cssi/SciSciGPT-SciSciNet huggingface dataset:
The tuberous sclerosis complex (TSC) pathway and mechanism of size control

We have identified three groups of growth-constraint genes using mosaic genetic screens in Drosophila melanogaster, including PTEN (phosphatase and tensin homologue deleted on chromosome 10), and the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2. Our studies show that all three groups of genes participate in mechanisms that regulate organ and organism size in animals. We propose that mechanisms of organ size control are critical targets for diseases, such as tumorigenesis, which require an increase in tissue size and total mass, and for evolutionary events that alter the size of organisms. Using genetic and biochemical methods, we have shown that Tsc1 and Tsc2 function in the insulin/phosphoinositide 3-kinase (PI3K)/Akt pathway. We have shown that Akt regulates the Tsc1-Tsc2 complex by directly phosphorylating Tsc2. We have shown further that S6 kinase (S6K) is a downstream component of the PI3K/Akt/TSC pathway and reduction of S6K activity can block TSC defects. Recent studies from many laboratories have now confirmed our findings in mice, rats and human patients, and have shown that drugs that antagonize S6K activities, such as rapamycin, diminish tumours in TSC-deficient mice and rats. Clinical trials based on these findings have begun. Given that other components of the pathway, such as PTEN, are also mutated in a large number of cancer patients and that these components regulate intracellular insulin signalling, therapeutics based on the knowledge of the pathway could have effects beyond the TSC patient population.
Comparison of Ross procedures and aortic valve allografts in children

Abstract Background . The Ross procedure is useful, but at times an allograft valve is the only alternative to a mechanical aortic prosthesis. Since 1994 the Ross procedure or aortic allograft replacement has been used exclusively for aortic valve replacement at our institution. Methods . Demographic, clinical, and echocardiographic data of 23 consecutive Ross and 8 allograft patients were compared. Results . Groups were similar in age and weight. The Ross group had fewer prior operations. There were no deaths or major complications in either group. The Ross group had no late complications of the autograft but 1 reoperation for pulmonary allograft stenosis. In the allograft group there was one reoperation for allograft insufficiency. Echocardiography was performed 2 to 11 days (mean, 4.3 days) after operation and 1 to 28 months (mean, 10.2 months) later. In the Ross group left ventricular wall thickness (mm) decreased from 11.0 ± 2.3 to 7.8 ± 1.7 ( p p = 0.0001). In the allograft group left ventricular wall thickness (mm) decreased from 10.5 ± 2.6 to 9.0 ± 2.6 (not significant), and left ventricular outflow tract maximal systolic velocity (m/sec) increased from 1.5 ± 0.9 to 1.9 ± 0.7 (not significant). Conclusions . The Ross procedure results in significant improvement in left ventricular wall thickness and outflow tract velocity not seen in allograft aortic valve replacements. The Ross procedure remains the preferred operation for children requiring aortic valve replacement.
Clinical Experience with BioMedicus Centrifugal Ventricular Support in 172 Patients

: One hundred and seventy-two patients at The Methodist Hospital in Houston, Texas, were placed on BioMedicus centrifugal ventricular support. One hundred thirty-nine patients were male and 33 were female with a mean age of 59.7 years. Reasons for support were post-cardiotomy cardiac failure (129 patients), cardiac allograft failure (17 patients), bridge to transplantation (10 patients), resuscitation (7 patients), postpercutaneous trans-luminal coronary angioplasty emergent (2 patients), and other (7 patients). Support was by left ventricular assist device in 108 patients, right ventricular assist device in 20 patients, and biventricular assist device in 44 patients. Eighty-four patients (48.8%) were weaned from the ventricular assist device, and 88 patients (51.2%) were not weaned. Thirty-four patients (20.0%) were discharged from the hospital. Complications included coagulopathy, renal insufficiency/failure, respiratory insufficiency/ failure, neurological deficits, sepsis, arrhythmias, and device-related complications. Overall causes of death were ventricular failure (55.1%), triage (13.0%), arrhythmias (9.4%), graft failure (5.9%), coagulopathy (4.3%), sepsis syndrome (2.9%), device-related (0.7%), and other (0.7%). BioMedicus centrifugal ventricular support can be implemented rapidly and easily. Device-related complications are few (1.2%), and it is relatively inexpensive when compared with other ventricular assist systems. This series demonstrates that a substantial number of patients may benefit from temporary centrifugal ventricular support.
Maintaining the calibration of an information system

Abstract The design and operation of an information system requires assumptions on the values of parameters which characterize the behavior of pertinent random processes. If these parameters remain constant over time at design values, system performance will be as specified. Otherwise, performance will vary from design and cost and service penalties will arise. A control chart procedure is introduced for monitoring system parameters and introducing appropriate action to reset them to design values as indicated. The control system is set so that the expected cost of monitoring is a minimum. A table of control system settings over a broad set of a priori assumptions is provided. Examples describing the procedure and use of the table are given.
Identifying likely student dropouts using fuzzy inferencing

