cssi/SciSciGPT-SciSciNet huggingface dataset:
Dielectric acoustic response to microwave pulses through thermoacoustic and electrostrictive effects

Acoustic waves generated by pulsed microwaves have been cited as a mechanism for microwave hearing [1],[2],[3]. More recently it has been demonstrated that acoustic waves are transduced in dielectric objects simulating the ocular lens when exposed to pulsed microwaves [4]. The effect has also been cited as the operant mechanism for cellular damage in studies of the murine ocular lens in vitro [5]. Three theories on the microwave auditory mechanism have been reviewed and compared by Lin [6], viz., the radiation pressure theory, the electrostrictive theory, and the thermoacoustic theory. Among them it was found that only the thermoacoustic mechanism could produce elastic waves of magnitude large enough to explain the experimental observations. Comparing to the magnitude of acoustic pressure generated in typical biological tissues, the electrostrictive effect was found to be about two orders of magnitude smaller, while the radiation pressure three orders of magnitude smaller [7].
Thermodynamic measurement and modeling of vinyl fluoride solubility in aqueous lithium Bis(trifluoromethylsulfonyl)imide Li+Tf2N− + H2O solutions

Abstract The solubility of gaseous vinyl fluoride (VF) was measured in lithium bis(trifluoromethylsulfonyl)imide (Li+Tf2N−) + water (H2O) solutions at salt compositions on a solute (VF) free basis of 20.15, 40.0, and 80.0 wt.% at isothermal conditions of approximately 283 K, 304 K, and 372 K using a volumetric view cell. The experimental results demonstrated that vinyl fluoride is highly soluble in aqueous Li+Tf2N− salt solutions and that solubility is directly proportional to salt loading with the greatest VF solubilities ( x V F ≈ 0.0629 ) observed in samples containing 80.0 wt.% Li+Tf2N−. The experimental phase equilibrium results were successfully modeled by a standard Peng-Robinson equation of state which utilized a van der Waals 1-parameter mixing rule and four binary interaction parameters (two temperature dependent and two temperature independent). The absolute average deviation (AAD) in pressure between experimental and regressed data was 1.71% indicating the excellent model fit. The significant thermodynamic vinyl fluoride sorption capacity of Li+Tf2N− + H2O solutions indicate their potential to be utilized as improved solvents for poly(vinyl fluoride) polymerization reactions.
Phrixosoma concavifrons – a sexually dimorphic Phrixosomatini (Coleoptera: Curculionidae) from the Udzungwa mountains in Tanzania

A new species of Phrixosoma from Tanzania is described and illustrated. This is a unique species for the genus in havinga strongly concave female frons. Several characters are described for the first time for this genus, including male andfemale genitalia, mouthparts, thoracic sutures, and several overlooked features of the mesoand metatibiae and sternal processes.
Macroalgal foraging preferences of juvenile green turtles (Chelonia mydas) in a warm temperate/subtropical transition zone

Understanding resource use and foraging requirements is important for the recovery of threatened and endangered marine turtles. Throughout their range, an increasing number of juvenile green turtles (Chelonia mydas) has been observed foraging and sheltering within man-made structures. These “artificial habitats” are ecologically important as they support the growth of attached macroalgae, a primary food resource of juvenile green turtles. A population of juvenile green turtles in the Trident Basin at Port Canaveral, Florida, USA (28.41°N, 80.59°W), has historically exhibited strong site fidelity. The purpose of this study was to compare the foraging of juvenile green turtles with the availability of macroalgal resources. Foraging (lavage) samples from 94 juvenile green turtles during a 2-year study period from September 2008 through April 2010 were analyzed with the data from two previous studies (1997 and 2002) to determine the patterns of foraging habits through time. Turtles predominantly foraged on species of red (Rhodophyta) and green (Chlorophyta) macroalgae; however, opportunistic foraging on flotsam and invertebrates was common. Selection for certain rhodophytes (i.e., Gelidiopsis planicaulis, Grateloupia filicina, and Hypnea spinella) and chlorophytes (i.e., Cladophora liniformis, Ulva flexuosa, U. lactuca, and U. prolifera) varied by sampling period. Temperature-driven changes in the macroalgal species composition drove inter-annual differences in foraging content between 2002 and 2010. In addition, after an extended cold event, foraging samples from several turtles contained macroalgae not present in the Basin which suggested that turtles moved out of the Basin to forage during this time or newly emigrated. Establishing baseline resource utilization is instrumental for identifying the quality and function of natural and artificial habitats supporting juvenile green turtles, as their populations continue to recover around the globe.
Express with caution: Epitope tags and cDNA variants effects on hERG channel trafficking, half-life and function.

