cssi/SciSciGPT-SciSciNet huggingface dataset:
SCF ubiquitin ligase targeted therapies

The clinical successes of proteasome inhibitors for the treatment of cancer have highlighted the therapeutic potential of targeting this protein degradation system. However, proteasome inhibitors prevent the degradation of numerous proteins, which may cause adverse effects. Increased specificity could be achieved by inhibiting the components of the ubiquitin-proteasome system that target specific subsets of proteins for degradation. F-box proteins are the substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes. Through the degradation of a plethora of diverse substrates, SCF ubiquitin ligases control a multitude of processes at the cellular and organismal levels, and their dysregulation is implicated in many pathologies. SCF ubiquitin ligases are characterized by their high specificity for substrates, and these ligases therefore represent promising drug targets. However, the potential for therapeutic manipulation of SCF complexes remains an underdeveloped area. This Review explores and discusses potential strategies to target SCF-mediated biological processes to treat human diseases.
Exercise for bone health: rationale and prescription

Purpose of reviewPatients frequently inquire about exercise as a means to improve bone strength and reduce osteoporotic fracture. Understanding the biologic mechanisms and the available clinical evidence supporting the role of exercise in bone health is the key to an educated discussion.Recent findi
Thermal Comparison of Reflective and Non-Reflective Roofs with Thin-Film Solar Panels

The present paper illustrates an experimental and comparative thermal analysis of reflective (white) and non-reflective (black) roofing membranes paired with thin-film solar photovoltaic panels. Tests were carried out on two different membranes, thermoplastic olefin (TPO), and ethylene propylene diene monomer (EPDM). Solar irradiance along with temperature readings on the surface, between the panel and membrane, and below the membrane were recorded for 16 months at 15 minute intervals. The data was processed and the temperature effect was observed. The interface temperatures for TPO/PV and EPDM/PV assemblies were found to be different, which could affect the performance of solar panels at various levels depending on the material type used in fabricating the photovoltaic panels.
Changing patterns of infectious diseases

In the 20 years that have passed since I received my medical degree, some of the most evident, striking, and interesting changes in patterns of diseases have occurred among those due to transmissible agents. Among other changes are the recognition of new diseases, new clinical manifestations for old diseases, new ecologic niches for traditional pathogens, and new modes of disease transmission. Implicated causes for these changes include alterations in lifestyle such as sexual behaviour, leisure activity, and dietary trends, along with the impact of immigration and the effects of medical progress. A review of these changing patterns demonstrates the dynamic nature of medicine and suggests lessons for medical education.
Curve skeleton-based shape representation and classification

Computing the average anatomy and measuring the anatomical variability within a group of subjects are common practices in Computational Anatomy. In this paper, we propose a statistical analysis framework for 2D/3D shapes. At the core of the framework is a parametric shape representation formulated as a concatenation of skeleton points and the discs centered at the points. This shape representation possesses an excellent capability of capturing both global structures and local details. The constructed Riemannian manifold shape space provides a mathematically sound foundation for various groupwise operations, such as calculating the mean shape and conducting structure-specific normalization. Experiments with 2D shapes and 3D human brain structures show the effectiveness of our framework in calculating the distances among different shapes.
Delaying generic competition--corporate payoffs and the future of Plavix.

In August, pharmacies began selling a cheaper, generic version of the blockbuster antiplatelet agent Plavix (clopidogrel). Dr. Miriam Shuchman explains why this was good news for patients but to those who produce and market the drug, it was a financial disaster.
Reliability analysis for dynamic configurations of systems with three failure modes

Abstract Analytical models for computing the reliability of dynamic configurations of systems, such as majority and k-out-of-n, assuming that units and systems are subject to three types of failures: stuck-at-0, stuck-at-1, and stuck-at-x are presented in this paper. Formulas for determining the optimal design policies that maximize the reliability of dynamic k-out-of-n configurations subject to three types of failures are defined. The comparisons of the reliability modeling functions are also obtained. The optimum system size and threshold value k that minimize the expected cost of dynamic k-out-of-n configurations are also determined.
Frequency Dependence of Gold Nanoparticle Superassembly by Dielectrophoresis