Fuzzy logic provides a methodology for reasoning using imprecise rules and assertions. Whereas a statement can only be true or false in classical logic, statements in fuzzy logic may be true or false to varying degrees. This enables fuzzy logic to deal with data and rules that are expressed in an imprecise manner using inexact linguistic expressions. Fuzzy inference is the process of formulating the mapping from a given input to an output using fuzzy logic. The mapping then provides a basis from which decisions can be made, or patterns discerned. Fuzzy expert systems are proving to be a powerful tool in business intelligence and decision support. This project concerns the development of a fuzzy expert system for identifying likely student dropouts at Columbus State University (CSU).According to a report released by the National Center for Public Policy and Higher Education, a low rate of college completion is a key concern in American higher education. According to ACT (the college testing service), the national average freshmen retention rate is 65.7%. From 2005 to 2010, this rate at CSU was 71%. Colleges and universities across the country, including CSU, are investigating this problem of student Retention, Progression and Graduation (RPG) in order to address it more effectively. The main aim of this research project is to build a fuzzy inference based model using a hybrid knowledge extraction process to predict how likely each freshman student will be to drop their program of study at the end of their first semester. Columbus State University database has student Retention, Progression and Graduation (RPG) data dating back to 1998. This historical data is being utilized to develop and evaluate the proposed fuzzy rule-based inferencing system.Knowledge extraction for the system will be performed using a top down (symbolic) as well as a bottom-up (data-based) approach. In the top-down approach, rules for the fuzzy model will be derived using the traditional knowledge extraction process involving domain expert interviews. Several persons in charge of university departments that have low retention rates will be interviewed to identify parameters that are significant determinants of student success. Fuzzy-rules designed using this knowledge will be weighted appropriately to reflect their level of significance. In the second phase of fuzzy rule derivation, results of data mining performed on student data will be utilized. A feedforward artificial neural network already trained using the student data will be subjected to weight analysis to derive additional rules for the fuzzy rule base, as well as for adjusting the significance of all rules. This hybrid neuro-fuzzy approach is expected to yield better performance than either a conventional fuzzy inferencing system or an artificial neural network.
Targeted expression of teashirt induces ectopic eyes in Drosophila

teashirt was initially identified as a gene required for the specification of the trunk segments in Drosophila embryogenesis and encodes a transcription factor with zinc finger motifs. We report here that targeted expression of teashirt in imaginal discs is sufficient to induce ectopic eye formation in non-eye tissues, a phenotype similar to that produced from targeted expression of eyeless, dachshund, and eyes absent. Furthermore, teashirt and eyeless induce the expression of each other, suggesting that teashirt is part of the gene network that functions to specify eye identity.
Varieties of Banking and Regional Economic Development in the United States, 1840-1860

It is sometimes asserted that a laissez-faire policy toward financial intermediaries tends to deepen financial development and accelerate economic growth. The two decades preceding the American Civil War provide a challenging case for this proposition because they witnessed something approaching a natural experiment. During those years the Federal government withdrew from the regulation of banking, a policy that was the final outcome of Andrew Jackson's war with the Second Bank of the United States. A wide range of experiments concerning entry into commercial banking were tried, from “free” banking to “socialized” banking. Moreover, other kinds of legislation affecting banking varied from state to state as well. While the regions of the United States differed in terms of economic structure, a common language, a common legal tradition, and, to some extent, a common culture permeated all regions. Thus, the period provides excellent conditions for observing the effects of financial legislation on the extent of financial intermediation. In this paper I will assess the impact on financial development of the three most important forms of regulation: the commercial banking laws, the usury laws, and the mutual savings banking laws.
Strategies for Extracting Structural Information from 2D IR Spectroscopy of Amyloid: Application to Islet Amyloid Polypeptide

The 37-residue human islet amyloid polypeptide (hIAPP or amylin) self-assembles into fibers, the assembly of which has been associated with the disease mechanism of type II diabetes. Infrared spectroscopy in conjunction with isotope labeling is proving to be a powerful tool for studying the aggregation process of hIAPP and other amyloid forming proteins with residue specific structure and kinetic information, but the relationship between the spectroscopic observables and the structure is not fully established. We report a detailed analysis of the linear and 2D IR spectra of hIAPP fibers isotope labeled at seven different residue positions. The features of the 2D IR spectra, including the frequencies, linewidths, intensities, and polarization dependence of the diagonal and cross-peaks, rely heavily on the position of the isotope labeled residue. In order to understand how these measured parameters depend on fiber secondary and tertiary structure, we have simulated 1D and 2D IR spectra utilizing idealized structural models in addition to a recently published solid-state NMR based model of the amyloid fibril. The analysis provides a more rigorous foundation for interpreting the infrared spectra of amyloids. In addition, we demonstrate that 2D IR spectra can be employed to distinguish between residues in beta-sheets versus those in turn regions, and that transitional residues between secondary structures can be identified by the suppression of their cross-peaks in 2D IR spectra. This latter approach is not limited to amyloid fibrils and will be generally useful in identifying regions of secondary structure in proteins using 2D IR spectroscopy and isotope labeling.
New medical ethics

