cssi/SciSciGPT-SciSciNet huggingface dataset:
Nonlinear frequency response of second harmonic generation in SAW IDT resonators

A general purpose finite element model that yielded directly the nonlinear frequency response of the second harmonic generation in SAW IDT resonators was developed. The model enabled us to study the effects of the nonlinear material constants, voltage drive, duty factor, and IDT geometry on f-2f nonlinear interactions. Specifically we have applied our model to the study of nonlinear frequency response of second harmonic generation in lithium niobate YX-127o SAW IDT resonators. Lithium niobate was chosen because a complete set of its nonlinear material constants was known and published in the literature. A complete set of nonlinear piezoelectric equations along with their material constants for a lithium niobate YX-127o SAW IDT 836 MHz resonator was implemented in a finite element program. Two sets of finite element matrix equations were derived for the fundamental SAW mode and its 2nd harmonic mode, respectively. We demonstrated how two frequency domain interfaces could be coupled together to simulate the f-2f nonlinear interactions. The fundamental Rayleigh SAW mode was excited by a drive voltage at the IDT that in turn generated the 2nd harmonic mode at twice the frequency. A higher voltage drive lead to higher 2f interactions. Effects of the 2nd harmonic generation on the fundamental SAW mode and its Q were observed when the voltage drive was greater than 0.5V. For example, when the drive voltage was 0.1V the fundamental mode was clean. But when the drive voltage was increased to 0.5V the fundamental mode exhibited Q reduction and stronger f-2f interactions were observed, namely, there were stronger interactions of the 2f BAW mode with the f SAW mode. There was an optimal duty factor of 0.4 to 0.5 for the least f-2f interactions. Thinner electrode thickness resulted in stronger f-2f interactions.
Can I Choose to Have Grit? Non-Cognitive Skills, Behavior, and School Choice.

With the introduction of school choice as a viable option of school reform, researchers have begun to look beyond academic achievement to the effects of choice on alternative outcomes. Recently, no...
Stable transgenerational epigenetic inheritance requires a DNA methylation-sensing circuit

Epigenetic states are stably propagated in eukaryotes. In plants, DNA methylation patterns are faithfully inherited over many generations but it is unknown how the dynamic activities of cytosine DNA methyltransferases and 5-methylcytosine DNA glycosylases interact to maintain epigenetic homeostasis. Here we show that a methylation-sensing gene regulatory circuit centered on a 5-methylcytosine DNA glycosylase gene is required for long-term epigenetic fidelity in Arabidopsis. Disrupting this circuit causes widespread methylation losses and abnormal phenotypes that progressively worsen over generations. In heterochromatin, these losses are counteracted such that methylation returns to a normal level over four generations. However, thousands of loci in euchromatin progressively lose DNA methylation between generations and remain unmethylated. We conclude that an actively maintained equilibrium between methylation and demethylation activities is required to ensure long-term stable inheritance of epigenetic information.
Cell Cycle Control by Ubiquitin-Dependent Proteolysis

The prime directive of the dividing cell is to pass on two identical copies of its genetic blueprint. This requires accurate replication of DNA and accurate segregation of replicated chromosomes. The cell cycle control machinery regulates progression from one phase of the chromosome cycle to the next, ensuring that DNA replication (S phase) alternates with chromosome segregation (mitosis) to maintain a constant ploidy. In most cells, growth is coordinated with division to maintain a constant average cell size; the length of the gap phases that occur before (G1) and after (G2) S phase must therefore be regulated. In contrast, early embryonic division occurs in the absence of cell growth, so that the cell cycle consists solely of rapidly alternating S and M phases. Despite these distinct physiologies, a common biochemical machinery regulates cell division in all eukaryotic cells.
Experimental demonstration of highly localized pulses (X waves) at microwave frequencies

A device that radiates transverse magnetic Bessel beams in the radiative near field is reported. The cone angle of the emitted radiation remains constant over a wide frequency range (18--30 GHz), allowing highly localized pulses (X waves) to be generated under a broadband excitation. The design process, based on ray optics, is discussed. Both frequency and time domain experimental results for a prototype are presented. The measured fields show close agreement with simulation results, and demonstrate the radiator's ability to emit X waves within its nondiffracting range.
The Augustinian Perspective on the Transmission of Original Sin and Assisted Reproductive Technologies

