cssi/SciSciGPT-SciSciNet huggingface dataset:
The Negative Reminding Effect: Reminding Impairs Memory for Contextual Information

Abstract Encountering events that are meaningfully related to prior episodes can prompt retrieval of those prior events. Reminders are events that prompt retrieval of prior learned information, while reminded materials are the events that are retrieved in response. Reminders are an important component of efficient and effective cognition because they partially automate the process of bringing relevant prior knowledge to bear on novel situations. Across four experiments, we investigated whether reminders boosts memory for the entire prior reminded episode or for only specific aspects of prior experiences that are relevant to the reminder. To do so, we combined a reminding procedure with a paradigm for measuring memory for the incidental context of encoding. Participants studied lists of words in which semantically related pairs (e.g., “volcano” and “erupt”) were presented across brief lags and in different color contexts. Memory for the content and color of the first-presented word in pairs (the reminded information) was measured. Recall of related word pairs was consistently greater than recall of unrelated pairs, in agreement with prior work on the reminding effect. However, when the color of related words differed across the pair, memory for the color of the reminded words was impaired compared to unrelated words. The results support a view of reminding as a leveling and sharpening process in which memory for the focal content of reminded episodes is enhanced, but differences in peripheral details are smoothed over. Such a process can lead to the acquisition and application of prototypical knowledge over experience.
THE ANSWER TO A MAIDEN’S PRAYER: HOMER CUMMINGS AND THE ORIGINS OF THE 1937 COURT PACKING PLAN

iv Introduction 1 Chapter OneThe Gathering Storm 13 Chapter TwoThe Battle for Pubic Opinion 46 Chapter Three“The Answer to a Maiden’s Prayer 75 Conclusion 110 Bibliography 121 Vita 124
Envisioning Automated Vehicles within the Built Environment: 2020, 2035, and 2050

This paper describes the purpose, methodology, instruments, organization and participant discussion results at the Friday Ancillary workshop: “Envisioning Automated Vehicles within the Built Environment: 2020, 2035, 2050” during the TRB/AUVSI Automated Vehicles Symposium 2014. This hands-on interactive workshop included 110 participants working as small teams of experts from a wide range of fields—city planning, infrastructure, architecture, car design, engineering, software, and systems—who collaborated on specific built world scenarios focused on the challenges and opportunities for AV/ATN implementation in the United States by regional transportation planning organizations.
Vaginal Injury During Stapled Anastomosis

We have witnessed the evolution of the stapler technology in the field of colorectal surgery within the last three decades. Improvements in technical innovations have allowed the surgeons to be able to create easier and safer stapled ultralow colorectal, coloanal, and ileal-pouch anal anastomosis. However, our innovative spirit of pushing the limits of low pelvic anastomosis on behalf of our patients has inevitably brought some complications with it. Vaginal injury during stapled anastomosis is a rare, but devastating complication, which can result in severe consequences if it is not recognized and appropriately addressed at the time of surgery. The most common reasons for this complication are patient-related factors such as narrow pelvis or reoperative pelvic surgery and more importantly lack of familiarity or respect for the pelvic anatomy and dissection by surgeons. In this chapter, we will share our experience on how to avoid vaginal injury, and when it happens how to fix this humbling and difficult complication.
A Real-Time Display for Tactile Images

The tactile array sensor is a key component of the multisensory integration work at the General Robotics and Active Sensory Perception Laboratory (GRASP Lab) at the University of Pennsylvania.
Renewable Energy in the United States

A review of studies of biomass potential in the United States finds a wide variation in the estimates. A number of specific policy-relevant questions about the potential of biofuels in the United States are answered. A recently published global analysis of the potential conflict between land needed for bioenergy and land needed for food is extended to the situation in the United States. A renewable energy supply scenario, capable of meeting the 2001 US energy demand, indicates that there is enough land to support a renewable energy system but that the utilization of biomass would be limited by its land requirement.
Synthesis and layout for analog and mixed-signal ICs in the ACACIA system

An increasing number of ICs require some core of analog circuitry for interfacing, wireless communication, multimedia data handling (speech, vision), etc. Despite substantial progress on CAD tools, these analog subsystems are still mostly designed by hand. This paper surveys progress on one proposed solution to this problem: a top-to-bottom tool suite for analog and mixed-signal designs under development at Carnegie Mellon University, called ACACIA. The principal focus of the ACACIA system is synthesis: of circuits and layouts, from cells to systems. We describe here briefly the core tools in ACACIA, focusing on cell-level circuit synthesis and layout, and mixed-signal system-level floorplanning, routing, and power grid design.
Writing Simulatable Specifications in SPECIAL