Abstract The author discusses recent efforts to define new medical codes of ethics and concludes that such attempts are unnecessary and doomed to fail in a field where progress is extremely unlikely.
Parallel Biogeography-Based Optimization With GPU Acceleration for Nonlinear Optimization

This paper presents a massively parallel Biogeography-based Optimization – Pattern Search (BBO-PS) algorithm with graphics hardware acceleration on bound constrained optimization problems. The objective of this study was to determine the effectiveness of using Graphics Processing Units (GPU) as a hardware platform for BBO-PS. GPU, the common graphics hardware found in modern personal computers (PC), can be used for data-parallel computing in a desktop setting. In this research, the BBO was adapted in the data-parallel GPU computing platform featuring ‘Single Instruction – Multiple Thread’ (SIMT). The global optimal search of the BBO was enhanced by the classical local Pattern Search (PS) method. The hybrid BBO-PS method was implemented in the GPU environment, and compared to a similar implementation in the common computing environment with a Central Processing Unit (CPU). Computational results indicated that GPU-accelerated SIMT-BBO-PS method was orders of magnitude faster than the corresponding CPU implementation. The main contribution of this paper was the parallelization analysis and performance analysis of the hybrid BBO-PS with GPU acceleration. The research result was significant in that it demonstrated a very promising direction for high speed optimization with desktop parallel computing on a personal computer (PC).Copyright © 2010 by ASME
Asynergistic Regression Based on Maximized Rank Correlation

The property of synergy and its detection are discussed. A response surface is said to possess synergy if it is monotone in each argument and its level curves are convex. Detecting this is useful in the study of combination drug therapies, where the goal is enhanced response with diminished side effect. One way to detect synergy is to fit a surface with linear level curves under the assumption of asynergy and observe the residuals. We explore an algorithm to accomplish this asynergistic regression via a reduction in dimensionality and connections to semiparametric monotonic linear index models (Cavanagh and Sherman, 1998). We see that the asynergistic model is a generalized version of the monotonic linear index model where the linear level curves are not restricted to be parallel.
Measurement of Brain pH Using 11CO2 and Positron Emission Tomography

We have examined the feasibility of measuring local brain pH in vivo with /sup 11/CO/sub 2/ and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue PCO/sub 2/ and the rapid fixation of /sup 11/C in tissue. From a reexamination of the basic theory, we argue that after administration of /sup 11/CO/sub 2/ the time-dependent distribution of /sup 11/C between tissue and blood is independent of the distribution of CO/sub 2/ already in the body, making it unnecessary to estimate local tissue PCO/sub 2/. Assuming that the blood--brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of /sup 11/CO/sub 2/ in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of /sup 11/C that accounts for regional variations in blood flow, CO/sub 2/ extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of /sup 11/CO/sub 2/. Tissue pH can then be calculated from one of the parameter values, a measurement ofmore » arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation.« less
Inference and Prediction for a General Order Statistic Model with Unknown Population Size.

Abstract Suppose that the first n order statistics from a random sample of N positive random variables are observed, where N is unknown. This, the general order statistic model, has been applied to the study of market penetration, capture—recapture, burn-in in repairable systems, software reliability growth, the estimation of the number of individuals exposed to radiation, and the estimation of the number of unseen species. Inference is to be made about the unknown parameters, especially N, and future observations are to be predicted. A Bayes empirical Bayes approach to inference is presented. This permits the comparison of competing, perhaps nonnested, models for the distribution of the random variables in a natural way. It also provides easily implemented inference and prediction procedures that avoid the difficulties of non-Bayesian methods. One such difficulty is that the maximum likelihood estimator of N may be infinite. Results are given for the case in which vague prior information about the model ...
Misuse Made Plain: Evaluating Concerns About Neuroscience in National Security

Misuse Made Plain: Evaluating Concerns About Neuroscience in National Security Kelly Lowenberg a , Brenda M. Simon a , Amy Burns b , Libby Greismann c , Jennifer M. Halbleib b , Govind Persad b , David L.M. Preston c , Harker Rhodes b & Emily R. Murphy d a Stanford Law School Center for Law and the Biosciences , b Stanford Law School , c Stanford University , d Stanford Law School and Director of SIGNAL , Published online: 16 Apr 2010.
The constraints of the valuation distribution for solving a class of games by using a best response algorithm

Infinite games with incomplete information are common in practice. First-price, sealed-bid auctions are a prototypical example. To solve this kind of infinite game, a heuristic approach is to discretise the strategy spaces and enumerate to approximate the equilibrium strategies. However, an approximate algorithm might not be guaranteed to converge. This paper discusses the utilisation of a best response algorithm in solving infinite games with incomplete information. We show the constraints of the valuation distributions define the necessary conditions of the convergence of the best response algorithm for several classes of infinite games, including auctions. A salient feature of the necessary convergence conditions lies in that they can be employed to compute the exact Nash equilibria without discretising the strategy space if the best response algorithm converges.
Astronomical Applications Of The New Goddard Si:Bi 16X16 Array Camera System

