cssi/SciSciGPT-SciSciNet huggingface dataset:
Rhodococcus Bacteremia in an Immunocompetent Patient

Rhodococcus species are uncommon opportunistic pathogens in humans; they are most commonly isolated from immunocompromised patients presenting with severe cavitating pulmonary infections. We present a case of Rhodococcus bacteremia in an immunocompetent patient. Although Rhodococcus species have distinctive colony morphology and Gram stain characteristics, they may be under-recognized or misinterpreted as normal flora in the clinical microbiology laboratory. Presumptive identification of these organisms is important to ensure appropriate empiric antimicrobial therapy.
Discovery of isotopes of elements with Z≥100

Abstract Currently, 163 isotopes of elements with Z ≥ 100 have been observed and the discovery of these isotopes is described here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.
Identifying and appraising how managers install strategy

Cases were profiled to identify tactics used by strategic managers to implement strategy and to determine which tactic was the most effective in promoting adoption. Analysis revealed that four archetype tactics were used almost exclusively. An ‘interventionist’ approach had the best results but was used in only one case in five. ‘Persuasion’ and ‘participation’ were next most effective tactics, and ‘edicts’ the least effective. The implications of these findings for strategic management practice and the needs for further research are discussed.
Abstract 273: Molecular markers promoting metastases to the brain via EMT: Genes, proteins, and functional analysis.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Brain metastasis is the most common cause of mortality and morbidity of many cancers and occurs in more than 40% of patients. The metastatic cascade entails an orderly sequence of steps enabling tumor cells to migrate from the primary tumor and colonize at secondary locations. The underlying mechanisms of metastatic dissemination to the brain remain to be defined. However, In order to achieve this metastatic potential a cancer cell may go through a cellular reprogramming process, namely epithelial-to-mesenchymal transition (EMT), and its counterpart mesenchymal-to-epithelial transition (MET), by acquiring multiple genetic alterations and a stem cell like phenotype. We hypothesized that EMT would play a crucial role in brain metastasis. In order to achieve our goal we studied the expression of markers of EMT, MET, and stem cells in metastatic brain tumor samples. Microarray analysis of metastatic tumors was also done using a plate form of 17,000 genes. Furthermore, functional analysis establishing the metastatic phenotype of cancer cells towards a cerebral environment was also demonstrated using metastatic cell lines. Our results demonstrated that the expressions of EMT markers (Snail, TWIST, pSTAT3, NFkB), as well as the mesenchymal marker Vimentin, were present in metastatic tumor samples. The stem cell marker CD44 was also highly expressed. Gene expression analysis established the high presence of transcriptional factors associated with differentiation and reprogramming. Lastly, Immunofluorescence analysis demonstrated the presence of the mesenchymal marker Vimentin in brain tumor specimens. Tumor cells grown in astrocytic media displayed an increased cell proliferation, as well as enhanced S-phase cell cycle entry using an EDU incorporation technique. Migration of primary tumor cells was significantly enhanced in astrocytic media as evidenced by scratch wound migration. Furthermore, the tumor cells have a greater affinity for astrocytic media as demonstrated by chemotatic migratory tests. Moreover, co-culture analysis of primary tumor cells with astrocytic cells shows amicable mutual growth with Immunofluorescence demonstrating cell-to-cell interaction via E-Cadherin. In conclusion results of this study suggests that reprogramming via EMT/MET plays a crucial step in brain metastasis, and that the cerebral milieu provides a suitable microenvironment for metastatic cells to grow and disseminate. Citation Format: Dhruve S. Jeevan, Sudeepta Sridhara, Alex Braun, Raj Murali, Meena Jhanwar-Uniyal. Molecular markers promoting metastases to the brain via EMT: Genes, proteins, and functional analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 273. doi:10.1158/1538-7445.AM2013-273
Antiapoptotic and Oncogenic Potentials of Hepatitis C Virus Are Linked to Interferon Resistance by Viral Repression of the PKR Protein Kinase

