cssi/SciSciGPT-SciSciNet huggingface dataset:
Non-sequential expression of multiple immunoglobulin classes by isolated B-cell clones

As humoral immunity to a given antigen is generally thought to display an early IgM response which is later dominated by IgG synthesis, it has long been thought that clones of antibody-producing cells switched from μ to γ (refs 1–5). The sequence of appearance of immunoglobulin classes produced by the progeny of isolated precursors (B cells) to antibody-forming cells may answer the questions (1) does a clone of cells switch from μ to γ to α, and (2) do all clones switch in the same order following antigen stimulation? Results presented here show that there is no order of expression of immunoglobulin class with time by B-cell clones stimulated by antigen in the presence of carrier help, because any class can appear first or simultaneously with any other class.
Block of HAC1 mRNA Translation by Long-Range Base Pairing Is Released by Cytoplasmic Splicing upon Induction of the Unfolded Protein Response

Abstract Expression of the yeast transcription factor Hac1p, which controls the unfolded protein response, is regulated posttranscriptionally. Hac1p is only produced when an intron at the 3′ end of its mRNA is removed by a nonconventional, regulated splicing reaction. We show that a previously unrecognized base-pairing interaction between the intron and the 5′ untranslated region is required and sufficient to block mRNA translation. Unspliced HAC1 mRNA is stable, located in the cytosol, and is associated with polyribosomes, yet does not produce protein, indicating that the ribosomes engaged on the mRNA are stalled. We show that the polysomal, cytoplasmic pool of HAC1 mRNA is a substrate for splicing, suggesting that the stalled ribosomes may resume translation after the intron is removed.
A hydrodynamics-based surge scale for hurricanes

Abstract Record hurricane surges over the last several years have demonstrated the need for an improved surge hazard warning scale for hurricanes. Here, a simple hydrodynamics-based surge scale for hurricane surge hazard is presented. This surge scale incorporates readily available meteorological information along with regional-scale bathymetry into a single measure of expected surge levels at the coast. We further outline an approach for estimating expected flood inundation and damages based on the alongshore extent of high surges during hurricanes. Comparisons between this new surge scale and historical hurricane observations show a measurable improvement over existing surge indices, including the Saffir–Simpson scale. It is anticipated that the proposed surge scale will improve public awareness of surge hazard and assist governments in communicating critical decisions regarding evacuation and emergency response.
What causes the flux excess in the heliospheric magnetic field

[1] Ulysses results indicate that the total magnetic flux inside the heliosphere, Φ, can be obtained from the radial field component measured at a single spacecraft multiplied by the square of the radial distance and averaged over a solar rotation, . However, that result is contrary to a large increase in Φ with distance, called the flux excess, that has been reported by Owens et al. (2008a) and attributed to variations in solar wind speed by Lockwood et al. (2009a, 2009b). Ulysses data and a mathematical simulation are used to show that the cause of the flux excess is the replacement of BR by the modulus, |BR|. The modulus rectifies some of the large amplitude magnetic field variations normally present in measurements of BR and increases the mean, relative to . The variance of the magnetic fluctuations, σ, decreases less rapidly with distance than BR and that produces a progressively larger error in resulting in the flux excess. The advisability of defining Φ in terms of |BR|, of using beyond 1 AU and the applicability of the Lockwood et al. (2009b) correction to are questioned.
Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17β-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1β and tumor necrosis factor-α (TNF-α) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17β-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1β and TNF-α and was also not affected by 17β-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10-7 M) significantly inhibited IL-1β plus TNF-α stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.
Lone Star Tick-Infecting Borreliae Are Most Closely Related to the Agent of Bovine Borreliosis

Although Borrelia theileri, the agent of bovine borreliosis, was described at the turn of the century (in 1903), its relationship with borreliae causing Lyme disease or relapsing fever remains undescribed. We tested the previously published hypothesis that spirochetes infecting Lone Star ticks (Amblyomma americanum) may comprise B. theileri by analyzing the 16S ribosomal DNAs (rDNAs) and flagellin genes of these spirochetes. B. theileri, the Amblyomma agent, and B. miyamotoi formed a natural group or clade distinct from but most closely related to that of the relapsing fever spirochetes. B. theileri and the Amblyomma agent were 97 and 98% similar at the nucleotide level within the analyzed portions of the 16S rDNA and the flagellin gene respectively, suggesting a recent divergence. The agent of bovine borreliosis might be explored as a surrogate antigen for the as-yet-uncultivatable Amblyomma agent in studies designed to explore the etiology of a Lyme disease-like infection associated with Lone Star ticks.
2000 SPR Award for distinguished contributions to psychophysiology.

Presentation to John Cacioppo on the occasion of the Award for Distinguished Contributions to Psychophysiology, Saturday October 21, 2000, San Diego.
Host response to infection: the role of CpG DNA in induction of cyclooxygenase 2 and nitric oxide synthase 2 in murine macrophages.