Dielectrophoresis is an effective method for capturing nanoparticles and assembling them into nanostructures. The frequency of the dielectrophoretic alternating current (ac) electric field greatly influences the morphology of resultant nanoparticle assemblies. In this study, frequency regimes associated with specific gold nanoparticle assembly morphologies were identified. Gold nanoparticles suspended in water were captured by microelectrodes at different electric field frequencies onto thin silicon nitride membranes. The resultant assemblies were examined by transmission electron microscopy. For this system, the major frequency-dependent influence on morphology appears to arise not from the Clausius-Mossotti factor of the dielectrophoretic force itself, but instead from ac electroosmotic fluid flow and the influence of the electrical double layer at the electrode-solution interface. Frequency regimes of technological interest include those forming one-dimensional nanoparticle chains, microwires, combinations of microwires and nanoparticle chains suitable for nanogap electrode formation, and dense three-dimensional assemblies with very high surface area.
SU-FF-T-61: A Pseudo-Tangential IMRT Technique for the Whole Large Left Breast Radiation Therapy Using Helios/Eclipse System

Purpose: A pseudo‐tangential IMRT (PT‐IMRT) technique was developed to achieve high dose uniformity for the whole large left breast (separations >24 cm and volumes > 1200cc) radiation therapy and to reduce the early and late skin and subcutaneous reactions. Method and Materials: The proposed PT‐IMRT technique basically combines two pairs of tangential beams with two additional beams angled less than 10 degree from each side. In most situations, the two additional beams were angled anterior to the tangential plane. An additional OAR was drawn around the high dose (>110%) area at the lateral side. The PT‐IMRT is an inverse planning approach. After the optimization, 2 cm skin flash was added to each beam. Multiple static segments were used for the IMRT delivery. For comparison purpose, four other plans were also run for each patient: an inverse tangential‐IMRT plan (T‐IMRT), a 3D plan, a forward field‐in‐field (FIF) plan and a forward electronic compensator (EC) plan (all use the tangential beams only.) In‐homogeneity correction was included in all plans. Dose volume histogram (DVH) was used for the evaluation of all plans. Results: The PT‐IMRT provided the best dose volume uniformity for PTV. The dose volume to heart and left lung for doses less than 15 Gy was 2–3% higher for PT‐IMRT, but was 2–3% lower for doses larger than 25 Gy. The dose increment to a point 1 cm deep and 5 cm right to the mid‐sternum inside the right breast was 2–5% higher compared to other four plans. The normal tissue volume for doses larger than 105% was significantly reduced with the PT‐IMRT compared to the other four plans. Conclusion: The PT‐IMRT resulted in the most homogenous dose distribution among all the five techniques and has the potential to reduce the early and late skin and subcutaneous reactions.
Chemical induction of male sterility in hexaploid triticale

Chemical gametocides Ethrel, RH-531, and Uniroyal D513 were used in 1972–1973 field studies to induce male sterility in hexaploid triticale cultivars 6TA 131, 6TA 385, and 6TA 204. In cultivar 6TA 131, applications of RH-531 at 1500 ppm reduced seed set to 7.3, 2.8, and 14.1% at pre-, early and midboot growth stages, respectively. Ethrel at concentrations up to 10,000 ppm was less effective than RH-531. Little or no reduction in seed set was observed with Uniroyal D513. Applications of three chemical gametocides increased seed protein and decreased plant height and 1000-kernel weight in each cultivar.
Microdialysis: A system for localized drug delivery into the brain

Abstract To determine why intrahypothalamic microinjections of pyrogen-free saline (PFS) often induce core temperature (T co ) rises, guide cannulas were implanted bilaterally into the preoptic-anterior hypothalamus (POA) of guinea pigs, 1 week later, injectors were inserted to 1 mm beyond the guides and either no injection or 1 μl PFS was administered. Injector insertion without injection evoked a 0.5°C T co rise within 40 min, culminating in 3.7 hr. PFS microinjection elicited a 0.9°C T co rise within 10 min, culminating in 3.8 hr. PFS injected 4 hr later caused a further T co rise. Indomethacin (10 mg/kg, IM), given 30 min before, prevented these effects. To determine whether microdialysis obviates them, a guide cannula was implanted unilaterally into the POA; 1 week later, a dialysis probe (nominal cutoff, 10 kD) was inserted to 1 mm beyond the guide. PFS or prostaglandin E 2 (PGE 2 , 1 μg/μl) was perfused 2 days later (2 μl/min for 3 hr). T co was unchanged during PFS perfusion but increased during PGE 2 perfusion to 1.5°C in 1.6 hr, and plateaued until 2 hr after dialysis. These results indicate the T co rise induced by PFS microinjection is mediated by prostaglandins, probably released due to tissue puncture by the injectors and injury by the PFS droplet. Microdialysis prevents these effects. It should, therefore, be preferred over microinjection for intracerebral drug administration.
Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.