Hepatitis C virus (HCV) is prevalent worldwide and has become a major cause of liver dysfunction and hepatocellular carcinoma. The high prevalence of HCV reflects the persistent nature of infection and the large frequency of cases that resist the current interferon (IFN)-based anti-HCV therapeutic regimens. HCV resistance to IFN has been attributed, in part, to the function of the viral nonstructural 5A (NS5A) protein. NS5A from IFN-resistant strains of HCV can repress the PKR protein kinase, a mediator of the IFN-induced antiviral and apoptotic responses of the host cell and a tumor suppressor. Here we examined the relationship between HCV persistence and resistance to IFN therapy. When expressed in mammalian cells, NS5A from IFN-resistant HCV conferred IFN resistance to vesicular stomatitis virus (VSV), which normally is sensitive to the antiviral actions of IFN. NS5A blocked viral double-stranded RNA (dsRNA)-induced PKR activation and phosphorylation of eIF-2α in IFN-treated cells, resulting in high levels of VSV mRNA translation. Mutations within the PKR-binding domain of NS5A restored PKR function and the IFN-induced block to viral mRNA translation. The effects due to NS5A inhibition of PKR were not limited to the rescue of viral mRNA translation but also included a block in PKR-dependent host signaling pathways. Cells expressing NS5A exhibited defective PKR signaling and were refractory to apoptosis induced by exogenous dsRNA. Resistance to apoptosis was attributed to an NS5A-mediated block in eIF-2α phosphorylation. Moreover, cells expressing NS5A exhibited a transformed phenotype and formed solid tumors in vivo. Disruption of apoptosis and tumorogenesis required the PKR-binding function of NS5A, demonstrating that these properties may be linked to the IFN-resistant phenotype of HCV.
Comparative In Vitro Efficacies and Antimicrobial Durabilities of Novel Antimicrobial Central Venous Catheters

We investigated the efficacies and durability of novel antimicrobial central venous catheters (CVCs) in preventing the adherence of microbial organisms to the surfaces of the CVCs. Novel antimicrobial CVCs investigated in this in vitro study were impregnated with antibiotics (minocycline and rifampin), with Oligon agent (silver, platinum, and carbon black), with approved antiseptics (chlorhexidine and silver sulfadiazine), or with a novel antiseptic agent, gendine, which contains gentian violet and chlorhexidine. When tested against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, gendine-coated CVC segments provided protection against bacterial adherence significantly more than all other types of tested CVCs (P < 0.05). Gendine-coated CVCs also provided better protection against Candida albicans and Candida parapsilosis than CVCs impregnated with antibiotics or with silver, platinum, and carbon (P < 0.02). After 28 days of being soaked in serum, the CVCs impregnated with chlorhexidine and silver sulfadiazine and the CVCs impregnated with silver, platinum, and carbon had lost antimicrobial activity against MRSA, P. aeruginosa, and C. parapsilosis, and the CVCs impregnated with minocycline and rifampin had lost activity against P. aeruginosa and C. parapsilosis. The CVCs impregnated with gendine maintained antimicrobial activities against MRSA, P. aeruginosa, and C. parapsilosis after 28 days of being soaked in serum. Central venous catheters impregnated with the novel investigational antiseptic gendine showed in vitro efficacy and provided protection against bacterial adherence more than other approved novel antimicrobial-coated CVCs.
On the Reflection Characteristics of a Reflectarray Element with Low-Loss and High-Loss Substrates

This paper revisits the loss phenomenon (particularly, the dielectric loss) for a microstrip patch in reflectarray mode, and discusses the reflection characteristics (magnitude and phase) for a reflectarray element with low- and high-loss substrates. First, the dielectric losses that occur in a lossy slab backed by a perfect electric conductor are both analytically and numerically investigated. Using similar numerical analysis, the reflectarray element (a patch on top of a slab backed by a conductor) is characterized, based on dielectric losses and reflection behavior. It is observed that for low-loss substrates, the dielectric loss decreases with increasing substrate thickness (as previously suggested in the literature). More importantly, for high-loss substrates, the dielectric loss no longer follows the expected trend (decreasing loss with increasing substrate thickness). The dielectric loss becomes a complex phenomenon, involving the dielectric loss tangent and substrate thickness. It is therefore noted that it is important to recognize the well-behaved and misbehaved phase-swing region for high-loss substrates for a reflectarray element. A simple circuit-model representation is provided for the reflectarray element. The anomalous phase behavior observed for high-loss substrates is explained using pole-zero analysis. Waveguide measurements are performed to quantify these reflectarray losses for low- and high-loss substrates. Finally, the loss mechanisms in a patch reflectarray (scattering mode) are compared to a patch antenna (radiation mode), using parameters such as reflection power and radiation efficiency, and similar loss mechanisms for both structures are apparent.
SAR Image Superresolution via 2-D Adaptive Extrapolation

In this paper, we present a description of a nonparametric two dimensional (2-D) procedure to extrapolate a signal, an extension of the Adaptive Weighted Norm Extrapolation (AWNE) method, and illustrate its application to SAR image formation. The benefits of the AWNE procedure are shown for synthetic data and for MSTAR data. Once the phase history is recovered, the AWNE method is applied to a subaperture or to the full set of frequency samples to extrapolate them to a larger aperture from which a superresolved complex SAR image is obtained. Use of the 2-D AWNE procedure proves to be superior to its one-dimensional separable version by reducing undesirable effects such as sidelobe interference, and variability in energy of the extrapolated data from row to row and column to column. To assess the performance of AWNE in enhancing prominent scatterers, reducing speckle, and suppressing clutter, we compare the superresolved images to the images formed with the traditional Fourier technique starting from the same phase history data. Fourier images are also compared with superresolved images formed using less data in order to assess the quality of the extrapolation and to quantify the method's ability to recover lost resolution. We illustrate performance by visual comparison and by the use of a geometric constellation of prominent point scatterers of the targets extracted from the images. A brief comparison with the 2-D versions of Capon and the linear prediction methods is illustrated and a hybrid AWNE/Capon approach is proposed.
Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: a retrospective analysis

