cssi/SciSciGPT-SciSciNet huggingface dataset:
Efficacy of Ketamine in Pediatric Sedation Dentistry: A Systematic Review.

Background Ketamine has been used as a safe and effective sedative to treat adults and children exhibiting high levels of anxiety or fear during dental treatment. Pediatric dentistry often involves patients with high levels of anxiety and fear and possibly few positive dental experiences. Patient management can involve behavioral approaches, as well as the use of sedation or general anesthesia with a variety of agents, including midazolam, diazepam, hydroxyzine, meperidine, and ketamine. The aim of this study was to investigate the clinical efficacy of ketamine use in pediatric sedation dentistry through systematic review and analysis. Methods A systematic review of publications between 1990 and 2015 was conducted using PubMed and MEDLINE databases maintained by the US National Library of Medicine and the National Institutes of Health. The keywords used were (ketamine) AND (dental OR dentistry) AND (sedation). The abstract and title of all potential publications were then screened for clinical trials and to remove non-English articles, non-human or animal trials, and other non-dental or non-relevant studies. Results A total of 1,657 citations were initially identified, reviewed, and screened, eventually resulting in inclusion of 25 clinical trials in this systematic review. Nineteen studies evaluated ketamine effects in pediatric dental sedation using oral (non-invasive) administration, three involved subcutaneous or intramuscular injection, and three were completed intravenously. Evidence analysis of these trials revealed the majority (n = 22/25) provided strong, positive evidence for the use of ketamine (alone or in combination) to reduce dental anxiety and behavioral non-compliance with the remainder suggesting equivocal results. Additional endpoints evaluated in some studies involved dosage, as well as time to achieve sedation effect. Conclusion The use of ketamine (alone or in combination) can provide safe, effective, and timely sedation in pediatric patients regardless of the route of administration.
Meteoric 7Be and 10Be as Process Tracers in the Environment

7Be (T1/2 = 53 days) and 10Be (T1/2 = 1.4 Ma) form via natural cosmogenic reactions in the atmosphere and are delivered to Earth’s surface by wet and dry deposition. The distinct source term and near-constant fallout of these radionuclides onto soils, vegetation, waters, ice, and sediments makes them valuable tracers of a wide range of environmental processes operating over timescales from weeks to millions of years. Beryllium tends to form strong bonds with oxygen atoms, so 7Be and 10Be adsorb rapidly to organic and inorganic solid phases in the terrestrial and marine environment. Thus, cosmogenic isotopes of beryllium can be used to quantify surface age, sediment source, mixing rates, and particle residence and transit times in soils, streams, lakes, and the oceans. A number of caveats exist, however, for the general application of these radionuclides as tracers in the environment, as steady deposition and geochemical immobility are not guaranteed in all systems. Here we synthesize and review scientific literature documenting the deposition and behavior of these nuclides at the Earth’s surface, focusing on current and potential applications for Earth scientists working to quantify terrestrial and marine processes.
Full-scale tilt-rotor hover performance

The hover performance of three full-scale rotors was measured at the Ames Outdoor Aerodynamic Research Facility. The rotors, all designed for tilt-rotor aircraft, were the original metal blades for the XV-15 Tilt Rotor Research Aircraft, a set of composite, advanced technology blades for the XV-15, and a 0.658-scale model of the proposed V-22A Osprey (JVX) rotor. The composite advanced technology blades for the XV-15 were tested with several alternate blade root and blade tip configurations. This paper presents the performance of these three rotors, shows the effects of tip Mach number and root and tip configuration changes on rotor performance, and presents data on rotor wake velocity distributions and tip vortex geometry. Measured rotor performance is compared with theoretical predictions, and the discrepancies are discussed.
LoopInvGen: A Loop Invariant Generator based on Precondition Inference

We describe the LoopInvGen tool for generating loop invariants that can provably guarantee correctness of a program with respect to a given specification. LoopInvGen is an efficient implementation of the inference technique originally proposed in our earlier work on PIE (this https URL). In contrast to existing techniques, LoopInvGen is not restricted to a fixed set of features -- atomic predicates that are composed together to build complex loop invariants. Instead, we start with no initial features, and use program synthesis techniques to grow the set on demand. This not only enables a less onerous and more expressive approach, but also appears to be significantly faster than the existing tools over the SyGuS-COMP 2018 benchmarks from the INV track.
Applications of Accelerator Mass Spectrometry in Toxicology: A Highly Sensitive Tool for Low-Level Isotope Measurements

Radioisotope tracing has long been an important means of determining various parameters of toxicological and biological significance. We review here the recent application of a mass spectrometric technique, accelerator mass spectrometry (AMS), to tracing isotopically-labeled chemicals in toxicological research. Accelerator mass spectrometry (AMS) is a nuclear detection method which separates and quantifies ions of rare isotopes with extremely high selectivity, sensitivity, and precision [1, 2, 3]. It is a technique well suited for tracing 14C and other isotopes (41Ca, 36C1,26A1,129I) through biological systems at levels between 103 - 106-fold lower than decay counting can achieve [4]. AMS can play a unique role in assessing the effects of chemicals in low dose chronic exposure situations, and in assessing the dosimetric relationships between high-dose animal studies and the very low doses typical for real human environmental exposures. The method can also be applied in pharmacokinetic studies, in human subjects studies, and in the general study of chemical interaction with biological systems.
FLT3 inhibitors in acute myeloid leukemia: Current and future:

