cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessment of Age, Period, and Birth Cohort Effects and Trends in Merkel Cell Carcinoma Incidence in the United States.

Importance Merkel cell carcinoma is an aggressive, cutaneous, neuroendocrine cancer that is increasing in incidence. Understanding why the incidence of Merkel cell carcinoma is increasing through underlying factors, such as age effects, calendar period of diagnosis effects, and birth cohort effects, can help guide resource allocation and design of screening programs. Objectives To evaluate the associations of patient age, calendar period of diagnosis, and birth cohort with the increasing incidence of Merkel cell carcinoma and to provide new incidence projections to 2030. Design, Setting, and Participants A cross-sectional retrospective study with age-period-cohort analysis and incidence projection modeling using data from the Surveillance, Epidemiology, and End Results Program database of 9 registries from 1987 to 2016 was conducted among 3720 patients with Merkel cell carcinoma. Statistical analysis was conducted from October 20, 2019, to July 29, 2020. Exposures Age effects (ie, physiology), period of diagnosis effects (ie, changes in diagnostics and clinical awareness), and birth cohort effects (ie, environmental risk factors) over time were assessed. Main Outcomes and Measures Incidence rates of Merkel cell carcinoma. Results Among the 3720 patients in the study (2200 male patients [59.1%]; median age, 77 years [interquartile range, 68-84 years]), during the period from 2012 to 2016, the age-adjusted Merkel cell carcinoma incidence rate was 0.66 per 100 000 (95% CI, 0.62-0.70), which represented a 3.5-times (95% CI, 3.0-4.2) increase from 1987 to 1991. The incidence of Merkel cell carcinoma increased with patient age across calendar periods and birth cohorts; the highest incidence rate was observed for those aged 85 years or older, with an age-adjusted rate from 2012 to 2016 of 14.6 per 100 000 for men and 5.5 per 100 000 for women. Although the birth cohort effect has continued to increase over time, the calendar period of diagnosis effect has started to plateau. It is projected that there will be 3023 new cases of Merkel cell carcinoma in 2020 and 5130 new cases in 2030, increased from an estimated 1933 cases in 2010. Conclusions and Relevance The slowing down of the period effect (ie, changes in diagnostics and awareness) found in this longitudinal cohort study suggests that part of the initial increased incidence of Merkel cell carcinoma was associated with increased detection. However, the projected increase in incidence rate is likely associated with the aging population and increasing risk factor exposure in more recent birth cohorts.
The Utility of Macroecological Rules for Microbial Biogeography

Macroecological rules have been developed for plants and animals that describe large-scale distributional patterns and attempt to explain the underlying physiological and ecological processes behind them. Similarly, microorganisms exhibit patterns in relative abundance, distribution, diversity, and traits across space and time, yet it remains unclear the extent to which microorganisms follow macroecological rules initially developed for macroorganisms. Additionally, the usefulness of these rules as a null hypothesis when surveying microorganisms has yet to be fully evaluated. With rapid advancements in sequencing technology, we have seen a recent increase in microbial studies that utilize macroecological frameworks. Here we review and synthesize these macroecological microbial studies with two main objectives: (1) to determine to what extent macroecological rules explain the distribution of host-associated and free-living microorganisms, and (2) to understand which environmental factors and stochastic processes may explain these patterns among microbial clades (archaea, bacteria, fungi, protists) and habitats (host-associated and free living; terrestrial and aquatic). Overall, 78% of microbial macroecology studies focused on free living, aquatic organisms. In addition, most studies examined macroecological rules at the community level with only 35% of studies surveying organismal patterns across space. At the community level microorganisms often tracked patterns of macroorganisms for island biogeography (74% confirm) but rarely followed latitudinal diversity gradients of macroorganisms (only 32% confirm). However, when microorganisms and macroorganisms shared the same macroecological patterns, underlying environmental drivers (e.g., temperature) were the same. Because we found a lack of studies for many microbial groups and habitats, we conclude our review by outlining several outstanding questions and creating recommendations for future studies in microbial ecology.
Transperineal Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy Combined with Standard Template Improves Prostate Cancer Detection.

Purpose:Transperineal (TP) prostate biopsy provides an effective approach to prostate cancer (PCa) detection. Although transrectal targeted biopsy has been well described, the specific advantage of...
Subjective Impact of the Economic Crisis on Households with Children in 17 European Countries

This paper investigates differences in the perceived impact of the economic crisis between adults in households with and without children in 17 European countries, using data from the Life in Transition Survey 2010. It also explores the channels through which the crisis affected adults in households with children and the ways in which they coped with the decline in income or economic activity. Overall, adults in households with children were more likely to report an impact of the crisis, with larger differences in countries with higher rates of monetary child poverty. There is evidence that adults in households with children prioritised expenditure on basic necessities, while cutting back on luxuries and holidays, but many still reported reduced consumption of staple foods as a result of economic difficulties.
Intrinsic Defect States in Protein Assemblages

