cssi/SciSciGPT-SciSciNet huggingface dataset:
How Does Order of Gameplay Impact Learning and Enjoyment in a Digital Learning Game

When students are given agency in playing and learning from a digital learning game, how do their decisions about sequence of gameplay impact learning and enjoyment? We explored this question in the context of Decimal Point, a math learning game that teaches decimals to middle-school students. Our analysis is based on students in a high-agency condition, those who can choose the order of gameplay, as well as when to stop. By clustering student mini-game sequences by edit distance – the number of edit operations to turn one sequence into another – we found that, among students who stopped early, those who deviated more from a canonical game sequence reported higher enjoyment than those who did not. However, there were no differences in learning gains. Our results suggest that students who can self-regulate and exercise agency will enjoy the game, but the type and number of choices may also have an impact on enjoyment factors. At the same time, more investigation into the amount and means of delivering instruction to maximize learning efficiency within the game is necessary. We conclude by discussing digital learning game design lessons to create a game that more closely aligns with students’ learning needs and affective states.
University Archives and the Slow Fuse of Possibility

In a 21 st century world hinged on lightning-fast information edited into 140-character sound bites, three events that occurred at UNCG in the years 1956, 1960, and 1963 engage current students. This article will show how the authors use the university archives in a first-year class, which explores education as a personal, local, and global question, to allow students to interrogate the place of history in their current educational process. By introducing our campus history and using archival materials that show the events from the perspectives of students, faculty, administration, and the public we encourage students to approach their own education with creativity and imagination- what Emily Dickenson called “the slow fuse of possibility” (in Greene, 2007). History is not merely the static story we believe it to be, but a fluid, challenging narrative that has implications on what and how students learn today. By digging into the past, students can, as Maxine Greene (2007) asks, “break with the ordinary, the given, the taken for granted and open doors to possibility” and think about the present with curiosity and imagination. Education stripped of historical context is just an endless loop of lectures and tests endured by students who wonder what disconnected bits of information have to do with the life they want to live. But when students see themselves as part of a lineage of learners they then have context for what we know and the places in which we learn. Adrienne Rich (1986) said, “I need to understand how a place on a map is also a place in history” as she contemplated her place in the world (p. 212). When we ask students to think about these historical moments, to connect them to current, global events we are reimagining the place of history, archives, and the campus we teach on as relevant to their education. UNCG does not exist only as we see it today, but is built on the stories and legacies of the students and faculty who have come before like Lucille Pugh, who attended what is now UNCG from 1899-1902 and was the first female lawyer in the country to defend an accused murder (Spartan Stories, April 7, 2014) or Virginia Tucker, a 1930 graduate, who was a NACA/NASA pioneer in aeronautics and mechanical engineering (Spartan Stories, March 2, 2015). By exploring the history of the campus, it becomes a living place where the work of today is built on the shoulders of those who came before and their college experience is tangled with the structural oppressions exist in all social institutions. This archival exploration asks students to explore how, when shown the history, they “can open out the structures of resistance, unbind the imagination, and connect what’s been dangerously disconnected” in their education (p. 214).
Spatiotemporal pattern of COVID-19 and government response in South Korea (as of May 31, 2020).

Abstract Objectives The aim of this study is to assess how COVID-19 clustered across districts in South Korea and to assess whether the pattern and duration of clusters changed following the country’s containment strategy. Methods We conducted spatiotemporal analysis of COVID-19 daily confirmed cases by 250 districts in South Korea from January 20 to May 31, 2020, obtained from the Korea Centers for Disease Control and Prevention and each provincial website. Global Moran’s I statistic was used for spatial autocorrelation analysis and retrospective space-time scan statistic was used to analyze spatiotemporal clusters of COVID-19. Results The geographical distribution showed strong spatial autocorrelation, with a global Moran’s I coefficient of 0.784 (p = 0.0001). Twelve statistically significant spatiotemporal clusters were identified by space-time scan statistic using a discrete Poisson model. The spatial pattern of clusters changed and the duration of clusters became shorter over time. Conclusions Results indicate that South Korea’s containment strategy of COVID-19 was highly effective in both early detection and mitigation, with recent clusters being small in size and duration. Lessons from South Korea should spark a discussion on epidemic response.
Imagining Exoplanets: Visualizing Faraway Worlds Using Global Climate Models

In the past decade, we’ve discovered over 4,000 exoplanets1, or faraway worlds orbiting other stars. However, we can’t yet take a clear picture of any of them, so how can we begin to imagine what they look like? Three teams at NASA’s Goddard Space Flight Center developed a unique approach to tackling this problem for an exoplanet called TOI-700 d. By combining 3D climate models, a newly-developed module for an exoplanet visualization tool, and Adobe After Effects, they successfully visualized possible scenarios for the planet (Figure 1) and offer an effective model for approaching future discoveries.
SUBMILLIMETER RECOMBINATION LINES IN DUST-OBSCURED STARBURSTS AND ACTIVE GALACTIC NUCLEI