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is responsible for the proliferation and survival of hematopoietic stem cells in acute myeloid leukemia. Although patients with FLT3 mutations have similar rates of remission following induction chemotherapy, relapse rates are significantly higher and patients with FLT3 mutations have significantly worse outcomes for overall survival and disease-free survival. Early FLT3 inhibitors, such as sorafenib, were non-selective and inhibited several tyrosine kinase receptors resulting in significant toxicity. The treatment of FLT3-positive acute myeloid leukemia has advanced recently with the development of a several FLT3-targeting agents that are either approved or in development. Midostaurin represents the first FDA-approved treatment targeted against FLT3, and there are several promising agents currently undergoing clinical trials. Although certain mutations confer resistance to earlier generation FLT3-targeted tyrosine kinase inhibitors, newer agents show activity in the presence of these mutations.
Protective effect of estrogen on E.coli invasion in primary human hepatocytes and HuH-7 carcinoma cells

2090 Escherichia coli (E.coli) is a frequent colonizer of gastrointestinal and urogenital tract of humans during nonpathogenic as well as pathogenic states. In women, estrogens have been shown to alter the susceptibility to infections during various stages of menstrual cycle. Also increased susceptibility to urinary tract infections is observed in post menopausal women. E.coli expressing Dr fimbriae (Dr) is clinically associated with chronic and recurrent infections. Dr E.coli attaches to and utilizes complement-decay accelerating factor (DAF, CD55) on host cells for internalization. We have shown that DAF is regulated by hormones in the human endometrium and is over expressed in endometrial carcinoma. Recent studies have established role of estrogen as an immunomodulator. However, its direct role in intracellular innate antibacterial response has not been established. Our hypothesis is that during bacterial infection, estrogen may effect bacterial invasion and may thus affect the outcome of inflammation. In susceptible individuals, this may result in the development of a chronic disease and carcinogenesis. In the present study, we investigated the role of estrogen in invasion by uropathogenic Dr E.coli in hepatocarcinoma HuH-7 cells and primary human hepatocytes obtained from NIH LTPADS (Liver Tissue Procurement and Distribution System), using a gentamicin protection assay. HuH-7 cells or primary hepatocytes seeded in 12 well plates for 24 hours were washed, serum starved for 18 hours and treated with 17Β- estradiol. Cells were treated with 0.1, 1.0 and 10 μM 17B-estradiol for 24 hrs and subjected to E.coli invasion. After gentamicin treatment, intracellular bacterial colony forming units (CFU) were determined. Results were expressed as a percent of bacterial CFU counts compared to untreated control cells (considered as hundred percent). Also, the effect of pretreatment of estrogen treated Huh-7 cells with ICI 182,780 (anti-estrogen) on E.coli invasion was determined. Dr E.coli was found to be invasive for both HuH-7 cells and primary human hepatocytes. Estrogen treatment of HuH-7 cells inhibited invasion by Dr E.coli at all estrogen doses compared to untreated cells. The highest percentage CFU count reduction was at 1μM treatment (62.87+/–19.23, p
Vertebral Metastasis from Primary Parotid Adenocarcinoma.

Background Parotid adenocarcinoma comprises 10% of all parotid cancers and does not frequently produce distant metastases. The most common site for metastases is the lung, and there have only been 2 reported cases of skeletal metastases. The purpose of this study is to report the first vertebral metastasis from a primary parotid adenocarcinoma. Patient records, imaging, and pathology from a case of vertebral metastasis of a primary parotid adenocarcinoma were reviewed. A literature review of parotid adenocarcinoma metastases was also performed and is presented. Case Description A 53-year-old male with a medical history of parotid adenocarcinoma treated with chemotherapy and radiation presented with back pain. Computed tomography and magnetic resonance imaging of the lumbar region showed a lytic lesion on the left side of the L4 vertebral body, and a biopsy confirmed the lesion was metastatic adenocarcinoma. Conclusions Distant metastases from a primary parotid adenocarcinoma are rare events, especially metastases to bone. This case represents the first vertebral metastasis from a primary parotid adenocarcinoma.
Orthodontic In Vivo Bond Strength: Comparison with In Vitro Results