An improved 4-18 micron array camera system has been developed at NASA Goddard Space Flight Center for astronomical protometry, using 16 x 16 Si:Bi (bismuth dope silicon) accumulation mode charge injection device (AMCID) with 256 active pixels. An astronomical observing program using this device has been carried out. The 16 x 16 device had sufficiently good sensitivity, uniformity and noise characteristics to be used for successful observations at the Steward Observatory Mt. Lemmon 60 and 61-inch telescopes in May 1983, and at the NASA Infrared Telescope Facility (IRTF) at Mauna Kea in August 1983. Initial results indicate that this detector has sensitivity and noise characteristics comparable to other devices from the same generation of Aerojet arrays.
P-505 - Comparative benefits and harms of second-generation antidepressants in the pharmacologic treatment of depression in older adults and populations with comorbid conditions

Introduction People with particular medical illnesses are at an increased risk of depression. Similarly, other psychiatric or behavioral illnesses increase the risk of depressive disorders. There is a growing interest in the comparative benefits and harms of second-generation antidepressants for treating depression with co-occurring illness. Objectives To compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive syndromes in certain demographic populations (e.g., older adults) and in subgroups with comorbidities. Methods We updated a comparative effectiveness review (CER) published in 2007 by the Agency for Healthcare Research and Quality searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias. In addition, investigators graded the strength of the body of evidence. Results Evidence on subgroups is sparse. Head-to-head RCTs often exclude subgroups. We found no studies designed to compare a particular subgroup with the general population. In older adults, efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. We found no head-to-head trials comparing efficacy and harms in different race or ethnic groups. Comparative evidence on comorbidities was limited to a subgroup analysis of depressed adults with generalized anxiety disorder. Conclusions There is a great need for research focusing directly on the efficacy and safety of second-generation antidepressants in these more vulnerable populations.
Angioscopy-assisted aneurysm clipping.

OBJECTIVE: To test the concept that endovascular angioscopy can assist surgical intracranial aneurysm clipping by providing an endoluminal view of the aneurysm-parent vessel complex. METHODS: A carotid bifurcation aneurysm was surgically created in a dog at the lingual artery origin. A balloon catheter was inflated proximal to the aneurysm to block proximal blood flow and allow endoluminal visualization. A flexible angioscope connected to a video monitoring system and to a high-intensity light source was then advanced within the catheter lumen and positioned immediately distal to the catheter tip. The aneurysm neck was clipped, and the clip was repositioned several times along the neck, with or without distal parent vessel compromise. Each time, the endovascular image on the monitor was interpreted by an observer blinded to the position of the clip. Clip position and image interpretation were communicated independently to a third person, who analyzed the correlation between them. RESULTS: Angioscopy allowed clear visualization of the extent of aneurysm neck occlusion (complete, incomplete, residual dog ear) after clip application, as well as the presence or absence of distal parent vessel compromise. Aneurysm neck configuration, size, presence of thrombus, and suture line definition were depicted. Critical structures external to the aneurysm-parent vessel complex were transilluminated by the high-intensity lamp. CONCLUSION: Although acknowledged as the treatment of choice for intracranial aneurysms, surgical exclusion can be accompanied by significant morbidity related to perforator occlusion, parent artery compromise, and/or persistent residual aneurysm. The availability of a device allowing visualization of an aneurysm from an endoluminal perspective theoretically could reduce the incidence of these complications. Angioscopy has the potential to become a useful adjunct during intracranial aneurysm clipping because it provides real-time endoluminal viewing of the aneurysm-distal parent vessel complex, which is sometimes obscured to the surgeon.
Introduction History and Invasion Patterns of Ammophila arenaria on the North Coast of California

European beachgrass (Ammophila arenaria [L] Link), introduced to stabilize sand, is fully naturalized in central and northern California and has supplanted populations of native dune plants in many areas, including the North Spit of Humboldt Bay. We interpreted air photos of the North Spit for the presence of Ammophila arenaria at three points in time: 1939/1942, 1962, and 1989. To quantify the spread and to detect invasion patterns of Ammophila, we then compiled maps using a geographic information system. We documented introduction dates and locations to improve the accuracy of our photo interpretation. Interpretation of the three photo series revealed invasion and expansion of Ammophila in both foredunes and inland dunes. The most dramatic increase in cover was found in the foredunes, whereas documented and presumed plantings were found mostly on inland dunes. Adjusting for intentional eradication, Ammophila cover on the North Spit was found to have increased between 1939 and 1989 by 574%. The square root of the area occupied by Ammophila on the North Spit increased linearly with time, conforming to biological invasion theory. Ammophila arenaria (L) Link, esta plenamente establecida en et norte y centra de California, donde ha suplantado as poblaciones de vegetacion autoctona de dunas en muchas areas, incluyendo la de “North Spit” en la Bahia de Humboldt. Interpretamos fotografias aereas del “North Spit” para detectar la presencia de Ammophila arenaria en tres momentos: 1939/42, 1962 y 1989. Los mapas fueron compliados utilizando sistemas de informacion geografica para cuantificar la expansion de Ammophila en et “North Spit” y detector patrones de invasion. Se documentaron fechas y lugares de introducion con la cinalidad del aumentar la presicion en la interpretacion de las fotografias aereas. La interpretacion de las tres series defotografias revelaron la invasion y expansion de Ammophila tanto en las dunas costeras como en las interiores. El aumento de cobertura mas pronunciado se detecto en las dunas costeras mientras que las plantaciones documentadas o supuestas fueron halladas principalmente en las dunas interiores. Ajustando para la erradicacion intencional, la cobertura de Ammophila en el area se incremento en un 574% entre 1939 y 1989. De acuerdo con la teori de invasion biologica, la raiz cuadrada del area ocupada por Ammophila en el “North Spit” aumento en forma lineal con respecto al tiempo.
Sol-gel silica for precision and multifunctional optics

