47D cells for 30 min. with epidermal growth factor (EGF) induced Akt phosphorylation at Ser473. EGF-induced Akt phosphorylation at Ser473 was suppressed by pretreatment of the cells for 3 hr with quercetin (25 μM) or LY 294002 (10 μM). Cells treated with quercetin and LY294002 displayed an apoptotic phenotype. Both quercetin and LY294002 stimulated the MAPK pathway. Our results demonstrate that pharmacologically safe doses of quercetin inhibit the Akt pathway, leading to suppression of cancer cell survival. This finding provides a molecular basis for designing treatment for patients with an activated PI3K/Akt pathway and provides a model to investigate natural compounds for anti-cancer activity.
Orbits of massive satellite galaxies - II. Bayesian estimates of the Milky Way and Andromeda masses using high-precision astrometry and cosmological simulations

National Science Foundation [DGE-1143953, 1228509]; NSF [AST-1211196, AST-156854]; HST [AR-12632]; NASA through a grant from the Space Telescope Science Institute [AR-12632]; NASA [NAS 5-26555]; FAS Science Division Research Computing Group at the Harvard University
Sustainable Methods for Impactful Service Learning in Computer Science (Abstract Only)

Service learning offers students of computer science an experiential opportunity to hone not only their technical skills of design and programming, but also the soft skills of teamwork, communication, and social/ethical behavior. With hard work and effective mentoring from faculty, the output of student work can also benefit community partners, assuming there is proper infrastructure in place to provide long-term project management and technical support. This Birds of a Feather session provides a discussion platform to share lessons learned and best practices related to establishing a sustainable service-learning program within an undergraduate computer-science curriculum, with a particular focus on balancing benefits to students and community partners with organizational overhead.
Interaction between neuronal calcium sensor protein 1 and lithium in pedunculopontine neurons

Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Postmortem studies showed increased expression of neuronal calcium sensor protein 1 (NCS‐1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Lithium (Li+) has been shown to effectively treat the mood disturbances in bipolar disorder patients. We previously showed that NCS‐1 at low levels increased, and at high levels decreased, gamma oscillations in RAS pedunculopontine neurons (PPN), and that Li+ decreased these oscillations. We previously described the effects of each agent on oscillations, G‐protein mechanisms, and Ca2+ currents. However, we designed the present experiments to determine the nature of the interaction of NCS‐1 and Li+ at physiological concentrations that would have an effect within minutes of application. As expected, Li+ decreased gamma oscillation amplitude, while NCS‐1 increased the amplitude of gamma oscillations. We identified NCS‐1 at 2 μmol/L as a concentration that increased gamma oscillations within 5–10 min, and Li+ at 10 μmol/L as a concentration that decreased gamma oscillations within 5 min. The combined application of NCS‐1 and Li+ at these concentrations showed that Li+ reduced the effects of NCS‐1 on oscillation amplitude within 5–10 min. These results demonstrate that at physiological levels, Li+ acts to reduce the effects of NCS‐1 so that, given over expression of NCS‐1, Li+ would have salutary effects.
William W. Cooper

The pioneers ofOperations Research (OR) came from many different social, economic, and educational backgrounds. Their entry into OR was often due to a chance meeting, an unrelated job opportunity, or the influence of a teacher. The William (Bill) Cooper story is a most amazing case in point. He rose from a most difficult social and economic milieu to become one of the most respected and honored members of the OR profession.
Optimization and performance of bifacial solar modules: A global perspective

Abstract With the rapidly growing interest in bifacial photovoltaics (PV), a worldwide map of their potential performance can help assess and accelerate the global deployment of this emerging technology. However, the existing literature only highlights optimized bifacial PV for a few geographic locations or develops worldwide performance maps for very specific configurations, such as the vertical installation. It is still difficult to translate these location- and configuration-specific conclusions to a general optimized performance of this technology. In this paper, we present a global study and optimization of bifacial solar modules using a rigorous and comprehensive modeling framework. Our results demonstrate that with a low albedo of 0.25, the bifacial gain of ground-mounted bifacial modules is less than 10% worldwide. However, increasing the albedo to 0.5 and elevating modules 1 m above the ground can boost the bifacial gain to 30%. Moreover, we derive a set of empirical design rules, which optimize bifacial solar modules across the world and provide the groundwork for rapid assessment of the location-specific performance. We find that ground-mounted, vertical, east-west-facing bifacial modules will outperform their south-north-facing, optimally tilted counterparts by up to 15% below the latitude of 30°, for an albedo of 0.5. The relative energy output is reversed in latitudes above 30°. A detailed and systematic comparison with data from Asia, Africa, Europe, and North America validates the model presented in this paper.
Use of Tissue Electric and Ultrasound Characteristics to Predict and Prevent Steam-Generated Cavitation During High-Power Radiofrequency Ablation