Depending on sequence, bacterial and synthetic DNAs can activate the host immune system and influence the host response to infection. The purpose of this study was to determine the abilities of various phosphorothioate oligonucleotides with cytosine-guanosine-containing motifs (CpG DNA) to activate macrophages to produce nitric oxide (NO) and prostaglandin E2 (PGE2) and to induce expression of NO synthase 2 (NOS2) and cyclooxygenase 2 (COX2). As little as 0.3 μg of CpG DNA/ml increased NO and PGE2 production in a dose- and time-dependent fashion in cells of the mouse macrophage cell line J774. NO and PGE2 production was noted by 4 to 8 h after initiation of cultures with the CpG DNA, with the kinetics of NO production induced by CpG DNA being comparable to that induced by a combination of lipopolysaccharide and gamma interferon. CpG DNA-treated J774 cells showed enhanced expression of NOS2 and COX2 proteins as determined by immunoblotting, with the relative potencies of the CpG DNAs generally corresponding to those noted for the induction of NO and PGE2 production as well as to those noted for the induction of interleukin-6 (IL-6), IL-12, and tumor necrosis factor. Extracts from CpG DNA-treated cells converted l-arginine to l-citrulline, but the NOS inhibitor NG-monomethyl-l-arginine (NMMA) inhibited this reaction. The COX2-specific inhibitor NS398 inhibited CpG DNA-induced PGE2 production and inhibited NO production to various degrees. The NOS inhibitors NMMA, 1400W, and N-iminoethyl-l-lysine effectively blocked NO production and increased the production of PGE2 in a dose-dependent fashion. Thus, analogues of microbial DNA (i.e., CpG DNA) activate mouse macrophage lineage cells for the expression of NOS2 and COX2, with the production of NO and that of PGE2 occurring in an interdependent manner.
The invasive Sorghum halepense harbors endophytic N2-fixing bacteria and alters soil biogeochemistry

Exoticplantsinvadingnewhabitatsfrequently initiate broad changes in ecosystem functioning. Sorghum halepense is an invasive grass capable of growing in nitrogen (N)-poor tallgrass prairie soils that creates near monocultures in once phylogenetically diverse-communities. The biogeochemistry of soils invaded by S. halepense was compared to that of un- invaded native prairie soils. Invaded soils contained two to four times greater concentrations of alkaline metals, micronutrients, and essential plant nutrients than native prairie soils. The notable exception was Ca +2 ,w hich was always significantly lower in invaded soils. The N- content of S. halepense above-ground biomass was 6.4 mg g −1 (320 mg N plant −1 ) and suggested a supplemental N source supporting plant growth. Altered soil biogeochemistry in invaded areas coupled with high above-ground biomass in N-poor soils suggested N2- fixing activity associated with S. halepense. Nitrogenase activity of plant tissues indicated that N2-fixation was occurring in, and largely restricted to, S. halepense rhizomes and roots. A culture approach was used to isolate these N2-fixing bacteria from plant tissues, and 16S rRNA gene sequencing was used to identify these bacterial isolates. Nitrogenase activity of bacterial isolates indicated several were capable of N2-fixation. In addition to N2-fixation, other roles involved in promoting plant growth, namely mobilizing phosphorus and iron chelation, are known for closest matching relatives of the bacterial isolates identified in this work. Our results indicate that these plant growth-promoting bacteria may enhance the ability of S. halepense to invade and persist by altering fundamental ecosystem properties via significant changes in soil biogeochemistry.
Alcohol use and cultural change in an indigenous population: a case study from Venezuela.

— Aims: To explore the historical and cultural context of problem drinking in a Latin American indigenous population and identify possible areas for intervention. Methods: Focus group discussions. Results: Participants reported that prior to 1945, binge drinking and fighting were part of cultural festivals held several times each year. Alcohol was brewed in limited quantities by specially qualified individuals. Limited family violence and injuries resulted. Increasing contact with Western civilization resulted in year-round access to large supplies of commercial alcohol and exposure to alcohol-misusing role models. Increased heavy drinking and decreases in subsistence farming resulted in escalation of problems, including hunger, serious injury, family violence, divorce and legal problems. Communities are beginning to regain control by prohibiting sale of alcohol in villages, sponsoring alcohol-free celebrations, and increasing involvement in religious activities. Conclusions: Though alcohol may cause devastating consequences in cultures in transition, studies of community responses may identify useful strategies for reducing alcohol-related harm.
Ground water contamination from agricultural sources: implications for voluntary policy adherence from Iowa and Virginia farmers' attitudes.

