cssi/SciSciGPT-SciSciNet huggingface dataset:
Variable cell positions and cell contacts underlie morphological evolution of the rays in the male tails of nematodes related to Caenorhabditis elegans.

Abstract As a first step toward understanding their mechanism of morphological evolution, we compare the morphology and development of the male genitalia in 10 species of Rhabditidae, the family of nematodes that includes Caenorhabditis elegans . We describe a number of variable morphological characteristics and focus in particular on the differing arrangements of the caudal papillae or rays within the acellular fan. We analyze the development of the ray cells within the epidermis of the last larval stage and identify changes in cell positions and cell contacts that underlie evolutionary changes in the arrangement of the rays. Epidermal cell positions were determined by means of indirect immunofluorescence staining with a monoclonal antibody directed towards adherens junctions. Similarities between the species in the cellular arrangements during the earliest developmental stages allow us to propose homologies between the rays in different species. Evolutionary changes in the positions and order of homologous rays are correlated with shifts in cell positions during development. The results suggest that genes for call recognition or adhesion proteins, or pattern formation genes that regulate cell recognition or adhesion proteins, may be important foci of evolutionary change affecting morphology.
Nonlinear Effects of Weather on Corn Yields

This paper examines the reduced-form relationship between weather and yields using a unique data set of maize yields and daily weather records covering the eastern USA for 1950-2004. Since weather variations in a fixed location are exogenous and random, the reduced-form relationship constitutes a viable natural experiment and is therefore clearly identified. The study finds a significant nonlinear relationship between temperature and maize yields that is roughly in line with the concept of degree days: yields increase with temperature at moderate temperatures (between 12°C and 25°C), but rapidly become negative at temperatures in excess of 30°C.
In Vivo and Scanning Electron Microscopy Imaging of Upconverting Nanophosphors in Caenorhabditis elegans

We show here that upconversion phosphors can be imaged both by infrared excitation and in a scanning electron microscope. We have synthesized and characterized for this work up-converting phosphor nanoparticles nonaggregated nanocrystals of size range 50-200 nm. We have investigated the optical properties of 50-200 nm nanoparticles and found a square dependence of the emitted visible fluorescence on the infrared excitation and verified that under electron excitation similar narrow band emission spectra can be obtained as is seen with IR upconversion. The viability of the nanoparticles for biological imaging was confirmed by imaging the digestive system of the nematode worm Caenorhabditis elegans, and we have confirmed using energy-dispersive X-ray analysis that the up-conversion nanoparticles can be identified in a scanning electron microscope at high spatial resolution.
Ozone- and Thermally Activated Films of Palladium Monolayer-Protected Clusters for Chemiresistive Hydrogen Sensing

Here we describe the chemiresistive H2-sensing properties of drop-cast films comprised of 3.0 nm average diameter hexanethiolate-coated Pd monolayer-protected clusters (C6 Pd MPCs) bridging a pair of electrodes separated by a 23 μm gap. The gas-sensing properties were measured for 9.6−0.11% H2 in a H2/N2 mixture. The sensing mechanism is based on changes in the resistance of the film upon reaction of Pd with H2 to form PdHx, which is known to be larger in volume and more resistive than pure Pd. As-prepared Pd MPC films are highly insensitive to H2, requiring O3 and thermal treatment to enhance changes in film resistance in the presence of H2. Exposure to O3 for 15 min followed by activation in 100% H2 leads to an increase in film conductivity in the presence of H2, with a detection limit of 0.11% H2. When exposed to temperatures of 180−200 °C, the conductivity of the film increases and a decrease in conductivity occurs in the presence of H2 with a detection limit of 0.21%. The sensing behavior reverses af...
A Critical Crossroad for BLM's Wild Horse Program

Although horses evolved in North America, they went extinct 10 to 12 thousand years ago. Spanish conquistadors returned domestic horses to the continent in the mid-1500s, and since then, domestic horses have escaped captivity and also were purposefully released onto western rangelands where they thrive today. Most free-roaming horse populations are managed primarily by the Bureau of Land Management (BLM) of the U.S. Department of the Interior ( 1 ).
Effect of Melt Convection and Solid Transport on Macrosegregation and Grain Structure in Equiaxed Al-Cu Alloys