Abstract Objectives Given a paucity of data, the aim of this study was to define predictors of steam pops (SPs) during open-irrigated radiofrequency ablation (RFA). Background SPs during RFA can lead to dire consequences, including perforation and stroke. Methods In an ex vivo bovine myocardium model, open-irrigated RFA was applied at 50 W for 60 s; intracardiac echocardiographic images for RFA with and without SPs was compared. Using an in vivo porcine model, open-irrigated RFA was applied at 50 W for 60 s, and RFA parameters of SPs were analyzed. A retrospective analysis was performed of recorded SPs during clinical ablation procedures over a 1-year period. Results For RFA SPs, there was 32% greater intracardiac echocardiographic tissue echogenicity than for RFA without SPs (p Conclusions Certain echocardiographic and biophysical parameters during open-irrigated RFA are associated with increased SP risks. These include greater tissue echogenicity, larger total impedance reduction, rapid rate of initial impedance reduction, and rapid increase in tissue echogenicity.
Addressing model uncertainty in item response theory person scores through model averaging

Item banks are often created in large-scale research and testing settings in the social sciences to predict individuals’ latent trait scores. A common procedure is to fit multiple candidate item response theory (IRT) models to a calibration sample and select a single best-fitting IRT model. The parameter estimates from this model are then used to obtain trait scores for subsequent respondents. However, this model selection procedure ignores model uncertainty stemming from the fact that the model ranking in the calibration phase is subject to sampling variability. Consequently, the standard errors of trait scores obtained from subsequent respondents do not reflect such uncertainty. Ignoring such sources of uncertainty contributes to the current replication crisis in the social sciences. In this article, we propose and demonstrate an alternative procedure to account for model uncertainty in this context—model averaging of IRT trait scores and their standard errors. We outline the general procedure step-by-step and provide software to aid researchers in implementation, both for large-scale research settings with item banks and for smaller research settings involving IRT scoring. We then demonstrate the procedure with a simulated item-banking illustration, comparing model selection and model averaging within sample in terms of predictive coverage. We conclude by discussing ways that model averaging and IRT scoring can be used and investigated in future research.
Complications of Transurethral Surgery

Despite advances in alternate techniques, transurethral surgery has remained the gold standard for treating urologic disorders of the prostate and bladder. Specifically, transurethral access has allowed urologist to perform transurethral resection of the prostate (TURP) and transurethral resection of bladder tumor (TURBT) to treat benign prostatic hyperplasia (BPH) and bladder tumors, respectively. These procedures are familiar to and used by most urologists, and have shifted surgical treatment away from a traditional open approach. TURP and TURBT have complications that are unique to them. However, because both use similar equipment, there is some overlap in the potential complications of these procedures. This chapter discusses the indications, technique, and complications of each procedure.
The Impact of a Mathematical Intelligent Tutoring System on Students’ Performance on Standardized High-Stake Tests

Recent research has suggested that standardized high-stakes tests, such as the SAT, have become increasingly important to policy makers, school districts, and society in general. Scoring well on these tests may determine the access to educational opportunities beyond high school. Unfortunately, recent reports have shown that Americans are falling behind their peers in other nations on comparable assessments (Gollub et al., 2002). Additionally, schools in the U.S. must adhere to the demands of the No Child Left Behind Act (NCLB). The policy states that federal district funding is dependent on student overall performance on standardized tests in mathematics, reading and other content areas. To alleviate the problem of U.S. students underachieving on standardized tests, educators must explore areas of pedagogy that have been empirically shown to be effective.
Stationary Vacuum-Polarization “ P Fields”: The Missing Element in Electromagnetism and Quantum Mechanics