Introduction Genetic mutations in KCNQ2 which encodes hERG, the alpha subunit of the potassium channel responsible for the IKr current, cause Long QT Syndrome, an inherited cardiac arrhythmia disorder. Electrophysiology techniques are used to correlate genotype with molecular phenotype to determine which mutations identified in patients diagnosed Long QT Syndrome are disease causing, and which are benign. These investigations are usually done using heterologous expression in cell lines, and often, epitope fusion tags are used to enable isolation and identification of the protein of interest. Methods and results Here, we demonstrate through electrophysiology techniques and immunochemistry, that both N-terminal and C-terminal myc fusion tags may perturb hERG protein channel expression and kinetics of the IKr current. We also characterize the impact of two previously reported inadvertent cDNA variants on hERG channel expression and half-life. Conclusion Our results underscore the importance of careful characterization of the impact of epitope fusion tags and conformational sequencing prior to genotype-phenotype studies for ion channel proteins such as hERG. This article is protected by copyright. All rights reserved
The Value of Rehabilitation Medicine for Patients Receiving Palliative Care.

Background:Rehabilitation medicine is a multidisciplinary field aimed at improving patients’ quality of life by improving function. Patients receiving palliative care frequently share common symptoms including fatigue, decreased functional independence, mood disorders, pain, and breathlessness. Many rehabilitation interventions can improve these symptoms.Objective:To evaluate the scope and effectiveness of rehabilitation interventions and exercise programs in improving quality of life and distressing symptoms in patients receiving palliative care.Methods:We conducted a literature review of cancer rehabilitation topics and techniques specifically applied to patients with life-limiting conditions. Exercise and other rehabilitation interventions were analyzed for their effects on common symptoms and disabilities experienced by this patient population.Conclusion:Current available literature supports the use of exercise programs and rehabilitation interventions to improve fatigue, mood, functional independence...
AutoAdmin Project at Microsoft Research: Lessons Learned.

The AutoAdmin project was started at Microsoft Research in 1996. The goal of AutoAdmin is to develop technology that makes database systems more self-tuning and self-managing. Initially, we focused mainly on the physical database design problem. In subsequent years we broadened our focus and studied a number of other problems: database monitoring, execution feedback for query optimization, flexible hinting mechanisms for query optimizers, query progress estimation and index defragmentation. One discipline we consistently followed in this project was that of implementing our techniques in the database server (in our case this was Microsoft SQL Server). This helped us better understand the applicability and limitations of our ideas and made it possible for our work to have impact on the Microsoft SQL Server product. In this article, we summarize some of the key technical lessons we have learned in the AutoAdmin project. Thus our discussions center around work done in AutoAdmin and does not cover the extensive related work done in other related projects in the database community (see [21] for an overview of work on self-tuning database systems). We focus our discussion on three problems: (1) physical database design, (2) exploiting feedback from execution for query optimization, and (3) query progress estimation. More details of AutoAdmin can be found on the project website [1].
Bilingual Families: Using Therapist-Facilitated Interpretation in Psychotherapy:

Families initiate psychotherapy with a narrative that identifies a mythological explanation for their suffering. Through narrative therapy, a therapist is able to reframe this mythological narrativ...
CNS penetration of the CDK4/6 inhibitor ribociclib in non-tumor bearing mice and mice bearing pediatric brain tumors.

Ribociclib, an orally bioavailable small-molecule CDK4/6 inhibitor is currently undergoing evaluation to treat pediatric central nervous system (CNS) tumors. However, it is crucial that it penetrates the brain and tumor. Thus, the objectives of the present study were to derive a clinically relevant mouse dosage for cerebral microdialysis studies, and to characterize ribociclib CNS penetration in non-tumor bearing mice and in mice bearing DIPGx7 (glioma) cortical allograft tumors. A plasma pharmacokinetic study of ribociclib (100 mg/kg, orally) was performed in CD1 nude mice bearing glioma cortical allografts to obtain initial plasma pharmacokinetic parameters and to derive D-optimal plasma sampling time-points for microdialysis studies. Using a cerebral microdialysis technique, the extracellular fluid (ECF) disposition of ribociclib was evaluated after a single oral ribociclib dose (100 mg/kg) in non-tumor bearing mice and in mice bearing glioma cortical allografts. A one-compartment plasma model with absorption and ECF compartments were fit to plasma and ECF concentration–time data using a nonlinear mixed effects modeling approach (NONMEM 7.2). The mean unbound ribociclib plasma exposure (6812 ng/ml*h) was similar to that observed clinically at recommended dosages in adults. The median ribociclib ECF to plasma partition coefficient (Kp,uu) in non-tumor bearing and glioma mice was 0.10 and 0.07, respectively, and was not statistically different (t test, p = 0.19). The CNS penetration observed was encouraging enough to move ribociclib forward with preclinical efficacy studies in models of pediatric brain tumors.
P102 Alternative splicing of the SLCO1B1 transporter in paediatric liver