St. Augustine of Hippo believed that original sin is transmitted through concupiscent intercourse. The new assisted reproductive technologies (ARTs) now allow humans to create children without any intercourse, thus opening the theological possibility for circumventing the transmission of original sin, if Augustine was correct in his theory. This article will first examine Augustine’s speculative theology of prelapsarian sexual intercourse and procreation, followed by his view on the postlapsarian transmission of original sin. Second, I will describe assisted reproductive technologies, with a focus on in-vitro fertilization. I will then, third, place ARTs within an Augustinian theology of the transmission of original sin, underscoring the implications for a free will, Protestant Christian anthropology, Christology, soteriology, and missiology. I will conclude the article by considering the role of historical theology for modern scientific advancements such as ARTs.
Regional variation of convective structure at monsoon onset across South America inferred from TRMM observations

The variation of precipitation in South America is characterized by different mechanisms that both initiate and sustain precipitation. Analysis to characterize regional differences is done utilizing datasets derived from the Tropical Rainfall Measuring Mission (TRMM) satellite as well as National Center for Environmental Prediction (NCEP) Reanalysis data. Four regions were studied. These included the Amazon Basin (West), northeast coast (East), location of the South Atlantic Convergence Zone (SACZ), and extreme southeastern Brazil (South). In these regions, variables such as rain rate, feature size, lighting flash counts, updraft strength, and thermodynamic fluxes were analyzed. Before onset in the Amazon Basin, sensible heat flux increases and is well correlated with increases in lighting flash counts that were observed using TRMM, implying thermodynamic forcing. After onset, the features become less electrified, however their frequency and rain rates increase. The East region experiences similar pre and post-onset behavior, however oceanic influence not only limits the vertical intensity of convection, but also acts to delay the timing of onset by two months, compared to the West. Fronts are the dominant driver of precipitation in the SACZ region, increasing in frequency as onset approaches. Time series analysis from TRMM illustrates high variability in precipitation and increases in frequency of features here that is consistent with an increase in frontal activity. Also, composite directional wind plots using NCEP 850 mb wind data, reveals interactions between the Tropics and sub-Tropics. Pre-onset MCCs dominate South time series and frontal intrusions drive precipitation in the post-onset period. Understanding distinct regional mechanisms of precipitation can increase the predictability of monsoon onset all over South America. This is important for those who live there and depend on seasonal rains for their livelihood. Also, knowing what mechanisms are working in different regions at different times of the year and incorporating their respective contributions to the global heat budget, we can increase the accuracy of global models. The next step would be to use these observations to model the observed regional variability and timing, and identify the contributions and long-term implications of heat release from the South American Monsoon System (SAMS) on the global scale.
Three Dimensional Formulation of Large Displacement Problems: The Zipper Frame Example

A zipper frame is a conventional braced frame with chevron type braces at all floors, connected through a zipper column linking their midpoints. Under lateral force, a 3 stories frame is expected to behave as follows: after the 1st floor braces buckle, the zipper column transmits the unbalance vertical force to the 2nd story, forcing them to buckle. The new unbalanced vertical force is then transmitted to the third story, which is designed to remain elastic. This is known as the zipper mechanism. Three shaking table tests were performed to evaluate the seismic response of a 3 story suspended zipper frame model. In every shaking table test performed, the braces buckled out of plane but the zipper mechanism did not always develop. Following the test results, a new analytical tool was developed to capture the 3 dimensional phenomena of buckling. It is based on the well known corotational formulation. Every element is described independently. The rigid body modes are removed by using a corotated coordinate system. Within the deformed shape, the element can undergo large rotations and large strains, which are evaluated respect to the corotated origin. The structural problem is solved in the state space, where displacements as well as velocities are variables. The final set of equations is a combination of differential and algebraic equations that is solved using the IDA software. This paper presents the main results of the shaking table tests as well as some general description of the proposed formulation and its capability to verify the shaking table findings.
Distributed policy processing in active-service based infrastructures: Research Articles

