cssi/SciSciGPT-SciSciNet huggingface dataset:
Ethanol, Zn2+ and insulin interact as progression factors to enhance DNA synthesis synergistically in the presence of Ca2+ and other cell cycle initiators in fibroblasts

In serum-starved NIH 3T3 fibroblasts, ethanol (30-80 mM) promoted the effects of insulin and insulin-like growth factor I (IGF-I) on DNA synthesis in a Zn(2+)-dependent manner. Ethanol and Zn(2+) were most effective when added shortly before or after insulin, indicating that all these agents facilitated cell cycle progression. The synergistic effects of ethanol, Zn(2+) and insulin (or IGF-I) on DNA synthesis required 1.1-2.3 mM Ca(2+), which seemed to act as the cell cycle initiator. When serum-starved cells were pretreated for 2 h with other cell cycle initiators such as 10% (v/v) serum, 50 ng/ml platelet-derived growth factor or 2 ng/ml fibroblast growth factor, subsequent co-treatments with 60 mM ethanol, Zn(2+) and insulin for an 18 h period again synergistically increased DNA synthesis. Of the various signal transducing events examined, ethanol stimulated cellular uptake of (45)Ca and it enhanced the stimulatory effects of insulin on p70 S6 kinase activity in a Zn(2+)-dependent manner. In contrast, ethanol inhibited insulin-induced activating phosphorylation of p42/p44 mitogen-activated protein kinases; these inhibitory ethanol effects were prevented by Zn(2+). The results show that, in NIH 3T3 fibroblasts, ethanol can promote cell cycle progression in the presence of a cell cycle initiator as well as Zn(2+) and insulin (or IGF-I).
A kinematic model of stretch-induced stress fiber turnover and reorientation

A kinetic model based on constrained mixture theory was developed to describe the reorganization of actin stress fibers in adherent cells in response to diverse patterns of mechanical stretch. The model was based on reports that stress fibers are pre-extended at a "homeostatic" level under normal, non-perturbed conditions, and that perturbations in stress fiber length destabilize stress fibers. In response to a step change in matrix stretch, the model predicts that stress fibers are initially stretched in registry with the matrix, but that these overly stretched fibers are gradually replaced by new fibers assembled with the homeostatic level of stretch in the new configuration of the matrix. In contrast, average fiber stretch is chronically perturbed from the homeostatic level when the cells are subjected to cyclic equibiaxial stretch. The model was able to describe experimentally measured time courses of stress fiber reorientation perpendicular to the direction of cyclic uniaxial stretch, as well as the lack of alignment in response to equibiaxial stretch. The model also accurately described the relationship between stretch magnitude and the extent of stress fiber alignment in endothelial cells subjected to cyclic uniaxial stretch. Further, in the case of cyclic simple elongation with transverse matrix contraction, stress fibers orient in the direction of least perturbation in stretch. In summary, the model predicts that the rate of stretch-induced stress fiber disassembly determines the rate of alignment, and that stress fibers tend to orient toward the direction of minimum matrix stretch where the rate of stress fiber turnover is a minimum.
Conjugated polymers: watching polymers dance.

Single-molecule spectroscopy allows fluctuations of conjugated polymer conformation to be monitored during solvent vapour annealing. Dramatic changes in fluorescence behaviour are observed and interpreted in terms of transformations between extended and collapsed polymer geometries.
SEQUENCE OF THE MACRONUCLEAR DNA ENCODING LARGE SUBUNIT RIBOSOMAL PROTEIN 29 (L29) IN EUPLOTES CRASSUS AND CYCLOHEXIMIDE SENSITIVITY

As a first step towards developing a DNA transformation method for the ciliated protozoan Euplotes crassus we determined the minimum inhibitory concentration (MIC) for cell division in the presence of cycloheximide (Chx) for several cell lines and the range of Chx sensitivity for 106 different progeny cell lines derived by mating two lines. All of the cell lines are highly sensitive to Chx. Progeny cell lines show a wider range of sensitivities than the parental lines. Because site-directed mutagenesis of the RPL29 gene encoding the large subunit ribosomal protein 29 (L29) has been used to generate a Chx-resistance marker (ChxR) for another ciliate, Tetrahymena thermophila [Yao and Yao, Proc. Natl. Acad. Sci. USA 88 (1991) 9493-9497], we isolated and sequenced the entire E. crassus macronuclear DNA carrying RPL29. The encoded peptide is 52-73% identical in sequence to L29 sequences from organisms ranging from T. thermophila and Saccharomyces cerevisiae to mouse. In E. crassus, the codon that has been mutated to confer Chx resistance in both S. cerevisiae and T. thermophila already encodes the amino-acid residue of one of the mutant forms identified in these other organisms. Thus, E. crassus RPL29 is not a convenient source of a selectable marker. Notable features of the macronuclear DNA carrying RPL29 are its extremely short non-coding regions and a TAG stop codon.
Post-translational modification of δ-crystallin in the embryonic chick lens

