cssi/SciSciGPT-SciSciNet huggingface dataset:
Perspectives on the Discovery of Vitamin B12

In high school, my propensity for chemistry was revealed by my receiving the highest refund in money in recognition of my breaking less glassware than anyone else in the class. The magnitude of my refund was more important than that of my grade. In four years at the University of Illinois under Speed Marvel and Roger Adams, I became completely addicted to organic chemistry. During doctoral studies at the University of Wisconsin, Homer Adkins did not approve of my spending three dollars of my fifty dollar monthly income for Gortner’s new book on biochemistry. After that, I dared not look at any biochemistry, but during three years at Yale as a postdoc, Professor Treat B. Johnson encouraged me to extrapolate organic chemistry not only to the biological but to the medical. So, when I left Yale I joined the newly established Laboratory for Pure Research at Merck and declined an offer to join a famous company to do research on polymers. At Merck, I thought I should have an M.D., but it was too late. I was married, had a daughter, and commuting to Columbia in New York City from Raway and keeping my job at Merck was not possible. However, 55 years later, I did receive an honorary M.D. In ′34, I became susceptible to medical goals and still am after almost five decades. At that early time at Merck, I was naive and yielded to the attraction of trying to purify the antipernicious anemia factor. I had the right boss who allowed me to have my head. At present, I am reading Arthur Kornberg’s —“For the Love of Enzymes”. On page 28 of the chapter on The Vitamin Hunters, Dr. Kornberg wrote that “nutrition cannot be left to the art of medicine and that the only answer is hard science and sustaining the faith that persistent scientific effort eventually solves most problems, often in a surprisingly novel way”.
Abstract 4416: Studies on role of acyl-CoA cholesterol acyltransferase (ACAT) expression in ovarian/endometrial cancer progression - An invitro study

INTRODUCTION: Cancer progression and tumorigenesis have been linked to alterations in cellular metabolic pathways of lipid and cholesterol synthesis in many cancers. Increased levels of cholesterol esters (CE) have been reported in breast cancer, leukemia, glioma and prostate cancer, but not exploited in detail in ovarian and endometrial cancers. Inside cells, excess free cholesterol is esterified by acyl-CoA cholesterol acyltransferase (ACAT) and stored as cholesteryl ester (CE) in lipid droplets (LDs). Cholesteryl ester accumulation may be a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway as observed in pancreatic cancer. In the present study, we focused on the role of ACAT and cholesterol esters in altered cholesterol metabolism in ovarian/endometrial cancer cell lines. METHODS: We studied the effect of abrogation of cholesterol esterification either by an ACAT-1 inhibitor/shRNA knockdown or via inhibition of PI3K/AKT/mTOR pathways and subsequent effect on ovarian/endometrial cancer cells proliferation, invasion, cell migration and tumorigenesis. The expression of ACAT was studied at the protein and mRNA levels in a panel of ovarian/ endometrial cancer cell lines and also in normal and ovarian cancer clinical samples. ACAT expression was assessed by western blotting, ELISA, quantitative RT-PCR and immunostaining techniques. RESULTS: Our results reveal an elevated expression of ACAT-1 at both protein and mRNA levels in ovarian and endometrial cancer cell lines as compared to primary cells. Our results also provide preliminary data on involvement of ACAT and cholesterol esters in the progression and metastasis of ovarian cancer. CONCLUSION: These studies may aid in the development of new biomarkers or treatment targets for ovarian/endometrial cancer. Citation Format: Vijayalakshmi N. Ayyagari, Xinjia Wang, Laurent Brard. Studies on role of acyl-CoA cholesterol acyltransferase (ACAT) expression in ovarian/endometrial cancer progression - An invitro study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4416. doi:10.1158/1538-7445.AM2017-4416
Issues and consequences of using nutrition to modulate the avian immune response

Abstract Combatting antimicrobial-resistant bacteria is a high priority for both public health and agriculture in the United States and globally. Antibiotic use in animals and humans is considered a major risk factor in the development of antibiotic-resistant bacteria in animals, humans, and the environment. A worldwide emphasis on research into the development of new alternatives to antibiotics is ongoing. Alternatives to antibiotics are broadly defined as any substance that can be substituted for therapeutic drugs, which are increasingly becoming ineffective against pathogenic bacteria, viruses, or parasites. One promising approach involves host-directed immunomodulatory therapies, whereby natural mechanisms in the host are exploited to enhance therapeutic benefit. The objective is to initiate or enhance protective antimicrobial immunity while limiting inflammation-induced tissue injury. The interaction between poultry nutrition, nutrients, and dietary factors and the bird’s immune response has long been known. However, the interplay between nutritional processes and the immune system is incompletely understood. Specifically, precise cellular and molecular immune responses invoked by feed components and the role of the gut barrier and microbiota on the interaction between the immune system and nutrition remains to be fully elucidated. Further, this review will point out some of the areas that have been either neglected when studying the effects of nutrition and nutrients on immune function (the effect of the gut microbiome) or the non-intentional effects of over-feeding various nutrients on the avian immune response (feed-induced inflammation and meta-inflammation).
Univariate or multivariate analysis for better prediction accuracy? A case study of heterogeneity in vehicle ownership

We contrast different modeling frameworks that offer alternative ways of capturing observed/unobserved heterogeneity. The model systems compared are: ordered logit, residential location cluster-bas...
Unraveling the Dynamics of the Brain through Modeling and Analysis

In this short note I share with the mathematics community some of my modeling experience in visual neuroscience. Proposing to view the brain as a large and complex dynamical system, I suggest a mathematical framework, and discuss some open problems on the dynamics of neuronal interactions that I believe are highly relevant to Computational Neuroscience.
Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder.