More and more applications in the Internet are requiring an intelligent service infrastructure to provide customized services. In this paper, we present an infrastructure, which can transparently and effectively provide customized active-services to end users and dynamically adapt to changing customized policies in large distributed heterogeneous environments. The infrastructure consists of two components: the policy agent and middleware box. Particularly, our technologies include: (1) Generic active-service based infrastructure, where the policy agent can integrate policies requested by applications, and middleware boxes can transparently execute services and (2) Distributed policy processing in the middleware box. We study two policy partitioning schemes to achieve conflict-free policies for distributed policy processing and guarantee the correctness of the policy execution. We conduct extensive performance evaluations on different schemes proposed. Our experimental results demonstrate that our policy partitioning schemes can effectively generate partition-capable and conflict-free policy sets. The evaluation results also show that distributed policy processing can achieve over 70p increase in performance/price ratio with proper assignment of the policy distribution degree compared to a purely centralized approach. Copyright © 2005 John Wiley & Sons, Ltd.
Human Slow Infections Caused by Prions

Creutzfeldt-Jakob disease (CJD) of humans and scrapie of animals are caused by infectious pathogens called prions. Two other human degenerative neurological diseases, kuru and Gerstmann-Strauss1er syndrome (GSS) are probably also caused by prions. Prions are composed largely, if not entirely, of protein molecules. No prion-specific polynucleotide has been identified. Purified preparations of scrapie prions contain high titers (≥109.5 ID50/ml), one protein (PrP 27–30) and amyloid rods (10–20 nm × 100–200 nm). Considerable evidence indicates that PrP 27–30 is required for and inseperable from scrapie infectivity. PrP 27–30 is derived from a larger protein, PrPSc, by protease digestion which is encoded by a cellular gene. A cellular isoform designated PrPC is encoded by the same gene and both proteins appear to be translated from the same 2.1 kb mRNA. A comparison of translated PrP cDNAs shows that human and rodent sequences are 90% homologous. Monoclonal antibodies to PrP 27–30 as well as antisera to PrP synthetic peptides specifically react with both PrPC and PrPSc, establishing their relatedness. PrPC is digested by proteinase K while PrPSc is converted to PrP 27–30, under the same conditions. Prion proteins are synthesized with signal peptides and are integrated into membranes. Detergent extraction of microsomal membranes isolated from scrapie-infected hamster brains solubilized PrPC but induced PrPSc to polymerize into amyloid rods. The prion amyloid rods generated by detergent extraction are identical morphologically except for length to extracellular collections of prion amyloid filaments which form plaques in scrapie- and CJD-infected brains. PrPSc accumulates during scrapie infection while the level of PrPC does not change. The chemical difference between PrPC and PrPSc are unknown but the organization of PrP gene suggests that this difference is the result of a post-translational modification.
Exploring privacy in location-based services using cryptographic protocols

Location-based services (LBS) are available on a variety of mobile platforms like cell phones, PDA's, etc. and an increasing number of users subscribe to and use these services. Two of the popular models of information flow in LBS are the client-server model and the peer-to-peer model, in both of which, existing approaches do not always provide privacy for all parties concerned. In this work, I study the feasibility of applying cryptographic protocols to design privacy-preserving solutions for LBS from an experimental and theoretical standpoint. In the client-server model, I construct a two-phase framework for processing nearest neighbor queries using combinations of cryptographic protocols such as oblivious transfer and private information retrieval. In the peer-to-peer model, I present privacy preserving solutions for processing group nearest neighbor queries in the semi-honest and dishonest adversarial models. I apply concepts from secure multi-party computation to realize our constructions and also leverage the capabilities of trusted computing technology, specifically TPM chips. My solution for the dishonest adversarial model is also of independent cryptographic interest. I prove my constructions secure under standard cryptographic assumptions and design experiments for testing the feasibility or practicability of our constructions and benchmark key operations. My experiments show that the proposed constructions are practical to implement and have reasonable costs, while providing strong privacy assurances.
Synthetic development: building mammalian multicellular structures with artificial genetic programs