It is commonly accepted that most software systems contain large numbers of errors that are not detected until delivery and testing by the customer. Some studies have determined that errors are most likely to be introduced in the design phase; perhaps up to two-thirds of all system errors are design errors. Formal specifications can be a useful vehicle for exposing design errors by forcing attention early in the system development process on “what the system should do.” Although specifications are an improvement over, say, natural language for describing systems, even if carefully read they cannot be expected to eliminate all design errors. Fortunately, because specifications are supposed to be complete, it is in principle possible to execute them with test data exactly as one would execute code. We call such an execution of specifications module simulation, where the module is assumed to be the unit that is specified.
Symmetric Stochastic Games of Resource Extraction: The Existence of Non-Randomized Stationary Equilibrium

A two-person discounted stochastic game (see, e.g., [15] and [17] for related references) is described by a tuple S,A 1 (s),A 2(s),q,r 1,r 2,β having the following interpretation: S, a non-empty Borel subset of a Polish space, is the set of all states of the system; A i (s), a non-empty Borel subset of a Polish space, is the set of actions available to player i(= 1,2), when the state is s ∈ S. It is typically assumed that for each i = 1,2, A i (s) ⊂ A i for all s ∈ S, where the A i ’s are themselves Borel subsets of Polish spaces. q defines the law of motion of the system by associating (Borel-measurably) with each triple (s, a 1, a 2 ) ∈ S x A 1 x A 2 a probability measure q[|s, a 1, a 2 ) on the Borel subsets of S. r 1 and r 2 are bounded measurable functions on S x A 1 xA 2; the function r i is the instantaneous reward function for player i. Lastly, β is the discount factor the players employ. Periodically, the players observe a state s ∈ S and pick actions a i ∈ A i (s), i = 1,2
The effects of salmon abundance and run timing on the performance of management by emergency order

We examine the effect of uncertainty in salmon run abundance and run timing on the ability of managers to achieve escapement goals using in-season regulation of fishery openings using a detailed model of the arrival of salmon and operation of the fishery, the information available to managers, and managers’ behavior. We supplement this management strategy evaluation by examining historical management performance of sockeye salmon (Oncorhynchus nerka) fisheries from Bristol Bay, Alaska. We find that uncertainty about run timing exacerbates the effects of uncertainty about salmon abundance. Early-arriving small runs and late-arriving large runs are especially problematic, as they produce in-season data that mimic that of a typically sized run with average run timing. Managers faced with an early-arriving small run will tend to overharvest the fish, particularly the earliest-arriving component. Managers faced with a late-arriving large run will tend to underharvest the fish, and harvest the latest-arriving c...
The solubility of sodium and potassium soaps and the phase diagrams of aqueous potassium soaps

Solubility data are provided and collected for the pure sodium and potassium soaps. Hydrolysis obscures the temperatures of solution but is obviated by the presence of a small excess of alkali. Each sodium soap has a large range of temperature between fair and high solubility, whereas the potassium soaps go abruptly into solution, at almost the same temperature and concentration of each soap. The only soaps that are even moderately soluble at room temperature are potassium laurate, myristate, and oleate, the potassium salt of acids from coconut oil, and the sodium oleate. The other sodium and potassium soaps of the saturated fatty acids require elevated temperatures for solution. Phase diagrams for the five commonest potassium soaps are developed and recorded.
Preoperative planning for total hip arthroplasty

Preoperative planning for total hip arthroplasty is essential for a successful outcome. This exercise includes a systematic templating procedure with the use of standard radiographs to ensure that appropriate implants are selected. Because hip anatomy is highly variable, a careful assessment of leg length and femoral head offset is needed to reproduce normal hip biomechanics. Preoperative planning for revision hip arthroplasty requires the additional assessment of component removal, bone loss, and special implant needs.
Elastic-plastic analysis of surface flaws using a simplified line-spring model

Abstract The line-spring model has proven to be an effective tool for evaluating fracture parameters in surface-cracked plates and shells. However, application of the model requires detailed numerical computations, necessitating the availability of a specialized computer code. For approximate engineering calculations a version of the model which is more convenient to implement computationally, would be useful. In this paper a simplified line-spring model is presented along with detailed illustration of its application. The simplification is accomplished by replacing the crack front with a crack of constant depth and treating the ligament “spring” as elastic perfectly plastic. Despite its simplicity the model gives reasonably accurate predictions of fracture parameters, such as the J-integral or crack opening displacement (COD) at the root of surface cracks. This will be demonstrated by comparing analytical results for J and COD with previously published experimental data for surface-cracked steel plates.
A functional analytic approach to uniqueness of solutions to some nonlinear Cauchy problems

On demontre un theoreme abstrait puissant sur l'unicite des solutions strictes d'equations differentielles non lineaires dans des espaces de Banach
Storms, floods, and the science of atmospheric rivers

[1] Imagine a stream of water thousands of kilometers long and as wide as the distance between New York City and Washington, D. C., flowing toward you at 30 miles per hour. No, this is not some hypothetical physics problem—it is a real river, carrying more water than 7–15 Mississippi Rivers combined. But it is not on land. It's a river of water vapor in the atmosphere. Atmospheric rivers (ARs) are narrow corridors of water vapor transport in the lower atmosphere that traverse long swaths of the Earth's surface as they bind together the atmospheric water cycle (Figure 1). The characteristic (indeed defining) dimensions of these ARs are (1) integrated water vapor (IWV) concentrations such that if all the vapor in the atmospheric column were condensed into liquid water, the result would be a layer 2 or more centimeters thick; (2) wind speeds of greater than 12.5 meters per second in the lowest 2 kilometers; and (3) a shape that is long and narrow, no more than 400–500 kilometers wide, and extending for thousands of kilometers, sometimes across entire ocean basins.
Ernest Henry Starling (1866-1927) on the formation and reabsorption of lymph.

