cssi/SciSciGPT-SciSciNet huggingface dataset:
P161 Autoantibodies: Angiotensinogen vs AT1R as a target, Is there a correlation?

Aim Autoantibody directed at the Angiotensin II Type 1 Receptor (AT1R) has been reported as detrimental to solid organ transplants. An ELISA based AT1R antibody test is available, but presents challenges including different methodology, lot-to-lot variability, and cost effectiveness among them. A Luminex bead based assay autoantibody panel is available, currently detecting 33 targets, with more targets in development. One of the targets on the assay is Angiotensinogen (AGT), the precursor to Angiotensin II. This assay overcomes many of the challenges of the AT1R ELISA test. The aim of this study is to compare results of AGT autoantibody detection using the bead panel to the results of the AT1R autoantibody detection using the ELISA based testing. Methods OneLambda AT1R ELISA kits were used to test 30 sera from transplant patients for the presence of AT1R antibody. The trays were read on the VictorX and results were calculated using either the OneLambda 4PL curve calculation software, or the Workout Plus software on the VictorX, (validated as equivalent to the OneLambda software). OneLamda Autoantibody kits were used to test for the presence of antibody to angiotensinogen (AGT). The kit is a Luminex bead-based assay. Results were read on the Luminex 3D and results were analyzed using Fusion Research 6 software. Results The Reference values for the AGT target were determined by the manufacturer in a non-transplant population of 139 people. 75% had MFI of 777 or less, 85% had MFI of 1045 or less, and 95% had MFI of 1739 or less. Download : Download high-res image (578KB) Download : Download full-size image Conclusions These results show that ranges are overlapping and MFI mean values of AGN as a continuous variable are not consistent with the level of AT1R We conclude that there is no suggestion of a correlation between the results of both assays.
Clinical, histopathologic, cystoscopic, and fluorescence in situ hybridization analysis of proliferative urethritis in 22 dogs.

Background Proliferative urethritis (PU) is a lower urinary tract disease of dogs characterized by frond-like lesions in the urethra. The etiology of PU is unknown, although an association with bacterial cystitis is reported. Objectives Deep-seated bacterial cystitis is associated with PU, particularly in dogs with neutrophilic or granulomatous inflammation. Animals Twenty-two client-owned dogs with PU and 5 control dogs euthanized for non-urinary disease. Methods In retrospective analysis, medical records of dogs with PU from 1986 to 2016 were reviewed. Signalment, clinical signs, cystoscopic findings, antimicrobial use, and results of urine, bladder, or urethral tissue cultures, if available, were recorded. Histopathology was reviewed and classified as lymphocytic-plasmacytic (LP), neutrophilic, LP-neutrophilic (LPN), granulomatous, or pleocellular. Eubacterial fluorescence in situ hybridization (FISH) was performed on 18 tissue samples (13 cases, 5 controls), with subsequent evaluation of bacterial species. Results Of the 22 dogs, 9 had LP urethritis, 6 had LPN, 4 had pleocellular, and 3 had neutrophilic urethritis. Of note, 7 of 13 PU samples were FISH+ for adherent or invasive bacteria; 1 of 5 controls were FISH+ for adherent bacteria. Five dogs had negative urine and tissue cultures when FISH was positive. There was no association detected between the type of urethral inflammation and the results of urine and tissue culture or FISH. Conclusions and clinical importance The type of inflammation varied widely in these 22 PU cases. Deep-seated bacterial urethritis could be contributing to the inflammatory process in some dogs, regardless of the inflammation type. Urine and tissue cultures likely underestimate bacterial colonization of the urethra in dogs.
Constrained Sparse Dynamic Time Warping

Dynamic time warping (DTW) has been applied to a wide range of machine learning problems involving the comparison of time series. An important feature of such time series is that they can sometimes be sparse in the sense that the data takes zero value at many epochs. This corresponds for example to quiet periods in speech or to a lack of physical activity. However, employing conventional DTW for such sparse time series runs a full search ignoring the zero data. So a fast dynamic time warping algorithm that is exactly equivalent to DTW was developed for the unconstrained case where there is no global constraint on the permissible warping path. It was called sparse dynamic time warping (SDTW). In this paper we focus on the development and analysis of a fast dynamic time warping algorithm for the constrained case where there is a global constraint on the permissible warping path, specifically limit the width along the diagonal of the permissible path domain. We call this constrained sparse dynamic time warping (CSDTW). A careful formulation and analysis are performed to determine exactly how CSDTW should treat the zero data. It is shown that CSDTW reduces the computational complexity relative to constrained DTW by about three times the sparsity ratio, which is defined as the arithmetic mean of the fraction of non-zero's in the two time series. Numerical experiments confirm the speed advantage of CSDTW relative to constrained DTW for sparse time series with sparsity ratio up to 0.2-0.3. This study provides a benchmark and also background to potentially understand how to exploit such sparsity when the underlying time series is approximated to reduce complexity.
Asymptotic Optimality of Constant-Order Policies in Joint Pricing and Inventory Control Models

