cssi/SciSciGPT-SciSciNet huggingface dataset:
Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer

Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolipid synthesis and efflux of Cav-1-sphingolipid particles containing mitochondrial proteins and lipids. We also demonstrate, using a prostate cancer syngeneic RM-9 mouse model and established cell lines, that this Cav-1-sphingolipid program evidences a metabolic vulnerability that is targetable to induce lethal mitophagy as an anti-tumor therapy. The mechanisms associated with Caveolin-1 (Cav-1) mediated metabolic changes in prostate cancer are unclear. Here, the authors show that Cav-1 promotes rewiring of cancer cell lipid metabolism towards a program of exogenous lipid scavenging and vesicle biogenesis that intersects with mitochondrial dynamics in prostate tumors.
Direct Feeding of the Black Hole at the Galactic Center with Radial Gas Streams from Close-In Stellar Winds

We show that the recently-discovered orbits of massive stars with closest approach of ~10^3 Schwarzschild radii from SgrA*, allow winds from these stars to provide the required mass deposition rate near the black hole horizon. The observed luminosity of SgrA* does not require viscous transport of angular momentum, as long as the total wind mass loss rate reaches ~10^{-6} solar masses per year from the close-in stars. The specific orbits of the nearest stars should cause modulation of the radio and infrared flux from SgrA* on a timescale of years in a predictable fashion.
Risk factors for fecal carriage of multidrug-resistant Escherichia coli in a college community: a penalized regression model

Abstract Background Bacterial antimicrobial resistance is a serious global public health threat. Intestinal commensal drug-resistant bacteria have been suggested as an important reservoir of antimicrobial resistant genes (ARGs), which may be acquired via food. We aimed to identify risk factors associated with fecal carriage of drug-resistant commensal Escherichia coli (E. coli) among healthy adults focused on their dietary habit. Methods We conducted a cross-sectional study targeting healthy adult volunteers in a college community. Fecal samples and questionnaires were obtained from 113 volunteers. We conducted backward elimination logistic regression and least absolute shrinkage and selection (LASSO) methods to identify risk factors. Results We analyzed responses from 81 of 113 volunteers who completed the questionnaire. The logistic regression and LASSO methods identified red meat consumption to be associated with increased risk (OR = 6.13 [1.83-24.2] and 1.82, respectively) and fish consumption with reduced risk (OR = 0.27 [0.08-0.85] and 0.82) for the carriage of multidrug-resistant E. coli, adjusted for gender, employment status, frequently-used supermarket, and previous travel. Conclusions Dietary habits are associated with the risk of fecal carriage of multidrug-resistant E. coli. This study supports the growing evidence that food may be an important source of ARGs present in human commensal E. coli.
Barriers to Upper Extremity Reconstruction for Patients With Cerebral Palsy.

BackgroundReconstructive surgery for upper extremity manifestations of cerebral palsy (CP) has been demonstrated to be safe and effective, yet many potential candidates are never evaluated for surg...
Psychiatric comorbidity associated with co-occurring autism spectrum disorder and substance use disorder

Abstract Background Although both autism spectrum disorder (ASD) and substance use disorder (SUD) are both commonly comorbid with other psychiatric conditions, there is a paucity of research on the overlap of these disorders. The primary aim of the present study was to identify the prevalence of psychiatric comorbidities in young adults with SUD and ASD compared to those with ASD only. Method Multivariate logistic regression controlling for age was used to compare the prevalence of psychiatric disorders in a sample of treatment-seeking adult outpatients with a) ASD without SUD and b) ASD with SUD. Psychiatric and SUD diagnoses were determined by semi-structured interview (SCID for DSM IV). Results The sample included 42 patients with ASD only (mean age ± SD = 26.2 ± 8.9 years) and 21 with ASD and SUD (35.2 ± 12.6). High rates of psychopathology were found in both groups. Comorbid conduct disorder (CD) was significantly more prevalent in the ASD + SUD group (25 %) compared to those without SUD (5%; p Conclusion In both groups, rates of psychopathology were high with CD being significantly more common in young adults with ASD and SUD. These findings highlight the importance of screening for CD in individuals with ASD to mitigate the potential development of comorbid SUD. Further research is needed to determine if CD is a true risk factor for SUD in the ASD population and identify other risk factors.
State of Scale-Up Development in Chemical Looping Technology for Biomass Conversions: A Review and Perspectives

