cssi/SciSciGPT-SciSciNet huggingface dataset:
Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs

Abstract Introduction Alzheimer apolipoprotein E ( APOE ) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to "coordinated lysosomal expression and regulation" (CLEAR) DNA motifs. Methods Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4. Computational modeling assessed interactions between apoE and mutated apoE with CLEAR or modified DNA. Results Three TFEB-regulated mRNA transcripts— SQSTM, MAP1LC3B , and LAMP2 —were lower in AD ɛ4/ɛ4 than in AD ɛ3/ɛ3 brains. Computational modeling predicted avid specific binding of apoE4 to CLEAR motifs. ApoE was found in cellular nuclei, and in vitro binding assays suggest competition between apoE4 and TFEB at CLEAR sites. Conclusion ApoE4-CLEAR interactions may account for suppressed autophagy in APOE ɛ4/ɛ4 carriers and, in this way, contribute to earlier AD onset.
Modal Discrimination in Parity-Time-Symmetric Single Microring Lasers

By selectively breaking parity-time (PT) symmetry for the specific whispering-gallery mode, the single mode lasing has been experimentally demonstrated in a single microring resonator. In this paper, we analyze the modal discrimination to show the robustness of the single mode operation in two different types of PT symmetric single microring lasers: one with the gain/loss grating, and the other with the gain/index/loss grating. We show that they both can exhibit much higher modal discrimination than the conventional microring resonator. The single mode operation is robust even if the gain and loss distribution is quasi-symmetric, i.e., the unbalanced perturbation amplitudes or duty cycles. Therefore, the PT symmetric single microring lasers can provide very stable single-mode operation.
Synthesis of N-Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids

N-Substituted 3-amino-4-halopyridines are valuable synthetic intermediates, as they readily provide access to imidazopyridines and similar heterocyclic systems. The direct synthesis of N-substituted 3-amino-4-halopyridines is problematic, as reductive aminations and base-promoted alkylations are difficult in these systems. A high yielding deprotection/alkylation protocol mediated by trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate is described, providing access to a wide scope of N-substituted 3-amino-4-halopyridines. This protocol furnishes many reaction products in high purity without chromatography. Similar reductive amination conditions were also established for deactivated anilines.
National Toxicology Program

This article is a revision of the previous edition article by Harihara M. Mehendale, volume 4, pp 549–550, © 2005, Elsevier Inc.
Elia Benamozegh’s Printing Presses: Livornese Crossroads and the New Margins of Italian Jewish History

An Italian rabbi, kabbalist, and thinker of Moroccan descent who lived in the Tuscan port city of Livorno, Elia Benamozegh (1823–1900) authored many works in Hebrew, Italian, and French and significantly influenced Christian–Jewish relations in Europe. Lesser known, however, is his role as a publisher.
Causal Therapies in Mucopolysaccharidoses: Enzyme Replacement Therapy

Enzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) is the treatment of choice for patients, since it specifically addresses the underlying cause of the disease. Intravenous weekly infusions of recombinant enzymes for MPS I, II, IVA, VI, and VII have proven to be safe and efficacious for somatic symptoms. ERT has been shown to decrease urinary glycosaminoglycan levels and organomegaly, while improving stamina of patients, respiratory function, and quality of life. Although early administration of ERT optimizes outcomes, adult patients still benefit from treatment. ERT has been successfully used as combination therapy with hematopoietic stem cell transplant for patients with MPS I and MPS II, improving patient's cognitive outcomes. Although patients can receive benefit from ERT, current challenges include lack of improvement of neurological manifestations, limited effect on bone disease, development of immune response toward the infused enzyme, and high cost. We will discuss the milestones achieved by intravenous ERT for MPS diseases as well as the current challenges.
Christian Short-Term Missions: Creating Global Citizens?

Thousands of affluent, white, young Americans travel overseas each year on mission trips organised by Christian churches and organisations. Like secular study-abroad and gap-year programmes, contem...
Providers' Involvement of Parents, Families, and Family Dynamics in Youth Weight Management Programs.

Family-based interventions are the current standard for the treatment of pediatric obesity, yet the details of how providers are involving family members, and the barriers to family involvement, ar...
Chance encounters/random processes

Abstract Biologically significant, low copy number cellular processes that behave randomly are increasingly being documented, calling for statistical models. As represented by a Poisson process model, memoryless (Markov), small numbers out of large, independent, reactant populations change state at time intervals given by the exponential distribution. Computer implementation by the Gillespie stochastic kinetics simulation algorithm takes into account probabilities of reactant productive encounters as well as the physical nature of the reaction. Statistical behavior modified by specific participant interactions, the addition to a polypeptide of residues by nucleation, propagation, and H-bonding is described by the configurational energy based Lifson–Roig model of polypeptide helix–coil transitions. Creating polypeptide partition functions that link the configurational energy to the probabilities of helix–coil conformations opens the way to calculating various molecular parameters characteristic of polypeptides in solution. Polynucleotides are open to similar types of analysis.
RadHAR: Human Activity Recognition from Point Clouds Generated through a Millimeter-wave Radar