ABSTRACT Background Response rates to systemic chemotherapy are low after tumor progression on oxaliplatin regimens. Hepatic arterial infusion (HAI) therapy in patients with tumor progression is a viable alternative. Patients and methods Thirty-nine heavily pre-treated patients (all receiving prior oxaliplatin) with unresectable colorectal hepatic metastases were treated with systemic CPT-11 and concurrent HAI floxuridine (FUDR) and dexamethasone (DEX). Results Partial responses were seen in 44% of patients. Median time to hepatic progression was 8.6 months, and median time to overall progression was 6.5 months. Median survival from time of initiation of HAI was 20.1 months [95% confidence interval (CI) 16.9–21.4] and from the initiation of treatment of metastatic disease, 32.01 months (95% CI 29.1–34.6). After a median follow-up of 19.1 months, seven patients (18%) proceeded to potentially curative surgery. Grade 3/4 toxic effects included neutropenia (13%), diarrhea (15%), intra-abdominal hemorrhage (2%), and bleeding duodenal ulcer (2%). Elevated liver function tests were seen, including bilirubin concentration >3 mg/dl (7%), alkaline phosphatase 2X baseline (20%), and aspartate aminotransferase >3X baseline (26%). Conclusions HAI FUDR/DEX plus systemic CPT-11 achieves a response rate of 44% and a median overall survival of 20 months in heavily pre-treated patients with colorectal hepatic metastases all receiving previous oxaliplatin; 18% of patients proceeded to surgical resection or ablation.
Coalescent Methods Are Robust to the Simultaneous Effects of Long Branches and Incomplete Lineage Sorting

It is well known that species with elevated substitution rates can give rise to disproportionately long branches in the species tree. This combination of long and short branches can contribute to long-branch artifacts (LBA). Despite efforts to remedy LBA via increased taxon sampling and methodological improvements in gene tree estimation, it remains unclear how long and short branches affect species tree estimation in the presence of incomplete lineage sorting (ILS). Here, we examine the combined influence of long external and short internal branches on concatenation and coalescent methods using both simulated and empirical data. Our results demonstrate that the presence of long and short branches alone does not obviously confound the consistency of concatenation and coalescent methods. However, when long external and short internal branches occur simultaneously with high ILS, concatenation methods can be misled, especially when two of these long branches are sister lineages. In contrast, coalescent methods are more robust under these circumstances. This is particularly relevant because this topological pattern also characterizes numerous ancient rapid radiations across the tree of life. Because short internal branches can increase th ep otential for ILS and gene tree discordance, our results collectively suggest that coalescent methods are more likely to infer the correct species tree in cases of ancient rapid radiations where long external and short internal branches are in close phylogenetic proximity.
Water loss from ester molecular ions upon electron impact

To date, in mass spectral studies of esters, a single reference to loss of water from the molecular ions has been noted. A series of aromatic esters which exhibit that sparsely observed phenomenon are reported herein. Through a combination of synthetic and deuterium labeling studies, support for a unique fragmentation route for the loss of water from these ester molecular ions has been obtained.
The Rise of Mortgage-Backed Securities: Struggles to Reshape Access to Credit in the USA

One of the most important outcomes of federal reregulation of the financial services sector since 1989 has been the completion of the shift from locally organized flows of credit to the housing sector, to a national mortgage-backed securities (MBS) market. In this paper the way in which the rise of MBSs has reshaped access to credit across social and spatial divisions is examined, and the implications of battles to shape the MBS market and of the practices of the two principal agencies in that market for the geography of financial exclusion are explored. Although the reregulation of the government-sponsored secondary markets promises to help break down entrenched patterns of financial exclusion, the government-sponsored enterprises are placed in the complex position of mediating social demands for more inclusionary credit practices and investor demands for continued high returns and low risks. It is unclear whether reform efforts will be sustained in the new political and economic environment of the mid-1...
Wind turbine response to parameter variation of analytic inflow vortices