Certain protein assemblies are known in which the bonding specificity is not conserved. This is thought to arise from a localized switching of the subunit conformation or intersubunit bonds into an inequivalent state. Such assemblies also commonly possess alternative polymorphic states — structural forms representing different spatial arrangements of subunit conformational or bonding states [1,2]. In the supercoiled helical flagellum, a strand of subunits is switched into an inequivalent “long” conformational state. The “normal” and “curly” polymorphic states of the flagellum are associated with different numbers of these switched-conformation strands [2].
Phenotyplc Analysis of Medulloblastoma with Monoclonal Antibodies

The classification of brain tumors discussed in this symposium and the existing WHO classification has been based largely upon a combination of light microscopic findings, anatomic regions In brain in which tumors arise, morphologic similarities of neoplastic cells to developing nervous system cells, combined with clinicopathologic correlations governed by prognostic implications. In contrast to such classification the most meaningful disease classifications are those based upon etiology. Since the etiology and molecular mechanisms of transformation and altered growth control for nervous system tumors remain unknown, it is not likely that it will be possible in the near future to classify brain tumors by either of those criteria. In many other tumor systems from extraneural body sites, particularly with the leukemias and lymphomas, phenotypic classification aided by monoclonal antibody analysis has made major contributions to classification schemata.
Abstract A73: De-convoluting therapeutic resistance in a pancreatic cancer model: Pharmacogenomic evaluation of intratumoral clonal heterogeneity

Background: The duration of therapeutic response in pancreatic adenocarcinoma to both targeted therapies and conventional chemotherapeutics is abysmal, greatly contributing to the 5-year survival rate of this disease remaining in the single digits. Given the high proliferative rate of these tumors, and the frequent occurrence of mutations in genes critical for maintaining genomic integrity, we hypothesized that rapid therapeutic resistance may largely be the consequence of intratumoral heterogeneity present at the onset of therapy. Materials and Methods: To address this question, an integrated genomic and pharmacologic survey was performed on a panel of clonal cell lines generated from a tumor arising in a Kras/Trp53 mutant mouse model (p48-Cre; LSL-Kras G12D ; LSL-Trp53 R172H ). Results: All lines screened maintained tumorigenicity upon allografting, and exhibited metastatic capacity. Whole exome sequencing confirmed that 94% of driver mutations found in the clonal lines were also present in the tumor. Importantly, each clonal line contains unique passenger mutations. Exposure of these lines to conventional chemotherapeutics in vitro (i.e. gemcitabine, doxorubicin, and vincristine) showed high variance in sensitivity, with 10-fold ranges of IC50s among the lines. Screening of the clonal cell lines with a kinase inhibitor library of 200 compounds, showed distinct vulnerabilities to targeted pathways between the lines. Gene expression profiling and pathway analysis highlighted variation in critical cellular pathways between the lines. Conclusions: Our results in this model system implicate ab initio drug resistance in these heterogeneous tumors as a major contributor to the poor therapeutic outcomes in this disease. This applies to conventional chemotherapy as well as targeted inhibitors. Citation Format: Eveline E. Vietsch, John K. Simmons, Ivana Peran, Marianne Stenstra, Beverly A. Mock, Anton Wellstein. De-convoluting therapeutic resistance in a pancreatic cancer model: Pharmacogenomic evaluation of intratumoral clonal heterogeneity. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A73.
Gender and Partner Compensation at America's Largest Firms

This study compiled the largest research sample on the gender gap in compensation at the 200 largest law firms by combining two large databases to examine the compensation disparities between men and women partners. The analysis elucidates the question of whether the difference is because women are less productive than men partners or because they are women. The Am Law 100 and 200 studies include gross revenue, profits, number of equity and non-equity partners, and the total number of lawyers at each firm. The Vault/MCCA Law Firm Diversity Programs study (Vault/MCCA) includes the gender ratios at each Am Law 200 firm. Our study covers the years 2002 through 2007, inclusive.We find that the ratio of women equity partners to women non-equity partners is 2.546 compared to a ratio of 4.759 for their men counterparts over the six year period studied. An increase of 1% in the proportion of women partners at a law firm is associated with 1.112% lowering of the overall compensation for all partners at the firm. This disparity in compensation between women and men partners exists even after controlling for the lower compensation of non-equity partners and the greater likelihood for women to remain non-equity partners. Furthermore, women partners are paid less despite the fact that they are not less productive than men partners in generating revenue per lawyer (RPL) for their firms.The average gross revenue of firms with the highest percentages of women lawyers was approximately $20 million dollars higher than firms with the lowest percentage of women lawyers, but the RPL of these firms dropped by approximately $120,000 per lawyer. The average compensation for the lawyers at a firm goes down as the proportion of women at a firm rises, indicating that women in all positions at a firm are paid less than their male counterparts. Nearly 80% of the Am Law 200 firms now utilize a two-tier structure of equity and non-equity partners. Firms are creating fewer equity partners and more non-equity partners. The development of two-tier partnerships, the lengthening of the time periods to make partner and equity partner, the reduction in the number of equity partners, the creation of new categories of permanent associates and permanent non-equity partners, the expanded number of permanent of counsel, and the demand for increased billable hours, have combined to increase income for a shrinking group of equity partners and to disadvantage women in large law firms.Our paper examines the gender differences in law firm compensation primarily through an empirical lens. The results have important implications in the area of economic discrimination research. Our statistical analysis concludes that women partners average compensation is less than that of men at the Am Law 200 firms, regardless of whether they are equity partners or non-equity partners. This gender disparity cannot be explained by lower productivity of women partners. It is more appropriately attributed to discriminatory practices under both disparate treatment and disparate impact analyses.
Review of The Horse in the City by Clay McShane and Joel A. Tarr