A spectroscopic analysis of electrons and photons shows that, with an extension of our usual concept of basis states, these particles admit essentially classical representations. By assigning mass and charge “lattices” to the vacuum state, we can define basic “particle-hole” and “antiparticle-antihole” vacuum-polarization excitation pairs, and we can deduce their equations of motion. We denote these (non-rotating) P-H and P-H pairs as “polarons” and “antipolarons.” With the aid of the polaron basis states, we can reproduce not only the photon, but also the “zeron,” which is the quantum of the wave packet that accompanies the photon. The photon is spectroscopically reproduced as a linked polaron-antipolaron pair in a rotational mode. The zeron is a rotating polaron that closely mimics the photon electromagnetically, but which carries only infinitesimal amounts of energy and momentum. In its motion through space, a wave train of rotating zerons induces a stationary polaron electric field pattern (a “P field”) of opposite polarity in the vacuum state. This static P field performs a number of crucial functions: (1) the P field “self-synchronizes” individual zerons into accurately correlated Ψ-wave packets, both for plane waves and for Ψ-wave interference patterns; (2) the electric field strength of the P field in overlapping interference regions is proportional to the square of the corresponding Ψ-wave amplitude, and in its steering mechanism this interference P field converts Ψ-wave amplitudes into quantum mechanical probability distributions; (3) the requirement that the P field must close on itself furnishes the quantization of atomic electron orbitals in accurate multiples of the de Broglie wavelength λ;(4) a pair of time-reversed (counter-rotating and spin-reversed) electrons, protons, or neutrons can share a common mutually-enhanced P field, thus creating the “pairing force” mechanism that dominates both atomic and nuclear structure, and which also leads to the Cooper pairs of superconductivity; (5) we can provide a physical basis for the Ψ-wave orthogonality relations that dictate atomic shell structure by imposing the requirement that the superposed P fields of two electrons in different orbitals do not (on the average) “steer” each other’s electrons. Classical electric E-field lines are reproduced as chains of linked polarons. and magnetic H-field lines are reproduced as linked-polaron loops, with the Lorentz force acting to prevent the collapse of the loops.
NMR Methods in Studies of Brain Ischemia

In vivo NMR spectroscopy has gained world-wide attention since the publication of the use of surface coils to noninvasively observe metabolic changes in whole animals (Ackerman et al., 1980). It has provided an attractive method for continuously monitoring metabolic changes in short time intervals in the physiological and pathophysiological states of an organ or a tissue of an individual animal (Shulman, 1979; Gadian, 1982; James and Margulis, 1984; Radda, 1986; Cohen, 1987). Due to relatively low sensitivity, NMR methods detect only those metabolites whose concentrations are ≥ 1.0 mM and that are not tightly bound to macromolecules or immobile cellular structures. A large number of NMR-observable nuclei have been used as naturally occurring or artificial probes for in vivo studies.
Reisig, Karl (1792–1829)

Christian Karl Reisig (1792–1829) was a classical philologist in Jena and Halle who is best remembered for introducing semantics as an independent discipline in Vorlesungen uber lateinische Sprachwissenschaft (1839). Reisig's ‘semasiology’ is typically construed as being limited to historical semantic shifts, a view that fails to appreciate the synchronic component of his investigation of meaning into the logical relationships between words.
Abstract 950: New strategy to sensitize pancreatic and bladder cancer to gemcitabine

Pancreatic Ductal Adenocarcinoma (PDAC), the major histological subtype of pancreatic cancer displays few symptoms for early detection and the majority of PDAC patients are diagnosed with advanced or metastatic disease. PDAC patients with advanced disease lack durable responses to chemotherapy and have a dismal prognosis. Gemcitabine is the cornerstone of care for advanced and metastatic PDAC. While the underlying mechanisms leading to gemcitabine resistance are likely to be multifactorial, there is a strong association between activating gemcitabine metabolism pathways and clinical outcome. Accordingly, strategies that lead to upregulation of signaling pathways and enzymes involved in generating the active metabolite may lead to improved outcome in PDAC. We have developed a potent, selective, small molecule inhibitor of casein kinase-1 delta (CK1δ) and demonstrated that inhibition of CK1δ activity specifically compromises the growth, survival and invasion of breast cancer cells that overexpress CK1δ. Notably, our lead compound, SR-3029 provokes pre-clinical tumor regression of triple negative breast cancer (TNBC), including lung metastatic TNBC and basal-like PDX breast cancer models. We observed that CK1δ is upregulated in other cancers including bladder cancer and demonstrated that SR-3029 acts in synergy with DNA damaging cytotoxic agents. Notably, the combination of gemcitabine with SR-3029 resulted in synergistic antiproliferative activity and impaired colony formation in both pancreatic and bladder cancer cells. Mechanistic studies demonstrate that silencing CK1δ or inhibition of CK1δ activity by SR-3029 induces a significant upregulation of deoxycytidine kinase (DCK; rate limiting enzyme for gemcitabine activation) both at the RNA and protein levels, which results in increased cellular DCK and its active gemcitabine metabolite. We evaluated the effect of SR-3029 alone and in combination with gemcitabine in an orthotopic pancreatic tumor mouse model and observed much improved tumor growth inhibition with combination treatment, concomitant with increased expression of DCK. In conclusion, our study suggests that CK1δ plays signaling roles in DNA metabolism and the combination of CK1δ inhibition with gemcitabine holds promise as a future therapeutic option for metastatic pancreatic cancer as well as other cancers. Citation Format: Simon Bayle, Francesca Vena, Andrii Monastyrskyi, William Roush, Derek Duckett. New strategy to sensitize pancreatic and bladder cancer to gemcitabine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 950.
Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for simultaneous quantifications of CZ48, lactone-stabilized camptothecin, and camptothecin and their pharmacokinetic and biliary evaluations in rats.