As larger wind turbines are placed on taller towers, rotors frequently operate in atmospheric conditions that support organized, coherent turbulent structures. It is hypothesized that these structures have a detrimental impact on the blade fatigue life experienced by the wind turbine. These structures are extremely difficult to identify with sophisticated anemometry such as ultrasonic anemometers. This study was performed to identify the vortex characteristics that contribute to high-amplitude cyclic blade loads, assuming that these vortices exist under certain atmospheric conditions. This study does not attempt to demonstrate the existence of these coherent turbulent structures. In order to ascertain the idealized worst-case scenario for vortical inflow structures impinging on a wind turbine rotor, we created a simple, analytic vortex model. The Rankine vortex model assumes that the vortex core undergoes solid body rotation to avoid a singularity at the vortex centre and is surrounded by a two-dimensional potential flow field. Using the wind turbine as a sensor and the FAST wind turbine dynamics code with limited degrees of freedom, we determined the aerodynamic loads imparted to the wind turbine by the vortex structure. We varied the size, strength, rotational direction, plane of rotation, and location of the vortex over a wide range of operating parameters. We identified the vortex conformation with the most significant effect on the blade root bending moment cyclic amplitude. Vortices with radii on the scale of the rotor diameter or smaller caused blade root bending moment cyclic amplitudes that contribute to high damage density. The rotational orientation, clockwise or counter-clockwise, produces little difference in the bending moment response. Vortices in the XZ plane produce bending moment amplitudes significantly greater than vortices in the YZ plane. Published in 2005 by John Wiley & Sons, Ltd.
Work-pattern differences between male and female orthodontists.

Introduction: Traditionally, most orthodontists have been men. In recent years, however, the number of women in dentistry and dental specialties, including orthodontics, has increased dramatically. Because practice patterns of male and female orthodontists might differ, they should be evaluated so that our schools can produce enough providers for the future. Methods: Questionnaires were mailed to 798 orthodontists; the response rate was 68.8%. Questions about practice behavior and productivity were designed to assess sex difference with respect to age, marital status, and number of children. Results: Number of children appeared to be a good predictor of days worked per week and length of leaves of absence for female orthodontists. Solo practitioners dominate the field of orthodontics, irrespective of age or sex. Although women were less likely than men to be practice owners, only 20% of the women responding were not in an ownership position. Women were slightly more likely to be involved in a group practice, they worked in fewer offices than men, and they employed fewer full-time and part-time people. Female nonowners were more likely to take longer leaves of absence. Overall, women worked slightly fewer days per week and spent fewer hours per week in direct patient care. Annually, they devoted 25 fewer days to practice than men, but, when adjusted for leaves of absence, men and women worked similar numbers of weeks in 1999. Conclusions: Among orthodontists, work patterns of men and women differ somewhat, but these differences might not be as significant as other factors; more study is required.
Indentation of plastically graded substrates by sharp indentors

The present paper investigates the indentation of plastically graded substrates by sharp indentors. Contact analysis of plastically graded surfaces can be particularly useful in the design of load-bearing devices such as gears, rollers and electric contacts found in many macro- and micro-electro-mechanical systems. Substrates made of plastically graded materials are often encountered in nature or are artificially produced as a result of chemical and/or physical surface treatments. The variation of the plastic properties depends on micro-structural or compositional changes of the material with depth. The analysis of indentation of plastically graded substrates by sharp indentors provide the load-penetration response, as well as the strains and stresses inside the substrate, at maximum loading and at complete unloading. The parametric analysis of the solutions enables the direct correlation of the plastic properties and the load-penetration curves obtained from instrumented indentation tests. The variation of the plastic properties can subsequently be related to important micro-structural parameters such as particle composition, dislocation density and grain size. The results of this work show how surface modifications can induce plastic graded properties that strengthen substrates against contact-induced damage.
Fuzzy modeling of software effort prediction

Software sizing is an important management activity for both customer and developer that is characterized by uncertainty. Fuzzy system modeling offers a means to capture and logically reason with uncertainty. The paper investigates the application of fuzzy modeling techniques to two of the most widely used software effort prediction models: the Constructive Cost Model and the Function Points model.
A four-channel bipolar monolithic preamplifier for RHIC dimuon pad readout

The authors present a four-channel, low-power-consumption bipolar monolithic preamplifier designed to amplify signals from pads with detector capacitance values from 20 pF to 50 pF used in an RHIC (Relativistic Heavy Ion Collider) dimuon experiment. The circuit utilizes a folded-cascode topology with a novel feedforward compensation that improves the low-capacitance transient response and provides self-biasing without resorting to bandgap or current references. The circuit was fabricated in the VHF dielectrically isolated complementary bipolar process. Data for gamma pre- and post-irradiation to 1.25 Mrad indicated that the dynamic characteristics of the circuit were unchanged and that the biasing and noise showed only a few percent change after exposure to radiation. >
Properties of plastic optical fibers