In the preface of this book, an editorial published in the New York Times, dated July 24, 1881, is cited. Entitled “The Horse in Cities,” the editorial notes how indispensable the horse had become to urban areas. This animal, which served as a “living machine,” was the power source for pulling wagons that distributed a variety of merchandise to homes and businesses, as well as for public transit vehicles that stimulated the expansion of the city outward from the central business district. Furthermore, its use as a leisure and recreational vehicle by the wealthy elite contributed to the creation of large city parks with internal roads limited to carriages. As with any urban transport mode, there was a dark side, and the message contained in the editorial was that the horse came with a high price and presented many problems. The basic problem was that the horse created what today are known as “negative side-effects,” which often overshadow the benefits to a society of increased mobility, status, and access to urban amenities. Among the problems created by the horse in cities were: disease such as the epizootic of 1872, which effectively brought the city to a standstill ; traffic safety brought about by the “misconduct” and “skittishness” of horses, thus placing riders and pedestrians at the “risk of death or maiming” ; health and sanitation caused by excrement, noise, air pollution, and dead animals ; fire risks caused by stables located in residential and commercial areas ; and high maintenance costs including items such as feed, housing, street cleaning, and disposal . Given these high costs and many potential system failures, it is not surprising that the editorial concluded that the horse was “indispensible” but only until a better substitute would be found. Little did the editorial writer know that help was on the way and that a new “horseless carriage” would soon emerge that would appear at first to have all the positive attributes and few, if any, negative ones.
Spatial pattern and spatial autocorrelation

The spatial pattern of a distribution is defined by the arrangement of individual entities in space and the geographic relationships among them. The capability of evaluating spatial patterns is a prerequisite to understanding the complicated spatial processes underlying the distribution of a phenomenon. Spatial autocorrelation indicates the extent to which the occurrence of one feature is influenced by similar features in the adjacent area. As such, statistics of spatial autocorrelation provide a useful indicator of spatial patterns. This study shows that quadrat analysis of spatial autocorrelation is not suitable for evaluating point patterns. The evaluation of spatial patterns for area features, using Moran's I coefficient, must take into consideration the log-linear relationship between map resolution and spatial autocorrelation. The topological structure of a complex spatial pattern can be revealed by the correlograms constructed based on higher-order spatial relationships. The spatial pattern can be characterized by the behavior of the correlogram's wavelength and amplitude within a specific range of spatial orders.
Two Heuristics for the Euclidean Steiner Tree Problem

The Euclidean Steiner tree problem is to find the tree with minimal Euclidean length spanning a set of fixed points in the plane, allowing the addition of auxiliary points to the set (Steiner points). The problem is NP-hard, so polynomial-time heuristics are desired. We present two such heuristics, both of which utilize an efficient method for computing a locally optimal tree with a given topology. The first systematically inserts Steiner points between edges of the minimal spanning tree meeting at angles less than 120 degrees, performing a local optimization at the end. The second begins by finding the Steiner tree for three of the fixed points. Then, at each iteration, it introduces a new fixed point to the tree, connecting it to each possible edge by inserting a Steiner point, and minimizes over all connections, performing a local optimization for each. We present a variety of test cases that demonstrate the strengths and weaknesses of both algorithms.
Energy-linked Ion Translocation in Submitochondrial Particles: I. CA++ ACCUMULATION IN SUBMITOCHONDRIAL PARTICLES

Abstract 1. Ca++ accumulation was shown to take place at pH 7.0 in submitochondrial particles. The particles were prepared from bovine heart mitochondria either by digitonin treatment or by sonic oscillation followed by osmotic shock and sedimentation at 26,000 x g. Both succinate and ATP (or ADP) were required for Ca++ accumulation. Carbonylcyanide ptrifluoromethoxyphenylhydrazone abolished the process, whereas rutamycin had no effect. 2. Under the same conditions, oxidation of DPNH in the presence of ATP was relatively ineffective in supporting Ca++ accumulation. In fact, DPNH or DPN inhibited significantly Ca++ accumulation that occurred during succinate oxidation. The inhibition by DPN was counteracted by rotenone, indicating that electron flow at the first site is required for the inhibition of Ca++ accumulation. 3. Oxidation of DPNH, generated with ethanol, alcohol dehydrogenase, and aldehyde dehydrogenase, gave rise to significant Ca++ accumulation when the reaction was carried out at pH 7.5 instead of pH 7.0. Oxidation of ascorbate in the presence of phenazine methosulfate and ATP supported Ca++ accumulation at pH 7.0, although somewhat less effectively than succinate, but considerably better than DPNH oxidation. All these processes of Ca++ accumulation were inhibited by addition of uncouplers. 4. Particles that had accumulated Ca++ released OH- when lysed with 0.03% Lubrol. The OH-:Ca++ ratio was close to unity over a wide range of Ca++ accumulated in the absence or presence of phosphate in the medium.
THE CODE CAUSE OF ACTION