Synthetic biology efforts began in simple single-cell systems, which were relatively easy to manipulate genetically (Cameron et al., 2014). The field grew exponentially in the last two decades, and one of the latest frontiers are synthetic developmental programs for multicellular mammalian systems (Black et al., 2017; Wieland and Fussenegger, 2012) to genetically control features such as patterning or morphogenesis. These programs rely on engineered cell–cell communications, multicellular gene regulatory networks and effector genes. Here, we contextualize the first of these synthetic developmental programs, examine molecular and computational tools that can be used to generate next generation versions, and present the general logic that underpins these approaches. These advances are exciting as they represent a novel way to address both control and understanding in the field of developmental biology and tissue development (Elowitz and Lim, 2010; Velazquez et al., 2018; White et al., 2018; Morsut, 2017). This field is just at the beginning, and it promises to be of major interest in the upcoming years of biomedical research.
Delay in receipt of newly prescribed oral anticancer drugs.

6541Background: Oral anticancer drug (OACD) prescriptions require coordination between clinicians, payers, specialty pharmacies, and financial assistance (FA) groups, which may delay patient receip...
Civil Cases in the Supreme Court's October 2018 Term

Commissioned by the American Judges Association, this paper briefly summarizes the U.S. Supreme Court's most significant rulings in civil cases during the October 2018 Term.
Consistent Interactions with Residents in Assisted Living Facilities Significantly Improved the Social and Emotional Competencies of 4 Year Olds

Social and emotional deficiencies in preschool classrooms is a growing concern and a consistent conversation among preschool teachers, caregivers, and parents of children. This study explored wheth...
Characteristic Monitoring and Assessment Method for Dynamic Wireless Charging System of Electric Vehicle

This paper presents three kinds of characteristic parameters: energy efficiency characteristics of wireless power transmission, characteristics of wireless charging device and vehicle state characteristics. In order to evaluate the charging state comprehensively, seven evaluation indexes, such as charging efficiency, fluctuation adaptability and migration resistance, are determined. A multi-index comprehensive evaluation method based on maximum deviation and entropy method is proposed. Experiments show that the method and indicators can effectively evaluate the operational status of the dynamic wireless charging system, rank and select the optimal operation status. The results show that the comprehensive evaluation method is effective and practical.
Gendered White Lies: Women Are Given Inflated Performance Feedback Compared With Men:

Are underperforming women given less truthful, but kinder performance feedback (“white lies”) compared with equally underperforming men? We test this hypothesis by using a “benchmark” of truthful (...
Routineeinsatz von Abdomensonographie und Oberbauch-CT beim Polytrauma Analyse der Therapierelevanz bei 105 Patienten

Einleitung: Im Rahmen einer prospektiven Erfassung von Schockraumpatienten wurde die Therapierelevanz der Oberbauch-Computertomographie (CT) gegen uber der etablierten Abdomensonographie (US) bewertet. Methoden: Von August 1996 bis Juli 1997 erfasten wir alle vom Notarzt als Polytrauma deklarierten Patienten (n = 248) im Schockraum mit einem speziell entwickelten Protokollbogen. CT wurde zusatzlich zur Sonographie eingesetzt, wenn der Patient nicht notfallmasig operiert werden musste und hamodynamisch stabil war (n = 105). Die Ergebnisse und deren Therapierelevanz beider Untersuchungsmethoden wurden getrennt voneinander prospektiv erfast. Ergebnisse: Bei insgesamt 27 von 105 Patienten (25,7 %) beeinfluste die Bildgebung das therapeutische Vorgehen. 76 Patienten zeigten einen unauffalligen US-Befund, die anschliesend durchgefuhrte CT hatte in 5 Fallen therapeutische Konsequenzen (6,6 %). In der Gruppe mit auffalligem Sonogramm (n = 29) fuhrte das CT in 12 Fallen (41,4 %) zu einer Anderung, der nach US festgelegten primaren Therapie. Schlusfolgerungen: Zusammenfassend liefert die CT nach unauffalligem US nur selten relevante Zusatzinformation. Im Gegensatz dazu fuhrt die CT bei auffalligem US haufig zu einer Therapieanderung.
Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity

The plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. The regulation of membrane asymmetry is a fundamental characteristic of membrane biology, and is crucial for signal transduction, vesicle transport, and cell division. The type-IV family of P-ATPases, or P4-ATPases, establish membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is still unclear how these enzymes sort through the spectrum of lipids within the membrane to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are two chemically divergent lipids, glucosylceramide (GlcCer) and phosphatidylcholine ((PC) or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. Surprisingly, application of lipids that are poor transport substrates differentially affect PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition; thus, providing feedback onto the function of the P4-ATPases.
Polyamines and Their Biosynthesis/Catabolism Genes Are Differentially Modulated in Response to Heat Versus Cold Stress in Tomato Leaves (Solanum lycopersicum L.)

Polyamines (PAs) regulate growth in plants and modulate the whole plant life cycle. They have been associated with different abiotic and biotic stresses, but little is known about the molecular regulation involved. We quantified gene expression of PA anabolic and catabolic pathway enzymes in tomato (Solanum lycopersicum cv. Ailsa Craig) leaves under heat versus cold stress. These include arginase 1 and 2, arginine decarboxylase 1 and 2, agmatine iminohydrolase/deiminase 1, N-carbamoyl putrescine amidase, two ornithine decarboxylases, three S-adenosylmethionine decarboxylases, two spermidine synthases; spermine synthase; flavin-dependent polyamine oxidases (SlPAO4-like and SlPAO2) and copper dependent amine oxidases (SlCuAO and SlCuAO-like). The spatiotemporal transcript abundances using qRT-PCR revealed presence of their transcripts in all tissues examined, with higher transcript levels observed for SAMDC1, SAMDC2 and ADC2 in most tissues. Cellular levels of free and conjugated forms of putrescine and spermidine were found to decline during heat stress while they increased in response to cold stress, revealing their differential responses. Transcript levels of ARG2, SPDS2, and PAO4-like increased in response to both heat and cold stresses. However, transcript levels of ARG1/2, AIH1, CPA, SPDS1 and CuAO4 increased in response to heat while those of ARG2, ADC1,2, ODC1, SAMDC1,2,3, PAO2 and CuPAO4-like increased in response to cold stress, respectively. Transcripts of ADC1,2, ODC1,2, and SPMS declined in response to heat stress while ODC2 transcripts declined under cold stress. These results show differential expression of PA metabolism genes under heat and cold stresses with more impairment clearly seen under heat stress. We interpret these results to indicate a more pronounced role of PAs in cold stress acclimation compared to that under heat stress in tomato leaves.
Towards an Inclusive Model of Makerspace Educator Professional Development: Implications for Students with Disabilities and At-Risk

This paper describes exploratory research that contributes to a more holistic model of professional development (PD) for middle school STEM teachers to support inclusive makerspace classrooms. Despite an increased focus on maker education in K-12 settings, teachers have reported limited support to deliver such instruction, especially with academically diverse learners. This case study examined instructional supports for teachers, including professional development and coaching focused on makerspace classroom activities, as well as structural conditions, the integration of metacognitive learning strategies, positive behavior supports, and Universal Design for Learning (UDL). Analysis of teacher interviews, surveys, and classroom observations revealed that teachers acknowledged the need for ongoing PD and the inclusion of UDL components into their lesson planning.
Comparing Psychometric Properties of the NIH Toolbox Cognition Battery to Gold-Standard Measures in Socioeconomically Diverse Older Adults.

Objective The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is an efficient computerized neuropsychological battery. This study investigated its psychometric properties in terms of sociodemographic characteristics and technology use in adults aged 57-87 (with an average age of 70). Methods Community-based participatory research procedures were used to enhance enrollment of adults with lower education and income backgrounds. Study procedures replicated work that compared the NIHTB-CB Crystallized and Fluid composites to analogous gold-standard (GS) measures and extended it by investigation of socioeconomic status and technology use-related differences in performance. Results The high correlations among the NIHTB-CB and GS analogous Crystallized and Fluid composites suggested good convergent validity. There was no evidence of significant education- or economic-related group differences in these associations. However, caution is needed as Cronbach's alpha that indicated the NIHTB-CB Fluid composite had questionable internal item consistency. The NIHTB-CB and GS measures demonstrated poor discriminant validity in the high school but not college-educated groups. Regression analyses found that comfort with technology use, income, education, and age predicted better cognitive test performance on the computerized and paper-pencil measures. Conclusions There is an urgent need to improve the understanding of socioeconomic disparities influence on test scores and brain health. Lack of discriminant validity in the cognitive tests indicates that these measures could result in diagnostic errors within noncollege-educated older adults. These findings reduce confidence in the use of the NIHTB-CB Fluid composite in older adults and support that there is a significant socioeconomic-related digital divide in comfort with technology use.
Association between Patient Portal use and Office Visits.