Background Alternative mRNA transcripts occur in >90% of human genes and may be triggered by developmental signals. The hepatic transporter OATP1B1 (gene name SLCO1B1) traffics substrates across the hepatic membrane, and shows age-related changes in protein expression. We aimed to predict novel isoforms of OATP1B1 by studying alternative splicing of SLCO1B1 in human paediatric post-mortem liver tissue, and the relationship of their mRNA expression with age. Methods mRNA expression of SLCO1B1 transcripts was determined using RNA sequencing (HISAT2/StringTie). Novel mRNA transcripts were considered of relevance when (1) the expression was >5% of the annotated isoform, (2) it was a SLCO1B7 and SCLO1B1 hybrid transcript, or (3) when the expression was associated with age. The software packages ORF-finder, TMpred and TOPO2 were used to predict the protein sequence and structure of the novel isoforms. Relationship of expression with age was studied with the Kruskal-Wallis test for age groups (fetal, 0–1.5 year, 1.5–6 year, 6–12 year and 12–18 year) and with Spearman correlation tests for age on continuous scale. Results In 97 hepatic post-mortem tissues (gestational age median 16.4 [range 14.7–41.3] weeks, postnatal age 0.36 [0 - 17] years) 27 novel mRNA transcripts were detected. Of these, 13 were relevant: 2 isoforms are predicted to translate into amino acid sequences similar to the annotated isoform for OATP1B1, 9 isoforms may translate into truncated versions, and the expression of 8 isoforms was associated with age. None of the isoforms had an ORF that covered the SLCO1B7 region. Conclusion We showed that novel SLCO1B1 mRNA isoforms potentially translate into OATP1B1 protein with unknown function, and that alternative splicing may well be a regulatory mechanism for SLCO1B1 expression during development. This data provides a better understanding of age-related changes in the expression of OATP1B1, and, with that, potentially improves prediction of disposition of endogenous and exogenous substrates. Disclosure(s) BG was supported, in part, by the Ter Meulen fund 2018 provided by the Royal Dutch Academy of Sciences. The National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland is funded by the National Institutes of Health (NIH) contract HHSN275200900011C, reference number, N01-HD-9-0011 and the Liver Tissue Cell Distribution System is funded by NIH contract number N01-DK-7-0004/HHSN267200700004C.
Printed Circuit Board (PCB) Layout

Once all the circuits have been designed, the next step is board layout. This is a very critical step in the development process because the effectiveness of the filtering circuits depends on where the components are placed relative to the DSP pins. Also, the board layout has a big effect on noise, crosstalk and transmission line effects so optimizing the layout can minimize these effects. This chapter covers the printed circuit board stackup and layout techniques for low noise and EMI.
Stabilization of extensive fine-scale diversity by spatio-temporal chaos

Abstract It has become recently apparent that the diversity of microbial life extends far below species level to the finest scales of genetic differences. Remarkably, extensive fine-scale diversity can coexist spatially. How is this diversity stable on long timescales despite selective or ecological differences and other evolutionary processes? Most work has focused on stable coexistence or assumed ecological neutrality. We present an alternative: extensive diversity maintained by ecologically-driven spatio-temporal chaos, with no assumptions about niches or other specialist differences between strains. We study generalized Lotka-Volterra models with anti-symmetric correlations in the interactions inspired by multiple pathogen strains infecting multiple host strains. Generally, these exhibit chaos with increasingly wild population fluctuations driving extinctions. But the simplest spatial structure, many identical islands with migration between them, stabilizes a diverse chaotic state. Some types (sub-species) go globally extinct, but many persist for times exponentially long in the number of islands. All persistent types have episodic local blooms to high abundance, crucial for their persistence as, for many, their average population growth rate is negative. Snapshots of the distribution of abundances show a power-law at intermediate abundances that is essentially indistinguishable from the neutral theory. But the dynamics of the large populations are much faster than birth-death fluctuations. We argue that this spatio-temporally chaotic “phase” should exist in a wide range of models, and that even in rapidly mixed systems, longer lived spores could similarly stabilize a diverse chaotic phase.
Response of Hysteretic Oscillators Under Nonstationary Random Excitation

Abstract Using nonparametric identification techniques, equivalent nonlinear memoryless systems are determined for a class of hysteretic oscillators subjected to broadband nonstationary random excitation. The oscillators are assumed to have time-invariant bilinear hysteretic properties. Numerical techniques are used to determine the time history of the response and excitation of the “exact” oscillator under a single random excitation record. This response is subsequently used with a time-domain nonparametric identification technique to determine by means of least-squares methods an equivalent nonlinear oscillator characterized by a doubly-indexed series of Chebyshev polynomials. The agreement between the mean-square response of the exact and approximate models is found to be good even when the oscillators are undergoing substantial nonlinear deformations.
Nitrite Improves Heart Regeneration in Zebrafish.