We consider a classical joint pricing and inventory control problem with lead times, which has been extensively studied in the literature but is notoriously difficult to solve due to the complex structure of the optimal policy. In this work, rather than analyzing the optimal policy, we propose a class of constant-order dynamic pricing policies, which are fundamentally different from base-stock list price policies, the primary emphasis in the existing literature. Under such a policy, a constant-order amount of new inventory is ordered every period and a pricing decision is made based on the inventory level. The policy is independent of the lead time. We prove that the best constant-order dynamic pricing policy is asymptotically optimal as the lead time grows large, which is exactly the setting in which the problem becomes computationally intractable due to the curse of dimensionality. As our main methodological contributions, we establish the convergence to a long-run average random yield inventory model with zero lead time and ordering capacities by its discounted counterpart as the discount factor goes to one, non-trivially extending the previous results in Federgruen and Yang (2014) that analyze a similar model but without capacity constraints.
Recombinant Human Coagulation Factor IX Expressed in HEK293 Cells: Influence of Serin Phosphorylation and Tyrosine Sulfation on Pharmacokinetic Properties in FIX-Knock-out Mice

Recombinant factor IX (rFIX) expressed in Chinese hamster ovary (CHO) cells has been shown to be safe and effective in clinical studies, but differs in pharmacokinetics from plasma-derived FIX (pdFIX). In clinical studies, CHO-derived rFIX had a 30–50 % lower in-vivo recovery when compared to pdFIX, whereas mean residence time and terminal half-life did not differ between preparations. Although rFIX shows high similarity to pdFIX in structure and function, differences in glycosylation and gamma-carboxylation degree can be detected. Moreover, although experimental proof has yet to be published, the lower degree of phosphorylation of amino acid serine 155, and the lower degree of sulfation of tyrosine 158 have been hypothesized to be causative for the lower in-vivo recovery of rFIX. These two modifications occur at less than 20 % for the tyrosine-sulfation and at less than 1 % for the serine phosphorylation in rFIX, whereas pdFIX has both modifications to more than 90 % completed. We identified human HEK293 cells to perform rFIX phosphorylation and sulfation to a higher extent than CHO cells. A rFIX-producing cell line derived from HEK293 cells was generated by stable transfection, and was adapted to suspension culture conditions to allow lab-scale fermentation. rFIX was produced and purified from a single fermentation run using two different down-stream process schemes: the first was able to enrich high-phosphorylated and -sulfated rFIX; the second to purify total rFIX from the supernatant at high yield. For pharmacokinetic comparison, these HEK293 materials, CHO-derived rFIX, and a pdFIX preparation were formulated in the same buffer. Determination of phosphorylation and sulfation by mass spectrometry showed a phosphorylation and sulfation degree of 50 % plus a 20 % single modification (phosphorylation or sulfation) for the HEK293-material purified by the modification enrichment method versus 15 % for both modifications plus a 15 % single modification for the material purified by the high-yield protocol. The values for CHO-derived rFIX and pdFIX were similar to those in the literature. Oligosaccharide mapping revealed glycosylation differences among CHO-, HEK293-, and pdFIX preparations, but high similarity between both HEK293-derived materials. We compared the pharmacokinetics of the various FIX preparations in FIX-knock-out mice. In-vivo recovery and area under the curve were statistically significantly higher for the high phosphorylated and sulfated HEK293-material than for total rFIX derived from HEK293 cells. However, these two parameters were lower for both HEK293-derived rFIX preparations than for CHO-derived rFIX, and lower for CHO-derived rFIX than for pdFIX. This may be due to glycosylation differences between these FIX preparations. Mean residence times and terminal half-lives were similar for all preparations. In summary, these findings emphasize that the degree of rFIX-sulfation and -phosphorylation influences the pharmacokinetic properties of rFIX.
Development of a Risk Score to Predict New Pacemaker Implantation After Transcatheter Aortic Valve Replacement

Abstract Objectives The aim of this study was to define risk factors and develop a predictive risk score for new pacemaker implantation (PMI) after transcatheter aortic valve replacement (TAVR). Background TAVR has become an accepted treatment alternative for patients with severe aortic stenosis at elevated surgical risk. New PMI is a common occurrence after TAVR and is associated with poorer outcomes. Methods All patients without prior valve procedures undergoing elective TAVR with the Edwards SAPIEN 3 at a single institution (n = 1,266) were evaluated. Multivariate analysis was performed to evaluate for predictors of PMI in this population in a derivation cohort of patients with complete data (n = 778), and this model was used to develop the Emory risk score (ERS), which was tested in a validation cohort (n = 367). Results Fifty-seven patients (7.3%) in the derivation cohort required PMI. In a regression model, history of syncope (odds ratio [OR]: 2.5; p = 0.026), baseline right bundle branch block (OR: 4.3; p 15.6% (OR: 1.9; p = 0.041) remained independent predictors of PMI and were included in the ERS. The ERS was strongly associated with PMI (per point increase OR: 2.2; p Conclusions A history of syncope, right bundle branch block, longer QRS duration, and higher degree of oversizing are predictive of the need for PMI after TAVR. Additionally, the ERS for PMI was developed and validated, representing a simple bedside tool to aid in risk stratification for patients for undergoing TAVR.
Changes in appetite-regulating hormones following food intake are associated with changes in reported appetite and a measure of hedonic eating in girls and young women with anorexia nervosa.