Contamination of ground water from agricultural sources has been documented in a majority of the contiguous United States. In this study, we examine the potential for voluntary adoption of management practices that reduce risk of ground water contamination and discuss how f arm operators' attitudes regarding the environment might affect the success of voluntary programs. Farmers' behavior and attitudes in Rockingham County, Virginia, and Big Spring Basin, Iowa, reveal that both groups consider the ground water issue to be a serious problem to which they are contributing. This awareness is a significant first step in prompting consideration of management practices that reduce the threat to ground water quality. We also found that the “worst offenders”—that is, farmers applying nitrogen well above agronomic recommendations-were those with the least concern about the problem. If major shifts in farming practices are to occur voluntarily, major incentives or disincentives are needed. Even though the concern about ground water quality is high, the documented risks perceived by farmers are not strongly convincing. The economic incentives for change are questionable at best. Voluntary adoption of best management practices is only one of several policy options. Ultimately, policies designed to reduce ground water contamination may need a mix of strategies, including economic incentives and disincentives, zoning and land use restrictions, environmental regulations, and bans on agricultural chemicals.
Field-Aligned Currents Near the Magnetosphere Boundary

This paper reviews present thinking about the structure of magnetospheric boundary layers and their roles in the generation of the field-aligned currents that are observed in the polar regions. A principal effect of the momentum loss by magnetosheath plasma to the magnetosphere boundary regions just within the magnetopause, whether it be by a diffusive process or by magnetic reconnection, is the tailward pulling of surface flux tubes relative to those deeper below the surface. The dayside region 1 currents at low altitudes flow along field lines in the resulting regions of magnetic shear. The direction of the shear and its magnitude, measured in the boundary region, confirm tht the polarities and intensities of the dayside region 1 currents can be accounted for by this process. The low latitude boundary layer, formerly thought to be threaded entirely by closed field lines, now appears to contain at least some open field lines, newly reconnected, that are in the process of being swept into the high latitude tail to form the plasma mantle. The open flux tubes of the flux transfer events, thought to be the product of patchy reconnection have a spiral magnetic structure whose helicity is such as to suggest currentsmore » having the polarities of the region 1 currents.« less
Tests of the infinite-order sudden approximation

Abstract The assumptions of the infinite-order sudden (IOS) approximation are examined by testing them on an accurately calculated scattering matrix. It was found that the accurate S matrix was not even roughly diagonal in the IOS representation. If, however, the elastic phase shift is removed from the scattering matrix, then the modified S matrix is approximately diagonal in the IOS representation.
A Review of “Sociology of Education: An A–Z Guide,”

Putting together a two-volume encyclopedia on any subject is no easy task, especially when one is trying to take a snapshot of a rapidly growing field like the sociology of education. Fortunately, ...
Development of tunable terahertz wire lasers

We report a novel tuning mechanism based on a “wire-laser” with subwavelength transverse dimensions(w≪λ). By manipulating the waveguided mode propagating outside the cavity, frequency tuning of ∼137GHz (3.6%) is demonstrated from a single-laser device at ∼3.8THz.
Performance of Coexisted WiFi and ZigBee Networks

We proposed a method for precisely monitoring the impact of WiFi networks on Zigbee networks. We utilized the characteristic of Zigbee that when working in lower transmit power, the interference will be reflected on the packet payload as corrupted bytes. Comparing with network analyzer, our system is easy to deploy and able to yield reasonable result. Comparing with collecting the metadata from the internal of the network, our system is not limited to specific network architecture. We conducted the experiment with our method in realistic environment when 20 WiFi access points and numerous clients are presented. Our result reveals that the duration of a consistent WiFi interference is distributed as power law. The same law applies on the interval between two WiFi consecutive interference. The experiment result reveals that the Zigbee transmission severely suffers the fast and frequent WiFi interference, which made it impossible to mitigate the interference with MAC layer approach. Moreover, the methodology of the experiment enables us to observe the interaction of WiFi and Zigbee in sub-packet level, which is more precise than typical measurement, such as packet loss rate or bit error rate.
Juvenile idiopathic arthritis and enthesitis-related arthropathies

Juvenile idiopathic arthritis (JIA) represents a spectrum of non-pyogenic inflammatory arthritides affecting children. The purpose of this pictorial review is to illustrate the imaging spectrum of JIA and the role of radiology in disease diagnosis and management.
Hotspot-Limited Microprocessors: Direct Temperature and Power Distribution Measurements

An experimental technique is presented, which allows for spatially-resolved imaging of microprocessor power (SIMP). In a first step this method utilizes infrared (IR) thermal imaging, while the processor is effectively cooled using an IR-transparent heat sink. In the second step the underlying power distribution is derived by determining the temperature fields for each individual power source on the chip. The measured chip temperature distribution is represented as a superposition of these temperature fields. The SIMP data reveals significant temporal and spatial variations of the microprocessor power/temperature distribution, which can be attributed to the circuit layout as well as to the varying utilization levels across the processor while running full workloads. In this paper we have applied the SIMP method to the dual core PowerPCtrade970MP microprocessor to measure detailed temperature and power distributions under full operating conditions. In the first part of the paper the impact of power and temperature limitations of high performance CMOS chips is discussed in detail, where we distinguish between hotspot-limited (or temperature-limited) and power-limited chips. The discussion shows the importance of temperature and power distributions for chip floor planning, layout, design and architecture. Second, we present the experimental details of the SIMP method, which is applied to the dual core PowerPC970MP to directly measure the temperature and power fields as a function of workload and frequency. A pronounced movement of the hotspot location is observed. Finally, the hotspot of a competitive microprocessor is compared by measuring temperature efficiencies (temperature increase/performance) for the same workloads and cooling conditions
Dielectric waveguides in two-dimensional photonic bandgap materials

