cssi/SciSciGPT-SciSciNet huggingface dataset:
Chapter 12: Reappraising the Constitutional Past: Rights of Personal Autonomy

Informational privacy is endangered, but constitutional protection for the autonomous conduct of personal life has been substantially enlarged over the course of the last half-century. These two facets of privacy rights are indeed in tension with one another. However, the different trend-lines should not occasion surprise, for in talking about informational privacy we have to think about the increasingly sophisticated technology available for tracking individual behavior, whereas in thinking about autonomy in personal life we need only consider relatively straightforward prohibitions or mandates the government must honor to permit individuals to conduct their personal affairs on their own terms. Some autonomy-in-personal-life conclusions reached by the modern Court are compatible with the extended Madisonian framework for interpretive supplementation of the text. Lawrence v. Texas, for instance, the 2003 decision that recognizes a constitutional right to engage in consensual sodomy, was decided in the context of supermajority national support for its conclusion, as evidenced by state law. In contrast, other personal autonomy decisions—in particular, Roe v. Wade’s recognition of an abortion right and Obergefell v. Hodges’s recognition of a right of same-sex marriage—were not accompanied by similar support. The justification for each—a qualified justification, it should be emphasized, since it is far better for the Court to engage in interpretive supplementation in the context of supermajority national support—is to be found in a conception of equality that insures individuals they won’t be treated as second-class citizens.
Physical and Mechanical Forces that Shape Heart Tube in the Chick Embryo

In the embryo, the heart is initially a simple tubular structure that undergoes complex morphological changes. This work focuses on the mechanisms that create the heart tube (HT). The early embryo is composed of three relatively flat primary germ layers called endoderm, mesoderm, and ectoderm. Endoderm and pre-cardiac cells located within bilateral regions of the mesoderm called heart fields (HFs) fold and fuse along the embryonic midline. Then both layers lengthen axially as the anterior intestinal portal (AIP) moves downward. Finally, the fused HFs thicken and expand to create the HT. Here, we combine experiments on chick embryos with computational modeling to explore physical mechanisms of heart tube formation. According to our hypothesis, differential anisotropic growth between mesoderm and endoderm drives ventral folding, and contraction along the AIP generates tension to elongate the HT. We test this hypothesis using biochemical perturbations of cell proliferation and contractility, as well as computational modeling. In embryos exposed to the mitotic inhibitor aphidicolin, little or no folding occurred, confirming that cell proliferation is required to initiate folding of HFs. To determine the effects of actomyosin contraction, we cultured Hamburger-Hamilton stage 5 embryos in media containing the myosin inhibitor blebbistatin. During incubation, folding occurred in treated embryos, but AIP descension proceeded at a progressively slower rate, showing that AIP downward motion is generated mainly by AIP contraction. Simulating these mechanisms in our computational model produces morphology in reasonable agreement with experiments. For the last phase, adding circumferential growth causes the HF to expand, creating the primitive HT, while radial growth increases the thickness of the heart wall. In conclusion, results of our study support our hypothesis for the creation of the heart tube.
Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension.

ABSTRACTIntroduction: Intraocular pressure (IOP)-lowering has been demonstrated to slow the progression or onset of visual field loss in open-angle glaucoma (OAG) or ocular hypertension (OHT). Pharmacological lowering of IOP is the most common initial intervention in patients with OAG or OHT, however, many patients will require more than one therapy to achieve target IOP. Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α analog for the reduction of IOP.Areas covered: Current knowledge concerning the mechanism of action of latanoprostene bunod is presented. Additionally, clinical safety and efficacy data from published Phase 1 (KRONUS), Phase 2 (VOYAGER, CONSTELLATION) and Phase 3 (APOLLO, LUNAR, JUPITER) studies are reviewed.Expert opinion: Latanoprostene bunod is a dual mechanism, dual pathway molecule, consisting of latanoprost acid, which is known to enhance uveoscleral (unconventional) outflow by upregulating matrix metalloproteinase expression and remodeling of the ciliary ...
An interstate highway affects gene flow in a top reptilian predator ( Crotalus atrox ) of the Sonoran Desert