We examine the use of submillimeter (submm) recombination lines of H, He, and He^+ to probe the extreme ultraviolet (EUV) luminosity of starbursts (SBs) and active galactic nuclei (AGNs). We find that the submm recombination lines of H, He, and He^+ are in fact extremely reliable and quantitative probes of the EUV continuum at 13.6 eV to above 54.6 eV. At submm wavelengths, the recombination lines originate from low energy levels (n = 20-50). The maser amplification, which poses significant problems for quantitative interpretation of the higher n, radio frequency recombination lines, is insignificant. Lastly, at submm wavelengths, the dust extinction is minimal. The submm line luminosities are therefore directly proportional to the emission measures (EM_(ION) = n_e × n_(ion) × volume) of their ionized regions. We also find that the expected line fluxes are detectable with ALMA and can be imaged at ~0."1 resolution in low redshift ultraluminous infrared galaxies. Imaging of the H I lines will provide accurate spatial and kinematic mapping of the star formation distribution in low-z IR-luminous galaxies, and the relative fluxes of the H I and He II recombination lines will strongly constrain the relative contributions of SBs and AGNs to the luminosity. The H I lines should also provide an avenue to constraining the submm dust extinction curve.
Endocytic Adaptors in Cardiovascular Disease

Endocytosis is the process of actively transporting materials into a cell by membrane engulfment. Traditionally, endocytosis was divided into three forms: phagocytosis (cell eating), pinocytosis (cell drinking), and the more selective receptor-mediated endocytosis (clathrin-mediated endocytosis); however, other important endocytic pathways (e.g., caveolin-dependent endocytosis) contribute to the uptake of extracellular substances. In each, the plasma membrane changes shape to allow the ingestion and internalization of materials, resulting in the formation of an intracellular vesicle. While receptor-mediated endocytosis remains the best understood pathway, mammalian cells utilize each form of endocytosis to respond to their environment. Receptor-mediated endocytosis permits the internalization of cell surface receptors and their ligands through a complex membrane invagination process that is facilitated by clathrin and adaptor proteins. Internalized vesicles containing these receptor-ligand cargoes fuse with early endosomes, which can then be recycled back to the plasma membrane, delivered to other cellular compartments, or destined for degradation by fusing with lysosomes. These intracellular fates are largely determined by the interaction of specific cargoes with adaptor proteins, such as the epsins, disabled-homolog 2 (Dab2), the stonin proteins, epidermal growth factor receptor substrate 15, and adaptor protein 2 (AP-2). In this review, we focus on the role of epsins and Dab2 in controlling these sorting processes in the context of cardiovascular disease. In particular, we will focus on the function of epsins and Dab2 in inflammation, cholesterol metabolism, and their fundamental contribution to atherogenicity.
Online Learning and Pricing for Service Systems with Reusable Resources

We consider a price-based revenue management problem with finite reusable resources over a finite time horizon. Stochastically arrived customers request an exponentially distributed service time and may balk and renege given insufficient resource. The resource unit, upon completion of serving one customer, can be released to serve the next customer immediately. The arrival, service, balking, and reneging rates all depend on the price being offered. In this paper, we assume that the firm does not know the mappings between these rates and prices, and thus it makes adaptive pricing decisions in each period based only on past sales to maximize the cumulative revenue. We propose two new multi-armed bandit (MAB) based learning algorithms, termed Batch Upper Confidence Bound (BUCB) algorithm and Batch Thompson Sampling (BTS) algorithm, for finding near-optimal pricing policies. Compared with prior pricing and MAB literature, the salient difficulties of this problem lie in (i) the unknown rate-and-price mapping information, (ii) the dynamic nature of reusable resources being committed over time, (iii) the transient behavior of the service system when the price changes, and (iv) unbounded and heavy-tailed distributions of observed random variables. Our proposed algorithms contain a Warm-up Phase to eliminate the heavy-tail effects and a Learning Phase to identify the optimal price. Our algorithms separate the Learning Phase into successive operational batches and select a price from a prescribed set in each batch using past sales collected in previous batches. The performance measure is cumulative regret, which is the difference between the revenue attained by our approach and by a clairvoyant optimal pricing policy under full distributional information. We prove that the cumulative regret is $O(\sqrt{PT\log (T)})$, where $T$ is the total number of time periods and $P$ is the cardinality of the feasible price set, and the result matches the lower bound up to a logarithmic factor. As an intermediate step, we also develop a coupling analysis for analyzing the time for a queue to reach the steady state from an empty state or from a steady state under another set of system parameters. Our numerical experiments demonstrate and confirm the efficacy of the proposed BUCB and BTS algorithms.
Inhibition of autophagy mitigates cell migration and invasion in thyroid cancer.