Macrosegregation in metal casting can be caused by thermal and solutal melt convection, and the transport of unattached solid crystals. These free grains can be a result of, for example, nucleation in the bulk liquid or dendrite fragmentation. In an effort to develop a comprehensive numerical model for the casting of alloys, an experimental study has been conducted to generate benchmark data with which such a solidification model could be tested. The specific goal of the experiments was to examine equiaxed solidification in situations where sinking of grains is (and is not) expected. The objectives were: 1) experimentally study the effects of solid transport and thermosolutal convection on macrosegregation and grain size distribution patterns; and 2) provide a complete set of controlled thermal boundary conditions, temperature data, segregation data, and grain size data, to validate numerical codes. The alloys used were Al-1 wt. pct. Cu, and Al-10 wt. pct. Cu with various amounts of the grain refiner TiB2 added. Cylindrical samples were either cooled from the top, or the bottom. Several trends in the data stand out. In attempting to model these experiments, concentrating on experiments that show clear trends or differences is recommended.
The paddlefish rostrum functions as an electrosensory antenna in plankton feeding

A novel electrosensory function is presented for the large, planktonfeeding, freshwater paddlefish, Polyodon spathula, along with a hypothesis which accounts for the distinctive, elongated rostrum ...
Production and Optical Constants of Ice Tholin from Charged Particle Irradiation of (1:6) C2H6/H2O at 77 K

Fifty separate irradiations of a 6:1 mixture of H2O/C2H6 ice conducted over a 5-month period have yielded sufficient tholin for the determination of its physical constants in the 0.06 to 40 micron range. While the imaginary part of the refractive index k was obtained by transmission measurements on thin-film samples and Kramers-Kronig analysis (KKA), the real part of the refractive index was obtained by KKA and ellipsometry; these data may prove useful in cometary and outer solar system spectrometric interpretation.
An interaction site analysis of the solution of groups for short chain molecules

Abstract An integral equation, the reference interaction site method (RISM), is solved for chain molecules (monomers, dimers, trimers, and tetramers) interacting with the site—site Lennard-Jones potentials in order to test the underlying assumptions of the group contribution (GC) solution theory. By using model molecules, we are able to satisfy precisely the prerequisites in the GC theory, then test unequivocally its hypotheses. In order to determine the level of assumptions in the GC theory, we put forward a general framework within which all GC hypotheses could be analyzed. We classify molecular mixtures into solutions of conformers, isomers, and crossmers. This is an elaboration of the “solutions of groups” idea. Each category represents a more advanced (and thus more restrictive) stage in GC postulation. Our tests show that the group conformality does not apply to the microscopic structures (the site—site pair correlation functions) for all categories of solutions (the failure of the strong hypothesis). However, the integrated properties (such as internal energy) can be made to obey group conformality (a success of the weak condition). We have determined the state variables and group quantities that are good correlators for a successful GC application. The mer number-density is a better correlator than the molecular number-density. We test the one-fluid and two-fluid theories of groups proposed earlier on monogroup compounds (e.g. model alkanes: methane, ethane, propane, and n -butane). For the internal energy, the GC prescription is found to describe best the negative (≈ attractive) energy contributions. However, the positive contributions to internal energy are dependent on the short-range geometry of molecular assembly and are thus nonconformal in the group sense. The same observations apply to model isomeric tetramers. From a molecular level analysis, we propose the correct ways for applying GC methods to the solutions of groups. This approach has given the essential basis for formulating accurate correlations for the thermodynamic properties of mixtures using GC theories.
U.S.-Latin American relations

Introduction: The Political, Economic, and Social Setting The Evolution of US-Latin American Relations The Monroe Doctrine and the Emergence of US Power Interventionism, Cooperation, and Revolution Castroism and the Challenge to US Power Contemporary Relations: Reagan, Bush, and Clinton Reagan's Reliance on Capital and Containment Elements of Latin American Policy Making Governmental Participants in Latin American Policy Making Non-governmental Participants in Latin American Policy Making Shaping US-Latin American Policy: The Human Element Key Issues of US-Latin American Relations The Fragile Hold of Democracy Responding to an Ever-changing Region Conclusion: The United States and the New Latin America.
Observations on the integument of the water mite Arrenurus major (Acari: Parasitengona).

A study of the integument of the aquatic mite Arrenurus major Marshall is presented. When the cuticle is examined with the unaided eye and the light microscope, it appears to possess numerous tiny pits. However, scanning electron micrographs of the cuticle reveal that it is a solid surface with topographical sculpturing of the epicuticle, indicating that the "pits" are an internal phenomenon. In cuticle which has been sectioned, areas devoid of cuticular material beneath the thin exocuticle are revealed. These areas are the pits which are goblet-shaped. The integument consists of five major strata. These are from the outside to the inside: (1) a superficial layer with a maximum observed thickness of 725 A, (2) an epicuticle with a thickness of about 900 A and composed of at least four sublayers, (3) an exocuticle with a thickness of about 1.5 A. Fibers of the exocuticle are arranged in a Bouligand pattern and exhibit a regularly occurring discontinuity with a spacing of 200 A. (4) An endocuticle ranging from 15 to 20 μ in thickness. The endocuticle is characterized by bandings which superficially resemble the lamellae of insects but are not homologous, microfibers which exhibit a preferred orientation, and the presence of the pits; and (5) an epidermis lying beneath the endocuticle and extending into the pits. Pore canals are present only in the exocuticle and have their origin at the apices of the pits. The pore canals contain a central filament, and a plug is present just beneath the epicuticle.
Update on the immunodeficiency diseases.