Abstract Background One third of patients with major depressive disorder (MDD) fail to respond to currently available antidepressant medications. Inflammation may contribute to treatment non-response through effects on neurotransmitter systems relevant to antidepressant efficacy. In post-hoc analyses, increased concentrations of inflammatory markers prior to treatment predict poor antidepressant response. However, limited data exists on whether depressed patients with multiple failed treatment trials in their current episode of depression exhibit increased inflammation. Methods Plasma concentrations of inflammatory markers were measured in unmedicated, medically stable patients with MDD (n = 98) and varying numbers of adequate antidepressant treatment trials in the current depressive episode as measured by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. Covariates including age, sex, race, education, body mass index (BMI) and severity of depression were included in statistical models where indicated. Results A significant relationship was found between number of failed treatment trials and tumor necrosis factor (TNF), soluble TNF receptor 2 (sTNF-R2) and interleukin (IL)-6 (all p Conclusions Measuring inflammatory markers and targeting inflammation or its downstream mediators may be relevant for depressed patients with multiple failed antidepressant treatment trials in their current depressive episode.
Inflammation in atherothrombosis: how to use high-sensitivity C-reactive protein (hsCRP) in clinical practice.

Inflammation is now recognized as a critical contributor to the atherothrombotic process, and measurement of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) is a proven method to better predict cardiovascular risk and target therapeutic interventions. Following recommendations from the Centers for Disease Control and the American Heart Association, many physicians now routinely evaluate hsCRP along with cholesterol levels as a part of global risk prediction. Levels of hsCRP 3 mg/L correspond to lower, moderate, and higher risk of cardiovascular events at all levels of the Framingham Risk Score and at all levels of metabolic syndrome. Interventions that lower hsCRP include diet, exercise, smoking cessation, statin therapy, and improved glycemic control. In addition to primary prevention, hsCRP is an important prognostic marker in acute coronary syndromes, following angioplasty, and in the long-term management of post-infarction patients. This article provides a clinically oriented overview of appropriate settings in which to measure hsCRP, how to interpret results, and how interventions to reduce vascular risk can be targeted on the basis of hsCRP findings.
Methionine requirement of pigs between 5 and 20 kilograms body weight

Four nursery experiments were conducted using a methionine (Met)-deficient feather meal-corn-soybean meal-dried whey basal diet (20% CP; 3,250 kcal of ME/kg, .11% choline, .19% Met, 1.00% cystine) supplemented with lysine, tryptophan, and histidine to determine the Met requirement of 5- to 10- and 10- to 20-kg pigs. Based on a true Met digestibility value of 81.6% estimated by a pig ileal digestibility assay, the Met-deficient basal diet contained .155% of digestible Met. A preliminary experiment (Exp. 1) indicated that pigs fed the Met-deficient basal diet when fortified adequately with Met could produce weight gains similar to those of pigs fed a 20% CP practical corn-soybean meal-dried whey diet. In Exp. 2 and 3, crossbred pigs weighing 5.8 kg initially were fed diets containing graded levels of digestible Met between .195 and .355%. Average daily gain increased quadratically (P less than .05) as the level of Met increased. When the data of Exp. 2 and 3 were examined together, the digestible Met requirement of 5- to 10-kg pigs was estimated to be .255% of the diet. In Exp. 4 and 5, crossbred pigs averaging 10 kg were fed digestible Met concentrations ranging from .155 to .315%. Average daily gain increased quadratically (P less than .05). The digestible Met requirement of 10- to 20-kg pigs was estimated at .255% for maximal weight gain, which was similar to that of 5- to 10-kg pigs. Assuming an 89% digestibility of Met in practical corn-soybean meal diets, the total Met level needed in practice would be .29%.(ABSTRACT TRUNCATED AT 250 WORDS)
Higher-Order Mesh Generation Using Linear Meshes [EM Programmer's Notebook]

A simple method for generating highorder, 3D surface meshes is presented. The higher-order meshes are suitable for investigating higherorder convergence in electromagnetic analysis codes. The mesh-generation algorithm uses two linear meshes: a coarse mesh and a refinement of the coarse mesh. The method is applied to both quadrilateral and triangle surface meshes. Mesh generation is validated by computing the discretization error for various meshes. Finally, integral equation error convergence of plane wave scattering from a conducting sphere is investigated in terms of mesh order and basis order. A reference implementation of the algorithms is made available.
Utilization and extravasation of peripheral norepinephrine in the emergency department.