Abstract Background Autophagy is a highly conserved process for maintaining cellular homeostasis. Upregulation of autophagy promotes metastasis by promoting the cancer stem cell state while also stimulating tumor cell migration and invasion. We hypothesized that autophagy upregulation would be critical for cancer stem cell maintenance as well as cellular migration and invasion in thyroid cancer. Methods Validated papillary (MDA-T32, MDA-T68), follicular (FTC-133), and anaplastic (ATC-8505c) human thyroid cancer cell lines in culture were first assessed for autophagic capacity after bafilomycin clamping. Cancer stem cells were quantified by flow cytometry for aldehyde dehydrogenase and thyrosphere formation assay. Scratch migration and Matrigel invasion assays were performed in the presence of known autophagy inhibitors: Lys05, chloroquine, and FIP200siRNA. Results Autophagy activity was observed across all cell lines. Thyrosphere formation, aldehyde dehydrogenase activity, and CD44 expression were reduced with inhibition of autophagy in MDA-T32, MDA-T68, FTC-133, and 8505c cells. Similarly, cell migration and invasion were attenuated: 42% (FIP200siRNA), 78% (Lys05), P Conclusion Autophagy is upregulated across multiple thyroid cancer subtypes. In thyroid cancer cell lines, inhibition of autophagy attenuates cancer stem cell viability, cell migration, and invasion suggesting a role for autophagy in the progression of thyroid cancer. Greater understanding of autophagy regulation in thyroid cancer will aid in developing targeted therapeutics.
Chapter 26 The Rapid Isolation, High-Resolution Electrophoretic Characterzation, and Purification of Nuclear Proteins

Publisher Summary This chapter describes the methods for the rapid isolation, high-resolution electrophoretic characterization, and purification of nuclear proteins. The chapter discusses a procedure for solubilizing “total” protein either from whole nuclei, from subnuclear preparations, or from various chromatographic or density-gradient fractions. The procedure yields nondegraded protein free of nucleic acid and polysaccharide contaminants, and following a single dialysis it is ready to load on high-resolution polyacrylamide gels. The electrophoretic procedures are also described. The procedures allow the direct visualization and quantitation of hundreds of polypeptides in submicrogram amounts. Selected procedures for obtaining purified proteins so that more complete characterizations of individual proteins can be obtained are outlined. The methods described for purifying specific polypeptides are reliable but yield denatured protein. The procedures outlined in the chapter can be instrumental in monitoring the progress of attempts to characterize nuclear proteins through more classical biochemical techniques. The methods for the protein purification through preparative sodium dodecyl sulfate (SDS)-gel electrophoresis and isoelectric focusing are also discussed.
Formulation and Solution Strategies

The basic field equations of elasticity theory have now been developed, and comprise a system of differential and algebraic relations among the stresses, strains, and displacements that express particular physics at all points within the body under investigation. In this chapter we wish to complete the general formulation by first developing boundary conditions appropriate for use with the field equations. These conditions specify the physics that occur on the boundary of a body, and generally provide the loading inputs that physically create the interior stress, strain, and displacement fields. While the field equations are the same for all problems, boundary conditions will be different for each problem. Therefore, proper development of boundary conditions is essential for problem solution, and thus it is important to acquire a good understanding of such development procedures. Combining the field equations with boundary conditions then establishes the fundamental boundary-value problems of the theory. This will eventually lead us into two different formulations, one in terms of displacements and the other in terms of stresses. Because these boundary-value problems are difficult to solve, many different strategies have been developed to aid in problem solution. We review, in a general way, several of these strategies, and later chapters incorporate many of these into the solution of specific problems.
Weaning from Mechanical Ventilation

During the past 25 years, there has been a significant increase in the number of patients that receive mechanical ventilation as a means of life support during surgery or life-threatening medical illness. Although mechanical ventilation has clear-cut benefits, it is also associated with a significant number of complications, such as decreased cardiac output, increased intracranial pressure, ventilator-associated pneumonia (VAP), and ventilator-induced lung injury (VILI). In addition, mechanical ventilation is expensive and hinders efficient patient movement through the intensive care unit.
Effect of Transjugular Intrahepatic Portosystemic Shunt on Thrombocytopenia Associated with Cirrhosis

Thrombocytopenia is a frequent complication of cirrhosis. Its pathogenesis is not well known, but it has been suggested that splenic congestion induced by portal hypertension may be a major contributory factor. However, the available data regarding the effect of portal decompression either by surgical shunts or transjugular intrahepatic portosystemic shunt (TIPS) on peripheral platelet count in cirrhotics is conflicting. We studied the effects of TIPS on platelet count and mean platelet volume, following a successful TIPS placement. The platelet count had a tendency to decrease but was not statistically significant (120,100 ± 72,100/mm3 before TIPS vs 99,800 ± 51,400/mm3 after TIPS). The mean platelet volume remained essentially unchanged (9.8 ± 1.5 fL before TIPS and 9.9 ± 1.5 fL after TIPS). These results confirm that TIPS has an unpredictable effect on platelet count in cirrhotic patients with thrombocytopenia. The lack of a consistent increase in the peripheral mean platelet volume following TIPS placement suggests that TIPS is unable to significantly enhance the release of platelets sequestered in the splenic compartment in portal hypertension.
Cooler winters as a possible cause of mass extinctions at the Eocene/Oligocene boundary.

