cssi/SciSciGPT-SciSciNet huggingface dataset:
Mueller tensor approach for nonlinear optics in turbid media

As plane-polarized light propagates through a turbid medium, scattering alters the phase and polarization differently in different locations. The corresponding depolarization of the beam complicates recovery of the rich information content contained within the polarization-dependence of second harmonic generation (SHG) microscopy. A theoretical framework connecting Jones and Stokes formalisms for describing optical polarization allows prediction of the polarization-dependent SHG produced from “ballistic”, but depolarized incident light. Measurements with collagen-rich tissue sections support the predictions of the framework. Partially polarized SHG produced from a depolarized source enabled recovery of local orientation distribution for collagen and local tensor information. Bridging the gap between SHG instigated by fully depolarized light and partially polarized light more common to practical turbid systems, a method for predicting local nonlinear optical susceptibility tensor elements was developed and applied to collagen in thick sections. Recovered values for the tensor element ratio ρ are in good agreement with previous results for thin tissue and literature reports.
Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women

Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.
Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease

The genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel disease and juvenile idiopathic arthritis are both clinically heterogeneous and known to be due in part to abnormal regulation of gene activity in diverse immune cell types. Comparative genomic analysis of these conditions is expected to reveal differences in underlying genetic mechanisms of disease. We performed RNA-Seq on whole blood samples from 202 patients with oligoarticular, polyarticular, or systemic juvenile idiopathic arthritis, or with Crohn’s disease or ulcerative colitis, as well as healthy controls, to characterize differences in gene expression. Gene ontology analysis combined with Blood Transcript Module and Blood Informative Transcript analysis was used to infer immunological differences. Comparative expression quantitative trait locus (eQTL) analysis was used to quantify disease-specific regulation of transcript abundance. A pattern of differentially expressed genes and pathways reveals a gradient of disease spanning from healthy controls to oligoarticular, polyarticular, and systemic juvenile idiopathic arthritis (JIA); Crohn’s disease; and ulcerative colitis. Transcriptional risk scores also provide good discrimination of controls, JIA, and IBD. Most eQTL are found to have similar effects across disease sub-types, but we also identify disease-specific eQTL at loci associated with disease by GWAS. JIA and IBD are characterized by divergent peripheral blood transcriptomes, the genetic regulation of which displays limited disease specificity, implying that disease-specific genetic influences are largely independent of, or downstream of, eQTL effects.
Therapy of Nonexudative Age-Related Macular Degeneration

Age related macular degeneration (AMD) is the leading cause of blindness among adults over the age of 65 in the Western world. The prevalence of AMD is expected to increase dramatically, from 1.75 million in 2000 to 2.95 million in 2020, due to the rapidly aging population. Given the large and now increasing burden of disease, the identification of modifiable risk factors and new avenues for preventive treatment has become increasingly important. The pathogenesis of macular degeneration is multi-factorial with genetic, environmental, and physiologic components. The retina is uniquely susceptible to oxidative damage, given its high metabolic activity and daily exposure to light. In addition, the presence of large numbers of lipids with double bonds makes it an ideal target for reactive oxygen species. The increasing incidence of macular degeneration with advancing age may be related to gradual dysfunction and degeneration of retinal tissues as oxidative damage accumulates. This cumulative damage may result in physiologic dysfunction, in addition to impaired auto-regulation with restricted exchange and processing of nutrients and metabolic byproducts with progressive disease. Nutrients which may modulate this oxidative damage include lutein, zeaxanthin, beta-carotene, C, E, and B vitamins, and zinc. A growing body of scientific evidence also implicates inflammatory processes in the pathogenesis and progression of macular degeneration. Clinical evidence suggests a role for a combination of antioxidants in reducing progression of AMD and a potential role for omega-3 fatty acids and macular xanthophylls in the prevention and treatment of macular degeneration. The Age Related Eye Disease Study 2 (AREDS2) will further examine the role of these micronutrients in the treatment of AMD.
Feasibility of using O-18 for PET proton beam range verification