Abstract Background Females with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN. Objective To examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls. Methods 68 females (36 AN, 32 controls) 10–22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 min following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 min after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 h after breakfast. Results AN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 min), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p Conclusions In young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN.
Ligand-based design of GLUT inhibitors as potential antitumor agents.

Abstract Glucose transporters (GLUTs) regulate glucose uptake and are often overexpressed in several human tumors. To identify new chemotypes targeting GLUT1, we built a pharmacophore model and searched against a NCI compound database. Sixteen hit molecules with good docking scores were screened for GLUT1 inhibition and antiproliferative activities. From these, we identified that compounds 2, 5, 6 and 13 inhibited the cell viability in a dose-dependent manner and that the IC50s of 2 and 6 are
Pelvic bone tumor resection: what a radiologist needs to know

Pelvic bone tumors present a diagnostic and therapeutic challenge. Due to the deep anatomic location and resultant late clinical presentation, pelvic bone tumors tend to be large and located in close proximity to pelvic viscera as well as vital neurovascular structures. Operative management of pelvic bone tumors is indicated for a variety of orthopedic oncologic conditions. In general, limb-sparing pelvic resection rather than hemipelvectomy with amputation of the ipsilateral limb is considered when a functional limb can be preserved without compromising the surgical margins. There are various options for pelvic resection and reconstruction, and the selection depends on tumor histology, anatomic location, and extent. The decision regarding choice of surgical procedure and reconstruction method for a pelvic bone tumor requires a thorough knowledge of the pelvic anatomy, and careful inspection of the anatomic extent. The surgical plan must strike a balance between acceptable functional outcome and acceptable morbidity. In this review, we describe the different types of pelvic resection techniques, and the vital role preoperative imaging plays in defining the anatomic extent of a pelvic bone tumor and subsequent surgical planning.
Chapter 12 – Forest Resources

Forests provide livelihoods, ecological benefits, and incomes for countries in sub-Saharan Africa (SSA). Economists determine the optimal use of forest resources considering the rotation interval and by maximizing the net present value of a stream of benefits. The success of new forestry laws and regulations will depend on how well countries address the cutting-edge issues of climate change, energy, community interest, and resolution of forest land ownership conflicts as the value of forest resources increases. Courts in SSA have addressed forest use conflicts within the context of the interaction between customary laws, statutes, stool, private, and government lands. The equitable balancing of the rights of indigenous land owners and the appropriate measure of damages where a concessionaire’s activities destroy the land and crops of farmers have also been addressed by courts.
Sexual Subcultures and HIV Prevention Methods: An Assessment of Condom Use, PrEP, and TasP Among Gay, Bisexual, and Other Men Who Have Sex with Men Using a Social and Sexual Networking Smartphone Application

Despite being grouped together in epidemiological risk categories, gay, bisexual, and other men who have sex with men (GBM) are not a homogenous group. In addition to traditional segmentation along race, ethnicity, and socioeconomic status, many GBM also identify with sexual subcultural communities. Previous research has shown differences across a variety of health outcomes between these sexual subcultural communities. The purpose of this study was to determine whether HIV prevention practices among GBM differed according to sexual subcultural community. The study was conducted in collaboration with a popular social and sexual networking smartphone application company. A total of 23,577 GBM responded to the survey. A latent class analysis identified 6 distinct classes related to sexual subcultural community identification. We found significant differences across sociodemographic characteristics, HIV prevention practices, and condomless anal sex in the past 6 months related to sexual subculture identification. Findings suggest that sexual subcultural identity is related to decision-making around HIV prevention among GBM. Differences in HIV prevention strategies are likely a function of group norms, unique shared experiences among GBM identifying with a particular sexual subculture community, and sociodemographic characteristics associated with these groups. As such, sexual subculture identity should be considered in developing interventions and social marketing campaigns to increase uptake of biomedical HIV prevention tools among GBM. Identifying group norms and shared experiences related to HIV prevention practices among sexual subcultures is necessary to understand the role these identities play in lives of GBM, especially as it relates to their sexual health and well-being.
Predictive Framework for FRP-Concrete Corrosion Repair

Abstract Fiber-reinforced polymers (FRPs) have been used for repairing chloride-induced corrosion in steel for more than 40 years. Since FRP is a barrier element, it cannot stop electrochemical rea...
Leaders Changing How They Act by Changing How They Think: Applying Principles of an Anti-Racist Principal Preparation Program