ContextNeuropsychiatric symptoms of dementia are common and associated with poor outcomes for patients and caregivers. Although nonpharmacological interventions should be the first line of treatment, a wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms; therefore, concise, current, evidence-based recommendations are needed.ObjectiveTo evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia.Evidence AcquisitionA systematic review of English-language articles published from 1966 to July 2004 using MEDLINE, the Cochrane Database of Systematic Reviews, and a manual search of bibliographies was conducted. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs) or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Trials reporting only depression outcomes were excluded. Data on the inclusion criteria, patients, methods, results, and quality of each study were independently abstracted. Twenty-nine articles met inclusion criteria.Evidence SynthesisFor typical antipsychotics, 2 meta-analyses and 2 RCTs were included. Generally, no difference among specific agents was found, efficacy was small at best, and adverse effects were common. Six RCTs with atypical antipsychotics were included; results showed modest, statistically significant efficacy of olanzapine and risperidone, with minimal adverse effects at lower doses. Atypical antipsychotics are associated with an increased risk of stroke. There have been no RCTs designed to directly compare the efficacy of typical and atypical antipsychotics. Five trials of antidepressants were included; results showed no efficacy for treating neuropsychiatric symptoms other than depression, with the exception of 1 study of citalopram. For mood stabilizers, 3 RCTs investigating valproate showed no efficacy. Two small RCTs of carbamazepine had conflicting results. Two meta-analyses and 6 RCTs of cholinesterase inhibitors generally showed small, although statistically significant, efficacy. Two RCTs of memantine also had conflicting results for treatment of neuropsychiatric symptoms.ConclusionsPharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia. Of the agents reviewed, the atypical antipsychotics risperidone and olanzapine currently have the best evidence for efficacy. However, the effects are modest and further complicated by an increased risk of stroke. Additional trials of cholinesterase inhibitors enrolling patients with high levels of neuropsychiatric symptoms may be warranted.
The potential energy curve for the B1IIu state of Li2

Abstract Multiconfiguration self-consistent field calculations of the potential curve for the B 1 Π u state of Li 2 show a 700 cm −1 high hump at 5.365 A in good agreement with experimental estimates of 930 ± 300 cm −1 and 523 ± 50 cm −1 .
Recognition of SAR images with enhanced scattering centers under extended operating conditions

In this paper we introduce the mean-square-error correlation filter for obscured targets. We derive from this algorithm that the DC-blocked phase-only filter is the best practical approximation to this filter for recognizing SAR images with enhanced scattering centers for both inputs and templates. The performance of the DC-blocked phase-only filter is tested in the recognition of SAR images from the MSTAR data base under extended and non-extended operating conditions. The heterogeneous correlation filter algorithm used to correlate totally different images is utilized to correlate distorted images under extending operating conditions.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Alternative bearings in total knee arthroplasty: risk of early revision compared to traditional bearings: An analysis of 62,177 primary cases

Background and purpose There is no substantial clinical evidence for the superiority of alternative bearings in total knee arthroplasty (TKA). We compared the short-term revision risk in alternativ...
Relationship of Body Mass and Net Worth for Retirement-Aged Men and Women:

This article examines linkages between body weight and socioeconomic status (SES) among Americans at or near retirement age. The authors hypothesize that (a) body weight relates negatively to SES, (b) this relationship is greater for women than men, and (c) the relationship attenuates when health, employment, and marital status are controlled. We use the 1992 Health and Retirement Study for this examination. SES is measured as net worth. Body weight is measured as body mass index and categorized as normal weight, overweight, and obese. Results indicate that, for women, overweight and obesity relate to lower logged networth. This relationship attenuates once covariates are considered. For men, overweight and obesity relate to higher logged net worth, even when covariates are considered. The findings suggest that greater weight has different meanings for men and women in this cohort; it might be related to success for men but a sociocultural detriment for women.
Estrogen Specificity of the Induction of Lipovitellin Synthesis and Evidence for a Specific Estrogen-Binding Component

Using male South African clawed toads, Xenopus laevis, administration of the common estrogens as well as estradiol-17α brought about the synthesis of both total soluble protein and the specific yolk protein, lipovitellin, in liver. This elevation in synthesis was both dose-responsive and estrogen specific; neither hydrocortisone, progesterone, nor testosterone promoted synthesis. The Parke-Davis compound, CN-55, 945–27, a known inhibitor of the binding of estrogen to specific receptor sites in mammalian tissues, inhibited the synthesis of lipovitellin indicating a possible requirement for binding protein in the Xenopus system. In cell-free preparations of liver, 3H-estradiol-17β was bound to a macromolecule fraction which was excluded by columns of Sephadex G-100 or G-200 in buffers of low ionic strength and sedimented at 11–12 S on linear sucrose gradients.
SOME EFFECTS OF STEROIDS ON CLEAVAGE OF RABBIT EGGS IN VITRO.