103 Objectives Accurate estimation of the Bragg-peak distal edge (BPDE) location is crucial in proton therapy dose delivery. Current range verification techniques include PET imaging which takes advantage of the β+ emitters produced following proton interaction within the patient body. However, such interactions produce negligible PET signal at the BPDE due largely to the decrease in proton energy with depth, which reduces the efficiency of β+ emitter production. The radionuclides produced also have a short half life (t1/2). Our objective is to investigate the feasibility of overcoming this limitation by infusing O-18 into the treatment volume and producing F-18 through the 18O(p,n)18F interaction while leveraging the longer F-18 t1/2 and its lower interaction cross section energy threshold. Methods Two sets of three water samples (98% O-18, 10% O-18, and 100% O-16) located at the center of modulation (COM) and at the BPDE were irradiated with a 155-MeV proton beam for 10 min. The samples were then counted in a gamma counter (GC) and imaged using microPET. In addition, two 2 mm thick water samples (98% O-18 and 100% O-16) were placed at each of four depths near the BPDE and were irradiated with a 160-MeV proton beam for 10 min. All samples were counted in a GC. Results GC results at COM showed an initial higher signal from 100% O-16 water which was surpassed by 98% O-18 water after 20 min from the onset of irradiation. The microPET images at 20 min post irradiation showed that 98% 18O water had much higher signal intensity at COM and BPDE compared to the 100% O-16. Results from the water samples at varying BPDE locations showed the 98% O-18 consistently had a higher count density than 100% O-16 suggesting that O-18 activation could lead to better BPDE identification. Conclusions 18O-enriched water results in a higher PET signal than does endogenous O-16 following proton beam irradiation. The signal increase should improve the determination of the BPDE location and may provide a reliable method of proton beam range verification
Clinical Decision Support Systems: Impacting the Future of Clinical Decision Making

With the increased focus on the prevention of medical errors that has occurred since the publication of the landmark Institute of Medicine report, To Err Is Human, computer-based physician order entry (CPOE) systems have been proposed as a key element of systems approaches to improving patient safety [1–4]. While CPOE systems alone can eliminate several types of errors, their major impact will be when they are linked to clinical decision support systems. Clinical decision support systems (CDSS) are computer systems designed to influence clinician decision making about individual patients when these decisions are made. If used properly, they have the potential to change the way medicine has been taught and practiced. This chapter will illustrate several types of CDSS, summarize current data on the use and effect of CDSS in practice, and will provide guidelines for users to consider as these systems begin to be incorporated in commercial systems and implemented outside the research and development settings.
Roughness-Induced Superomniphobic Surfaces: Lessons from Nature

Self-cleaning surfaces are of interest in various applications, including self-cleaning windows, windshields, exterior paints for buildings and navigation ships, utensils, roof tiles, textiles, and solar panels. Low adhesion and drag reduction in fluid flow is of interest in many applications including micro-/nanofluidics-based biosensor applications (Bhushan, 2010). To reduce pressure drop and volume loss in micro-/nanochannels, it is desirable to minimize the drag force in the solid–liquid interface. Low adhesion/drag also exhibits antifouling of interest in various applications including membranes used in desalination and water purification (Bixler and Bhushan,2012).
Evaluating regional climate-electricity demand nexus: A composite Bayesian predictive framework

Abstract Climatic variations significantly influence the shape of end-use electricity demand curves. Although the climate sensitivity of end-use electricity demand is well-established, projecting medium- and long-term future demand remains a significant challenge—mostly due to a multitude of uncertainties involved in the modeling process. In this paper, we leveraged a state-of-the-art Bayesian approach to develop rigorously validated regional prediction models of the climate–demand nexus conditioned on the intensity level of demand. The prediction models were developed for the residential and commercial sectors for the top eight energy-intensive states in the U.S. A key contribution of this work was to illustrate the asymmetry in the sensitivity of load to climate. More specifically, our results demonstrated a greater sensitivity of the high-intensity end-use demand to climate variability as compared to the moderate-intensity end-use demand. In addition, our results helped identify mean dew point temperature as the key predictor of the climate-sensitive portion of both residential and commercial electricity demands, irrespective of the demand intensity levels. Wind speed was identified as the second most important predictor of the high-intensity (i.e., ≥ 3rd quartile) end-use demand, while electricity price was found to be the key predictor of the moderate-intensity (i.e.,
Treatment Patterns and Outcomes Associated With Palbociclib Plus Letrozole for Postmenopausal Women With HR−/HER2− Advanced Breast Cancer Enrolled in an Expanded Access Program