Experimental and theoretical studies of the optical properties of large-core step-index plastic optical fibers (POF’s) and graded-index POF’s are reported. A set of criteria and analyses of physical parameters is developed in the context of major issues of POF applications in short-distance communication systems. Analyses are presented to show how the measured POF optical attenuation affects the overall performance in wavelength-division multiplexing and how the use of perfluorinated polymers can overcome limitations inherent in current POF materials. Results of POF optical bandwidth measurements by direct picosecond time-domain methods are reported, and their relationship to refractive-index profiles are theoretically analyzed by the WKB and finite-element methods. Two high-resolution optical techniques of refracted near-field and transverse interferometric methods are presented and are used to measure the index profiles of large-core POF’s. Results reveal that the index profile of currently available graded-index POF is not parabolic, which significantly limits its bandwidth compared with that of a true parabolic graded-index profile.
Quality control of highly multiplexed proteomic immunostaining with quantum dots: Correcting for crosstalk

The process of developing molecular assays for disease diagnosis and prognosis requires cross-disciplinary research which monitors quality and reproducibility at all levels. This paper discusses challenges in the quality control of highly multiplexed Quantum Dot (QD) staining and provides a method for improving accuracy of QD quantification in two phases. Phase one is the estimation of unintended crosstalk between multiplexed QD-antibody reporters, and phase two is digital correction of this crosstalk. Results show that crosstalk varies among tissues and reagents, and in some cases it can be on the same order of magnitude as the original intended signal. In cases where target protein expression is assumed to be independent, crosstalk can be empirically estimated from imaging data and corrected for. This work is expected to improve the overall reproducibility and quantification of multiplexed QD staining.
METHODS IN INFANT NUTRITION RESEARCH: BALANCE AND GROWTH STUDIES

Ziegler, E. E. and Fomon, S. J. (Department of Pediatrics, College of Medicine, University of Iowa, Iowa City). Methods in infant nutrition research: balance and growth studies. Acta Paed Scand, Suppl. 299:90, 1982.—Questions of infant nutrition can often be answered by metabolic balance studies or by studies of food intake and growth. The methods used by the authors for these approaches are described and an example of each is given. Balance studies demonstrated that lactose was more effective than a corn starch hydrolysate in promoting absorption of calcium, magnesium and manganese. A study of food intake and growth provided convincing evidence of the ability of infants to digest starch adequately after 6 weeks of age. There was a suggestion that some infants less than 6 weeks of age had limited ability to digest starch.
A latent variable model for chemogenomic profiling

Motivation: In haploinsufficiency profiling data, pleiotropic genes are often misclassified by clustering algorithms that impose the constraint that a gene or experiment belong to only one cluster. We have developed a general probabilistic model that clusters genes and experiments without requiring that a given gene or drug only appear in one cluster. The model also incorporates the functional annotation of known genes to guide the clustering procedure. Results: We applied our model to the clustering of 79 chemogenomic experiments in yeast. Known pleiotropic genes PDR5 and MAL11 are more accurately represented by the model than by a clustering procedure that requires genes to belong to a single cluster. Drugs such as miconazole and fenpropimorph that have different targets but similar off-target genes are clustered more accurately by the model-based framework. We show that this model is useful for summarizing the relationship among treatments and genes affected by those treatments in a compendium of microarray profiles. Availability: Supplementary information and computer code at http://genomics.lbl.gov/llda Contact: flaherty@berkeley.edu
The Other Sun: Non-Sacrificial Mutilation and the Severed Ear of Georges Bataille

Georges Bataille's first text, “Notre-Dame de Rheims,” is in many ways not quite part of his oeuvre. Virtually unknown until after the author's death, its religiosity is generally considered an aberration in the context of his other writings. Yet traces of this text and the sentiment that inspired it can be found in an undercurrent of silent mourning that runs through many of his early articles on art and literature. Against the strong presence of the eye in the conceptual universe that Bataille constructs during the interwar period, this essay delineates a metaphorical order that centers on the ear, revealing an enduring sense of what can be described as a non-sacrificial, melancholy fetishism, in contrast with the orgiastic exuberance of sacrifice that dominates his work.
Great Expectations (a)

A Japanese construction manager in Nepal is faced with a local work force that seems to him to have unreasonable demands and requests. After having several confrontations with his local engineering staff, he must decide how to handle a situation that is deteriorating day by day. The brief B case (UVA-OB-0740) describes how the manager handled the situation so students can compare their suggestions with what happenedright or wrong.
After the Destruction of Jewish Vilna: Abraham Sutzkever's Poetry, Testimony, and Cultural Rescue Work, 1944-1946

Colonel Smirnov: … He is Abram Gerzevitch Suzkever, a Jewish writer, who, together with his family, became victim of the German fascist criminals who had temporarily occupied the territory of the L...
Performance Contracting in School Health

(1982). Performance Contracting in School Health. Health Education: Vol. 13, Tools for Health Education Research, pp. 45-46.
Clinical Factors Associated with Weight Loss Related to Infection with Human Immunodeficiency Virus Type 1 in the Multicenter AIDS Cohort Study