Accurate human activity recognition (HAR) is the key to enable emerging context-aware applications that require an understanding and identification of human behavior, e.g., monitoring disabled or elderly people who live alone. Traditionally, HAR has been implemented either through ambient sensors, e.g., cameras, or through wearable devices, e.g., a smartwatch, with an inertial measurement unit (IMU). The ambient sensing approach is typically more generalizable for different environments as this does not require every user to have a wearable device. However, utilizing a camera in privacy-sensitive areas such as a home may capture superfluous ambient information that a user may not feel comfortable sharing. Radars have been proposed as an alternative modality for coarse-grained activity recognition that captures a minimal subset of the ambient information using micro-Doppler spectrograms. However, training fine-grained, accurate activity classifiers is a challenge as low-cost millimeter-wave (mmWave) radar systems produce sparse and non-uniform point clouds. In this paper, we propose RadHAR, a framework that performs accurate HAR using sparse and non-uniform point clouds. RadHAR utilizes a sliding time window to accumulate point clouds from a mmWave radar and generate a voxelized representation that acts as input to our classifiers. We evaluate RadHAR using a low-cost, commercial, off-the-shelf radar to get sparse point clouds which are less visually compromising. We evaluate and demonstrate our system on a collected human activity dataset with 5 different activities. We compare the accuracy of various classifiers on the dataset and find that the best performing deep learning classifier achieves an accuracy of 90.47%. Our evaluation shows the efficacy of using mmWave radar for accurate HAR detection and we enumerate future research directions in this space.
Teaching an Old Yellow Jacket New Tricks – Adopting Change Management

“The measure of intelligence is the ability to change.” – Albert EinsteinThe Information Technology (IT) Change Management process exists to help control the life cycle of strategic, tactical, and operational changes to IT services through standardized procedures. The goal of Change Management is to control risk and minimize disruption to associated IT services and business operations.Georgia Institute of Technology introduced IT Change Management in 2017. This paper and subsequent presentation will briefly describe and define change management and how it fits into the ITSM model. It will then discuss Georgia Tech's process, as well as how we managed adoption. Finally, we will summarize the first year of data, and share our successes and our lessons learned.This document and presentation endeavor to present a clearer understanding of IT change management, how it can work in a higher education setting and how a large research institution traversed adoption of change management.
Plasma-free water droplet shattering by long-wave infrared ultrashort pulses for efficient fog clearing

High-power lasers can be used to clear a foggy or cloudy atmosphere by exploding and shattering water microdroplets into smaller fragments. The physics of laser–droplet interaction strongly depend on the excitation wavelength and pulse duration, and new techniques with optimized energy requirements that enable lossless long-distance propagation are urgently needed. In this work, a novel and elegant way of water droplet shattering by sub-µJ long-wave infrared ultrashort laser pulses is proposed, making it possible to practically avoid undesirable electron plasma generation in a water droplet and optical breakdown in air. A multiphysics study is performed, which takes into account a hierarchy of physical processes including free carrier plasma kinetics underpinned by a full-vector nonlinear Maxwell solver and the thermomechanical dynamics of pressure waves followed by droplet shattering into smaller fragments described by Navier–Stokes equations. Our results are crucial both for understanding the fundamental nature of water excitation with long-wave infrared radiation and for development of laser applications such as atmospheric communications.
Sex-segregated range use by black-and-white ruffed lemurs (Varecia variegata) in Ranomafana National Park, Madagascar.

Ranging behavior is one important strategy by which nonhuman primates obtain access to resources critical to their biological maintenance and reproductive success. As most primates live in permanent social groups, their members must balance the benefits of group living with the costs of intragroup competition for resources. However, some taxa live in more spatiotemporally flexible social groups, whose members modify patterns of association and range use as a method to mitigate these costs. Here, we describe the range use of black-and-white ruffed lemurs (Varecia variegata) at Mangevo, an undisturbed primary rainforest site in Ranomafana National Park, Madagascar and characterize sex-differences in annual home range area, overlap, and daily distances traveled. Moreover, we characterized seasonal variability in range use and ask whether ranging behaviors can be explained by either climatic or reproductive seasonality. We found that females used significantly larger home ranges than males, though sexes shared equal and moderate levels of home range overlap. Overall, range use did not vary across seasons; though within sexes, male range use varied significantly with climatic variation. Moreover, daily path length was best predicted by day length, female reproductive state, and sex. While the patterns of range use and spatial association presented here share some similarities with 9bisexually bonded9 community models described for chimpanzees, we argue that ruffed lemurs represent yet another community model wherein 9neighborhoods9 of overlapping males and females affiliate with each other moreso than with other, more distantly located community members, and to the exclusion of members from adjacent communities.
Location of a single histidine within peptide carriers increases mRNA delivery