The purpose of the present study was to test a new in vivo debonding device and compare in vivo bond strengths recorded by this device with in vitro bond strengths recorded by a universal testing machine such as the Instron. For the in vitro part of the study, 60 extracted premolar teeth were divided into 2 groups of 30 each. Both groups of 30 teeth had 3M Unitek Victory Twin brackets, precoated with Transbond XT composite resin, bonded to them. Shear bond strength tests were carried out in vitro using the universal testing machine on one group of 30 teeth while the debonding device was used on the other group of 30 teeth. The mean shear bond strength of the group debonded using the universal machine was 11.02 MPa and that of the group debonded with the debonding device was 12.82 MPa. For the in vivo part of the study, 8 patients randomly assigned to the research clinician from patients in The University of Alabama School of Dentistry, Department of Orthodontics, had a total of 60 premolar teeth bonded with 3M Unitek Victory Twin brackets. Following comprehensive orthodontic treatment (average time of 23 months), shear bond strength tests were carried out using the debonding device, which can measure debonding forces in vivo. The mean shear bond strength recorded in vivo was 5.47 MPa. Statistically significant differences were found between all 3 groups tested. The results appear to indicate that mean bond strengths recorded in vivo following comprehensive orthodontic treatment are significantly lower than bond strengths recorded in vitro.
Heterogeneous Integration of CIS, LED, MEMS, and VCSEL

In this chapter, the heterogeneous integration of CIS (CMOS image sensor), heterogeneous integration of LED (light-emitting diode), heterogeneous integration of MEMS (microelectromechanical systems), and heterogeneous integration of VCSEL (vertical cavity surface emitted laser) and PD (photodiode) detector will be presented. Emphasis is placed on providing some examples of each of these heterogeneous integrations.
(E)-1-(5-Methyl­thio­phen-2-yl)-N-(4-nitro­phen­yl)methanimine

The title compound, C12H10N2O2S, was synthesized via the acid-catalyzed condensation of 4-nitro­aniline and 5-methyl-2-thio­phene­carboxaldehyde in a methanol–water solution. The dihedral angle between the benzene and thio­phene rings is 54.62 (3)°. No directional inter­actions could be identified in the extended structure.
A Model for Simulating the Robotic Pushing of Dirt

In this paper we present a model for simulating the pushing of dirt. This is a complex problem requiring the study of the action space for the robot, a deformable model for movable earth, the interaction between the robot’s pushing surface and the environment, and techniques that will allow this model to simulate such a scenario. We present our novel framework for studying this problem including the grid-based model of the environment, a simplified earth pushing robot model, and action strategies to model the pushing of dirt from one area of the environment to another.
Relationship Between Pharmacy Students’ Use of Self-Regulated Learning Strategies and Course Outcomes

Objective. To determine the relationship between student-reported, self-regulated learning (SRL) with use of supplementary material, and overall performance in an advanced therapeutics course in a Doctor of Pharmacy program. Methods. A modified version of the Self-Regulated Strategy Inventory (SRSI-SI) was used to measure three distinct SRL factors: managing study behaviors, managing environment, and maladaptive regulatory behaviors. An instructor created a supplemental 36-question practice quiz and flashcard activity. The in-class assessment and the three SRL factors were analyzed using the practice quiz, and the association between overall course grade and score in each factor domain was determined by regression. Results. Two-hundred seven students (98%) completed the SRSI. One hundred fifty-eight (79%) students reported using the optional practice quiz and doing so was associated with significantly higher in-class quiz scores (8.2 vs 7.6 out of 10) and higher overall course grade (88.0% vs 85.3%). Students reporting use of the optional practice quiz were significantly less likely to report poor study behaviors, inability to manage study environment, and maladaptive study habits. Lower overall course grades were significantly associated with maladaptive study habits. Conclusion. A positive association was determined between use of instructor-created supplemental activities and in-class quiz scores, self-regulated study behaviors, and overall course performance. Maladaptive study habits were associated with a modest negative correlation with overall course grade. The results suggest that when instructors create optional supplementary activities and assessments, many of the students who would benefit the most from the use of these activities fail to utilize the opportunity for extra practice.
COST1 balances plant growth and stress tolerance via attenuation of autophagy

In plants, macroautophagy/autophagy has been reported to function in various biotic and abiotic stress-response pathways, but few direct regulators linking stress and autophagy have yet been identified. Other than the conserved nutrient sensing kinase TOR (Target of Rapamycin), negative regulators that can directly modulate plant autophagy are unknown. We recently identified a mutant, termed cost1 (Constitutively Stressed 1), which has strong drought tolerance with constitutive induction of autophagy and broad expression of normally stress-responsive genes. The COST1 protein negatively regulates autophagy by direct interaction with the key autophagy adaptor ATG8E, thus directly linking autophagy and drought tolerance. Moreover, plant growth and development in a cost1 mutant is greatly retarded, suggesting that COST1 controls the tradeoff between growth and stress tolerance.
Teacher Educator Experiences of iPad Integration in Pre-Service Teacher Education: Successes and Challenges.