The Eocene/Oligocene boundary, at about 33.7 Myr ago, marks one of the largest extinctions of marine invertebrates in the Cenozoic period1. For example, turnover of mollusc species in the US Gulf coastal plain was over 90% at this time2,3. A temperature change across this boundary—from warm Eocene climates to cooler conditions in the Oligocene—has been suggested as a cause of this extinction event4, but climate reconstructions have not provided support for this hypothesis. Here we report stable oxygen isotope measurements of aragonite in fish otoliths—ear stones—collected across the Eocene/Oligocene boundary. Palaeotemperatures reconstructed from mean otolith oxygen isotope values show little change through this interval, in agreement with previous studies5,6. From incremental microsampling of otoliths, however, we can resolve the seasonal variation in temperature, recorded as the otoliths continue to accrete new material over the life of the fish. These seasonal data suggest that winters became about 4 °C colder across the Eocene/Oligocene boundary. We suggest that temperature variability, rather than change in mean annual temperature, helped to cause faunal turnover during this transition.
Federated identity-management protocols

For authentication, one answer to the workshop question “where have all the protocols gone?” is “into federated identity management”. At least this is what many influential industrial players are currently striving for. The best-known examples are Microsoft Passport, the Liberty Alliance's proposals, and WS-Federation. While there have been many political discussions about Passport, in particular its privacy, and some technical studies of operational risks, there is almost no public literature about the actual protocols and their security. We start with an overview of the driving factors in this space, the security properties desirable and achievable under the given design constraints, and the protocols proposed so far. We present a new protocol, BBAE, with better privacy and scalability, i.e., absence of single points of control, than prior proposals. We also discuss particular difficulties of rigorously treating a protocol that can be a profile in current standardization efforts.
The Fast Food Industry: Company Benefits and Stress

The purpose of this research was to obtain feedback from employees and management personnel in the fast food industry and: (1) identify benefits most and least desired; (2) identify stress factors ...
Gas mixtures for spark gap closing switches with emphasis on efficiency of operation

The efficient operation of a spark gap closing switch requires a gaseous medium with large breakdown strength, low conduction voltage, and a short formative time lag. Gas properties necessary to achieve these requirements are identified and discussed. Based on available knowledge of such properties, a number of binary (e.g., c-C/sub 4/F/sub 8/, or l-C/sub 3/F/sub 6/, or n-C/sub 4/F/sub 10/, or C/sub 3/F/sub 8/, or C/sub 6/F/sub 6/ in Ar or He or H/sub 2/) and ternary gas mixtures (e.g., c-C/sub 4/F/sub 8/, or n-C/sub 4/F/sub 10/, or C/sub 3/F/sub 8/ in Ar or He + C/sub 2/H/sub 2/ or another low ionization onset additive) have been identified which may be suitable for use in spark gap closing switches.
Antisperm contraceptive vaccines: where we are and where we are going?

Citation Naz RK. Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 2011; 66: 5–12 This is a review of current status and future perspectives on the development of antisperm contraceptive vaccines (CV) and immunocontraceptives. The development of antisperm CV is an exciting proposition. There is a strong rationale and recent data indicating that this proposition can translate into reality. The search for novel sperm-specific antigens/genes, that can be used for CV, continues using various recent developing technologies. Various approaches of proteomics, genomics, reproductive biology, mucosal immunity and vaccinology and several novel technologies such as gene knockout technology, phage display technology, antibody engineering, differential display technique, subtractive hybridization, and hybridoma technology are being used to delineate sperm-specific antigens and construct CV. Various sperm antigens/genes have been delineated, cloned, and sequenced from various laboratories. Vaccination with these sperm antigens (recombinant/synthetic peptide/DNA) causes a reversible contraceptive effect in females and males of various animal species, by inducing a systemic and local antisperm antibody response. The efficacy is enhanced by combination vaccination, including peptides based on various sperm antigens. Several human novel scFv antibodies with unique complementarity-determining regions (CDRs), that react with specific well-defined fertility-related sperm antigens, have been synthesized. These human infertility-related antibodies may find application in the development of novel immunocontraceptives. Besides finding the novel sperm antigens, the present and future focus is on enhancing the immunogenicity, bioefficacy, and on obliterating the inter-individual variability of the immune response, and proceeding for primate and human clinical trials. Multi-epitope vaccines combining sperm proteins involved in various steps of fertilization cascade have been found to enhance the immunogenicity and bioefficacy of the contraceptive effect. The in vitro synthesis of infertility-related human scFv antibodies may provide unique once-a-month immunocontraceptives, the first of its kind, for human use. The multi-epitope CV and preformed engineered human antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response.
Generation of a Transcriptome in a Model Lepidopteran Pest, Heliothis virescens, Using Multiple Sequencing Strategies for Profiling Midgut Gene Expression