Roads can substantially impact the population connectivity of a wide range of terrestrial vertebrates, often resulting in loss of genetic diversity and an increase of spatial genetic structure. We studied the Western Diamond-backed Rattlesnake (Crotalus atrox), a large and abundant venomous predator, to test the hypothesis that a large and relatively new roadway in Arizona (Interstate Highway I-10) is a barrier that impacts gene flow and population genetics via habitat fragmentation. Based on 72 C. atrox sampled from three specific sampling sites (“subpopulations”) on both the west and east corridors of I-10, we used 30 nuclear microsatellite DNA loci and three mitochondrial DNA genes (2615 bp) to assess genetic diversity and structure, estimate effective population size (N e ), and describe patterns of gene flow. We found no evidence for loss of genetic diversity or a decrease in N e between the three subpopulations. Our microsatellite analysis showed that two subpopulations in close proximity (4 km), but separated by I-10, showed greater levels of genetic differentiation than two subpopulations that were separated by a greater distance (7 km) and not by I-10 or any other obvious barriers. Mitochondrial DNA analyses showed no significant genetic differentiation nor any indication of historically impeded gene flow. Tajima’s D and mismatch distribution tests revealed that demographic expansion is occurring in the overall population (all three subpopulations). Bayesian clustering and spatial genetic autocorrelation analyses of microsatellite data showed resistance to gene flow at the approximate location of I-10. Simulations that investigated gene flow between the subpopulations (with and without a highway barrier present) were consistent with our molecular results. We conclude that I-10 has reduced gene flow in a population of an important reptilian predator of the Sonoran Desert in southern Arizona and make conservation recommendations for reversing this trend.
Existence of weak conical Kähler–Einstein metrics along smooth hypersurfaces

The existence of weak conical Kahler–Einstein metrics along smooth hypersurfaces with cone angle between $$0$$ and $$2\pi $$ is obtained by studying a family of Aubin’s (J Funct Anal 57:143–153, 1984) continuity paths and obtaining a uniform $$C^2$$ estimate by a local Moser’s iteration technique. As soon as the $$C^0$$ estimate is achieved, the local Moser’s iteration technique could improve the rough $$C^2$$ estimate in Chen et al. (J Am Math Soc 28:183–197, 2015) to a uniform $$C^2$$ estimate. Since in the cases of negative and zero Ricci curvature, the $$C^0$$ estimate is unobstructed, the weak conical Kahler–Einstein metrics are obtained; while in the case of positive Ricci curvature, the $$C^0$$ estimate is achieved under the assumption of the properness of the Twisted K-Energy. The method used in this paper does not depend on the bound of the holomorphic bisectional curvature of any global background conical Kahler metrics.
A 4 MHz Chaotic Oscillator Based on a Jerk System

Chaotic oscillators have a wide range of possible applications including random number generation (RNG), a stimulation source for characterization of MEMS devices, spread spectrum communications, and audio range and RF noise sources. Some distinct characteristics of chaotic systems include topological mixing, determinism, long-term aperiodic behavior, sensitivity to initial conditions, as well as a spread spectrum response. In particular, the aperiodic behavior and sensitivity to initial conditions make chaotic oscillators an ideal candidate for RNG. In practice, one of the more important aspects of a RNG is the speed at which data/bits can be generated. In electronics, as the frequency of operation increases, so do the design restrictions and challenges. In addition, many of these chaotic systems are based on nonlinearities or complex math functions that are difficult to implement in electronic circuitry. Through careful selection of the system’s structure, complex behavior can be achieved in electronic circuitry with minimized component count, footprint and power consumption. Additionally, this concept reduces the design complexity compared to traditional techniques, and the jerk chaos architecture can aid in increasing the fundamental frequency by minimizing feedback paths in the chaotic oscillator. Presented in this work is a printed circuit board electronic implementation of a 4 MHz chaotic jerk system that exhibits complex, rich dynamics using very simple electronic circuits.
Abstract 168: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 5 (TAC vs Baseline; 6.21 ± 0.28 vs 4.59 ± 0.36, p<0.05). Ejection fraction (EF) was maintained at Day 5 (79±5 vs 82±7%), but gradually decreased thereafter (30 days; 51±12%, p<0.05). LC3-II was decreased (-40.0%, p<0.05) while p62 accumulated (1.84 fold, p<0.05) significantly at Day 5. Both Mt ATP content (-65.6%, p<0.05) and production (-90.3%, p<0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microsco...
Fiber-based Optical Thermocouples for In-Situ Temperature Sensing in Extreme Environments

We develop an optical thermocouple for use in extreme environments by depositing a Dy:YAG film on a sapphire fiber using pulsed laser deposition. Temperature sensing is achieved by way of two-color photoluminescence thermometry.
‘Strong’ states and strategic governance: A model of territorial variation in state presence:

Regions of limited state presence persist in weak states, but does unevenness persist even in so-called ‘strong’ states? An underlying assumption behind weak states is that they lack capacity to br...
MYOCARDIAL SCAR PATTERNS IN WOMEN WITH SUSPECTED CORONARY VASOMOTOR DYSFUNCTION: A REPORT FROM THE WOMEN’S ISCHEMIA SYNDROME EVALUATION