In this yearlong qualitative study, situated within cognitive and social constructivist theory, the authors investigate the adoption of tablets (iPads) by a group of nine teacher educators for use ...
The Decline of the US Labor Share Across Sectors

We provide novel insights on the functional distribution of income in the postwar US economy, based on a Log Mean Divisia Index decomposition of the labor share by 14 sectors. We identify contributions from four components: real compensation, labor productivity, employment shares, and relative prices. The results are presented for the entire period as well as golden age (1948–1979) and neoliberal era (1979–2017), painting a detailed picture of structural changes. We find that (1) real compensation and labor productivity dominate; (2) manufacturing plays an important role in the recent decline of the labor share; (3) employment shifts toward service sectors with higher labor shares have buffered the decline; and (4) relative prices of services are increasing. We discuss these results in the context of Baumol’s and Lewis’s seminal contributions. Both theories build on the notion of coexistence of progressive and stagnant activities, which is documented in our sectoral decomposition.
Abortion and the Mission of MCH: Perspectives of MCH and Family Planning Professionals in Health Departments.

Prior research shows that maternal and child health (MCH) and family planning (FP) divisions in health departments (HDs) engage in some abortion-related activities, largely when legally mandated; some agencies also initiate abortion-related activities. Yet little is known about health department MCH/FP professionals’ views on how abortion-related work aligns with their professional mission. Between November 2017 and June 2018, we conducted in-depth interviews with 29 MCH/FP professionals working in 22 state and local HDs across the U.S. We conducted inductive thematic analysis to identify themes regarding participants’ professional mission and values in relation to abortion-related work. Participants described a strong sense of professional mission. Two contrasting perspectives on abortion and the MCH/FP mission emerged: some participants saw abortion as clearly outside the scope of their mission, even a threat to it, while others saw abortion as solidly within their mission. In states with supportive or restrictive abortion policy environments, professionals’ views on abortion and professional mission generally aligned with their overall state policy environment; in states with middle-ground abortion policy environments, a range of perspectives on abortion and professional mission were expressed. Participants who saw abortion as within their mission anchored their work in core public health values such as evidence-based practice, social justice, and ensuring access to health care. There appears to be a lack of consensus about whether and how abortion fits into the mission of MCH/FP. More work is needed to articulate whether and how abortion aligns with the MCH/FP mission.
Complementary Roles of Specific Cysteines in Keratin 14 toward the Assembly, Organization, and Dynamics of Intermediate Filaments in Skin Keratinocytes

We recently showed that inter-keratin disulfide bonding plays an important role in the assembly, organization, and dynamics of keratin intermediate filaments in skin keratinocytes. In particular, cysteine 367 located in the central α-helical rod domain of keratin 14 is necessary for the formation of a stable perinuclear network of keratin filaments (with type II partner keratin 5) in skin keratinocytes analyzed by static and live cell imaging. Here, we show that two additional cysteine residues located in the non-helical head domain of K14, Cys-4 and Cys-40, also participate in inter-keratin disulfide bonding and tandemly play a key role complementary to that of Cys-367 in the assembly, organization, and dynamics of keratin filaments in skin keratinocytes in primary culture. Analysis of K14 variants with single or multiple substitutions of cysteine residues points to a spatial and temporal hierarchy in how Cys-4/Cys-40 and Cys-367 regulate keratin assembly in vitro and filament dynamics in live keratinocytes in culture. Our findings substantiate the importance and complexity of a novel determinant, namely inter-keratin disulfide bonding, for the regulation of several aspects of keratin filaments in surface epithelia.
Characterization of the membrane-coating Nup84 complex

Nuclear pore complexes (NPCs) function as selective gates for nucleocytoplasmic transport. Although the NPC was discovered more than half a century ago, our knowledge of NPC components in atomic detail has exploded only over the past few years. Recent structural, biochemical, and in vivo studies of NPC components, in particular the membrane-coating heptameric Nup84 complex, have shed light onto the NPC architecture as well as onto its dynamic nature. Striking similarities were revealed between the components of the NPC and of coat protein complexes in the endocytic and secretory pathways, supporting their common evolutionary origin in a progenitor protocoatomer. Here, we summarize these findings and discuss emerging concepts that underlie the molecular architecture and the dynamics of the NPC. We conclude that the uncovered principles are not limited to the NPC, but are likely to extend to other macromolecular assemblies.
Fully persistent arrays for efficient incremental updates and voluminous reads

The array update problem in a purely functional language is the following: once an array is updated, both the original array and the newly updated one must be preserved to maintain referential transparency. We devise a very simple, fully persistent data structure to tackle this problem such that each incremental update costs O(1) worst-case time, a voluminous sequence of r reads cost in total O(r) amortized time, and the data structure use O(n + u) space, where n is the size of the array and u is the total number of updates. A sequence of r reads is voluminous if r is Ω(n) and the sequence of arrays being read forms a path of length O(r) in the version tree. A voluminous sequence of reads may be mixed with updates without affecting either the performance of reads or updates.
Where the Winds Hit Heavy on the Borderline: Mental Disability Law, Theory and Practice, Us and Them

This Symposium is brought to you for free and open access by the Law Reviews at Digital Commons at Loyola Marymount University and Loyola LawSchool. It has been accepted for inclusion in Loyola of Los Angeles Law Review by an authorized administrator of Digital Commons at LoyolaMarymount University and Loyola Law School. For more information, please contact digitalcommons@lmu.edu.
A comparative evaluation of parallel garbage collector implementations