The chemical looping technology is an emerging technology for the efficient conversion of biomass to heat, power, fuel, and value-added chemicals. Chemical looping uses a metal oxide oxygen carrier to fully or partially oxidize the biomass feedstock, which avoids N2 dilution to the CO2 or syngas product. Thus, chemical looping technology can convert biomass to sequestration-ready CO2 or high purity syngas, which leads to the potential for negative carbon emission and enhanced energy efficiency in biomass conversions. Various chemical looping processes for biomass conversions, using different oxygen carrier materials and reactor designs, have been studied ranging from lab scale to pilot scale. This article reviews the current state of development in the scale-up of chemical looping technology for biomass conversions. It also provides perspectives on the chemical looping technology of relevance to various biomass conversion issues including CO2 capture, utilization and sequestration, biomass feedstock collection, handling and conversion enhancement, choice of reaction schemes, fuel and air reactor designs and operation, operational load variation, fate of pollutants and effect of ashes. Representative process configurations, reactor designs, oxygen carrier material selections, and the testing results are described along with the technology challenges, their potential solutions, and future research needs.
COVID-19 infection in former living kidney donors.

The COVID-19 pandemic brought living donor kidney transplant programs across the United States to a near halt in March 2020. As programs have begun to reopen, potential donor candidates often inquire about their risk of a COVID-19 infection and its potential impact on kidney function after donation. To address their concerns, we surveyed 1740 former live kidney donors at four transplant centers located in New York and Michigan. Of these, 839 (48.2%) donors responded, their mean age was 46 ± 12.5 years, 543 (65%) were females, and 611 (73%) were white. Ninety-two donors (11%) had symptoms suggestive of a COVID-19 infection with fever (48%) and fatigue (43%) being the most common. Among those with symptoms, 42 donors underwent testing and 16 tested positive. Testing was more common among donors with private insurance, and a positive test result was more common among young black donors. Only one donor surveyed required hospitalization and none required dialysis. Fourteen donors have recovered completely and two partially. Our survey highlights that a COVID-19 infection in former donors results in a mild disease with good recovery. These data will be useful for transplant programs to counsel living donors who are considering kidney donation during this pandemic.
Designing for Inherent Control in Liquid-Metal Advanced Small Modular Reactors

Simulation results are presented for a design strategy that seeks to achieve inherent control and passive safety for liquid-metal advanced small modular reactors. The approach places an increased r...
Latent infection of CD4 + T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy

Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4+ T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 x 10(5) cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy.
Disks Around Post-Main Sequence Binaries

We propose that at least two stars on or near the AGB have long-lived orbiting disks: HD 44179, the central star in the Red Rectangle, and BM Gem, a carbon-rich star with an oxygen-rich circumstellar envelope. The CO emission from both of these disks has a spike with a width near ∼2 km s−1, indicating disk radii of ∼1016 cm. The dust in such disks is therefore quite cold (near T ∼ 50 K for the Red Rectangle) and may emit primarily at submillimeter wavelengths. The disks around stars where there is also substantial mass loss may not be easily observable; there could be many as yet undiscovered disks around AGB stars
The Missing Instrument: Dirty Input Limits

This article evaluates an environmental protection instrument that the literature has hitherto largely overlooked, Dirty Input Limits (DILs), quantitative limits on the inputs that cause pollution. DILs provide an alternative to cumbersome output-based emissions trading and performance standards. DILs have played a role in some of the world's most prominent environmental success stories. They have also begun to influence climate change policy, because of the impossibility of imposing an output-based cap on transport emissions. We evaluate DILs' administrative advantages, efficiency, dynamic properties, and capacity to better integrate environmental protection efforts. DILs, we show, not only have significant advantages that make them a good policy tool, they also have the capacity to help us fruitfully reconceptualize environmental law in more holistic fashion.
Human immunodeficiency virus type 1 entry into T cells: more-rapid escape from an anti-V3 loop than from an antireceptor antibody.

Abstract The entry of human immunodeficiency virus type 1 into two T-cell lines has been analyzed to determine the relative time courses with which virus entry can be blocked (i) by washing, (ii) by adding a monoclonal antibody to the V3 loop of gp120 that neutralizes without blocking CD4 binding (0.5 beta), or (iii) by adding an antireceptor monoclonal antibody that competes for virus binding (leu3a). During entry into C8166 cells, 50% escape from the wash as well as the anti-V3 loop antibody required 20 min, whereas 50% escape from the leu3a block required 45 minutes. In contrast, during entry into H9 cells, 50% escape from the wash block required 50 min, 50% escape from the anti-V3 loop antibody required 110 min, and 50% escape from the antireceptor antibody required 190 min. These results demonstrate that the times required for entering virus to escape each of the blocks were cell type specific. They also demonstrate that V3 loop-dependent steps occur relatively early in entry and suggest that binding of gp120 to CD4 is important for late as well as early steps in human immunodeficiency virus type 1 entry.
Patients with antineutrophil cytoplasmic antibody-associated vasculitis have defective Treg cell function exacerbated by the presence of a suppression-resistant effector cell population.