Abstract The sol-gel method of producing silica optics results in both fully dense Type V gel-silica and a Type VI gel-silica intermediate product. Advantages of the Type V gel-silica for net shape precision optics are described. Uses of the Type VI gel-silica as multifunctional optical components is discussed, including transpiration cooled windows, fast radiation-hard scintillating detectors and solid state dye lasers.
Simulation of southern california forest fires

Wildland fire spread has been simulated using a computer model. Reasonable success has been achieved in matching computed results with the observed fire perimeters. The model for this effort was based upon existing Forest Service sub-models augmented with ancillary programs to process the fuel, terrain, and meteorological data collected from the selected fires. Refinements to the model were made based upon sensitivity studies of the numerous input parameters. The simulation runs performed during this study gave insight into the improvements required to employ the model operationally.
Rapid identification of pyloricCampylobacter in Peruvians with gastritis

PyloricCampylobacter have been reported to colonize the gastric mucosa of many persons, especially in association with gastritis and peptic ulcer disease. These reports have, so far, come from countries in the developed world. We report that pyloricCampylobacter appear to be equally common in persons from a developing country (Peru) who have gastritis. Our examination of the histopathology associated with these organisms suggests that mucin depletion is associated with active colonization. Two simple diagnostic methods have been found which compare favorably to silver staining of biopsy materials and which appear to have value in the rapid and facile identification of these organisms: hematoxylin-eosin staining of biopsies and Gram staining of cytology specimens obtained by brushing the gastric mucosa.
Oedema in acute myocardial infarction

A 61-year-old man presented with inferior ST-segment elevation acute myocardial infarction and underwent prompt thrombolysis. Subsequent invasive coronary angiography revealed an occluded right coronary and no significant epicardial stenosis in the left coronary system. Cardiovascular magnetic resonance (CMR) with a …
A simple, sensitive and specific radioreceptor assay for β-adrenergic antagonist drugs

Abstract A radioreceptor assay for β-adrenergic blocking drugs described here is based on the ability of the blood content of drugs to compete with the binding of 3 H-dihydroalprenolol ( 3 H-DHA) to β-adrenergic receptors in calf cerebellar membranes. Plasma protein greatly inhibits the binding of 3 H-DHA to β-receptors by binding the 3 H-DHA so it is unavailable to the β-receptors. As little as 0.01 ml of human plasma in a final volume of 1 ml reduces binding 25–45%. Assays conducted on plasma dialysates can be performed without such inhibition. The radioreceptor assay is simple to perform as 100 samples can be processed in a morning. It is sensitive, detecting low nanomolar concentrations of plasma propranolol, and it is specific. No drugs clinically employed other than β-blocking agents compete for β-receptor binding. The assay detects all pharmacologically active metabolites of β-blocking drugs as well as the parent drug.
The Biological Effect of an Antisense Oligonucleotide Depends on Its Route of Endocytosis and Trafficking

We demonstrate that the biological effect of an oligonucleotide is influenced by its route of cellular uptake. Utilizing a splice-switching antisense oligonucleotide (SSO) and a sensitive reporter assay involving correction of RNA splicing, we examined induction of luciferase in cells treated either with various concentrations of an unconjugated (“free”) SSO or an SSO conjugated to a bivalent RGD ligand that promotes binding to the αvβ3 integrin (RGD-SSO). Under conditions of equal accumulation in cells, the RGD-SSO consistently had a greater effect on luciferase induction than the unconjugated SSO. We determined that the RGD-SSO and the unconjugated SSO were internalized by distinct endocytotic pathways, suggesting that the route of internalization affects the magnitude of the biological response.
Politicizing the International Criminal Court: The Convergence of Politics, Ethics, and Law

Politicizing the International Criminal Court: The Convergence of Politics, Ethics, and Law. By Steven C. Roach. Lanham, MD: Rowman & Littlefield, 2006. 213p. $75.00 cloth, $26.95 paper. No political scientist predicted that the world would witness the establishment of an International Criminal Court (ICC) by 2002, and as of yet, there are few compelling explanations for this phenomenon. Steven Roach addresses the next set of questions that the ICC raises for political scientists, namely, how it will impact international political outcomes, and how it will be forced to cope with pressures from states and other actors. Roach's work is an important first step toward a political understanding of the role of the ICC in world politics and demonstrates political scientists' growing interest in international law.
On the choice and replacement of chief financial officers