Heliothine pests such as the tobacco budworm, Heliothis virescens (F.), pose a significant threat to production of a variety of crops and ornamental plants and are models for developmental and physiological studies. The efforts to develop new control measures for H. virescens, as well as its use as a relevant biological model, are hampered by a lack of molecular resources. The present work demonstrates the utility of next-generation sequencing technologies for rapid molecular resource generation from this species for which lacks a sequenced genome. In order to amass a de novo transcriptome for this moth, transcript sequences generated from Illumina, Roche 454, and Sanger sequencing platforms were merged into a single de novo transcriptome assembly. This pooling strategy allowed a thorough sampling of transcripts produced under diverse environmental conditions, developmental stages, tissues, and infections with entomopathogens used for biological control, to provide the most complete transcriptome to date for this species. Over 138 million reads from the three platforms were assembled into the final set of 63,648 contigs. Of these, 29,978 had significant BLAST scores indicating orthologous relationships to transcripts of other insect species, with the top-hit species being the monarch butterfly (Danaus plexippus) and silkworm (Bombyx mori). Among identified H. virescens orthologs were immune effectors, signal transduction pathways, olfactory receptors, hormone biosynthetic pathways, peptide hormones and their receptors, digestive enzymes, and insecticide resistance enzymes. As an example, we demonstrate the utility of this transcriptomic resource to study gene expression profiling of larval midguts and detect transcripts of putative Bacillus thuringiensis (Bt) Cry toxin receptors. The substantial molecular resources described in this study will facilitate development of H. virescens as a relevant biological model for functional genomics and for new biological experimentation needed to develop efficient control efforts for this and related Noctuid pest moths.
The Mobile Element Systems in Maize

Mobile element systems in maize have evolved from a distant curiosity of the 1950s to a prominent subject of study and research of the 1980s that has brought into the scientific arena a large number of investigators. This was largely stimulated by the findings associated with the IS elements, the Mu1 virus, and the Tn series in bacteria.
Effect of viscosity on retention time and hydrodynamic lift forces in sedimentation/steric field-flow fractionation

Abstract Particles entrained in fluid flow between parallel bounding walls tend to be driven by hydrodynamic forces, acting perpendicular to the direction of flow, towards certain equilibrium positions between the walls. Sedimentation field-flow fractionation is a technique that is well suited to the measurement of these forces, particularly in the regions close to the walls. Forces much stronger than those due to fluid inertial effects are commonly observed in the near-wall regions. A study is presented here of the influence of carrier fluid viscosity on these hydrodynamic lift forces. The carrier viscosity is varied via two different methods: (1) various ternary mixtures of water, glycerol, and ethanol were used that varied in viscosity while being of constant density and (2) the temperature of the FFF system was raised, changing the carrier viscosity while not significantly altering its density. The near-wall lift forces are shown to be dependent on fluid viscosity. An empirical equation describing the apparent dependence is presented.
Performance of Fukuda Stepping Test as a function of the severity of caloric weakness in chronic dizzy patients.

Background: The purpose of the Fukuda Stepping Test (FST) is to measure asymmetrical vestibulospinal reflex tone resulting from labyrinthine dysfunction. The FST is a low cost evaluation for dizzy patients; however, when compared with gold standard caloric irrigation unilateral weakness (UW) value $25%, the FST has not been shown to be a sensitive tool for identifying unilateral vestibular hypofunction. Purpose: The purpose of this technical report is to further evaluate the clinical utility of FST with and without headshake as a function of increased caloric asymmetry for individuals with unilateral peripheral vestibular pathology. Research Design: Retrospective review of FST results with and without head shaking component as compared to gold standard, caloric irrigation UW outcome values at four severity levels: 0‐24% UW (normal caloric value); 25‐50% UW (mild caloric UW); 51‐75% UW (moderate caloric UW); 76‐100% UW (severe caloric UW).
L-asparaginase from Erwinia carotovora. An improved recovery and purification process using affinity chromatography.

A large-scale process was developed to purify L-asparaginase from submerged cultures ofErwinia carotovora. Cells from 880 L of fermentation broth were harvested and washed using a plate and frame type filter press. A cellular acetone powder was prepared from the washed cells by suspending the cells twice in acetone and the residual acetone was removed by washing the acetone powder in the filter press with 10 mM phosphate buffer (pH 7.0). The cellular acetone powder was extracted with 10 mM borate buffer at pH 9.5. The enzyme-rich borate extract was recovered by filtration and clarified by an in-line bag filter. The filtrate was adjusted to pH 7.5 and filtered through a 1-µm bag filter precoated with Celite and then through a 0.22-µm cartridge filter. The cell-free extract, containing 21xl06 IU of enzyme and 448 g of total protein, was applied to an L-Asparagine Sepharose 6 Fast Flow affinity column (9 L) using a bag filter loaded with Cell Debris Remover as an in-line prefilter. The affinity gel was prepared by coupling L-Asn at pH 9.0 to epoxy-activated Sepharose 6 Fast Flow beads. A total of 14x106 IU of enzyme (35 g protein) was eluted at pH 9.0 in 10.5 L. The eluted enzyme was determined to be greater than 90% pure using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The total process time from whole broth to affinity
COLD-PCR: a new platform for highly improved mutation detection in cancer and genetic testing