Women with suspected ischemia and no obstructive coronary arteries (INOCA) have an 8% prevalence of myocardial scar. However scar patterns are not well described in relation to coronary vasomotor function. 367 symptomatic women with suspected INOCA underwent cardiac magnetic resonance imaging with
‘Sharing things with people that I don’t even know’: help-seeking for psychological symptoms in injured Black men in Philadelphia

Objectives: Psychological distress is common in survivors of traumatic injury, yet across United States’ trauma systems, it is rare that standard injury care integrates psychological evaluation and...
Internationalizing Communication Curriculum: An Assignment Examining Relational Communication Across Cultures

The base of relational communication curriculum is Eurocentric. Given the importance of global citizenship and cross-, as well as, inter- cultural communication competencies the following paper out...
Transparency and Quality in Higher Education Markets

Since applicants are generally hard-put to know just how much they are really learning, let alone how much they can expect to learn at a school they have never seen, they do not make enlightened choices. They rarely possess either the time or the information to explore all the promising options available to them and usually have only a limited basis for comparing the options they do consider. Under these conditions, competition does not necessarily cause good instruction to drive out bad. Instead, students often flock to courses with superficial appeal or to institutions with established reputations even though the education they receive is only mediocre.... [C]ompetition does not inspire universities or their faculties to do as much as they might to improve their instruction in the way that it forces computer companies to work at improving their products (Bok, 2003, pp. 161-162).
The economic botany of the paulownias

The wood of paulownia is strong and light. It is extensively employed in eastern Asia for building, furniture, musical instruments, chests, clogs and plywood. The potentiality of using paulownia wood in the aeronautical age for the manufacture of crating and boxing lumber for airplane express or freight shipment is highly appraised. The possibilities of employing paulownia wood in small boat building and for carving and the use of paulownia chips as bedding in dairy barns or as litter in chicken houses are excellent. The Chinese practice of administering parts of paulownias for the growth of hair and in other fields of medicine are reviewed. These practices await scientific investigation and evaluation.
Life Course Trajectories of Negative and Positive Marital Experiences and Loneliness in Later Years: Exploring Differential Associations.

Loneliness is relatively common among older adults in the United States, and there can be significant physical, psychological, and cognitive impairments associated with feelings of loneliness. Consequently, this study seeks to uncover determinants of loneliness, particularly the impact of couples' negative and positive marital experiences (i.e., marital strain and strength) over the life course on loneliness in later adulthood. To accomplish this goal, an integrated analytical framework is utilized, incorporating growth curves within an actor-partner interdependence model, to capture the initial level and the rate of change in marital strain and strength over a period of 25 years (from 1991 to 2015) with a sample of 257 couples in enduring, long-term marriages. Couples first participated in the Iowa Youth and Family Project in 1989 and most recently participated in the Later Adulthood Study in 2015. The confirmatory factor analyses showed that latent constructs of marital strain and marital strength are distinct constructs. The univariate growth curve analyses showed that there were significant interindividual variations in the initial level (1991) and rate of change (1991-2015) in marital strain and marital strength for both husbands and wives. While the initial level and rate of change in perceived marital strain from 1991 to 2015 was generally of consequence for both spouses' loneliness in 2015 (actor and partner effects), only actor effects were noted for marital strength. Findings are discussed as they relate to health policies and interventions focusing on the well-being of married couples in later life.
Documentation of ENDS Use in the Veterans Affairs Electronic Health Record (2008-2014).

Author(s): Conway, Mike; Mowery, Danielle L; South, Brett R; Stoddard, Gregory J; Chapman, Wendy W; Patterson, Olga V; Zhu, Shu-Hong
GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

ABSTRACT Advances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB
Food taboos, health beliefs, and gender: understanding household food choice and nutrition in rural Tajikistan

Household nutrition is influenced by interactions between food security and local knowledge negotiated along multiple axes of power. Such processes are situated within political and economic systems from which structural inequalities are reproduced at local, national, and global scales. Health beliefs and food taboos are two manifestations that emerge within these processes that may contribute beneficial, benign, or detrimental health outcomes. This study explores the social dimensions of food taboos and health beliefs in rural Khatlon province, Tajikistan and their potential impact on household-level nutrition. Our analysis considers the current and historical and political context of Tajikistan, with particular attention directed towards evolving gender roles in the wake of mass out-migration of men from 1990 to the present. Considering the patrilieneal, patrilocal social system typical to Khatlon, focus group discussions were conducted with the primary decision-making groups of the household: in-married women, mothers-in-law, and men. During focus groups, participants discussed age- and gender-differentiated taboos that call for avoidance of several foods central to the Tajik diet during sensitive periods in the life cycle when micronutrient and energy requirements peak: infancy and early childhood (under 2 years of age), pregnancy, and lactation. Participants described dynamic and complex processes of knowledge sharing and food practices that challenge essentialist depictions of local knowledges. Our findings are useful for exploring entaglements of gender and health that play out across multiple spatial and temporal scales. While this study is situated in the context of nutrition and agriculture extension, we hope researchers and practitioners of diverse epistemologies will draw connections to diverse areas of inquiry and applications.
Enhanced light extraction from organic light-emitting diodes by reducing plasmonic loss through graded photonic super-crystals

