cssi/SciSciGPT-SciSciNet huggingface dataset:
Opportunities and limitations of the exercise of foreign policy power by a very small state: the case of Trinidad and Tobago

The idea that a microstate such as Trinidad and Tobago can possess and use ‘power,’ a trait generally associated with a high level of military and economic capability, would appear to a traditional realist to be absurd. This is largely because power is still seen as exercised at the global systemic level or at regional levels that are globally significant. However, small states generally focus their foreign policies on smaller circles, primarily neighbours and dominant bilateral partners. By moving the power analysis (back) to the state (foreign policy) level, extending the definition of ‘power’ to include status (‘position’) and actual attempts to get others to adopt an influencer's preferences, and employing the newer views of power as soft and smart, this article argues that even very small states can exercise power within limited domains as long as they possess certain capabilities (in this case, energy resources) and are ready to seize available opportunities. The evidence shows, however, that the re...
Understanding electrokinetics at the nanoscale: A perspective

Electrokinetics promises to be the microfluidic technique of choice for portable diagnostic chips and for nanofluidic molecular detectors. However, despite two centuries of research, our understanding of ion transport and electro-osmotic flow in and near nanoporous membranes, whose pores are natural nanochannels, remains woefully inadequate. This short exposition reviews the various ion-flux and hydrodynamic anomalies and speculates on their potential applications, particularly in the area of molecular sensing. In the process, we revisit several old disciplines, with some unsolved open questions, and we hope to create a new one.
Designing a reverse logistics operation for short cycle time repair services

Abstract An important means for companies to differentiate themselves, as well as increase profitability, in highly competitive environments is through the use of service management, i.e., those activities and interactions which follow a product's sale. One of the most important service management activities is repair services. And the existence, effectiveness, and efficiency of service management activities, such as repair services, depend heavily on effective reverse logistics operations. Because reverse logistics operations and the supply chains they support are significantly more complex than traditional manufacturing supply chains, an organization that succeeds in meeting the challenges presents a formidable advantage that is not easily duplicated by its competitors. This paper discusses the competitive value of service management activities, particularly repair services, as well as the importance of the supporting role of effective reverse logistics operations for the successful and profitable execution of repair service activities. In addition, the manuscript presents a case study of a major international medical diagnostics manufacturer to illustrate how a reverse logistics operation for a repair service supply chain was designed for both effectiveness and profitability by achieving a rapid cycle time goal for repair service while minimizing total capital and operational costs.
Incidence and significance of decreases in systolic blood pressure during graded treadmill exercise testing.

Abstract The incidence of decreases in peak systolic blood pressure during treadmill exercise was investigated in 460 patients with definite or suspected coronary heart disease. All patients were studied with coronary cineangiography. Exercise was continued to one of the following end points: chest pain, 85 to 90 percent of the patient's age-predicted maximal heart rate, ventricular tachycardia or a sustained decrease of 10 mm Hg or more below the peak level of systolic blood pressure. Twenty-two patients with 75 percent or greater stenosis of one or more major coronary arteries manifested a decrease in systolic pressure 10 mm Hg or more during exercise. These included 15 (17 percent) of 88 patients with three vessel, 7 (7 percent) of 101 with two vessel and 0 of 90 with single vessel disease. The decrease in pressure was reproducible in the seven patients who underwent a second exercise test before alteration of therapy; this decrease was abolished in the six patients who exercised again after coronary bypass graft surgery. A decrease in systolic pressure of 10 mm Hg or more also occurred during exercise testing in 3 of 23 patients with noncoronary organic heart disease; all 3 had an obstructive cardlomyopathy that had not been suspected clinically. Only 1 of 158 subjects with chest pain and no demonstrable heart disease had a decrease in systolic blood pressure with exercise. Declines in blood pressure were not observed during 650 maximal exercise tests performed on 560 clinically normal men. In conclusion, if one excludes subjects with cardiomyopathy or significant heart valve disease, a sustained exercise-induced decrease in peak systolic blood pressure of 10 mm Hg or more is a highly specific sign of multiple vessel coronary artery disease. This phenomenon is best explained by acute left ventricular pump failure secondary to extensive myocardial ischemia.
Foraging in Tropical Rain Forests: The Case of the Penan of Sarawak, East Malaysia (Borneo)