Background Previously, we determined that four-branched histidine-lysine (HK) peptides were effective carriers of plasmids and small interfering RNA. In the present study, we compared several branched HK carriers and, in particular, two closely-related H3K4b and H3K(+H)4b peptides for their ability as carriers of mRNA. The H3K(+H)4b peptide differed from its parent analogue, H3K4b, by only a single histidine in each branch. Methods A series of four-branched HK peptides with varied sequences was synthesized on a solid-phase peptide synthesizer. The ability of these peptides to carry mRNA expressing luciferase to MDA-MB-231 cells was investigated. With gel retardation and heparin displacement assays, the stability of HK polyplexes was examined. We determined the intracellular uptake of HK polyplexes by flow cytometry and fluorescence microscopy. The size and polydispersity index of the polyplexes in several media were measured by dynamic light scattering. Results MDA-MB-231 cells transfected by H3K(+H)4b-mRNA polyplexes expressed 10-fold greater levels of luciferase than H3K4b polyplexes. With gel retardation and heparin displacement assays, the H3K(+H)4b polyplexes showed greater stability than H3K4b. Intracellular uptake and co-localization of H3K(+H)4b polyplexes within acidic endosomes were also significantly increased compared to H3K4b. Similar to H3K(+H)4b, several HK analogues with an additional histidine in the second domain of their branches were effective carriers of mRNA. When combined with DOTAP liposomes, H3K(+H)4b was synergistic in delivery of mRNA. Conclusions H3K(+H)4b was a more effective carrier of mRNA than H3K4b. Mechanistic studies suggest that H3K(+H)4b polyplexes were more stable than H3K4b polyplexes. Lipopolyplexes formed with H3K(+H)4b markedly increased mRNA transfection.
Viscera affectum anno: the gut beyond eating behaviours.

One of the most pleasurable, yet dangerous, activities of our daily life is eating. But once food has been swallowed, all we can do is to trust our gut. Several remarkable studies published in 2020 have expanded our knowledge on how the gut is intertwined with essential behaviours beyond food.
Focused Cardiac Ultrasound (FOCUS) in Pediatric Intensive Care

Point-of-care ultrasound (POCUS) is continuing to grow in the field of pediatric critical care. The use of this invaluable bedside tool includes a range of applications dedicated to procedural practice as well as evaluations of vital organs like the heart, lung, and assessment of volume status and fluid response [1]. Pediatric critical care fellowships have begun to include comprehensive training of POCUS in their fellowship curriculum to ensure quality image acquisition and interpretation, although training is still highly variable and institution specific [2]. POCUS cardiac ultrasound, or more commonly known as focused cardiac ultrasound (FOCUS), can provide valuable information on cardiac function in critically ill patients in the pediatric ICU. With sufficient didactic and clinical experience, non-cardiologists are able to competently assess the heart for specific cardiac pathology and perform at the level of cardiologists [3, 4]. The following review provides a detailed explanation of the technique of FOCUS and the potential pathology that can be identified.
Negotiation All Around

Many of us picture negotiations as having a diplomatic or business context, and focusing on matters such as ending armed conflict or sealing multi-million dollar deals. In our minds, negotiations connote people in suits discuss weighty things. However, the literature on negotiation solidly agrees on one thing. The spectrum of negotiation interactions we engage in goes far beyond the limits of this preconception, and includes many - perhaps most - of our interpersonal interactions, in our personal, family and professional lives. In this paper, I present the wide range of negotiation activity we engage in, through the perspectives offered by leading books on negotiation. This resource aims to provide negotiation teachers and trainers with a convenient teaching resource to supplement classroom activities on this topic.
Age and Year of HIV Diagnosis are Associated with Perceptions of Discrimination and Internalized Stigma Among Sexual Minority Men Who Use Substances

Discrimination and internalized stigma are barriers to engagement in HIV self-care among men who have sex with men (MSM) living with HIV. However, differences in perceptions of discrimination and internalized stigmas by age, year of HIV-diagnosis, and race are poorly understood. We assessed differences in reported discrimination related to HIV, race, sexual orientation, and substance use and internalized stigmas among 202 MSM living with HIV who use substances. Younger participants reported higher levels of all types of discrimination and internalized stigmas (p-values < 0.001–0.030). Those diagnosed after the advent of antiretrovirals reported higher levels of discrimination related to HIV, sexual orientation, and substance use, as well as internalized stigma related to HIV and substance use (p-values 0.001–0.049). We explored perceived community HIV stigma, which accounted for associations involving age and year of diagnosis. Age, year of diagnosis, and race should be considered when assessing and intervening with stigma.
Inverse Design of Near-Field Transducer for Heat-Assisted Magnetic Recording Using Topology Optimization