The effects of steroids on mammalian ova were studied by culturing fertilized rabbit eggs in media containing different concentrations of 1 of 12 different steroids. Progesterone, as recorded earlier, inhibited cleavage at concentrations of 0.03 mid or higher. Testosterone propionate also inhibited cleavage but not so effectively as progesterone. At the same concentrations the estrogens caused ova to fragment. None of the other steroids tested showed any obvious effect on the eggs. These results are interpreted as effects related to the phospholipid layer of the cell membrane. (Endocrinology 75: 706, 1964)
A model of panic and agoraphobic development

-A model for the development of agoraphobia with panic attacks is proposed. The initiating clinical manifestation is the sudden appearance of spontaneous panic. The inter-panic chronic anxiety may have several components: i.e. conditioning, increasing autonomic distress, and sensitization to the panic leading to avoidance. The illness course is quite variable but usually chronic. The spontaneous panic is blocked by imipramine with primary pharmacological anti-panic effects. However, no direct effect of imipramine upon either anticipatory anxiety or avoidance behaviour is hypothesized. Among the psychotherapies, direct in vivo exposure mobilizes the patient more rapidly than office based therapy. Our data are consonant with the theory that the avoidances of agoraphobia are secondary to spontaneous panic attacks, and that the primary benefits of imipramine and exposure therapy are in their respective effects on panic and avoidance. Moreover, laboratory challenge studies, brain imaging studies, and genetic studies all point to a biological diathesis for panic disorder.
ALDH2 Activator Inhibits Increased Myocardial Infarction Injury by Nitroglycerin Tolerance

Nitroglycerin, which treats impaired cardiac function through vasodilation as it is converted to nitric oxide, is used worldwide for patients with various ischemic and congestive cardiac diseases, including angina pectoris. Nevertheless, after continuous treatment, the benefits of nitroglycerin are limited by the development of tolerance to the drug. Nitroglycerin tolerance is a result of inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme essential for cardioprotection in animals subjected to myocardial infarction. Here, we tested the hypothesis that the tolerance that develops as a result of sustained nitroglycerin treatment increases cardiac injury by subsequent myocardial infarction. In a rat model of myocardial infarction, 16 hours of prior, sustained nitroglycerin treatment resulted in infarcts that were twice as large as those in untreated control animals and in diminished cardiac function at 3 days and 2 weeks after the myocardial infarction. We also sought to identify a potential treatment to protect against this increased cardiac damage. Nitroglycerin inhibited ALDH2 activity in vitro, an effect that was blocked by Alda-1, an activator of ALDH2. Co-administration of Alda-1 with the nitroglycerin prevented the nitroglycerin-induced increase in cardiac dysfunction after myocardial infarction in rats, at least in part by enhancing metabolism of reactive aldehyde adducts that impair normal protein functions. If our animal studies showing that nitroglycerin tolerance increases cardiac injury upon ischemic insult are corroborated in humans, activators of ALDH2 such as Alda-1 may help to protect patients with myocardial infarction from this nitroglycerin-induced increase in cardiac injury while maintaining the cardiac benefits of the increased nitric oxide concentrations produced by nitroglycerin.
A dual maximum principle for discrete-time linear systems with economic applications

A discrete-time linear optimal control problem with given initial and terminal times, state control constraints, and variable end points is set forth. Corresponding to this primal control problem, or maximization problem, is a dual linear control problem, or minimization problem. A dual maximum principle is proved with the aid of the duality theory of linear programming, where the dual of the Hamiltonian of the primal control problem is the Hamiltonian of the dual control problem. A discrete-time analog of the Hamilton-Jacobi equation is derived; and economic applications are discussed.
A Rapid, Strong, and Convergent Genetic Response to Urban Habitat Fragmentation in Four Divergent and Widespread Vertebrates