Abstract CZ48, a prodrug of camptothecin (CPT), has a broad spectrum of antitumor activity against various types of human tumors without severe toxicity in preclinical human tumor-xenografted mouse models, which facilitates further preclinical and clinical pharmacokinetic (PK) evaluations of CZ48. In this study, a UHPLC–MS/MS method was developed and validated to simultaneously quantify CZ48 and CPT in rat plasma and bile. Detection was performed using the API 3200 Q Trap triple quadrupole mass spectrometer in a positive ion mode. Chromatographic separation was achieved on Waters ACQUITY UPLC BEH Shield RP18 column with a gradient elution at a flow rate of 0.45 ml/min, using mobile phases of 0.1% acetic acid in water (A) and 0.1% acetic acid in acetonitrile (B). The method was linear at the concentration ranges of 0.98 (LLOQ) −1000 ng/ml of CZ48 and CPT in rat plasma and 3.9 (LLOQ) −1000 ng/ml in bile. Intra- and inter-day accuracy and precision values did not deviate by more than 6.57% and 10.15% for CZ48 and CPT, respectively, in plasma, and 12.09% and 13.48% in bile. Extraction recoveries of CZ48 were 90.18–95.42% from plasma and 86.51 −91.66% from bile. The recoveries of CPT were 91.56–97.06% from plasma and 84.89–89.15% from bile. No significant matrix effects were observed in plasma and bile within 14.00% and 16.19%, respectively. CZ48 and CPT in plasma were stable after extraction process and different storage conditions, including bench-top, processed sample in autosampler, three cycles of freeze and thaw, and long-term (3 month) stability at −80 °C. The application of the validated method was demonstrated by a PK study after an intravenous dose of CZ48 in rats.
Parameters Affecting Dynamics of 3-Dimensional Seismic Isolation

Seismic base isolation systems are mainly used to reduce seismic demands and minimize earthquake effect on structure performance. In this study, the fundamental dynamic response of structures with ...
Doping CdTe Absorber Cells using Group V Elements

Arsenic dopant was incorporated in CdTe absorber layers in high-efficiency CdTe cells using feedstock doped with 1018cc-1for sublimation of films. The goal of the work was to develop a feasible method for creating a hole density equal to, or greater than that currently achievable using copper doping using a CuCl treatment. Doping with arsenic resulted in a modest increase in open-circuit voltage (V OC ) and a large improvement in fill-factor and conversion efficiency when compared with copper-doped devices with similar structure. All experiments were performed in the presence of cadmium overpressure to encourage dopant activation in tellurium vacancy sites. Arsenic incorporation was measured using Secondary Ion Mass Spectrometry (SIMS) at 4E +16 atoms/cc-1,about four times greater incorporation than previously seen by the authors. Using a CdSeTe/CdTe graded absorber and arsenic doping, a conversion efficiency of 16.79% was achieved.
Enhanced Absorption in Amorphous Silicon Solar Cells Using Plasmonic and Photonic Crystals – Measurement and Simulation

We develop experimentally and theoretically plasmonic and photonic crystals for enhancing thin film silicon solar cells. Thin film amorphous silicon (a-Si:H) solar cells suffer from decreased absorption of red and near-infrared photons, where the photon absorption length is large. Simulations predict maximal light absorption for a pitch of 700-800 nm for photonic crystal hole arrays in silver or ZnO/Ag back reflectors, with absorption increases of ~12%. The photonic crystal improves over the ideal randomly roughened back reflector (or the ‘4n2 limit’) at wavelengths near the band edge. We fabricated metallic photonic crystal back-reflectors using photolithography and reactive-ion etching. We conformally deposited a-Si:H solar cells on triangular lattice hole arrays of pitch 760 nm on silver back-reflectors. Electron microscopy demonstrates excellent long range periodicity and conformal a-Si:H growth. The measured quantum efficiency increases by 7-8 %, relative to a flat reflector reference device, with enhancement factors exceeding 6 at near-infrared wavelengths. The photonic crystal back reflector strongly diffracts light and increases optical path lengths of solar photons.
From Character and Visual Identity to Theme—Gardens: Design of Parks and Public Open Space in Postmodern Singapore

Following a postmodern trend, planners attempted to address the social and cultural challenges posed by the rapid and extensive post-war urban growth, by advocating a revival of contextualism and regionalism, as well as the use of vernacular and popular culture icons in urban design. Singapore’s parks and gardens were conceptualized as an island-wide ‘cultural system’ meant to construct place identity and ‘imageability’ in support of the larger picture of nation building realized through the welfare-state public housing policy. Parks’ design was thematized to reflect in various manner the state’s ‘multicultural theme’, used to redirect tourism marketing strategies and the sociopolitical constructions of an ‘imagined community’.
Can Test Anxiety Interventions Alleviate a Gender Gap in an Undergraduate STEM Course