Objective Vasopressors are typically administered through central venous catheters (CVC) due to a historical risk of extravasation with peripheral administration. However, CVC insertion is a time-consuming process that may delay vasopressor administration and is associated with complications. The Virginia Commonwealth University Health System (VCUHS) Emergency Department (ED) implemented a protocol that recommends peripheral norepinephrine (pNE) be administered through an 18 gauge or larger at or above the antecubital fossa or the external jugular vein with a maximum dose of 20 μg/min. This study characterizes the use and incidence of extravasation in all adult patients who received pNE initiated in the VCUHS ED. Methods This was an observational, retrospective cohort study in adult patients from March 2016 to March 2019. Of the 331 patients that were screened, 177 met inclusion criteria. Data were analyzed using descriptive statistics. Results Patients had a median age of 60 years and 59% were male. The median APACHE II score was 25 with an overall hospital mortality of 27%. A majority of patients received pNE for distributive shock (63%). Approximately 69% received pNE through an antecubital infusion site. The median total pNE duration was 62 min (IQR 32, 142). Eighty-four percent of patients received a central line. Only 2.3% of patients had confirmed extravasation in addition to another 2.3% where extravasation could not be excluded, for a total rate of 4.5%. None had subsequent extremity injury. Conclusions Administration of pNE according to the VCUHS ED protocol resulted in a low extravasation rate.
Key Phrase Classification in Complex Assignments.

Complex assignments typically consist of open-ended questions with large and diverse content in the context of both classroom and online graduate programs. With the sheer scale of these programs comes a variety of problems in peer and expert feedback, including rogue reviews. As such with the hope of identifying important contents needed for the review, in this work we present a very first work on key phrase classification with a detailed empirical study on traditional and most recent language modeling approaches. From this study, we find that the task of classification of key phrases is ambiguous at a human level producing Cohen's kappa of 0.77 on a new data set. Both pretrained language models and simple TFIDF SVM classifiers produce similar results with a former producing average of 0.6 F1 higher than the latter. We finally derive practical advice from our extensive empirical and model interpretability results for those interested in key phrase classification from educational reports in the future.
Autocrine regulation of cell proliferation by ERa in breast cancer cells

3040 Estrogens are steroid hormones that are indispensable for normal mammary gland development. The primary function of estrogens is to stimulate mammary epithelial cell proliferation, which is mediated by estrogen receptors (ERs). There are two known types of estrogen receptors - ERa and ERb, with ERa being the primary type of estrogen receptor mediating mammary epithelial cell proliferation. Consistent with their function in cell proliferation, extensive exposure to estrogens during a woman’s lifetime and abnormal expression of estrogen receptor impose higher risk to breast cancer. Indeed, ERa is found abnormally expressed in about 70% of diagnosed breast carcinomas. ERa is a diagnostic biomarker for breast cancer as well as a therapy target by Tamoxifen and other selected ER modulators (SERMs). Despite the significant role of ERa in normal mammary gland development and breast cancer, the molecular mechanism of how ERa mediates cell proliferation is not fully understood. Contrary to most cell receptors that mediate cell proliferation, ERa-positive cells as marked by immunohistochemical staining are dissociated from proliferating cells labeled by radioactive isotope or the cell proliferation marker Ki-67. It is generally believed that ERa expressing cells don’t proliferate, instead these ERa-positive cells will release some growth factors to stimulate the neighbouring cells to proliferate - the paracrine regulation of cell proliferation by ERa. In our studies, we evaluated the expression of ERa in different phases of cell cycle in ERa-positive breast cancer cells. We found that ERa is present in all four phases of the cell cycle. Consistently, we found that ERa colocalized with Ki-67 and the cyclins (D, E, A, and B) for different phases of cell cycle progression. In cells treated with ICI182780, E2 stimulation leads to cell proliferation. A recent study in mouse mammary glands suggested that the dissociation of ERa with cell proliferation marker could be caused by the rapid degradation of ERa when stimulated by E2. In the ERa-positive breast cancer cells, we found that ERa is also quickly down-regulated by E2 stimulation, indicating that the presence of ERa in all phases of the cell cycle is not caused by the defective ERa degradation. In summary, our data indicate that ERa can mediate estrogen-stimulated cell proliferation in an autocrine manner in ERa-positive breast cancer cells.
Teamwork in Space Exploration

The safety and success of astronaut crews depends not only on avoiding technical errors but also human errors due to ineffective teamwork. In this chapter we discuss team attitudes, behaviors, and cognitions, and provide an overview of the goals of astronaut and flight control teams. We discuss relevant literature on each team skill, implications for team skills in spaceflight, and new possibilities for future research and applications of the science. As NASA continues to push boundaries and explore the universe, organizational decision makers should not forget about the teams of astronauts on the front lines and the critical team skills they need for mission success.
Rotational Dyad Statistics and Energy Migration in Miscible and Immiscible Polystyrene/Poly(Vinyl Methyl Ether) Blends