Objective The development of pathogenic antineutrophil cytoplasmic antibodies (ANCAs) can result in systemic small vessel vasculitis. However, the breakdown in immune tolerance that results in the induction and persistence of ANCAs is not well understood. We undertook this study to test our hypothesis that abnormal T cell regulation is central to disease pathogenesis in patients with ANCA-associated vasculitis (AAV). Methods Peripheral blood samples were obtained from 62 patients with AAV and 19 healthy controls for flow cytometric analysis of CD4+ T cell populations. Functional T cell studies were performed with fluorescence-activated cell sorted CD4+ T cell populations stimulated with anti-CD3/anti-CD28. Results We demonstrated two separate abnormalities in T cell regulation in patients with AAV. First, we showed that the Treg cell frequency was increased in the peripheral blood of patients with active disease, but Treg cells from patients with AAV had decreased suppressive function. Treg cells from patients with active disease disproportionately used a FoxP3 isoform lacking exon 2, which might alter Treg cell function. Second, we identified a CD4+ T cell population with increased frequency that was resistant to Treg cell suppression, produced proinflammatory cytokines, and was antigen experienced. Conclusion AAV is associated with disruption of the suppressive Treg cell network and with increased frequency of a distinct proinflammatory effector T cell subset that comprises the majority of peripheral CD4+ T cells.
Providing Feedback to Equation Entries in an Intelligent Tutoring System for Physics

Andes, an intelligent tutoring system for Newtonian physics, provides an environment for students to solve quantitative physics problems. Andes provides immediate correct/incorrect feedback to each student entry during problem solving. When a student enters an equation, Andes must (1) determine quickly whether that equation is correct, and (2) provide helpful feedback indicating what is wrong with the student's entry. To address the former, we match student equations against a pregenerated list of correct equations. To address the latter, we use the pre-generated equations to infer what equation the student may have been trying to enter, and generate hints based on the discrepancies. This paper describes the representation of equations and the procedures Andes uses to perform these tasks.
CNN. II. Applications and VLSI circuit realizations

For pt.I, see ibid., p.144-5, 1992. Several different classes of cellular neural network (CNN) applications are reviewed, and a very exhaustive list of publications is given. The application potential of CNN relies on the innovative architecture, and as well on a successful high-speed or low-cost hardware implementations. The characterization of the CNN VLSI circuit realization is based on a fully tested high-speed analog chip. >
Targeting the PD-1 pathway: a promising future for the treatment of melanoma

Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1–PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.
Tayib Salih: ideology and the craft of fiction

Tayib Salih: ideology and the craft of fiction, Wail Hassan, Syracuse: Syracuse University Press, 2003, xviii + 199 pp. (paperback), ISBN 0-8156-3037-9 Sudan is the largest country in Africa. It is...
Immobilization of soot particles in a silica matrix: A sorbent-carrier system for studying organic chemical sorption.

A new method for studying sorption with diesel and hexane soot was developed, tested, and applied. A commercial silica-based chromatography medium was used as an inert inorganic carrier for immobilization (entrapment) of soot particles and their aggregates, thus creating a combined sorbent for sorption of hydrophobic organic chemicals (HOCs). After precombustion to remove potential organic carbon contaminants, the silica particles and soot samples were mixed under dry conditions that allowed the soot to be incorporated within the pore structure of the much larger (>180 μm) carrier particles. Unincorporated soot was removed by multiple rinses with Milli-Q water. Sorption rate and equilibrium experiments were conducted, using phenanthrene as a probe HOC. Strong nonlinear sorption of phenanthrene was observed, in agreement with results previously obtained using air-bridge and flocculation-based methods. Batch kinetic studies suggested that 60 d of prewetting is required to obtain full water saturation, as pe...
Defect reduction methodologies: pellicle yield improvement