Abstract Purpose To evaluate treatment patterns and clinical outcomes of patients who received palbociclib in combination with letrozole in any line of therapy for treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer in an expanded access program (EAP) in the United States. Patients and Methods A retrospective chart review study was conducted of patients previously enrolled in the palbociclib EAP. Complete data from time of initial diagnosis of metastatic breast cancer until date of chart abstraction were obtained. Clinical outcomes as assessed by site investigators included clinical benefit rate, progression-free survival, and overall survival. Survival was descriptively assessed using Kaplan-Meier methods. Results Of 238 patients enrolled in the EAP, data from 126 patients were included. Median age was 62.5 years at EAP enrollment; 25% had de novo metastatic disease. Visceral disease was present in 71% of patients. The disease of most patients was heavily pretreated; nearly 60% of patients had received 3 or more prior lines for metastatic disease before initiating palbociclib + letrozole therapy. Most patients (87%) had received prior endocrine therapy, and 68% had received prior chemotherapy for metastatic disease. Patients with prior endocrine therapy for metastatic disease had a clinical benefit rate of 30%, while those with prior chemotherapy had a 26% clinical benefit rate. Patients receiving 2 or more prior lines had 6- and 12-month progression-free survival rates of 35% and 21%, respectively, and 12- and 24-month overall survival rates of 62% and 35%, respectively. Conclusion Most patients derived benefit from palbociclib + letrozole treatment despite having received multiple prior treatment lines for metastatic disease.
Detectability, Duality, and Surplus Extraction

We study surplus extraction in the general environment of McAfee and Reny (1992), and provide two alternative proofs of their main theorem. The first is an analogue of the classic argument of Cremer and McLean (1985, 1988), using geometric features of the set of agentsâ beliefs to construct a menu of contracts extracting the desired surplus. This argument, which requires a finite state space, also leads to a counterexample showing that full extraction is not possible without further significant conditions on agentsâ beliefs or surplus, even if the designer offers an infinite menu of contracts. The second argument uses duality and applies for an infinite state space, thus yielding the general result of McAfee and Reny (1992). Both arguments suggest methods for studying surplus extraction in settings beyond the standard model.
Nonreciprocal Components Based on Switched Transmission Lines

Nonreciprocal components, such as isolators and circulators, are critical to wireless communication and radar applications. Traditionally, nonreciprocal components have been implemented using ferrite materials, which exhibit nonreciprocity under the influence of an external magnetic field. However, ferrite materials cannot be integrated into IC fabrication processes and, consequently, are bulky and expensive. In the recent past, there has been strong interest in achieving nonreciprocity in a nonmagnetic IC-compatible fashion using spatio-temporal modulation. In this paper, we present a general approach to nonreciprocity based on switched transmission lines. Switched transmission lines enable broadband, lossless, and compact nonreciprocity and a wide range of nonreciprocal functionalities, including nonreciprocal phase shifters, ultra-broadband gyrators and isolators, frequency-conversion isolators, and high-linearity/high-frequency/ultra-broadband circulators. We present a detailed theoretical analysis of the various nonidealities that impact insertion loss and provide design guidelines. The theory is validated by experimental results from discrete-component-based gyrators and isolators and a 25-GHz circulator fabricated in a 45-nm SOI CMOS technology.
POEM for Esophageal Achalasia.

Over the past decade, per-oral endoscopic myotomy has been shown to be a durable minimally invasive approach to the treatment of esophageal achalasia. Patients with suspected achalasia should under...
A primer on single-cell genomics in myeloid biology.

Purpose of review Understanding the fast-moving field of single-cell technologies, as applied to myeloid biology, requires an appreciation of basic molecular, informatics, and biological concepts. Here, we highlight both key and recent articles to illustrate basic concepts for those new to molecular single-cell analyses in myeloid hematology. Recent findings Recent studies apply single-cell omics to discover novel cell populations, construct relationships between cell populations, reconfigure the organization of hematopoiesis, and study hematopoietic lineage tree and fate choices. Accompanying development of technologies, new informatic tools have emerged, providing exciting new insights. Summary Hematopoietic stem and progenitor cells are regulated by complex intrinsic and extrinsic factors to produce blood cell types. In this review, we discuss recent advances in single-cell omics to profile these cells, methods to infer cell type identify, and trajectories from molecular omics data to ultimately derive new insights into hematopoietic stem and progenitor cell biology. We further discuss future applications of these technologies to understand hematopoietic cell interactions, function, and development. The goal is to offer a comprehensive overview of current single-cell technologies and their impact on our understanding of myeloid cell development for those new to single-cell analyses.
Hitting the Vasopressor Ceiling: Finding Norepinephrine Associated Mortality in the Critically Ill