Abstract “Pulse-chase” experiments demonstrated that newly synthesized δ-crystallin is post-translationally modified in the cultured, 15-day-old embryonic chick lens. Analysis by isoelectric focusing in sucrose density gradients showed that the post-translational modification of δ-crytallin results in a small decrease in its average isoelectric point, amounting to approximately 0·1 of a pH unit. The subunit molecular weight of δ-crystallin before and after modification was indistinguishable by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. This post-translational modification should be considered when accounting for the reported electrophoretic heterogeneity of δ-crystallin.
Comparison by Simulation of Energy Consumption and WSN Lifetime for LEACH and LEACH-SM

Abstract Extending the period of operation ( lifetime ) of wireless sensor networks (WSNs) is one of the most critical issues. Lifetime limitations are due to limited energy resources. Available research results reveal that significant improvement in WSN lifetime can be achieved by using spares (spare nodes). At the moment of WSN deployment, the minimum required coverage of WSN targets is assured by primaries (primary nodes). Spares, if activated, would provide an above-threshold (more than required), redundant target coverage, so they can be switched off initially. They are ready to be switched on when any primary exhausts its energy. The spares must be properly managed. Mismanagement includes redundant and above-threshold coverage, which increase transmission of redundant data to cluster heads (collecting information from regular nodes , that is, primary nodes that are not cluster heads). Therefore, mismanaged spares can shorten WSN lifetime instead of extending it. We measured WSN lifetime by simulating the behavior of a single node. This paper presents the impact of spares and duration of the Nap interval of cluster heads on the WSN lifetime. We generate results based on different executions representing different scenarios.
A formal total synthesis of aklavinone via a blocked anthraquinone tautomer

Abstract An advanced intermediate in the Kishi synthesis of aklavinone was prepared. Juglone was converted into enone 4. Quinone 6 was then prepared from 4 by Michael addition and elimination of PhSOH and HCN.
SU-E-J-132: Sensitivity Evaluation of Organ Based Registration for Pancreatic IGRT

Purpose: Soft-tissue-based CBCT registration is not always straightforward. Typical image guidance is based on use of generic registration criteria that may not be adequately sensitive to PTV and critical organ positioning errors. This work presents a novel organ-based registration criterion to help quantify registration results and guidance. Methods: Ten pancreatic cancer patients treated using IGRT were included. Five individual CBCTs for each patient were manually registered to the planning CT by an expert. Instead of calculating the cross-correlation (CC) for the entire imaging volume, the CC values of the PTV and critical normal tissue (limited to a 1-cm ring around the PTV), were calculated as references. The CBCT images were then intentionally shifted in three axes by 1, 3, 5, 8, and 10 mm. New CC values were computed between the shifted CBCT and planning CT. The organ based CC was called sensitive to a given shift size when the p-value between new and reference CC values for the 5 CBCTs was <0.05. Results: The average reference CC was 0.23 (0.06–0.41). Despite the low correlation values, the CC-PTV is sensitive to average registration errors ≥ 5, 3 and 5 mm in the sup/inf, ant/post and right/left directions, respectively. Critical organ cross-correlation is sensitive to registration errors ≥ 7, 4 and 6 mm in these directions. 3/10 patients showed particularly poor sensitivity (≥ 8 mm) due to low reference CC, heavy contrast presence in the planning CT or small PTV volume. Conclusion: CBCT of upper abdomen tends to have very low similarity to the planning CT, affecting registration accuracy and reliability. This organ-based registration method focuses on the PTV and the most critical tissues, and shows improved sensitivity to positioning errors that may not be easily resolved by visual inspection. This work supported in part by grant 1R03CA173273-01
Modeling and analysis of hospital emergency department: An analytical framework and problem formulation

In this paper, we propose an analytical framework for modeling and analysis of hospital emergency departments (ED). Using such a framework, we intend to develop methods that can be used to improve ED performance through redistributing limited resources and through identifying and mitigating bottlenecks. Specifically, the following problems will be addressed: (1) analytical modeling and investigation of patient flow and quality of care (e.g., patient outcome or length of stay) in emergency departments, (2) identifying the factors that impede ED performance in the strongest manner and obtaining optimal distribution of limited resources for the best quality of care, and (3) determine optimal workforce configuration and resource allocation to achieve desired performance. A system-theoretic method is proposed to model ED as a complex network with split, parallel, closed, and re-entrant structures, for performance analysis, bottleneck mitigation and resource allocation.
Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma.