Gender gaps in exam scores or final grades are common in introductory college science and engineering classrooms, with women underperforming relative to men with the same admission test scores or college grade point averages. After failing to close a historically documented gender gap in a large introductory biology course using interventions targeted at training a growth mindset, we implemented interventions designed to reduce student test anxiety. We combined evidence-based exercises based on expressive writing and on reappraising physiological arousal. We also used a valid measure to quantify test anxiety at the start and end of the course. This instrument measures an individual's self-declared or perceived test anxiety-also called trait anxiety-but not the immediate or "state" anxiety experienced during an actual exam. Consistent with previous reports in the literature, we found that women in this population declared much higher test anxiety than men and that students who declared higher test anxiety had lower exam scores than students who declared lower test anxiety. Although the test anxiety interventions had no impact on the level of self-declared trait anxiety, they did significantly increase student exam performance. The treatment benefits occurred in both men and women. These data suggest that 1) a combination of interventions based on expressive writing and reappraising physiological arousal can be a relatively easy manner to boost exam performance in a large-enrollment science, technology, engineering, and mathematics (STEM) course and encourage emotion regulation; 2) women are more willing than men to declare that they are anxious about exams, but men and women may actually experience the same level of anxiety during the exam itself; and 3) women are underperforming in STEM courses for reasons other than gender-based differences in mindset or test anxiety.
Poisoning Attack on Load Forecasting

Short-term load forecasting systems for power grids have demonstrated high accuracy and have been widely employed for commercial use. However, classic load forecasting systems, which are based on statistical methods, are subject to vulnerability from training data poisoning. In this paper, we demonstrate a data poisoning strategy that effectively corrupts the forecasting model even in the presence of outlier detection. To the best of our knowledge, poisoning attack on short-term load forecasting with outlier detection has not been studied in previous works. Our method applies to several forecasting models, including the most widely-adapted and best-performing ones, such as multiple linear regression (MLR) and neural network (NN) models. Starting with the MLR model, we develop a novel closed-form solution to quickly estimate the new MLR model after a round of data poisoning without retraining. We then employ line search and simulated annealing to find the poisoning attack solution. Furthermore, we use the MLR attacking solution to generate a numerical solution for other models, such as NN. The effectiveness of our algorithm has been tested on the Global Energy Forecasting Competition (GEFCom2012) data set with the presence of outlier detection.
Multivariate Density Estimation

Exploring and identifying structure is even more important for multivariate data than univariate data, given the difficulties in graphically presenting multivariate data and the comparative lack of parametric models to represent it. Unfortunately, such exploration is also inherently more difficult.
Developing an Effective Campus Sexual Assault Prevention Task Force: Lessons Learned From Multiple Midwestern Universities:

Background/Aim. Developing a comprehensive prevention strategy requires a coordinated effort among campus stakeholders. Creating a campus sexual assault prevention task force consisting of key stak...
Therapeutic Application of Calcium Antagonists in Gastroenterology

As a gastroenterologist and a clinician, I look after patients who may benefit from therapy with calcium channel blockers. I would like to share with you some of the experiences we have had over the last few years, which may provide some insight into the clinical role these agents currently have in the gastrointestinal (GI) tract and also allow for some speculation about future directions.
SARS-CoV-2 Genomic Surveillance Reveals Little Spread Between a Large University Campus and the Surrounding Community

COVID-19 has had high incidence at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are not well understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities. We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan-Ann Arbor and the surrounding community during the Fall 2020 semester (August 16th through November 24th). We sequenced complete SARS-CoV-2 genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total confirmed cases in Washtenaw County over the study interval. Phylogenetic analysis identified over 200 introductions into the student population, most of which were not related to other student cases. There were two prolonged transmission clusters among students that spanned across multiple on-campus residences. However, there were very few genetic descendants of student clusters among non-students during a subsequent November wave of infections in the community. We conclude that outbreaks at the University of Michigan did not significantly contribute to the rise in Washtenaw County COVID-19 incidence during November 2020. These results provide valuable insights into the distinct transmission dynamics of SARS- CoV-2 among IHE populations and surrounding communities.
Patterns of Trophic Evolution: Integration and Modularity of the Cichlid Skull