Background: Urbanization is a major cause of habitat fragmentation worldwide. Ecological and conservation theory predicts many potential impacts of habitat fragmentation on natural populations, including genetic impacts. Habitat fragmentation by urbanization causes populations of animals and plants to be isolated in patches of suitable habitat that are surrounded by non-native vegetation or severely altered vegetation, asphalt, concrete, and human structures. This can lead to genetic divergence between patches and in turn to decreased genetic diversity within patches through genetic drift and inbreeding. Methodology/Principal Findings: We examined population genetic patterns using microsatellites in four common vertebrate species, three lizards and one bird, in highly fragmented urban southern California. Despite significant phylogenetic, ecological, and mobility differences between these species, all four showed similar and significant reductions in gene flow over relatively short geographic and temporal scales. For all four species, the greatest genetic divergence was found where development was oldest and most intensive. All four animals also showed significant reduction in gene flow associated with intervening roads and freeways, the degree of patch isolation, and the time since isolation. Conclusions/Significance: Despite wide acceptance of the idea in principle, evidence of significant population genetic changes associated with fragmentation at small spatial and temporal scales has been rare, even in smaller terrestrial vertebrates, and especially for birds. Given the striking pattern of similar and rapid effects across four common and widespread species, including a volant bird, intense urbanization may represent the most severe form of fragmentation, with minimal effective movement through the urban matrix.
Measurement of software service quality for large telecommunications systems

Attention is given to software service quality measurement in the telecommunications switching environment. Environment dynamics and the composition of customer satisfaction are explained. Measurements are made at gaps in the software delivery process, and management is responsible for the success of the measurement process. It is concluded that software service quality measurement can be a strategic tool that can help increase a supplier's competitiveness. >
Comparing the expressive power of access control models

Comparing the expressive power of access control models is recognized as a fundamental problem in computer security. Such comparisons are generally based on simulations between different access control schemes. However, the definitions for simulations that are used in the literature make it impossible to put results and claims about the expressive power of access control models into a single context and to compare such models to one another in a meaningful way.We propose a theory for comparing the expressive power of access control models. We perceive access control systems as state-transition systems and require simulations to preserve security properties. We discuss the rationale behind such a theory, apply the theory to reexamine some existing work on the expressive power of access control models in the literature and present three results. We show that: (1) RBAC with a particular administrative model from the literature (ARBAC97) is limited in its expressive power; (2) ATAM (Augmented Typed Access Matrix) is more expressive than TAM (Typed Access Matrix), thereby solving an open problem posed in the literature; and (3) a trust-management language is at least as expressive as RBAC with a particular administrative model (the URA97 component of ARBAC97).
Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.

Abstract Background: Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied. Objective: We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. Methods: In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months. Results: Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 ± 0.9 (mean ± SE) and 2.5 ± 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 ± 1.3 ( P P P Conclusion: Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin. (J Am Acad Dermatol 2003;49:83-90.)
An extended classification of inter-instruction dependency and its application in automatic synthesis of pipelined processors

The conventional classification of inter-instruction dependencies (data, anti and output dependencies) provides a basic scheme for the analysis of pipeline hazards in pipelined instruction set processors. However, it does not consider the relative spatial positions of micro-operations in the pipeline, thus providing limited hints to hardware designers and compiler writers about the hazard resolution in generalized pipeline structures. The authors propose an extension to the conventional classification of dependencies, which is capable of encapsulating the spatial/temporal relationship and providing precise hardware/software resolution strategies. With the extended classification and its associated hardware/software resolution strategies, they are able to systematically analyze the potential register-related pipeline hazards for a given pipeline structure, determine appropriate resolution strategies, and explore the tradeoff between hardware and software complexities. The methodology enables the systematic synthesis of high performance pipelined micro-architectures, and is useful to derive the back-end of the supporting compilers. >
Contingencies of Self-Worth and Appearance Concerns Do Domains of Self-Worth Matter?

Heightened body surveillance can have negative effects on physical and psychological well-being, but little is known about the factors that contribute to this chronic surveillance. The authors tested a model that examined whether staking self-worth in certain domains was associated with decreased or increased body surveillance and appearance satisfaction in a sample of 115 Black and 222 White college women. Results indicated that investing self-worth in appearance and approval from others was associated with increased body surveillance and reduced appearance satisfaction whereas self-worth based in academic competence, God’s love, and family support was associated with less body surveillance and more appearance satisfaction. Tests of racial differences revealed that our model operated similarly across race. However, the structural paths of appearance contingency to body surveillance, academic competence contingency to body surveillance, and family support contingency to appearance satisfaction were strong...
Should Universalism Trump Cultural Relativism in Counseling