Ernest Henry Starling laid the groundwork for our modern understanding of how the interstitial fluid, which he referred to as ‘lymph', is regulated. Together with his colleague, William Bayliss, he provided the crucial insight into how fluid is driven out of the capillary to form interstitial fluid. That was to measure (estimate) the capillary pressure in different parts of the circulation and to relate changes in these pressures to altered lymph formation. In addressing how interstitial fluid re-enters the circulation, he was able to show that this occurs not only via the lymphatics, but also by re-entering the capillaries, mediated by the oncotic pressure of the plasma proteins. Starling's discoveries put to rest all notions that the processes of filtration and reabsorption of fluid are mediated by the ‘vital activity' of cells. They could be explained entirely on the basis of physic-chemical forces. Based upon his insights from animal experiments, he was able to explain the genesis of edema (dropsy) in a number of disease states, including venous obstruction, cardiac disease and inflammatory conditions.
Evaluation of various high-order-accuracy schemes with and without flux limiters

Conventional high-order schemes with reduced levels of numerical diffusion produce results with spurious oscillations in areas where steep velocity gradients exist. To prevent the development of non-physical oscillations in the solution, several monotonic schemes have been proposed. In this work, three monotonic schemes, namely Van Leer's scheme, Roe's flux limiter and the third-order SHARP scheme, are compared and evaluated against schemes without flux limiters. The latter schemes include the standard first-order upwind scheme, the second-order upwind scheme and the QUICK scheme. All the above schemes are applied to four two-dimensional problems: (i) rotation of a scalar ‘cone’ field, (ii) transport of a scalar ‘square’ field, (iii) mixing of a cold with a hot front and (iv) deformation of a scalar ‘cone’ field. These problems test the ability of the selected schemes to produce oscillation-free and accurate results in critical convective situations. The evaluation of the schemes is based on several aspects, such as accuracy, economy and complexity. The tests performed in this work reveal the merits and demerits of each scheme. It is concluded that high-order schemes with flux limiters can significantly improve the accuracy of the results.
Induction of the Manganese Superoxide Dismutase Gene by Sphingomyelinase and Ceramide

The present study reports the effect of ceramide generated by hydrolysis of membrane sphingomyelin with bacterial sphingomyelinase (SMase) and of cell-permeable ceramide analogues on the expression of manganese superoxide dismutase (MnSOD). Incubation of the rat primary astrocytes with SMase led to a time- and dose-dependent increase in MnSOD activity. The increase in MnSOD activity was accompanied by an increase in MnSOD protein and mRNA. A similar effect on the expression of MnSOD was observed with the addition of cell-permeable ceramide analogues (C2 and C6). On the other hand, C2-dihydroceramide (N-acetylsphinganine), which lacks the functional critical double bond, was ineffective in inducing the expression of MnSOD. Nuclear run-on analysis showed that SMase and ceramide increased the rate of transcription of the MnSOD gene. Besides astrocytes, SMase was also found to induce the expression of MnSOD in rat mesangial cells, C6 glial cells, PC12 cells, and human skin fibroblasts. Markedly higher expression of mRNA, protein, and activity of MnSOD in skin fibroblasts from patients with Farber disease, a human disorder with pathognomonic accumulation of ceramide due to a deficiency of ceramidase, than in normal skin fibroblasts indicate that ceramide may act as a physiological inducer of MnSOD gene expression. However, stimulation of ceramide-mediated DNA fragmentation by antisense knockdown of MnSOD suggests that induction of MnSOD by ceramide is a protective response of the cell.
Imaging of T-cell interactions with antigen presenting cells in culture and in intact lymphoid tissue

The development of an effective immune response requires cell-cell contact between T cells and antigen-bearing cells of several types (dendritic cells, B cells, infected tissue cells). Recent advances in light microscopy have led to intense investigation of the molecular events that accompany these cell interactions, especially the redistribution of membrane proteins into discrete organized subdomains within the zone of cell-cell contact termed the 'immunological synapse'. Here we discuss two aspects of our own studies in this area. First, we highlight results from our in vitro analysis of the role of the cytoskeletal ezrin, radixin, moesin adapter proteins in the exclusion of CD43 from the well-defined T cell receptor (TCR) and integrin-rich zones of the synapse. Based on the molecular mechanism uncovered in this work, we propose a new model for how TCR-signaled changes in cytoskeletal organization indirectly influence both protein distributions and the efficiency of signaling between T cell and presenting cell. We then discuss the development of a new method for dynamic visualization of T cell - dendritic cell interactions in intact lymphoid tissue. The remarkable longevity of monogamous lymphocyte-presenting cell interactions is discussed, differences between our observations and those of others are laid out in detail, and prospects for future application of this technical approach to analysis of early immune responses in lymphoid organs and of effector lymphocyte function in tissues are presented.
Public employee pensions and the local labor budget