• Newer understanding of the development of the immune system and novel methods to repair these defects promise cures for previously fatal diseases. The advances stem from the ability to define the developmental stages and describe the diseases at the gene level. Coordinate with this progress, recombinant DNA technology may soon permit the precise correction of the defect. For the moment, gene replacement is accomplished at the cellular level by bone marrow transplantation. Here too, rapid clinical advances now permit the use of nonsibling donors. The long-term results are equivalent to those obtained in the past when only HLA-matched siblings could donate. There is now a support group that is of inestimable value to the families of those who suffer from immunodeficiency. Thus, there has been both technological and social progress in the area of primary immunodeficiency. The future is clearly brighter each year. (AJDC. 1990;144:983-992)
Phenotypic Variation Including Retinitis Pigmentosa, Pattern Dystrophy, and Fundus Flavimaculatus in a Single Family With a Deletion of Codon 153 or 154 of the Peripherin/RDS Gene

Background and Objectives: Mutations of the peripherin/RDSgene have been reported in autosomal dominant retinitis pigmentosa, pattern macular dystrophy, and retinitis punctata albescens. We report herein the occurrence of three separate phenotypes within a single family with a novel 3—base pair deletion of codon 153 or 154 of the peripherin/RDS gene. Design: Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics. Setting: University medical centers. Patients: A 75-year-old woman, her two daughters (aged 44 and 50 years), and her 49-year-old son were screened for peripherin/RDSmutations because of the presence of multiple phenotypes within the same family. Results: The mother presented at age 63 years with a profoundly abnormal electroretinogram (ERG) and adult-onset retinitis pigmentosa that progressed dramatically over 12 years, with marked loss of peripheral visual field. One daughter developed pattern macular dystrophy at age 31 years. At age 44 years, her ERG was moderately abnormal but her clinical disease was limited to the macula. Another daughter presented at age 42 years with macular degeneration and over 10 years developed the clinical picture of fundus flavimaculatus. Her peripheral visual field was preserved but her ERG was moderately abnormal. The son had onset of macular degeneration at age 44 years. Pericentral scotomas were present and the ERG was markedly abnormal. Fluorescein angiography revealed punctate pigment epithelial transmission defects. Conclusions: A 3—base pair deletion of codon 153 or 154 of the peripherin/RDSgene can produce clinically disparate phenotypes even within the same family.
Metallothionein in Fish: Review of Its Importance in Assessing Stress from Metal Contaminants

Abstract Metallothionein, a low-molecular-weight protein whose apoprotein, thionein, is induced by exposure to cadmium, copper, mercury, and zinc, plays an important role in the transport and storage of heavy metals; it also provides a protective role against the toxic effects of these metals by sequestering and thus reducing the amount of the free metal ions. Interest in the detoxification role of metallothionein in fisheries research and aquatic toxicology has increased because of the increasing contamination of aquatic habitats by heavy metals. Reports of laboratory and field investigations have shown that metallothionein synthesis is induced in fishes during chronic and acute exposures to metals. There is also evidence of the presence in fish of low-molecular-weight inorganic-binding proteins that are different from metallothionein, as well as evidence that cadmium is not sequestered by metallothionein in rainbow trout Salmo gairdneri. The sequestering of metal contaminants by metallothionein and subs...
Photoresponses of Chaoborus larvae

Abstract The diel vertical migration of Chaoborus larvae is a well known phenomenon. In order to quantify the ability of larvae to utilize underwater light cues in their migration, we measured photoresponses of fourth-instar Chaoborus punctipennis larvae in the laboratory. The action spectrum for these larvae was characterized by a maximum in sensitivity at 400 nm, a plateau at a lower sensitivity from 480 to 560 nm, and a region of much lower sensitivity at wavelengths longer than 620 nm. Dark-adapted larvae exhibited a positive phototaxis at low light intensity which shifted to a negative phototaxix as light intensity increased. At 540 nm the threshold intensity was 1.5 × 10−9 W/m2 for positive phototaxis and about 10−6 W/m2 for negative phototaxis. Light adaptation decreased sensitivity and altered the phototactic pattern. Larvae have a clear circadian rhythm in negative phototaxis, in which greatest responsiveness occurs early in the day. We suggest that the rhythm in photoresponsiveness primarily controls the timing of the downward migration at dawn.
Gene transfer to cultured human endometrial stromal cells: a model to study cyclooxygenase-2 gene regulation.