In working out the details of the great pleading reform of i848, the New York "Commissioners on Practice and Pleadings" attempted to employ a technique based upon two utterly inconsistent principles. The failure of the courts which have had to interpret the Code to recognize this inconsistency has been one of the prime causes of the difficulty experienced in carrying out the pleading reforms intended by the codifiers. On the one hand the codifiers intended to ameliorate the harshness and inelasticity of the common law system of pleading by the adoption of equitable principles. On the other hand they desired to make an inelastic code-a statute-so that judge or lawyer might read and see at a glance what the procedural rule was. One was a principle looking toward convenience in trial work-ease and efficiency in doing court business; the other was a principle of rigidity, and, as apparently it was hoped and expected, of clarity and definiteness.' The result of attempting to serve both these incongruous ideals at the same time is well shown in the matter of joinder of parties. The Commissioners say that they intend to adopt the equity principle 2
Non-motor symptoms in essential tremor: A review of the current data and state of the field.

Background The motor features of essential tremor (ET) include its hallmark element, kinetic tremor, yet non-motor features are increasingly being recognized as an accompanying part of what was previously viewed as a solely motor disorder. Given the evolving state of the ET field with respect to these non-motor features, the purpose of this manuscript is to critically review the current data.
A Theoretical Foundation for Pointwise Evaluation Measures

Purpose of Lesson To provide a theoretical foundation for two types of pointwise evaluation measures: (1) those based on stress differences between the smoothed and the finite element stresses (see Lesson 18 ) and (2) those based on residuals contained in the augmented solution.
Intra-areal and corticocortical circuits arising in the dysgranular zone of rat primary somatosensory cortex that processes deep somatic input.

Somesthesis-guided exploration of the external world requires cortical processing of both cutaneous and proprioceptive information and their integration into motor commands to guide further haptic movement. In the past, attention has been given mostly to the cortical circuits processing cutaneous information for somatic motor integration. By comparison, little has been examined about how cortical circuits are organized for higher order proprioceptive processing. Using the rat cortex as a model, we characterized the intrinsic and corticocortical circuits arising in the major proprioceptive region of the primary somatosensory cortex (SI) that is conventionally referred to as the dysgranular zone (DSZ). We made small injections of biotinylated dextran amine (BDA) as an anterograde tracer in various parts of the DSZ, revealing three distinct principles of its cortical circuit organization. First, its intrinsic circuits extend mainly along the major axis of DSZ to organize multiple patches of interconnections. Second, the central and peripheral regions of DSZ produce differential patterns of intra-areal and corticocortical circuits. Third, the projection fields of DSZ encompass only selective regions of the second somatic (SII), posterior parietal (PPC), and primary motor (MI) cortices. These projection fields are at least partially separated from those of SI cutaneous areas. We hypothesize, based on these observations, that the cortical circuits of DSZ facilitate a modular integration of proprioceptive information along its major axis and disseminate this information to only selective parts of higher order somatic and MI cortices in parallel with cutaneous information. J. Comp. Neurol. 521:2585–2601, 2013. © 2013 Wiley Periodicals, Inc.
In vitro investigation of skin damage due to microscale shearing

Despite several studies dealing with the mechanical and tribological properties of skin, the majority of these investigations have been performed at macroscopic levels. However, because of the multilayer structure of skin, it is necessary to perform studies at microscopic scales to reveal the effect of individual layer constituents on the overall skin response to mechanical stimuli. To bridge the gap in knowledge of the micromechanical behavior of skin, a custom-made mechanical tester, optical microscopy, and cross-sectional histology were used to examine the deformation and tribological behavior of porcine skin subjected to various normal and shear loadings. Representative friction and wear results of skin tested under unidirectional and reciprocating (cyclic) shearing (scratching) conditions are interpreted in terms of the scratching speed, normal load, and number of scratch cycles to illustrate the effects of stratum corneum, cellular epidermis, and dermis on the friction and wear characteristics of skin. Depending on the normal load and scratch time (cycles), different friction mechanisms (i.e., adhesion, plowing, and squeeze-film lubrication) and wear mechanisms (i.e., surface plasticity/plowing, bulk shearing, cohesive failure, tearing, and delamination) were found to control shear-induced skin damage. The results of this study provide insight into microscale friction and wear processes influencing the mechanical response of skin subjected to normal and shear surface tractions. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4078–4086, 2014.
Magnetization transfer of fluoxetine in the human brain using fluorine magnetic resonance spectroscopy