Systemic racism and the impending inequities in schooling persist, making it apparent the concept of race still matters when it comes to educational leadership. In response, this chapter examines l...
Effect of Phenylephrine Push Before Continuous Infusion Norepinephrine in Patients With Septic Shock

Background IV pushes of phenylephrine may be used for patients with septic shock with the intent of rapidly achieving mean arterial pressure (MAP) goals. However, the clinical effectiveness and safety of this approach are unclear. Research Question In patients with septic shock, is administration of a phenylephrine push before norepinephrine initiation associated with a higher incidence of hemodynamic stability? Methods This retrospective, multicenter cohort study included adult patients with septic shock initiated on norepinephrine. Propensity scores for initial phenylephrine push receipt were generated, and patients receiving an initial phenylephrine push were propensity score-matched 1:2 to those not receiving an initial phenylephrine push. The primary outcome was achievement of hemodynamic stability (defined as maintaining MAP of ≥ 65 mm Hg for at least 6 h without an increase in continuous infusion vasoactive agent dosage) within 3 and 12 h of norepinephrine initiation. Results Of 1,317 included patients, 181 received an initial phenylephrine push; 141 phenylephrine push patients were matched to 282 patients not receiving a phenylephrine push. More patients who received a phenylephrine push achieved hemodynamic stability at hour 3 than those who did not receive a phenylephrine push (28.4% vs 18.8%; risk difference, 10%; 95% CI, 0.9%-18%). Phenylephrine push receipt was associated independently with hemodynamic stability within 3 h (adjusted OR, 1.8; 95% CI, 1.09-2.97), but not at 12 h (adjusted OR, 1.42; 95% CI, 0.93-2.16). Phenylephrine push receipt was associated independently with higher ICU mortality (adjusted OR, 1.88; 95% CI, 1.1-3.21). Interpretation Phenylephrine pushes were associated with a higher incidence of early, but not sustained, hemodynamic stability and were associated independently with higher ICU mortality. Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.
Rules of evidence in psychophysiological investigations.

Conventional rules encourage an investigator to focus primarily on quantifiable data. In psychophysiological studies, however, the most relevant data may be nonquantifiable, at least at the present time. Behavior, visceral or general, does not necessarily depend on the quantity of a particular stress, but rather is the result of a complex interactive central processing of afferent signals, reflecting more the relevance of actuating factors than their quantitative features. Thus, the rules of evidence must ask not only for measurement, when possible, but for context as well and for data on related intangibles that determine the significance of an experience to an affected individual. Such an inquiry requires the perspicacity of a skilled and disciplined observer. As the practiced ear of a well-trained cardiologist can draw reliable anatomical inferences from listening to the heartbeat, so the eyes and ears of an educated physician should be able to determine the significance of events to his patient with a fair degree of reliability. Both the physician and the cardiologist, however, must deal with the potential distortion brought on by their own biases. Despite problems of bias, lack of replicability, and the need to persist in efforts toward precise measurement, progress continues in understanding the contribution of psychosocial stresses to a variety of gastrointestinal, cardiovascular, respiratory, cutaneous, and other bodily disturbances and the pathways and neurohumoral mechanisms whereby they are mediated. The agenda now calls for developing new strategies for dealing with the powerful intengibles that activate the mechanisms. Meanwhile, as Robert Morrison once cautioned, “We must not expect a science to know more than it does.”
Aggregate consumption and debt accumulation: an empirical examination of US household behaviour

The outbreak of the financial crisis in 2008 witnessed a significant contraction in US consumption spending, as households began deleveraging following a period marked by historically high levels of household borrowing. These events call into question the canonical life-cycle theory of consumption, with its benign view of debt as a neutral instrument of optimal intertemporal expenditure smoothing. This paper draws attention to an alternative, post-Keynesian account of consumption spending in which current income, household borrowing and household indebtedness all affect current consumption. Central to the analysis is an empirical investigation of US consumption spending since the 1950s. The results of this inquiry cast doubt on the life-cycle hypothesis, but are congruent with the alternative, post-Keynesian account of consumption.
The Killing of Osama Bin Laden and Anwar Al-Aulaqi: Uncharted Legal Territory

In this paper, the author systematically examines the various legal arguments that were prompted by the killings of Osama Bin Laden and Anwar Al-Aulaqi. The author reviews the relevant international law—including jus ad bellum and jus in bello issues—as well as the relevant domestic law to ascertain the lawfulness of the killings.
Characteristics of Burn-Injured Children in 117 U.S. PICUs (2009-2017): A Retrospective Virtual Pediatric Systems Database Study.