In a planar organic light-emitting diode (OLED), over 50% of emitted lights are trapped as a waveguide mode in the organic-indium tin oxide layer and as a surface plasmon polariton mode at the metal and organic layer interface. The light extraction efficiency into the glass substrate is greatly enhanced when the organic/Al interface of the OLED is patterned with a graded photonic super-crystal (GPSC), by destroying the plasmonic resonance condition through graded patterns and by scattering the surface plasmon polariton into the glass. The light extraction efficiency increases with the area fraction of graded regions in the GPSC. The efficiency can reach above 68.5%, 72.9%, and 78.9% for octagonal, square, and triangular GPSCs with area fractions of the graded regions of 53.9%, 78.5%, and 90.7%, respectively. The light extraction efficiency goes up to 83.0%, 81.2%, and 79.0% at the wavelengths of 447, 507, and 608 nm, respectively, in OLED patterned with triangular GPSC, compared with the targeted efficiency of 70%.
The Law School Special Event: Lessons Learned in Our 20th Year

2006 marked Regent Law School’s 20th Anniversary. This short article, part of Toledo’s Deans’ Leadership in Legal Education series, discusses what we learned during our anniversary year--from experiences both good and bad--about creating events that are meaningful in the life of the law school.
Utilization of phytate and nonphytate phosphorus in chicks as affected by source and amount of vitamin D3

Commercial and laboratory-strain crossbred chicks responded (P < .01) markedly to 1alpha-hydroxycholecalciferol (1alpha-OH D3) during the 2nd and 3rd wk of life. Bone-ash responses exceeded 50% when this compound was added at 20 microg/kg to phosphorus (P)-deficient corn-soybean meal diets containing surfeit levels (25 microg/kg) of cholecalciferol (D3). Phosphorus excretion was decreased (P < .01) and, thus, retention was increased (P < .01) when 1alpha-OH D3 was supplemented. A P-deficient (.10% P) casein-amino acid purified diet, devoid of D3, was used to determine whether 15 microg/kg of D3 was sufficient to facilitate optimal absorption of the nonphytate P contained in this diet. Bone ash responded to .075% P addition (KH2PO4), and chicks fed diets with .175% nonphytate P exhibited further bone-ash responses to 15 microg/kg of D3 or 10 microg/kg 1alpha-OH D3. Higher levels of either of these D3 compounds did not produce additional responses. This suggested that 15 to 25 microg/kg of D3 in a P-deficient corn-soybean meal diet (.28% phytate P and .14% nonphytate P) is more than adequate to facilitate optimal absorption of the nonphytate P present in the diet. A P-deficient casein-dextrose diet (.13% nonphytate P and 15 microg/kg D3) was fed in the final chick assay, and chicks fed this diet did not show bone ash responses to 1alpha-OH D3 or to microbial-derived phytase (1,470 units/kg). Thus, with P-deficient corn-soybean meal diets containing at least 15 microg D3/kg, 1alpha-OH D3 supplementation markedly increased weight gain and bone ash because it increased the utilization of phytate P.
Estimation, Confidence Intervals, and Large-Scale Hypotheses Testing for High-Dimensional Mixed Linear Regression

This paper studies the high-dimensional mixed linear regression (MLR) where the output variable comes from one of the two linear regression models with an unknown mixing proportion and an unknown covariance structure of the random covariates. Building upon a high-dimensional EM algorithm, we propose an iterative procedure for estimating the two regression vectors and establish their rates of convergence. Based on the iterative estimators, we further construct debiased estimators and establish their asymptotic normality. For individual coordinates, confidence intervals centered at the debiased estimators are constructed. Furthermore, a large-scale multiple testing procedure is proposed for testing the regression coefficients and is shown to control the false discovery rate (FDR) asymptotically. Simulation studies are carried out to examine the numerical performance of the proposed methods and their superiority over existing methods. The proposed methods are further illustrated through an analysis of a dataset of multiplex image cytometry, which investigates the interaction networks among the cellular phenotypes that include the expression levels of 20 epitopes or combinations of markers.
Taxing Twenty-First Century Sins