Fluorine magnetic resonance spectroscopy ((19)F MRS) measurements of fluoxetine and metabolite concentration in the human brain underestimate true drug levels because of a bound, MRS-"invisible" pool of drug molecules. Magnetization transfer (MT) spectroscopy may be a useful technique for characterizing this bound pool of fluoxetine in the brain. Six subjects on consistent daily doses of fluoxetine underwent (19)F MT spectroscopy on a 1.5-T scanner using a train of three preparation pulses at -3000 Hz off resonance with 0.5 W of peak power deposition in tissue. One subject was scanned at multiple time points after initiation of drug therapy. Magnetization transfer signal contrast was quantified using VARPRO-based time domain fitting software. Magnetization transfer signal contrast was quantifiable with mean MT signal depression of 12.5% (SD = 5.0, n = 6). An inverse relationship between brain concentration and the MT signal contrast of fluoxetine was found (r = -.82, Spearman coefficient =.007). This study is the first in vivo application of (19)F MT spectroscopy and the first to demonstrate a quantifiable MT effect for a psychotropic medication in the human brain. Findings suggest that fluoxetine is substantially bound in the brain and that individual differences, inversely related to brain concentration, can be detected in the magnitude of MT contrast.
ESTROGEN EFFECT ON CALCIUM UPTAKE BY BONE

Cord blood plasma has high concentrations of estrone (E1), estradiol (E2) and estriol (E3). E2 causes hypocalcemia in newborn rats and in parathyroidectomized (PTX) adults. Since kidney and intestine have been excluded as sites of this action, bone is the presumptive locus of calcium (Ca) sequestration. Uniform discs from the calvaria of newborn rats and young mice were incubated in Krebs' solution. The addition of E2 to the medium or prior E2 injection of the donors increased Ca uptake by 60-100%. Nitromiphene, a competitive blocker of estradiol, prevented this effect and eliminated hypocalcemia after E2 in vivo. Discs from donors injected with parathyroid extract (PTE) showed decreased Ca uptake; when both PTE and E2 were given, uptake equalled that of uninjected controls. Since E2 lowers Ca in PTX rats. Its effect on bone must be independent of, as well as opposite to, that of parathyroid hormone. E1, thought to be active only after hepatic conversion to E2, caused hypocalcemia in vivo but not in vitro. E3 was inert both in vivo and in vitro. These findings suggest that the high plasma estrogen concentrations present in the neonate may contribute to hypocalcemia through a direct effect on bone.
Optimal Dynamic Pricing Policies for an M/M/s Queue

We consider the problem of maximizing the long-run average expected reward per unit time in a queuing-reward system, which we formulate as a semi-Markov decision process. Control of the system is effected by increasing or decreasing the price charged for the facility's service in order to discourage or encourage the arrival of customers. We assume that the arrival process is Poisson with arrival rate a strictly decreasing function of the currently advertized price, and that the service times are independent exponentially distributed random variables. The reward structure consists of customer payments and holding costs possibly nonlinear. At each transition customer arrival or service completion, the manager of the facility must choose one of a finite number of prices to advertize until the next transition. We show that there exist optimal stationary policies and that each possesses the monotonicity property: the optimal price to advertize is a nondecreasing function of the number of customers in the system. An efficient computational algorithm is developed that, in a finite number of steps, produces a stationary policy that is optimal.
Novobiocin does not inhibit DNA repair in an active gene.

Novobiocin, an inhibitor of type II topoisomerase, has been reported to inhibit u.v.-induced DNA repair in a number of established mammalian cell lines; we have confirmed this general observation in primary cultures of human epidermal keratinocytes. Using a recently developed technique for measuring pyrimidine dimer frequencies in genomic restriction fragments, we have determined the extent of DNA repair in the active, essential dihydrofolate reductase (DHFR) gene. Novobiocin did not affect repair of the DHFR gene in keratinocytes or in a Chinese hamster ovary (CHO) cell line over a 24-h period following irradiation with 20 J/m2 u.v. These findings suggest that qualitative differences exist in the repair pathways in different genomic regions; topoisomerase II may not have an essential role in repair of active genes but may be required for repair of other regions in the genome.
Life cycle of the marine alga Phaeocystis: A conceptual model to summarize literature and guide research