Abstract Objective: To compare and optimize conditions for gene transfer to human endometrial stromal cells derived from primary culture and to determine the effect of interleukin-1β (IL-1β) and phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, on the promoter activity of the human cyclooxygenase-2 ( COX-2 ) gene. Design: Prospective controlled study. Setting: Academic research laboratory. Patient(s): Women undergoing benign gynecologic surgery for indications other than endometrial diseases. Intervention(s): Endometrial stromal cells were used for transient transfection study. Main Outcome Measure(s): Luciferase activity in transfected endometrial stromal cells. Result(s): Gene transfer mediated by cationic lipid was more efficient and more consistent. Lipofectamine, a polycationic lipid, yielded the highest efficiency. Phorbol 12-myristate 13-acetate (30 nM) and IL-1β (100 ng/mL) increased COX-2 promoter activity by 2.6-fold and 2.2-fold, respectively. Conclusion(s): Induction of COX-2 by IL-1β and PMA suggests that COX-2 and prostaglandin have important roles in the growth and differentiation of endometrial stromal cells. This model can be used to explore the roles of different promoter regulatory elements in COX-2 gene activation.
Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse.

Purpose Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. Methods and Materials From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. Results Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p = .006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. Conclusions Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated. © 2002 Wiley Periodicals, Inc. Head Neck 24: 236–246, 2002; DOI 10.1002/hed.10017
Change-point analysis as a tool to detect abrupt climate variations

Recently, there have been an increasing number of studies using change-point methods to detect artificial or natural discontinuities and regime shifts in climate. However, a major drawback with most of the currently used change-point methods is the lack of flexibility (able to detect one specific type of shift under the assumption that the residuals are independent). As temporal variations in climate are complex, it may be difficult to identify change points with very simple models. Moreover, climate time series are known to exhibit autocorrelation, which corresponds to a model misspecification if not taken into account and can lead to the detection of non-existent shifts. In this study, we extend a method known as the informational approach for change-point detection to take into account the presence of autocorrelation in the model. The usefulness and flexibility of this approach are demonstrated through applications. Furthermore, it is highly desirable to develop techniques that can detect shifts soon after they occur for climate monitoring. To address this, we also carried out a simulation study in order to investigate the number of years after which an abrupt shift is detectable. We use two decision rules in order to decide whether a shift is detected or not, which represents a trade-off between increasing our chances of detecting a shift and reducing the risk of detecting a shift while in reality there is none. We show that, as of now, we have good chances to detect an abrupt shift with a magnitude that is larger than that of the standard deviation in the series of observations. For shifts with a very large magnitude (three times the standard deviation), our simulation study shows that after only 4 years the probabilities of shift detection reach nearly 100 per cent. This reveals that the approach has potential for climate monitoring.
Primary environmental care for sustainable livelihood: a UNICEF perspective:

Children constitute nearly half the population of the South. They are the worst affected victims of resource degradation and environmental pollution. They are also increasingly deprived of the mechanisms for acquiring knowledge values and survival skills as parents have less time to devote to their care and nurturing and schools are either inaccessible or ill-equipped for providing relevant education. At UNCED world leaders and NGO representatives have emphasized the necessity for human-centered poverty-focused approaches to environment and development. Agenda 21 endorsed the goals agreed upon at the World Summit for Children and appealed for ratification of the Convention on the Rights of the Child. As follow-up UNICEF is adopting the "primary environmental care" approach to enable children and women to meet their basic needs by using and protecting natural resources optimally. Priority is given to the poorest groups living in environmentally vulnerable areas to fostering opportunities for enhanced livelihood and to building partnerships with NGOs. (authors)
Basal Ganglia activity in pathological gambling: a fluorodeoxyglucose-positron emission tomography study.

Background: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex. We extended our studies to include functional alterations of the striatum and thalamus in a cohort of patients with PG before and after treatment with lithium. Methods: Twenty-one patients with PG who met lifetime comorbid bipolar spectrum diagnoses and a comparison group of 21 age- and sex-matched controls underwent a baseline positron emission tomography (PET) scan. Sixteen of these patients entered a randomized double-blind placebo-controlled parallel-group-design trial of lithium and underwent a follow-up PET scan at week 10. Anatomical MRI were obtained and the structures outlined on consecutive axial slices. These individual hand-drawn templates were used to identify structures on the PET scan of each patient, and the rGMR was measured. Results: The PG patients had a decrement of the rGMR in the ventral parts of the striatum and thalamus, and an increment of the rGMR in the dorsal parts as compared with the controls. Lithium treatment increased the ventral caudate rGMR to a trend level in the patients, but had no effect on the metabolism of either the putamen or the thalamus. Conclusion: Because of their extensive connectivity to the frontal cortex, striatal and thalamic functional alteration may contribute to faulty decision making processes in PG patients. By increasing the ventral rGMR of the caudate nucleus, lithium treatment may reduce cognitive dysfunction and symptoms in PG patients.
Probing receptor-ligand interactions by sedimentation equilibrium