Certain cultural customs and practices are viewed as abhorrent by many people, yet contemporary American counselors rarely criticize any specific culture. In this article, the authors explore why counselors abstain from such criticism. Furthermore, the authors demonstrate that universalism, often regarded as a politically incorrect and an academically archaic philosophy, is manifestly prevalent within the world's religious and political realms, as well as within the counseling profession. The authors assert that universalism should be prevalent within the counseling profession and that it can be integrated with multicultural principles. Finally, the authors suggest a procedure for identifying universal principles and practices.
Integrating log-ratio position processing for the Los Alamos Proton Storage Ring extraction line

The Los Alamos Proton Storage Ring (PSR) is a compressor ring intended to accept 1-msec-long proton macropulses from the LAMPF linear accelerator and compress these pulses to 250 nsec in length. Beam position monitor sensors of the terminated strip-line design centered at 200 MHz are provided in the transport line from LAMPF, the PSR injection line, the PSR ring, and the extracted beam line. Strip-line sensors used in conjunction with phase processing are a good match for linac transport lines and PSR injection lines where there exists a strong 200-MHz frequency component but lead to difficulties in the ring and extracted beam line where this component tends to wash out. This paper describes the development of Integrating Log-Ratio processing techniques, which utilize the original strip line sensors to achieve a major improvement in position monitoring for the extracted beam line. The design concepts are discussed and the present hardware is described in detail. Operational difficulties encountered during the development process are discussed and actual beam-related results are provided. >
2-thioindoles as precursors to spiro-fused indolines: synthesis of (+/-)-dehaloperophoramidine.

which contains vicinal quaternary centers, was established with the help of extensive 2DNMR experiments and was later validated by the total synthesis developed by Fuchs and Funk. Preliminary biological data indicated that perophoramidine is cytotoxic to HMT 116 colon carcinoma cells and is able to induce apoptosis by poly(adenosine-5’-diphosphateribose)polymerase (PARP) cleavage. Our interest in the synthetic chemistry of 2-thioindoles, combined with the novel structural features of perophoramidine and its preliminary biological data, induced us to initiate a program to target its synthesis. Described herein are our preliminary results in this area and the synthesis of ( )dehaloperophoramidine. We considered several synthetic routes to the perophoramidine skeleton, but ultimately settled upon the approach illustrated in Scheme 2. We envisioned that the intramolecular coupling between the 3-position of a 2-thioindole with a pendant electrophile would serve to generate one of the perophoramidine spiro-fused rings; the resulting thioimidate
Economic impact of switching from an open to a closed enteral nutrition feeding system in an acute care setting.

Background: This study compared an open-system (OS) enteral nutrition (EN) delivery system with a closed system (CS). Factors evaluated included nursing time for administration, patient safety factors, and cost of formula and supplies. Materials and Methods: This study analyzed the cost of formula and supplies in 1 major academic medical center. Data were collected on patients requiring EN in acute care settings. Information collected included formula type and amount of formula ordered and delivered. Results: The average daily cost to feed each adult patient using delivered volume with the OS was $3.84 compared with $4.31 if the patient had been receiving EN from a CS. Considering waste costs, the average cost to feed increased to $4.21 compared with $4.80, respectively. After factoring in increased nursing time with the OS, the cost increased to $9.83. For pediatric patients, formula delivery reached 1 L in only 2% of patient days. The average cost to feed each patient each day using actual delivered vol...
Analysis of Teaching Resources for Implementing an Interdisciplinary Approach in the K-12 Classroom

Articles from the National Science Teacher Association (NSTA) publications were analyzed to investigate resources available for teachers who want to implement interdisciplinary approaches into the science classroom. All articles in each journal from 2004 through 2008 were read an analyzed; approximately 13% of Science & Children (elementary), 21% of Science Scope (middle), and 17% of The Science Teacher (high school) articles met the interdisciplinary approach criteria. Results show that overall, reading, writing, art, and technology are the subjects most commonly integrated into science. Surprisingly, math is rarely discussed across all school levels. Comparing the articles across different school levels, Science Scope articles have the highest number of integrated articles, whereas The Science Teacher had the fewest number of integrated articles.
Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.
Remarks on Charney's Note on Geostropic Turbulence

Abstract Charney in 1971 generalized results for two-dimensional (2D) turbulence to quasigeostrophic (QG) turbulence and obtained two results that have important implications for the atmosphere. The first is an attempt to prove that, similar to 2D turbulence, energy in QG turbulence goes only upscale in the net. The second is a demonstration that 3D QG motion in terms of a 3D wavenumber in a stretched coordinate is isomorphic to 2D turbulence. Charney's proofs are shown here to be problematic.
Understanding and managing breast milk jaundice