Abstract This paper reviews literature on the life cycle of the marine algal genus Phaeocystis, and organizes existing information in the form of a qualitative conceptual model of life-cycle stages, stage transitions, ecosystem inputs and outputs, and internal and external controlling factors. Conceptualization is the first phase of modeling, typically continued in later quantitative phases by mathematical formulation, calibration of parameters, dynamic simulation, and different forms of systems analysis. Qualitative conceptualization can also promote multidisciplinary interactions and structure early stages of scientific inquiry. To exploit the qualitative benefits of conceptual modeling, the goals of this paper are to: (1) review the literature of Phaeocystis life-cycle biology and ecology; (2) from the material of this review, construct, a conceptual life-cycle model covering all Phaeocystis species; and (3) show how this model, a platform for further quantitative development, is also used as a qualitative tool to guide empirical research. The conceptual model includes known and putative life-cycle stages, colony size classes, and genetic, physiological, semiotic, and ecological information expressed or potentially expressed across the genus. It consists of 15 compartments. Seven are single-celled: Solitary Diploid Flagellates (x1), Solitary Diploid Non-flagellates (x2), Benthic Solitary Diploid Non-Flagellates (x3), Solitary Diploid Flagellated Macrozoospores (x8), Solitary Haploid Flagellated Microzoospores (x9), Solitary Haploid Microflagellates (x10), and Solitary Haploid Mesoflagellates (x11). The remaining eight compartments represent the New stage, and Small, Medium, and Large size classes of Healthy/Growing Colonies (x4–x7), and Senescent/Declining Colonies (x12–x15). Six flow types interconnect the compartments: (a) physical transport, (b) solitary cell transformations, (c) solitary cell↔colony transitions, (d) colony growth and differentiation, (e) colony senescence, and (f) syngamy of solitary haploid cells. Boundary inputs and outputs include flows associated with transport, nutrient exchange, chemical signals, and grazing and cell lysis. Factors controlling flows include genetics, cellular and organismal biology, info-chemistry, and ecology.
SU-E-T-74: Assessing Effects of Ion Collection Efficiency in Flattening Filter-Free (FFF) Beams on Three TrueBeam Machines

IntroductionA TrueBeam linear accelerator (TB‐LINAC) is a new generation digital linear accelerator designed to deliver both standard flattened and flattening filter‐free (FFF) beams. It has been reported that incomplete ion collection efficiency of an ion chamber occurs in FFF beams; however, recent works reported considerable differences in variation of ion collection efficiency. To ensure accurate dosimetry, we further investigated the ion collection efficiency under FFF conditions on three TB‐LINAC units.MethodsEach TB‐LINAC is capable of delivering photon beams from 4MV to 15MV, electron beams from 6MeV to 22MeV, and 6MV‐FFF and 10MV‐FFF photon beams. Ion collection efficiency of an ionization chamber for various dose rates at various locations under 6MV, 10MV, 6MV FFF and 10MV FFF conditions was measured, quantified as Pion. The standard Boag's two‐voltage technique was used to calculate Pion.All these measurements were conducted in a standard Wellhofer water tankwith a compact ion‐chamber (CC13, IBA dosimetry, Germany). ResultsVariations of ion collection efficiency of the chamber CC13 are less than 0.3% in standard 6MV and 10MV from 5cm depth to the 35cm depth under 40×40cm2 under the dose rates ranging from 100MU/min to 600MU/min. Variations of Pion of the chamber CC13 are 1.2% (from 1.015±0.002 to 1.002±0.001) under 6MV FFF and 2.0% (from 1.023±0.006to 1.002±0.001) from dmax to the 18cm‐off‐axis point at 35cm depth under 40×40cm2. Variations of ion collection efficiency are less than 0.1% across dose rates from 400MU/min to 1400MU/min in 6MV FFF and less than 0.2% across dose rates from 400MU/min to 2400MU/min in 10MV FFF at various locations.ConclusionVariations of Pion in FFF beams are much greater than those in the corresponding flatten beams. Given the approximate 2% variation in 10MV FFF, proper correction may be considered for the incomplete ion collection efficiency in 10MV FFF.
A novel role for the proteasomal chaperone PSMD9 and hnRNPA1 in enhancing IκBα degradation and NF-κB activation – functional relevance of predicted PDZ domain–motif interaction

PSMD9 is a PDZ domain containing chaperone of proteasome assembly. Based on the ability of PDZ-like domains to recognize C-terminal residues in their interactors, we recently predicted and identified heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as one of the novel interacting partners of PSMD9. Contingent on the reported role of hnRNPA1 in nuclear factor κB (NF-κB) activation, we tested the role of human PSMD9 and hnRNPA1 in NF-κB signaling. We demonstrated in human embryonic kidney 293 cells that PSMD9 influences both basal and tumor necrosis factor α (TNF-α) mediated NF-κB activation through inhibitor of nuclear factor κB α (IκBα) proteasomal degradation. PSMD9 mediates IκBα degradation through a specific domain-motif interaction involving its PDZ domain and a short linear sequence motif in the C-terminus of hnRNPA1. Point mutations in the PDZ domain or deletion of C-terminal residues in hnRNPA1 disrupt interaction between the two proteins which has a direct influence on NF-κB activity. hnRNPA1 interacts with IκBα directly, whereas PSMD9 interacts only through hnRNPA1. Furthermore, hnRNPA1 shows increased association with the proteasome upon TNF-α treatment which has no such effect in the absence of PSMD9. On the other hand endogenous and trans-expressed PSMD9 are found associated with the proteasome complex. This association is unaffected by PDZ mutations or TNF-α treatment. Collectively, these interactions between IκBα, hnRNPA1 and proteasome bound PSMD9 illustrate a potential mechanism by which ubiquitinated IκBα is recruited on the proteasome for degradation. In this process, hnRNPA1 may act as a shuttle receptor and PSMD9 as a subunit acceptor. The interaction sites of PSMD9 and hnRNPA1 may emerge as a vulnerable drug target in cancer cells which require consistent NF-κB activity for survival.
Diagnosis of NMOS DRAM functional performance as affected by a picosecond dye laser