Paternalists have recently turned their attention toward meat, plastic bags, automation, and carbon. Each one allegedly creates tax-justifying externalities: meat harms the environment and health; plastic bags have a negative environmental impact; automation—whether through artificial intelligence or robots—displaces workers; carbon feeds climate change. But time and time again, experts and policymakers appeal to questionable social science to make a case for a tax on these products. For each one, the weight of all the evidence—not just what experts highlight—suggests that no tax is warranted.
Systemic Immunotherapy with Micellar Resiquimod-Polymer Conjugates Triggers a Robust Antitumor Response in a Breast Cancer Model

Resiquimod is an immunopotent toll-like receptor 7/8 agonist with antitumor activity. Despite being potent against skin cancers, it is poorly tolerated systemically due to toxicity. Integrating resiquimod into nanoparticles presents an avenue to circumvent the toxicity problem. Herein, the preparation of degradable nanoparticles with covalently bound resiquimod and their systemic application in cancer immunotherapy is reported. Dispersion in water of amphiphilic constructs integrating resiquimod covalently bound via degradable amide or ester linkages yields immune-activating nanoparticles. The degradable agonist-nanoparticle bonds allow the release of resiquimod from the carrier nanoparticles. In vitro assays with antigen presenting cells demonstrate that the nanoparticles retain the immunostimulatory activity of resiquimod. Systemic administration of the nanoparticles and checkpoint blockade (aPD-1) to a breast cancer mouse model with multiple established tumors triggers antitumor activity evidenced by suppressed tumor growth and enhanced CD8+ T-cell infiltration. Nanoparticles with ester links, which hydrolyze more readily, yield a stronger immune response with 75% of tumors eliminated when combined with aPD-1. The reduced tumor growth and the presence of activated CD8+ T-cells across multiple tumors suggest the potential for treating metastatic cancer.
Abstract 007: Rural Southwest County Jail May Not Meet Recommendations For A Heart-healthy Diet During Pregnancy; A Descriptive Study

Introduction: Pregnancy aged women are the fastest growing incarcerated population in the US. These women have little to no autonomy while incarcerated, including their nutritional intake. Inadequa...
Escape Dynamics in Learning Models

This article illustrates and characterizes how adaptive learning can lead to recurrent large fluctuations. Learning models have typically focused on the convergence of beliefs towards an equilibrium. However in stochastic environments, there may be rare but recurrent episodes where shocks cause beliefs to escape from the equilibrium, generating large movements in observed outcomes. I characterize the escape dynamics by drawing on the theory of large deviations, developing new results which make this theory directly applicable in a class of learning models. The likelihood, frequency, and most likely direction of escapes are all characterized by a deterministic control problem. I illustrate my results with two simple examples.
C-SPECT/CT-2: Design concepts and performance potential

495 Objectives: Since we presented a platform, C-SPECT/CT (formerly called MarC-SPECT), for cardiac imaging 2 years ago, we have advanced it to a 2nd-generation design that has further improved performance potential. Methods: The C-SPECT platform is based on a large stationary C-shaped detector and collimator assembly, which surrounds a patient sitting upright on a smart-chair. After a scout imaging, the smart-chair moves the patient’s heart to a predetermined imaging volume (PIV), which allows a large number of emission projections to be acquired simultaneously. The collimator system uses slit-slat design: a multi-slit plate sits in front of a stack of slats. Each of the (>12) slits, oriented axially and orthogonal to the slats, casts a non-overlapping projection of the PIV on the detector. The geometric efficiency (GE) of the previous design was estimated to be more than double that of conventional dual-head SPECT systems. This 2nd-generation design replaces the parallel slats with converging slats to form a variation of cone-beam geometry and increase GE further. This geometry simplifies the integration of a CT by placing an x-ray-tube on the focal line of the cone as a point source. To mitigate distortions in cone-beam imaging, more projections could be sampled by stepping the patient/chair axially at each rotational stop in both SPECT and CT acquisitions. Results: We estimate that the GE of C-SPECT/CT-2 can be doubled from that of our previous design, and is more than four times that of dual-head SPECT systems. The use of an x-ray-CT promises high-quality attenuation maps for quantitative image reconstruction. These performance gains require a longer detector system in axial dimension and a more complex reconstruction algorithm. Conclusions: C-SPECT/CT-2 offers unprecedented GE for cardiac imaging and has potential for dynamic cardiac SPECT. Research Support: NIH
Targeting Y-box binding protein-1 (YB-1) in Her-2 over-expressing breast cancer cells induces apoptosis via the signal transducer and activator or transcription-3 (STAT3) pathway and suppresses tumor growth.