Heat-assisted magnetic recording (HAMR) is one of the next generation technologies in data storage that can increase the areal density to beyond 1.5 Tb/in2. Near-field transducer (NFT) is a key component of the HAMR system that locally heats the recording medium by concentrating light below the diffraction limit using surface plasmons. In this work, we use density-based topology optimization for inverse design of NFT for a desired temperature profile in the recording medium. We first perform an inverse thermal calculation to obtain the required volumetric heat generation (electric field) for a desired temperature profile. Then an inverse electromagnetic design of NFT is performed for achieving the desired electric field. NFT designs for both generating a small heated spot size and a heated spot with desired aspect ratio in recording medium are demonstrated.
IPCC and the Deep Sea: A Case for Deeper Knowledge

IPCC reporting culture and structure leads to a failure to highlight potential vulnerabilities and risk in areas where research is largely absent. Nowhere is this more obvious than in treatment of the deep ocean (waters below 200 m), where climate research is in its infancy, but human exploitation of resources is on the rise. Understanding climate-induced changes in deep- sea environments, ecosystems and their services, including carbon cycling and climate regulation, is fundamental to future ocean sustainability and to decisions about active climate remediation.
Implementing an Application Programming Interface for PROMIS Measures at Three Medical Centers

Background There is an increasing body of literature advocating for the collection of patient-reported outcomes (PROs) in clinical care. Unfortunately, there are many barriers to integrating PRO measures, particularly computer adaptive tests (CATs), within electronic health records (EHRs), thereby limiting access to advances in PRO measures in clinical care settings. Objective To address this obstacle, we created and evaluated a software integration of an Application Programming Interface (API) service for administering and scoring Patient-Reported Outcomes Measurement Information System (PROMIS) measures with the EHR system. Methods We created a RESTful API and evaluated the technical feasibility and impact on clinical workflow at three academic medical centers. Results Collaborative teams (i.e., clinical, information technology [IT] and administrative staff) performed these integration efforts addressing issues such as software integration as well as impact on clinical workflow. All centers considered their implementation successful based on the high rate of completed PROMIS assessments (between January 2016 and January 2021) and minimal workflow disruptions. Conclusion These case studies demonstrate not only the feasibility but also the pathway for the integration of PROMIS CATs into the EHR and routine clinical care. All sites utilized diverse teams with support and commitment from institutional leadership, initial implementation in a single clinic, a process for monitoring and optimization, and use of custom software to minimize staff burden and error.
Kathleen Mears Lecture: Electroneurodiagnostic Technology: Will It Withstand the Test of Time? Issues Regarding Professional Status, Education, and Credentialing

ABSTRACTThe roles of healthcare professions are being reevaluated, redesigned, and reengineered as a result of healthcare reform. To see how well Electroneurodiagnostic Technology is positioned to endure, we need to examine the following questions: Have we clearly defined our profession, and identified a need and role for our services? How adequate are we at preparing individuals to meet the needs and roles we define? Is voluntary credentialing important and are the current credentialing processes effective? What changes should we consider for the future in order to secure our survival? As a profession, we must come together to clearly define Electroneurodiagnostic Technology, champion our services, and establish core education requirements.
Mechanisms of Drug Interactions II

Drug interactions continue to be an important consideration for patients receiving antimicrobial chemotherapy. The clinical significance of drug interactions in patients receiving anti-infectives has been spotlighted by numerous reports of drug interactions among patients taking antiretroviral therapy (1). As a result, considerable progress has been made in describing the mechanisms by which drug interactions occur; this has led to increased ability to recognize and manage clinically significant drug interactions. Although much of the success in managing drug interactions can be attributed to increased knowledge of cytochrome P450 (CYP)-mediated drug metabolism, drug transport mechanisms are increasingly recognized as a means by which clinically relevant drug interactions occur among anti-infective agents (2).
Technical note: recombinant LHRH fusion protein suppresses estrus in heifers.

A recombinant luteinizing hormone-re- leasing hormone (LHRH) fusion protein was evaluated for its effectiveness in suppression of estrus in heifers. Eight heifers were randomly assigned to two equal treatment groups. Treatments consisted of recombi- nant ovalbumin-LHRH-7 or recombinant ovalbumin (control). This recombinant chimeric fusion protein con- sisted of ovalbumin with seven LHRH peptides (oval- bumin-LHRH-7). The plasmid for this protein was ex- pressed in E. coli and was collected and purified as an insoluble protein. One milligram of the respective proteins was suspended in 2 mL of Z-Max adjuvant and administered by intramammary injection three times
Binding and phasing of Escherichia coli single-stranded DNA-binding protein by the secondary structure of phage G4 origin of complementary DNA strand synthesis (G4oric).