While sedimentation equilibrium is most commonly used to characterize the molecular weight and state of association of single proteins, this technique is also a very powerful tool for probing the interactions between two or more different proteins, and can characterize both the binding stoichiometry and the equilibrium constants. To resolve the complex binding interactions that can occur in such systems, it is crucial to globally fit data from many experiments to a common binding model, including samples made with different mixing ratios and a wide range of total concentration. It is often also essential to constrain the parameters during fitting so that the fits correctly reproduce the molar ratio of proteins used in making each sample. We have applied this methodology to probe mechanisms of receptor activation for a number of hematopoietic receptors and their cognate ligands, using receptor extracellular domains expressed as soluble proteins. Such data can potentially help in the design of improved or new protein therapeutics, as well as in efforts to create small- molecular mimetics of protein hormones through structure- based drug design. Sedimentation equilibrium has shown that stem cell factor, erythropoietin, and granulocyte-colony stimulating factor can each dimerize their respective receptors in solution, but the mechanism of ligand-induced receptor dimerization for these three systems are strikingly different.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Hamstring Strains: Expediting Return to Play

Strains to the hamstring muscle group are prevalent and, unfortunately, often recurrent, with prolonged rehabilitation and persistent disability. Most hamstring injuries are of a single muscle near the muscle-tendon junction. Rarely, the hamstring muscle group may avulse from the ischial tuberosity. The diagnosis can usually be made by history and physical exam, but MRI can be used to help pinpoint the extent and location of the injury. Initial treatment typically consists of rest, ice, compression, elevation, and pain relief. There is no consensus on optimal rehabilitation, but functional exercises with stretching and strengthening have been emphasized.
An IR Navigation System for Pleural PDT.

Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.
Mystery Case: Frontal meningoencephalocele causing recurrent bacterial meningitis

A 34-year-old woman presented initially with meningococcal meningitis and with Streptococcus mitis meningitis 6 months later. A right cribriform plate area meningoencephalocele was discovered on MRI at the second episode. In retrospect, this abnormality was present on initial MRI (figure). The patient recalled intermittent watery rhinorrhea for 1 year preceding the first meningitis episode, but without head trauma. The anterior cranial fossa defect was repaired, without recurrence of rhinorrhea or meningitis in 2-year follow-up.
Comparison of Two Methods of Marking the Visual Axis on the Cornea During Radial Keratotomy

We compared two methods of marking the visual axis on the cornea during radial keratotomy surgery in 34 eyes of patients participating in the National Eye Institute Prospective Evaluation of Radial Keratotomy. The locations of the corneal light reflections produced by an optical centering device and by the operating microscope filament were identical in 18 eyes, overlapped partially or touched in ten eyes, and were separate in the remaining six eyes. The two corneal marks in this last group were close enough to make little practical difference. The two methods can be used interchangeably in clinical practice.
Optimized components in truss synthesis.

Mathematical programming in optimized truss design noting reduction of components under buckling
Interpretation and considerations on the safety evaluation of human drug metabolites

The final Food and Drug Administration guidance on the safety testing of drug metabolites was published in February 2008. Discussions of the role and applications of this guidance were addressed at several public scientific meetings over the past year. One of the main differences between the draft and the finalized guidance is that in the latter, the human metabolite level was correlated to the parent drug level in plasma, whereas this parameter was considered in relationship to administered dose or total exposure in the draft guidance. The parent drug concentration in plasma has traditionally been the parameter commonly measured in animals during drug development and the one used to estimate drug clinical levels and to assess human risk. Moreover, circulating parent drug in general is the molecule with the intended therapeutic and pharmacologic effect. Therefore, it is appropriate to compare metabolite concentration to that of the parent drug. This report elaborates on this issue and supports other alternative rational and scientific approaches on the design of nonclinical studies that may be needed to test a human drug metabolite.
From Hope to Action Creating Spaces to Sustain Transformative Habits of Mind and Heart