Aims: Nitrite is reduced to nitric oxide (NO) under physiological and pathological hypoxic conditions to modulate angiogenesis and improve ischemia-reperfusion injury. Although adult mammals lack the ability to regenerate the heart after injury, this is preserved in neonates and efforts to reactivate this process are of great interest. Unlike mammals, the adult zebrafish maintain the innate ability to regenerate their hearts after injury, providing an important model to study cardiac regeneration. We thus explored the effects of physiological levels of nitrite on cardiac and fin regeneration and downstream cellular and molecular signaling pathways in response to amputation and cryoinjury. Results: Nitrite treatment of zebrafish after ventricular amputation or cryoinjury to the heart in hypoxic water (∼3 parts per million of oxygen) increases cardiomyocyte proliferation, improves angiogenesis, and enhances early recruitment of thrombocytes, macrophages, and neutrophils to the injury. When tested in a fin regeneration model, neutrophil recruitment to the injury site was found to be dependent on NO. Innovation: This is the first study to evaluate effects of physiological levels of nitrite on cardiac regeneration in response to cardiac injury, with the observation that nitrite in water accelerates zebrafish heart regeneration. Conclusion: Physiological and therapeutic levels of nitrite increase thrombocyte, neutrophil, and macrophage recruitment to the heart after amputation and cryoinjury in zebrafish, resulting in accelerated cardiomyocyte proliferation and angiogenesis. Translation of this finding to mammalian models of injury during early development may provide an opportunity to improve outcomes during intrauterine fetal or neonatal cardiac surgery.
Software Engineering for Infrastructure and Configuration (SEConfig) - Workshop Report

Errors in con gurations, rather than source code, have become one of the major causes of system failures, resulting in security vulnerabilities, application outages, and incorrect program execu- tions. We report on the structure and results of the rst Interna- tional Workshop on Software Engineering for Infrastructure and Con guration Code. Our aim in organizing this jworkshop was to
Delay-Constrained GNR Routing for Layer Minimization

It is known that graphene nanoribbon (GNR)-based devices and interconnects can be a better alternative in nano-scale designs. In this article, given a set of GNR nets with delay constraints in a GNR routing plane, a delay-constrained routing algorithm can be proposed to minimize the number of the used layers with satisfying the non-crossing constraints between the two GNR nets and the delay constraints on the given GNR nets in multiple-layer delay-constrained GNR routing. The routing process in our proposed algorithm can be divided into two sequential steps: initial assignment and iterative routing. In the initial assignment step, based on the source-to-target transformation of the multiple-pin nets and the definition of the delay-constrained routing patterns on the GNR nets with the tight delay constraints, a set of necessary delay-constrained routing patterns on the GNR nets can be first assigned onto a minimal set of used layers and the remaining GNR nets can be further assigned onto the available layers. In the iterative routing step, based on the assignment result of the GNR nets, the assigned GNR nets can be routed by using one routability-driven obstacle-aware routing process without considering the delay constraints and the delay-violated GNR nets can be rerouted by using one iterative delay-constrained rip-up-and-rerouting process with considering the delay constraints. Compared with the combination of the source-to-target transformation of the multiple-pin nets and one multiple-layer planar routing process using two single-layer GNR routing algorithms, the experimental results show that our proposed delay-constrained algorithm can use less CPU time and reasonable wirelengths to decrease 38.6% and 35.0% of the number of used layers on the given GNR nets with two different sets of delay constraints for eight tested examples on the average, respectively.
Airway nitrite is increased in extremely preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and significantly contributes to mortality and morbidity with few predictive biomarkers. Given that nitrites have been implicated in pathways associated with lung disease, we hypothesized that nitrite levels would be altered in the airways of premature infants diagnosed with BPD. This was a prospective cohort study of extremely low birth infants (< 28 weeks’ gestation) at the University of Alabama at Birmingham. Nitrite levels from tracheal aspirates (TAs) were compared between intubated and ventilated infants with BPD and gestation matched full term (FT) controls. TA derived nitrite levels from day one after birth were also compared between preterm infants who did and did not develop BPD. Infants with BPD were found to have significantly elevated nitrite levels in their tracheal aspirates compared to gestation matched FT controls (p < 0.05). There was a trend for increased nitrite levels on postnatal day one in infants that developed BPD compared to infants that did not develop BPD (p = 0.05). In conclusion, nitrite levels are significantly increased in airways of infants with BPD. Data from a larger cohort are needed to further support the utility of nitrite for BPD prediction. Not applicable.
The resurgence of post-LASIK epithelial ingrowth

We are reporting a case of a 32-year-old female who presented with a gradual painless progressive decrease in vision in the right eye for 2 months. She underwent laser in situ keratomileusis (LASIK) for myopia in both eyes 8 years back. The right eye showed rolled flap margin with epithelial ingrowth extending from margin to pupillary area. Mechanical debridement was done along with flap wash and mitomycin-C and bandage contact lens placement. Visual acuity showed improvement on follow-up. However, the recurrence was noted at 6-month follow-up. This case highlights the challenges in the management of epithelial ingrowth.
The Hirota τ-function and well-posedness of the KdV equation with an arbitrary step-like initial profile decaying on the right half line

We are concerned with the Cauchy problem for the KdV equation on the whole line with an initial profile V0 which is decaying sufficiently fast at +∞ and arbitrarily enough (i.e. no decay or pattern of behaviour) at −∞. We show that this system is completely integrable in a very strong sense. Namely, the solution V( x, t)admits the Hirota τ -function representation V (x, t) =− 2∂ 2 x log det � I + M x,t � , (0.1) where Mx,t is a Hankel integral operator constructed from certain scattering and spectral data suitably defined in terms of the Titchmarsh–Weyl m-functions associated with the two half-line Schr¨ odinger operators corresponding to V0. We show that V( x, t)is real meromorphic with respect to x for any t> 0. We also show that under a very mild additional condition on V0 representation (0.1) implies a strong well-posedness of the KdV equation with such V0’s. Among others, our approach yields some relevant results due to Cohen, Kappeler, Khruslov, Kotlyarov, Venakides, Zhang and others.
The Marine Natural Product Furospinulosin 1 Induces Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cell Spheroids, But Not in Cells Grown Traditionally with Longer Treatment.

Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute’s connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study.
Becoming Killable: White-tailed deer management and the production of overabundance in the Blue Hills

This paper examines the implementation of a white-tailed deer management program in the Blue Hills Reservation outside of Boston, Massachusetts. Drawing on the concepts of biopolitics, we explore h...
The association between sleep deficits and sedentary behavior in people with mild Parkinson disease.

Purpose: Sleep deficits are a common nonmotor symptom of Parkinson disease (PD). People with mild PD also achieve less physical activity (PA) than healthy older adults (HOA), but the relationship b...
Galactose-Decorated Liver Tumor-Specific Nanoliposomes Incorporating Selective BRD4-Targeted PROTAC for Hepatocellular Carcinoma Therapy

This research deals with the development of asialoglycoprotein receptors (ASGPR) directed nanoliposomes incorporating a novel BRD4 (Bromodomain-containing protein 4) protein-targeted PROTAC (Proteolysis Targeting Chimera), ARV-825 (ARV) (GALARV), and to investigate the anticancer efficacy of GALARV for specific delivery in hepatocellular carcinoma. GALARV were prepared using the modified hydration method and characterized for their physicochemical properties as well as anticancer activity using 2D and 3D cell culture models. ARV and GALARV (93.83 ± 10.05 nm) showed significant in vitro cytotoxicity and apoptosis in hepatocellular carcinoma cells. GALARV also demonstrated a substantially higher intracellular concentration of ARV compared to non-targeted nanoliposomes (~3 fold) and ARV alone (~4.5 fold), showed good physical stability and negligible hemolysis. Immunoblotting results depicted substantial downregulation of target BRD4 protein, oncogenic c-Myc, apoptotic Bcl-2, and survivin proteins. Notably, GALARV treatment resulted in significant apoptosis and subsequent inhibition of the cell viability of 3D tumor spheroids of hepatocellular carcinoma. These results suggest that GALARV is a novel actively targeted PROTAC-based nanotherapeutic approach for hepatocellular carcinoma. Funding Information: The work was supported by the College of Pharmacy and Health Sciences, St. John’s University, Queens, NY. Declaration of Interests: The authors declare no conflict of interest.
Confabulation, amnesia and motor memory loss as a presentation of apparent ITPR1 antibody autoimmune encephalitis.

A 59-year-old woman presented to the hospital with acute, hypoactive altered mental status. Her symptoms had begun 3 days prior when she developed hallucinations, urinary and faecal incontinence, and somnolence. She also exhibited confabulations, amnesia, motor memory loss and a wide-based gait. Medical, psychiatric and neurological evaluations including imaging and laboratory workup were unrevealing. Treatment for possible Wernicke encephalopathy and psychosis with high-dose intravenous thiamine and antipsychotic medications did not lead to improvement. After discharge, a send-out cerebrospinal fluid autoimmune encephalitis panel resulted positive for the newly identified neuronal inositol triphosphate receptor one (ITPR1) antibody. This prompted readmission for intravenous steroids, plasmapheresis and intravenous immunoglobulin, which yielded mild clinical improvement. Here, we describe confabulations and psychiatric symptoms as novel manifestations of the primary presentation of anti-ITPR1 encephalitis in an effort to promote faster recognition of this disease and early initiation of treatment in suspected cases.
Predictive situation awareness reference model using Multi-Entity Bayesian Networks

Predictive Situation Awareness (PSAW) emphasizes the ability to make predictions about aspects of a temporally evolving situation. Higher-level fusion to support PSAW requires a semantically rich representation to handle complex real world situations and the ability to reason under uncertainty about the situation. Multi-Entity Bayesian Networks (MEBN) are rich enough to represent and reason about uncertainty in complex, knowledge-rich domains. In previous applications of MEBN to PSAW, the models, called MTheories, were constructed from scratch for each application. Designing models from scratch is inefficient and fails to build on the experience gained from prior work. In this paper, we argue that applications of MEBN to PSAW share similar goals and common model elements. We propose a reference model for designing a MEBN model for PSAW and evaluate our model on a case study of a defense system.
Cycloamyloses as Catalysts

Publisher Summary This chapter describes catalysis by cycloamyloses. The distinguishing feature of cycloamylose catalysis, the feature that leads to their catalytic selectivity, is complexation of the substrate at a discrete site of the cycloamylose molecule. Thus, catalysis by the cycloamyloses results from prior equilibrium complexation of the substrate at this active site, followed by intracomplex participation of functional groups of the cycloamylose molecule. The chapter discusses the physical properties of the cycloamyloses, including the structure of the active site, and the mechanisms by which the cycloamyloses selectively alter reaction rates. The addition of reagents to aqueous solutions of the cycloamyloses decreases the cycloamylose solubility. The chapter examines the effect of the cycloamyloses on the solubilities of the added reagents. The solubilities of a series of aliphatic acids, ranging from hexanoic to dodecanoic, are increased by factors ranging from 1.2 to 30 in the presence of the cycloamyloses.
Slow Viral Infections