PCR is widely employed as the initial DNA amplification step for genetic testing and cancer biomarker detection. However, a key limitation of PCR-based methods, including real-time PCR, is the inability to selectively amplify low levels of variant alleles in a wild-type allele background. As a result, downstream assays are limited in their ability to identify subtle genetic changes that can have a profound impact on clinical decision-making and outcome or that can serve as cancer biomarkers. We developed COLD-PCR (co-amplification at lower denaturation temperature-PCR) [Li, Wang, Mamon, Kulke, Berbeco and Makrigiorgos (2008) Nat. Med. 14, 579-584], a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence. Consequently, COLD-PCR amplification from genomic DNA yields PCR products containing high-prevalence variant alleles that can be detected. Since PCR constitutes a ubiquitous initial step for almost all genetic analysis, COLD-PCR provides a general platform to improve the sensitivity of essentially all DNA-variation detection technologies including Sanger sequencing, pyrosequencing, single molecule sequencing, mutation scanning, mutation genotyping or methylation assays. COLD-PCR combined with real-time PCR provides a new approach to boost the capabilities of existing real-time mutation detection methods. We replaced regular PCR with COLD-PCR before sequencing or real-time mutation detection assays to improve mutation detection-sensitivity by up to 100-fold and identified novel p53/Kras/EGFR (epidermal growth factor receptor) mutations in heterogeneous cancer samples that were missed by all existing methods. For clinically relevant micro-deletions, COLD-PCR enabled exclusive amplification and isolation of the mutants. COLD-PCR is expected to have diverse applications in the fields of biomarker identification and tracing, genomic instability, infectious diseases, DNA methylation testing and prenatal identification of fetal alleles in maternal blood.
A study of factors associated with the ability to maintain weight loss

Abstract The purpose of this study was to determine whether it is possible to predict which patients will have the most success in maintaining weight loss following an in-hospital weight reduction program. Subjects included 175 severely obese women who elected hospitalization for 3 weeks while they participated in a weight reduction program (average loss, 15 pounds). They were followed for 18 to 24 months after discharge. During hospitalization the women were studied intensively, and factors associated with the etiology of obesity were measured. The Minnesota Multiphasic Personality Inventory (MMPI) and Michill Adjective Rating Scale (MARS) psychological tests were used along with a comprehensive history questionnaire containing questions on many factors implicated in the etiology of obesity, including weight history, medical history, eating habits, obesity of family members, and demographics. Of the 89 factors examined, only 3 were found to be significantly related to an ability to maintain weight loss following discharge: the Control and Responsibility scales of the MMPI and a combination of number of meals a day and time of strong appetite. These factors, though statistically significant, were not adequate to predict which women would be able to maintain weight loss. The lack of importance of a large number of common etiologic factors in predicting weight loss suggests that future studies should concentrate on determining what etiologic factors change in subjects losing weight and what factors enable these subjects to make the necessary changes.
Additional notes on Tubiluchus corallicola (Priapulida), based on scanning electron microscope observations

Cuticular differentiations on the body surface and the pharyngeal armature of adult Tubiluchus corallicola van der Land were examined with the scanning electron microscope. The morphology of abdominal tumuli, flosculi and tubuli, and of pectinate teeth and fimbrillae on the pharynx is described, and an attempt is made to interpret their functional properties. Taking into account the structural details, relative size, and topographic arrangement in relevance to interaction with the interstitial environment, we assume that tumuli are protective, flosculi chemoreceptive, and tubuli adhesive, and that the pharyngeal armature is a scraping mechanism for feeding on epigrowth on sand grains.
U.S. government recognizes new institutional form

Abstract A new institutional form has been growing in the United States since World War II for helping to accomplish technology-intensive public programs and improve public policy. The form — a so-called “Federally-Funded Research and Development Center” (FFRDC) — has now been officially recognized at a very high level of the Government. This article describes FFRDCs and their history, lists the important roles they can play on public problems, and concludes that the advantages they offer will not be fully utilized if they continue to be treated by some as an anomaly in the institutional makeup of the U.S. economy.
Pain management in the trauma setting

One critical aspect of trauma management is dealing with pain. It is, nowadays, well understood that appropriate treatment of pain in injured patients would improve care results. Injured patients are often experiencing considerable pain while being clinically unstable. Such instability makes these patients susceptible to analgesic interventions. Morbidity and mortality are high among trauma patients due to various effects on their vital systems. Trauma complications, such as hypovolemia, coagulopathies, and head or spine injuries, are frequently encountered and would limit several pain relief approaches. In the recent decades, there have been significant advances in posttraumatic pain management. This added to the increased awareness of the consequences of undertreating posttraumatic pain, has produced adaptation of therapeutic concepts, such as multimodal and multidisciplinary approaches to pain in injured patients. The following text serves as a concise discussion of the management of pain in the trauma setting. We outlined posttraumatic pain concept, pathophysiology, clinical presentation, clinical approach and treatment. Towards the end of the text, we devoted special headlines to discuss some specific scenarios that might require a particular management.
Selective area epitaxy of InGaN quantum well triangular microrings with a single type of sidewall facets