Abstract This paper examines the causes and consequences of public employee pension funding by local governments. The pension funding decision is analyzed within the context of two models: one where current taxpayers stay and pay employees' future retirement benefits and a second model where current taxpayers move and thereby hope to avoid paying future retirement benefits. The empirical results test the alternative models for a sample of 60 large U.S. cities using data for local police and fire services. The effects of underfunding on local wages and employment is then examined and found to be significant. Implications for national pension funding policy are drawn.
High Expression of Plasmid-Encoded Tetracycline Resistance Gene inE. coliCauses a Decrease in Membrane-Bound ATPase Activity

Abstract Expression of the plasmid pBR322-encoded tetracycline-resistant gene ( tet ) is known to cause other pleiotropic effects in addition to mediating the efflux of tetracycline from bacterial host cells. We have recently reported that expression of the tet gene in plasmid pKH47, a high-copy-number derivative of pBR322, causes growth inhibition of Escherichia coli cells harboring this plasmid. In this paper we report that reduced membrane-bound ATPase activity is found in E. coli cells containing plasmid pKH47. This effect is dependent on the presence of an intact tet gene and reduces the ability of the cells to grow in a minimum medium containing succinate as the sole carbon source. The same effect is more dramatically observed in cells containing an unrelated plasmid in which tet gene expression is under the control of the tac promoter.
Application of dual-genome oligonucleotidearray-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes

Purpose: Mitochondrial disorders constitute a group of clinically and genetically heterogeneous diseases for which molecular diagnosis has been a challenge. The current procedures for diagnosis of mitochondrial DNA deletion and depletion syndromes based on Southern analysis and quantitative polymerase chain reaction are particularly inefficient for determining important parameters of deletion endpoints and percent heteroplasmy. We have developed an improved approach for routine analyses of these disorders in a clinical laboratory. Methods: A custom-designed oligonucleotide array-based comparative genomic hybridization platform was developed to provide both tiled coverage of the entire 16.6-kb mitochondrial genome and high-density coverage of nuclear genes involved in mitochondrial biogenesis and function, for quick evaluation of mitochondrial DNA deletion and depletion. Results: For initial validation, the performance of this array was characterized in 20 samples with known mitochondrial DNA deletions and 12 with apparent depletions. All previously known deletions were clearly detected and the break points were correctly identified by the oligonucleotide array-based comparative genomic hybridization, within the limits of resolution of the array. The extent of mitochondrial DNA depletion and the percentage of deletion heteroplasmy were estimated using an automated computational approach that gave results comparable to previous methods. Conclusions from subsequent application of this approach with >300 new clinical samples have been in 100% concordance with those from standard methods. Finally, for one sample, we were able to identify an intragenic deletion in a nuclear gene that was responsible for the observed mitochondrial DNA depletion. Conclusion: We conclude that this custom array is capable of reliably detecting mitochondrial DNA deletion with elucidation of the deletion break points and the percentage of heteroplasmy. In addition, simultaneous detection of the copy number changes in both nuclear and mitochondrial genomes makes this dual genome array of tremendous value in the diagnoses of mitochondrial DNA depletion syndromes.
657, a method for estimating tetrahedral bond angles

A regular tetrahedron has six spatial angles. The sum of these spatial angles for a tetrahedron with all four groups the same (CA4) is 6 × 109.4712206°. To the nearest degree that value is 657°. For a tetrahedron with one group different (CA3B), there are two different bond angles. The sum of these two angles can be approximated to be 219°, one third of 657°. For a tetrahedron with disubstitution by the same group (CA2B2), the approximate sum involves three different angles: ∠ACA + ∠BCB + 4 ∠ACB = 657°. For a tetrahedron with disubstitution by two different groups (CA2BD), the approximate sum uses four different angles: ∠ACA + ∠BCD + 2 ∠ACB + 2 ∠ACD = 657°. For a tetrahedron with all groups different (CABDE), the approximate sum comes from six angles. Examples of each type are given along with the limitations of the method.
Dithionite reduction of pyridinium salts: an AM1 study

Abstract The dithionite reduction of some simple pyridinium salts was examined using the AM1 molecular orbital approximation. The reaction is highly selective, resulting in the almost exclusive formation of the 1,4-dihydropyridine derivatives. Electronic and steric effects do not seem to be responsible for this selectivity. A study of the relative thermodynamic stabilities, as reflected by the estimated heats of formation δHf, was performed for the 1,2,1,6, and 1,4 isomers of the intermediate sulfinate and sulfinic acid adducts, and for the reaction products. The relative stability of the products ( 1,4 ⪢ 1,6 ⪢ 1,2) is in agreement with the experimental findings, which indicate the preferential formation of the 1,4 isomers, suggesting thermodynamic control of the products. An equilibration of the products by a hydride transfer with the pyridinium salt can also explain the formation of the thermo-dynamically most stable 1,4-dihydropyridines.
Rolling Planning Horizons: Error Bounds for the Dynamic Lot Size Model