The pelliclization process at Intel during the first half of 1991 was not in control. Weekly process yield was trending downward, and the range of the weekly yield during that time frame was greater than 40%. A focused effort in process yield improvement, that started in the second half of 1991 and continued through 1992, brought process yield up an average of 20%, and reduced the range of the process yield to 20 - 25%. This paper discusses the continuous process improvement guidelines that are being followed to reduce variations/defects in the pelliclization process. Teamwork tools, such as Pareto charts, fishbone diagrams, and simple experiments, prioritize efforts and help find the root cause of the defects. Best known methods (BKM), monitors, PMs, and excursion control aid in the elimination and prevention of defects. Monitoring progress and repeating the whole procedure are the final two guidelines. The benefits from the use of the continuous process improvement guidelines and tools can be seen in examples of the actions, impacts, and results for the last half of 1991 and the first half of 1992.
Methylation of 1,8-dihydroxy-9,10-anthraquinone with and without use of solvent-free technique ☆

A convenient and environmentally friendly solvent-free procedure has been developed for dimethylation of 1,8-dihydroxy-9,10-anthraquinone with excellent yield. A highly selective monomethylation of 1,8-dihydroxy-9,10-anthraquinone in refluxing tetraglyme makes monomethylated peri-dihydroxy-9,10-anthraquinones easily available. Alternatively, irradiation in a domestic microwave oven has been employed for the solvent-free monomethylation of 1,8-dihydroxy-9,10-anthraquinone.
PAWNEE WAR TALES

One night a warrior sat in his lodge with many friends about him listening to his experiences while on the war-path. As the night wore on and he continued to tell of his exploits, a great longing seized him and he asked his friends if they would accompany him the next morning, for he had decided to start on the war-path again. On that same night three other warriors sat in their lodges and told their friends of their own experiences in war, and a great longing to fight filled the breast of each of these warriors; then they asked their friends to go with them on the morrow, for they too had decided to start on the war-path again. Before the break of day the four warriors and their men were on the way to the country of the enemy. During the day the scouts from each party met and at night the four parties came together. The scouts resented the presence of one another, for every scout preferred to have the country to himself, but the four leaders joined forces and traveled together to the enemy's country. One day the leaders sat down in a valley and sent out men to kill buffalo. The men went out, killed a buffalo, and started to skin it. When they had it about half skinned, the buffalo rolled over, jumped up, and ran away with its skin flapping up and down. The men were dumb with astonishment for a time; then they went on and killed another buffalo, skinned it, cut up the meat and took it to camp where the leaders were. While they were roasting the meat, the men who had been out to kill buffalo told the leaders
Magnetic phases in three-flavor color superconductivity

The best natural candidates for the realization of color superconductivity are quark stars---not yet confirmed by observation---and the extremely dense cores of compact stars, many of which have very large magnetic fields. To reliably predict astrophysical signatures of color superconductivity, a better understanding of the role of the star's magnetic field in the color-superconducting phase that is realized in the core is required. This paper is an initial step in that direction. The field scales at which the different magnetic phases of a color superconductor with three quark flavors can be realized are investigated. Going from weak to strong fields, the system first undergoes a symmetry transmutation from a color-flavor-locked (CFL) phase to a magnetic-CFL (MCFL) phase, and then a phase transition from the MCFL phase to the paramagnetic-CFL (PCFL) phase. The low-energy effective theory for the excitations of the diquark condensate in the presence of a magnetic field is derived using a covariant representation that takes into account all the Lorentz structures contributing at low energy. The field-induced masses of the charged mesons and the threshold field at which the $\mathrm{CFL}\ensuremath{\rightarrow}\text{ }\text{ }\mathrm{MCFL}$ symmetry transmutation occurs are obtained in the framework of this low-energy effective theory. The relevance of the different magnetic phases for the physics of compact stars is discussed.
158. Real-Time Visualization of Neuronal Differentiation and Neurite Projection Using an Indicator HSV Amplicon Vector