While uniprocessor garbage collection is relatively well understood, experience with collectors for large multiprocessor servers is limited and it is unknown which techniques best scale with large memories and large numbers of processors. In order to explore these issues we designed a modular garbage collection framework in the IBM Jalapeno Java virtual machine and implemented five different parallel garbage collectors: non-generational and generational versions of mark-and-sweep and semi-space copying collectors, as well as a hybrid of the two. We describe the optimizations necessary to achieve good performance across all of the collectors, including load balancing, fast synchronization, and inter-processor sharing of free lists. We then quantitatively compare the different collectors to find their asymptotic performance both with respect to how fast they can run applications as well as how little memory they can run them in. All of our collectors scale linearly up to sixteen processors. The least memory is usually required by the hybrid mark-sweep collector that uses a copying collector for its nursery, although sometimes the non-generational mark-sweep collector requires less memory. The fastest execution is more application-dependent. Our only application with a large working set performed best using the mark-sweep collector; with one exception, the rest of the applications ran fastest with one of the generational collectors.
Kanban Cell Neuron network Stock Trading System (KCNSTS)

A novel system for machine cognition predicts stock trading signals. The system uses the Kanban cell (KC), Kanban cell neurons (KCN), and Kanban cell neuron networks (KCNN), patent pending. The KC is an asynchronous AND-OR gate without feedback and is self-timing. Input data is processed until input is equal to output. For the KCN, input data is a four-valued logic (4VL) based on the 2-tuple as four logical values in the set of {"", 01, 10, 11} of four-valued bit code (4vbc) with "" equivalent to 00. The algorithm is a linear, multivariate, clustering formula which is not piecewise continuous. Multiple KCNs in the KCNN emulate the human neuron with nine logical inputs and one output. The KCNN model in parallel is scalable for large data sets. The model is adaptable as a forward-looking rules-engine as based on bivalent trial and error. The real-time algorithm is implemented by a look up table (LUT) to occupy 64 KB in software. In hardware access to a sparsely filled LUT is minimized with a 2-bit value per logical signal to occupy 194 KB. On a $40 device the LUT processes at 1.8 BB KCNs per second or about 1600 times faster than in software. KCNN is applied to analytics for time series of econometrics as the Kanban Cell Neuron Stock Trading System (KCNSTS). Virtual examples are given for the prediction of trading signals. For 129-trading days, 24 Asian electronic traded funds (ETF) produced an annualized 6% return on 70 no-charge trades. For 49-trading days, one OTC stock produced an annualized 67% return on 10 trades.
The Aftermath of Hobby Lobby: HSAs and HRAs as the Least Restrictive Means

In Burwell v. Hobby Lobby Stores, Inc., the U.S. Supreme Court held that, under the Religious Freedom Restoration Act of 1993 (RFRA), closely-held corporations’ employer-sponsored medical plans need not provide forms of contraception to which the shareholders of such corporations object on religious grounds. The question now arises how the President, the Congress and the Departments of Health and Human Services (HHS), Treasury and Labor ought to respond to the Hobby Lobby decision.The best alternative is to require any employer which objects to providing contraception to fund for their respective employees independently-administered health savings accounts (HSAs) or health reimbursement arrangements (HRAs). An HSA or HRA permits the covered employee to spend employer-provided, pre-tax health care dollars on any medical service the employee chooses without implicating the employer in the employee’s spending decision. The HSA/HRA alternative respects the religious rights of sponsoring employers since, unlike conventional insurance or self-insured health plans, the sponsoring employer’s plan does not provide a menu of choices which frames the employees’ decisions. Simultaneously, the HSA/HRA approach respects the autonomy of employees to spend health care dollars on whatever medical services such employees select including services to which the employer objects.For RFRA purposes, HSAs and HRAs are analogous to cash wages which the employer pays the employee and which the employee spends as he chooses. Under the HSA/HRA approach, there would be no need for the employer objecting to contraception to certify its objections to anyone. The employer would simply establish an HSA or HRA for each employee to spend as she wishes. Such accounts are the “least restrictive means” by which the federal government can assure women of the ability to obtain contraception which they seek with employer-provided, pre-tax health care dollars without burdening the religious beliefs of employers who object to such contraception. The HSA/HRA response to Hobby Lobby is a compelling compromise as a matter of law and public policy.
A Framework for Collecting and Defining Requirements for Data Warehousing Projects

In this paper we address the issue of failure of data warehousing projects due to inadequate requirements collection and definition process. We describe a framework that can help accomplish the objective of developing a business-driven, actionable set of requirements. The framework consists of a series of steps to facilitate collection and definition of requirements in data warehousing projects. The paper also addresses the difficult yet common issue of end-users' limited availability during the requirements collection process and proposes an approach that can serve to alleviate this problem.
An examination of the central sites of action of cannabinoid-induced antinociception in the rat