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA A14 Her-2 is over-expressed in 20-30% of breast carcinomas, where it is associated with poor outcome and very high rates of relapse. Unfortunately, inhibiting Her-2 itself has been met with limited success in many cases. Perhaps this is because additional molecular targets lay farther downstream of Her-2. The Y-box binding protein-1 (YB-1) is a transcription/translation factor co-expressed in primary breast tumors harboring amplified Her-2. It also induces Her2 itself along with its dimerization partner EGFR by directly binding to their promoters. Therefore we addressed whether tumors cells that over-express Her-2 are dependent upon YB-1 for sustained growth. Small interfering RNAs targeting YB-1 induced apoptosis in BT474-1 and Au565 breast cancer cells known to have Her-2 amplifications. To address the underlying mechanism for YB-1 mediated survival the potential role for STAT3 was pursued. We determined that inhibition of YB-1 decreased P-STAT3S727 and therefore MCL-1. This was accompanied by decreased P-mTORS2448, total mTOR, and P-ERK1/2T202/Y204. Alternatively, constitutively active STAT3 rescued YB-1 induced apoptosis correlative with increased MCL-1. Furthering the role of STAT3 in these cells, we demonstrate that knocking it down recapitulated the induction of apoptosis. Finally, targeting YB-1 with two different siRNA's remarkably suppressed tumor cell growth in soft agar by >90% and delayed tumorigenesis in nude mice. We therefore conclude that Her-2 over-expressing breast cancer cells dependent upon YB-1 for survival suggesting a new therapeutic target.
Heme-spin label studies of hemoglobin. II. Spin-labeled oxy- and deoxyhemoglobins.

Abstract Heme spin-labeled oxyferrohemoglobin was prepared by the recombination of mono-spin-labeled protoheme with human apohemoglobin and subsequent reduction with a ferredoxin reductase system. The spin-labeled oxyhemoglobin exhibited optical and oxygen-binding properties indistinguishable from those of native hemoglobin. The electron paramagnetic resonance spectrum of the spin label attached to the heme-moiety showed that the labels were moderately immobilized in the protein. Upon deoxygenation, the resonance amplitude was decreased to less than 50% of the original amplitude and there were small changes in the EPR line shape. Comparison between the optical and EPR measurements during the deoxygenation process clearly showed that the EPR changes are not proportional to the optical changes. This result is contrary to the model of oxygen binding to hemoglobin provided by the induced fit theory. Since the EPR change has no "isosbestic point," it was concluded that the microscopic conformation in the vicinity of the heme can take more than two states during the oxygenation process. It was also shown that the EPR line shape of the heme spin-labeled oxyhemoglobin is different from that of the met form. This result suggests a conformational difference between these two hemoglobins in the dissolved state.
Hydrostatic and Nonhydrostatic Nested Modeling of Straits in the Philippines Archipelago

Abstract : This study utilizes nested nonhydrostatic models embedded in hydrostatic models to simulate and predict the submesoscale dynamics of straits at high spatial and temporal resolutions. The goal of this work is to understand the submesoscale dynamics of straits and the impact of these dynamics on the throughflow in the straits. The Navy requires the ability to forecast features and circulations forced by these dynamics on scales that impact naval operations, i.e. kilometers to meters.
Completion of the proof of the Pauli exclusion principle from a self-consistent field theory of electrodynamics

In a previous paper, it was proven that anecessary condition to yield all of the physical consequences of the Pauli exclusion principle is that the nonlinear, closed set of coupled covariant spinor field equations, whose structure is implied by fully exploiting the principle of relativity, entails two of then coupled particle fields thatA) are in the same state of motion,B) have the same inertial masses andC) have a mutaually repulsive electromagnetic interaction. In this paper, it is shown that conditionsA), B), C) aresufficient to yield the Pauli exclusion principle, within the structure of this field theory—thus completing the proof. The general structure of the interaction field amplitude of the nonlinear spinor field theory is then explored further, and the scattering cross-section in defined in terms of it. It is emphasized that, within this field theory, the elementarity of the (predetermined) «interaction» of a closed system is primary, replacing the elementarity of the (nondeterministic) «particle» of an open system, according to the quantum theory. The influence of the Pauli principle on the general form of the scattering cross-section is discussed.
Challenges in the Use of in silico Tools for Predicting Peptides Binding to HLA-Class II Molecules of HCV E1, E2, and P7