Top of pageAbstract Stem cell-based replacement therapy has great potential in treating neurological disorders, including brain and spinal cord injuries. Although several studies have demonstrated neuronal and glial differentiation of transplanted neural stem cells (NSCs) in vivo, the efficacy of the transplanted NSCs to generate neurons and of the newly generated neurons to form new synaptic connections with the remaining host neurons still needs clarification. To address these issues, we have constructed an HSV amplicon-based indicator vector that allows visualization of neuronal differentiation and neurite projection. Synapsin I (SYN) is a well characterized gene that expresses selectively in neurons. Thiel and colleagues found that a 400-bp 5' untranslated promoter region of SYN directed prominent expression of a reporter gene in various neuronal cell lines, but that no expression was detected in cell lines derived from non-neuronal tissue (Thiel G et al., PNAS 1991). On the other hand, microtubule- associated protein tau-reporter fusion protein has been used as a genetic reporter to visualize neuronal processes in vivo (Callahan CA et al., PNAS 1994). We, therefore, combined the two genetic elements in the context of HSV amplicon vectors, producing an indicator herpes simplex virus (HSV) amplicon vector, HSV-SYN-tauR, that carries tau fused with a monomeric red fluorescent protein (mRFP, Campbell et al., PNAS 2002) under the control of the 400- bp SYN promoter. When a mixed culture of mouse cortical neurons and glia was transduced with the HSV-SYN-tauR amplicon vector, RFP reporter was expressed only in neurons along their neurites, allowing visualization of every axon, dendrite, and spine. Time-lapse imaging of mixed cortical cultures transduced with the HSV-SYN-tauR amplicon vector allowed noninvasive real-time monitoring of extension and retraction of the neurites of live neurons. This indicator HSV amplicon vector could prove useful in studying neuronal differentiation, neurite projections, and regeneration of neuronal networks in vitro and in vivo.
Local adaptation despite high gene flow in the waterfall‐climbing Hawaiian goby, Sicyopterus stimpsoni

Environmental heterogeneity can promote the emergence of locally adapted phenotypes among subpopulations of a species, whereas gene flow can result in phenotypic and genotypic homogenization. For organisms like amphidromous fishes that change habitats during their life history, the balance between selection and migration can shift through ontogeny, making the likelihood of local adaptation difficult to predict. In Hawaiian waterfall-climbing gobies, it has been hypothesized that larval mixing during oceanic dispersal counters local adaptation to contrasting topographic features of streams, like slope gradient, that can select for predator avoidance or climbing ability in juvenile recruits. To test this hypothesis, we used morphological traits and neutral genetic markers to compare phenotypic and genotypic distributions in recruiting juveniles and adult subpopulations of the waterfall-climbing amphidromous goby, Sicyopterus stimpsoni, from the islands of Hawai'i and Kaua'i. We found that body shape is significantly different between adult subpopulations from streams with contrasting slopes and that trait divergence in recruiting juveniles tracked stream topography more so than morphological measures of adult subpopulation differentiation. Although no evidence of population genetic differentiation was observed among adult subpopulations, we observed low but significant levels of spatially and temporally variable genetic differentiation among juvenile cohorts, which correlated with morphological divergence. Such a pattern of genetic differentiation is consistent with chaotic genetic patchiness arising from variable sources of recruits to different streams. Thus, at least in S. stimpsoni, the combination of variation in settlement cohorts in space and time coupled with strong postsettlement selection on juveniles as they migrate upstream to adult habitats provides the opportunity for morphological adaptation to local stream environments despite high gene flow.
ITCZ Breakdown in Three-Dimensional Flows

The intertropical convergence zone (ITCZ) is observed to undulate and at times break down into a series of tropical disturbances in several days. Some of these disturbances may develop into tropical cyclones and move to higher latitudes, while others dissipate, and the ITCZ may reform in the original region. It has been proposed that the ITCZ may break down because of its heating-induced potential vorticity (PV) anomalies. Here this process is examined in three-dimensional simulations using a primitive equation model. A simulation of the ITCZ in a background state of rest is compared to simulations in different background flows. The effect of different vertical structures of the prescribed heating is also examined. Deep heating induces a positive PV anomaly in the lower troposphere, leading to a reversal of the PV gradient on the poleward side of the heating, while the induced PV anomaly at upper levels is negative, leading to a reversal of the PV gradient on the equatorward side of the heating. The response at upper levels leads to a weaker PV gradient change, but the response is greater in areal extent than the lowertropospheric response. For shallow heating, the lower-tropospheric PV response is greater than that for deep heating, and there is no upper-tropospheric PV response. The ITCZ lasts longer before breaking in this case than in the deep heating case. Effects of the background flow are mainly felt in the deep heating cases. When the background flow enforces the PV-induced wind field, ITCZ breakdown occurs more rapidly, whereas when the background flow is opposite to the PV-induced flow, ITCZ breakdown takes longer and the ITCZ may dissipate before breakdown.
Diabetes mellitus related bone metabolism and periodontal disease

Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.
Limitations of travel data for rate computations.