Objective To evaluate programmed death ligand 1 (PD-L1) expression in urothelial carcinoma of the bladder in relationship with tumor-infiltrating CD8+ T cells. Materials and Methods Tissue microarrays were prepared from 56 cystectomy specimens performed at our hospital (1994-2002). PD-L1 immunoexpression was assessed using the murine antihuman PD-L1 monoclonal antibody 5H1. Extent of membranous PD-L1 expression was assigned in each spot. Spots showing ≥5% expression were considered positive. Average PD-L1 expression per tumor was also calculated (5% positivity cutoff). "High CD8 density" was defined as the presence of ≥60 CD8+ intraepithelial lymphocytes per high power field in a given spot. A tumor was considered high density if ≥50% of its spots were of high density. Results PD-L1 expression was positive in approximately 20% of tumors. None of the benign urothelium spots expressed PD-L1. High CD8 density was observed in approximately 20% of cases. CD8 density did not correlate with PD-L1 expression. Overall survival (OS) and disease-specific survival (DSS) rates were 14% and 28%, respectively (median follow-up, 31.5 months). PD-L1 expression was associated with age at cystectomy ( P = .01). Remaining clinicopathologic parameters were not associated with PD-L1 expression or CD8 density. High CD8 density was associated with favorable OS ( P = .02) and DSS ( P = .02). The same was true when CD8 density was adjusted for demographic and clinicopathologic parameters. There was no correlation between PD-L1 expression and outcome. Conclusion High intratumoral CD8+ T cell density is associated with better OS and DSS in invasive urothelial carcinoma of the bladder. We found no correlation between PD-L1 expression and outcome.
Paraneoplastic pemphigus in association with Castleman's disease.

Background Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with lymphoproliferative neoplasms, and frequently with a very rare tumour, Castleman's disease. Objectives To analyse the clinical history, immunopathological and histopathological findings in 28 patients with a confirmed diagnosis of PNP and Castleman's disease. Methods Sera from all patients were assayed by indirect immunofluorescence (IF) and immunoprecipitation (IP) for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay for detection of desmoglein (Dsg)1 and Dsg3 autoantibodies. Results Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions were seen in 19 of 28. Twenty cases of Castleman's disease were of the hyaline vascular type, four were of plasmacytoid type and four were of mixed type. Striking findings included pulmonary destruction leading to bronchiolitis obliterans in 26 patients and fatal outcome due to respiratory failure in 22 patients with pulmonary involvement. Histological findings included lichenoid and interface dermatitis with variable intraepithelial acantholysis. Direct IF showed deposition of IgG and C3 in the mouth and skin in 24 of 28 patients. However, indirect IF detected serum IgG autoantibodies in all patients. IP revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 19 patients. Dsg3 and Dsg1 autoantibodies were present in 22 and 11 patients, respectively, and plectin autoantibodies in 23 patients. Conclusions PNP in association with Castleman's disease presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins are the most diagnostic markers. Pulmonary injury with respiratory failure is the cause of death in most cases.
Behavior of the Solution of a Random Semilinear Heat Equation

We consider a semilinear heat equation in one space dimension, with a random source at the origin. We study the solution, which describes the equilibrium of this system, and prove that, as the space variable tends to infinity, the solution becomes a.s. asymptotic to a steady state. We also study the fluctuations of the solution around the steady state.
Detection of delayed density dependence: effects of autocorrelation in an exogenous factor

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Simple thermodynamic model for the specific-heat anomaly and several other properties of crystals with the fluorite structure

The effect of a simple modification of the form of the Gibbs free energy that is normally used to describe the presence of Frenkel defects in crystals with the fluorite structure is examined. It is found that interactions among the high concentration of defects, present in these materials at high temperatures, can provide an adequate explanation of the observed specific heats and equilibrium concentrations of defects in Pb${\mathrm{F}}_{2}$, Sr${\mathrm{Cl}}_{2}$, and Ba${\mathrm{F}}_{2}$. It is found that in order to obtain satisfactory quantitative agreement between the calculated and measured defect concentrations and specific heats, it is necessary to presume Frenkel-defect formation entropies that are in serious disagreement with values obtained from most electrical-conductivity measurements, but consistent with several other values. We also compare calculated values of several other quantities to the experiment.
Preferential loss or inactivation of chromosome Z4 APRT allele in CHO cells.

In CHO cells, heterozygotes for the adenine phosphoribosyltransferase (APRT)locus arise spontaneously at high frequencies. However, such heterozygotes always yield APRT− mutants at low spontaneous rates. In an attempt to determine whether differences in the genomic environments of the two CHO APRTalleles might render one gene more susceptible to high-frequency spontaneous inactivation or deletion, we have mapped the functional APRTallele in four different spontaneous APRTheterozygotes. In each case, the functional APRTgene was found to reside on the Z7 chromosome; it was always the Z4 APRTallele that had been lost or inactivated. Two of these heterozygotes were shown to be physically hemizygous while the other two retained two copies of the APRT gene, indicating that the high-frequency event can involve either spontaneous deletion or inactivation.
Optimizing nano-dynamic mechanical analysis for high-resolution, elastic modulus mapping in organic-rich shales