The breastfed infant with prolonged unconjugated hyperbilirubinaemia can present a vexing clinical dilemma. Although it is a frequently observed and usually benign finding, prolonged jaundice in the breastfed newborn requires a thoughtful evaluation that excludes possible pathological aetiologies. While recommendations for the treatment of unconjugated hyperbilirubinaemia in the first 7 days of life are straightforward, the approach to the breastfeeding infant with jaundice that persists beyond the immediate neonatal period is less clearly delineated. A sound understanding of bilirubin physiology and familiarity with current literature must guide the management of the otherwise well breastfeeding infant with prolonged unconjugated hyperbilirubinaemia.
CYTOCHEMICAL OBSERVATIONS ON THE RELATIONSHIP BETWEEN LYSOSOMES AND PHAGOSOMES IN KIDNEY AND LIVER BY COMBINED STAINING FOR ACID PHOSPHATASE AND INTRAVENOUSLY INJECTED HORSERADISH PEROXIDASE

After incubation of formalin-fixed, frozen sections of kidney and liver from peroxidase-treated rats in an azo dye medium for acid phosphatase, and after subsequent incubation of the same sections with benzidine, phagosomes were stained blue and lysosomes were stained red in the same cells. It was observed that newly formed phagosomes were separate from preexisting lysosomes in the tubule cells of the kidney and in the Kupffer cells of the liver at early periods after treatment with peroxidase. At later periods, the color reactions for acid phosphatase and peroxidase occurred in the same granules. The reaction of peroxidase decreased gradually and disappeared from the phago-lysosomes after 2 to 3 days, whereas the reaction for acid phosphatase persisted. In the liver, most of the injected protein was concentrated in large phagosomes located at the periphery of the cells lining the sinusoids. The peribiliary lysosomes showed a relatively weak reaction for peroxidase in the proximity of the portal veins. After pathological changes of permeability, phagosomes and lysosomes lost their normal location and fused, in the interior of many liver cells, to form large vacuoles or spheres. The effects of a reduced load of peroxidase and the effects of the pretreatment with another protein (egg white) on the phago-lysosomes of the kidney were tested. The relationship of the fusion of phagosomes with lysosomes to the size of normal and pathological phago-lysosomes was discussed.
Modeling and numerical simulation of the internal thermochemistry of automotive airbag inflators

Abstract This paper provides a comprehensive description of the coupled thermochemical processes that occur during the firing of an automotive airbag inflator. A mathematical model is developed to simulate the transient, thermochemical events associated with ignition and combustion of a pyrotechnic automotive airbag gas-generator unit (inflator). The governing equations for the airbag inflator model are derived by expressing conservation conditions for mass and energy in the interior combustion chamber, filter/cooling screens, exterior plenum, and discharge tank. Following a brief description of the model development and physical assumptions made in the analysis, two series of test calculations are presented. The first series of calculations is for a baseline test case of a conventional pyrotechnic inflator system that is characteristic of a standard discharge tank validation experiment. Transient pressure and temperature profiles generated by the airbag inflator model are presented along with properties at the exit nozzles. A parametric study demonstrates the usefulness of airbag inflator simulations in assessing the sensitivity of airbag pressure curves to various design parameters such as propellant and hardware properties and hardware dimensions. The second series of calculations illustrates the influence of pre-pressurized inert gas on the performance of a pre-pressurized pyrotechnic inflator system. Performance of the inflators is measured in terms of pressure-time and temperature-time profiles in the inflator and discharge tank as well as pressure-time integrals at specified times after ignition. The pre-pressurized pyrotechnic inflator shows certain advantages over conventional pyrotechnic units, including significantly lower requirements for solid propellant mass, lower operating temperature, more uniform performance at hot and cold ambient conditions, and higher thermal efficiency. The chemical composition of the inert gas, pre-pressurized system is also shown to influence the working process of the inflator.
Limb excursion during quadrupedal walking: how do primates compare to other mammals?

Primate quadrupeds are said to use relatively large limb excursions for mammals of their body size. Until recently, this claim was based on a comparison of hindlimb excursion data derived from small samples of primates and non-primates. Using video recordings collected at zoos and primate research centres, the present study documents this contrast on much wider samples of quadrupedal mammals. The results indicate that while on average hindlimb excursion is relatively larger in quadrupedal primates, this contrast is somewhat less dramatic than first reports suggested. Comparisons between the data reported here and previously collected forelimb excursion data reveal a surprising asymmetry between the fore- and hind excursions for most mammalian species. Most commonly, forelimb excursion exceeds that of the hindlimb. We suggest that this is related to a complementary asymmetry in limb length (forelimbs shorter than hind) for the purpose of achieving equal step lengths for both pairs of limbs. Relatively large hindlimb excursions in primates have been related to a mechanism that reduces stresses on the forelimbs and then recovers mechanical energy during gait. We suggest that large excursions of both the fore- and hindlimbs are linked to other alterations in gait parameters, such as step length, contact time, and limb compliance, that have been adopted in quadrupedal primates to facilitate locomotion along slender arboreal substrates.
Development and maintenance of choice in a dynamic environment.