Excimer fluorescence is developed as a quantitative probe of isolated chain statistics and intermolecular segment density for miscible and immiscible blends of polystyrene (PS) with poly(vinyl methyl ether) (PVME). Rotational isomeric state calculations combined with a one-dimensional random walk model are used to explain to explain the dependence of the excimer to monomer intensity ratio on PS molecular weight for 5% PS/PVME blends. A model for a three-dimensional random walk on a spatially periodic lattice is presented to explain the fluorescence of miscible PS/PVME blends at high concentrations. Finally, a simple two-phase morphological model is employed to analyze the early stage of phase separation kinetics.
Inverse Approach for the Average Convection Coefficient Induced by a Forced Fluid Flow Over an Annular Fin of Rectangular Profile Using Tip Temperature Measurements

The objective of the present paper is to develop a simple algebraic computational procedure for the estimation of the average convection coefficient of a forced fluid flow over an annular fin of rectangular profile within the platform of inverse heat conduction problems. The data required is the tip temperatures of an annular fin of rectangular profile, which are measured in an experimental setup. Based on nonlinear regression analysis, an empirical correlation equation is constructed for the dimensionless average tip temperature depending upon the dimensionless thermo–geometrical parameter and the radius ratio. When compared against the outcome of a direct heat conduction problem, the good quality of the estimated average convection coefficient for the annular fin of rectangular profile demonstrates the feasibility of the simple algebraic computational procedure.
Fusogeneic Membrane Glycoproteins for Cancer Gene Therapy

There are currently no vector systems available that are efficient enough or targeted enough to transduce all of the tumor cells in a patient with even a single copy of a therapeutic gene (1–4). Ideally, therefore, the genes used for gene transfer therapy of cancer should be able to achieve two major goals. The first is to kill tumor cells locally with high efficiency. The second is to stimulate potent antitumor immunity such that distant metastases, to which genes cannot be delivered, can also be eradicated.
Risk Education A Worldview Analysis of What is Present and Could Be

Risk, risk analysis, risk management and risk-based decision-making are ubiquitous ideas in the modern world. Consequently, risk education is emerging as a new field of research. However, just as the defining of risk and what it entails is a contested topic, so too is the field of risk education research open to many possible approaches. In this paper notions of risk, particularly as they play out in research on risk education, are analyzed (within an ethical space) using a theoretical framework based on the Traditional Western and an Indigenous worldview. Through this analysis, along with the identification of the kinds of knowledge and ways of knowing currently being valued in the research, other kinds of knowledge and ways of knowing that may prove just as important emerge.
Predicting memory-access cost based on data-access patterns

Improving memory performance at software level is more effective in reducing the rapidly expanding gap between processor and memory performance. Loop transformations (e.g. loop unrolling, loop tiling) and array restructuring optimizations improve the memory performance by increasing the locality of memory accesses. To find the best optimization parameters at runtime, we need a fast and simple analytical model to predict the memory access cost. Most of the existing models are complex and impractical to be integrated in the runtime tuning systems. In this paper, we propose a simple, fast and reasonably accurate model that is capable of predicting the memory access cost based on a wide range of data access patterns that appear in many scientific applications.
The acoustic nonlinearity parameter in Fluorinert up to 381 K and 13.8 MPa

This work reports on the determination of the acoustic nonlinearity parameter, B/A, from measured sound speed data, in Fluorinert FC-43 at temperatures up to 381 K and pressures up to 13.8 MPa using the thermodynamic method. Sound speed was measured using Swept Frequency Acoustic Interferometry at 11 pressures between ambient and 13.8 MPa along 6 isotherms between ambient and 381 K. Second-order least-squares polynomial fits of measured sound speeds were used to determine temperature and pressure dependence. A room temperature B/A = 11.7 was determined and this parameter was found to increase by a factor of 2.5 over the temperature/pressure range investigated.
“Meddling” or “Steering”

The latest flap in Hong Kong’s contentious world of higher education concerns the unwillingness of the government-appointed council of the Hong Kong Institute of Education to reappoint Paul Morris as president.
Overcoming incomplete perception with util distinction memory

This paper presents a method by which a reinforcement learning agent can solve the incomplete perception problem using memory. The agent uses a hidden Markov model (HMM) to represent its internal state space and creates memory capacity by splitting states of the HMM. The key idea is a test to determine when and how a state should be split: the agent only splits a state when doing so will help the agent predict utility. Thus the agent can create only as much memory as needed to perform the task at hand—not as much as would be required to model all the perceivable world. I call the technique UDM, for Utile Distinction Memory.
Terapia de Aceitação e Compromisso: modelo, dados e extensão para a prevenção do suicídio

The present article briefly describes ACT, its underlying model, and the evidence in support of its efficacy. In order to provide an example of how to extend ACT to new problems, the paper then extends ACT thinking to the prevention of suicide and suicidality. ACT, both its model and applied techniques, appears to be supported by the evidence, suggesting that further extensions are warranted.
Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat-fed rats.