An elastic modulus mapping technique based on spatially continuous dynamic nanoindentation is applied to map microscale variations in a fine-grained, kerogen-rich shale consisting of inorganic minerals with an interpenetrating network of microscale pores filled with organic matter. Advantages and limitations of the application of this technique to shales are explored through varying sample preparation and scanning procedures. Filtering techniques are developed to remove data that are negatively impacted by topography and other issues inherent to the mapping technique. As a result, spatial variations of elastic modulus in kerogen-rich regions are seen at substantially higher resolution than has previously been reported. Spatial resolution and continuous mapping across high stiffness-contrast material boundaries are further improved with stringent sample preparation and the use of a sharp tip. Typical modulus values measured by this technique include approximately 10 GPa for kerogen, 15–45 GPa for clay depending on the morphology and orientation, and 50–70 GPa for quartz.
Intestinal and renal handling of oxalate loads in normal individuals and stone formers

The renal handling and intestinal absorption of dietary oxalate are believed to be risk factors for calcium oxalate stone formation. In this study, we have examined the time and dose effects of soluble oxalate loads on the intestinal absorption and renal handling of oxalate in six stone formers (SF) and six normal individuals (N) who consumed diets controlled in oxalate and other nutrients. Urinary and plasma oxalate changes were monitored over 24 h after ingestion of 0, 2, 4, and 8 mmole oxalate loads, containing a mixture of 12C- and 13C2-oxalate. There were significant time and dose dependent changes in urinary oxalate excretion and secretion after these loads. However, there were no significant differences between SF and N in both the intestinal absorption and the renal handling of oxalate loads, as measured by the urinary excretion of oxalate (P = 0.96) and the ratio of oxalate to creatinine clearance (P = 0.34). 13C2-oxalate absorption studies showed three of the subjects, two SF and one N, had enhanced absorption with the 8 mmole load. A clear difference in absorption was demonstrated in these individuals during the 8–24 h interval, suggesting that in these individuals there was greater oxalate absorption in the large intestine as compared to the other subjects. This enhanced absorption of oxalate warrants further characterization.
Laparoscopic trocar site hernias.

ABSTRACT Five patients with laparoscopic trocar site incisional hernias are presented. These occurred following laparoscopic cholecystectomy (4) and pelvic laparoscopy (1). The hernias appeared fro...
Quasi-cournot behavior in a multimarket, multiplant setting

This paper introduces multimarket selling options, capacity constraints and quasi-Cournot conjectures into oligopolistic rivalry. It is shown that increased output responses between rivals that are producing below capacity will effect output reductions for all markets, but that increased output responses between rivals that are producing at capacity will effect an output increase in at least one market and might even result in a capacity extension and output increases in all markets.
Update in lung cancer and mesothelioma 2012.

Lung cancer remains the number one cause of cancer-related death in the United States among both men and women. It is estimated that in 2013, there will be more than 200,000 new diagnoses of lung cancer and nearly 160,000 deaths (1). Despite the discovery and application of targeted therapies, the overall survival (OS) remains poor, with an overall 5-year survival approximating 16%. In addition, there are a growing number of cases among former smokers and never smokers. However, based on research advances in 2012, there is enthusiasm that improvements in early detection, coupled with tobacco cessation and the application of novel genetic and genomics technologies, will lead to improved outcomes.
Effect of multistress on the lifetime characteristics of magnet wires used in flyback transformer

This work presents the results of the effect of multistress on the lifetime characteristics of fine gauge magnet wires used in the flyback transformers, adjustable speed drives, motor windings, ignition coils. Accelerated life tests are performed on AWG 43 gauge Polyesterimide insulated magnet wires. This study uses pulse voltages. Multistress includes high temperature, high frequency, and high voltages. Lifetime analysis provides statistical information such as lifetime characteristics, probability of failures, and lifetime percentiles. This study uses Weibull distribution to model life characteristics. The failure data of the aging tests is used to obtain parameters of the frequency-electrical-thermal life model. The life model is used to describe the behavior of insulation in the presence of multistress and is also used to estimate the lifetime of magnet wires at any desired stress level. The parameters of the frequency-electrical-thermal life model used in this study are obtained by regression analysis.
Green and Sustainable Cyber-Physical Security Solutions for Body Area Networks

Wireless sensor-based Body Area Networks (BAN) can play a major role in providing individualized health-care. Given their limited power sources, sensors in BAN have to be energy-efficient to ensure longevity and safety of the network. Recent years have seen the emergence of a new class of security solutions for BANs, called cyber-physical security solutions, which enable plug-n-play secure communication within a BAN using environment derived features. However, due to this environment-coupled nature, they require signal processing and mathematical routines which can be potentially very energy-intensive for individual sensors. In this paper, we characterize the "energy footprint" of a cyber-physical security solution, the Physiological signal based Key Agreement (PKA). The goal is to - 1) compute PKA's energy consumption, and 2) determine whether prominent energy scavenging techniques can be used to meet its requirements. Our results show that the energy requirements of PKA is small and is sustainable by many of the prominent energy scavenging techniques, such as body heat and ambulation, making it a "green" solution for large scale deployments.
Grid interactions and stability analysis of distribution power network with high penetration of plug-in hybrid electric vehicles