A key axis of diversification among cichlid species is trophic specialization, and much effort has been dedicated to revealing the factors that have contributed to the vast array of feeding morphologies that have evolved in this group. While the physical environment, especially within the large East African lakes, has undoubtedly facilitated their evolutionary success, there must also be intrinsic attributes of cichlids that have increased their evolutionary potential. The modular design of organisms has been credited for promoting diversity across metazoans. This is because the mixing and matching of preexisting anatomical “units” is a more efficient way to expand ecological diversity than the independent evolution of each component part. We suggest that modularity may also play an important role in cichlid craniofacial diversification. We review work focused on describing modularity in cichlids at multiple levels of biological organization—e.g., genetic, anatomical, and functional—and how each can explain the pattern and pace of morphological evolution in this group. We show further how changes in the action of a single molecular pathway—the Hedgehog signal transduction pathway—can promote integration at multiple levels. We consider this pathway to be a molecular “hotspot” for early and ongoing diversification in this group. Understanding the factors that promote and constrain biological diversity is an important topic in evolutionary biology. As cichlid researchers, we are in a unique position to contribute key insights into this question.
Chapter 7 Comprehension Processes in Reading Ambiguous Sentences: Reflections from Eye Movements

Publisher Summary This chapter reviews different types of ambiguity. One of the primary findings is that the different types of ambiguity are handled in different ways by the language processing system. The research relies very heavily upon eye movement recording during reading to make inferences about how ambiguous sentences are processed. The eye movements provide a very good on-line record of moment-to-moment comprehension processes and provide a relatively natural reading situation so that a good sense can be produced of how people normally process ambiguous sentences. The results are plausible and convincing, and the cross-modal priming situation rarely occurs during more normal real-world situations.
Identification of the major Mr 100,000 substrate for calmodulin-dependent protein kinase III in mammalian cells as elongation factor-2.

The major substrate for Ca2+/calmodulin-dependent protein kinase III in mammalian cells is a species of Mr 100,000 that has a primarily cytoplasmic localization. This substrate has now been identified as elongation factor-2 (EF-2), a protein that catalyzes the translocation of peptidyl-tRNA on the ribosome. The amino acid sequence of 18 residues from the N-terminal of the Mr 100,000 CaM-dependent protein kinase III substrate purified from rat pancreas was found to be identical to the N-terminal sequence of authentic rat EF-2 as previously deduced from nucleic acid sequencing of a cDNA (Kohno, K., Uchida, T., Ohkubo, H., Nakanishi, S., Nakanishi, T., Fukui, T., Ohtsuka, E., Ikehara, M., and Okada, Y. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 4978-4982). CaM-dependent protein kinase III phosphorylated EF-2 in vitro with a stoichiometry of approximately 1 mol/mol on a threonine residue. Amino acid sequencing of the purified tryptic phosphopeptide revealed that this threonine residue lies within the sequence: Ala-Gly-Glu-Thr-Arg-Phe-Thr-Asp-Thr-Arg (residues 51-60 of EF-2). The Mr 100,000 protein was stoichiometrically ADP-ribosylated in vitro by the addition of diphtheria toxin and NAD. The Mr 100,000 protein was photoaffinity labeled with a GTP analog and the protein had an endogenous GTPase activity that could be stimulated by the addition of salt-washed ribosomes. These properties are all characteristic of EF-2. Dephospho-EF-2 could support poly(U)-directed polyphenylalanine synthesis in a reconstituted elongation system when combined with EF-1. In the same system, phospho-EF-2 was virtually inactive in supporting polypeptide synthesis; this effect could be reversed by dephosphorylation of phospho-EF-2. These results suggest that intracellular Ca2+ inhibits protein synthesis in mammalian cells via CaM-dependent protein kinase III-catalyzed phosphorylation of EF-2.
Teaching Badminton to Groups.

(1980). Teaching Badminton to Groups. Journal of Physical Education and Recreation: Vol. 51, Including Leisure Today, pp. 26-28.
One-component plasma structure factor in tabular form

The one-component plasma structure factor $S(q,\ensuremath{\Gamma})$ has been computed with a hypernetted-chain equation modified by the hard-sphere bridge function. The structure factor is tabulated for reduced wave number $0.1\ensuremath{\le}q\ensuremath{\le}25.0$ and Coulomb coupling parameter $0.1\ensuremath{\le}\ensuremath{\Gamma}\ensuremath{\le}180$. The hypernetted-chain results are in excellent agreement with Monte Carlo calculations. This table should be useful for calculations on dense plasmas and liquid metals.
Chemotaxonomic Investigation of Cotylelobium Species (Dipterocarpaceae) using Flavonoid Analysis

During the chemotaxonomic investigation of Dipterocarpaceae, three flavonoid aglycones : flavonol quercetin, flavonol kaempferol and flavone apigenin and four glycosides : Quercetin 3-glucoside, apigenin 5- glucoside, kaempferol 3,5- glucoside and quercetin 3-rutinoside were isolated from the leaves of two species of Cotylelobium ( C. lewisianum, and C. scabriusculum ). The isolated flavonoids can be used as chemotaxonomic markers. Myricetin, luteolin and proanthocyanidins were not decteted in this investigation. Both the species of Cotylelobium can be regarded as advanced in flavonoid patterns because of the absence of myricetin and loss of proanthocyanidins. The data of the flavonoid patterns and the outcome of cluster analysis are taxonomically useful to resolve the controversies over the systematic arrangement of the species and also suggest the need for a revision of classification of the genus Cotylelobium. Key words: Dipterocarpaceae; Flavones. Flavonols; Chemotaxonomy; Cluster analysis. DOI: 10.3126/sw.v6i6.2629 Scientific World , Vol. 6, No. 6, July 2008 24-26
Analysis of environmental factors in familial versus sporadic Paget's disease of bone--the New England Registry for Paget's Disease of Bone.