The origin of phage G4 DNA complementary strand synthesis (G4oric) consists of three stem-loop structures (stem loops I, II, and III) that have been proposed as a recognition site for primase during primer RNA (pRNA) synthesis (Godson, G. N., Barrell, B. G., Staden, R., and Fiddes, J. C. (1978) Nat. New Biol. 276, 236-247; Fiddes, J. C., Barrell, B. G., and Godson, G. N. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 1081-1085; Sims, J., Capon, D., and Dressler, D. (1979) J. Biol. Chem. 254, 12615-12628). It is generally considered that the double-stranded DNA stem-loop structure is not coated with Escherichia coli single-stranded DNA-binding protein (SSB), but is recognized by primase as naked DNA (Kornberg, A., and Baker, J. (1992) DNA Replication, 2nd Ed., p. 280, W. H. Freeman & Co., New York). Using small G4oric single-stranded DNA fragments of various sizes (302, 278, 149, and 100 nucleotides) consisting of the core 100-nucleotide stem-loop region plus differing lengths of 3'- and 5'-flanking sequence as substrates for gel retardation and DNase I and micrococcal nuclease digestion, we show that under conditions of pRNA synthesis, two SSB tetramers bind to the stem-loop structure. With increasing lengths of 5'- and 3'-flanking sequence, more SSB tetramers are added. Regardless of the number of SSB tetramers bound, however, the region of DNA containing the pRNA initiation site is always left accessible to nuclease digestion. In situ copper-phenanthroline footprinting of individual gel shift assembly intermediates shows that on the 302-nucleotide G4oric, the first two SSB tetramers assemble at random, but the addition of more SSB tetramers results in formation of a unique structure. In this structure, SSB tetramers protect both sides of stem loop III plus the intervening region between stem loops III and I, but leave most of stem loop I and the CTG pRNA initiation site accessible to copper-phenanthroline. Primase can only synthesize pRNA when the stem-loop structure is saturated with SSB and presumably in the unique configuration. The G4oric stem-loop structure therefore appears to dictate the phasing of SSB to leave a primase recognition site as free DNA.
Everyone is a Curator: Human-Assisted Preservation for ORE Aggregations

The Open Archives Initiative (OAI) has recently created the Object Reuse and Exchange (ORE) project that denes Resource Maps (ReMs) for describing aggregations of web resources. These aggregations are susceptible to many of the same preservation challenges that face other web resources. In this paper, we investigate how the aggregations of web resources can be preserved outside of the typical repository environment and instead rely on the thousands of interactive users in the web community and the Web Infrastructure (the collection of web archives, search engines, and personal archiving services) to facilitate preservation. Inspired by Web 2.0 services such as digg, deli.cio.us, and Yahoo! Buzz, we have developed a lightweight system called ReMember that attempts to harness the collective abilities of the web community for preservation purposes instead of solely placing the burden of curatorial responsibilities on a small number of experts.
Automatic Classification of Containment and Support Spatial Relations in English and Dutch

The need to communicate and reason about space is pervasive in human cognition. Consequently, most languages develop specialized terms for describing relationships between objects in space --- spatial prepositions. However, the specific set of prepositions and the delineations between them vary widely. For example, in English containment relationships are categorized as inand support relationships are classified as on. In Dutch, on the other hand, three different prepositions are used to distinguish between different types of support relations: op, aan, and om. In this paper we show how progressive alignment can be used to model the formation of spatial language categories along the containment-support continuum in both English and Dutch.
The Ontogeny and Fate of NK Cells Marked by Permanent DNA Rearrangements

A subset of NK cells bears incomplete V(D)J rearrangements, but neither the consequence to cell activities nor the precise developmental stages in which recombination occurs is known. These are important issues, as recombination errors cause cancers of the B and T lineages. Using transgenic recombination reporter mice to examine NK cell dynamics in vivo, we show that recombination+ NK cells have distinct developmental patterns in the BM, including reduced homeostatic proliferation and diminished Stat5 phosphorylation. In the periphery, both recombination+ and recombination− NK cells mediate robust functional responses including IFN-γ production, cytolysis, and tumor homing, suggesting that NK cells with distinct developmental histories can be found together in the periphery. We also show that V(D)J rearrangement marks both human cytolytic (CD56dim) and immunoregulatory (CD56bright) populations, demonstrating the distribution of permanent DNA rearrangements across major NK cell subsets in man. Finally, direct quantification of rag transcripts throughout NK cell differentiation in both mouse and man establishes the specific developmental stages that are susceptible to V(D)J rearrangement. Together, these data demonstrate that multipotent progenitors rather than lineage-specified NK progenitors are targets of V(D)J recombination and that NK cells bearing the relics of earlier V(D)J rearrangements have different developmental dynamics but robust biological capabilities in vivo.
A)HISTORICAL SCIENCE

In contrast to many other human endeavors, science pays little attention to its history. Fundamental scientific discoveries are often considered to be timeless and independent of how they were made. Science and the history of science are regarded as independent academic disciplines. Although most scientists are aware of great discoveries in their fields and their association with the names of individual scientists, few know the detailed stories behind the discoveries. Indeed, the history of scientific discovery is sometimes recorded only in informal accounts that may be inaccurate or biased for self-serving reasons. Scientific papers are generally written in a formulaic style that bears no relationship to the actual process of discovery. Here we examine why scientists should care more about the history of science. A better understanding of history can illuminate social influences on the scientific process, allow scientists to learn from previous errors, and provide a greater appreciation for the importance of serendipity in scientific discovery. Moreover, history can help to assign credit where it is due and call attention to evolving ethical standards in science. History can make science better.
Real-world effects of once vs greater daily inhaled corticosteroid dosing on medication adherence