There are many viruses that are not cleared from the body after they infect an individual. These include the herpes simplex viruses, hepatitis B, and five other viruses that are discussed in this chapter. The viruses are presented in chronologic fashion based on discovery, focusing on the possible sequelae that chronic infection with these viruses can cause. Adult T-cell lymphoma/leukemia (ATLL), an aggressive leukemia/lymphoma, remains a difficult disease to treat. A section reviews the natural course of human immunodeficiency virus (HIV) in the infected individual and follows it with an in-depth review of the major sequelae, listed by organ system. The immune system takes the brunt of the effects of HIV since these cells are the target of the virus. As an individual becomes infected, HIV quickly decimates the immune system. The chapter focuses first on the effect of HIV itself and only briefly mentions the infections that can affect the nervous system. Peripheral neuropathies have become the most common neurologic complication in the highly active antiretroviral therapy (HAART) era. They have been classified as inflammatory demyelination polyradiculoneuropathy, mononeuropathy multiplex or radiculopathy, distal symmetric polyneuropathy (DSP), and toxic neuropathy from antiretroviral therapy. Although pulmonary hypertension (PAH) may be associated with human herpesvirus 8 (HHV-8), HIV has been associated with pulmonary hypertension when no other organisms have been identified.
Translational research--implementation of NHLBI Obesity Guidelines in a primary care community setting: the Physician Obesity Awareness Project.

Background: Greater than 65 percent of the United States (US) population is overweight, with 32 percent obese. It is a problem in both developed and developing nations. While guidelines exist, counseling by physicians about obesity and weight loss is inconsistent, and physician approaches to obesity management have limited success. This study attempted to increase involvement in translating proven research into practice to improve physician awareness and improve outcomes of overweight/obesity. Twenty-one physicians in a suburban, middle class population in the Midwestern United States participated.Methods: Physician obesity awareness, weight, height, BMI, blood pressure, lipids, and glycohemoglobin were measured from 641 patients at baseline and were compared to 631 at 12-month follow-up. All 21 physicians received academic detailing and were presented with their clinical outcomes. Ten physicians received an Enhanced Intervention. They were additionally asked to place a sticker in the chart of their overweight or obese patients.Results: Fifty-three percent of physicians were not comfortable discussing obesity with their patients at baseline, decreasing to 0% at followup (p=0.041). Reference to obesity management by Intervention physicians increased from 2.4% to 9.2% (p=0.001) while for Enhanced Intervention physicians documentation increased from 3.9% to 15.6% (p=0.002). Those patients in the Enhanced Intervention group lost an average of 6.19 lbs (3.3%) (p=0.083) during the one year period versus 4.6 lbs (2.5%) (p=0.20) in the Intervention group. The BMI dropped 1.2 in the Intervention group and 0.72 in the Enhanced Intervention group. The data from both groups was pooled at both baseline and follow-up. The average weight of patients decreased from 185.7 lbs to 180.3 lbs (excluding outliers weighing >311 lbs). This 5.4 pound loss was significant (p=0.027). The BMI decreased from 30.1 to 29.1 (p=0.095). Cardiovascular co-morbidities improved.Conclusion: Obesity and overweight have a very high prevalence in a primary care community based settings. Clinicians are not comfortable diagnosing and managing obese and overweight patients. A combination of academic detailing and presentation of outcomes to physicians will improve their awareness and result in improved clinical outcomes including weight loss.
Regulation of CD44E by DARPP-32-dependent activation of SRp20 splicing factor in gastric tumorigenesis

CD44E is a frequently overexpressed variant of CD44 in gastric cancer. Mechanisms that regulate CD44 splicing and expression in gastric cancer remain unknown. Herein, we investigated the role of DARPP-32 (dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000) in promoting tumor growth through regulation of CD44 splicing. Using western blot and quantitative real-time PCR analysis, our results indicated that knockdown of endogenous DARPP-32 markedly reduces the expression of CD44 V8-V10 (CD44E). Using a quantitative splicing luciferase reporter system, we detected a significant increase in the reporter activity following DARPP-32 overexpression (P<0.001). Conversely, knocking down endogenous DARPP-32 significantly attenuated the splicing activity (P<0.001). Further experiments showed that DARPP-32 regulates the expression of SRp20 splicing factor and co-exists with it in the same protein complex. Inhibition of alternative splicing with digitoxin followed by immunoprecipitation and immunoblotting indicated that DARPP-32 has an important role in regulating SRp20 protein stability. The knockdown of endogenous DARPP-32 confirmed that DARPP-32 regulates the SRp20-dependent CD44E splicing. Using tumor xenograft mouse model, knocking down endogenous DARPP-32 markedly reduced SRp20 and CD44E protein levels with a decreased tumor growth. The reconstitution of SRp20 expression in these cells rescued tumor growth. In addition, we also demonstrated frequent co-overexpression and positive correlation of DARPP-32, SRp20 and CD44E expression levels in human gastric primary tumors. Our novel findings establish for the first time the role of DARPP-32 in regulating splicing factors in gastric cancer cells. The DARPP-32-SRp20 axis has a key role in regulating the CD44E splice variant that promotes gastric tumorigenesis.
Integrated processors in internetworking applications