Abstract This paper provides empirical evidence regarding why firms replace their CFOs. Empirical tests are based on a sample of 2,227 CFO appointments over the 1984–1997 time period. Key findings reported in the paper are: (a) external CFO succession rate is markedly higher than the external CEO succession rate, (b) the incidence of retirement is less common for serving CFOs as compared to the top executive, (c) CFO turnover is preceded by negative excess returns, (d) CFO turnover is preceded by a decline in operating return on assets in the pre-period, (e) announcements of CFO turnover are associated with a significant negative stock price reaction when old CFO quits and firm replaces with an internal appointment, and (f) CFO turnover is preceded by abnormally high CEO turnover. Overall, evidence is consistent with the hypothesis that CFO turnovers are disciplinary. Evidence is also consistent with the hypothesis that rapid sales growth accompanied by weak operating performance leads firms to bring in outside talent.
Radioactivity and supernova remnant evolution

Abstract I comment on several areas where radioactivity is relevant to supernova remnant evolution: the possibility that the protrusions observed in the Vela remnant are due to clumps formed by the radioactive Ni bubble effect, the status of the RX J0852 X-ray source which is a possible source of the γ-ray line from 44 Ti decays, and the possible origin of extinct radioactivities in the solar system.
Thermal, olfactory, and tactile stimuli increase oral grasping of an artificial nipple by the newborn rat

Caesarean-delivered rat pups tested before any suckling experience show oral grasp responses after stimulation with an artificial nipple. Manipulating the sensory stimuli present at the time of testing alters behavioral responses to the nipple. Specifically, when the nipple is warm, when pups are tested in the presence of amniotic fluid or milk odor, or when pups are tested in the presence of a conspecific, oral grasping of the artificial nipple is increased. Pups respond to the nipple with a shorter latency, show more oral grasp responses, and the individual grasp responses are longer in duration. The experiments suggest that the newborn rat pup exhibits a basic set of behaviors in response to the nipple early in development and that sensory stimuli normally present during the expression of suckling increase oral appetitive behaviors evoked by the nipple. © 1998 John Wiley & Sons, Inc. Dev Psychobiology 33: 317–326, 1998
Comparison of Component Fatigue Test Data With Proposed EAF Methodologies for Austenitic Stainless Steel

The U.S. Nuclear Regulatory Commission (NRC) currently requires evaluation of the effect of environmental fatigue for both license renewal and new plants. NRC required the use of methodology in EPRI MRP-47, Rev. 1 addressing NUREG/CR-5704, be used for license renewal of stainless steel (SS) components, and NUREG/CR-6909 for use in new plants. These two methodologies are based on applying an environmental correction factor (Fen ) on the number of in-air design cycles. These factors are applied to the fatigue usage from each individual range of stress (or range of strain). The focus of this paper is to compare the two aforementioned methodologies; this includes comparison of the fatigue curve as well as the comparison of the environmental correction factors (Fen ). Fatigue test results data reported by others are also compared with these two methodologies. It is important to evaluate the impact of using any of those methodologies on the design fatigue life of the components. It is concluded that NUREG/CR-5704 is more severe than NUREG/CR-6909 in the LCF (low-cycle fatigue) regime, while NUREG/CR-6909 is more severe elsewhere, and both NUREG’s extremely underestimate fatigue life in PWR environment. It is also concluded that the current ASME-code fatigue curve for stainless steel reasonably estimates fatigue life in an LWR environment with reasonable margins.Copyright © 2009 by ASME
Fractal-like exciton transport and fusion in disordered naphthalene

Abstract Steady-state fluorescence and phosphorescence spectra od semi-crystalline naphthalene are presented. Singlet and triplet exciton transport are strongly dependent on temperature and degree of annealing. Analysis of delayed fluorescence decays reveals fractal-like transport in the more disordered samples.
Technetium: A toxic waste product of the nuclear fuel cycle: Effects on soybean growth and development

Technetium-99 (99Tc) is formed in significant amounts (6.2% fission yield) during fission in both nuclear reactors and nuclear bombs. The effects of technetium on soybeans (Glycine max) were studied in relation to (a) cytochemical events in the apical meristems of germinating seedlings; (b) growth responses to 0, 0.04, 0.2, 1.0, 5.0, and 20.0 ppm Tc; (c) growth responses to varying levels of Tc after a prior 5-day germination on Tc-free media, and (d) response to Tc in the presence of added manganese.
Sparge gas composition affects biomass and ajmalicine production from immobilized cell cultures of Catharanthus roseus