The purpose of the current study was to examine the enzymatic profile [phosphofructokinase (PFK), beta-hydroxyacyl-CoA dehydrogenase (HADH), and citrate synthase (CS)] in gastrocnemius muscle, heart, and liver in rats allowed ad libitum access to a high-fat diet (HFD, 45% of kcal from corn oil). Male Wistar rats were fed a low-fat diet (LFD, 12% of kcal from corn oil) for a 2-wk baseline period after which some continued on the LFD and others were placed on the HFD. After 1 wk on the HFD, rats were categorized as obesity-resistant (OR), -intermediate (OI), or -prone (OP) on the basis of body weight gain (OR, lower tertile; OI, middle tertile; OP, upper tertile). At 1, 2, and 5 wk, rats from each group were killed (n = 9-14 from each group/time point) after a 24-h fast. At the end of the 5-wk dietary period, weight gain was 114.8 +/- 4.3 in LFD, 125.2 +/- 3.7 in OR, 147.1 +/- 4.1 in OI, and 173.7 +/- 3.5 g in OP rats (OP > OI > OR, LFD; P or = 0.72, P < 0.001). After 1 wk on the HFD, significant correlations between the ratio of PFK/HADH (an indication of the relative capacity for glycolysis vs. beta-oxidation, r = 0.4, P = 0.03) and HADH/CS (an indication of the capacity for beta-oxidation relative to total oxidative capacity, r = -0.56, P = 0.001) in the gastrocnemius muscle and weight gain were observed. At week 2, significant correlations between these ratios and weight gain were observed in the gastrocnemius, liver, and heart. In contrast, these ratios were not significantly correlated with weight gain at 5 wk. These results suggest that rats most susceptible to weight gain or a HFD are characterized by a continuous increase in energy intake (explaining approximately 50% of the variance in weight gain) and an early tissue enzymatic profile that favors carbohydrate over fat use.
Covalently conjugated transforming growth factor-β1 in modular chitosan hydrogels for the effective treatment of articular cartilage defects

Approaches to control precisely growth factor presentation to a tissue defect in a sustained fashion are of increasing interest for a number of complex tissue engineering applications. Although transforming growth factor beta-1 (TGF-β1) plays a key role in promoting chondrogenesis, the therapeutic use of TGF-β1 is limited by its inherent protein instability, requiring high amounts of the protein that can cause adverse side effects with inefficient cartilage formation. In this work, we have developed strategies to stabilize TGF-β1 signaling in the injectable, visible blue light inducible chitosan (MeGC) hydrogel system for specific use in cartilage regeneration. We successfully modulated delivery of TGF-β1 with reduced burst release in a complex biological environment of serum and cells by covalently conjugating the protein to MeGC hydrogels with preserving type II collagen, one of the major cartilaginous extracellular matrix (ECM) components. The hydrogel system supported cellular condensation and deposition of cartilaginous ECM by encapsulating adipose derived stem cells in vitro. We confirmed further the ability of these TGF-β1 functionalized hydrogel systems to promote cartilage regeneration in challenging healing environments such as in a rat partial-thickness chondral defect model which present a limited source of subchondral bone marrow elements. These results suggest a new injectable delivery modality of therapeutic agents to improve clinical cartilage repair.
Diversity in presenting manifestations of systemic lupus erythematosus in children.

Abstract Objective: To describe the diversity in presenting manifestations of systemic lupus erythematosus (SLE) in children. Study design: Initial clinical and laboratory manifestations of 39 children, who fulfilled ≥4 American College of Rheumatology criteria for SLE, were retrospectively analyzed. Results: Median age at onset was 12 years. The male to female ratio was 1:18.5, and racial/ethnic backgrounds were white 41%, black 33%, and Hispanic 26%. Initial manifestations included musculoskeletal 74%, cutaneous 72%, constitutional 67%, neurologic 28%, renal 28%, lymphadenopathy 15%, and Raynaud’s phenomenon 10%. Laboratory abnormalities at presentation to our clinic included elevated erythrocyte sedimentation rate 87%, anemia 72%, lymphopenia 59%, leukopenia 31%, proteinuria or cellular casts 44%, low C3 or C4 level 77%, antinuclear antibodies 97%, and anti-double-stranded DNA 95%. One third (33%) presented with features not initially suggestive of SLE. Six patients presented with unusual manifestations including parotitis, quadriplegia, chorea, severe abdominal pain, persistent cough, and dizziness. However, 85% of patients with atypical manifestations had abnormal complete blood count or urinalysis results at presentation. Conclusion: Presenting manifestations of SLE in children are diverse. A detailed history, thorough review of systems, complete physical examination, complete blood count, urinalysis, and a high index of suspicion help to make the correct diagnosis of SLE in patients with atypical presentations. (J Pediatr 1999;135:500-5)
Development of a Multi-Component Damage Assessment Model (MDAM) for Time-Dependent Mixture Toxicity with Toxicokinetic Interactions

A new mixture toxicity model was developed to predict the time-dependent toxicity of a mixture with toxicokinetic interactions directed specifically toward addressing biotransformation. The Damage ...
Meter‐Long Multiblock Copolymer Microfibers Via Interfacial Bioorthogonal Polymerization