Abstract Background There is no consensus on what dose of norepinephrine corresponds with futility. The purpose of this study was to investigate the maximum infusion and cumulative doses of norepinephrine associated with survival for patients in medical and surgical intensive care units (MICU and SICU). Materials and Methods A retrospective review was conducted of 661 critically ill patients admitted to a large academic medical center who received norepinephrine. Univariate, multivariate, and area under the curve analyses with optimal cut offs for maximum infusion rate and cumulative dosage were determined by Youden Index. Results The population was 54.9% male, 75.8% white, and 58.7 ± 16.1 y old with 384 (69.8%) admitted to the MICU and 166 (30.2%) admitted to the SICU, including 38 trauma patients. Inflection points in mortality were seen at 18 mcg/min and 17.6 mg. The inflection point was higher in MICU patients at 21 mcg/min and lower in SICU patients at 11 mcg/min. MICU patients also had a higher maximum cumulative dosage of 30.7 mg, compared to 2.7 mg in SICU patients. In trauma patients, norepinephrine infusions up to 5 mcg/min were associated with a 41.7% mortality rate. Conclusion A maximum rate of 18 mcg/min and cumulative dose of 17.6 mg were the inflection points for mortality risk in ICU patients, with SICU patients tolerating lower doses. In trauma patients, even low doses of norepinephrine were associated with higher mortality. These data suggest that MICU, SICU, and trauma patients differ in need for, response to, and outcome from escalating norepinephrine doses.
Design and in situ biosynthesis of precision therapies against gastrointestinal pathogens

Gastrointestinal pathogens employ a variety of mechanisms to damage host tissue, acquire nutrients, and evade treatment. To supplement broad-spectrum antimicrobials, there has been increasing interest in designing molecules that target specific taxa and virulence processes. Excitingly, these antivirulence therapies may be able to be synthesized by gut-resident microbes, thereby enabling delivery of these drugs directly to the spatial and temporal site of infection. In this review, we highlight recent progress in our understanding of small molecules that inhibit specific virulence mechanisms. We additionally discuss emerging methods to discover pathogen-specific and mechanism-specific peptides and small proteins. Finally, we cover recent demonstrations of probiotics engineered to produce antimicrobials in response to pathogen-specific cues in the gut. Collectively, these advances point to an emerging integrative approach to treatment of gastrointestinal diseases, comprising microbiologists, peptide chemists, and synthetic biologists.
In vivo 1 H MR spectroscopy with J-refocusing.

Purpose The goal of this study was to propose a novel localized proton MR spectroscopy (MRS) sequence that reduces signal loss due to J-modulation in the rat brain in vivo. Methods Sprague-Dawley rats were studied at 9.4 T. A semi-LASER sequence with evenly distributed echo-time (TE ) was used, and a 90° J-refocusing pulse was inserted at TE /2. Proton spectra were acquired at two TE s (30 and 68 ms), with and without the J-refocused pulse. Data were processed in MATLAB and quantified with LCModel. Results The J-refocused spectrum acquired at TE = 30 ms did not show any signal losses due to J-modulation and had comparable spectral pattern to the one acquired with semi-LASER using the minimum achievable TE . Higher signal amplitudes for glutamine, γ-aminobutyric acid and glutathione led to more reliable quantification precision for these metabolites. The refocused signal intensities at TE = 68 ms were also unaffected by J-modulation but were smaller than the signals at TE = 30 ms mainly due to transverse T2 relaxation of metabolites. Conclusion The proposed localized MRS sequence will be beneficial in both animal and human MRS studies when using ultra-short TE is not possible while also providing more reliable quantification precision for J-coupled metabolites.
Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or "priming," altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long-term sequelae may be due to a failure to recover from EtOH-induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and thereby perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents.
Large-Signal Stability Analysis for Inverter-Based Dynamic Microgrids Reconfiguration

Compared to conventional microgrids (MGs) with pre-defined and static topology, dynamic MGs feature varying electric boundaries and enhanced operational resiliency. This paper evaluates the operation stability of inverter-based dynamic MGs in terms of fulfilling the requested MGs topology change and associated network reconfiguration, which falls into the category of large-signal stability analysis. A complete nonlinear state-space model of inverter-based dynamic MGs is derived, where coordinated controls among inverters along with the effect of communication delays have been considered. In response to reconfiguration demands, an evaluation scheme is developed to determine whether the system could perform seamless topology variation without losing synchronism. Specifically, the system’s stability region is quantified by the domain of attraction (DoA) around the desired operating point using Takagi-Sugeno fuzzy modeling (T-S multimodeling). The large-signal stability of a multi-bus inverter-based dynamic MG with both interface inverters and sectionalizing switches have been analyzed. The stability regions estimated under different scenarios of topology variation have been validated using time-domain simulation in MATLAB/Simulink. The developed evaluation scheme is used to quantify the effects of control gain designs and communication delays on system large-signal stability.
Enforcement of Forum-Selection Clauses in Federal Court After Atlantic Marine