This study focuses on the effects of plug-in hybrid vehicles (PHEV) on the power system network. PHEVs are expected to be commercialized in near future. PHEVs will introduce a new type of load with extraordinary characteristics than the regular household loads. PHEVs may have significant effects on the existing power system networks, if they do not charged during off-peak load periods. A new peak demand period, distribution line capacities, electricity market prices, and power system level problems due to the harmonics and reactive power problems associated with PHEV chargers are the possible issues that may cause problems in the power systems. A new peak demand period, the need for additional distribution lines, additional harmonics and reactive power injection are among the issues that need be investigated due to integration of PHEVs. In this study, stability of a distribution power network integrated with PHEVs is analyzed. In this study it is been assumed that PHEVs do not necessarily need to be charge during off-peak load demand times.
Fuzzy systems based automatic freeway incident detection

This paper examines the feasibility of developing the fuzzy systems based automatic incident detection algorithms to improve the implementation of the real-time computerized freeway traffic management systems. >
Technosphere Insulin (Afrezza) A New, Inhaled Prandial Insulin

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of Technosphere insulin (TI), a new inhaled insulin product. Data Sources: Searches were conducted in PubMed/MEDLINE, Scientific Citation Index, and abstracts from both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) meetings from 2005 to August 2014, utilizing the search terms Afrezza, Technosphere, Afresa, and inhaled insulin. References were reviewed to identify additional sources. Study Selection and Data Extraction: Studies with adequate sample sizes, evaluating clinically relevant end points were included. Data Synthesis: TI is approved by the Food and Drug Administration as a bolus insulin to treat patients with type 1 and type 2 diabetes. Its glucose-lowering properties are less than that of rapid-acting insulins, but it does demonstrate less hypoglycemia. TI’s kinetics make it the fastest absorbed of any insulin available, although its overall onset of action appears...
Formal Modeling and Analysis of Software Architecture: Components, Connectors, and Events

Developing a good software architecture for a complex system is a critically important step for insuring that the system will satisfy its principal objectives. Unfortunately, today descriptions of software architecture are largely based on informal “box-and-line” drawings that are often ambiguous, incomplete, inconsistent, and unanalyzable. This need not be the case. Over the past decade a number of researchers have developed formal languages and associated analysis tools for software architecture. In this paper I describe a number of the representative results from this body of work.
QUALITY DRUG THERAPY IN CHILDREN: FORMULATIONS AND DELIVERY

The majority of medications that a chronically ill child under the age of 12 may receive are not formulated for easy or accurate administration. The younger the child the more likely this lack of appropriate formulation exists. Even in the instance of extemporaneously compounded pediatric formulations, generally there are no data on the bioavailability of these products. Therefore, administration of medication is inherently a less precise process in children than in adults. This precision is further reduced by the equipment employed in drug delivery, particularly intravenous delivery. This lack of precision has led to medication errors, drug-drug incompatibilities, and unnecessary and inappropriate blood level monitoring. Often, clinicians are unsure as to whether a lack of desired effect is related to the child, the delivery system, or the formulation. When a drug is formulated for pediatric use, several factors unique to pediatrics must be examined. Additives, including common preservatives and sugar, m...
Histone deacetylase 3 is required for maintenance of bone mass during aging

Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKO(OCN) mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKO(OCN) mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKO(OCN) mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKO(OCN) mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging.
Evaluation of the thyroid nodule.

Thyroid nodules are very common in the general population. The prevalence of palpable thyroid nodules is only approximately 4–7%, but the prevalence of ultrasound–detectable nodules is between 19 and 67% [1]. Twenty to forty–eight percent of patients with apparently solitary thyroid nodules palpated on physical exam will have additional sonographically detectable nodules [2,3]. Thyroid nodules are more common in women than in men by a ratio of about 4 to 1, and increase in frequency with age and with decreasing iodine intake 4]. Thyroid nodules are also more common in patients who have a history of head and neck irradiation, developing at a rate of about 2% per year compared with 0.1% per year in patients without a history of significant radiation exposure [5].
Optimizing drug therapy with Reinforcement Learning: The case of Anemia Management

Optimal management of anemia due to End-Stage Renal Disease (ESRD) is a challenging task to physicians due to large inter-subject variability in response to Erythropoiesis Stimulating Agents (ESA). We demonstrate that an optimal dosing strategy for ESA can be derived using Reinforcement Learning (RL) techniques. In this study, we show some preliminary results of using a batch RL method, called Fitted Q-Iteration, to derive optimal ESA dosing strategies from retrospective treatment data. Presented results show that such dosing strategies are superior to a standard ESA protocol employed by our dialysis facilities.
Part-time Work Among Pediatricians Expands