The availability of new technologies has resulted in a plethora of connectivity methods between computer users. Connectivity solutions between Local Area Networks (LANs) and Wide Area Networks (WANs) in client-server computing applications are continuously being developed to give single users, telecommuters, small office/home office (SOHO) and LANs at remote sites easy access to corporate resources. The most imminent users' need is the capability to communicate across heterogeneous networks, at times separated geographically by significant distance, both internal and external to administrative boundaries. Platforms that support a variety of WAN link protocols, such as Frame Relay, Point-to-Point Protocol (PPP), Multi-link Point-to-Point Protocol (MLPPP), CCITT X.25 are necessary to facilitate the communications between the enterprise and remote networks or single users. This paper examines and analyzes the employment of advanced integrated silicon communication controllers as cost effective and flexible platforms in internetworking applications.
Topically Applied Diacylglycerols Increase Pigmentation in Guinea Pig Skin

Exposure of human and murine melanocytes in vitro to the diacylglycerol (DAG) 1-oleoyl-2-acetyl-sn-glycerol (OAG) markedly increases melanin production within 24 h. To determine whether OAG can increase melanin production in vivo , increasing concentrations of OAG (10–60 mg/ml) in propylene glycol were applied daily for 5 d to shaved guinea pigs. Dose-dependent increased pigmentation was visible first on days 17–22 and persisted for 10–14 weeks. Peak epidermal melanin content in OAG-treated sites was more than twice that of untreated or vehicle-treated sites, as assessed by computerized image analysis of Fontana-Masson stained biopsy cross sections. In another experiment to assess the mechanism of DAG-mediated pigmentation, guinea pigs received twice daily separate applications of OAG, dipalmitoylglycerol (diC 16 ), dioctanoylglycerol (diC 8 ), each 50 mg/ml, 20 μl/application, and propylene glycol vehicle alone for 5 d. Increased pigmentation was visible after 10 d in the OAG and diC 8 sites but not in diC 16 or vehicle sites. These results correlate with the reported ability of these compounds to activate protein kinase C in vitro . In a final experiment, guinea pigs received OAG 25 mg/ml three times daily to one test site, and once daily ultraviolet B (70 mJ/cm 2 , equivalent to 0.6 minimal erythemal dose) radiation to another for 10 d. The OAG and ultraviolet B test sites developed comparable pigmentation by both clinical and histologic criteria. Our data demonstrate that topically applied DAGs can produce a long-lasting increase in epidermal pigmentation, presumably through protein kinase C activation, which clinically and histologically closely resembles ultraviolet-induced tanning.
Hexamethonium sensitivity of the swim musculature of the pteropod mollusc, Clione limacina

Swimming in reduced electrophysiological preparations of the pteropod mollusc, Clione limacina, was blocked by bath application of hexamethonium even though pattern generator activity continued with this treatment. Neuromuscular recordings indicated that hexamethonium blocked synaptic input from Pd-3 and Pd-4 motoneurons to slow-twitch muscle cells, while connections from Pd-1A and Pd-2A motoneurons to fast-twitch muscle cells were variable in their response to hexamethonium—synaptic inputs were suppressed in most cases and occasionally blocked, but the latter only with high concentrations and long incubations. Acutely dissociated wing muscle cells showed a concentration-dependency in the percentage of contracted cells with bath application of acetylcholine, and this contractile activity was blocked in preparations that were first bathed in hexamethonium. Intracellular recordings from dissociated slow-twitch muscle cells showed conductance-increase depolarizations of approximately 20 mV following 1 s pressure ejections of 10−4 M acetylcholine from micropipettes placed immediately adjacent to the muscle cells. These responses were blocked when hexamethonium was bath applied prior to the pressure-applied acetylcholine. The results suggest the Pd-3/Pd-4 motoneuron to slow-twitch muscle cell junctions are cholinergic with nicotinic-like receptors, while the Pd-1A/Pd-2A to fast-twitch muscle cell connections are likely cholinergic, but with a different receptor type.
Effects of × Rays on Cell Lethality and Micronuclear Number in the Ciliate Spathidium spathula*