A new and tight bound is placed on the error induced by imposing a finite time horizon T on the dynamic lot size model. This bound equals the value of perfect information about the data beyond the time horizon T. With this bound, one can assess the value of using the dynamic lot size model repeatedly on a rolling basis with a time horizon of T periods. When this bound is low the time horizon is long enough. When this bound is not low, it may pay to invest in forecasts of demands for later periods, thereby increasing the time horizon.
Square-IT and Plan-Merge: Decision Support Systems for High Quality Manufacturing Setup Sequences

Square-IT and Plan-Merge are software agents which assist in the process of creating manufacturing plans for small batch prismatic machined parts. Squaring is the process of generating a sequence of operations that prepares the stock so all surfaces are parallel or perpendicular to each other. Most automated process planning programs, and many machinists, perform squaring as a separate process completed prior to manufacturing the part. Although this practice simplifies planning, many opportunities for efficiency are lost when squaring and shaping the part into its final form are achieved in two completely separate plans. A far more efficient plan (i.e. fewer setups) can be achieved when squaring and feature cutting are treated as two types of operations included in a single, more globally efficient plan. Square-IT and Plan-Merge together perform this process of merging these two types of operations. The efficiency savings are dramatic. Setups can be reduced by 10 to 40 percent. Reducing set-ups also increases accuracy of the part by reducing opportunities for error. In future work we hope to adapt Square-IT and Plan-Merge so that they can be used as training tools that teach proper squaring and planning efficiency principles.Copyright © 2002 by ASME
Appearance potential study of N4,5-level of light rare earth metals and their oxides

Abstract Appearance potential spectroscopy (APS) probes the binding energy of core levels and local conduction band states of solid surfaces. Soft X-ray APS (SXAPS) and Auger electron APS (AEAPS) respectively measure the differential X-ray fluorescence and secondary electron yields as a function of incident electron energy. We have obtained the N 4,5 -level SXAPS and AEAPS spectra of La, Ce, Pr, Nd and Sm metals and their oxides. The N 4,5 -level AEAPS studies of these metals have not been reported previously. The comparison of the two spectra shows a strong resemblance. Both exhibit multiplet structure below the expected 4d excitation threshold and a broad, 10–20 eV wide peak above threshold followed by small peaks of decreasing intensity. AEAPS peaks are more intense and narrower than SXAPS peaks. The data are used to gain an understanding of the decay mechanism following the excitation of the core levels in these spectroscopies. The spectra recorded from oxidized metals do not show any major changes in the spectral features except for the chemical shift of the threshold. The shifts for all metal oxides are less than 1.0 eV except for Sm which is 2.5 eV. The similarity of the metal and oxide spectra indicates that the APS spectra are dominated by atomic rather than band effects.
Behavior of a bisphenol‐A‐based polybenzoxazine exposed to ultraviolet radiation

An interaction mechanism for a bisphenol-A-based polybenzoxazine resin exposed to ultraviolet radiation is proposed. Fourier transform infrared spectroscopy indicated that a carbonyl-containing species was formed when cured 6,69-bis(2,3-dihy- dro-3-methyl-4H-1,3-benzoxazinyl)isopropylidene (BA-m) resin was exposed to ultravi- olet radiation (l . 290 nm) in the presence of ambient air at room temperature. The isopropylidene linkage was the reactive site of cleavage and oxidation. It was apparent from model compound studies that this structure was severed, resulting in the forma- tion of a 2,6-disubstituted benzoquinone. Model compound studies also demonstrated that the BA-m polymer backbone structure, the Mannich bridge, which was present in and characterized all the polybenzoxazines, neither cleaved nor oxidized in the pres- ence of ultraviolet radiation in a detectable manner under the conditions of this study. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2687-2701, 2000
Developmental changes in young children's knowledge about the mind

Abstract In this article we propose an account of the early development of children's knowledge about the mind and report two studies designed to test a part of it. According to this “connections-representations” account, young children begin their discovery of the mental world by learning that they and other people have internal experiences or mental states that connect them cognitively to external objects and events-experiences such as seeing them, hearing them, and wanting them. Later, they realize that the same object can be seriously (other than in pretense) mentally represented in different, seemingly contradictory ways: for example, as A in appearance, B in reality, C according to their perceptual or conceptual perspective, and D according to another person's. The results of both studies confirmed the prediction that 3-year-olds would perform well on appearance-reality and perceptual perspective-taking tasks requiring only an understanding of cognitive connections, but perform poorly on tasks requiring an understanding of seemingly-contrary-to-fact mental representations. To illustrate, children of this age had little difficulty determining that they could hear but could not see a noise-making object located on the experimenter's side of a barrier, and that the experimenter could see it (connections-level tasks). In contrast, they were largely unable to say, for instance, that a toy bear held behind a large elephant mask and emitting a cat sound looked like an elephant, sounded like a cat, and really was a toy bear (representations-level tasks)—even though the experimenter had actually told them previously what it looked like, sounded like, and really was. The article concludes with speculations about the possible origins of connections and representations knowledge and observations about the significance of these acquisitions for the child's development.
Many different tumor types have polyclonal tumor origin: Evidence and implications