Bailey et al. (1989) and Headland (1987) have recently proposed hypotheses stating that human foragers are unable to live in undisturbed tropical rain forests without some reliance on cultivated foods. The present discussion considers these hypotheses, as well as some of the evidence by which they have been tested. Four conceptual problems in the way these hypotheses have been formulated are identified: (1) assumptions about the relationship between key features of tropical forest ecosystems and human subsistence potential, (2) in-consistencies in the definition of “pure foraging,” (3) adherence to a dichotomy between foraging and agriculture, the result being that conscious and unconscious effects of exploitation on the demographic parameters of key resources is ignored, and (4) problems in defining the significance of ecotones. I consider the case of Penan hunter-gatherers of Borneo, a population which, by virtue of their reliance on the sago palm Eugeissona utilis, contradicts the conclusions of Bailey et al. and Headland. I consider salient aspects of Penan reliance on Eugeissona, and describe how Penan exploitation of this resource may positively effect its availability. This case is seen to provide a challenge to the hypotheses of Bailey et al. and Headland, not only in the extent to which it contradicts their conclusions but, more significantly, in what it reveals about the assumptions upon which their hypotheses are based. This points to the need for greater precision in the definition of future hypotheses about foraging in tropical forests.
ENHANCED GROWTH AND EXPERIMENTAL METASTASIS OF CHEMICALLY INDUCED TUMOR IN ULTRAVIOLET IRRADIATED SYNGENEIC MICE

— Recent studies have shown that ultraviolet (UV) irradiation induces a systemic effect which enhances subsequent tumor induction by benzo[a]pyrene in a manner which is dependent on the dose of benzo[a]pyrene. The present study was designed to test whether UV-B irradiation renders mice susceptible to subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene. The sources of UV-B irradiation were banks of 6 Westinghouse FS-40 sunlamps, situated 20 cm above the mouse cages. Female BALB/cAnNHsd received five 30-min dorsal UV-B radiation treatments per week for 12 weeks, resulting in a total dose of approx. 6.4 × 105 J m-2. Two to seven days after termination of UV treatments, syngeneic regressor tumor cells (BP2) induced by benzo[a]pyrene were injected subcutaneously or intravenously into irradiated mice and unirradiated controls. By 38 days post subcutaneous implantation, 24/30 and 3/30 BP2 implants were detectable in the irradiated and unirradiated mice, respectively. Ultraviolet irradiated mice were also unable to reject lung colonies resulting from intravenous administration of BP2 cells, although they were rejected by unirradiated mice. The mean number of lung colonies per mouse was 16- to 35-fold greater in UV irradiated mice than in unirradiated controls, at 14 to 17 days post injection. Thus, UV irradiation rendered mice, with no known exposure to benzo[a]pyrene, susceptible to a subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene.
Comparison of at-wavelenth inspection, printability, and simulation of nanometer-scale substrate defects in extreme ultraviolet lithography (EUVL)

We report on the comparison of defect printability experimental results with at-wavelength defect inspection and printability modeling at extreme ultraviolet (EUV) wavelengths. Two sets of EUV masks were fabricated with nm- scale substrate defect topographies patterned using a sacrificial layer and dry-etch process, while the absorber pattern was defined using a subtractive metal process. One set of masks employed a silicon dioxide film to produce the programmed defects, whereas the other set used chromium films. Line-, proximity- and point-defects were patterned and had lateral dimensions in the range of 0.2 micrometer X 0.2 micrometer to 8.0 micrometer X 1.5 micrometer on the EUV reticle, and a topography in the range of 8 nm - 45 nm. Substrate defect topographies were measured by atomic force microscopy (AFM) before and after deposition of EUV-reflective Mo/Si multilayers. The programmed defect masks were then characterized using an actinic inspection tool. All EUVL printing experiments were performed using Sandia's 10x- reduction EUV Microstepper, which has a projection optics system with a wavefront error less than 1 nm, and a numerical aperture of 0.088. Defect dimensions and exposure conditions were entered into a defect printability model. In this investigation, we compare the simulation predictions with experimental results.
Circuits controlling energy balance and mood: Inherently intertwined or just complicated intersections?

Recent reports of adverse psychiatric events from seemingly different types of weight loss therapies highlight a previously underestimated overlap between CNS circuits that control energy balance and those that regulate mood. In this Perspective, we discuss a few potential brain sites where the homeostatic and the hedonic pathways may intersect and suggest that a better understanding of both pathways is necessary for the development of more effective and safer antiobesity therapies.
Current therapeutic uses of lenalidomide in multiple myeloma

Thalidomide has demonstrated a broad spectrum of pharmacological and immunological effects, with potential therapeutic applications that span a wide spectrum of diseases: cancer and related conditions; infectious diseases; autoimmune diseases; dermatological diseases; and other disorders such as sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory derivative lenalidomide has more potent antitumour and anti-inflammatory effects. The molecular mechanisms of antitumour activity of lenalidomide have been extensively studied in multiple myeloma (MM). It directly induces growth arrest and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to bone marrow extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the bone marrow milieu; and augments host antitumour immunity. Importantly, lenalidomide induces significant clinical responses even in patients with relapsed/refractory MM. Therefore, lenalidomide represents a new class of antitumour agents that is useful in the treatment of MM. Lenalidomide has received fast track designation from the FDA for the treatment of MM and myelodysplastic syndromes.
Simultaneous measurement of irradiance and reflected radiance in field determination of special reflectance.