Abstract Microinjections of low doses of the potent and selective cannabinoids WIN 55,212-2 and CP 55,940 into the lateral ventricle produce long-lasting reduction in sensitivity to noxious thermal stimuli (1). To determine the central distribution of ventricularly administered WIN55,212-2, we microinjected an analgesic dose of the drug with [3H]WIN55,212-2. At the peak time of antinociception, the radiolabeled drug was confined to periventricular sites throughout the brain. The contribution of particular periventricular structures to the antinociceptive effect was evaluated using intracerebral microinjection techniques and the tail-flick test. Guide cannulae were implanted above the following periventricular structures: the medial septal area, lateral habenlua, perihypothalamic area, arcuate nucleus of the hypothalamus, dorsal raphe nucleus and the dorsolateral and ventrolateral aspects of the periaqueductal gray. Microinjections of WIN55,212-2 (5 μg/0.5 μl) into the medial septal area, lateral habenula, perihypothalamic area, arcuate nucleus, and ventrolateral periaqueductal gray did not significantly affect tail-flick latencies. By contrast, microinjections of WIN55,212-2 into the dorsolateral periaqueductal gray and the dorsal raphe significantly elevated tail-flick latencies. The results of this study indicate that at least two periventricular structures within the brain are involved in cannabinoid antinociception.
Molecular and Genetic Characterization of Nicotiana glutinosa L. Chromosome Segments in Tobacco mosaic virus-Resistant Tobacco Accessions

Tobacco mosaic virus (TMV)-resistant flue-cured tobacco (Nicotiana tabacum L.) cultivars have been developed using the N gene derived from N. glutinosa L. Their adoption has been low, however, because of unfavorable linkage drag effects. Strategies to overcome this problem might include pursuit of alternative introgression events and/or use of molecular markers for selection against deleterious alien chromatin. Previous workers demonstrated the presence of a TMV-resistance mechanism on more than one chromosome of the tobacco genome. The objectives of this research were to determine the relative genomic positions of TMV resistance loci in a set of 12 TMV-resistant tobacco accessions and to use amplified fragment length polymorphism (AFLP) markers for characterization of this material with respect to linked alien chromatin. Five accessions were found to carry a TMV resistance gene on chromosome H. Seven accessions were found to carry a resistance factor on an alternative chromosome. Polymerase chain reaction results indicated that the N gene from N. glutinosa is responsible for resistance in all 12 accessions. A set of 168 AFLP markers specific to the N. glutinosa donor chromosome was identified and used to reveal variability among the 12 accessions for the relative amounts of N. glutinosa chromatin linked to the N gene. The relative propensity for crossing over within the alien segment when in different genomic positions was evaluated in BC 1 F 1 families derived from three different accessions. Lines possessing the N gene on chromosome H may be of greater practical value because of relatively smaller introgressed alien segments and increased potential for obtaining crossover events within the segments.
ASSESSING AND REDRESSING COMPREHENSION ARTIFACTS IN SOCIAL INTERVENTION RESEARCH

variation manipulation had a considerable impact on those who could be identified as having understood the complex features of the treatment. This article details a methodology for discriminating knowledgeable from nonknowledgeable respondents, and outlines the manner in which this categorization can be validated in secondary analysis settings. In addition, the use of the empirically derived categorization as a
Responses of Golden Shiner Minnows to Chemical Cues from Snake Predators

Studies of a limited number of species of fish in the superorder Ostariophysi have shown they they exhibit strong antipredator behaviour to conserved alarm substance in feces and in other byproducts from predatory fish that have consumed ostariophysans. Our experiments examined the ability of a previously untested ostariophysan to recognize chemical cues from two species of snake predators. In Experiment 1, shoals of golden shiners (Notemigonus chrysoleucas) exhibited strong shelter-seeking responses to water which contained waste byproducts from either a sympatric snake or an allopatric snake which had been fed golden shiners but not to a distilled water control. There was no difference in response to the sympatrie snake predator, northern water snakes (Nerodia sipedon), compared to the allopatric snake predator, black-bellied garter snakes (Thamnophis melanogaster). In Experiment 2, individual shiners exhibited vigourous dashing when presented with water which contained waste byproducts from N. sipedon fed golden shiners but exhibited a much weaker response to water which contained waste byproducts from N. sipedon fed green swordtails (Xiphophorus helleri, a non-ostariophysan) or to a water control. These results suggest that the alarm substance produced in the epidermis of the golden shiners is conserved in snake waste byproducts. Experiment 3 showed that there was little difference in shelter-seeking behaviour by shoals of shiners when presented with water in which N. sipedon had soaked, water in which T. melanogaster had soaked, or a distilled water control. Thus it appears that secretions from the skin of these predators may not be chemically labelled.
Methylxanthine activation of noradrenergic unit activity and reversal by clonidine.

Abstract Methylxanthines increase central noradrenergic turnover by an unknown mechanism. Isobutyl methylxanthine (IBMX, 0.5–16 mg/kg i.v.) was found in this study to increase firing rates of noradrenergic neurons in the locus coeruleus, supporting increased impulsed flow as one possible mechanism for increased noradrenergic turnover, Naloxone (1 mg/kg i.p.) pretreatment potentiated the effects of IBMX, while clonidine (0.01 mg/kg i.v.) reversed increases in activity. Some of the behavioral effects of methylxanthines are consistent with increased noradrenergic activity.
Lipid synthesis in cultured human embryonic fibroblasts.