Few ideas have gained such strong acceptance in the scientific community as the monoclonal origin of tumors; the idea that tumors start with a single mutated cell (or a single clone of cells) that go on to accumulate additional mutations as a tumor develops. The certainty with which this concept is held by the scientific community reflects the length of time it has been unchallenged and the experimental difficulty in obtaining direct evidence to the contrary. Yet, recent findings regarding X chromosome inactivation patch size indicate that the X-linked marker data previously interpreted as evidence of monoclonal tumor origin is actually more consistent with polyclonal tumor origin, a situation where two or more cells or clones of cells interact to initiate a tumor. Although most tumors show homotypy for X-linked markers (as expected given the bias conferred by X chromosome inactivation patch size), the literature contains numerous examples of tumors with X-linked marker heterotypy, examples of which encompass 24 different tumor types. Chimeric models have yielded direct unequivocal demonstrations of polyclonality in rodent and human tumors. Also, mutational data are consistent with polyclonal tumor origin. Methods that analyze levels of tumor-associated oncogene and tumor suppressor gene mutations demonstrate that initiated cells are much more common in normal tissues than previously realized. Also, while tumors have higher levels of mutation than normal tissues, oncogenic mutations frequently are present as subpopulations within tumors, rather than as the pure mutant populations expected to develop from a single initiated cell. Understanding the mutational basis of tumor etiology has important practical significance for assessing cancer risk, as well as in modeling and treating cancer. Therefore, the scientific community needs to re-examine this issue and consider the implications of polyclonal origin for, perhaps, a majority of tumors, encompassing many different tumor types.
Novel ways for tracking rays

Rays no longer just represent the trajectories traversed by a beam of light but they describe the general transport properties of high-frequency fields. Viewed within the framework of wave spectra, ray fields are localized spectral objects synthesized by constructive spectral interference. The spectral flesh within these objects can be trimmed to the bare bones for the simplest type of ray field, a local plane wave, but must be augmented in ray transition regions near caustics, shadow boundaries, diffraction centers, etc., where more-intricate wave phenomena occur. Thus ray tracing along ray paths generally involves a succession of bare-bones and fleshed-out (uniformized) spectral entities that can furnish in a highly effective manner the amplitude and the phase of the high-frequency field in a complex environment. Relevant spectral concepts are discussed, including those for complex rays that describe evanescent fields and Gaussian beams and those leading to collective treatment of multiple reflected or diffracted contributions.
Building the Evidence Base for Integrative Approaches to Care of Cancer Survivors

Like hospice and palliative care, the integrative medicine movement began as edgy outsiders. But in the last 10–15 years, integrative oncology practices, often tied with integrative medicine programs, are being established in major medical institutions across the country. Many are embedded in medical centers that are leaders in the development and provision of the most advanced modern technologies for cancer care. This issue of JNCI Monographs focuses on the role of integrative oncology in care of cancer survivors; the editors have brought together commentaries on the “state of the science.” We at the National Center for Complementary and Alternative Medicine together with our partners in the Office of Cancer Complementary and Alternative Medicine at the National Cancer Institute are the main National Institutes of Health supporters of that science. Our shared goal is a rigorous evidence base to guide patient decisions and to help providers make sensible recommendations: a solid scientific basis, assessing both risks and benefits. Not surprisingly, since integrative oncology is a relatively new movement, the science is just beginning. It is already very clear that approaches that fall under the general rubric “integrative oncology” are meeting important and often neglected needs. Two things are driving change. In part, the integrative oncology movement is a response to patient demand. Patients are asking for change—for access to an approach to care that is seen as more “holistic,” perhaps gentler, perhaps more optimistic. Change is also being driven by providers. Some physicians, including a number of oncologists, see in the integrative medicine movement an opportunity to develop a style of practice that will facilitate changed relationships with patients: less emphasis on technical advice, more emphasis on healing, defined broadly, on provision of emotional and spiritual supports, on creation of positive expectations, on encouragement to healthy living. By and large, when integrative practitioners offer “alternative” practices, it is as a complement to modern “mainstream medicine.” And by and large, patients interested in integrated approaches, do not want (and are not well-served by) care that does not integrate effective mainstream techniques for cure, prolongation of life, or substantive palliation. National Center for Complementary and Alternative Medicine has decided, through a year-long strategic planning process (1), to focus our resources on research on benefits and risk of complementary health practices for symptom management, particularly pain management, but also fatigue, loss of sleep, loss of appetite. A variety of complementary approaches and a number of practitioners from disciplines outside mainstream medicine are increasingly part of the integrative approach to symptom management. This monograph will, we hope, stimulate continued interest in testing these approaches and in their continued improvement. Our patients deserve nothing less.
A selective approach to the management of Gunshot wounds to the back