We investigate the performance and guiding properties of waveguides fabricated in a finite two-dimensional (2-D) photonic bandgap (PBG) structure. Confinement in the direction perpendicular to the plane of periodicity is achieved by fabricating the 2-D PBG structure in a high dielectric layer enclosed by two lower dielectric layers. Simulations using the finite-difference time-domain (FDTD) method are performed to investigate the energy transport in such waveguides. Good qualitative agreement is found with the experimental observations.
A three-trophic-level analysis of the effects of plant hybridization on a leaf-mining moth

We investigated relationships between host plant hybridization in the Quercus grisea x Q. gambelii species complex and the distribution and performance of a leaf-mining moth in the genus Phyllonorycter. In 2 years at two sites Phyllonorycter densities were lowest on Q. grisea and increased through the categories of hybrid host plants to Q. gambelii. Direct host plant effects on Phyllonorycter performance were consistent with Phyllonorycter distribution; unexplained mortality of larvae in the mines, which is often associated with direct plant effects, decreased from Q. grisea through the hybrids to Q. gambelii. Plant hybridization influenced parasitism of Phyllonorycter. Parasitism was density dependent, and across all densities was higher on Q. grisea and Q. gambelii than on hybrid host plants.
Genetic diversity in honey bee colonies enhances productivity and fitness

Honey bee queens mate with many males, creating numerous patrilines within colonies that are genetically distinct. The effects of genetic diversity on colony productivity and long-term fitness are unknown. We show that swarms from genetically diverse colonies (15 patrilines per colony) founded new colonies faster than swarms from genetically uniform colonies (1 patriline per colony). Accumulated differences in foraging rates, food storage, and population growth led to impressive boosts in the fitness (i.e., drone production and winter survival) of genetically diverse colonies. These results further our understanding of the origins of polyandry in honey bees and its benefits for colony performance.
Using multiband correlation models for the invariant recognition of 3-D hyperspectral textures

We develop a method for the recognition of three-dimensional (3-D) textures in hyperspectral images. Textures are modeled using subspaces of multiband correlation functions that represent texture variability over a range of solar angles and atmospheric conditions. These subspace models are used to enable texture recognition that is invariant to these environmental variables. The multiband correlation model captures within and between spectral band spatial characteristics. We present a method that can be used to optimize the selection of the multiband correlation functions for a given texture discrimination problem. We demonstrate the effectiveness of the approach using texture recognition experiments that consider 2016 texture samples from 168 hyperspectral images that were synthesized for a 3-D scene over a range of conditions. The results show that 3-D textures can be accurately recognized over a wide range of conditions using a small number of multiband correlation functions.
Psychopaths Are Impaired in Social Exchange and Precautionary Reasoning

Psychopaths show a profound lack of morality and behavioral controls in the presence of intact general intellectual functioning. Two hallmarks of psychopathy are the persistent violation of social contracts (i.e., cheating) and chronic, impulsive risky behavior. These behaviors present a puzzle: Can psychopaths understand and reason about what counts as cheating or risky behavior in a particular situation? We tested incarcerated psychopaths' and incarcerated nonpsychopaths' reasoning about social contract rules, precautionary rules, and descriptive rules using the Wason selection task. Results were consistent with our hypotheses: Psychopaths (compared with matched nonpsychopaths) showed significant impairment on social contract rules and precautionary rules, but not on descriptive rules. These results cannot be accounted for by differences in intelligence, motivation, or general antisocial tendency. These findings suggest that examination of evolutionarily identified reasoning processes can be a fruitful research approach for identifying which specific mechanisms are impaired in psychopathy.
Relationship of mMRC and CAT scores in COPD patients