Objectives To describe characteristics and outcomes of children with burn injury treated in U.S. PICUs. Design Retrospective study of admissions in the Virtual Pediatric Systems, LLC, database from 2009 to 2017. Setting One hundred and seventeen PICUs in the United States. Patients Patients less than 18 years old admitted with an active diagnosis of burn at admission. Interventions None. Measurements and main results A total of 2,056 patients were included. They were predominantly male (62.6%) and less than 6 years old (66.7%). Cutaneous burns were recorded in 92.1% of patients, mouth/pharynx burns in 5.8%, inhalation injury in 5.1%, and larynx/trachea/lung burns in 4.5%. Among those with an etiology recorded (n = 861), scald was most common (38.6%), particularly in children less than 2 years old (67.8%). Fire/flame burns were most common (46.6%) in children greater than or equal to 2 years. Multiple organ failure was present in 26.2% of patients. Most patients (89%) were at facilities without American Burn Association pediatric verification. PICU mortality occurred in 4.5% of patients. On multivariable analysis using Pediatric Index of Mortality 2, greater than or equal to 30% total body surface area burned was significantly associated with mortality (odds ratio, 5.40; 95% CI, 2.16-13.51; p = 0.0003). When Pediatric Risk of Mortality III was used, greater than or equal to 30% total body surface area burned (odds ratio, 5.45; 95% CI, 1.95-15.26; p = 0.001) and inhalation injury (odds ratio, 5.39; 95% CI, 1.58-18.42; p = 0.007) were significantly associated with mortality. Among 366 survivors (18.6%) with Pediatric Cerebral Performance Category or Pediatric Overall Performance Category data, 190 (51.9%) had a greater than or equal to 1 point increase in Pediatric Cerebral Performance Category or Pediatric Overall Performance Category disability category and 80 (21.9%) had a new designation of moderate or severe disability, or persistent vegetative state. Conclusions Burn-injured patients in U.S. PICUs have a substantial burden of organ failure, morbidity, and mortality. Coordination among specialized facilities may be particularly important in this population, especially for those with higher % total body surface area burned or inhalation injury.
Legitimate Authority and Just War

Recent just war theory discussions have emphasized the just cause and right intention prongs of jus ad bellum, but have offered only cursory analysis of the legitimate authority prong in the American context. This article argues that legitimate authority depends in part on domestic law and that the sovereign's war powers must be exercised in accordance with the rule of law. In the American context, where sovereignty is divided, the Constitution's allocation of war powers should guide analysis. The article provides a survey of executive and congressional powers over war and hostilities, and then applies those legal rules to conflicts in Libya, Syria, and North Korea.
Beyond the first glance: anthracyclines in AML.

In this issue of Blood , [Burnett et al][1] present the results of United Kingdom (UK) National Cancer Research Council Acute Myeloid Leukemia 17 (NCRI AML17), a randomized comparison of daunorubicin (90 vs 60 mg/m2) in induction in 1206 patients with acute myeloid leukemia (AML), showing no benefit
Prebiotics as Infant Foods

Publisher Summary This chapter discusses the various forms of infant foods and the prebiotics used to supplement these foods. It emphasizes on the available clinical studies in this age group. The addition of prebiotics to infant foods has generated enthusiasm because “the bifidus factor” from breast milk can be reproduced. Enriched infant milk formula offers practical solutions in daily clinical practice for the treatment of hard stools. However, the effects of prebiotic supplementation may be far more profound by modulating the immune system in a beneficial way, thereby reducing the incidence of infections and atopy. The longest follow-up is 2 years and limited to a single study. All reported intervention studies are short-term. Particular attention should be paid to the specific type of prebiotic used, as it is clear from the current data that results of clinical studies with a particular ingredient may not be extrapolated. The desired “bifidogenic effect” of prebiotics is probably only the top of the iceberg as each structure may have direct effects (e.g., binding of pathogens). Therefore, prebiotics cannot be viewed merely as a “prodrug” for probiotics. Our considerations of these food supplements for infants should not be any different from our considerations of bioactive drugs, especially since important health claims, such as immune modulation, are put forward. Dosages, clarity about composition, and possible side effects need careful attention.
The Mccarran-Ferguson Exemption from the United Stated Antitrust Laws: Recent Developments

This paper was presented at a conference sponsored by the Korean Competition Law Association on the subject of antitrust exemptions and the insurance industry. It analyzes recent developments in four areas: theoretical critiques of McCarran-Ferguson immunity, legislative developments, recent judicial interpretations and international approaches to antitrust exemptions. It argues that the allocation of power and deference is at the heart of the American doctrine and issues of federalism predominate. To the extent that McCarran-Ferguson was designed to clarify the balance of state and federal power to regulate and to set a clear substantive standard, the project has failed. Though the exemption has been criticized from all directions since adoption, legislative reform has been unavailing, demonstrating that a "one way rachet" is at work: once embedded in the law, exemptions are difficult to remove despite criticism, confusion among the courts, and proffers of compromise. A version of the American immunity covering information exchanges among firms in the insurance industry, currently the subject of a block exemption of the European Commission, is due to sunset in 2010 unless extended. As part of its oversight responsibilities, DG Comp conducted a sector inquiry and opened a public consultation into the need for the block exemption, concluding, as a preliminary matter, that claims for the exemption are unpersuasive, and is inclined to allow the block exemption to expire and rely on the general competition rules to protect necessary and pro-competitive activities in the business of insurance. At the end of the day, however, some consensus can be observed. There is wide agreement that antitrust laws are a consumer welfare prescription, exemptions should be adopted only when necessary to remedy market failures and then construed narrowly, and data dissemination and other agreements in the business of insurance are likely pro-competitive when analyzed under the rule of reason.
Identification of when a Langmuir probe is in the sheath of a spacecraft: The effects of secondary electron emission from the probe