The relation between a number of potential risk factors and change in body mass index per semester was examined in a community-based cohort of 1,809 homosexual and bisexual men seropositive for human immunodeficiency virus type 1 (HIV-1). The men were followed semiannually for up to 6.5 years between 1984 and 1990. A total of 9,735 person-semesters of observations were available for analysis. A Markov-type autoregressive model, adjusting for previous body mass index, was used to predict the change in body mass index over each person-semester. Overall, the cohort was gaining weight. An asymptomatic participant 1.8 m in height whose CD4+ cell count was > 750/microliters gained a mean of 0.5 kg each person-semester. In bivariate autoregressive models, diarrhea, fever, oral thrush, acquired immunodeficiency syndrome (AIDS), and CD4+ lymphocyte counts of < 100 and 100-199 cells/microliters were all associated with a significant decrease in body mass index. A significant inverse association was also found between change in body mass index and lymphadenopathy and herpes zoster, but when the intercept coefficient was added, no overall decrease in body mass index was seen in these models. In a final multivariate model, diarrhea was less strongly associated with a change in body mass index (p = 0.057), although AIDS (p = 0.009), fever (p = 0.006), thrush (p = 0.002), and a CD4+ lymphocyte count of < 100 cells/microliters (p < 0.001) all remained independently associated with a decrease in body mass index. Lymphadenopathy and a CD4+ lymphocyte count of 100-199 cells/microliters were also significant covariates in the final model, but neither of the beta coefficients exceeded that of the intercept, indicating that they were not independently associated with a decrease in body mass index. These findings suggest that the importance of diarrhea as a cause of HIV-related weight loss may have been over-estimated in previous clinic-based studies. AIDS and nonspecific markers of progression (fever, thrush, and a CD4+ count of < 100 cells/microliters) were the best predictors of weight loss during a semester.
Effect of Upstream Unsteady Flow Conditions on Rotor Tip Leakage Flow

A study has been conducted, using unsteady three-dimensional Reynolds-averaged Navier-Stokes simulations to determine the impact on rotor performance of the interaction between the stator wakes and rotor tip clearance flow. The key effects of the interaction are: (1) a decrease in loss and blockage associated with tip clearance flow; (2) an increase in passage static pressure rise. Performance benefit is seen in the whole operability range of interest, from near design to high loading. The benefit is modest near design and increases with loading. Significant beneficial changes occur when the phenomenon of tip clearance flow double-leakage is present. Double-leakage occurs when the tip clearance flow passes through the tip gap of the neighboring blade. Double-leakage typically takes place at high loading but can be present at design condition, as well. A benefit due to unsteady interaction is also observed in the operability range of the rotor. A new generic causal mechanism is proposed to explain the observed changes in performance. It identifies the interaction between the tip clearance flow and the pressure pulses, induced on the rotor blade pressure surface by the upstream wakes, as the cause for the observed effects. The direct effect of the interaction is a decrease in the time-average double-leakage flow through the tip clearance gap so that the stream-wise defect of the exiting tip flow is lower with respect to the main flow. A lower defect leads to a decrease in loss and blockage generation and hence an enhanced performance compared to that in the steady situation. The performance benefits increase monotonically with loading and scale linearly with upstream wake velocity defect.© 2002 ASME
Cost avoidance from dose rounding biologic and cytotoxic antineoplastics

Background To reduce product wastage, our institution allows automatic dose rounding of biologic and cytotoxic anticancer agents. The purpose of this project was to determine the actual annual cost avoidance due to pharmacist-managed automatic dose rounding of anticancer treatments. Methods Financial impact was assessed within the context of our departmental standard work which supports automatic dose rounding of biologic anticancer agents (±10%) and cytotoxic anticancer agents (±5%) to the nearest vial size for body surface area- or weight-based doses. Exclusions to automatic dose rounding include multiple dose vial products, pediatric orders, clinical trial drugs, and parenteral busulfan. The amount of cost avoidance for each rounded dose was determined using the product acquisition cost of the smallest available product amount. Data were collected from anticancer treatment orders for the fiscal year 1 July 2013 to 30 June 2014. Results A total of 6216 doses of anticancer drugs were checked for dose rounding during the period of data collection. Almost $200,000 in product acquisition cost was avoided with pharmacist-managed automatic dose rounding. Six different biologic products accounted for approximately 7% of the total doses analyzed and 78% of the cost avoidance. Fifteen drugs comprised the array of cytotoxic agents rounded. Approximately, 37% and 4% of the biologic and cytotoxic doses were rounded up to the vial size. Conclusion Routine dose rounding of biologic anticancer agents (±10%) and cytotoxic products (±5%) achieved cost avoidance through reduction of drug wastage at our institution.
Prismatic Equivalence – A New Case of Underdetermination: Goethe vs. Newton on the Prism Experiments

Goethe's objections to Newton's theory of light and colours are better than often acknowledged. You can accept the most important elements of these objections without disagreeing with Newton about light and colours. As I will argue, Goethe exposed a crucial weakness of Newton's methodological self-assessment. Newton believed that with the help of his prism experiments, he could prove that sunlight was composed of variously coloured rays of light. Goethe showed that this step from observation to theory is more problematic than Newton wanted to admit. By insisting that the step to theory is not forced upon us by the phenomena, Goethe revealed our own free, creative contribution to theory construction. And Goethe's insight is surprisingly significant, because he correctly claimed that all of the results of Newton's prism experiments fit a theoretical alternative equally well. If this is correct, then by suggesting an alternative to a well-established physical theory, Goethe developed the problem of underdete...
Isolation, amino acid analyses and refolding of subunits of pig heart succinyl-CoA synthetase.