There are several validated questionnaires to assess symptoms in patients with COPD. For the assessment of symptoms in COPD, the GOLD document recommends either the use of a modified British Medical Research Council (mMRC) questionnaire or the chronic obstructive pulmonary disease assessment test score (CAT). Furthermore, GOLD proposes that a cut-off value of 2≤ in mMRC can substitute a cut-off value of 10≤ in CAT. However, no report can be found in the literature showing that those cut-off values are interchangeable. Therefore, we set out to investigate the relationship of those cut-off values. We studied 89 (70 men) consecutive, Caucasian, COPD patients. They had (mean±SD): age=69±8 y, pack-years=100±74 y, FEV1, %pred=47±20, FVC, %pred=73±24, and FEV1/FVC, %=51±12. Chronic dyspnoea was rated according to the mMRC 5-point dyspnoea scale. Health status was measured with the CAT. All patients reported some degree of dyspnoea (mMRC was 2.7±1.4). CAT score was 21±10. mMRC was significantly correlated with CAT score (r=0.788, p<0.0001). Backward stepwise regression between mMRC score and the individual CAT’s questions showed that some questions (1, 2, 7, and 8) did not significantly add to the capacity of the equation to predict the mMRC score (r=0.790, p<0.05). mMRC was ≥2 in 65/89 (73%) patients and CAT was ≥10 in 77/89 (87%) patients. Statistical analysis showed that those cut-off values were significantly correlated (p<0.001). In COPD, mMRC dyspnoea score is closely related to CAT score, and hence these assessment tools may be used interchangeably.
Opto-electronic characterization of CdTe solar cells from TCO to back contact with nano-scale CL probe

We used cathodoluminescence (CL) (spectrum-per-pixel) imaging on beveled CdTe solar cell sections to investigate the opto-electronic properties of these devices from the TCO to the back contact. We used a nano-scale CL probe to resolve luminescence from grain boundary (GB) and grain interior (GI) locations near the CdS/CdTe interface where the grains are very small. As-deposited, CdCl2-treated, Cu-treated, and (CdCl2+Cu)-treated cells were analyzed. Color-coded CL spectrum imaging maps on bevels illustrate the distribution of the T=6 K luminescence transitions through the depth of devices with unprecedented spatial resolution. The CL at the GBs and GIs is shown to vary significantly from the front to the back of devices and is a sensitive function of processing. Supporting D-SIMS depth profile, TRPL lifetime, and C-V measurements are used to link the CL data to the J-V performance of devices.
Origin and fate of IgE-bearing lymphocytes: modulation of IgE isotype expression on Peyer's patch cells.

The absence of precursor B lymphocytes bearing membrane bound IgE (sIgE) from bone marrow (1,2) and Peyer’s patches of conventionally raised (C) adult rats, and the presence of high numbers of these cells in PP (2), but not bone marrow (2) of germ-free (GF) rats suggests that environmental antigens, such as bacteria, may play a role in “natural” regulation of IgE isotype expression. We have now succeeded in modulating IgE isotype expression on GF rat PP cells so that they resemble those of C rats. The data suggest that exposure to gut flora influenced these changes, either directly or through the mediation of sThy 1+ regulatory T cells (see 3,4).
1,25-Dihydroxyvitamin D induces the glutamate transporter SLC1A1 and alters glutamate handling in non-transformed mammary cells

Genomic profiling of immortalized human mammary epithelial (hTERT-HME1) cells identified several metabolic genes, including the membrane glutamate transporter, SLC1A1, as 1,25-dihydroxyvitamin D3 (1,25D) regulated. In these studies we have surveyed the effects of 1,25D on known glutamate transporters and evaluated its impact on cellular glutamate handling. We confirm that expression of SLC1A1 and all of its known transcript variants are significantly upregulated in hTERT-HME1 cells following 1,25D treatment. Expression of the full-length cognate protein, EAAT3, is correspondingly increased in 1,25D treated hTERT-HME1 cells. Under the same conditions, the expression of two other glutamate transporters--SLC1A6 (EAAT4) and SLC1A2 (EAAT2 or GLT-1)--is enhanced by 1,25D while that of SLC1A3 (EAAT1 or GLAST) and SLC7A11 (xCT) is decreased. Glutamate is not essential for growth of hTERT-HME1 cells, and supplemental glutamate (up to 0.5 mM) does not abrogate the growth inhibitory effects of 1,25D. These data suggest that extracellular glutamate is not a major contributor to cellular energy metabolism in hTERT-HME1 cells under basal conditions and that the growth inhibitory effects of 1,25D are not secondary to its effects on glutamate handling. Instead, the effects of 1,25D on glutamate transporters translated to a decrease in cellular glutamate concentration and an increase in media glutamate concentration, suggesting that one or more of these transporters functions to export glutamate in response to 1,25D exposure. The reduced cellular glutamate concentration may also reflect its incorporation into the cellular glutathione (GSH) pool, which is increased upon 1,25D treatment. In support of this concept, the expression of GCLC (which codes for the rate-limiting enzyme in GSH synthesis) and genes which generate reducing equivalents in the form of NADPH (ie, G6PD, PGD, IDH2) are elevated in 1,25D-treated cells. Taken together, these data identify 1,25D as a physiological regulator of multiple membrane glutamate transporters that impacts on overall cellular glutamate handling.
Inactivation of Escherichia coli O157:H7, Listeria monocytogenes, and Lactobacillus leichmannii by combinations of ozone and pulsed electric field