A registry for Paget's Disease (PD) was created to study the environmental and familial features of this disorder. This study examines the first 202 people enrolled. Those with a family history of PD (20%) suffered earlier deformity and fracture, and tended to have grandparents born abroad. These findings suggest heritage is important in PD; the role of environment remains unclear. Introduction: The New England Registry for Paget's Disease of Bone is a database that was created to explore the distribution and determinants of disease frequency. Methods: Using a case-series design, we explored the association of environmental factors in expression of the disease, comparing those patients with familial Paget's disease to those with sporadic Paget's disease (PD). Results and Conclusions: Analysis of the first 202 patients enrolled in the registry revealed a positive family history (FH) in 41 (20%). Significant findings in this cohort included an earlier age of onset (51 years FH+ versus 59 years FH?, p < 0.05), a trend to a higher incidence of bone deformity (49% versus 33%, p < 0.1), and an increased fracture rate (27% versus 11%, p < 0.05). Persons with a FH of PD were less likely to record the United States or Canada as their grandparents' birthplace (p < 0.01), and sibships tended to be larger (p < 0.05). A history of measles infection, childhood exposure to pets, milk ingestion, year of immigration to the United States, birth order, level of education, and functional status did not distinguish the two groups. The database confirms the high prevalence of familial PD and supports the theory that heritable factors are important in the pathogenesis of this focal disorder of bone metabolism.
Supramolecular self-assembly of multiblock copolymers in aqueous solution.

A unique pH-dependent phase behavior from a copolymer micellar solution to a collapsed hydrogel with micelles ordered in a hexagonal phase was observed. Small-angle neutron scattering (SANS) was used to follow the pH-dependent structural evolution of micelles formed in a solution of a pentablock copolymer consisting of poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl methacrylate)) (PDEAEM25-b-PEO100-b-PPO65-b-PEO100-b-PDEAEM25). Between pH 3.0 and pH 7.4, we observed the presence of charged spherical micelles. Increasing the pH of the micelle solution above pH 7.4 resulted in increasing the size of the micelles due to the increasing hydrophobicity of the PDEAEM blocks above their pKa of 7.6. The increase in size of the spherical micelles resulted in a transition to a cylindrical micelle morphology in the pH range 8.1−10.5, and at pH >11, the copolymer solution undergoes macroscopic phase separation. Indeed, the phase separated copolymer ...
Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis

OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3sigma, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3sigma were the only markers that were significantly associated with tumour grade and 14-3-3sigma was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible.
Total internal reflection fluorescence microscopy: application to substrate-supported planar membranes

The use of total internal reflection illumination in fluorescence microscopy (TIRFM) is reviewed with emphasis on application to fluorescent macromolecules that specifically and reversibly bind to planar model membranes supported on glass or quartz substrates. Several methods for characterizing macromolecular motion and organization are discussed: the measurement of equilibrium binding curves to obtain values for equilibrium binding constants; the measurement of fluorescence photobleaching recovery curves to obtain values of kinetic rate constants and surface diffusion coefficients; and the measurement of fluorescence intensities as a function of the evanescent field polarization to characterize orientational order. Applications to cell-substrate contact regions are summarized and future directions of TIRFM are outlined.
Determination of nicotinamide and metabolic products in urine by high-performance liquid chromatography.

Abstract A high-performance liquid chromatographic procedure has been developed for the quantitation of nicotinamide, nicotinic acid, nicotinuric acid, 1-methylnicotinamide and 1-methyl-2-pyridone-5-carboxamide in rat and human urines. The procedure utilizes a Varian Model 5020 liquid chromatograph with a UV detector, and an Altex 15 cm × 4.6 mm Ultrasphere-ODS column, employing a linear ion-pair mobile phase gradient. Solvent A contains 10 mM concentrations of pentanesulfonic acid (PSA), tetramethylammonium chloride (TMA) and KH???PO4, and solvent B contains PSA, TMA and acetonitrile. Different pH values for solvent A vary the retention times and thus the separation of the five compounds. Temperature of the system is critical. The conditions found most satisfactory were pH 3.30 and 24.5°C.
Three dimensional shear wave elastographic reconstruction of ablations