Objective The objective of this study was to track trends in part-time employment among pediatricians from 2000 to 2006 and to examine differences within subgroups of pediatricians. Methods As part of the Periodic Survey of Fellows, national random samples of American Academy of Pediatrics members were surveyed in 2000, 2003, and 2006. These surveys shared questions concerning working part-time and other practice characteristics. Roughly 1600 pediatricians were included in each random sample. Totals of 812 (51%), 1020 (63%), and 1013 (62%) pediatricians completed the surveys in 2000, 2003, and 2006, respectively. Analyses were limited to nonretired, posttrainee pediatricians. Results The number of pediatricians who reported that they work part-time increased from 15% in 2000, to 20% in 2003, to 23% in 2006. The pattern of increased part-time work from 2000 to 2006 held for many subgroups, including men, women, pediatricians who were younger than 40 years, pediatricians who were aged >or=50 years, pediatricians who worked in an urban inner city, pediatricians who worked in suburban areas, general pediatricians, and subspecialist pediatricians. Those who were working part-time were more satisfied within their professional and personal activities. Part-time pediatricians worked on average 14.3 fewer hours per week in direct patient care. Conclusions Increases in part-time work are apparent throughout pediatrics. The possible continued growth of part-time is an important trend within the field of pediatrics that will need to be monitored.
The boundary node method for three‐dimensional linear elasticity

The Boundary Node Method (BNM) is developed in this paper for solving three-dimensional problems in linear elasticity. The BNM represents a coupling between Boundary Integral Equations (BIE) and Moving Least-Squares (MLS) interpolants. The main idea is to retain the dimensionality advantage of the former and the meshless attribute of the later. This results in decoupling of the ‘mesh’ and the interpolation procedure.For problems in linear elasticity, free rigid-body modes in traction prescribed problems are typically eliminated by suitably restraining the body. However, an alternative approach developed recently for the Boundary Element Method (BEM) is extended in this work to the BNM. This approach is based on ideas from linear algebra to complete the rank of the singular stiffness matrix. Also, the BNM has been extended in the present work to solve problems with material discontinuities and a new procedure has been developed for obtaining displacements and stresses accurately at internal points close to the boundary of a body. Copyright © 1999 John Wiley & Sons, Ltd.
Imitation is the Sincerest Form of Flattery: Warren Buffett and Berkshire Hathaway

We analyze Berkshire Hathaway’s equity portfolio over the 1976 to 2006 period and explore potential explanations for its superior performance. Contrary to popular belief, we find Berkshire Hathaway invests primarily in large-cap growth rather than “value” stocks. Over the period the portfolio beat the benchmarks in 27 out of 31 years, on average exceeding the S&P 500 Index by 11.14%, the value-weighted index of all stocks by 10.92%, and a Fama and French characteristic-based portfolio by 8.56% per year. Although beating the market in all but four years can statistically happen due to chance, incorporating the magnitude by which the portfolio beats the market makes a luck explanation extremely unlikely even after taking into account ex-post selection bias. We find that Berkshire Hathaway’s portfolio is concentrated in relatively few stocks with the top five holdings averaging 73% of the portfolio value. While increased volatility is normally associated with higher concentration we show the volatility of the portfolio is driven by large positive returns and not downside risk. The market appears to under-react to the news of a Berkshire Hathaway stock investment since a hypothetical portfolio that mimics the investments at the beginning of the following month after they are publicly disclosed also earns significantly positive abnormal returns of 10.75% over the S&P 500 Index. Our evidence suggests the Berkshire Hathaway triumvirates of Warren Buffett, Charles Munger, and Lou Simpson posses’ investment skill unlikely to be explained by Efficient Market Theory.
N-Terminal Pro-B-Type Natriuretic Peptide for Predicting Coronary Disease and Left Ventricular Hypertrophy in Asymptomatic CKD Not Requiring Dialysis