The effects of irradiation fluctuations on measured reflectance values have been determined to evaluate whether data collected in sunny or partly cloudy conditions are sufficiently in agreement that they may be used for remote or satellite sensing data collection (e.g. op discuss quantification). Simultaneous measurements were obtained of irradiance and reflected radiance using two Exotech GTR 100 mode Landsat ground-truth radiometers. (AIP)
Access strategies for revision or explantation of the Charité lumbar artificial disc replacement.

Background Several lumbar disc prostheses are being developed with the goal of preserving mobility in patients with degenerative disc disease. The disadvantage of lumbar artificial disc replacement (ADR) compared with anterior interbody fusion (ALIF) is the increased potential for displacement or component failure. Revision or removal of the device is complicated by adherence of the aorta, iliac vessels, and the ureter to the operative site. Because of these risks of anterior lumbar procedures, vascular surgeons usually provide access to the spine. We report our experience with secondary exposure of the lumbar spine for revision or explantation of the Charite disc prosthesis. Methods Between January 2001 and May 2006, 19 patients with prior implantation of Charite Artificial Discs required 21 operations for repositioning or removal of the device. Two patients had staged removal of prostheses at two levels. One patient had simultaneous explantation at two levels. The mean age was 49 years (range, 31 to 69 years; 56% men, 42% women). The initial ADR was performed at our institution in 14 patients (74%). The mean time from implantation to reoperation was 7 months (range, 9 days to 4 years). The levels of failure were L3-4 in one, L4-5 in nine, and L5-S1 in 12. Results The ADR was successfully removed or revised in all patients that underwent reoperation. Three of the 12 procedures at L5-S1 were performed through the same retroperitoneal approach as the initial access. One of these three, performed after a 3-week interval, was converted to a transperitoneal approach because of adhesions. The rest of the L5-S1 prostheses were exposed from a contralateral retroperitoneal approach. Four of the L4-5 prostheses were accessed from the original approach and five from a lateral, transpsoas exposure (four left, one right). The only explantation at L3-4 was from a left lateral transpsoas approach. Nineteen of the 22 ADR were converted to ALIF. Two revisions at L5-S1 involved replacement of the entire prosthesis. One revision at L4-5 required only repositioning of an endplate. Access-related complications included, in one patient each, iliac vein injury, temporary retrograde ejaculation, small-bowel obstruction requiring lysis, and symptomatic, large retroperitoneal lymphocele. There were no permanent neurologic deficits, deep vein thromboses, or deaths. Conclusions Owing to vascular and ureteral fixation, anterior exposure of the lumbar spine for revision or explantation of the Charite disc replacement should be performed through an alternative approach unless the procedure is performed ≤2 weeks of the index procedure. The L5-S1 level can be accessed through the contralateral retroperitoneum. Reoperation at L3-4 and L4-5 usually requires explantation and fusion that is best accomplished by way of a lateral transpsoas exposure.
Optimization of Exciton Trapping in Energy Transfer Processes

In this paper, we establish optimal conditions for maximal energy transfer efficiency using solutions for multilevel systems and interpret these analytical solutions with more intuitive kinetic networks resulting from a systematic mapping procedure. The mapping procedure defines an effective hopping rate as the leading order picture and nonlocal kinetic couplings as the quantum correction, hence leading to a rigorous separation of thermal hopping and coherent transfer useful for visualizing pathway connectivity and interference in quantum networks. As a result of these calculations, the dissipative effects of the surrounding environments can be optimized to yield the maximal efficiency, and modulation of the efficiency can be achieved using the cumulative quantum phase along any closed loops. The optimal coupling of the system and its environments is interpreted with the generic mechanisms: (i) balancing localized trapping and delocalized coherence, (ii) reducing the effective detuning via homogeneous line-broadening, (iii) suppressing the destructive interference in nonlinear network configurations, and (iv) controlling phase modulation in closed loop configurations. Though these results are obtained for simple model systems, the physics thus derived provides insights into the working of light harvesting systems, and the approaches thus developed apply to large-scale computation.
Automated Sample Mounting and Alignment System for Biological Crystallography at a Synchrotron Source

High-throughput data collection for macromolecular crystallography requires an automated sample mounting and alignment system for cryo-protected crystals that functions reliably when integrated into protein-crystallography beamlines at synchrotrons. Rapid mounting and dismounting of the samples increases the efficiency of the crystal screening and data collection processes, where many crystals can be tested for the quality of diffraction. The sample-mounting subsystem has random access to 112 samples, stored under liquid nitrogen. Results of extensive tests regarding the performance and reliability of the system are presented. To further increase throughput, we have also developed a sample transport/storage system based on "puck-shaped" cassettes, which can hold sixteen samples each. Seven cassettes fit into a standard dry shipping Dewar. The capabilities of a robotic crystal mounting and alignment system with instrumentation control software and a relational database allows for automated screening and data collection to be developed.
Hematologic studies on dogs receiving low doses of total body irradiation.