This article is the third in a series of explorations by three university professors committed to issues of social justice in a progressive professional development master’s degree program for practicing teachers. Building on the lessons learned from earlier explorations into the impact of their teaching practice in earlier JTE issues—“Beyond Reflective Competency: Teaching for Audacious Hope-in-Action” and “Dancing on the Threshold of Meaning: Recognizing and Understanding the Growing Edge”—this third article asks, “So what?” and responds by showing how these three authors moved past the entry points of reflective practice, to the edges of meaning making, and finally to creating transformative curricular experiences for teachers. This article speaks to the particular theoretical discoveries from the earlier articles and also uses real curricular examples to highlight what was learned as the authors tried to use their theories to improve their practice.
Micro volume rotating disk electrode (RDE) amperometric detection for a bead-based immunoassay

Abstract The application of the rotating disk electrode (RDE) directly on a micro drop of 50 μl has been developed for electrochemical detection in a bead-based immunoassay for the model analyte mouse IgG. The enzyme label alkaline phosphatase (ALP) was used for enzymatic turnover of the substrate 4-aminophenyl phosphate (PAPP) to the electroactive product 4-aminophenol (PAP). The determination of 4-aminophenol by the RDE has a linear range from 1.9 × 10 −8 to 1.9 × 10 −4 M. Direct analysis in a drop minimizes enzyme product dilution, a key requirement in achieving very low limits of detection. Furthermore, the detection scheme allows enzyme turnover to be monitored continuously, thus reducing errors associated with obtaining data at fixed times as in flow injection analysis. An unoptimized calibration curve for mouse IgG was obtained from 50 to 5000 ng/ml.
Francisella DnaK inhibits tissue-nonspecific alkaline phosphatase.

Following pulmonary infection with Francisella tularensis, we observed an unexpected but significant reduction of alkaline phosphatase, an enzyme normally up-regulated following inflammation. However, no reduction was observed in mice infected with a closely related Gram-negative pneumonic organism (Klebsiella pneumoniae) suggesting the inhibition may be Francisella-specific. In similar fashion to in vivo observations, addition of Francisella lysate to exogenous alkaline phosphatase (tissue-nonspecific isozyme) was inhibitory. Partial purification and subsequent proteomic analysis indicated the inhibitory factor to be the heat shock protein DnaK. Incubation with increasing amounts of anti-DnaK antibody reduced the inhibitory effect in a dose-dependent manner. Furthermore, DnaK contains an adenosine triphosphate binding domain at its N terminus, and addition of adenosine triphosphate enhances dissociation of DnaK with its target protein, e.g. alkaline phosphatase. Addition of adenosine triphosphate resulted in decreased DnaK co-immunoprecipitated with alkaline phosphatase as well as reduction of Francisella-mediated alkaline phosphatase inhibition further supporting the binding of Francisella DnaK to alkaline phosphatase. Release of DnaK via secretion and/or bacterial cell lysis into the extracellular milieu and inhibition of plasma alkaline phosphatase could promote an orchestrated, inflammatory response advantageous to Francisella.
Managed Care, Rationing, And Quality: A Tangled Relationship

Managed care, in defending its position against the current anti-managed care backlash, must demonstrate that it does, in fact, represent the “good guys.”
Effects of list length and first-trial reward upon concurrent discrimination performance

Abstract Rhesus monkeys were given 2304 two-trial object discrimination problems that were presented as members of lists consisting of two, four, or eight problems. The problems within each list were presented concurrently, Trial 1 for all problems in the list being presented before initiation of Trial 2 for any problem. Each problem involved exposure of a single object on Trial 1, which was either rewarded or not rewarded, followed by presentation of the Trial 1 object along with a second object on Trial 2. Performance varied inversely with list length, and this effect became more prominent as a function of training. Performance after Trial 1 nonreward was substantially better than that after Trial 1 reward, and this effect became enhanced both with continued training and with increased list length. The findings were discussed in terms of Bessemer's short-term memory analysis of learning set.
Procedure costs and outcomes associated with pharmacologic management of peripheral arterial disease in the department of defense

This study was undertaken to determine if differences existed between pharmacologic treatments of peripheral arterial disease (PAD) with respect to PAD-related costs and health care outcomes in the United States Department of Defense health care system. We performed a retrospective review of hospital and prescription data to explore the effects of at least 90 days of aspirin, pentoxifylline, papaverine, or dipyridamole on 4 PAD-related outcomes: number of PAD-related invasive procedures (INV), number of PAD-related examination procedures (EXM), number of PAD-related hospitalization days (HDAYS), and cost of PAD-related procedures (COST) during 5 years. A covariate representing the number of PAD-related hospitalizations before the study period was used to attempt to control for severity of disease state. General linear models were used in the analyses. A statistically significant difference was seen between treatment groups for a linear combination of INV, EXM, HDAYS, and COST when controlling for past PAD-related hospitalizations (P < 0.014). A statistically significant relationship existed between treatment groups and INV (P < 0.041). The pentoxifylline treatment group had a statistically significant higher covariate-adjusted mean INV compared with the aspirin treatment group (P < 0.043). Also, PAD-related past hospitalizations were significantly related to EXM (P < 0.006). Our results appear to support the use of aspirin as a preventive treatment in PAD compared with pentoxifylline or dipyridamole.
Brain metastases from esophageal cancer: a phenomenon of adjuvant therapy?