Extant research on the relationship between portal use and office visits is mixed. Some researchers have stated that there is no correlation between the two events, others have found a positive correlation, and still others have found a negative correlation between portal use and office visits. Through the use of system-generated data from two different portal systems, we demonstrate the correlation between portal visits and office visits. We also demonstrate how this correlation differs between two institutions and across three demographic attributes. We performed a retrospective bivariate correlation analysis between portal visits and office visits. The correlation analysis was followed by an application of Fisher’s z transformation of the correlation coefficients to determine significant differences in correlation across ethnicity, gender, and age. We found a positive and statistically significant correlation between portal visits and office visits among both hospital patients (n = 2,594, r = .239, p < .000) and university health service patients (n = 1,233, r = .596, p < .000). This correlation varies significantly across the dimensions of ethnicity, gender, and age. Our findings support the importance of portal use in the care continuum. Future research should aim to better understand the nuance of personal characteristics on the relationship between portal visits and office visits. Knowing these nuances can assist practitioners with further promoting patient self-engagement through portal use.
Plasma Activated Low-temperature Die-level Direct Bonding with Advanced Wafer Dicing Technologies for 3D Heterogeneous Integration

In this paper, we have demonstrated a plasma activated low-temperature die-level oxide-oxide direct bonding with advanced wafer dicing technologies. This evaluation used blanket 300-mm silicon wafers. $1\ \mu\mathrm{m}$ Tetraethyl orthosilicate (TEOS) oxide was deposited by plasma-enhanced chemical vapor deposition (PECVD) directly on the silicon (Si) wafer surface, followed by chemical mechanical planarization (CMP). Atomic Force Microscopy (AFM) was used to examine the roughness of the wafer surface before dicing and it showed $\mathrm{R}_{\mathrm{a}}$ . Several dicing technologies such as diamond blade dicing, step-cut blade dicing, bevel blade dicing, and stealth laser dicing were evaluated for this integration scheme. In the end, diamond blade dicing has the most compatibility with many materials, but it led to large chipping on the edges of the die. Stealth laser dicing achieves edge chipping of less than $2\ \mu\mathrm{m}$ , which is the least amount of damage among of all dicing methods tested in this study. In the bonding test, the 10 mm square silicon die was bonded to a 35-mm square silicon substrate. Both silicon die and substrate are of thickness $760\ \mu\mathrm{m}$ . Prior to direct oxide-oxide bonding, both silicon die, and substrate went through a two-step cleaning process. The detailed process of the plasma activated die-level direct bonding is discussed.
Propagation of phase along the imposed magnetic field

When the direction of phase propagation coincides with the direction of the imposed magnetic field, or the reverse thereof, we have what is known as longitudinal propagation (θ p = 0 or π). Because of the axial symmetry round the imposed magnetic field, the direction of group propagation is then the same as the direction of phase propagation (θ g = 0 or π); it may be verified from Equation (6.34) that, when θ p = 0, we also have θ g = 0. The magnitude of the group velocity along the direction of the imposed magnetic field is, however, different from the magnitude of the phase velocity. Phase propagation along the imposed magnetic field will be discussed in this chapter, and group propagation in the following chapter.
Claudins and alveolar epithelial barrier function in the lung

The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair.
Machine Mentality and the Nature of the Ground Relation