Langmuir probes on spacecraft have been used for characterizing the ambient plasma parameters in space. When their boom is short compared to the Debye length, the probes remain immersed in the spacecraft sheath, causing the current-voltage (I-V) characteristics to deviate from that of a probe far away from the spacecraft. We present identification of when a Langmuir probe is in a sheath, based on the secondary electron (SE) emission from the probe itself. The I-V characteristics of a spherical probe are investigated in a plasma sheath above a conducting plate. Plasmas with cold and hot electrons (1 eV and 10 eV), as well as monoenergetic electrons (50–100 eV), are created. The derivative (dI/dV) of the probe I-V curves shows that in addition to a “knee” at a potential more positive than the plasma potential, an additional knee appears at a sheath potential at the probe location. This additional knee is created due to the SE emission from the probe and is identified as an indication of the probe being immersed in the sheath. Our experimental results reproduced the aspects of the Cassini Langmuir probe I-V characteristics, suggesting that at times, the probe may have been immersed in the sheath of the spacecraft in Saturn's magnetosphere, and SE emission from the probe itself may have significantly altered its I-V characteristics.
Scaffolder – Software for Reproducible Genome Scaffolding.

Assembly of short-read sequencing data can result in a fragmented non-contiguous series of genomic sequences. Therefore a common step in a genome project is to join neighboring sequence regions together and fill gaps in the assembly using additional sequences. This scaffolding step, however, is non-trivial and requires manually editing large blocks of nucleotide sequence. Joining these sequences together also hides the source of each region in the final genome sequence. Taken together, these considerations may make reproducing or editing an existing genome build difficult. The software outlined here, “Scaffolder,” is implemented in the Ruby programming language and can be installed via the RubyGems software management system. Genome scaffolds are defined using YAML - a data format, which is both human and machine-readable. Command line binaries and extensive documentation are available. This software allows a genome build to be defined in terms of the constituent sequences using a relatively simple syntax to define the scaffold. This syntax further allows unknown regions to be defined, and adds additional sequences to fill gaps in the scaffold. Defining the genome construction in a file makes the scaffolding process reproducible and easier to edit compared with FASTA nucleotide sequence. Scaffolder is easy-to-use genome scaffolding software. This tool promotes reproducibility and continuous development in a genome project. Scaffolder can be found at http://next.gs.
An Introduction to the Philosophy of Art: Identifying and evaluating art

Why we go on arguing about which works are good The identification and evaluation of objects or performances as works of art is often a process fraught with passion and difficulty. We care about some favorite works that we regard as successful – certain books or movies or paintings – in the way we care about our friends. They appeal to us both immediately and deeply. We often remember them, revisit them, reread them, or rehear them. We recommend them to others, and we are then pleased if the work engages them and sometimes disappointed or troubled if it does not. Prices in the art market and publishing industry depend on what people respond to, as does support by governments and foundations for work in progress. We often have trouble, however, saying why we respond to a work in the way we do, especially when we are faced with original work. We worry about being taken in, and we can be hesitant to display our enthusiasms. Yet most of us cannot help giving ourselves over to some objects or performances, even to some new and difficult work. Just how and why are we moved to do this? Are there any procedures for being right (at least more often) about which works genuinely have artistic value? What are the relative roles of feeling (liking) and reason in our responses to art? Does reason even play a role? Are or can there be experts in the identification and evaluation of works of artistic value, authorities whose verdicts deserve our deference?
Dynamic behavior of a translating flexible beam with a prismatic joint

The dynamic modeling of a single-link flexible beam having both rotational and translation motions and the effects of higher-order dynamics on the response of the beam are investigated. In the literature, modeling of flexible link has often been carried out with the assumed modes technique. In this approximation, only two or three modes are retained and the rest are truncated, which in many cases is inadequate for high performance control system development. In this study, an analytical model of the beam, characterized by an infinite number of modes, is developed using Euler-Bernoulli beam equation and modal expansion method. The infinite-dimensional transcendental transfer function for the manipulator is formulated without modal approximation that is conveniently transformed into state-space form. A preliminary study of the beam acceleration is conducted through computer simulations to demonstrate the effects of higher-order dynamics. In this approach, adding modes or increasing the order of transfer function is straightforward and provides a straightforward check of the effect of ignoring higher-order terms. A numerical example is presented to illustrate the results.
Structures of high-mannose and complex oligosaccharides of mouse TSH and free alpha-subunits after in vitro incubation of thyrotropic tissue with TRH.