A picosec pulsed dye laser beam was at selected wavelengths successfully used to simulate heavy-ion single-event effects (SEEs) in negative channel NMOS DRAMs. A DRAM was used to develop the test technique because bit-mapping capability and previous heavy-ion upset data were available. The present analysis is the first to establish such a correlation between laser and heavy-ion data for devices, such as the NMOS DRAM, where charge collection is dominated by long-range diffusion, which is controlled by carrier density at remote distances from a depletion region. In the latter case, penetration depth is an important parameter and is included in the present analysis. A single-pulse picosecond dye laser beam (1.5 microns diameter) focused onto a single cell component can upset a single memory cell; clusters of memory cell upsets (multiple errors) were observed when the laser energy was increased above the threshold energy. The multiple errors were analyzed as a function of the bias voltage and total energy of a single pulse. A diffusion model to distinguish the multiple upsets from the laser-induced charge agreed well with previously reported heavy ion data.
Triggering the cellular change to neoplasia

~ No Tumors II II I , Initiation and promotion as stages in the natural history of neoplasia. From the results of the experiments outlined in Figure 1, two distinct stages in the development of epidermal neoplasms in mouse skin-initiation and promotion-can be defined, together with some of their characteristics. In line 1, a single application of the initiating agent (usually a carcinogenic polycyclic hydrocarbon in the skin experiments) is applied at a dose such that no neoplasms result. Obviously, higher doses or repeated applications of such carcinogenic agents would result in neoplasms, but this will be considered later. As can be seen from line 2, the application of the initiating agent followed by the repeated application to the skin of an entirely different agent, termed the promoter, results in neoplasms in 100% of the animals. In these experiments, the promoting agent utilized was the irritant natural product, croton oil. More recently, the active ingredient of croton oil, tetradecanoyl phorbol acetate (TPA), has been employed with essentially
Whistle Blowing: Preventive Strategies

Imagine working for a company that produces medical supplies. Suppose that one day, it is discovered that one of the products the firm produces could be harmful to a small segment of the population using that particular product. It is believed that knowingly producing and marketing this product is wrong and that something must be done. However, there are only three choices available: ignore the situation, report it internally within the organisation, or report it externally through channels such as the Justice Department or publicly exposing it to the news media (Barnett, 1992). This is an ethical dilemma faced by many employees every day. Each of the three choices holds both positive and negative consequences which will greatly determine the outcome of an individual's decision.
Effects of β6 amino acid hydrophobicity on stability and solubility of hemoglobin tetramers

The relationship between different amino acids at theβ6 position of hemoglobin and tetramer stability was addressed by a site-directed mutagenesis approach. Precipitation rates during mechanical agitation of oxyhemoglobins with Gln, Ala, Val, Leu and Trp at the β6 position increased 2, 5, 13, 21 and 53 times, respectively, compared with that for Hb A. There was a linear relationship between the log of the precipitation rate constant and amino acid hydrophobicity at the β6 position, suggesting that enhanced precipitation of oxy Hb S during mechanical agitation results in part from increased hydrophobicity of β6 Val. Deoxyhemoglobin solubility increased in the order of β6 Ile, Leu, Val, Trp, Gln, Ala and Glu suggesting that hydrophobic interactions between β6 Val and the acceptor site of another hemoglobin molecule during deoxy-Hb S polymerization not only depend on hydrophobicity but also on stereospecificity of the amino acid side chain at the β6 position. Furthermore, our results indicate that hydrophobic amino acids at the β6 position which promote tetramer instability in the oxy form do not necessarily promote polymerization in the deoxy form.
The effect of amphetamine on the behaviour of decerebrate domestic chicks.

Abstract 1. Decerebration reduced the increase in peeps observed in normal 5-day old chicks injected with d-amphetamine. 2. The increase in short calls, the appearance of forced locomotion, head shakes and wing drooping, and the decrease in the duration of eye closure were not affected. 3. Forebrain mechanisms are considered important for the generation of amphetamine-induced peeps, but not other behaviour.
New perspective in the experimental study of atmospheric turbulence: a volume scanning crossed-path lidar technique

A new volume-scanning crossed-path lidar technique for studying atmospheric intermittency in the surface and boundary layers is proposed. This technique provides a spatial resolution of 25 m and a temporal resolution of several seconds, and it permits us to study turbulent structures and processes in the atmospheric surface and boundary layers by performing a volumetric mapping of the optical refractive index structure parameter field. Unlike radar and acoustic sounders, this technique is not affected by humidity fluctuations. Lidar performance estimates show that the proposed technique is practical.
Experimental studies in childhood schizophrenia: Analysis of self-destructive behavior