For the first time, pig heart succinyl-CoA synthetase has been refolded from its isolated subunits after denaturation. Amino acid analyses of pig heart succinyl-CoA synthetase and its subunits were performed. Subunits were isolated by gel filtration in neutral 6 M-urea. The amino acid composition of the native enzyme bears a strong resemblance to that of the Escherichia coli enzyme. Application of the various methods for comparing amino acid compositions [Cornish-Bowden (1983) Methods Enzymol. 91, 60-75] shows that the degree of relatedness between the alpha-subunits of the pig heart and E. coli enzymes and between the beta-subunits of the two synthetases is intermediate between ‘strong’ and ‘weak’. As for the E. coli synthetase, it is unlikely that the alpha-subunit arises from the larger beta-subunit by post-translational modification. The pig heart enzyme contains a single tryptophan residue, which is located in the beta-subunit. Excitation of the enzyme at 295 nm resulted in a typical tryptophan emission spectrum. Refolding of enzyme denatured in 6 M-guanidine hydrochloride or of alpha- and beta-subunits isolated in this solvent required the presence of either ethylene glycol or glycerol, optimally at 20-25% (v/v). GTP-Mg2+ did not stimulate reactivation of the enzyme, in contrast with the result obtained with ATP-Mg2+ in the reconstitution of the enzyme from E. coli. Yields of 60% and 40% were obtained in the refolding of denatured enzyme and isolated subunits respectively. The fluorescence spectrum of the refolded protein was essentially the same as that of native enzyme. Unrecovered activity could not be accounted for in the form of protein aggregates. The specific activity of refolded enzyme that had been separated from inactive protein on a Bio-Sil TSK 250 column was the same as that of native enzyme. Km values for GTP of 27 microM and 14 microM were determined for native and refolded enzyme respectively.
Failure of antibody-coated bacteria and bladder washout tests to localize infection in spinal cord injury patients.

Abstract The validity of the antibody-coated bacteria test and Fairley washout procedure to determine whether urinary tract infections were of kidney or bladder origin in spinal cord injury patients was assessed by comparing test results with those obtained from culture of ureteral urine specimens. It was concluded that neither the presence of antibody-coated bacteria nor a positive bladder washout test can be considered as definitive evidence that bacteriuria is of renal origin in these patients.
Development of Experimental Myopia in Chicks in a Natural Environment.

Purpose The hypothesis that outdoor exposure might protect against myopia has generated much interest, although available data find only modest clinical efficacy. We tested the effect of outdoor rearing on form-deprivation myopia in chicks, a myopia model markedly inhibited by high-intensity indoor laboratory lighting. Methods Unilaterally goggled cohorts of White Leghorn chicks were maintained in a species-appropriate, outdoor rural setting during daylight hours to the extent permitted by weather. Control chicks were reared indoors with incandescent lighting. Besides ocular refraction and ultrasound, we determined dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in retina and vitreous and measured mRNA expression levels of selected clock and circadian rhythm-related genes in the retina/RPE. Results Myopia developed in the goggled eyes of all cohorts. Whereas outdoor rearing lessened myopia by 44% at 4 days, a protective effect was no longer evident at 11 days. Outdoor rearing had no consistent effect on retinal or vitreous content of dopamine or DOPAC. Conforming to prior data on form-deprivation myopia, retina and vitreous levels of DOPAC were reduced in goggled eyes. Compared with contralateral eyes, the retinal expression of clock and circadian rhythm-related genes was modestly altered in myopic eyes of chicks reared indoors or outdoors. Conclusions Outdoor rearing of chicks induces only a partial decrease of goggle-induced myopia that is not maintained, without evidence that retinal dopamine metabolism accounts for the partial myopia inhibition under these outdoor conditions. Although modest, alterations in retinal gene expression suggest that studying circadian signals might be informative for understanding refractive mechanisms.
A 34-Year-Old Pregnant Woman With Cough, Chest Pain, and a Left Upper Lobe Mass