High-molecular-weight multiblock copolymers are synthesized as robust polymer fibers via interfacial bioorthogonal polymerization employing the rapid cycloaddition of s-tetrazines with strained trans-cyclooctenes. When cell-adhesive peptide is incorporated in the tetrazine monomer, the resulting protein-mimetic polymer fibers provide guidance cues for cell attachment and elongation.
Position Control Using Acceleration-Based Identification and Feedback With Unknown Measurement Bias

A position-command-following problem for asymptotically stable linear systems is considered. To account for modeling limitations, we assume that a model is not available. Instead, acceleration data are used to construct a compliance (position-output) model, which is subsequently used to design a position servo loop. Furthermore, we assume that the acceleration measurements obtained from inertial sensors are biased. A subspace identification algorithm is used to identify the inertance (acceleration-output) model, and the biased acceleration measurements are used by the position-command-following controller, which is constructed using linear quadratic Gaussian (LQG) techniques.
A model of price and quantity adjustments in primary commodity markets

Abstract This paper presents a dynamic, simultaneous model of price and quantity adjustments in world primary commodity markets. The model is formulated in a disequilibrium framework, emphasizing particularly the role of price adjustment. In addition to the price equation, commodity consumption and production equations are also specified. The empirical analysis of the model is carried out with the annual data of six primary commodities: coffee, cocoa, rubber, copper, tin, and sugar. This includes the estimation of price, consumption, production equations, the simulation tests of complete structural models for these six commodities, and the derivation of dynamic responses (measured by elasticities) of commodity prices to changes in world income, world inflation, and commodity outputs. Dynamic simulations strongly confirm the commonly observed self-generating and recurring boom-and-bust cycles of primary commodity prices. This finding lends credibility to the models constructed.
Perception by action versus perception for action

There are numerous theories and empirical approaches that consider the crucial nature of action in perception. These include: Gibson's direct perception [1], the ‘two visual systems’ hypothesis [2], perceptual–motor calibration [3], space perception revealed through action [4], and visual–motor imagery [5,6]. Alva Noe's ‘enactive’ approach to perception defined in Action in Perception makes connections with several of the ideas listed above within the framework of defining visual consciousness. There are many ways to frame questions about the role of action in perception.
Element composition of inner ear lymphs in cats, lizards, and skates determined by electron probe microanalysis of liquid samples

Siliconized, glass micropipets whose tips were filled with oil were used to obtain small (<100 nl) liquid samples from perilymphatic and endolymphatic regions of the inner ears of anesthetized animals: 3 cats, 19 alligator lizards (Gerrhonotus multicarinatus), and 8 skates (Raja erinacea). Samples of cerebrospinal fluid and seawater were also obtained for skates. Electron probe microanalysis was used to measure the concentrations of the following elements in each sample: K, Na, Cl, Ca, Mg, P, S. The Na and K concentrations in cat perilymph (Fig. 1 and Table 2) agree with previous estimates (Table 4) while endolymph samples show relatively low Na and high K concentrations. From a comparison of our results with previous work (Table 3), we infer that contamination of endolymph samples with perilymph is relatively low in our study, and that no large species difference in endolymph content is indicated by present data available for mammals. Our results show that Cl concentration is higher and Ca and Mg concentrations are lower in endolymph than in perilymph. The composition of perilymph in cats and alligator lizards is roughly the same (Figs. 1 and 2, Table 2). Uncontaminated endolymph samples in lizards were apparently difficult to obtain, although the compositions of a few samples suggest that endolymph K concentration is high and Na concentration is low. In skates the concentration of Na is nearly the same in the two inner ear lymphs (Fig. 3 and Table 2), in contrast to the roughly hundredfold ratio of perilymph to endolymph Na concentrations found in the higher vertebrates. The element composition of perilymph is correlated with the composition of seawater in which the skates were kept, whereas the endolymph composition shows no such correlation.
Determination of Extractables and Leachables from Single-Use Systems

Single-use systems have been increasingly used in biopharmaceutical manufacturing processes. Despite their multitude of advantages, these plastic and elastomeric assemblies also draw concerns about chemical compounds that may migrate to finished products and impact product quality or safety. Evaluation of such extractables/leachables and their potential impact remains a challenge to many suppliers and end users. Based on extensive experience on filter extractables study, a practical and science-based approach for determination of extractables/leachables from single-use systems used in biomanufacturing has been developed. The general procedure is presented through a case study.
A Theoretical Description of Microdialysis with Mass Transport Coupled to Chemical Events

A random-walk simulation of microdialysis is used to examine how a reaction that consumes analyte in the medium external to the probe affects the extraction and recovery processes. The simulations suggest that such a reaction can promote the extraction process while simultaneously inhibiting the recovery process, which appears to be consistent with recent experimental evidence of asymmetry in the extraction and recovery of the neurotransmitter, dopamine, during brain microdialysis. This suggests that quantitative microdialysis strategies that rely on the extraction fraction as a measure of the probe recovery value, such as the no-net-flux method, will produce an underestimate of the analyte concentration in the external medium when that analyte is consumed by a reaction in the external medium. Furthermore, if experimental conditions arise under which the kinetics of the reaction are changed, then changes in the extraction and recovery processes are likely to occur as well. The implications of these theoretical findings for the quantitative interpretation of in vivo microdialysis results obtained for the neurotransmitter dopamine are examined.
Admission to intensive care unit at the end-of-life: is it an informed decision?