Summary and Conclusion1. Data showing qualitative and quantitative differences in the peripheral blood and bone jmarrow of the dog following administration of single or divided doses of 100 r total body irradiation presented. 2. The accepted pattern of leukocytic radiosensitivity (lymphocyic > granulocytic) is observed after admionistration of 100 r in one dose or in 2 doses of 50 r. 3. Administration of 10 or 25 r per dose shows a reversal of this sensitivity apparent in the occurrence of an increased number of granulocytes in the blood and bone marrow in the absence in band forms in the post-irradiation biopsy specimen indicates an increase in maturation in the bone marrow. 5. The sudy of the peripheral blood may be valuabel as an indicator of bone marrow activity when only small doses of x-ray are used.
A new method for determining critical pulse width in laser material processing

By scribing narrow line grooves on a metal sample surface with short laser pulses having a scanned pulse width from 14 ps to 40 fs, and then examining the pattern of debris, we demonstrate a simple method for determining the critical pulse width in laser material processing beyond damage threshold.
Mentoring the Parentified Child: The Professional Development of the Latina(O) Psychologist:

Psychology graduate programs actively recruit Latino students. Nonetheless, Latino students remain a minority in their classes, clinical training programs, and professions. Given the paucity of Lat...
Mitigating effects on STAP processing caused by an inclined array

This paper presents several techniques for mitigating the effects of an inclined linear array on STAP algorithms. A new technique, termed Doppler Warping is shown to completely mitigate the effects of the array inclination on the STAP algorithm by shifting the Doppler filters to track the Doppler frequency variation of clutter over range. After establishing the effects of array inclination on STAP algorithms, several techniques are presented to reduce the array inclination effects. Doppler Warping is shown to be computationally very inexpensive and to completely mitigate the effects of array inclination. Covariance analysis results are presented.
Real-Time Models of Electrostatically Actuated Cantilever Probes With Integrated Thermal Sensor for Nanoscale Interrogation

Microcantilevers with integrated thermal sensor for topography measurement, which can be electrostatically actuated, are well suited for a highly parallel dynamic-mode operation where multiple cantilevers scan the media. Interpretation of data in dynamic-mode operation utilizing such cantilevers is complex because of diverse forces acting on the cantilever that include electrostatic, interatomic, structural, thermal, and, possibly, magnetic forces. In addition, the thermal sensor introduces new dynamics making interpretation of measured data challenging. In this paper, tractable models that are suited for real-time purposes, which can quantitatively predict the cantilever motion and the thermal-sensor measurement, are presented. Furthermore, it is demonstrated that all parameters of the model can be estimated solely from thermal-sensor data. This paper also provides a comprehensive understanding of the dynamics of the thermal sensor.
Predictors of complications associated with closure devices after transfemoral percutaneous coronary procedures.

To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 8092273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints@aacn.org. devices approved by the Food and Drug Administration have replaced manual compression and are associated with decreased length of stay and increased comfort and satisfaction for patients. These devices include an implantable collagen plug (VasoSeal, Datascope Corp, Montvale, NJ) and a percutaneous suture device (Perclose, Perclose, Inc, Redwood City, Calif ). Compared with traditional methods used to achieve hemostasis, these closure devices have high overall levels of safety and efficacy. Major complications such as vascular repair surgery, bleeding requiring transfusion, and infection associated with the collagen plug are 2.9%, and the incidence of minor complications, including hematoma, bleeding, and pseudoaneurysm, is 7.2% or less. Complications associated with the percutaneous suture device are 11% or less. Despite these remarkable statistics, identification of risk factors and predictors of complications Jenny B. Hamner, RN, DSN, CCRN E. Jean Dubois, RN, MSN, CRNP Tanya P. Rice, RN, BSN Transfemoral percutaneous coronary procedures have evolved in the past several years as a mainstay in both diagnostic and interventional cardiology. However, safe management of vascular access sites after removal of percutaneous catheters remains a serious concern. Manual compression of the site, the traditional method for closure of the femoral artery, is associated with a complication rate of up to 5%, marked discomfort and immobility for patients, and prolonged hospitalization. New techniques for management of vascular access sites after diagnostic or interventional transfemoral percutaneous coronary procedures have been introduced to increase patients’ comfort and promote a safe recovery. Specifically, new vascular closure ClinicalArticle
Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders

The tyrosine kinase inhibitor imatinib mesylate inhibits the function of the Bcr-Abl oncoprotein associated with Philadelphia-positive chronic myelogenous leukemia (CML). Anagrelide suppresses megakaryocyte proliferation and differentiation. The objectives of this study were to investigate the feasibility and safety of imatinib mesylate and anagrelide combination therapy in patients with Ph-positive CML or chronic myeloproliferative disorders (MPD) with persistent thrombocythemia. This study was a retrospective review of all available records of patients with chronic MPD presenting to the M.D. Anderson Cancer Center between October 1998 and May 2002, treated with imatinib mesylate combined with anagrelide. Of 22 patients identified, 18 had Ph-positive CML (chronic phase, 16 patients; accelerated phase, 2 patients), 1 had agnogenic myeloid metaplasia (AMM), 2 had essential thrombocythemia (ET) and 1 had MPD transformed into refractory anemia with excess blasts (RAEB). The median age was 57 years (range 26–82 years). The median dose of imatinib mesylate administered was 400 mg (range 300–800 mg) and the median dose of anagrelide was 1.5 mg (range 0.5–4.0 mg). Imatinib mesylate and anagrelide combination therapy was feasible and tolerable. Of the 18 patients with Ph-positive CML, 15 in chronic phase and 1 in accelerated phase achieved a complete hematologic response (CHR), and 9 of the 18 achieved cytogenetic response (complete in 8 patients). No responses were noted in patients with AMM, ET or MPD transformed into RAEB. The combination of imatinib mesylate and anagrelide was safe and was associated with an 89% CHR rate in patients with CML in chronic phase and persistent thrombocythemia.
A Shrinkage Approach for Modeling Non-stationary Relational Autocorrelation

Recent research has shown that collective classification in relational data often exhibit significant performance gains over conventional approaches that classify instances individually. This is primarily due to the presence of autocorrelation in relational datasets, meaning that the class labels of related entities are correlated and inferences about one instance can be used to improve inferences about linked instances. Statistical relational learning techniques exploit relational autocorrelation by modeling global autocorrelation dependencies under the assumption that the level of autocorrelation is stationary throughout the dataset. To date, there has been no work examining the appropriateness of this stationarity assumption. In this paper, we examine two real-world datasets and show that there is significant variance in the autocorrelation dependencies throughout the relational data graphs. We develop a shrinkage technique for modeling this non-stationary autocorrelation and show that it achieves significant accuracy gains over competing techniques that model either local or global autocorrelation dependencies in isolation.
An Empirical Analysis of the Demand for Multiple Peril Crop Insurance

Knowledge of factors affecting farmer purchases of crop insurance is essential for evaluating the soundness and profitability of crop insurance programs. Despite this importance, the demand for crop insurance has received limited empirical attention. The present paper reports on an empirical assessment of the demand for crop insurance by Iowa corn producers. Adverse selection in the insured pool suggests that producers with differing levels of loss-risk have different demand elasticities. Loss-risk is included in the empirical analysis and is found to influence the elasticity of demand. Results show average demand elasticities of about −0.32 for relative insured acres and −0.73 for liability per planted acre. Implications for the actuarial soundness of the industry are provided.
On-chip test generation for combinational circuits by LFSR modification

A new on-chip test generation technique based on the built-in self test (BIST) and deterministic test generation concepts has been proposed. Given a test set, the test patterns can be regenerated on the chip and applied to the circuit under test without the use of any external test equipments. A systematic procedure for the modification of a basic linear feedback shift register (LFSR) to realize the on-chip test generation hardware is given. Since the delay introduced by the modification of the LFSR is only two gate delays, at-speed testing of circuits is feasible. Experiments are conducted and test application time and hardware overhead are compared with a known test technique under the same fault coverage conditions. It is shown that both test cost and test application time can be decreased significantly by using the proposed technique.
Constraint Management of Reduced Representation Variables in Decomposition-Based Design Optimization

In decomposition-based design optimization strategies, such as Analytical Target Cascading (ATC), it is sometimes necessary to use reduced dimensionality representations to approximate functions of large dimensionality whose values need to be exchanged among subproblems. The reduced representation variables may not be physically meaningful, and it can become challenging to constrain them properly and define the model validity region. For example, in coordination strategies like ATC, representing vector-valued coupling variables with improperly constrained reduced representation variables can lead to poor performance or convergence failure. This paper examines two approaches for constraining effectively the model validity region of reduced representation variables based on proper orthogonal decomposition: a penalty value-based heuristic and a support vector domain description. An ATC application on electric vehicle design helps to illustrate the concepts discussed.
Labor Mismatch and Skill Premia