A 34-year-old white woman who was 30 weeks' pregnant initially presented to her primary care physician with a cough for which she was given antibiotics, but she had persistent symptoms. These were followed by chest pain, as a result of which she was referred to our department. She had a past medical history of hypertension, and currently was in her sixth pregnancy, with no reported complications in the previous pregnancies. Review of systems was otherwise negative. She had a three-pack-year smoking history, but denied smoking during her current pregnancy.
Left Ventricular Function Across the Spectrum of Body Mass Index in African Americans: The Jackson Heart Study

Abstract Objectives This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals. Background Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood. Methods Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC. Results The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (β = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue. Conclusions Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction.
Gradient-on-a-Chip with Reactive Oxygen Species Reveals Thresholds in the Nucleus Response of Cancer Cells Depending on the Matrix Environment

Oxidative stress-mediated cancer progression depends on exposure to reactive oxygen species (ROS) in the extracellular matrix (ECM). To study the impact of ROS levels on preinvasive breast cancer cells as a function of ECM characteristics, we created a gradient-on-a-chip in which H2O2 progressively mixes with the cell culture medium within connected microchannels and diffuses upward into the ECM of the open cell culture window. The device utilizes a paper-based microfluidic bifurcating mixer insert to prevent leakage and favor an even fluid distribution. The gradient was confirmed by measuring H2O2 catalyzed into oxygen, and increasing oxidative DNA damage and protective (AOP2) response were recorded in 2D and ECM-based 3D cell cultures. Interestingly, the impact of ROS on nuclear shape and size (annunciating phenotypical changes) was governed by the stiffness of the collagen I matrix, suggesting the existence of thresholds for the phenotypic response to microenvironmental chemical exposure depending on E...
The diverse actions of astrocytes during synaptic development

In the developing brain, cortical circuits are established through a complex process of synaptogenesis, maturation, and synaptic pruning. Astrocytes carry out diverse functions during each of these stages to facilitate the formation of complex networks. Recent work has begun to demonstrate that these heterogeneous roles during excitatory synaptic development are determined by the astrocyte population, brain region, and neuron type. This review will focus on current findings which highlight cell type specific mechanisms of excitatory synaptogenesis, as well as multiple mechanisms engaged by astrocytes to facilitate synaptic maturation and pruning.
An Inexpensive, In-House-Made, Microdialysis Device for Measuring Drug–Protein Binding

An inexpensive, in-house made microdialysis device is described that is suitable for measuring the binding of small molecules including drug candidates to serum proteins or other macromolecules. The device is based on the standard equilibrium dialysis method to measure the fraction of low molecular weight compound bound to proteins. It is constructed from a standard polypropylene 96-well plate, dialysis tubing, and low viscosity epoxy resin. The device can be readily prepared for a small fraction of the cost of a commercial, multichamber microdialysis device. Drug–protein binding results are provided, which validates the device.
Heterogeneity and Plasticity of Melanoma: Challenges of Current Therapies

ABSTRACT The heterogeneity and plasticity of aggressive melanoma presents for­midable challenges in the design of current therapies. Plasticity is defined as the phenotype of cancer cells expressing properties normally related to stem cells, including the expression of genes associated with multiple cellular phenotypes and appearing as undifferentiated, embryonic-like cells. The multipotent pheno­type of these tumor cells, expressing vascular, embryonic, and cancer stem cell (CSC) capabilities, offers new insights into their functional adaptation and resis­tance to current therapies. This chapter highlights major advances in research that (i) help clarify the underlying challenges associated with angiogenesis inhibitor therapy; (ii) discuss important implications of the discovery of reactivation of the normally dormant Nodal embryonic signaling pathway that underlies the CSC phenotype, unregulated tumor growth and metastasis, and resistance to current therapies; and (iii) demonstrate the advantage of using combinatorial strategies to effectively target heterogeneous melanoma subpopulations to eliminate relapse and disease progression.
Getting pain on the table in primary care physical exams

Using conversation analysis and a dataset of 171 video recordings of US primary care encounters (2003-2005), this paper examines patients' unsolicited pain informings - e.g. "that hurts" - during the physical examination phase of acute care visits. I argue that when patients experience pain in a physical exam but have not been asked a question like "does that hurt?", they face an interactional dilemma. Having presented their health problem to a doctor, they have tacitly set in motion epistemic and interactional asymmetries through which the doctor investigates the problem on their behalf. In this context, volunteering unsolicited pain information could facilitate progress towards an accurate diagnosis, but it could also be heard as independently asserting the relevance of pain to what the doctor is doing, thereby departing from the previously established asymmetries. I show that patients manage this dilemma by using turn design practices to implicitly account for unsolicited pain informings as motivated by a virtual solicitation and/or a sudden pain sensation. With these practices, patients manage to share potentially relevant pain information without accountably being heard to assert its relevance to the doctor's diagnostic inquiry. This achievement demonstrates how asymmetries in doctor-patient communication are a joint accomplishment of both doctors and patients, and are incarnate in the details of everyday clinical interactions.