Background: N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level predicts underlying heart disease in the general population. However, because NT-proBNP clearance may depend on renal function, the significance of an elevated level in patients with chronic kidney disease (CKD) without cardiac symptoms is uncertain. We sought to determine whether there is an association between NT-proBNP level and coronary artery disease (CAD) and left ventricular hypertrophy (LVH) in this population. Methods: We enrolled 207 ambulatory patients with CKD not on dialysis therapy. Medical records were reviewed for cardiac history and risk factors. NT-proBNP and troponin T (cTnT) levels were measured. Echocardiograms were analyzed from 99 patients. Results: NT-proBNP levels were elevated in 116 patients (56%), and 67 patients (33%) had experienced prior CAD events (myocardial infarction or revascularization). The prevalence of advanced age, diabetes, prior CAD events, myocardial injury (cTnT > 0.03 ng/mL [>0.03 μg/L]), and LVH increased, whereas glomerular filtration rate decreased, across quartiles of NT-proBNP levels. After adjustment for glomerular filtration rate, cTnT level, age, and diabetes, NT-proBNP remained an independent indicator of prior CAD events compared with quartile 1 (cTnT range, 4 to 116 pg/mL) for quartile 2 (range, 122 to 490 pg/mL): odds ratio, 1.6; 95% confidence interval, 0.5 to 5.0; for quartile 3 (range, 490 to 1,819 pg/mL): odds ratio, 5.3; 95% confidence interval, 1.7 to 16.2; and for quartile 4 (>1,975 pg/mL): odds ratio, 4.1; 95% confidence interval, 1.3 to 13.5. For patients with echocardiograms, NT-proBNP level predicted prior CAD events independent of LVH. Conclusion: NT-proBNP level elevation in asymptomatic patients with CKD reflects underlying ischemic heart disease and hypertrophy independent of renal function in a population with anticipated high cardiac morbidity.
Characterization of a novel and spontaneous mouse model of inflammatory arthritis

Mouse models of rheumatoid arthritis (RA) have proven critical for identifying genetic and cellular mechanisms of the disease. Upon discovering mice in our breeding colony that had spontaneously developed inflamed joints reminiscent of RA, we established the novel IIJ (inherited inflamed joints) strain. The purpose of this study was to characterize the histopathological, clinical, genetic and immunological properties of the disease. To begin the IIJ strain, an arthritic male mouse was crossed with SJL/J females. Inheritance of the phenotype was then tracked by intercrossing, backcrossing and outcrossing to other inbred strains. The histopathology of the joints and extraarticular organ systems was examined. Serum cytokines and immunoglobulins (Igs) were measured by ELISA and cytometric bead array. Transfer experiments tested whether disease could be mediated by serum alone. Finally, the cellular joint infiltrate and the composition of secondary lymphoid organs were examined by immunohistochemistry and flow cytometry. After nine generations of intercrossing, the total incidence of arthritis was 33% (304 of 932 mice), with females being affected more than males (38% vs. 28%; P < 0.001). Swelling, most notably in the large distal joints, typically became evident at an early age (mean age of 52 days). In addition to the joint pathology, which included bone and cartilage erosion, synovial hyperproliferation and a robust cellular infiltration of mostly Gr-1+ neutrophils, there was also evidence of systemic inflammation. IL-6 was elevated in the sera of recently arthritic mice, and extraarticular inflammation was observed histologically in multiple organs. Total serum Ig and IgG1 levels were significantly elevated in arthritic mice, and autoantibodies such as rheumatoid factor and Ig reactive to joint components (collagen type II and joint homogenate) were also detected. Nevertheless, serum failed to transfer disease. A high percentage of double-negative (CD4-CD8-) CD3+ TCRα/β+ T cells in the lymphoid organs of arthritic IIJ mice suggested significant disruption in the T-cell compartment. Overall, these data identify the IIJ strain as a new murine model of inflammatory, possibly autoimmune, arthritis. The IIJ strain is similar, both histologically and serologically, to RA and other murine models of autoimmune arthritis. It may prove particularly useful for understanding the female bias in autoimmune diseases.
On the Seasonality of the Hadley Cell

Abstract The annual march of the climatological mean meridional circulations (MMCs) in the NCEP–NCAR reanalyses is dominated by two components of roughly comparable mean-squared amplitude: 1) a seasonally invariant pair of “Hadley cells” with rising motion centered near and just to the north of the equator and subsidence in the subtropics, and 2) a seasonally reversing, sinusoidally varying “solsticial” cell with ascent in the outer Tropics of the summer hemisphere and subsidence in the outer Tropics of the winter hemisphere. The meridional structure and seasonal evolution of the solsticial cell are suggestive of a close association with the monsoons. These results are consistent with previous analyses of the mean meridional circulation based on radiosonde data.
Asymmetric Timeliness and Delayed Recognition of Bad News

This article examines whether the asymmetric timeliness measure captures delayed recognition of bad news and in which manner this delayed recognition occurs. I find that negative earnings changes of firms with high asymmetric timeliness have significant predictive power for future earnings changes of low-asymmetric-timeliness firms in the same industry. In contrast, the negative earnings changes of firms with low asymmetric timeliness do not have predictive power for future earnings changes of high-asymmetric-timeliness firms in the same industry. Moreover, neither type of firm has predictive power for the other group when earnings changes are positive. This result suggests that high-asymmetric-timeliness firms recognize the effects of a common negative shock before low-asymmetric-timeliness firms. Further, low-asymmetric-timeliness firms have more frequent and smaller negative earnings changes, suggesting that the eventual recognition of negative news “trickles out” as opposed to being recognized in an “earnings bath.”
The Prevention of Misbranded Food Labeling: The Nutrition Labeling and Education Act of 1990 and Alternative Enforcement Mechanisms