Abstract Background Nonadherence to inhaled corticosteroids (ICSs) for asthma maintenance therapy is common and is associated with poor asthma outcomes. Simplifying dosing regimens for some chronic disease conditions has resulted in better adherence; however, little is known regarding the effect of ICS dosing on adherence for the treatment of asthma. Objective To determine whether once daily dosing is associated with higher adherence to ICS therapy when compared with 2 or more times daily dosing among patients with asthma. Methods Six years of pharmacy claims data were linked with prescription information to estimate ICS therapy adherence for patients with asthma 12 to 56 years of age who were members of a large health maintenance organization. Patient follow-up continued from the initial ICS fill until one of the following: the last ICS fill in the observation period, a switch of ICS dosing regimen, or the initiation of ICS and long-acting β-agonist combination therapy. Adherence was estimated by calculating a continuous multiple-interval measure of medication availability. Regression models were used to assess the relationship between adherence in patients treated with once daily vs 2 or more times daily ICS therapy. Results Among the 1,302 patients who met the inclusion criteria, 17% were prescribed once daily therapy, and 83% were prescribed 2 or more times daily therapy. Models comparing ICS adherence among individuals following once daily and 2 or more times daily ICS regimens suggested that once daily dosing was associated with an approximately 20% increase in adherence. This significant difference persisted among subgroups defined by sex, race/ethnicity, age, and asthma severity. Conclusion Once daily dosing was associated with higher adherence to ICS therapy; this included clinically relevant subgroups.
Stability Enhancement of Partially-Oxidized Porous Silicon Nanostructures Modified with Ethyl Undecylenate1

The thermal reaction of ethyl undecylenate with a hydrogen-terminated porous silicon surface takes place at 85 °C to yield an organic monolayer covalently attached to the surface through Si−C bonds. The presence of traces of water in ethyl undecylenate induces a partial oxidation of the surface and leads to a surface that is composed of alkylated and oxidized regions. A PSi surface with a comparable chemical composition was prepared by the direct reaction of an electrochemically anodized PSi surface (in 1 M H2SO4) with anhydrous ethyl undecylenate. The physical and chemical properties of the functionalized surfaces have been characterized using photoluminescence, transmission infrared, and X-ray photoelectron spectroscopies. The derivatized surfaces proved to be very stable in boiling CCl4 and water, and against corrosion when exposed to 100% humidity in air.
High speed characteristics of VCSELs

The high speed characteristics of Vertical Cavity Surface Emitting Lasers (VCSELs) for use in modern high bandwidth fiber optical networks is presented. An equivalent circuit model based on microwave network analyzer S11 measurements is developed. The dynamic operation of multi- transverse mode VCSELs is also investigated. Experimentally, a laser with two orthogonally polarized modes is examined. We show that each of the transverse laser modes may have significantly different rise and fall times. A multimode rate equation model is used to predict the exact pulseshape for each mode. The laser gain is saturated by the total optical intensity, and the sum of the modal powers is shown to have a constant rise and fall time. The system performance in terms of the bit error rate is also investigated. We demonstrate that selective attenuation of the optical modes can lead to an increase in the bit error rate due to polarization partitioning noise.
A variable redefinition approach for the lot sizing problem with strong set-up interactions

We address a variant of the Joint Replenishment Problem, in which the products can only be produced in fixed proportions to each other. Such problems occur commonly in the manufacture of sheet metal and die-cast parts and some chemical products. We call it the Strong Interaction Problem (SIP). The general instance of the problem is NP-complete while single nest instances are polynomially solvable. We establish the boundary at which the problem becomes hard. We also present an exact algorithm for solving the problem using a variable redefinition approach. Computational testing on randomly generated problems indicates that our algorithm is several orders of magnitude faster than solution of the problems without reformulation using existing algorithms and commercial software.
Acquired-cell immune deficiency syndrome

Abstract Acquired-cell immune deficiency syndrome is a symptom complex characterized by opportunistic infections and acquired immune deficiency in homosexual men. This article presents a case of acquired-cell immune deficiency syndrome in which the initial clinical findings were those of severe oral stomatitis.
Microdosimetric Aspects of Proton-Induced Nuclear Reactions in Thin Layers of Silicon

A computer simulation model which calculates the energy deposited within a small sensitive volume embedded in a larger volume as a result of nuclear interactions anywhere in the larger volume is outlined. The model is tested by comparison with the pulse-height spectra measured in silicon surface barrier detectors as a result of exposure to protons at different energies. The model is then used to provide physical insight into the role played by the nuclear recoil in localized energy deposition about a nuclear interaction.
Experiments on the Stability of Viscous Flow Between Rotating Cylinders. VI. Finite-Amplitude Experiments