SYNOPSIS. Spathidium spathula irradiated with 0 to 55 kr of × rays showed one or more of the following kinds of behavior: (1) Death of an undivided cell (primary death); (2) death of a descendant of an irradiated cell (secondary death); (3) permanent injury including one or more of the following: low daily division rate, excessive macronuclear enlargement, total loss of micronuclei, cytostome replication, heavy pigmentation, and decreased motility; (4) temporary division retardation for 1 to 2 days followed by apparent complete recovery; and (5) no apparent injury. The first 3 kinds of behavior increased with increasing dosage from 15 to 25 to 55 kr. At 6 kr only the last 2 categories were observed. The LD50 for 8 days was 46 kr for both primary and secondary death, or 60 kr for primary death alone. Micronuclear number varied greatly following irradiation in lines showing either permanent or temporary injury. Two different responses occurred: (1) The micronuclear number averaged about twice the normal number of 20 with a large range (0 to 360) 1 day after exposure. The number gradually decreased during the next 2 days; (2) some cells lost all micronuclei following irradiation, the incidence increasing with dose. At 55 kr complete loss of micronuclei occurred in 96% of the surviving lines.
Biosynthesis of the Unsaturated 14-Carbon Fatty Acids Found on the N Termini of Photoreceptor-specific Proteins

Abstract In the vertebrate retina, a number of proteins involved in signal transduction are known to be N-terminal acylated with the unusual 14 carbon fatty acids 14:1n-9 and 14:2n-6. We have explored possible pathways for producing these fatty acids in the frog retina by incubation in vitro with candidate precursor fatty acids bearing radiolabels, including [3H]14:0, [3H]18:1n-9, [3H]18:2n-6, and [3H]18:3n-3. Rod outer segments were prepared from the radiolabeled retinas for analysis of protein-linked fatty acids, and total lipids were extracted from the remaining retinal pellet. Following saponification of extracted lipids, fatty acid phenacyl esters were prepared and analyzed by high pressure liquid chromatography (HPLC) with detection by continuous scintillation counting. Transducin, whose α-subunit (G) is known to bear N-terminal acyl chains, was extracted from the rod outer segments and subjected to SDS-polyacrylamide gel electrophoresis and fluorography to detect radiolabeled proteins. G was also subjected to methanolysis, and the resulting fatty acyl methyl esters were analyzed by HPLC. The identities of HPLC peaks coinciding with unsaturated species of both phenacyl esters and methyl esters were confirmed by reanalyzing them after catalytic hydrogenation. The results showed that 14:1n-9 can be derived in the retina from 18:1n-9 and 14:2n-6 from 18:2n-6, most likely by two rounds of β-oxidation, but that neither is produced in detectable amounts from 14:0. Retroconversion of unsaturated 18 carbon fatty acids to the corresponding 14 carbon species showed specificity, in that 18:3n-3 was not converted to 14 carbon fatty acids in detectable amounts. Myristic acid (14:0), 14:1n-9, and 14:2n-6 were all incorporated into G. A much less efficient incorporation of 18:1n-9 into G was also observed, but no radiolabeling of G was observed in retinas incubated with 18:3n-3. Thus, retroconversion by limited β-oxidation of longer chain unsaturated fatty acids appears to be the most likely metabolic source of the unusual fatty acids found on the N termini of signal transducing proteins in the retina.
Revisiting the role of nephrectomy for advanced renovascular disease.

Abstract Background Despite the advances in antihypertensive therapy and renal revascularization, there remains a group of patients in whom renovascular disease leads to renal atrophy and treatment-resistant hypertension. Methods We performed an observational cohort study in which we reviewed blood pressures, renal function, and predictors of response in 74 patients who underwent nephrectomy of a small kidney for uncontrolled hypertension between 1990 and 2000. Results The median age of the patients was 65 years; 43 (58%) were women. Thirty-five patients (47%) underwent nephrectomy as part of combined revascularization of the contralateral kidney. Associated atherosclerotic diseases were common (28% to 49%), as were prior renal revascularization (21 [28%]) and hypertensive urgency/emergencies (23 [31%]). The mean (± SD) long axis of the affected kidney was 8 ± 2 cm, and the mean function of the kidney (based on radioisotope renography) was 12% ± 11% of total renal function. The average systolic blood pressure fell from 168 ± 19 mm Hg to 136 ± 18 mm Hg ( P P P Conclusion Our results suggest that in selected patients with resistant hypertension and renal artery disease that has resulted in atrophic kidneys with reduced function, nephrectomy can improve blood pressure control without further loss in overall renal function.
A role for monoubiquitinated FANCD2 at telomeres in ALT cells

Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome instability and an increased risk of cancer. Because of these similarities, we have investigated whether there is a relationship between the FA protein, FANCD2 and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML bodies in immortalized telomerase-negative cells. These cells maintain telomeres by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not colocalize with telomeres or PML bodies in cells which express telomerase. Using a siRNA approach we find that FANCA and FANCL, which are components of the FA nuclear core complex, regulate FANCD2 monoubiquitination and the telomeric localization of FANCD2 in ALT cells. Transient depletion of FANCD2, or FANCA, results in a dramatic loss of detectable telomeres in ALT cells but not in telomerase-expressing cells. Furthermore, telomere loss following depletion of these proteins in ALT cells is associated with decreased homologous recombination between telomeres (T-SCE). Thus, the FA pathway has a novel function in ALT telomere maintenance related to DNA repair. ALT telomere maintenance is therefore one mechanism by which monoubiquitinated FANCD2 may promote genetic stability.