Abstract Despite their low solubility in aqueous medium, dissolved gases play important roles in the cultivation and successful scale-up of plant cell cultures. In this paper, the effects of O 2 and CO 2 on growth and secondary metabolism were investigated using the production of ajmalicine from Catharanthus roseus cultures. The effects of gas composition were investigated using shear-protected alginate-immobilized cells (diameter 2 and CO 2 . A wider range of concentrations (10–95% O 2 , 0.03–10% CO 2 by mole) was studied to explore potential benefits or drawbacks. Sparge gas composition significantly altered growth and ajmalicine production. Low and high O 2 concentrations (10, 90, 95% O 2 ) were either inhibitory or toxic to growth and ajmalicine production. The effects of CO 2 depended on O 2 concentration. At lower O 2 concentrations (21% O 2 ), increasing the CO 2 concentration decreased both growth and specific ajmalicine production. At higher O 2 concentrations (78.4% O 2 ), increasing the CO 2 concentration decreased growth while specific ajmalicine production was not affected. In these studies, extracellular ajmalicine concentration was maximized with a gas mixture of 50% O 2 + 0.03% CO 2 .
Development of a Rap1 Flare.Dc Biosensor for Quantitative Measurement of Spatio-Temporal Dynamics In Vivo

Polarization is a fundamental process required for directed cell migration, cell-type specification, tissue development and asymmetrical division. The small GTPase Rap1 is a well-known mediator of both mitogenic and adhesion responses and has been identified as the primary regulator of neuronal and T-cell polarization. To determine the role of Rap1 in T-cell polarity we have developed a dual-chain biosensor based on intermolecular FRET that enables the spatio-temporal dynamics of Rap1 activity to be measured in individual living cells. The FRET generated by this dual-chain sensor is a measure of the binding interaction between cerulean-tagged Rap1 and an affinity reagent fused to yPet. To facilitate expression of the sensor and to reduce cell-to-cell heterogeneity in the stoichiometry of components we have engineered a tandem viral-2A (tv-2A) mediated expression vector that achieves over 99% separation of proteins when both chains of the biosensor are transfected as a single gene. In living cells this novel Rap1 biosensor showed a > 10-fold increase in FRET upon activation, and is sufficiently bright to image Rap1 activity at concentrations that do not interfere with normal cell motility. The intermolecular design of this biosensor enables native regulation of Rap1 localization by CAAX-box modification and is well suited to fluorescence lifetime imaging microscopy (FLIM), a technique that greatly enhances quantitative accuracy and multiplexing potential.
Single-Molecule Dynamics of the Calcium-Dependent Activation of Plasma-Membrane Ca2+-ATPase by Calmodulin

The plasma membrane calcium-ATPase (PMCA) helps to control cytosolic calcium levels by pumping out excess Ca2+. PMCA is regulated by the Ca2+ signaling protein calmodulin (CaM), which stimulates PMCA activity by binding to an autoinhibitory domain of PMCA. We used single-molecule polarization methods to investigate the mechanism of regulation of the PMCA by CaM fluorescently labeled with tetramethylrhodamine. The orientational mobility of PMCA-CaM complexes was determined from the extent of modulation of single-molecule fluorescence upon excitation with a rotating polarization. At a high Ca2+ concentration, the distribution of modulation depths reveals that CaM bound to PMCA is orientationally mobile, as expected for a dissociated autoinhibitory domain of PMCA. In contrast, at a reduced Ca2+ concentration a population of PMCA-CaM complexes appears with significantly reduced orientational mobility. This population can be attributed to PMCA-CaM complexes in which the autoinhibitory domain is not dissociated, and thus the PMCA is inactive. The presence of these complexes demonstrates the inadequacy of a two-state model of Ca2+ pump activation and suggests a regulatory role for the low-mobility state of the complex. When ATP is present, only the high-mobility state is detected, revealing an altered interaction between the autoinhibitory and nucleotide-binding domains.
69 Economic Burden of Congenital Heart Disease on Families

Objective: The economic burden of pediatric illness and its social impact on families has not been described in the area of congenital heart disease (CHD). The purpose of this study was to describe the economic burden of CHD as experienced by families. Methods: An exploratory inquiry using semi-structured interviews was conducted. A pruposive sampling technique was use to identify parents of children with varying CHD complexity and socioeconomic status (SES) admitted for congenital heart surgery at a tertiary care center. Complexity of CHD was approximated using the Risk Adjustment for Congenital Heart Surgery Method (RACHS-1). SES was estimated using Hollingshead's Four Factor Index Scale. Structured interviews guided by 6 questions focusing on the meaning of cost and the impact on social functioning on the family were conducted. Interviews lasted 45 minutes to 1 hour. All interviews were auditaped and transcribed verbatim. Data were numbered, sorted, and coded using NVIVO software. Three researchers independently examined the data to identify thematic categories. Results: Of the 20 interviews, the meaning of cost resulted in the emergence of two themes, uncertainty and lifestyle change. Data could be further sorted into 3 underlying categories of financial, emotional and family burden. Inter-rater reliability was 91%. As a result of increased disease complexity, families seem to experience a high level of stress in terms of finances, emotional drain, and family member burden. Families who received a prenatal diagnosis verbalized economic burden as an early stressor and altered personal spending prior to birth. Perception of the economic impact of the child's condition was dependent on baseline SES. Conclusion: Although the complexity of disease seems to increase economic burden, timing of diagnosis and baseline SES were also noted to contribute to economic stress.
A 250-year high-resolution record of Pb flux and crustal enrichment in central Greenland