Sherry et al 1 investigated the rate of US citizen injury deaths abroad in their recent article ‘Rates of intentionally caused and road crash deaths of US citizens abroad’. They make an admirable attempt to create injury rates, something that is missing from much of the research on US citizen deaths abroad. However, we feel they have failed to adequately inform the reader of data limitations. The statement in the Discussion …
Historiometric Methods in Social Psychology

Historiometry is a correlational methodology that applies quantitative analyses to archival data concerning historic individuals and events, with the goal of testing nomothetic hypotheses about human behavior. Although not as common as laboratory experiments, this approach was first used in social psychological research about a century ago. Since then, historiometric studies have made important contributions to the scientific understanding of human social behavior. These contributions have touched upon such core issues as attitudes and beliefs, aggression and violence, group dynamics, and leadership. Although the technique must often admit certain disadvantages, historiometry also enjoys some distinct advantages.
Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival.

Importance With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary. Objective To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States. Design, Setting, and Participants A retrospective cohort study using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64 157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection. Main Outcomes and Measures Difference in primary tumor resection rates over time. Results Of the 64 157 patients with stage IV CRC, 43 273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 ( P P P P Conclusions and Relevance The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.
Improved strain-anneal crystal growth technique

A new method of growing iron single crystals* of predetermined orientation is described. *U.S. Patent No. 3694269. This technique differs from the conventional strain-anneal method in that pulse heating is used to suppress random nucleation of undesired grains ahead of the growth interface, rather than a traveling “sharp” temperature gradient which is often difficult to attain. The procedures used to grow large α-iron single crystals with the new technique are fully described. A significant advantage of this method is that large oriented single crystals, 25 cm (10 in.) or greater in length, can be grown from rods or strip in a few hours, with a much higher probability of success than can be obtained with the conventional technique, which typically requires several days to obtain crystals of this size.
MILTON'S VIABLE ATTACK ON PRIOR RESTRAINT IN THE AREOPAGITICA

(1984). MILTON'S VIABLE ATTACK ON PRIOR RESTRAINT IN THE AREOPAGITICA. Free Speech Yearbook: Vol. 23, No. 1, pp. 42-50.
A test of the Hirshfeld definition of atomic charges and moments

The Hirshfeld population analysis scheme which carves the molecular density into atomic density contributions is tested. This method does not require a reference to basis sets or their respective locations, but is based on a different physical and mathematical footing. The advantage of this method is that, when the molecular deformation density converges to the true solution, the computed net charges will necessarily converge. This method also allows a straightforward definition for “local” moments. About 36 molecules have been used to compute the conventional Mulliken and Lowdin population analyses with STO3G, 6311G** and Dunning-Hay split valence basis sets. These results have been compared to the estimates provided by the Hirshfeld model. The charges found in the Hirshfeld method are smaller than those from the other methods.
Monte Carlo Analysis of Pion Contribution to Absorbed Dose from Galactic Cosmic Rays

Accurate knowledge of the physics of interaction, particle production and transport is necessary to estimate the radiation damage to equipment used on spacecraft and the biological effects of space radiation. For long duration astronaut missions, both on the International Space Station and the planned manned missions to Moon and Mars, the shielding strategy must include a comprehensive knowledge of the secondary radiation environment. The distribution of absorbed dose and dose equivalent is a function of the type, energy and population of these secondary products. Galactic cosmic rays (GCR) comprised of protons and heavier nuclei have energies from a few MeV per nucleon to the ZeV region, with the spectra reaching flux maxima in the hundreds of MeV range. Therefore, the MeV - GeV region is most important for space radiation. Coincidentally, the pion production energy threshold is about 280 MeV. The question naturally arises as to how important these particles are with respect to space radiation problems. The space radiation transport code, HZETRN (High charge (Z) and Energy TRaNsport), currently used by NASA, performs neutron, proton and heavy ion transport explicitly, but it does not take into account the production and transport of mesons, photons and leptons. In this paper, we present results from the Monte Carlo code MCNPX (Monte Carlo N-Particle eXtended), showing the effect of leptons and mesons when they are produced and transported in a GCR environment.
Combining electron microscopic with x-ray crystallographic structures.

Analgorithm has been developed for placing three-dimensional atomic structures into appropriately scaled cryoelectron microscopy maps. The first stage in this process is to conduct a three-dimensional angular search in which the center of gravity of an X-ray crystallographically determined structure is placed on a selected position in the cryoelectron microscopy map. The quality of the fit is measured by the sum of the density at each atomic position. The second stage is to refine the three angles and three translational parameters for the best (usually 25 to 100) fits. Useful criteria for this refinement include the sum of densities at atomic sites, the lack of atoms in negative or low density, the absence of atomic clashes between symmetry-related positions of the atomic structure, and the distances between identifiable features in the map and their positions on the fitted atomic structure. These refinements generally lead to a convergence of the originally chosen, top scoring fits to just a few (about 3 to 8) acceptable possibilities. Usually, the best remaining fit is clearly superior to any of the others.
Changes in hepatic lipid composition after infection by LP-BM5 murine leukemia virus causing murine AIDS.