Pulsed electric field (PEF) and ozone technologies are nonthermal processing methods with potential applications in the food industry. This research was performed to explore the potential synergy between ozone and PEF treatments against selected foodborne bacteria. Cells of Lactobacillus leichmannii ATCC 4797, Escherichia coli O157:H7 ATCC 35150, and Listeria monocytogenes Scott A were suspended in 0.1% NaCl and treated with ozone, PEF, and ozone plus PEE Cells were treated with 0.25 to 1.00 microg of ozone per ml of cell suspension, PEF at 10 to 30 kV/cm, and selected combinations of ozone and PEF. Synergy between ozone and PEF varied with the treatment level and the bacterium treated. L. leichmannii treated with PEF (20 kV/cm) after exposure to 0.75 and 1.00 microg/ml of ozone was inactivated by 7.1 and 7.2 log10 CFU/ml, respectively; however, ozone at 0.75 and 1.00 microg/ml and PEF at 20 kV/cm inactivated 2.2, 3.6, and 1.3 log10 CFU/ml, respectively. Similarly, ozone at 0.5 and 0.75 microg/ml inactivated 0.5 and 1.8 log10 CFU/ml of E. coli, PEF at 15 kV/cm inactivated 1.8 log10 CFU/ml, and ozone at 0.5 and 0.75 microg/ml followed by PEF (15 kV/cm) inactivated 2.9 and 3.6 log10 CFU/ml, respectively. Populations of L. monocytogenes decreased 0.1, 0.5, 3.0, 3.9, and 0.8 log10 CFU/ml when treated with 0.25, 0.5, 0.75, and 1.0 microg/ml of ozone and PEF (15 kV/cm), respectively; however, when the bacterium was treated with 15 kV/cm, after exposure to 0.25, 0.5, and 0.75 microg/ml of ozone, 1.7, 2.0, and 3.9 log10 CFU/ml were killed, respectively. In conclusion, exposure of L. leichmannii, E. coli, and L. monocytogenes to ozone followed by the PEF treatment showed a synergistic bactericidal effect. This synergy was most apparent with mild doses of ozone against L. leichmannii.
Richard Epstein's Classical Liberal Constitution: What Might Benjamin Franklin Have Thought?

This essay accepts the normative vision Richard Epstein sets forth in The Classical Liberal Constitution, but refracts that vision through some considerations of positive political economy. In response to a questioner who asked at the conclusion of the Constitutional Convention what kind of constitution had been created, Benjamin Franklin is reported to have answered “a republic, if you can keep it.” Franklin’s response shows that he recognized that regimes are subject to constitutional erosion. This essay applies Franklin’s insight to Epstein’s formulation. The original liberal republic has not been kept. Epstein sets forth a judicial path along which that path might be recovered. Considerations from political economy suggest that more than judicial interpretation is at work in the constitutional erosion Epstein describes, and some understanding of those extra-judicial processes is also significant for any effort aimed at restoring a liberal republic.
Nonparametric analysis of bivariate gap time with competing risks

This article considers nonparametric methods for studying recurrent disease and death with competing risks. We first point out that comparisons based on the well-known cumulative incidence function can be confounded by different prevalence rates of the competing events, and that comparisons of the conditional distribution of the survival time given the failure event type are more relevant for investigating the prognosis of different patterns of recurrence disease. We then propose nonparametric estimators for the conditional cumulative incidence function as well as the conditional bivariate cumulative incidence function for the bivariate gap times, that is, the time to disease recurrence and the residual lifetime after recurrence. To quantify the association between the two gap times in the competing risks setting, a modified Kendall's tau statistic is proposed. The proposed estimators for the conditional bivariate cumulative incidence distribution and the association measure account for the induced dependent censoring for the second gap time. Uniform consistency and weak convergence of the proposed estimators are established. Hypothesis testing procedures for two-sample comparisons are discussed. Numerical simulation studies with practical sample sizes are conducted to evaluate the performance of the proposed nonparametric estimators and tests. An application to data from a pancreatic cancer study is presented to illustrate the methods developed in this article.
Abstract CN07-03: Polymorphisms in miRNA binding sites as risk factors for cancer development

Purpose: Ovarian cancer is the single most deadly form of cancer specific to women, largely due to a lack of known risk factors or genetic markers. The KRAS oncogene and altered levels of the microRNA let‐7 are associated with increased risk of developing solid tumors, such as ovarian cancer. We investigated a single nucleotide variant (rs61764370) that disrupts a let‐7 microRNA binding site in the KRAS oncogene as a biomarker of ovarian cancer risk. Methods: Specimens were obtained from non‐selected ovarian cancer patients in three independent cohorts (n = 445) and two independent ovarian case‐control studies. Specimens from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 52) and their family members were also collected. Results: rs61764370 is in greater than 30% of non‐selected ovarian cancer cases and is a marker for a significant increased risk of developing ovarian cancer by case control analysis (n = 201, OR = 2.46, CI = 1.14–5.29, p = .020). This was validated in a second independent ovarian case‐control (n = 648). Furthermore, rs61764370 was identified in 58% of HBOC patients without BRCA1 or BRCA2 mutations (n = 24, p Conclusions: These findings support the hypothesis that rs61764370 is a genetic marker of increased risk of developing ovarian cancer, and suggests that rs61764370 may be a new biomarker of risk for HBOC families without other known genetic abnormalities. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN07-03.
Computer Games: Environments for Developing Spatial Cognition?