Contrary to the predictions of the 2 × 2 × 2 Heckscher–Ohlin model, empirical evidence shows that trade liberalization causes the skill premium to increase in some developing countries and to decrease in others. This paper develops a North–South model in which complex and simple goods are produced. The former is produced using skilled workers, while the latter is produced using skilled and unskilled workers. Labor markets feature search frictions. In this context, trade liberalization increases the skill premium in the North, while the impact on the skill premium in the South depends on skill abundance. The higher the skill abundance in a developing country, the higher the average productivity among skilled workers compared with unskilled workers. This leads to a higher employment of skilled workers in simple occupations, or labor mismatch. Therefore, the increase in the price of the simple good in the South, due to trade liberalization, leads to an increase in the wage of the mismatched workers. This offsets any negative impact on the skill premium caused by the decrease in the wage of skilled workers in complex occupations or the increase in the wage of unskilled workers in simple occupations. The opposite impact on the skill premium takes place in countries that are less skill abundant in the South. A threshold empirical estimation, on 50 developing and developed countries, shows that there is a statistically significant skill abundance threshold, below which the coefficient on the relationship between openness and wage inequality is negative and above which the estimate is positive.
Species Extrapolation of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models to Investigate the Developmental Toxicology of Ethanol Using In vitro to In vivo (IVIVE) Methods

To provide useful alternatives to in vivo animal studies, in vitro assays for dose-response assessments of xenobiotic chemicals must use concentrations in media and target tissues that are within biologically-plausible limits. Determining these concentrations is a complex matter, which can be facilitated by applying physiologically-based pharmacokinetic (PBPK) models in an in vitro to in vivo extrapolation (IVIVE) paradigm. We used ethanol (EtOH), a ubiquitous chemical with defined metrics for in vivo and in vitro embryotoxicity, as a model chemical to evaluate this paradigm. A published series of life-stage PBPK models for rats was extended to mice, yielding simulations that adequately predicted in vivo blood EtOH concentrations (BECs) from oral, intraperitoneal, and intravenous routes in nonpregnant and pregnant adult mice. The models were then extrapolated to nonpregnant and pregnant humans, replicating BEC data within a factor of two. The rodent models were then used to conduct IVIVEs for rodent and whole-embryo culture embryotoxicity data (neural tube closure defects, morphological changes). A second IVIVE was conducted for exposure scenarios in pregnant women during critical windows of susceptibility for developmental toxicity, such as the first 6-to-8 weeks (prerecognition period) or mid-to-late pregnancy period, when EtOH consumption is associated with fetal alcohol spectrum disorders. Incorporation of data from human embryonic stem cell studies led to a model-supported linkage of in vitro concentrations with plausible exposure ranges for pregnant women. This effort demonstrates benefits and challenges associated with use of multispecies PBPK models to estimate in vivo tissue concentrations associated with in vitro embryotoxicity studies.
Determinants of impedance during radiofrequency catheter ablation in humans.

Radiofrequency catheter ablation has become the treatment of choice for selected patients with paroxysmal supraventricular tachycardia due to atrioventricular node reentry or the Wolff-Parkinson-White syndrome. 1–3 Despite encouraging results described in several series, the optimal energy delivery strategy has not been defined. Lesion formation occurs during radiofrequency ablation as the result of resistive heating at the electrode-tissue interface.4 The magnitude of heat generation is proportional to power density at the point of contact.5 Electrosurgical units currently being used for radiofrequency ablation have a low source impedance and therefore approximate constant voltage sources. With such a device, one preselects a given output voltage. Applied power is proportional to the square of this output voltage and is inversely proportional to the load impedance imposed by the ablation catheter, patient and indifferent electrode. Thus, the effectiveness of any given energy application may be influenced by the impedance of the system. This study characterizes impedance during radiofrequency catheter ablation in humans, and defines the relation between clinical and ablation parameters, and measured impedance.
Mechanistic interpretation of CO oxidation turnover rates on supported Au clusters