To determine whether incubation of mouse thyrotropic tissue with TRH in vitro influenced the oligosaccharide structure of TSH, thyrotropic tumor tissue or pituitary tissue was incubated in vitro with [3H]mannose or with [35S]sulfate and [3H]methionine, in the absence or presence of TRH for times up to 24 h. [3H]mannose-labeled oligo-saccharides from intracellular TSH and free α-subunits were analyzed by paper chromatography, and were predominantly Man9GlcNAc and Man8GlcNAc units both in the absence and presence of TRH. The [35S]sulfate/[3H]methionine ratio in secreted molecules was greater for TSH than for free α-subunits; within TSH heterodimers the ratio was greater for β-subunits than α-subunits. The [35S]/[3H] ratio was not altered in TSH or free α-subunits by TRH. Analyses of [3H]mannose-labeled charged oligosaccharides by HPLC anion-exchange chromatography revealed similar types of oligosaccharides present on TSH subunits and free α-subunits (having one or two sulfate residues, one or two sialic aci...
A critical case for Brownian slow points

LetXt be a Brownian motion and letS(c) be the set of realsr≧0 such that uXr+t−X r u≦c√t, 0≦t≦h, for someh=h(r)>0. It is known thatS(c) is empty ifc 1, a.s. In this paper we prove thatS(1) is empty a.s.
Specific induction of transitions and transversions of G-C base pairs by 4-nitroquinoline-1-oxide in iso-1-cytochrome c mutants of yeast.

Abstract The base-pair changes induced by the highly carcinogenic agent, 4-nitroquinoline-1-oxide, have been determined from the reversion rates of defined tester strains and from the amino acid replacements of revertant iso-1-cytochromes c . The mutant codons and the base-pair changes of reverse mutations of 14 cyc 1 mutants were previously determined from alterations of iso-1-cytochromes c in intragenic revertants. These 14 cyc 1 mutants, which were used as tester strains, included nine mutants with altered AUG initiation codons, an ochre (UAA) mutant, an amber (UAG) mutant and three frameshift mutants (Stewart et al. , 1971,1972; Stewart & Sherman, 1972,1974; Sherman & Stewart, 1973). NQO † induced a high rate of reversion in the initiation mutant cyc 1-131, the only mutant in the group which reverts to normal iso-1-cytochrome c by a G · C → A · T transition. In addition, NQO produces a significant rate of reversion of all cyc 1 mutants which revert by G · C transversions, e.g. the amber (UAG) mutant and the initiation mutants containing AGG, and probably CUG mutant codons. It did not revert the ochre mutant which contains no G · C base pairs. Ten NQO-induced revertants of the amber mutant cyc 1-179 contained the expected replacements of residues of tyrosine, and ten NQO-induced revertants of each of the cyc 1-131 and cyc 1-133 initiation mutants all contained the expected normal iso-1-cytochrome c . The structures of these iso-1-cytochromes c and the pattern of reversion of the tester strains indicate that base-pair substitutions arise at G · C base pairs which are the site of NQO attack. Thus NQO induces G · C → A · T transitions, G · C → T · A transversions and possibly G · C → C · G transversions. Because of its mode of action, NQO may be useful in less-defined systems for identifying G · C base pairs in mutant codons.
A New Research Architecture for the Simulation Era

This chapter proposes a novel research architecture for social scientists who want to employ simulation methods. The new framework gives an integrated view of a research process that involves simulation modelling. It highlights the importance of the theoretical foundation of a simulation model and shows how new theory-driven hypotheses can be derived that are empirically testable. The paper describes the different aspects of the framework in detail and shows how it can help structure the research efforts of scholars interested in using simulations.
Synthesis of U(IV) imidos from Tp*2U(CH2Ph) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) by extrusion of bibenzyl

Addition of organic azides, N3R (R = 2,4,6-trimethylphenyl (Mes), phenyl (Ph), 1-adamantyl (Ad)), to a solution of the uranium(III) alkyl complex, Tp*2U(CH2Ph) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) (1), results in the formation of a family of uranium(IV) imido derivatives, Tp*2U(NR) (2-R). Notably, these complexes were synthesized in high yields by coupling of the benzyl groups to form bibenzyl. The uranium(IV) imido derivatives, 2-Mes, 2-Ph, and 2-Ad, were all characterized by both 1H NMR and IR spectroscopy, and 2-Mes and 2-Ad were also characterized by X-ray crystallography. In the molecular structure of 2-Mes, typical κ3-coordination of the Tp* ligands was observed; however in the case of 2-Ad, one pyrazole ring of a Tp* ligand has rotated away from the metal centre, forcing a κ2-coordination of the pyrazoles. This results in a uranium–hydrogen interaction with the Tp* B–H. Treating these imido complexes with para-tolualdehyde results in multiple bond metathesis, forming the terminal uranium(IV) oxo complex, Tp*2U(O), and the corresponding imine.
Atoms-in-molecules treatment of Li 2 + and Li2 using optimum Gaussian approximations of Li+ and Li eigenstates