We describe here the pathways by which human embryonic fibroblasts synthesize lipids. In these studies, we quantitated the phospholipids by their phosphorus content and by their acyl components. These determinations defined both the chemical composition of the cellular membranes as well as their metabolic turnover. Using radiolabeled precursors, we have shown (a) synthesis of the glycerol moiety via glycolysis and the action of glycerokinase, (b) utilization of both exogenously added and endogenously synthesized fatty acids, (c) synthesis de novo of phosphatidyl choline and phosphatidyl ethanolamine from their base precursors, and (d) the methylation of phosphatidyl ethanolamine yielding phosphatidyl choline. Dividing cells synthesized phosphoglyceride more rapidly than cells in the stationary phase. However, considerable turnover of cellular lipid did occur in the stationary phase.
Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells

Oral tolerance is a long recognized method to induce peripheral immune tolerance. Oral tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. Low doses of oral antigen induce active suppression, whereas high doses induce clonal anergy and deletion. Oral antigen preferentially generates a Th2(IL-4/IL-10)- or a Th3(TGF-beta)-type response. Th3-type cells are a unique T-cell subset which primarily secrete TGF-beta, provide help for IgA and have suppressive properties for Th1 and other immune cells. Th3-type cells appear distinct from the Th2 cells as CD4(+) TGF-beta-secreting cells with suppressive properties in the gut have been generated from IL-4-deficient animals. In vitro differentiation of Th3-type cells from Th0 precursors from TCR transgenic mice is enhanced by culture with TGF-beta, IL-4, IL-10 and anti-IL-12. Because regulatory T cells generated by oral antigen are triggered in an antigen-specific fashion but suppress in an antigen-nonspecific fashion, they mediate bystander suppression when they encounter the fed autoantigen at the target organ. Thus, mucosal tolerance can be used to treat inflammatory processes that are not autoimmune in nature. Mucosal antigen has also been used to treat animal models of stroke and of Alzheimer's disease. Induction of low-dose oral tolerance is enhanced by oral administration of IL-4 and IL-10. Coupling antigen to CTB or administration of Flt-3 ligand enhances oral tolerance. Anti-B7.2 but not anti-B7.1 blocks low-dose, but not high-dose oral tolerance. High-dose oral tolerance is blocked by anti-CTLA-4. CD25(+) CD4(+) regulatory T-cell function also appears to be related to TFG-beta.
Cylindrically orthotropic circular plates with large deflections

Es werden die Verschiebungs- und Spannungszustande in einer Kreisplatte mit grossen Durchbiegungen und zylindrischer Orthotropie mit Hilfe zweier Methoden untersucht, namlich der Methode des kleinen Parameters vonPoincare und einer modifizierten Methode vonGalerkin.
Three-dimensional effects in thin film fracture mechanics

Abstract This paper presents the results of a three-dimensional finite element analysis of the mechanics of crack growth and decohesion in a highly compliant thin film bonded to a rigid substrate. Essential features of the model are a surface-breaking initial crack which has penetrated to the film-substrate interface, and a remote biaxial residual stress field in the film. Computational analyses show that, in the absence of decohesion, the stress intensity factor along the leading edge of the crack reaches a steady state value when the crack is about twice the film thickness. This steady state condition gives rise to a nearly parabolic crack front along the leading edge. The computed results also confirm the existence of high interface stresses that are the driving force for film decohesion. When decohesion is permitted, the stress intensity factor is observed to increase with debond opening angle. The equilibrium state between crack propagation and decohesion may be determined from the respective stress intensity factors and fracture toughness of the film and the interface.
Performance of the APS optical slope measuring system

Abstract An optical slope measuring system (OSMS) was recently brought into operation at the Advanced Photon Source of the Argonne National Laboratory. This system is equipped with a precision autocollimator and a very accurate mirror-based pentaprism on a scanning stage and kept in an environment-controlled enclosure. This system has the capability to measure precision optics with sub-microradian rms slope errors as documented with a series of tests demonstrating accuracy, stability, reliability and repeatability. Measurements of a flat mirror with 0.2 μrad rms slope error are presented which show that the variation of the slope profile measurements with the mirror setting at different locations along the scanning direction is only 60 nrad and the corresponding height error profile has 2 nm rms.
Down-regulation of protein kinase C activity preferentially attenuates high K(+)-stimulated tyrosine hydroxylase activity in adrenal chromaffin cells cultured with insulin-like growth factor-I.