Forum-selection clauses are important agreements that limit exposure to risk of litigation in an undesired locale. The enforcement of forumselection clauses in the U.S. federal court system was not always certain, but today, such agreements are broadly considered enforceable. Courts, however, are split as to whether such clauses are governed by state or federal law and as to the proper procedural mechanism for enforcement. Recently, in Atlantic Marine Construction Co. v. U.S. District Court, the U.S. Supreme Court made strides toward resolving these disagreements among lower courts. This Note explores the history of enforcement of forum-selection clauses in federal court and articulates the legal complexities that remain in the wake of Atlantic Marine. It argues that Atlantic Marine implicitly resolved the choice-of-law split in favor of applying state substantive law to determine a forum clause’s validity and federal procedural law to determine its enforceability. To effectuate this implicit resolution, this Note proposes that courts engage in a two-step analysis in evaluating motions to enforce forum-selection clauses and that litigants bring such motions under Federal Rules of Civil Procedure 12(b)(6), 12(c), or 56.
Use of Water Hyacinth (Eichhornia crassipes) in Upgrading Small Agroindustrial Wastewater Treatment Plants

Water hyacinth ( Eichhornia crassipes ) was found to be useful in enhancing the final discharge quality of some agroindustrial wastewaters treated in lagoon systems. With a hydraulic retention time (HRT) of 5 days, the macrophyte was able to further reduce the biochemical oxygen demand (BOD) of anaerobically and aerobically treated palm oil mill effluent by 40% to 50 mgl -1 , accompanied by remarkable removal of ammoniacal nitrogen (AN) and total kjeldahl nitrogen (TKN) by 53.7% and 68.8% respectively. It also assisted in the settling of suspended solids (SS) to below 20 mgl -1 . In the secondary treatment of small-scale piggery effluent, the aquatic weed was found in a pilot field investigation to be 17-112% more efficient than algae in removing BOD and COD loads from a reconstituted effluent. A study at an institutional farm confirmed that >97% reduction of the major pollutional parameters was achieved. Introduction of hyacinth to a pilot plant treating sugar refinery wastewater resulted in the removal of BOD, COD and SS by 43.5%, 35.8% and 21.9% respectively with a HRT of 7 days. However, a chloride content exceeding 100 mgl -1 would inhibit its healthy growth. In the tertiary treatment of natural rubber processing effluent, removals of 85% BOD, 80% COD, 88% SS, 50% AN and 53% TKN were achieved with a HRT of 10 days. Increasing the HRT to 15 days resulted in higher removal efficiencies. Harvesting data indicated that the average biomass produced was 6-10% per day. The average growth rate of the aquatic plant could be as high as 505kg ha -1 day -1 on dry weight basis.
Perioperative Pain Management and Orthopedic Surgery

Given the nature of orthopedic surgery, moderate to severe pain should be anticipated with almost every major procedure. To achieve a reasonable degree of patient satisfaction, a well-designed plan to control acute pain should be a part of every procedure. Ideally, the plan should be presented to patients before they go to the operating room so that they will understand their role in the plan and can participate fully. This approach assures the patient that some intervention to deal with acute pain will be implemented before excruciating pain is felt.
The Assault on Managed Care: Vicarious Liability, Class Actions, and the Patient's Bill of Rights

The current level of public dissatisfaction has engendered a long list of proposed reforms that seek to increase the overall level of public regulation of Managed Care Organizations (MCOs), by limiting the scope of preemption under ERISA, by expanding doctrines of vicarious liability and implied agency, by adopting a patient's bill of rights, and by exposing them to class actions by disappointed plan participants. In response, this paper argues that most of these reforms are ill-conceived, in the sense that they do not hold any realistic possibility of improving the performance of the health care system relative to the current set of tort and contract doctrines that are now in place. Direct actions against MCOs for example are likely to hamper their mission to contain costs. The usual conditions that make vicarious liability sensible, for example, are not likely to pertain here when physician groups have assets to meet anticipated claims against them. And the use of class actions runs the serious risk of introducing dubious claims for liability based on some broadside allegations of fraud when their proper function is restricted to allowing the amalgamation of individual claims that would otherwise be too costly to pursue on an individual basis. The real problem with MCOs is that in conditions of scarcity, the public is unable to reconcile its inconsistent demands for low premiums ex ante with comprehensive and deep coverage ex post.
Component Testing: An Extended Abstract

The software industry has made and continues to make attempts to address the problems of large-scale software development. Recent slips of major products indicate that the problems with today’s development approaches are getting worse. We plan on eliminating these problems by creating software with components that are well factored and finished. Since the cost of revisiting a component after shipment is high, we plan on pushing the quality of a component to a high level. A summary of our testing techniques follows.
Minimizing the Potential for Drug Bioactivation of Drug Candidates to Success in Clinical Development