The ion technique is applied to a variety of experiments in Couette flow: determination of the critical Taylor number; determination of wavenumber and waveform of the vortices; establishment of the laws that the square of the amplitude and the amplification factor both vary as the difference between the Taylor number and the critical Taylor number; and finally certain studies of the growth and decay of vortices as the Taylor number is changed. The experimental data are compared with the results of integration of the exact equations for the linear stability problem by means of a high-speed computer. These theo­retical values were obtained by P. H. Roberts and are presented in an appendix to this paper.
Connexin 26 Gene Therapy of Human Bladder Cancer: Induction of Growth Suppression, Apoptosis, and Synergy with Cisplatin

The connexin 26 (Cx26) gene encodes a protein involved in gap junctional intercellular communication and is a putative tumor suppressor. We constructed a Cx26 adenovirus vector (Ad-Cx26) and used it to infect human bladder cancer cell lines UM-UC-3, UM-UC-6, UM-UC-14, and T24. Infection with Ad-Cx26 suppressed the growth of these cell lines in vitro and prevented tumor formation in vivo. Cell cycle accumulation or arrest at the G1 phase was noted in UM-UC-3 cells and at the G2/M phase in UM-UC-6, UM-UC-14, and T24 cells. Apoptosis was noted in UM-UC-3, UM-UC-6, and UM-UC-14 cells both in vitro and in vivo. These effects were not seen with control adenovirus (Ad-CTR) or mock infection. Ad-Cx26 did not significantly alter the growth of the immortalized normal human bladder cell line SV-HUC. Direct injection of Ad-Cx26 into established UM-UC-3 and UM-UC-14 tumors in nude mice resulted in Cx26 expression, apoptosis, and significantly decreased growth compared with Ad-CTR treated tumors. Delayed resumption of ...
Stylistic properties and regulatory fit: Examining the role of self-regulatory focus in the effectiveness of an actor's vs. observer's visual perspective

Abstract Building on regulatory focus research, we investigate how certain visual elements of an advertising message, such as stylistic properties, contribute to regulatory fit and persuasion. Across three experiments, we examine how the visual perspective (actor's vs. observer's) through which a product is depicted in an ad affects product evaluations among participants with different regulatory foci (promotion- vs. prevention-focused). Specifically, we find that when an actor's perspective is used in an ad to portray a product, regulatory fit occurs among promotion-focused (vs. prevention-focused) participants and they report more favorable product evaluations; conversely, when an observer's perspective is used, regulatory fit occurs among prevention-focused (vs. promotion-focused) participants and they evaluate the product more favorably. An analysis of internal vs. external evaluation thoughts helps explain the persuasion effects.
A porous silicon based particle filter for microsystems

A porous silicon (PS) based particle filter has been fabricated and tested for integrated microsystems. By engineering the morphology of the porous silicon membrane, depth filtration with high collection efficiency in the submicron range (0.3∼ 1 μm), low pressure-drop, and large filtration capacity (0.5 mg/cm 2 ) has been demonstrated. With the PS particle filter, on-board gas filtration can be achieved.
Dynamical and Voltage Profile Stability of Inverter-Connected Distributed Power Generation

We present a systematic stability analysis of inverter-connected distributed generation. Our approach is to replace simulations with much faster and more informative analysis using transfer functions. The transfer functions characterize the dynamics of the interconnected feedback loops in the system. The methodology is applicable to different types of inverters, including droop inverters. It also may be applied to distribution systems with arbitrary topology. The analysis allows evaluation of system stability and performance, subject to frequency, load, and power set-point disturbances. By means of two examples we demonstrate how the proposed approach can help in analysis and engineering of the distribution systems with acceptable frequency and voltage profile responses to both distributed generation power and grid frequency disturbances.
TRANSCRIPTIONAL INHIBITION OF MANGANESE SUPEROXIDE DISMUTASE (SOD2) GENE EXPRESSION BY DNA METHYLATION OF THE 5' CPG ISLAND

Manganese superoxide dismutase (MnSOD) enzyme activity and SOD2 gene expression have often been reported to decrease during the development of cancer. SOD2 has also been implicated as a candidate tumor suppressor gene for human malignant melanoma. Genomic DNA methylation patterns are also known to change during carcinogenesis and serve as a mechanism for tumor suppressor gene inactivation. We hypothesized that decreased SOD2 gene expression in some malignant cell populations may be due, at least in part, to methylation of upstream transcriptional regulatory sequences in the SOD2 gene. To test this hypothesis we transfected methylated and unmethylated SOD/2-CAT promoter-reporter constructs in cells known to express the SOD2 gene. Our results indicate that methylation of specific cytokines in the SOD2 5' flanking region is sufficient to repress transcriptional activity of the SOD2 promoter by at least 50%. Moreover, we show that this transcriptional repression was likely mediated by inhibition of AP-2 DNA binding and transactivation from a methylated AP-2 binding site in the SOD2 promoter. DNA methylation may provide a mechanism for transcriptional inactivation of the SOD2 gene during the development of some cancers.
Synthese von Fluoro‐λ5‐monophosphazenen und Fluoro‐1, 3‐diaza‐2λ5, 4λ5‐diphosphetidinen mittels der Staudinger‐Reaktion