Abstract The purpose of this study was to determine whether the loss of protein kinase C (PKC) from adrenal chromaffin cells affected the enhancement of high K + - and forskolin-stimulated tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2) activity observed in cells treated with insulin-like growth factor-I (IGF-I). Forskolin-stimulated tyrosine hydroxylase activation was not affected by down-regulation of PKC. High K + -stimulated tyrosine hydroxylase activity decreased substantially after treating the cells for ∼18 h with active, but not inactive, phorbol ester (300 nM). After down-regulation of PKC, high K + -stimulated tyrosine hydroxylase activity in cells cultured with IGF-I decreased by 61 ± 5% ( n = 14) compared to 36 ± 8% ( n = 14) in cells cultured without IGF-I. These data suggest that PKC is required for the enhancement of high K + -stimulated tyrosine hydroxylase activity observed with IGF-I treatment.
tcdC Genotypes Associated with Severe TcdC Truncation in an Epidemic Clone and Other Strains of Clostridium difficile

Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAP1 epidemic clone. This clone is characterized by an 18-bp deletion in the tcdC gene and increased production of toxins A and B in vitro. TcdC is a putative negative regulator of toxin A&B production. We characterized tcdC genotypes from a collection of C. difficile isolates from a hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone. Sequence analysis of tcdC was performed on DNA samples isolated from 199 toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously described 18- or 39-bp deletions. The remaining isolates comprised 15 unique genotypes. Of these, 5 genotypes contain 18- or 36-bp deletions. Of these five genotypes, one is characterized by a single nucleotide deletion at position 117 resulting in a frameshift that introduces a stop codon at position 196, truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates in this collection comprising the epidemic clone are characterized by this genotype. This result suggests that severe truncation of TcdC is responsible for the increased toxin production observed in strains belonging to the BI/NAP1 clone and that the 18-bp deletion is probably irrelevant to TcdC function. Further investigations are required to determine the effect of this and other tcdC genotypes on toxin production and clinical disease.
Antiplatelet therapy with clopidogrel and aspirin in vascular diseases: clinical evidence for and against the combination

The focus of this review is to discuss the hypothesis that justifies the use of dual antiplatelet therapy of aspirin and clopidogrel versus monotherapy with aspirin in arterial vascular disease. By analyzing the CLARITY-TIMI and COMMIT trials, the authors discuss the appropriate use of aspirin plus clopidogrel for patients suffering acute myocardial infarction. In contrast, in the CHARISMA trial, the combination was not justified in stable high-risk patients with documented coronary disease, cerebrovascular disease or symptomatic peripheral artery disease. In two additional cardiovascular studies, the CURE and the PCI-CURE trials, the benefit of the drug combination was evident in those patients who underwent percutaneous coronary intervention and coronary artery bypass grafting. Finally, two focused cerebrovascular studies, the CARESS and the MATCH trials, were analyzed. The CARESS trial demonstrated the clinical benefit of this combination in an acute clinical setting. However, the combination proved to...
Studies on dissociation of mouse prolactin from mouse hepatic receptors

Abstract The influence of pH, temperature, ethylene glycol, urea, chaotropic anions and excess unlabelled secreted mouse prolactin (smPRL) on the dissociation kinetics of 125I-iodosmPRL from mouse hepatic receptors was investigated. The destabilization of smPRL-receptor complexes by chaotropic anions followed the typical trend of the Hofmeister series: I − > Br − > Cl − > F − . Increasing the temperature of the dissociation reaction from 8°C to 23°C and 30°C caused partial dissociation of 125I-iodosmPRL-receptor complexes. Dissociation of 125I-iodosmPRL from mouse hepatic receptors was pH dependent, with the slowest rate of dissociation occurring at pH 8 and the fastest rate of dissociation occurring at pH 5 and 6. Both ethylene glycol and urea accelerated the rate of dissociation of 125I-iodosmPRL from mouse hepatic receptors in a concentration-dependent manner. Dissociation of 125I-iodosmPRL from mouse hepatic receptors was 6-fold faster in the presence of excess unlabelled smPRL than in its absence. The results of these investigations suggest that both protonation/de-protonation reactions and hydrophobic interactions play important roles in stabilizing the smPRL-receptor complex. In addition, they suggest that cooperative interactions may be involved in the binding of smPRL to mouse hepatic receptors.
Lysine 194 Is Functional in Isocitrate Lyase from Escherichia coli

Lysine 194 in conserved stretch 1 of tetrameric isocitrate lyase from Escherichia coli has been replaced by using the restriction-enzyme-site elimination method of directed mutagenesis. Expression of subunits of each variant and of wild-type (wt) enzyme was equivalent and all variants assembled into tetrameric proteins. The variants K194R and K194H had kcat values relative to that of wt enzyme taken as 100 of 11 and 7, respectively. Km values for Mg2+-Ds-isocitrate (in mM units) were: 0.13 for wt-enzyme; 0.12 for the K194R variant; and 0.55 for the K194H variant. Substitution at position 194 of Leu or Glu resulted in zero catalytic activity. These results establish that Lys 194 is another functional residue in conserved stretch one of isocitrate lyase from E. coli besides H184, K193, C195, and H197. Because K194 can be specifically replaced by the basic residues His and Arg with resultant lowered activity and by His with an increased Km value, it may contribute to a cation center and facilitate substrate binding as well as orientation of the developing transition state.