John Searle distinguished between weak and strong artificial intelligence (AI). This essay discusses a third alternative, mild AI, according to which a machine may be capable of possessing a species of mentality. Using James Fetzer's conception of minds as semiotic systems, the possibility of what might be called ``mild AI'' receives consideration. Fetzer argues against strong AI by contending that digital machines lack the ground relationship required of semiotic systems. In this essay, the implementational nature of semiotic processes posited by Charles S. Peirce's triadic sign relation is re-examined in terms of the underlying dispositional processes and the ontological levels they would span in an inanimate machine. This suggests that, if non-human mentality can be replicated rather than merely simulated in a digital machine, the direction to pursue appears to be that of mild AI.
The Relationship between DNA Methylation and Telomere Length in Dyskeratosis Congenita

The regulation of telomere length (TL) is a complex process, requiring the telomerase enzyme complex and numerous regulatory proteins. Epigenetic regulation may also be important in telomere maintenance. Specifically, methylation at subtelomeres is associated with changes in TL in vitro and in mouse models. Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by exceedingly short telomeres and mutations in telomere biology genes. To understand the interaction between methylation and TL in humans, we measured LINE-1, pericentromeric (NBL2), and subtelomeric (D4Z4) methylation in peripheral blood DNA derived from 40 patients with DC and 51 mutation-negative relatives. Pearson's correlation coefficient and linear regression models were used to evaluate the relationship between age-standardized lymphocyte TL measured by flow FISH and % DNA methylation. No differences in % subtelomeric, LINE-1, or pericentromeric methylation between patients with DC and relatives were noted except for an increase in % subtelomeric methylation in DC patients with a telomerase-complex mutation (TERC, TERT, DKC1, or TCAB1) (63.0% in DC vs. 61.8% in relatives, P = 0.03). Positive correlations between TL and DNA methylation at LINE-1 (r = 0.39, P = 0.01) and subtelomeric (r = 0.32, P = 0.05) sites were present in patients with DC. The positive correlation between TL and % LINE-1 methylation was restricted to TINF2 mutations. In contrast, statistically nonsignificant inverse correlations between TL and % LINE-1 (r = -0.17), subtelomeric (r = -0.20) were present in unaffected relatives. This study suggests an interaction between TL and both subtelomeric and LINE-1 methylation, which may be altered based on mutation status of telomere biology genes.
Suppressor genes for nonsense mutations. I. The Su-1, Su-2 and Su-3 genes of Escherichia coli.

Three suppressor genes in Escherichia coli , which act on the N1 class of phosphatase nonsense mutations, have been genetically analyzed. The Su-1 gene maps near the histidine region of the chromosome, the Su-3 gene near the tryptophan region, and the Su-2 gene in another (unidentified) region. Each suppressor gene can exist in either an active state, called Su + , or an inactive state, called Su − . The presence of one active suppressor gene, either Su-1 + , Su-2 + or Su-3 + , is a sufficient condition for suppression of N1 phosphatase nonsense mutations. The same phosphatase mutation may respond differently to each suppressor gene, as indicated by differences in specific enzymic activities of the phosphatase molecules produced by the suppressed mutants. It appears that each suppressor gene causes a different structural alteration in the phosphatase molecule. Fine-structure genetic detail within the Su-1 gene has been revealed by analysis of Su − mutations isolated in an Su-1 + strain. There are several closely linked sites in the Su-1 gene at which Su − mutations can occur. The resulting mutants differ in their suppressor phenotypes; some are partially active (leaky mutants) whereas others are inactive. Suppression of a nonsense mutation can be highly efficient, resulting in as much as 55% of the standard amount of phosphatase synthesis. Nevertheless, there is no measurable difference in growth rate between pairs of Su + and Su − strains that are isogenic except for the suppressor mutation. This suggests that the nonsense codon involved with the N1 class of phosphatase mutations (the UAG codon) is not used as a normal chain-terminating codon.
The Current Disruption Myth