Abstract The severe hepatic disorders in patients with acquired immune deficiency syndrome (AIDS) is often attributed to a variety of other factors which could affect hepatic function. To evaluate the mechanism of liver damage in murine AIDS-induced immune-suppressed animal, a murine model of AIDS (MAIDS), caused by infection with LP-BM5 murine leukemia virus was used at a late stage of the disease. Retroviral infection significantly increased hepatic cholesterol, triacylgycerol and the cholesterol/phospholipid ratio. Similarly, the proportions of palmitic, palmitoleic, linoleic, ratios of linoleic to arachidonic and saturated to unsaturated fatty acids were significantly lower while the proportion of oleic, docosatetraenoic and docosahexenoic fatty acids were significantly increased in the retrovirus infected mice. Hepatic dysfunction as evidenced by increased serum transaminase levels were also observed in the retrovirus infected animals. The data suggest that the liver damage in murine AIDS is induced by retroviral infection and the desaturase enzymes system necessary to maintain regular balance of the fatty acids in the cells may be affected during retroviral infection.
Fabrication of cantilever probes with integrated piezoresistive read- out and built-in piezoelectric actuators

Micromachined cantilevers used as force probes in atomic force microscopy are extremely sensitive to a variety of environment factors such as acoustic noise, temperature and humidity. This unwanted interference can be exploited to produce highly sensitive systems with proper design and under precise conditions. In this paper, we report the development of a new generic process for the fabrication of a microprobe with integrated piezoresistive read-out and built-in piezoelectric actuators. The mechanical performance of cantilever probes of various dimensions was studied. The result from the Finite Element Analysis (FEA) was compared to the experimental results. Application of this probe in a nondestructive, general-purpose, near-field nanomechanical imaging system will be discussed.
Significance of Warm Prestress to Crack Initiation during Thermal Shock.

Abstract During a loss of coolant accident (LOCA) followed by operation of the emergency core cooling system, the inside wall of a nuclear pressure vessel is subjected to high thermal stresses that can cause extension of a pre-existing flaw. During this event the crack-tip stress intensity factor, KI, may achieve its maximum value early in the transient, but the critical level for crack initiation, KIc, may not be reached until minutes later at which time the loading has decreased from its peak. It is shown that this phenomenon, termed warm prestress (WPS), can preclude crack extension when KI equals or exceeds KIc. NRL has conducted an experimental study, employing three-point bend specimens, to investigate the potential for elevation in KIc by WPS, and to translate the significance of this behavior into structural terms in the sense of minimizing crack extension in a nuclear vessel during a LOCA. From the experiments it is concluded that the mechanisms associated with WPS act to elevate the KIc of the material at the crack tip and that this fact can greatly minimize crack extension that would have been predicted theoretically without consideration of WPS. The experiments demonstrated that failure never occurs during the unloading portion of the simulated LOCA path. This finding is of major significance to the integrity of a vessel. For example, with relatively deep cracks there is a combination of conditions wherein initiation ordinarily would be predicted as KIc is reached along a decreasing KI path. For this set of conditions the present research studies have shown that the WPS phenomenon will preclude all such crack initiation. In terms of margin of safety against fracture it is shown that the elevation in KIc caused by WPS is not uniform but depends upon the WPS level, the degree of unloading, and the increment between the temperature of WPS and the failure temperature. For LOCA conditions, however, it is concluded that WPS can result in an effective elevation in KIc up to the WPS level assuming, of course, that metallurgically the material is capable of exhibiting this level of toughness. In terms of structural significance it is clear that WPS by itself cannot prevent the initiation of shallow cracks. Specifically, for a reference calculational vessel under the worst combination of conditions including a long, axial flaw and severe radiation embrittlement it is shown that a shallow crack can extend to a relative depth of 0.34 of the wall thickness; further crack extension is prevented by WPS. However, cracks having initial depths greater than 0.2 of the wall are prevented, by WPS, from extending any amount. Finally, it was observed that an elastic analysis of crack extension during a LOCA has predicted nearly complete penetration of the wall without consideration of WPS. Factoring WPS into the same analysis results in predicted crack extension of greatly reduced proportions such that complete penetration of the wall does not occur. Thus, WPS may form a key element upon which to base the assurance of vessel integrity during a LOCA.
Lifetime history of relapse from exercise