Four pigeons were exposed to a concurrent procedure similar to that used by Davison, Baum, and colleagues (e.g., Davison & Baum, 2000, 2006) in which seven components were arranged in a mixed schedule, and each programmed a different left:right reinforcer ratio (1:27, 1:9, 1:3, 1:1, 3:1, 9:1, 27:1). Components within each session were presented randomly, lasted for 10 reinforcers each, and were separated by 10-s blackouts. These conditions were in effect for 100 sessions. When data were aggregated over Sessions 16-50, the present results were similar to those reported by Davison, Baum, and colleagues: (a) preference adjusted rapidly (i.e., sensitivity to reinforcement increased) within components; (b) preference for a given alternative increased with successive reinforcers delivered via that alternative (continuations), but was substantially attenuated following a reinforcer on the other alternative (a discontinuation); and (c) food deliveries produced preference pulses (immediate, local, increases in preference for the just-reinforced alternative). The same analyses were conducted across 10-session blocks for Sessions 1-100. In general, the basic structure of choice revealed by analyses of data from Sessions 16-50 was preserved at a smaller level of aggregation (10 sessions), and it developed rapidly (within the first 10 sessions). Some characteristics of choice, however, changed systematically across sessions. For example, effects of successive reinforcers within a component tended to increase across sessions, as did the magnitude and length of the preference pulses. Thus, models of choice under these conditions may need to take into account variations in behavior allocation that are not captured completely when data are aggregated over large numbers of sessions.
Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. The present study was conducted in healthy middle aged people (40–60 years old) with a low dose of curcumin (80 mg/day) in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19) or placebo (N = 19) for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.
The Alert Conscious State: Controlled Processing of Episodic and Affective Data

The descriptions presented thus far in this volume have emphasized the separate individual elements of consciousness but have not really addressed the single integrated quality of awareness as we know it. In this chapter those processes that bring together those disparate elements into a single unified whole will be discussed.
Abstract 166: Brief Compression Only Cardiopulmonary Resuscitation Training Video and Homemade Manikin Improves CPR Skills in Untrained Individuals

Each year in the United States over 300,000 people experience cardiac arrest outside of the hospital. Only about 40% of these people initially receive cardiopulmonary resuscitation (CPR) from a bystander. We assessed the hypothesis that a brief 6-minute internet-based video and homemade manikin would improve compression-only CPR skills. Methods: This was a parallel-design study with pre and post training evaluations of compression rate, depth, and whether the emergency number (911) was called for help. We recruited subjects currently certified and never certified in CPR. Our video provided compression-only CPR instruction using a homemade manikin reproduced by viewers using common items (towel, t-shirt, and toilet paper roll). Chest compression skills were objectively judged using a Resusci Anne Skillreporter. Results: Twenty-four subjects were recruited: 12 currently CPR certified and 12 never-certified in CPR. Prior to viewing the video, never-certified subjects had an initial average compression rate per minute of 64.3 +/- 43.6 (mean +/- SD), compression depth of 26.8 +/- 17.1 mm, and 4 subjects (33%) called for help. After viewing the video, never-certified subjects had an increase in average compression rate to 103.9 +/- 20.7 per minute (p=0.006), a non-significant increase in depth to 35.4 +/- 11.1 mm, and 9 subjects called for help (75%). CPR certified subjects had an initial (pre-video) average compression rate of 119.3 +/- 15.2 per minute, compression depth of 46.3 +/- 10.4 mm, and 8 subjects (67%) called for help. After viewing the video, CPR certified subjects had a non-significant increase in average compression rate to 120.7 +/- 12.8 per minute, clinically insignificant compression depth decrease to 43.8 +/- 9.8 mm (p=0.022), and all 12 subjects (100%) called for help. One-factor analysis of variance testing revealed a significantly increased compression rate in never-certified compared with certified subjects (p=0.004). Conclusions: The use of a brief video and homemade CPR tool can significantly improve chest compression rate and increase calls for help in previously untrained individuals, compared with CPR certified individuals. Compression depths remained overall inadequate (