Abstract Triangular microrings have been formed by selective area epitaxy of GaN and InGaN quantum wells (QWs) on patterned (0 0 0 1) AlN/sapphire. SiO 2 patterns consist of triangular ring openings oriented with edges parallel to two different orientations. InGaN QW microrings with each edge parallel to the 〈1 1 0 0〉 direction have very rough sidewalls while microrings with each edge parallel to the 〈1 1 2¯ 0〉 direction exhibit well formed and smooth sidewalls as a result of the generation of a single type of {1 1 0 1} facets on the inner and outer sidewalls. These {1 1 0 1} facets demonstrate similar cathodoluminescence (CL) spectra that appear to be the superposition of two peaks at photon energies ∼2.5 eV (500 nm) and 2.7 eV (460 nm). Moreover, spatially matched striations are observed in the CL intensity images and surface morphologies of the {1 1 0 1} sidewall facets. The observed striations are found to be related to subtle surface morphologies of the underlying GaN structures.
A yeast protein similar to bacterial two-component regulators

Many bacterial signaling pathways involve a two-component design. In these pathways, a sensor kinase, when activated by a signal, phosphorylates its own histidine, which then serves as a phosphoryl donor to an aspartate in a response regulator protein. The Sln1 protein of the yeast Saccharomyces cerevisiae has sequence similarities to both the histidine kinase and the response regulator proteins of bacteria. A missense mutation in SLN1 is lethal in the absence but not in the presence of the N-end rule pathway, a ubiquitin-dependent proteolytic system. The finding of SLN1 demonstrates that a mode of signal transduction similar to the bacterial two-component design operates in eukaryotes as well.
Autologous and allogeneic cellular therapies for high-risk pediatric solid tumors.

Since the 1950s, the overall survival (OS) of children with cancer has gone from almost zero to approaching 80%. While there have been notable successes in treating solid tumors such as Wilms tumor, some childhood solid tumors, exemplified by diseases like high-risk neuroblastoma and metastatic sarcomas, have continued to elude effective therapy[1]. With the use of megatherapy techniques such as tandem transplantation, dose-escalation has been pushed to the edge of dose-limiting toxicities, and any further improvements in event-free survival (EFS) will have to be achieved through novel therapeutic approaches. In this chapter, we will review the status of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for many pediatric solid tumor types. The vast majority of the clinical experience in transplant for pediatric solid tumors is in the autologous setting, so we will review some general principles of autologous HSCT, followed by an examination of HSCT for diseases such as Hodgkin disease, Ewing sarcoma, and neuroblastoma. Finally, we will look to the future of cell-based therapies by considering some experimental approaches to effector cell therapies. (1) Principles of autologous HSCT Prior to the introduction of high-dose chemotherapy (HDC) with autologous stem cell rescue (also called autologous HSCT), marrow tolerance was the limiting factor in the escalation of chemotherapy for the treatment of malignancies. With the ability to safely harvest, store and re-infuse a patient’s own hematopoietic stem cells, doses of cytotoxic therapies for cancer could safely proceed beyond marrow tolerance, thereby allowing more intense treatment of certain malignancies. Two approaches to the use of HDC with stem cell rescue include: (1) myeloablative regimens, meaning that no hematopoietic recovery can occur without the stored HSCs; and (2) sub-myeloablative HDC regimens in which stem cell rescue is used to speed recovery, decrease toxicity and decrease the interval between courses of chemotherapy, although it is not absolutely required for engraftment[2–3]. Although the increased treatment intensity may improve disease-free survival for patients with some malignancies, this must be balanced with the increased treatment-related mortality associated with the higher doses of cytotoxic agents, as well as the potential late effects of more intense cytotoxic treatments and radiotherapeutic regimens in young children. Criteria that may help define circumstances in which HDC with stem cell rescue would be most beneficial include: (1) a tumor with good response to induction chemotherapy, but a poor 3 or 5-year EFS; and (2) a HDC regimen that can utilize multiple agents active against the disease, especially if the agents differ from those used during induction therapy. Although the use of HDC with stem cell rescue is controversial in most diseases, diseases such as Hodgkin disease and high-risk neuroblastoma (discussed below) meet the design criteria listed above and have demonstrated improved outcomes in clinical trials.
Ultrastructure and Ecology of Calycomonas ovalis Wulff, 1919, (Chrysophyceae) and Its Redescription as a Testate Rhizopod, Paulinella ovalis N. Comb. (Filosea: Euglyphina)1

An exceptional bloom (109 cells/liter) of a unicellular alga, Aureococcus anophagefferens, in Narragansett Bay, RI, was accompanied by unusually high numbers (6 times 106 tests/liter) of vase-shaped cells of Calycomonas ovalis Wulff, hitherto considered a flagellated chrysophyte. Phase contrast light microscopy showed the characteristic oval lorica or test of C. ovalis, ca. 3.0 times 4.5 μm. Transmission electron microscopy of thin sections of natural populations revealed, however, that C. ovalis is actually a rhizopod within a test of electron-dense scales. This estuarine, planktonk testacean extends a pseudopodium through a narrow pseudostome and lacks chloroplasts or flagella. It is a bacterivore and feeds primarily on unicellular cyanobacteria. The morphology, ultrastructure, and cell division of C. ovalis are described. These characteristics place C. ovalis with the genus Paulinella (Sarcodina: Filosea: Euglyphina), which at present contains the single species, P. chromatophora Lauterbom. Calycomonas ovalis is thus assigned to Paulinella as P. ovalis n. comb.
Teleconsultation with a developing country: student reported outcomes of learning.