There is a major deficiency in the end-of-life care offered to patients dying in the intensive care unit (ICU). Hypothesis: Hospitalized dying patients had informed discussions on endof-life and palliative care options before admission to ICU. Patients and methods: A descriptive non-interventional study was performed at a teaching hospital to examine if patients who died in hospital had informed discussions on end-of-life care before admission to ICU. The impact of these discussions on subsequent patient care: aggressive therapy in the ICU, the quality of palliation, use of hospice care services and utilization of hospital resources were examined. Data were collected from medical records for all hospital deaths over 24 months. Results: Of 252 hospital deaths, 196 (78%) were treated and subsequently 165 (65%) died in the ICU. Patients treated either in the ICU or general hospital wards had similar frequency of ultimately or rapidly fatal pre-existing disease (47% versus 62%, P: ns) and readmission to hospi...
Liver-kidney transplantation in the Model for Endstage Liver Disease era: is it overdone?

Purpose of review Simultaneous liver-kidney transplantation is increasing. This stimulates concern about unnecessary kidney transplantation (for acute kidney failure, hepatorenal syndrome) in liver transplant candidates. Recent findings Liver transplants are allocated by the Model for Endstage Liver Disease (MELD) score - a number heavily weighted by the serum creatinine. The serum creatinine value varies depending upon the laboratory where it is measured, is different between genders without a correction factor in MELD and is generally inaccurate as a marker of kidney function in liver failure. Criteria for dual transplantation vary between programs and there is no official oversight of the practice. Up to 6.5% of simultaneous transplant candidates on dialysis at listing discontinue dialysis before transplant. Furthermore, simultaneous liver-kidney transplant compared with liver transplant alone improves survival only for those liver candidates on dialysis at transplant. Summary It is time to review the allocation of kidney allografts to liver transplant candidates to avoid inappropriate transplantation. More complete investigation of kidney function following simultaneous liver-kidney transplantation is needed, in addition to improved methods to determine the recoverability of renal dysfunction in liver transplant candidates. Before an optimal algorithm is possible, however, basic and clinical investigation will be needed.
Polymethylmethacrylate particles stimulate bone resorption of mature osteoclasts in vitro.

Background Interaction between wear particle debris and the cells at the implant-bone interface is an important contributory factor to periprosthetic bone loss seen in arthroplasties.Method To investigate the effect of this particle-induced response on different stages of osteoclast maturation, polymethylmethacrylate (PMMA) particles were added to a murine osteoclastogenic bone marrow cell culture system at either day 0, day 4, or day 8 of culture, which represented PMMA particle stimulation of precursor osteoclasts, mature osteoclasts, or end-stage osteoclasts, respectively. The number of TRAP-posi-tive multinucleate cells (MNCs) and the degree of bone resorption in culture were measuredResults Treatment of precursor osteoclasts with PMMA particles resulted in a statistically significant increase in TRAP-positive MNCs that persisted for 4 days, but there was no significant increase in bone resorption. Addition of particles to mature osteoclasts resulted in a significant increase in the number of TRAP-pos...
The geodemographic correlates of broadband access and availability in the United States

The Telecommunications Act of 1996 (TA96) was a complex piece of legislation that included a variety of mandates for the telecommunications market and its providers in the United States. A particularly important strategic goal of the TA96 was to establish regulatory policies that promote competition, innovation, and investment in broadband services and facilities. This includes the timely rollout of advanced telecommunication services to all Americans regardless of location, race, age or socioeconomic status. This paper documents the spatial and temporal distribution of advanced telecommunication services in the United States from December 1999 to June 2002, paying special attention to broadband availability at the local level. In addition, this paper explores local socioeconomic and demographic trends relating to broadband availability through the use of a nationwide geodemographic classification system. Results suggest that broadband availability is no longer simply a question of geography (i.e. urban vs. rural). Rather, there exists a complex and dynamic interplay between geography, socioeconomic status, market forces and policy--all of which shape the current broadband landscape.
The World's Nicest Grown‐Up: A Fantasy Theme Analysis of News Media Coverage of Fred Rogers