We investigate signs and symptoms of current disruption and diversion on the basis of resistive MHD simulations of magnetotail dynamics. The simulations generally support the view that the local occurrence of anomalous dissipation (here modeled by a resistive term) leads to the reduction (disruption) and diversion of cross-tail current. However, the dynamic relation between the occurrence of resistivity and its effects differs from views originally derived from circuit analogies. The primary myth addressed here is the expectation that current disruption is the direct consequence of anomalously enhanced dissipation, so that the current disruption region and the dissipation region should be collocated. We find that the initial consequence of enhanced resistance indeed is a reduction of the local cross-tail current threading the region of enhanced resistance. However, this local reduction is accompanied by a diversion of current around that region, so that there are no global consequences. The later, more global, current changes result from the plasma dynamics (flows) rather than from the local dissipation. Hence the region of reduced cross-tail current is distinct (located earthward) from the region of enhanced resistivity. The region of dipolarization, the most commonly considered indicator of current disruption, again is distinct from the region of current reduction. This region expands in all three space directions, which might affect the timing between satellites. The energy changes are consistent with the expected conversion of magnetic into kinetic and thermal energy. However, these processes are not highly localized and the release or conversion regions also are not collocated with the region of enhanced resistivity.
Concomitant administration of sGC stimulators with common classes of anti-hypertensive agents results in increased efficacy in spontaneously hypertensive rats

Background Soluble guanylate cyclase (sGC) stimulators demonstrate smooth muscle relaxation and vasodilation via the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway. A novel class of sGC stimulators, the pyrazole-pyrimidines, was synthesized with the objective of creating a potent, once-a-day (QD) oral treatment for cardiovascular diseases. Several compounds from this class were identified as potent stimulators of sGC in vitro (EC50 = 40-287 nM). These compounds were evaluated in pharmacokinetic (PK) and blood pressure pharmacodynamics (PD) in vivo rat and dog models and were shown to exhibit sustained compound exposure (Thalf = >7 hours in preclinical species) after oral dosing, predicting QD dosing in humans. Further, they significantly decreased mean arterial blood pressure (MAP (≥ 10mmHg) after oral dosing. The potential for sGC stimulators to work in combination with reference antihypertensive therapies was assessed in an in vivo PD assay in a spontaneous hypertensive rat (SHR) model. Doses of losartan, atenolol, amlodipine, and our sGC stimulators that induced an effect (< 30mmHg) on MAP were chosen. IWP-121, a representative sGC stimulator, was shown to provide additional MAP lowering effects when combined with losartan, atenolol, or amlodipine, resulting in an increase in overall blood pressure effects between 5-50%. By linking compound concentration to blood pressure change for each compound alone and in combination, we were able to assess the PK/PD relationships for the individual and combined effects.
Anisotropy Lengthens the Decay Time of Turbulence in Molecular Clouds

The decay of isothermal turbulence with velocity anisotropy is investigated using computational simulations and synthetic observations. We decompose the turbulence into isotropic and anisotropic components with total velocity dispersions {sigma}{sub iso} and {sigma}{sub ani}, respectively. We find that the decay rate of the turbulence depends on the crossing time of the isotropic component only. A cloud of size L with significant anisotropy in its turbulence has a dissipation time, t{sub diss} = L/(2{sigma}{sub iso}). This translates into turbulent energy decay rates on the cloud scale that can be much lower for anisotropic turbulence than for isotropic turbulence. To help future observations determine whether observed molecular clouds have the level of anisotropy required to maintain the observed level of turbulence over their lifetimes, we performed a principal component analysis on our simulated clouds. Even with projection effects washing out the anisotropic signal, there is a measurable difference in the axis-constrained principal component analysis performed in directions parallel and perpendicular to the direction of maximum velocity dispersion. When this relative difference, {psi}, is 0.1, there is enough anisotropy for the dissipation time to triple the expected isotropic value. We provide a fit for converting {psi} into an estimate for the dissipation time,more » t{sub diss}.« less
Synthesis and study of naphthacenedione (TQ) as a photosensitizer for one-electron oxidation of DNA

[reaction: see text] Photosensitizers are useful for the study of one-electron oxidation of DNA. Most such photosensitizers absorb light in the UV spectral region. We report the synthesis and investigation of a 5,12-naphthacenedione (TQ) derivative as a DNA photosensitizer. Irradiation of a TQ-linked duplex with visible light results in reaction of the DNA that is characteristic of one-electron oxidation. The results from TQ sensitization are identical, within experimental error, with that of a well-studied anthraquinone derivative.