[1] Records of contaminant deposition from ice cores document the impact of changing emissions on remote regions. While variations in Greenland ice core Pb concentrations before and after 1970 have been attributed primarily to leaded gasoline emissions, discontinuous coarse sampling in these studies provided limited temporal resolution. Using a continuous, high-resolution record of Pb and other trace element concentrations from 1750 to 1998, we show that large, sustained increases in Pb deposition in Greenland occurred >50 years before the introduction of leaded gasoline and that non-gasoline lead contamination likely accounted for >50% of the cumulative increase in lead deposition and crustal enrichment since industrialization. After 1970, mandated emission reductions led to a >75% decline in annual lead flux, with most of the decline occurring from 1970 to 1985. Additional elemental and isotopic tracers will be needed to provide Pb provenance.
SCA window optimization in Mössbauer spectroscopy: The case of constant background

The optimum condition for setting the single channel analyzer /SCA/ has been studied with respect to the time required for data acquisition in Mossbauer spectroscopy. It has been found that, regardless what the peak height to background ratio may be, for most practical purposes the best point to cut off the constant background is where the intensity of the Mossbauer peak drops to about 20% of its full height.
Goals, Congruence, and Positive Well-Being: New Empirical Support for Humanistic Theories:

Although some have suggested that humanistic theories and quantitative methodologies are inherently contradictory, this article will try to demonstrate that they can be quite complementary. To this...
Differential glycosylation of two glycoproteins synthesized by murine B cells in response to IL-4 plus IL-5.

We sought to determine whether selected cytokines, known to stimulate profoundly B-cell activation and differentiation, also have as yet unrecognized effects upon the glycosylation of secreted Ig and/or membrane-associated proteins. The glycosylation of both secreted IgM and membrane-bound MHC Class-I synthesized by CH12LX cells was detected by enzyme-lectin conjugates in immunoabsorption assays. Stimulation of B cells with IL-4 plus IL-5 significantly decreases the terminal glycosylation of secreted IgM, whereas LPS has a minor effect, despite the fact that both stimuli are equipotent for IgM secretion. Neither LPS nor IL-4 plus IL-5 affect MHC Class-I expression. However, IL-4 plus IL-5 substantially increases the terminal glycosylation of MHC Class-I produced from both mIgM(+)and mIgA(+)CH12LX cells. LPS has no or a modest effect on the terminal glycosylation of MHC Class-I produced from CH12LX cells. These results suggest that Th(2)-derived cytokines differentially influence the glycosylation of secreted and membrane-associated glycoproteins of B cells. In turn, this might elucidate the basis of aberrant glycosylation reported in conditions such as IgA nephropathy, cancer and rheumatoid arthritis.
Effect of No-Flow Boundaries on Viscous Fingering in Porous Media of Large Aspect Ratio

We report on a boundary effect associated with the preferential propagation of viscous fingers along no-flow boundaries in miscible displacements in two-dimensional (2D) rectilinear geometries near conditions of transverse equilibrium (TE) (large values of the generalized aspect ratio RL). It is shown that this effect intensifies with an increase in the mobility ratio, and diminishes with increased permeability disorder, and as the system departs from conditions of TE. The effect disappears altogether if periodic boundary conditions are used. We show that this effect results from the violation of the no-slip condition at no-flow boundaries, associated with Darcy’s law. It must be considered in simulations of viscous fingering in relatively homogeneous media, near conditions of TE, particularly when gravity segregation occurs.
Indoramin in heart failure: Possible adverse effects on hemodynamics and exercise capacity

Indoramin is an α1-adrenergic antagonist vasodilator of potential value in heart failure. We measured hemodynamics and exercise capacity in 12 patients with heart failure, before and after 1 week of indoramin dosing, 75 mg b.i.d. Maximal hemodynamic effects 2 hours after the first dose of indoramin consisted of reduced mean systemic arterial pressure from 96.0 ± 15.3 to 87.9 ± 15.3 mm Hg (P < 0.05) and pulmonary wedge pressure from 23.6 ± 7.8 to 16.9 ± 6.6 mm Hg (P < 0.001). Heart rate, cardiac index, and total systemic resistance did not change acutely after indoramin, but after 1 week mean systemic arterial pressure was still reduced whereas cardiac index fell from 2.69 ± 0.38 to 2.32 ± 0.44 L/min/m2 (P < 0.05) and total systemic resistance rose from 20.4 ± 2.8 to 21.9 ± 4.0 U (P < 0.1). After 1 week maximal exercise oxygen uptake fell from 16.8 ± 5.6 to 12.5 ± 3.5 ml/min/kg (P < 0.02). This limited observation suggests that indoramin is a predominant venodilator acutely in patients with heart failure but that despite this effect it may worsen functional capacity and hemodyanmics during continuous dosing in these patients. Clinical Pharmacology and Therapeutics (1986) 40, 567–574; doi:10.1038/clpt.1986.225