Background Brain metastases from esophageal cancers are uncommon, yet our impression was that they occurred more frequently than expected after esophagectomy plus adjuvant therapy. Therefore, we determined (1) incidence and prevalence of, risk factors for, and survival after development of brain metastases following esophagectomy for esophageal cancer, and (2) their association with adjuvant therapy. Methods From 1985 to 2002, 403 patients (52%) underwent esophagectomy alone and 369 esophagectomy plus adjuvant therapy (118 [15%] preoperative only, 124 [16%] postoperative only, and 127 [16%] both). Hazard-function methodology was used to characterize time-related occurrence of brain metastases and risk factors. Inferences were confirmed by propensity analysis. Results Twenty-nine patients developed brain metastases, 20 within 1 year; 6 had undergone surgery alone, and 23 had adjuvant therapy. Prevalence was 2.5% 5 years after surgery alone, but 8.4%, 7.0%, and 18.4% after preoperative adjuvant therapy only, postoperative adjuvant therapy only, and both, respectively (p Conclusions A dose-related increased incidence of brain metastases after adjuvant therapy for esophageal cancer cannot be explained by increased longevity. Adjuvant therapy itself, not just advanced disease, appears to create conditions conducive to developing these rapidly fatal metastases.
Biobanking: The Melding of Research with Clinical Care

The number of biobanks around the world has increased dramatically, owing in part, to the need for researchers to have access to large numbers of samples for genomic research. Policies for enrolling participants, returning research results and obtaining samples and data can have a far reaching impact on the type of research that can be performed with each biobank. Research using biobank samples includes studies of the impact of environmental and other risk exposures on health, understanding genetic risks for common disease, identification of biomarkers in disease progression and prognosis, and implementation of personalized medicine projects. This research has been instrumental in the progress of genetic and genomic research and translational medicine. This article will highlight some of the controversies and recent research associated with biobanking over the past year.
Energy dependence of the 12C(16O, α) reaction

The energy dependence of the 12C(16O, α) reaction was measured at incident energies of Elab=112−191 MeV. In the range ofEx(24Mg)=30−56 MeV, the excitation energies of the structures in the inclusive α spectrum were found to vary continuously as a function of incident energy in this region. This fact indicates that these structures do not represent excitations in 24Mg, but rather that they originate from a different process such as a sequential ejectile decay.
The proximity of (algebraic) geometric programming to linear programming

Geometric programming with (posy)monomials is known to be synonomous with linear programming. This note reduces algebraic programming to geometric programming with (posy)binomials.
Inactivation of human synovial fluid phospholipase a2 by the marine natural product, manoalide

The marine natural product, manoalide (MLD), was investigated to determine if this drug inhibited purified human synovial fluid phospholipase A2 (HSF-PLA2). Utilizing classical Michaelis-Menten kinetics, apparent Km and Vmax values for HSF-PLA2 of 1.34 mM and 0.47 mumol [3H]palmitic acid released/min/mg protein were obtained using dipalmitoylphosphatidylcholine (DPPC) as the substrate, and 38.0 microM and 18.8 mumol [3H]arachidonic acid released/min/mg protein with Escherichia coli as a natural substrate. These kinetic parameters were utilized subsequently to evaluate the inhibitory effects of manoalide on HSF-PLA2. Inhibition of HSF-PLA2 by MLD was concentration and time dependent with IC50 values of 0.2 and 0.02 microM for DPPC and E. coli respectively. Dialysis studies and examination of DPPC or E. coli hydrolysis versus enzyme concentration indicate that MLD is an irreversible inhibitor of HSF-PLA2. Substrate specificity was also examined in the absence and presence of MLD using dipalmitoylphosphatidylethanolamine (DPPE) as a substrate. MLD inhibited the hydrolysis of DPPE (greater than 90% inhibition at 2 microM), and preliminary results indicate that DPPC was more readily hydrolyzed than DPPE under the substrate conditions of the assay. While the cellular source of secreted HSF-PLA2 is unknown, these studies indicate that MLD can inactivate secreted phospholipase A2 isolated from patients with inflammatory joint disease.
Detection of leakage in inflatable genitourinary devices.