Kinetic and isotopic data are used to interpret the mechanistic role of gaseous H2O molecules and of nonreducible (Al2O3) and reducible (TiO2 ,F e 2O3) supports on CO oxidation turnovers catalyzed by small Au clusters (<5 nm). H2O acts as a co-catalyst essential for O2 activation and for catalyst stability in CO oxidation at near-ambient temperatures, but also inhibits rates via competitive adsorption at higher H2O pressures. The effects of CO, O2, and H2O pressures on CO oxidation turnover rates, the absence of 16 O2/ 18 O2 and 16 O2/H2 18 O exchange, and the small H2O/D2O kinetic isotope effects are consistent with quasi-equilibrated molecular adsorption of CO, O2, and H2O on Au clusters with the kinetic relevance of H2O-mediated O2 activation via the formation of hydroperoxy intermediates ( � OOH), which account for the remarkable reactivity and H2O effects on Au clusters. These elementary steps proceed on Au clusters without detectable requirements for support interface sites, which are no longer required when H2O is present and mediates O2 activation steps. Rate enhancements by H2O were also observed for CO oxidation on Pt clusters (1.3 nm), which is also limited by O2 activation steps, suggesting H2O-aided O2 activation and � OOH species in oxidations involving kinetically-relevant O2 activation. These intermediates
Bcl-2-mediated inhibition of apoptosis in rat cardiac allografts worsens development of graft coronary artery disease

Abstract Background: We hypothesized that adenovirally mediated Bcl-2 transfection of donor hearts would reduce the apoptosis that occurs during acute rejection while worsening the development of chronic graft coronary artery disease (GCAD). Methods: PVG donor hearts were treated with either AdvBcl-2 or AdvNull virus before heterotopic transplantation into ACI rats. Bcl-2 expression was assessed on post-operative day 4 (POD) 4 by western blot. Apoptosis was measured using 99m Technetium-bound–annexin V imaging and caspase 3 activity assay. Allograft survival was determined in a separate cohort of animals. Long-term–treated animals were then assessed for measures of GCAD on POD 90. Results: Western blot analysis showed upregulation of Bcl-2 expression in AdvBcl-2–treated hearts. 99m Tc–annexin V images demonstrated decreased uptake in the AdvBcl-2 group (1.41 ± 0.33% vs 1.94 ± 0.37%, p = 0.026). Caspase 3 activity was also significantly lower in this treatment group (0.112 ± 0.032 vs 0.204 ± 0.096, p = 0.049). Allograft survival was similar in both groups, respectively (7.7 ± 1.2 vs 6.8 ± 1.5 days, p = 0.340). GCAD, as determined by percent luminal narrowing (5.9 ± 6.1% vs 1.6 ± 1.5%, p = 0.039), intima-to-media ratio (5.1 ± 5.1% vs 1.5 ± 1.7%, p = 0.040) and percent of affected vessels (15.1 ± 9.9% vs 5.3 ± 4.4%, p = 0.009), was higher for the AdvBcl-2 group. Conclusion: Treatment of cardiac allografts with AdvBcl-2 resulted in a reduction of apoptosis that did not significantly improve short-term graft survival, but worsened chronic GCAD.
Using Benefit and Cost Information to Evaluate a Food Safety Regulation: HACCP for Meat and Poultry

In July 1996, U.S. Department of Agriculture's (USDA) Food Safety and Inspection Service (FSIS) promulgated the Hazard Analysis and Critical Control Point (HACCP) regulation for meat and poultry plants. Each plant is required to develop a HACCP plan,' subject to FSIS approval and verification. Based on risk assessment, HACCP is expected to be more effective in removing pathogens from meat and poultry than current visual inspection (NAS). In this paper we apply the opportunity cost paradigm to examine industry costs of complying with HACCP, conduct a sensitivity analysis for the benefits component, and discuss economic incentives from HACCP.
Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor

Multiple nuclear transcription factors including E-26-like protein 1 (Elk-1) have been found in neuronal dendrites, yet the functional significance of such localization has not yet been explained. Here we use a focal transfection procedure, 'phototransfection', to introduce Elk1 mRNA into specific regions of live, intact primary rat neurons. Introduction and translation of Elk1 mRNA in dendrites produced cell death, whereas introduction and translation of Elk1 mRNA in cell bodies did not produce cell death. Elk-1 translated in dendrites was transported to the nucleus, and cell death depended upon transcription, supporting the dendritic imprinting hypothesis and highlighting the importance of the dendritic environment on protein function. Our demonstration of the utility of phototransfection for spatially controlled introduction of mRNAs opens the broader opportunity to use this method to introduce selected quantities of small molecules into discrete regions of live cells to assess their biological functions.
Breaking down the barriers: fMRI applications in pain, analgesia and analgesics