The application of in silico tools for the development of T-cell vaccines is crucial. Yet, due to myriad of polymorphisms of human T-lymphocytic antigen challenges, such therapeutic opportunities present unique roadblocks. There is an obvious advantage in using immunoinformatics (i.e., significantly decreasing cost related to laboratory expenses). A previous publication looked at random binding and nonbinding peptides in order to test the practicality of using such in silico tools to obtain possible immunogenic peptides. The present in silico study applied the same basic approaches to an applicable problem that was to identify promiscuous peptide vaccine candidates for hepatitis C virus (HCV) infection. The data sets used, included the proteins HCV E1, E2 and P7 as the binders (non-self antigens) and the GAD65 and ICA69, which have an association with diabetes, as non-binders (self-antigens). The in silico tools utilized were ProPred, MHC2PRED, and RANKPEP. The resulting differences were identifiable in each of the statistical parameters examined. Variations in the outcomes were evident by the dissimilarities found among the major indices of evaluation Sensitivity, Specificity, Accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Matthews's correlation coefficient (MCC) of the percentages of the predicted promiscuous peptides to HLA-DRB1*0101, *0301, and *0401. The conclusion from this study indicates that more work needs to be done in order to enhance the predictability of programs for the identification of peptide vaccine candidates for HCV. Such programs should not be solely relied upon without in vitro assay verification.
Motor third-party liability insurance

Motor Third Party Liability Insurance (MTPL) ensures that damage to third party health and property caused by an accident for which driver and/or owner of the car were responsible is covered. A policy may be taken out by the owner of a vehicle or by a lawful possessor authorized by the owner on behalf of the owner. Compulsory MTPL Insurance is a financial protection system built to prevent any grievance that third parties could face, due to lack of solvency of first party who caused bodily injury or property damage following any event related to a car accident. Motor insurance is generally measured non-life insurers' strongest class of business in terms of premium volume. In most markets, it is characterized by high competition and cyclical fluctuations in results. Non-life insurers' motor result is thus likely to have a particularly strong impact on the overall result. In most countries, MTPL insurance is compulsory in order to protect the public. World Bank studies in Africa, Central Asia, and Europe have shown that motor insurance premiums represent at least 30 percent of all non-life premium income. This phenomenon may be explained by the rapid rise of motor fleets. MTPL insurance has been introduced in the formerly centrally planned economies only in the past decade, but it is poorly understood. Motorists are inclined to view it as a form of tax that they are at liberty to evade, rather than as a protection against their personal liability a concept that is not familiar to the general public. Motor insurance has the potential to be a powerful tool in the promotion of personal responsibility. If communicated effectively, the link between the consequences of causing an accident and the economics of paying for those consequences will of itself gradually lead to improved driving.
A Moveable Feast: Do Mobile Media Technologies Mobilize or Normalize Cultural Participation?

This research draws on national survey data in the United States to investigate the variation of mobile cultural participation by the access to mobile Internet devices, the intensity, diversity, and specific types of app use, sociodemographic characteristics, and in-person cultural participation. Results show that the access to mobile Internet devices and diverse app use, especially recreational and work-related app use, are positively related to mobile cultural participation. The Hispanic lead, the reversed educational gap, and the disappeared urban–rural divide in mobile cultural participation suggest that it offers members of disadvantaged groups a more accessible venue for cultural participation. The stronger relationships between mobile Internet devices, in-person and mobile cultural participation among the less educated support the mobilization thesis.
Protecting against unexpected system calls

This paper proposes a comprehensive set of techniques which limit the scope of remote code injection attacks. These techniques prevent any injected code from making system calls and thus restrict the capabilities of an attacker. In defending against the traditional ways of harming a system these techniques significantly raise the bar for compromising the host system forcing the attack code to take extraordinary steps that may be impractical in the context of a remote code injection attack. There are two main aspects to our approach. The first is to embed semantic information into executables identifying the locations of legitimate system call instructions; system calls from other locations are treated as intrusions. The modifications we propose are transparent to user level processes that do not wish to use them (so that, for example, it is still possible to run unmodified third-party software), and add more security at minimal cost for those binaries that have the special information present. The second is to back this up using a variety of techniques, including a novel approach to encoding system call traps into the OS kernel, in order to deter mimicry attacks. Experiments indicate that our approach is effective against a wide variety of code injection attacks.
FTIR spectroscopic kinetic analysis of alkaline phosphatase under hyperbaric manipulation.