Abstract Objectives Improved manufacturing techniques and stronger materials have significantly reduced but not eliminated the incidence of hydraulic leakage in the inflatable genitourinary devices. This study was designed to test the efficacy of pressure dissipation and volume loss as potential tests for the detection of site-specific hydraulic leakage in the inflatable penile prosthesis (IPP) and the artificial sphincter (AS) and compare their efficacy with the current standard—the ohmmeter technique. Methods Five IPPs and ASs were dismantled to achieve five reservoirs and cuff-pump assemblies. Each component was inspected visually and then tested for volume, pressure, and electrical resistance over 5 minutes. Next a needle puncture was deliberately made in these components, and the experiment was repeated. The in vivo pseudocapsule was simulated by an elastic covering, made from antiembolic hose. Results The techniques of pressure, volume, and ohmmeter testing were not able to detect current leakage in all the components, with the pseudocapsule in place. Conclusions None of the currently available tests qualify for the label of “gold standard” in accurately detecting hydraulic leakage. We currently recommend testing the device's integrity by visual inspection in vivo, starting with the reservoirs. If a leakage is detected, the reservoir alone is replaced. If no leakage is found, we recommend that the entire unit be removed and replaced. If the malfunctioning device is more than 2 years old, we suggest that it be entirely replaced. UROLOGY ® 47 : 97–101, 1996.
The Folacin Requirements of Broiler Chicks and Quail (Coturnix coturnix japonica)

Abstract Six experiments were conducted to investigate the effect of dietary composition on the folacin requirement of broiler chicks and to determine the folacin requirement of growing Japanese quail. The folacin requirement of both chicks and quail could not be determined when an isolated soybean protein based diet containing 0.44 mg. folacin per kilogram was used. Dietary composition affects folacin requirement of growing broiler chicks. Three values for the folacin requirement of growing broiler chicks were determined when three different basal diets were fed. With a low-glycine, casein based diet, growth was limited more by glycine than folic acid which improved growth only at 1.69 mg./kg. When 0.7% glycine was added to this casein diet, the folacin requirement was determined to be between 0.34 and 0.49 mg./kg. diet. However, with a casein-gelatin based diet, the folacin requirement was found to be between 0.12 and 0.27 mg./kg diet. Folacin deficiency in growing Japanese quail caused poor feathering, high mortality, leg weakness and cervical paralysis. A curly-toe symptom was observed in coturnix chicks fed low levels of folacin and might also be a consequence of folacin deficiency. The folacin requirement of growing Japanese quail was found to be 0.30 to 0.36 mg./kg. diet when a casein-gelatin based diet was fed.
Dearterialization with mucopexy versus haemorrhoidectomy for grade III or IV haemorrhoids: short-term results of a double-blind randomized controlled trial.

Aim There is scepticism regarding anatomical rationale and Doppler guidance for ligation of haemorrhoidal arteries. The null hypothesis of this randomized controlled trial (RCT) was that there is no difference in pain following dearterialization or haemorrhoidectomy for grade III/IV internal haemorrhoids in a minimum of three quadrants. Method This was a single-centre, double-blind RCT. Patients were allocated to dearterialization or haemorrhoidectomy. Included haemorrhoids were grade III, prolapsing but reducible; and grade IV, chronic non-incarcerated. The primary end-point was pain. Patients with external component, acute incarcerated grade IV or recurrent haemorrhoids were not included. The interventions were dearterialization (with Doppler guidance and mucopexy) or haemorrhoidectomy. The main outcome measure was the Brief Pain Inventory (BPI). Results Twenty dearterialization patients were comparable to 20 haemorrhoidectomy patients for age (P = 0.107), body mass index (P = 0.559), race (P = 0.437), American Society of Anesthesiology score (P = 0.569), comorbidities (P = 0.592), grade (P = 0.096), quadrants (P = 0.222), Fecal Incontinence Quality-of-Life Score (FIQOL; P = 0.388), coping (P = 0.532), depression (P = 0.505), embarrassment (P = 0.842), and Short Form Health Survey (SF-12) physical components (P = 0.337), SF-12 mental components (P = 0.396) and constipation (P = 0.628) scores. Dearterialization patients had shorter operative time (36 vs 54 min, P = 0.043) with less pain (P = 0.011) and urinary retention (P = 0.012). Dearterialization patients had first bowel movement earlier (1.3 vs 4.6 days, P = 0.001), less pain (P = 0.011) and lower pain intensity (P = 0.001). Narcotic requirements were reduced in dearterialization patients (25% vs 100%, P = 0.001), with less medication (4.9 vs 112 pills, P = 0.001) and shorter regimen (0 vs 7 days, P = 0.001). BPI did not differ on days 1, 3, 5, 7 and 14 except for less pain in dearterialization patients. At 3 months, symptomatic relief was the same with no differences in BPI, FIQOL or SF-12. Conclusion Compared with haemorrhoidectomy, dearterialization led to less pain in grade III/IV haemorrhoids.