This paper presents an algorithm for three dimensional (3D) reconstruction of tumor ablations using ultrasound electrode vibration elastography. Shear wave velocity, which is used as a surrogate for tissue stiffness, is estimated by perturbing the ablation needle and tracking frame-to-frame displacements using radiofrequency ultrasound echo data. This process is repeated over many imaging planes that share a common axis of intersection collinear with needle. A 3D volume is reconstructed by solving an optimization problem which smoothly approximates shear wave velocities on a stack of transverse planes. The mean shear wave velocity estimates obtained in the phantom experiments are within 20% of those measured using a commercial shear wave imaging system.
A chemurgic survey of the desert flora in the American Southwest

While commercial utilization of the desert flora in the American Southwest is still scarcely begun, there are possibilities of obtaining stock feed, alcohol, paper pulp, sugars, starches, resins, gums, alkaloids, oils and other extractives from the xerophytic plants of the region.
Robust Bayesian approaches for clinical trial monitoring

The interim monitoring and final analysis of data arising from a clinical trial require an inferential method capable of convincing a broad group of potential consumers: doctors; patients; politicians; members of the media, and so on. While Bayesian methods offer a powerful and flexible analytic framework in this setting, this need to convince a diverse community necessitates a practical approach for studying and communicating the robustness of conclusions to the prior specification. In this paper we attempt to characterize the class of priors leading to a given decision (such as stopping the trial and rejecting the null hypothesis) conditional on the observed data. We evaluate the practicality and effectiveness of this procedure over a range of smoothness conditions on the prior class. First, we consider a non-parametric class of priors restricted only in that its elements must have certain prespecified quantiles. We then obtain more precise results by further restricting the prior class, first to a non-parametric class whose members are quasi-unimodal, then to a semi-parametric normal mixture class, and finally to the fully parametric normal family. We illustrate all of our comparisons with a dataset from an AIDS clinical trial that compared the effectiveness of the drug pyrimethamine and a placebo in preventing toxoplasmic encephalitis.
Elevation of Oxytocin and the Oxytocin-Associated Neurophysin in the Plasma of Normal Women during Midcycle*

A positive correlation was observed between the midcycle elevation of estrogen (E) and the level of oxytocin- and estrogen-stimulated neurophysin (ESN), the protein carrier of oxytocin, in the plasma of five of six women. The time of the maximal level of E was associated with a level of oxytocin significantly greater than that in either the early follicular or late luteal phase (P less than 0.025). Likewise, the level of ESN at midcycle was greater than the level of ESN in the early follicular or late luteal phase (P less than 0.01). Other than states of lactation or pregnancy, this is the only described cyclic secretion of oxytocin in humans. Since oxytocin chronologically correlates with a rise in the level of E at midcycle, a role for oxytocin in ovulation may be considered.
Importance of assessing changes in ventricular response to atrial fibrillation during evaluation of new heart failure therapies: Experience from trials of flosequinan☆

This study evaluated the effects of flosequinan on ventricular rate in patients with congestive heart failure and atrial fibrillation to determine whether this agent has a facilitatory effect on atrioventricular conduction and whether such an effect may be deleterious. Flosequinan is known to have a dose-dependent positive chronotropic effect on the sinus node, but its effect on atrioventricular conduction has not been evaluated. An excessive increase in ventricular rate during the treatment of heart failure could raise a safety concern and counterbalance beneficial responses. Data were analyzed from 338 patients participating in three similarly designed placebo-controlled exercise trials with flosequinan who also underwent ambulatory electrocardiographic monitoring. The effects of two doses of flosequinan on supine, standing, ambulatory, and exercise heart rates and on exercise capacity in patients in sinus rhythm and atrial fibrillation were compared. Flosequinan increased heart rate in a dose-dependent manner, in patients both with sinus rhythm and atrial fibrillation. A 100 mg once daily dose produced significant increases, in both rhythms, ranging from 6 to 11 beats/min, in supine and standing heart rate, ambulatory heart rate, and exercise heart rate. With a dose of 75 mg twice daily, heart rates under these conditions increased by >20 beats/min in flosequinan-treated patients in atrial fibrillation, a change significantly greater than that observed with placebo or flosequinan, 100 mg once daily and also more than in patients in sinus rhythm treated with the same dose. These results indicate that flosequinan facilitates atrioventricular nodal conduction, increasing the ventricular response in atrial fibrillation, especially at higher dosages. This finding could result from a direct drug action, such as phosphodiesterase inhibition, or reflex sympathetic activation. This response is of sufficient magnitude potentially to impair left ventricular function and interfere with clinical benefit. The effect of heart-failure drugs on ventricular responses in atrial fibrillation should be examined to provide insight into potential mechanisms of both action and safety in this common patient group.