Abstract Background Gunshot wounds to the back with retroperitoneal trajectories have been traditionally managed under the same guidelines as anterior gunshot wounds. Recent work has suggested that selective nonoperative management of anterior abdominal gunshot wounds is safe. The role of this policy in gunshot wounds to the back, where retroperitoneal organ injuries may be more difficult to detect clinically, has not been investigated. Objective To examine if selective nonoperative management based on clinical assessment is a safe alternative to mandatory exploration for gunshot wounds to the back. design Prospective study. Setting Large-volume level-1 university affiliated trauma center. Patients and Methods Two hundred and three consecutive patients with gunshot wounds to the back were managed according to a protocol during a 12-month period. Patients with hemodynamic instability or peritonitis underwent urgent operation. The rest of the patients were observed with careful serial clinical examinations. Results: Eleven patients underwent an emergency room thoracotomy and were excluded. Four more patients were operated upon, despite the absence of abdominal findings, because of associated spinal cord injuries (2 patients), inability to observe due to need for repair of an associated peripheral vascular injury (1 patient), and participation in another protocol of aggressive evaluation of asymptomatic patients with suspected diaphragmatic injuries (1 patient). Of the remaining 188 patients, 58 (31%) underwent laparotomy (56 therapeutic, 2 negative) and 130 (69%) were initially observed owing to negative clinical examination. Following the development of increasing abdominal tenderness, 4 of these 130 (3%) underwent delayed explorations, which were all nontherapeutic. The sensitivity and specificity of initial clinical examination in detecting significant intraabdominal injuries were 100% and 95%, respectively. Conclusions Mandatory laparotomy is not necessary for gunshot wounds of the back. Clinical examination is a safe method of selecting patients for nonoperative management. An observation period of 24 hours is adequate for patients with no abdominal symptoms.
An ecological theory for the sudden origin of multicellular life in the late precambrian.

Abstract According to modern ecological theory, high diversity at any trophic level of a community is possible only under the influence of cropping. Until herbivores evolved, single-celled algae of the Precambrain were resource-limited, and a small number of species saturated aquatic environments. In the near-absence of vacant niches, life diversified slowly. Because the changes required to produce the first algae-eating heterotrophs were therefore delayed, the entire system was self-limiting. When the “heterotroph barrier” was finally crossed in the late Precambrian, herbivorous and carnivorous protists arose almost simultaneously, for no major biological differences separate the two groups. These events automatically triggered the formation of a series of self-propagating feedback systems of diversification between adjacent trophic levels. Comparable systems arose among multi-cellular groups, which radiated rapidly from the newly diversifying protist taxa. The sudden proliferation of complex food webs formed by taxa invading previously vacant adaptive zones produced an explosive diversification of life over a period of a few tens of millions of years. The rapid appearance of skeletons in various groups, though of special geological importance, was no more dramatic than other aspects of the radiation. The overall rate of diversification was comparable to rates for less-extensive adaptive radiations of the Phanerozoic.
Integrating clinical/dermatoscopic findings and fluorescence in situ hybridization in diagnosing melanocytic neoplasms with less than definitive histopathologic features.

Background Early diagnosis of melanoma remains of paramount importance, because it has been widely demonstrated that survival is strongly related to Breslow thickness. Several studies have shown that dermatoscopy improves accuracy in the diagnosis of melanoma. Although histopathology is considered the gold standard to differentiate melanoma from nevi, there are some cases of melanoma in which the histopathologic features are less than definitive. It has also been demonstrated that fluorescence in situ hybridization can be used to differentiate melanomas from nevi based on chromosomal copy number aberrations. Objective In this study we present a case series to demonstrate the value of combining fluorescence in situ hybridization and dermatoscopy/clinical history to enhance diagnostic capability for selected cases of early melanoma. Methods Cases were identified that had dermatoscopic findings or clinical history highly suggestive of melanoma and fluorescence in situ hybridization evaluation positive for melanoma, but histopathologic features that were less than definitive. Two dermatopathologists performed independent histologic analysis of specimens and two dermatologists experienced in dermatoscopy reviewed dermatoscopic and clinical data. Results Nine cases meeting inclusion criteria were identified. In 6 cases the histologic differential diagnosis was dysplastic nevus versus early melanoma whereas in 3 cases the differential diagnosis included Spitz nevus versus early melanoma. Limitations Limitations of this study include restrictive inclusion criteria and study design restricted to a case series. Conclusion This exploratory study demonstrates that in a subset of early melanoma cases, combining multiple diagnostic modalities such as dermatoscopy and molecular techniques with histology enhances detection of early melanoma.
Simple quantitative optical method for monitoring the extent of mixing applied to a novel microfluidic mixer