Durch die Umsetzung trivalenter Phosphorfluoride, RnPF3−n (n = 1, 2; R = R2N, (CH2)5N, O(CH2)4N, RO, (CH2O)2, Alkyl, Aryl) mit Phenylaziden, XC6H4N3 (X = H, 4-CH3, 4-Cl, 4-Br, 4-NO2, 3-NO2), wurden 35 Tetrafluoro- und 2-Difluorodiazadiphosphetidine sowie 4 Difluoro- und 30 Monofluoro-α5-monophosphazene dargestellt. PF3 reagiert nicht mit Phenylazid. Der Einflus der Substituenten auf die Konstitution der Reaktionsprodukte wird diskutiert. Kinetische Messungen ermoglichten die Bestimmung der Substituentenkonstanten σPI fur (CH2)5N, O(CH2)4N und R(C6H5)N (R = CH3, C2H5, n-C4H9). Synthesis of Fluoro-λ5-monophosphazenes and Fluoro-1,3-diaza-2λ5,4λ5-diphosphetidines by Means of the Staudinger Reaction 35 Tetrafluoro- and 2 difluorodiaza-diphosphetidines as well as 4 difluoro- and 30 monofluoro-λ5-monophosphazenes were prepared by the Staudinger reaction between tervalent phosphorus fluorides, RnPF3−n (n = 1, 2; R = R2N, (CH2)5N, O(CH2)4N, RO, (CH2O)2, alkyl, aryl) and phenylazides, XC6H4N3 (X = H, 4-CH3, 4-Cl, 4-Br, 4-NO2, 3-NO2). PF3 does not react with phenylazide The influence of substituents on the structure of the reaction products is discussed. Kinetic measurements allowed to determine the constants λPI of the substituents (CH2)5N, O(CH2)4N and R(C6H5)N (R = CH3, C2H5, n-C4H9).
Measures to improve security in a microkernel operating system

An operating system forms the foundation for all of the user's computer activities. Therefore, it should be trustworthy and function flawlessly. Unfortunately, today's operating systems, such as Windows and Linux, fail to deliver to this ideal, because they suffer from fundamental design flaws and bugs. Their monolithic kernel tend be overloaded with functionality that runs at the highest privilege level. This easily introduces bugs and breaches the Principle of Least Authorization (POLA) with all the related risks. Microkernel operating systems have a different design that makes them less vulnerable to these problems. A microkernel provides only a minimal set of abstractions that runs at the highest privilege level. Extended operating system functionality is typically available by means of user-space servers. By splitting an operating system into small, independent parts, the system becomes less complex and more robust, because the smaller parts are more manageable and help to isolate faults, respectively. This paper reviews the concepts and mechanisms used to improve security in Microkernel Operating system and described in brief about two real-world microkernel operating system, trying to achieve security as its goal.
Attitude differences of volunteers and nonvolunteers and of susceptible and nonsusceptible hypnotic subjects

Abstract A form of the Semantic Differential, containing 9 concepts related to hypnosis and research, was administered to 96 hypnotically inexperienced male Ss. The Ss were later asked to volunteer for a hypnotic experiment, and the hypnotic susceptibility of all volunteers (N = 51) was then determined. Semantic Differential responses of volunteers and nonvolunteers and of highly susceptible and unhyp-notizable Ss were compared. Differences between groups, in both comparisons, were generally not statistically significant, a finding which suggests that there is no simple relationship between paper-and-pencil measures of attitudes and volunteering for hypnotic experiments or hypnotizability.
Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts

Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including proto-oncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK- selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process.
Expanding Sexual Selection Gradients; A Synthetic Refinement of Sexual Selection Theory

Sexual selection is usually modeled as fitness differences that are mediated through variation in the number of mates obtained (variance in mating success, VMS). Nevertheless, empirical studies increasingly posit sexual selection even when VMS is low or does not contribute to variance in fitness, as is the case in females of many species. In these contexts, evolution by sexual selection is only plausible if it is mediated through variation in mate quality (VMQ) rather than exclusively through variation in the number of mates (VMS). However, we lack a formal theoretical foundation for sexual selection in these cases. Here, I argue the need for an explicit, formal treatment of how VMQ may result in sexual selection. Building upon the conceptually powerful framework of sexual selection gradients, I propose a graphical heuristic model that aims to serve as a foundation for future formal models. I close by discussing the implications of this perspective for sexual selection research in general, with particular attention to predictions that the model generates for the action of sexual selection on female traits.