This qualitative study explored the benefits of implementing (international) teleconsultation in a Master of Science in Occupational Therapy (MSOT) curriculum. Twenty-one students provided supervised teleconsultative services to individuals with disabilities in Guatemala and were responsible for completing assessments, setting goals, and providing resources to address goals and improve quality of life. Data were collected through student presentations and coded for relevant themes. Analysis revealed new learning in the areas of the occupational therapy process, cultural awareness, and technology. Three themes emerged: Increased Understanding of Awareness of and Challenges to Working with People of Different Culture ; Need for Adaptability and Flexibility as Practicing Clinicians ; Emerging Role of Technology in Occupational Therapy. Based on results from this study, occupational therapy academicians should consider implementing similar programs into curricula and conduct related research in order to promote not only student learning, but also to advance the use of technology in occupational therapy practice.
Inorganic-Organic Hybrid Nanocomposites for Photovoltaic Applications

Hybrid photovoltaic concepts based on a nanoscale combination of organic and inorganic semiconductors are promising way to enhance the cost efficiency of solar cells through a better use of the solar spectrum, a higher ratio of interface-to-volume, and the flexible processability of polymers. In this work, two types of thin film solar cells have been developed. In both types of solar cells, poly-N-vinylcarbazole (PVK) is used as electron donor, cadmium sulfide (CdS) and titanium dioxide (TiO2) nanocrystals are used as electron acceptors, respectively. Since TiO2 has a wide band gap and can only absorb UV light, in the second type of solar cell, ruthenium dye is used as photo-sensitizer. The preliminary results of photoconductive and photovoltaic characteristics of these two inorganic-organic composites are presented.
Induction of p202, a modulator of apoptosis, during oncogenic transformation of NIH 3T3 cells by activated H-Ras (Q61L) contributes to cell survival.

Previous studies have revealed that p202 (52 kDa), an interferon (IFN) and differentiation-inducible protein, negatively regulates cell proliferation and modulates cell survival. However, the role of p202 in transformed cells remains to be investigated. Here we report that constitutive expression of oncogenic H-Ras (Q61L) in NIH 3T3 cells, which resulted in cell transformation, was associated with increases in the steady-state levels of 202 RNA and protein. Interestingly, the increase in p202 levels in transformed cells correlated with increases in the activity of the transcription factor c-Jun/AP-1, which bound to the two potential AP-1 DNA binding sites (the AP-1CS1 and AP-1CS2) in the 5'-regulatory region of the 202 gene in gel mobility shift assays. Furthermore, the site-directed mutagenesis, coupled with promoter-reporter analyses, revealed that these two AP-1 DNA binding sites contribute to the regulation of the 202 gene in Ras transformed cells. Because treatment of transformed cells with a specific inhibitor of MEK (PD 98059) resulted in significant decreases in the levels of p202, these observations raise the possibility that in transformed cells Ras/Raf/MEK pathway regulates the transcriptional activation of the 202 gene. Significantly, decreases in the levels of p202 in Ras transformed NIH 3T3 cells under reduced serum conditions increased the susceptibility to apoptosis. Collectively, our observations support the idea that the transcriptional increases in the levels of p202 by oncogenic H-Ras in NIH 3T3 cells are needed for cell survival.
41 Renal Transplant Surveillance Biopsy Results in Children Receiving Steroid Free Immunosuppression

Introduction: Interstitial fibrosis (IF) is frequently present in renal biopsy specimens obtained from transplant recipients who receive tacrolimus (TAC) and prednisone as maintenance immunosuppression, especially in those in whom the associated trough TAC levels are elevated. In contrast, little information exists on the kidney histology of patients on a steroid free (SF) immunosuppression regimen. The role that the exposure to TAC [trough levels or area under the curve (AUC)] has on biopsy findings remains poorly defined.
Automated Contour Ordering In Moire Topograms

A method is described for ordering the fringes in an ordinary moire topogram. It requires no a priori shape information and resolves "hill-or-valley" ambiguities using local surface reflectance properties. The theoretical and practical constraints of this method are discussed, and analyzed examples are presented as experimental evidence.
Geometry of the minimum zone flatness functional: planar and spatial case

The zone straightness and flatness functional is constructed from the definition of the measure. The geometry of the straightness functional is illustrated in the plane, and in three dimensions, a novel means to visually represent flatness is described using the zone separation body. The zone separation body is a new construction that is uniquely associated with every measurement dataset and can be used to represent the flatness functional visually.