Variations in human drug-metabolizing enzymes can produce subtle evidence of potential toxicity. There are indications that some substructures found in drugs can form reactive metabolites that are involved in toxicities in humans. This article discusses the recent efforts to overcome and assess the problem of reactive metabolites in drug discovery and development, which might help to evaluate the safety profile of new drug candidates for idiosyncratic drug reactions (IDRs) during the preclinical phase. Keywords: drug toxicity; drug-metabolizing enzymes; reactive metabolites; drug development; idiosyncratic drug reactions
Use of Concentration Index for Pavement Design

The application of the concentration index to pavements is illustrated. The problem with the design of flexible airfield pavements under newly developed jumbo-jet aircraft, as represented by the Lockheed C-5A Galaxy and the Boeing 747, is examined. These aircraft are equipped with extremely large multiple-wheel landing gears. It is found that the CBR design equation can be used to evaluate the pavement performance under multiple-wheel gear assemblies when the equivalent single-wheel load is computed by the concentration index method. The concentration index is approximately independent of the load, gear configuration, and soil strength but varies with the depth.
Power supply variation effects on timing characteristics of clocked registers

Violations in the timing constraints of a clocked register can cause a synchronous system to malfunction. The effects of variations in the power supply voltage (V/sub DD/) on the timing characteristics of registers are investigated in this paper. The sensitivity of the setup time and data propagation delay to power supply variations is demonstrated for four different register designs. Design modifications are proposed in order to enhance the robustness of each register design under V/sub DD/ variations.
The possible origin of power-law magnetic relaxation in high-Tc superconductors

Abstract The power-law magnetic relaxation of high-Tc superconductors can be derived from the flux-creep equation by using the logarithmic-current dependence of the effective pinning energy. The exponent β and relaxation rate R of power law are represented by elementary parameters; activation barrier γ, current density J0, attempt velocity V0, and grain dimension d. The validity of this theory is confirmed by experiments on a melt-textured YBa2Cu3O7−δ sample. Using this theory, average pinning energy as functions of temperature, applied field, and process of this sample has been calculated and discussed.
Isotope separation during thin film compound growth

Recently, Stark hypothesized the existence of isotope separation during the growth of thin film compounds. Interestingly, the model predicted that it may be possible to observe a reverse isotope separation, one where the heavier isotope is found at greater concentrations farther from the material source. The physical situation in which the observation was hypothesized as possible was when the film grew by a grain boundary diffusion based process. All other mechanisms appear to yield either no separation or a normal positive separation in which the lighter isotope is found at greater concentrations farther from the source. Lim and Stark and Aly and Stark have observed isotope separation in the growth of thin film transition metal silicides; their experiments found the so-called reverse isotope separation in the growth of these compounds at the low growth temperatures where grain boundary diffusion is expected.
Influence of Foliar Leaching on Root Uptake and Translocation of Calcium-45 to the Stems and Foliage of Phaseolus vulgaris

Inorganic and organic metabolies may be leached from the foliage of many plants by aqueous solutions, including rain, dew and mist. Leaching is a widespread natural phenomenon and 61 metabolites have been characterized in plant leachates. When a plant is leached intermittently for 18 consecutive days, the loss of a particular nutrient may be 3 to 8 times the initial concentration of that nutrient in the leaves. The nutrients lost by leaching are replenished by a redistribution of nutrients from other plant parts and by root uptake and translocation from the root medium. Thus, it would seem that the rate of root uptake and translocation of nutrients to the stems and foliage should be greater in a plant which was being leached than in a similar plant which was not being leached.
Increased Sensitivity of RyR2 to Activation by Ca2+ and cADP-Ribose during Diabetes