This experimental study investigated whether fifth, seventh, and ninth grade students participating in selected computer games utilizing spatial skills would improve their scores on a spatial ability measure. A significant treatment effect in favor of the experimental conditions was found in the analyses of covariance. No significant interaction or main effects were found for grade level or sex, indicating that males and females at all three grade levels seemed to benefit from this experience. These results suggest that certain computer games may enhance the development of spatial ability as measured by the Mental Rotation Test. Identified spatial components of the two games included visual perception and discrimination, differentiation of opposite obliques, visualization of transformations in series, the use of referent systems, and the development and updating of cognitive maps.
Abstract 3682: Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells.

Withaferin A (WA), a constituent of the Ayurvedic medicine plant Withania somnifera, exhibits in vivo efficacy against human breast cancer xenografts in athymic mice as well as spontaneous mammary cancer development in MMTV-neu transgenic mice. However, the mechanism underlying anticancer effect of WA is not fully understood. The present study was undertaken to determine the role of Notch family of transcription factors in anticancer effects of WA using human breast cancer cells as a model. Notch activation is linked to mammary carcinogenesis as evidenced by the following observations: (a) overexpression of activated Notch1 and Notch3 in transgenic mice blocks mammary gland development but induces tumorigenesis of the breast; (b) high level expression of Notch1 and its ligands is associated with poor outcome in breast cancer; (c) expression of Notch ligand Jagged1 is associated with recurrence in lymph node-negative breast cancer; and (d) Notch1 is involved in migration and invasion of human breast cancer cells. The present study reveals differential effect of WA treatment on activation of Notch1 versus Notch2 in human breast cancer cells. Exposure of MDA-MB-231 (an estrogen-independent cell line with mutant p53) and MCF-7 (an estrogen-responsive cell line with wild-type p53) human breast cancer cells to pharmacological concentrations of WA (2 and 4 μM) resulted in cleavage (suggesting activation) of Notch2, which was accompanied by transcriptional activation of Notch as evidenced by RBP-Jk, HES-1A/B, and HEY-1 luciferase reporter assays. On the other hand, WA treatment caused a decrease in levels of both transmembrane and cleaved (active) Notch1. The WA-mediated activation of Notch2 was associated with induction of γ-secretase complex components presenilin1 and/or nicastrin. Inhibition of MDA-MB-231 and MDA-MB-468 cell migration resulting from WA exposure was statistically significantly augmented by knockdown of Notch2 using siRNA and shRNA. Activation of Notch2 was not observed in cells treated with withanone or withanolide A, which are structural analogs of WA. Moreover, withanone and withanolide A were practically inactive against MDA-MB-231 cell migration. The results of the present study suggest that anti-metastatic effect of WA may be augmented in the presence of Notch2 inhibitors. This study was supported by the grant CA142604 awarded by the National Cancer Institute. Citation Format: Joomin Lee, Anuradha Sehrawat, Shivendra V. Singh. Differential effect of withaferin A treatment on activation of Notch1 and Notch2 in human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3682. doi:10.1158/1538-7445.AM2013-3682
Understanding the Structure of Contractual and Covenantal Social Relations: Implications for the Sociology of Religion

Social scientists have largely abandoned the analysis of distinctions between tribal (family and clan) and industrial (marketplace and organizational) types of social relations. In this paper we draw a distinction between contractual and covenantal social relations which, we argue, parallels that societal level dichotomy on an interpersonal level. It is the thesis of this paper that contracts and covenants are alternative and qualitatively different types of social relations. As industrial societies have become increasingly contractual, the form and logic of the covenants have been ignored. In the present historical context of dominant power resting with individuals whose resources are created primarily within contractual social relations, covenantal forms tend largely to be denigrated. The social sciences, historically developed with presuppositions which also serve as the justification for contracts, have contributed to this denigration. We begin, therefore, by comparing the form and logic covenants and contracts. Using this distinction, we then analyze the controversy over new religions as illustrative of the continuing structural conflict between these types of social relations. We conclude with a call for a sociology of religion which does not presuppose the logic of either type but rather is broad enough to encompass both contractual and covenantal social relations. Social scientists have largely abandoned the analysis of distinctions between tribal (family and clan) and industrial (marketplace and organizational) forms of social relations which informed the work of early theorists such as Toennies, Durkheim, Main, Redfield and Wirth. As contemporary theorists increasingly have come to rely upon theory appropriate only to the industrial fonn, an important qualitative distinction has been obscured. The thesis developed
Cognitive Behavioral Therapy for Depression

This chapter addresses the treatment of depression from a CBT perspective. It provides examples of interventions, both cognitive and behavioral, to address depressive symptoms. A case is also presented to elucidate CBT techniques.
Composition, regulation, and function of the cytoskeleton in mammalian eggs and embryos.