This article addresses the necessity for truthful, non deceptive labels on food for human consumption. Nondeceptive food labels, which the consumer ultimately deciphers, are crucial in today's marketplace. Public concern for truthful, non deceptive labels recently increased due to the proliferation of health-related claims which serve as a direct link to specific diseases. In response, Congress enacted comprehensive legislation which expressly addresses health-related claims and truth-in-Iabeling. Prior to discussing the misbranded food label, this article provides an overview of the impetus for the Federal Food, Drug and Cosmetic Act [hereinafter FDCA]. Judicial decisions which evidence the support for nondeceptive food labels in terms of economic deception and misrepresentation are highlighted. In addition, a section-by-section analysis of the Nutrition Labeling and Education Act of 1990 is provided. This crucial legislation aims to alleviate the misleading and confusing information about food products. Finally, this article concludes with a discussion of suggested enforcement mechanisms. These recommendations provide an incentive for self-regulation.
The Dynamics of Small and Large Molecules in the Extracellular Space and Cerebrospinal Fluid Following Local Cold Injury of the Cortex

The spread of 14C sucrose through the brain was the same as the spread of Evan’s blue over the first 6 h after a cold injury to the cortex. The CSF level of sucrose was elevated (p < .001) from the 4th to the 24th h with a maximum at the 6th h. Autoradiographs showed the density of sucrose was greatest in the periventricular area at 6 h and that sucrose was completely cleared from the brain by 24 h. C14 dextran (75,000 mol wt) also showed significantly increased CSF levels 4–24 h after a cold injury with a maximum at 6 h. On autoradiography the dextran could be seen in the subarachnoid space and ventricles at 6 h. Dextran was still seen in the brain at 24 h.
A Pure Theory of Metropolitan Redistribution Patterns: Modifications Upon Tiebout's Model

Tiebout’s (1956) theory about redistribution of population and the bundle of public goods, ever since, has been a major reference for many of recent endeavors to explain spatial redistribution patterns in metropolitan areas. In this paper, based on Tiebout’s rationale and by proposing major modifications on how his hypothesis would work better, I developed a theory of metropolitan redistribution patterns that improves conceptualization of current residential patterns in metropolitan areas. The theory clarifies that households do not relocate to solely maximize their locational utility, but rather residential mobility across metropolitan areas is an outcome of continuous adjustments in consumption of housing services and location of residence over the course of households’ lifecycles. Based on this theory, the discussion section provides a monocentric conceptual model and a multi-centric GIS-based model of population redistribution patterns that to further verify the validity of the hypothesis.
Thermal stress analysis of anisotropic plates with temperature dependent material properties and free edge boundary conditions

High-performance aerospace vehicles of today and the future must withstand such conditions as high loads and extreme temperatures. It is important for designers to be able to predict structural reactions due to environmental variables. Difficulties in analysis arise due to the changes induced in the physical properties as a result of the high temperatures, and in the anisotropic nature of the materials. This study examines the combined effect of high temperature and material anisouopy for thermally stressed plates with free edge boundary conditions.
The effect of training on lactic acid excretion.

To determine the effect of training on the lactic acid excreted in the urine after exercise, an untrained subject began regular exercise twice a week for two weeks, and then daily for three weeks. The exercise consisted in carrying a 30 pound load on a treadmill with 7 inch steps for 5 minutes at a rate of between 80 and 85 steps per minute. Samples of urine were collected immediately before, and for approximately half an hour after exercise. The rate of lactic acid excretion before exercise was determined, and the subsequent excess above this resting rate was attributed to the exercise. The results of these determinations at various periods during the experiment are given in the accompanying table. It shows a definite decrease in the excess of lactic acid as the experiment proceeded. Subjectively this decrease was accompanied by somewhat less distress during exercise and by less fatigue afterward. This decrease might be explained by assuming an increased mechanical efficiency, so that less lactic acid wa...
Fertility and Hatchability of Chicken Eggs Produced by Hens with Induced Hyperthermy

Abstract Funk (1937) reported that the fertility and hatchability of chicken eggs declined noticeably when the average weekly temperature was above 80°F. Heywang (1944) reported that temperatures above 97° were detrimental to chickens. It has not been shown that this decline is associated with increased body temperature in the hen, but, since the sperm is stored in the hen's body it might be hypothesized that hyperthermy reduced egg fertility and hatchability in the summer. The experiments were designed to test this hypothesis. MATERIAL AND METHODS Three tests with 10 hens in each were made between March 20 and April 20 on 14 White Leghorn and 18 Leghorn×New Hampshire cross pullets 14 months old. Before and after the experimental hyperthermy, the hens were housed in individual cages in an open-walled cage house. The semen used to inseminate the hens was obtained from New Hampshire males kept in a moderately cool room. For …