A novel scheme that allows the quantification of the extent of diffusive mixing between two fluids is introduced. The method, which relies upon an increase in the fluorescence intensity of fluorescein at basic pH, allows quantification of the extent of interdiffusion without requiring a full three dimensional mapping of the concentration of the dye. This allows for the characterization of mixers that could otherwise only be characterized by confocal microscopy, such as microfluidic mixing devices. The detection scheme is used to characterize a novel and highly efficient microfluidic mixer that is based on the principle of creating small fluid striations, and has been fabricated with polymeric laminate films. In this and many other mixers, the fluidic interfaces are oriented orthogonal to the optical axis, so that spatial variations in the intensity that change with the extent of mixing cannot be imaged. A 1.8 and 3.0-fold enhancement in the rate of mixing over that in a straight channel was seen after the first and second mixing units, respectively. This mixing detection scheme allows easy and inexpensive comparison of different types of mixers over a wide range of conditions.
Effect of methylglyoxal-bis (guanylhydrazone), an inhibitor of spermidine and spermine synthesis, on cell cycle traverse.

Abstract Flow cytometric analysis of the cellular DNA content and high pressure liquid chromatographic analysis of the cellular concentration of the polyamines putrescine, spermidine and spermine have been performed on exponentially growing populations of rat brain tumor cells following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG). This drug has previously been found to be a potent inhibitor of S-adenosyl- l -methionine decarboxylase, the enzyme that catalyzes the initial step in spermidine and spermine biosynthesis. MeGAG was found to inhibit cell proliferation within one generation time. During this time it produced an increase in the fraction of cells with a 2 C DNA content (cells in the G 1 phase of the cell cycle). Continued accumulation of cells in the G 1 phase occurred with sustained treatment. Drug treatment also resulted in a marked decrease in the cellular spermidine and spermine concentraions. Cells did not emerge from their G 1 -arrest after the addition of spermidine or fresh medium and apparently had become irreversibly blocked by the drug. We suggest that (1) growth inhibition by MeGAG was due to depletion of the cellular pools of spermidine and spermine, and that (2) the cells accumulated in the G 1 phase of the cell cycle because of a possible requirement for spermidine and spermine during the subsequent phases (S, G 2 and M), the period during which polyamine biosynthesis and accumulation take place in continuously dividing mammalian cells.
University-Industry Synergy: An Eclectic Dialog for Revised Relationships

The Industry Perspective column will address many of the hot issues that cross industry-academia boundaries and interests.
Cardiobacterium hominis endocarditis: Two cases and a review of the literature.

Cardiobacterium hominis, a member of the HACEK group (Haemophilus parainfluenzae, Haemophilus aphrophilus, and Haemophilus paraphrophilus, Actinobacillus actinomycetemcomitans, C. hominis, Eikenella corrodens, and Kingella species), is a rare cause of endocarditis. There are 61 reported cases of C. hominis infective endocarditis in the English-language literature, 15 of which involved prosthetic valve endocarditis. There is one reported case of C. hominis after upper endoscopy and none reported after colonoscopy. Presented here are two cases of C. hominis prosthetic valve endocarditis following colonoscopy and a review of the microbiological and clinical features of C. hominis endocarditis. Patients with C. hominis infection have a long duration of symptoms preceding diagnosis (138±128 days). The most common symptoms were fever (74%), fatigue/malaise (53%), weight loss/anorexia (40%), night sweats (24%), and arthralgia/myalgia (21%). The most common risk factors were pre-existing cardiac disease (61%), the presence of a prosthetic valve (28%), and history of rheumatic fever (20%). Of the 61 cases reviewed here, the aortic valve was infected in 24 (39%) and the mitral valve in 19 (31%) patients. The average duration of blood culture incubation before growth was detected was 6.3 days (range, 2–21 days). Complications were congestive heart failure (40%), central nervous system (CNS) emboli (21%), arrhythmia (16%), and mycotic aneurysm (9%). C. hominis is almost always susceptible to β-lactam antibiotics. Ceftriaxone is recommended by the recently published American Heart Association guidelines. The prognosis of C. hominis native valve and prosthetic valve endocarditis is favorable. The cure rate among 60 patients reviewed was 93% (56/60). For prosthetic valve endocarditis, the cure rate was 16/17 (94%). Valve replacement was required in 27 (45%) cases.
NF-κB mediated transcription in human monocytic cells and endothelial cells

Abstract Monocytes and endothelial cells become activated at sites of inflammation and contribute to the pathology of many diseases, including septic shock and atherosclerosis. In these cells, induction of genes expressing various inflammatory mediators, such as adhesion molecules, cytokines, and growth factors, is regulated by NF-κB/Rel transcription factors. Recent studies have identified components of the signal transduction pathways leading to the activation of NF-κB/Rel proteins. Inhibition of these signaling pathways provides a novel therapeutic approach to prevent inducible gene expression in both monocytes and endothelial cells. (Trends Cardiovasc Med 1998;8:138–142). © 1998, Elsevier Science Inc.