This article applies fantasy theme analysis (Bormann, 1972, 1976, 1982, 1983, 2000) to explain the rhetorical vision that emerges from newspaper and broadcast news coverage of American television personality Fred Rogers. For the past 3 decades, journalists have framed Rogers as a calming influence and treated him with deference and respect. Journalists have created a fantasy about Rogers that holds him up as the embodiment of television’s potential, potential that can be realized only by returning to the quiet tolerance and the power of imagination at the heart of Mister Rogers’ Neighborhood. For reporters in this interpretive community, Rogers offers hope for those struggling to raise children. A rhetorical vision of Rogers as “the world’s nicest grown-up,” the “Dalai Lama of television,” and “the Pied Piper of children’s television” is constructed out of the fantasy themes by journalists stepping outside their usual role as objective observers. Journalists who start off skeptical of Rogers and his approach find themselves captivated by his message, and they insert this experience into their coverage of Rogers, making it a key fantasy theme. Fred Rogers is one of the most revered figures in the history of U.S. television. His half-hour program, Mister Rogers’ Neighborhood, ran for PBS for more than 3 decades. His friendly, reassuring approach to teaching life’s lessons has earned him generations of fans. Rogers is devoted to the idea that television can educate children through a mix of simple but profound storytelling and the encouragement of imagination. This article applies fantasy theme analysis (Bormann, 1972, 1976, 1982, 1983, 2000) to explain the rhetorical vision that emerges from newspaper and broadcast news coverage of Rogers since Mister Rogers’ Neighborhood went on the air in the late 1960s. Reporters celebrate the virtues exemplified by Rogers—hard work,
Numerous proplyd candidates in the harsh environment of the Carina Nebula

We report the discovery of dozens of compact objects in the Carina Nebula (NGC 3372) that closely resemble proplyds (photoablating protoplanetary disks and dark silhouette disks) seen previously in the Orion Nebula. This is the first detection of a large number of such objects outside Orion. They imply that low- and intermediate-mass star formation is proceeding actively in Carina, despite threatening conditions imposed by very hot massive stars. The proplyd candidates that we have detected are larger than those in Orion but more compact than irregular molecular globules within the H II region. Smaller proplyds may still be lurking in Carina, waiting to be discovered. Orion apparently lacks objects of comparable size, and we consider several explanations. Larger proplyds may come from larger and more massive circumstellar disks surrounding young Herbig Ae/Be stars that should be numerous in Carina. Alternatively, far-UV radiation from the massive star η Car may have, in the recent past, enhanced photoablation and expanded proplyd ionization fronts. Some unusual proplyd candidates may also imply that time-dependent effects associated with η Car's current evolutionary state may be critical.
Tonsillitis in Dogs Due to Hemolytic Streptococci

Conclusion(1) Hemolytic streptococci are constantly present in the tonsilsof apparently normal dogs (92.3%). They occur in predominant numliers in acute tonsillitis of dogs and are secondary invaders in the bronchopneumonia of distemper. (2) Experimentally acute tonsillitis is produced by swabbing freshly isolated canine strains on the surface of the tonsils of dogs. A human strain (S. epidenzictrs failed to produce a reaction. (3) The streptococci from dogs conform to the animal type and differ from the human type.
In vitro studies on oxidative and lipid metabolism in the immature macaque monkey.

Summary The effects of diets differing qualitatively in fatty acid composition on blood and tissue lipids and upon oxidative and lipid biosynthetic pathways in monkeys ( Macaca mulatta ) have been followed. The milk-fat diet, as compared with the vegetable-fat diet, led to higher serum cholesterol, serum total lipid and liver cholesterol values. Adrenal cholesterol was lower in the milk-fat group, but kidney cholesterol values were higher. [1- 14 C]Acetate and [2- 14 C]mevalonate incorporation into cholesterol in the liver was lower in the milk-fat group, so that the hypercholesterolemia observed in the latter group is not attributable to increased cholesterol synthesis. Other metabolic changes are described for the two groups.
Genomic response to interferon-α in chimpanzees: Implications of rapid downregulation for hepatitis C kinetics†

The mechanism of the interferon-alpha (IFN-alpha)-induced antiviral response during hepatitis C virus (HCV) therapy is n o t completely understood. In this study,we examined the transcriptional response to IFN-alpha in uninfected chimpanzees after single doses of chimpanzee, human, or human-pegylated IFN-alpha. Liver and peripheral blood mononuclear cell (PBMC) samples were used for total genome microarray analysis. Most induced genes achieved maximal response within 4 hours, began to decline by 8 hours, and were at baseline levels by 24 hours postinoculation, a time when high levels of circulating pegylated IFN-alpha were still present. The rapid downregulation of the IFN-alpha response may be involved in the transition between the observed phase I and phase II viral kinetics during IFN-alpha therapy in HCV-infected patients. The response to all three forms of IFN-alpha was similar; thus, the reasons for previous failures in antiviral treatment of chimpanzees with human IFN-alpha were not due to species specificity of IFN-alpha. The response to IFN-alpha was partially tissue-specific. A total of 1778 genes were altered in expression by twofold or more by IFN-alpha, with 538 and 950 being unique to the liver or PBMC, respectively. Analysis of the IFN-alpha and IFN-gamma responses in primary chimpanzee and human hepatocytes were compared as well. IFN-alpha and IFN-gamma induced partially overlapping sets of genes in hepatocytes. In conclusion, the response to IFN-alpha is largely tissue-specific, and the response is rapidly downregulated in vivo, which may have a significant influence on the kinetics of antiviral response.