Abstract This paper reports on three studies concerned with investigating variables which controlled self-destructive behaviors in a schizophrenic child. The self-destructive behaviors included head- and arm-banging which was usually so intense that the child's skin was discolored, bruised, and swollen. Methodologically, the experimental procedure followed an intrasubject replication design which involved repeated presentations of the same experimental variables in order to insure reliability. The results illustrate the lawfulness and regularity which characterized the self-destructive behavior. The data clearly show the functional relationships between very specific environmental operations and the self-destruction: reinforcement and extinction of other behaviors in a given setting controlled the frequency and magnitude of self-destructive behavior, and delivery of sympathetic comments, contingent upon the occurrence of self-destructive behavior, increased its frequency and magnitude. Conceptually, the system which best fit the observed relationships inyolves a consideration of self-destructive behavior as learned, operant, or instrumental social behavior.
Detection of infectious prions in urine

Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrPSc). The mechanism of prion transmission is unknown. In this study, we attempted to detect prions in urine of experimentally infected animals. PrPSc was detected in ∼80% of the animals studied, whereas no false positives were observed among the control animals. Semi-quantitative calculations suggest that PrPSc concentration in urine is around 10-fold lower than in blood. Interestingly, PrPSc present in urine maintains its infectious properties. Our data indicate that low quantities of infectious prions are excreted in the urine. These findings suggest that urine is a possible source of prion transmission.
A power law model for the flow stress and strain-rate sensitivity in CP titanium

1. (1) Using the power law equation, σ∗ = σ∗0 × (⋅ϵ⋅ϵ0)RTHo, the material parameters for a CP titanium system were evaluated with values σ∗0 = 1,324 MPa, ϵ0 = 4.01 × 107 s−1 and H ° = 50,160 J/mol. The resulting power law equation was able to yield curves that followed the temperature dependence of the internal stress, the total flow stress and the strain-rate sensitivity S with considerable precision to approximately 500 K. 2. (2) It was also demonstrated that it is possible to explain quantitatively the plateau in the flow stresstemperature diagram above 500 K by assuming the flow stress in this region is the sum of three component stresses; the internal stress, the effective stress and a dynamic strain aging stress due to oxygen. 3. (3) It was further shown that a drop in the strain rate sensitivity parameter, S, at 650 K could be explained by the present treatment.
Promoting Caring in Children and Families as Prevention of Violence Strategy

Promoting caring in children is a powerful venue to prevent violence in our society. This article reviews the roots of violence, explores the various contexts of violence, and then describes how caring can be used to prevent violence. In particular, the role that families and schools can play in helping children develop caring is discussed.
Stoichiometric Alkane Dehydrogenation with Tp‘PtMe2H to Form Tp‘Pt(η2-olefin)(H) Complexes

Gentle heating of Tp‘PtMe2H (1) in alkane solvents in the presence of B(C6F5)3 results in C−H activation of the alkane solvent, R−H, to give Tp‘Pt(Me)(H)(R) intermediates. Further heating leads to formation of Tp‘Pt(η2-olefin)(H) complexes via methane elimination followed by β-hydride elimination, a stoichiometric alkane to olefin conversion.
Above and Below Left–Right: Ideological Narratives and Moral Foundations

Why do people vary in their views of human nature and their visions of the good society? Why do many people categorize themselves as “liberal,” “conservative,” “libertarian,” “socialist,” and so on...
High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study.

We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were followed for 6 months after receiving a six-week course of oral high-dose cholecalciferol or placebo. Vitamin D insufficiency and deficiency was present at baseline in 82.5% and 52.5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
Growth of lithium niobate thin films by solid source MOCVD

Lithium niobate (LiNbO3) epitaxial thin films have been grown on c-plane sapphire and LiTaO3 (LT) substrates using solid-source MOCVD. The structural quality of LiNbO3 (LN) films grown on LT was found to be higher than for films grown on sapphire. Films on LT have a single in-plane orientation over a wide range of deposition temperatures (500 degree(s) to 750 degree(s)C), while growth on sapphire often leads to a small percentage of 60 degree(s) misoriented grains. The surface roughness of LN films on LT substrates is also much less than for films deposited on c-sapphire under similar conditions. While sapphire is a less suitable substrate for the deposition of optical quality films, it has provided an opportunity to study the effects of surface microstructure on film quality. Our findings are described. Prism- coupled, thin film analysis has revealed optical losses as low as 2 dB/cm (TMo mode) in 1000 angstroms thick LN films deposited on c-sapphire and 5 approximately 6 dB/cm (TEo mode) in 5000 angstroms films deposited on LT. Using LT, we have been able to deposit high crystalline quality LN films with very smooth surfaces below the Curie temperature of the substrate (600 degree(s)C), and etching techniques have revealed that the polarity of these films follows that of the substrate. This result suggests the possibility of depositing LN on periodically poled LT substrates for quasi-phase matched optical interactions.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.