This review summarizes functional magnetic resonance imaging (fMRI) findings that have informed our current understanding of pain, analgesia and related phenomena, and discusses the potential role of fMRI in improved therapeutic approaches to pain. It is divided into 3 main sections: (1) fMRI studies of acute and chronic pain. Physiological studies of pain have found numerous regions of the brain to be involved in the interpretation of the 'pain experience'; studies in chronic pain conditions have identified a significant CNS component; and fMRI studies of surrogate models of chronic pain are also being used to further this understanding. (2) fMRI studies of endogenous pain processing including placebo, empathy, attention or cognitive modulation of pain. (3) The use of fMRI to evaluate the effects of analgesics on brain function in acute and chronic pain. fMRI has already provided novel insights into the neurobiology of pain. These insights should significantly advance therapeutic approaches to chronic pain.
Transient current propagation along a wire penetrating a circular aperture in an infinite planar conducting screen

The shielding properties of a wire penetrating an infinite planar screen are considered. Time domain results are presented for the case of a transient current pulse propagating along the wire. These results are obtained by first computing numerical solutions for the problem in the frequency domain and then utilizing the inverse Fourier transform. Two double exponential pulses with differing characteristics are considered. Numerical results for the two pulses are compared to determine the effects of the pulse characteristics on the shielding properties of the geometry. Applications to via structures in high-speed circuits are also briefly discussed. It is observed that even for very small apertures, the effect of the screen on the low-frequency pulse is negligible. As the pulse width decreases, the effect of the screen becomes more prominent. For the high-frequency case, the pulse is significantly affected by the screen. Unlike the low-frequency pulse, the amplitude of the high-frequency pulse is dependent on the aperture size. Even for large apertures, the attenuation becomes significant as the current propagates down the wire. It is shown that as the width of the input pulse decreases, the distortion in the pulse shape becomes more pronounced. This effect is especially important in applications related to high-speed integrated circuits. >
From hot dogs to host cells: how the bacterial pathogen Listeria monocytogenes regulates virulence gene expression

Environmental pathogens are organisms that normally spend a substantial part of their lifecycle outside of human hosts, but when introduced into humans are capable of causing disease. Such organisms are often able to transition between disparate environments ranging from the soil to the cytosol of host cells. The food-borne bacterial pathogen Listeria monocytogenes serves as a model system for understanding how an environmental organism makes the transition into mammalian hosts. A transcriptional regulatory protein known as PrfA appears to serve as a critical switch, enabling L. monocytogenes to transition from the outside environment to life within the host cell cytosol. PrfA is required for the expression of many L. monocytogenes gene products associated with virulence, and multiple mechanisms serve to regulate the expression and activity of PrfA. Increasing evidence suggests that specific environmental stresses help prime L. monocytogenes for life within the host, and cross-talk between the stress resp...
A new control for multi-phase buck converter with fast transient response

The new high performance microprocessors require the power supply to provide high current, fast transient response, and tight voltage regulation. Interleaved multiphase synchronous buck converters have recently been adopted in the industry to meet the requirements. To achieve current sharing among the multiple phases, a new control scheme is developed to combine current mode control with V/sup 2/ control. It has the advantages of fast transient speed, inherent current shaking and easy compensation. In this paper, the principle and implementation of the new control is presented and the transient response is shown. The small signal model of multiphase converter with the new control is derived and applied in converter analysis and voltage loop compensation.
COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members.

Background The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. Methods The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. Results Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P 0.10). Conclusion The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history.
Compulsory Licensing for Public Health Needs: The TRIPS Agenda at the WTO after the Doha Declaration on Public Health

Paragraph 6 of the Doha Declaration directs the WTO Council for TRIPS (“TRIPS Council”) to address the problems that Members with insufficient or no manufacturing capacity may have in making effective use of compulsory licensing, and to report to the General Council by the end of 2002. Paragraph 6 frames in a rather limited way a set of concerns raised by developing Members. This set of concerns relates to the foreseeable reduction of off-patent medicines that will be available for export and import as TRIPS Agreement transition periods applicable to developing and least developed countries expire. It concerns the ability of Members to grant compulsory licenses that predominantly supply import markets of other Members, and the right of Members to make use of the Article 30 TRIPS Agreement exception to authorize the making and export of pharmaceutical products. Ultimately, it implicates deeper concerns regarding restrictions the TRIPS Agreement imposes on Members in the adoption of exceptions to patenting and on safeguard measures taken to address public health needs. This paper addresses in detail options for amending the TRIPS Agreement to fulfill the objective of the Doha Declaration to promote access to medicines for all.
Race, Reform, and Regulation of the Electoral Process: Democracy in the United States, 2020 and Beyond

Developing a research agenda to support a decade-long process of electoral reform requires, first, determining how ambitious reform goals should be for a single decade. This paper proposes a moderately ambitious goal of a “state of the art” voting infrastructure, in comparison to even more ambitious possibilities, and describes some of its key features - including “war-gaming” exercises to test for vulnerabilities and a Model Code to resolve disputes over the counting of presidential ballots.