Expectation energies for the Li+, Li and Li− ground states and for the 1s 22p Li excited state are individually minimized with respect to variation of parameters in Gaussian lobe expansions of the 1s, 2s and 2p AO's. A new technique is used to control 1s–2s orthonormality. The resulting approximate many-electron atomic eigen-functions are utilized for determining interatomic matrix elements in atoms-in-molecules (AIM) calculations on the two lowest energy 1 ∑ states of Li2 and on the lowest energy 2 ∑ g + and 2 ∑ states of Li 2 + . For R greater than 4 a.u., convergence to exact theoretical AIM limits, within about 0.001 h.u., is obtained by using three-term expansions. Three-structure Li2 and two-structure Li 2 + AIM energies are above experimental by 0.005 and 0.007 h.u., respectively. It is conjectured that an AIM model extended to permit scaling of valence electrons independently of innershell electrons would reduce significantly these energy differences.
[D68] Compliance display using a tilting-plate tactile feedback device

This paper presents a tactile display device for replicating compliance sensation when interacting with deformable and non-deformable compliant objects in a virtual environment. Two small tilting plates approximately reproduce surface deformations of a compliant object. In addition to tactile information, kinesthetic information is rendered through a modified haptic paddle force feedback device. The tilting plates are moved in conjunction with the measured position of the user's finger as they pressed into the virtual surface. In a psychophysical experiment, we evaluated the effect of adding tilting motion of the device's actuated plates on the perceived compliance of a virtual surface with a kinesthetic stiffness of 60 N/mm. The experiment results indicate that tilting rates of 5, 10, and 20 deg/cm reduced the perceived stiffness of the surface by 3, 9, and 17 N/m, respectively. The advantages of the new device include its light-weight, low-cost, and simple design. These device features make it practical to integrate this compliance display with user interfaces for applications such as video games or even robotic surgery.
Subharmonic resonance of oblique interfacial waves by a progressive surface wave

Experimental and theoretical investigations into the generation of internal gravity waves by monochromatic progressive surface waves are presented. Using the method of nonlinear resonant interactions, a triad consisting of a single surface wave and two oblique internal waves in a two–layer model is considered. A multiple scales analysis is adopted and the boundary value problem is expanded in a power series of the surface–wave steepness. At the leading order, the linear harmonics are obtained and the conditions for resonance are determined. A second–order analysis is then used to derive temporal evolution equations for the internal–wave amplitudes. As a consequence of having a single generating train of the surface waves, two oblique trains of internal waves of much shorter wavelength are found to be resonated exponentially in time. Both linear and nonlinear bounds on surface–wave frequency, density ratio and interaction angle are found, demonstrating that the instability is highly narrow banded. It is found that the internal waves grow most rapidly at the linear cut–off values. Experimental evidence is presented and demonstrates good agreement with the theoretical results. Discussion of an application of the theory to the nonlinear energy transfer between very–low–frequency waves in the deep ocean is then provided.
In vitro synthesis of dehydroepiandrosterone sulfate by an adrenal adenoma.

Tritium-labeled 17α-hydroxypregnenolone and dehydroepiandrosterone were incubated, respectively, with slices and a microsome-free supernatant of a human adrenal adenoma which was removed from a patient with hirsutism and masculinization. The percentage of conversion from 17αhydroxypregnenolone to dehydroepiandrosterone sulfate was 10.6 (with ACTH) and 13.2 (without ACTH) with the slices. There was a 35.1 % conversion of dehydroepiandrosterone to dehydroepiandrosterone sulfate with the microsome-free supernatant system. Radiochemical homogeneity of the isolated dehydroepiandrosterone sulfate was verified by paper chromatography, paper electrophoresis, countercurrent distribution, column chromatography and, after solvolysis, by characterization of the free steroid. The study indicates that a steroid sulfokinase (or sulfokinases) is present in human adrenal adenomatous tissue.
Cytoplasmic dynein/dynactin mediates the assembly of aggresomes.

Aggresomes are pericentrosomal cytoplasmic structures into which aggregated, ubiquitinated, misfolded proteins are sequestered. Misfolded proteins accumulate in aggresomes when the capacity of the intracellular protein degradation machinery is exceeded. Previously, we demonstrated that an intact microtubule cytoskeleton is required for the aggresome formation [Johnston et al., 1998: J. Cell Biol. 143:1883-1898]. In this study, we have investigated the involvement of microtubules (MT) and MT motors in this process. Induction of aggresomes containing misfolded DeltaF508 CFTR is accompanied by a redistribution of the retrograde motor cytoplasmic dynein that colocalizes with aggresomal markers. Coexpression of the p50 (dynamitin) subunit of the dynein/dynactin complex prevents the formation of aggresomes, even in the presence of proteasome inhibitors. Using in vitro microtubule binding assays in conjunction with immunogold electron microscopy, our data demonstrate that misfolded DeltaF508 CFTR associate with microtubules. We conclude that cytoplasmic dynein/dynactin is responsible for the directed transport of misfolded protein into aggresomes. The implications of these findings with respect to the pathogenesis of neurodegenerative disease are discussed.