Abstract For the first time, high-pressure infrared spectroscopy has been used in an enzyme kinetics study. This technique allows not only the investigation of kinetics under very high pressure, but it also allows simultaneous determinion of changes in the secondary structure of enzymes at the corresponding pressures. In the present study, a classical enzyme reaction, the conversion of p -nitrophenol phosphate into p -nitrophenol by alkaline phosphatase was selected to demonstrate the potential of infrared spectroscopy as an alternative physical method in the high-pressure study of enzyme kinetics. The rate constants of this enzyme reaction have been determined as a function of pressure in the range 0.001–14 kbar. The first-order rate constants thus obtained increases with increasing pressure up to 8.3 kbar. At this pressure, the reaction rate decreases abruptly due to the denaturation of the enzyme arising from the conformational changes of some a -helical segments in the enzyme molecules into β-sheet structure. The present results suggest that the pressure-enhanced overall hydrogen-bond strength in the amide groups of the enzyme is one of the factors which stimulate the enzyme activity. Moreover, the dissociation of the dimeric enzyme into its subunits does not inhibit the enzyme activity but only attributes to a slight change in activation volume.
Perturbational profiling of nanomaterial biologic activity.

Our understanding of the biologic effects (including toxicity) of nanomaterials is incomplete. In vivo animal studies remain the gold standard; however, widespread testing remains impractical, and the development of in vitro assays that correlate with in vivo activity has proven challenging. Here, we demonstrate the feasibility of analyzing in vitro nanomaterial activity in a generalizable, systematic fashion. We assessed nanoparticle effects in a multidimensional manner, using multiple cell types and multiple assays that reflect different aspects of cellular physiology. Hierarchical clustering of these data identifies nanomaterials with similar patterns of biologic activity across a broad sampling of cellular contexts, as opposed to extrapolating from results of a single in vitro assay. We show that this approach yields robust and detailed structure–activity relationships. Furthermore, a subset of nanoparticles were tested in mice, and nanoparticles with similar activity profiles in vitro exert similar effects on monocyte number in vivo. These data suggest a strategy of multidimensional characterization of nanomaterials in vitro that can inform the design of novel nanomaterials and guide studies of in vivo activity.
The influence of urine from asymptotic laboratory populations on sexual maturation in prairie deermice

Male and female prairie deermice housed singly from weaning (21 days) until 40 days of age had urine from one of the following sources applied daily to their nostrils: sexually mature laboratory population males or females, and sexually mature breeder males or females from our laboratory colony. Other males and females were treated with water. Records were obtained of the weights of the tests, seminal vesicles and bacula of males and the ovaries and uteri of females at 40 days of age.
Linear and nonlinear energy harvesters for powering pacemakers from heart beat vibrations

Linear and nonlinear piezoelectric devices are introduced to continuously recharge the batteries of the pacemakers by converting the vibrations from the heartbeats to electrical energy. The power requirement of the pacemakers is very low. At the same time, after about 10 years from the original implantation of the pacemakers, patients have to go through another surgical operation just to replace the batteries of their pacemakers. We investigate using vibration energy harvesters to significantly increase the battery life of the pace makers. The major source of vibrations in chest area is due to heartbeats. Linear low frequency and nonlinear mono-stable and bi-stable energy harvesters are designed according to especial signature of heart vibrations. The proposed energy harvesters are robust to variations of heart beat frequency and can meet the power requirement of the pacemakers.
A content analysis of sexual themes in Playboy cartoons

Critics of pornography have argued that the way men and women are portrayed in these media create images that can result in harmful gender socialization. The cartoons from all 1985 issues of Playboy were coded for the presence or absence of four themes that have been identified by these critics. It was found that, when these themes appeared, women were more often the victim of sexual coercion, were more often depicted as sexually naive and childlike, and were more often shown with a more attractive body than were the men in the cartoons.
Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: Initial description of a new variable

Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (<5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P <.001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.
Interleukin-15 Promotes Angiogenesisin Vivo

Abstract IL-15, a cytokine with biological functions on cells of lymphoid lineage similar to those of IL-2, mediates its activities through the β and γ chains of the IL-2/15R and its own α chain. Unlike IL-2, IL-15 also binds to endothelial cells with high affinity. We report here that IL-15 is a stimulator of angiogenesis in vivo. When injected subcutaneously into nude mice, IL-15 consistently induced neovascularization of Matrigel plugs. Endothelial cells were found to express the IL-15R α chain and the IL-2/15R β and common γ chains. IL-15 induced the rapid tyrosine phosphorylation of proteins in endothelial cells, but did not stimulate endothelial cell proliferation in vitro. These findings document a previously unrecognized biological property of IL-15 and emphasize the role of IL-15 as an important mediator outside the immune system.
Matrix Roots of Eventually Positive Matrices

Abstract Eventually positive matrices are real matrices whose powers become and remain strictly positive. As such, eventually positive matrices are a fortiori matrix roots of positive matrices, which motivates us to study the matrix roots of primitive matrices. Using classical matrix function theory and Perron–Frobenius theory, we characterize, classify, and describe in terms of the real Jordan canonical form the p th-roots of eventually positive matrices.