Most research on relapse from exercise has investigated one relapse episode following a structured program. The present study examined the patterns and determinants of the lifetime history of relapse from exercise in a community population. Subjects were 1.811 randomly selected residents of San Diego, California who completed an extensive mailed survey. Subjects reported the number of times over their lifetime that they had exercised vigorously for at least six months and then stopped exercising for at least three months. Approximately 60% of subjects reported zero relapses, 20% reported one or two relapses, and 20% reported three or more relapses. Relapse histories of current exercisers and current nonexercisers were virtually identical. The most commonly reported reason for the last relapse was injuries for both nonexecisers and exercisers. Multiple regression analyses were used to identify correlates of exercise relapse history. These data indicate that cross-sectional surveys of exercise behavior are inadequate to characterize exercise behavior in a population, and injuries are probably a major cause of relapse.
Flow-Mediated Regulation of G-Protein Expression in Cocultured Vascular Smooth Muscle and Endothelial Cells

Abstract—G-proteins have been implicated in the transduction of a number of flow-induced responses. We determined whether flow can modulate vascular endothelial or smooth muscle cell G-protein signaling. By use of a perfused transcapillary coculture system that permits the chronic exposure of cultured endothelial cells (ECs) and smooth muscle cells (SMCs) to physiological shear stresses, cocultures were exposed to stepwise increases in flow up to (1) 2 mL/min (low flow: 0.5 dyne/cm2), or (2) 44 mL/min (high flow: 15 dyne/cm2) and maintained for 72 hours before SMCs and ECs were harvested separately. Using Western blot analysis, EC Giα3 expression was significantly increased (41±2.9%) by high-flow conditions compared with low-flow. The changes in G-protein expression were associated with a significant increase in endothelial nitric oxide synthase (eNOS) activity, elevated prostacyclin levels in the perfusing media, increased pertussis toxin–catalyzed ADP ribosylation of Giα substrates, and enhanced agonist...
Intermembrane Molecular Contacts by Polymyxin B Mediate Exchange of Phospholipids

Direct intermembrane exchange of dimyristoylphosphatidylmethanol is mediated by polymyxin B (PxB), a cationic amphipathic cyclic decapeptide. The possibility that the phospholipid exchange is mediated by solubilization of phospholipids or by fusion of vesicles is ruled out. By kinetic and spectroscopic methods it is shown that the exchange occurs directly through vesicle-vesicle contacts formed by a few PxB molecules. The contact is stable on the time scale of several minutes such that neither PxB nor the vesicles in the pair forming a contact exchange with excess vesicles. Several contacts may be formed on a vesicle, which leads to the formation of a cluster of vesicles, and the lipid molecules on the outer monolayers of vesicles exchange throughout the cluster. Kinetics of substrate replenishment during processive interfacial catalysis suggests that the exchange of anionic lipids over the contact occurs at a rate considerably faster than 300 s-1. The exchange through the contact is specific for certain lipids, and phospholipids with a modified head group or phospholipase A2 bound to a vesicle are not transferred to the other vesicle in contact. Since this phenomenon has not been described before, possible implications of direct vesicle-vesicle exchange of phospholipids through peptide-mediated molecular contacts are discussed. Such a mechanism for intermembrane transfer of phospholipids could be responsible for intracellular trafficking and sorting of phospholipids; it could be a necessary first step for the sequence of events leading to budding, vesiculation, and secretion; and PxB-mediated transfer between the inner and outer membranes of Gram-negative bacteria could also account for its antibiotic action.
Integrative Understanding of Emergent Brain Properties, Quantum Brain Hypotheses, and Connectome Alterations in Dementia are Key Challenges to Conquer Alzheimer's Disease

The biological substrate for cognition remains a challenge as much as defining this function of living beings. Here, we examine some of the challenges to understand normal and disordered cognition in humans. We use aspects of Alzheimer’s disease and related disorders to illustrate how the wealth of information at many conceptually separate, even decoupled, physical scales — in particular at the Molecular Neuroscience versus Systems Neuroscience/Neuropsychology levels — presents a challenge in terms of true interdisciplinary integration towards a coherent understanding. These unresolved dilemmas include critically the as yet untested Quantum Brain hypothesis, and the embryonic attempts to develop and define the so-called Connectome in humans and in non-human models of disease. To mitigate these challenges, we propose a scheme incorporating the vast array of scales of the space and time (space-time) manifold from at least the subatomic through cognitive-behavioral dimensions of inquiry, to achieve a new understanding of both normal and disordered cognition, that is essential for a new era of progress in the Generative Sciences and its application to translational efforts for disease prevention and treatment.