In prior studies others and we found an increase in spontaneous Ca2+ release in ventricular myocytes isolated from streptozotocin-induced diabetic rat hearts. To date, molecular mechanisms underlying this phenomenon remains poorly defined. This study tests the hypothesis that the sensitivity of RyR2 to be activated by intrinsic modulators is altered during diabetes. Diabetes was induced in male Sprague-Dawley rats using streptozotocin. Ten weeks after injection, diabetic rats were divided into two groups: one group was treated with insulin for two weeks while the other group received no treatment. At the end of this time, cardiac and myocyte functions were assessed using echocardiography and high-speed video edge detection. Evoked Ca2+ transients were also assessed using confocal microscopy. Expression of RyR2 was assessed using RT-PCR and Western blots, while RyR2 activity and responsiveness to Ca2+, cADP-ribose and AMP-PCP were assessed using [3H]ryanodine binding and single channel analyses. After 12 weeks of diabetes, ejection fraction and fraction shortening were reduced by >25%. Rate of evoked Ca2+ release was slowed as was the time to peak myocyte contraction. Expression of RyR2 and the total amount of [3H]ryanodine bound at 200μM Ca2+ were reduced by ≈ 40%. However, the Kd for ryanodine remained essentially unchanged (5.2nM). Interestingly, in [3H]ryanodine binding and single channel assays, diabetic RyR2 was activated to a greater extentby low Ca2+ (0.53 μM and 1 μM), AMP-PCP (1mM) and cADP-ribose (1 μM). Two-weeks of insulin, initiated after 10 weeks of diabetes, treatment blunted these changes. These new data indicate that the increase in spontaneous Ca2+ release seen in diabetic myocytes stems in part from alterations in the responsiveness of RyR2 to activation by intrinsic ligands. Funded in part by NIH HL085061 and the Nebraska Redox Biology Center.
Nurses’ Perceptions of Error Communication and Reporting in the Intensive Care Unit

AbstractObjectives:To describe models of nursing communication about medical error.Methods:Intensive care unit nurses at 4 hospitals that had implemented evidence-based practices to reduce hospital-acquired infections participated in focus groups. They discussed medical error decision making regardi
Shearing of synovial fluid activates latent TGF-β

Summary Objective TGF-β is synthesized in an inactive latent complex that is unable to bind to membrane receptors, thus unable to induce a cellular biological response until it has been activated. In addition to activation by chemical mediators, recent studies have demonstrated that mechanical forces may activate latent TGF-β via integrin-mediated cellular contractions, or mechanical shearing of blood serum. Since TGF-β is present in synovial fluid in latent form, and since normal diarthrodial joint function produces fluid shear, this study tested the hypothesis that the native latent TGF-β1 of synovial fluid can be activated by shearing. Design Synovial fluid from 26 bovine joints and three adult human joints was sheared at mean shear rates up to 4000 s −1 for up to 15 h. Results Unsheared synovial fluid was found to contain high levels of latent TGF-β1 (4.35 ± 2.02 ng/mL bovine, 1.84 ± 0.89 ng/mL human; mean ± radius of 95% confidence interval) and low amounts ( Conclusions Results confirmed the hypothesis of this study and suggest that shearing of synovial fluid might contribute an additional biosynthetic effect of mechanical loading of diarthrodial joints.
Comparative analysis of the expression patterns of Wnts and Frizzleds during early myogenesis in chick embryos

During embryogenesis, the transduction of Wnt signals through Frizzled receptors is thought to play integral roles in myogenesis and somite patterning. However, little is known about which Wnt-Frizzled interactions are required for skeletal myogenesis. Thus, we sought to determine which Wnts and Frizzled exhibit expression patterns that are spatiotemporally consistent with the expression of two myogenic determination factors: Myf-5 and MyoD. To accomplish this, we first isolated partial cDNAs for six chick Frizzled orthologues and then compared the expression patterns of chick Frizzleds and Wnts to myogenic and somite patterning factors, such as Myf-5, MyoD, Sonic Hedgehog (Shh), Pax-1 and Pax-3 in Hamburger and Hamilton stage 10 chick. We used these data to generate a schematic composite of expression patterns at the level of the segmental plate and developing somites (stage V) that shows multiple Frizzled and Wnt transcripts expressed in tissues that are overlapping and adjacent to Myf-5 and MyoD expressing tissues.
Optimum sorghum planting dates in western Sudan by simulated water budgets

Abstract The Soil-Plant-Air-Water (SPAW) model previously developed and tested was used to simulate soil water budgets and crop water-stress for sorghum in the dryland region of western Sudan. Limited climatic data were combined with general observations of sorghum growth and soils to provide daily water budgets at one site for 11 years. Probability distribution of computed water budget components and water-stress index resulting from simulation of nine possible planting dates for each year were used to determine the optimum planting period for minimal crop water-stress. The water budget analysis showed a distinct optimum planting period of June 20 to July 10 with planting in early July as the most likely for best production. These results agreed well with general experience. The technique will be similarly useful for other locations, for research designs of soil water management, yield forecasting, and planning and management of agricultural resources.
Investigating the accuracy of subjective clustering and bootstrap application to subjective clustering using an empirical population