The cytoskeleton of the mammalian egg and early embryo is highly unique when compared to the cytoskeleton of their somatic cell brethren. Although all three cytoskeletal systems, actin filaments, microtubules, and intermediate filaments, are present as early as the unfertilized egg; each system has adapted features that allow the egg and early embryo to meet the strict demands of the developmental process. The major demands placed upon eggs and embryos are developmental transitions (i.e., fertilization, compaction, blastocyst formation, germ layer formation and gastrulation), each of which must be traversed in order for the embryo to form a new individual. To successfully complete all of the necessary processes during early development, eggs and embryos must call upon many signal transduction mechanisms, cytoskeletal components, and genes that are both unique to embryogenesis and ubiquitous among many types of somatic cells. It is the goal of this review to provide some current details into the mechanisms that drive early development primarily focusing on the cytoskeletal components eggs and embryos have adapted to promote embryogenesis.
Osteoimmunology: Relation to Disease and Therapy

The association between inflammation and bone loss long has been recognized, leading to speculation that cells of the immune system participate in the control of bone remodeling. The discovery that the receptor activator of NF-κB (ligand) RANKL/RANK system plays a pivotal role in both adaptive immunity and osteoclastogenesis has provided molecular evidence firmly linking the immune system and bone. Although studies from our laboratory and from others have shown that activated T cells secrete RANKL, it was Kong et al. [38] who demonstrated that T cell–derived RANKL plays a pivotal role in an experimental bone loss model. It now is clear that T cells regulate bone homeostasis by causing bone marrow (BM) stromal cells (SCs) and osteoblasts (OBs) to release osteoclastogenic cytokines and Wnt ligands and to drive bone turnover in inflammatory states. Under physiological conditions, B cells are also critical for the regulation of bone turnover as they are a significant source of OPG in the BM microenvironment [44]. Consequently, lymphocytes play critical roles in the stabilization of bone homeostasis. Pathological disruption of immune function as occurs during HIV-1 infection contributes to bone destruction though an imbalance in the RANKL/OPG ratio.
Abstract 33: NSCLC cells internalize ATPin vitroandin vivousing multiple endocytotic pathways

Upregulated glycolysis in cancer, the Warburg effect, has been studied for almost one century. However, the biological reasons for the upregulation are still debated and the effect is far from fully understood. One of the major controversies related to the effect is the role of ATP synthesis. Intratumoral ATP concentrations are found to be 10⁁3-10⁁4 times higher than those in normal tissues of the same cell origin. However, whether and how cancer cells use the abundant extracellular ATP was unknown until we recently reported that cancer cells internalize ATP by macropinocytosis (1). Extracellular ATP was found to increase intracellular ATP concentration and promote cell proliferation and drug resistance in cancer cells (1). Here we report that, using a nonhydrolyzable fluorescent ATP (NHF-ATP) as an ATP surrogate, high and low molecular weight dextrans as endocytosis tracers and fluorescence microscopy detection, cultured human NSCLC A549 and H1299 cells as well as xenografted A549 tumors were found to internalize ATP at concentrations within the reported intratumoral ATP concentrations. Endocytosis inhibitor studies show that in addition to macropinocytosis, clathrin- and caveolae-mediated endocytoses contribute to the ATP internalization, which led to a ∼30% increase in intracellular ATP level after 45 min of ATP incubation. This increase cannot be accounted for by purinergic receptor signaling or increased intracellular ATP synthesis rates. Internalization of NHF-ATP and dextran exhibits time-dependent profiles parallel to the extracellular ATP-induced intracellular ATP level elevation. All these demonstrate the observed ATP increase is a result of internalization of extracellular ATP and NHF-ATP is a powerful tool for studying ATP internalization. These findings significantly deepen our understanding of the Warburg effect by showing how cancer cells in tumors take up intratumoral ATP and perform previously unrecognized biological functions. It strongly suggests ATP-sharing among cancer and stromal cells and identifies multiple novel anticancer targets (2). 1. Qian Y, Wang X, et al., Cancer Lett. 351(2014): 242-5. 2. Chen X, Qian Y, Wu S. Free. Radic. Biol. Med. 79(2015): 253-263. Citation Format: Yanrong Qian, Xuan Wang, Yunsheng Li, Yanyang Cao, Xiaozhuo Chen. NSCLC cells internalize ATP in vitro and in vivo using multiple endocytotic pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 33.