For a new product to be successful in today's market, engineers need to identify representative customer needs. One approach to identify representative needs from a large number of needs is Subjective Clustering (SC). A set of clusters obtained from SC is a point estimate of clusters generated by a population of customers. Another approach is to apply Bootstrap (BS) to SC. By applying BS to SC, engineers can draw an inference about population primary clusters. This paper compares the accuracy of estimating population primary clusters using SC and Bootstrap applied to SC (BS-SC). The authors recruited participants to perform the clustering experiments and assumed that these participants consist a population. The authors randomly sampled subsets of participants and evaluated how accurately SC and BS-SC identify population primary clusters. When the sample size is small relative to the population, BS-SC estimated population primary clusters more accurately than SC.Copyright © 2006 by ASME
An Electromechanical Demand Regulated Liquid Breathing System

The process of breathing liquid requires consideration of several problems not typical in gas respiration. These problems stem from the physical properties of liquid such as density, viscosity, and low diffusivity of gases which increase respiratory work. The objective of this study was to develop and study the feasibility of a demand controlled system for providing mechanical assistance and ameliorating respiratory work during liquid breathing.
Investigations on the Q and CT Bands of Cytochrome c Submonolayer Adsorbed on an Alumina Surface Using Broadband Spectroscopy with Single-Mode Integrated Optical Waveguides

In this work, we report experimental results on the molar absorptivity of cytochrome c adsorbed at different submonolayer levels onto an aluminum oxide waveguide surface; our data show a clear dependence of the protein optical properties on its surface density. The measurements were performed using the broadband, single-mode, integrated optical waveguide spectroscopic technique, which is an extremely sensitive tool able to reach submonolayer levels of detection required for this type of studies. This investigation focuses on the molar absorptivity at the Q-band (centered at 525 nm) and, for the first time to our knowledge, the weak charge transfer (CT) band (centered at 695 nm) of surface-adsorbed cyt c. Polarized light in the spectral region from 450 to 775 nm was all-coupled into an alumina thin film, which functioned as a single-mode planar optical waveguide. The alumina thin-film waveguide used for this work had a thickness of 180 nm and was deposited on a glass substrate by the atomic layer deposition process. The protein submonolayer was formed on the alumina waveguide surface through electrostatic adsorption from an aqueous buffer solution at neutral pH. The optical properties of the surface-adsorbed cyt c were investigated for bulk protein concentrations ranging from 5 nM to 8200 nM in the aqueous buffer solution. For a protein surface density of 2.3 pmol/cm 2 , the molar absorptivity measured at the charge transfer band was 335 M -1 cm -1 , and for a surface density of 15 pmol/cm 2 was 720 M -1 cm -1 , which is much closer to the value of cyt c dissolved in an aqueous neutral buffer (830 M -1 cm -1 ). The modification of the protein molar absorptivity and its dependence on the surface density can most likely be attributed to conformational changes of the surface-adsorbed species.
Compressed Air Efficiency: A Case Study Combining Variable Speed Control with Electronic Inlet Valve Modulation

This paper discusses an energy efficient compressed air system at an industrial automation components manufacturing facility. The authors performed and energy assessment as part of the DOE’s Industrial Assessment Center program and followed up with additional investigations on the compressed air system.
Applying Classical Control Theory to Energy-Economics Modeling-A Tool to Explain Model Behavior in Response to Varied Policy Decisions and Changing Inputs

Classical control theory is applied to the field of energy-economics using the Dartmount model COAL as an illustration. Control theory can assist in establishing the credibility of existing energy-economic systems models, since it presents a better understanding of model response. The application of these models requires a translation of DYNAMO type conventions into differential equations and flow diagram usually used for control system analysis. The response of the model to parameter changes and model inputs can become routine analyses using classical control theory methodology. In the case of the COAL model it was shown that the model output does not experience detectable oscillations even when input oscillations are introduced. The model as formulated represents a well damped system, which may not be what the authors expected in their representation of the real system.
Cell imaging beyond the diffraction limit using sparse deconvolution spatial light interference microscopy

We present an imaging method, dSLIM, that combines a novel deconvolution algorithm with spatial light interference microscopy (SLIM), to achieve 2.3x resolution enhancement with respect to the diffraction limit. By exploiting the sparsity of the phase images, which is prominent in many biological imaging applications, and modeling of the image formation via complex fields, the very fine structures can be recovered which were blurred by the optics. With experiments on SLIM images, we demonstrate that significant improvements in spatial resolution can be obtained by the proposed approach. Moreover, the resolution improvement leads to higher accuracy in monitoring dynamic activity over time. Experiments with primary brain cells, i.e. neurons and glial cells, reveal new subdiffraction structures and motions. This new information can be used for studying vesicle transport in neurons, which may shed light on dynamic cell functioning. Finally, the method is flexible to incorporate a wide range of image models for different applications and can be utilized for all imaging modalities acquiring complex field images.