cssi/SciSciGPT-SciSciNet huggingface dataset:
A kinetic dissection of the fast and superprocessive kinesin-3 KIF1A reveals a predominant one-head-bound state during its chemomechanical cycle

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.
Generating single-stranded DNA circles with minimal resources.

Abstract Single-stranded circular oligonucleotides are heavily utilized in rolling circle amplification and rolling circle transcription technologies. Although various reported methodologies are available to synthesize circular, single-stranded DNA (ssDNA), the unduly complicated protocols and the associated cost minimize the utility of these methodologies to a non-expert or a beginner in the field. Our protocol provides the simplest yet robust synthesis of circular ssDNA templates to be utilized in various applications, using minimal resources. • In this manuscript, we describe the most basic approach to synthesize circular ssDNA. • Our method utilizes the minimal resources, yet it is robust. • The utility of the methodology is very high for a non-expert or a beginner in the field.
Characterization of cytoplasmic lipid droplets in each region of the small intestine of lean and diet-induced obese mice in response to dietary fat.

This study reflects the dynamics of fat absorption along the length of the small intestine in lean and obese mice in the physiological response to dietary fat. We identified unique features of cyto...
Examining High School Students’ Gendered Beliefs about Math: Predictors and Implications for Choice of STEM College Majors:

Utilizing the High School Longitudinal Study, a nationally representative sample of U.S. high school students, this study investigates the factors that predict different beliefs about gendered math...
Physiology, Growth, and Inhibition of Microbes in Foods

This chapter addresses three issues: (i) the ability of bacteria to use different biochemical pathways to generate the energy required to grow under adverse conditions in foods; (ii) the interaction of bacteria and foods in ecosystems in which the cells may exist in a variety of physical and physiological states and in which the roles of intrinsic and extrinsic factors and (iii) the kinetics of microbial growth. It talks about microbial physiology and metabolism, and glycolytic pathways such as Embden-Meyerhof-Parnas Pathway and Entner-Doudoroff Pathway. It also discusses the heterofermentative catabolism, homofermentative catabolism, tricarboxylic acid cycle, aerobes, anaerobes, the regeneration of NAD, and respiration, bioenergetics. The food ecosystem is composed of intrinsic factors, which are inherent to the food (i.e., pH, water activity [aw], and nutrients) and extrinsic factors, which are external to it (i.e., temperature, gaseous environment, and the presence of other bacteria). In addition, the chapter focuses on the physiological and genetic responses that bacteria utilize in osmoregulation. Bacteria are classified as psychrophiles, psychrotrophs, mesophiles, and thermophiles according to how temperature influences their growth. Microbial growth in foods is a complex process governed by genetic, biochemical, and environmental factors.
Topological phase transitions in ultracold Fermi superfluids: The evolution from Bardeen-Cooper-Schrieffer to Bose-Einstein-condensate superfluids under artificial spin-orbit fields

We discuss topological phase transitions in ultracold Fermi superfluids induced by interactions and artificial spin-orbit fields. We construct the phase diagram for population-imbalanced systems at zero and finite temperatures, and analyze spectroscopic and thermodynamic properties to characterize various phase transitions. For balanced systems, the evolution from Bardeen-Cooper-Schrieffer to Bose-Einstein-condensate superfluids in the presence of spin-orbit effects is only a crossover as the system remains fully gapped, even though a triplet component of the order parameter emerges in the helicity basis. However, for imbalanced populations, spin-orbit fields induce a triplet component for the order parameter in the helicity basis, and may produce nodes in the quasiparticle excitation spectrum leading to bulk topological phase transitions of the Lifshitz type. Additionally a fully gapped phase exists, where a crossover from indirect to direct gap occurs, but a topological transition to a gapped phase possessing Majorana fermion edge states does not occur.
Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses

ABSTRACT Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the “host jumping” potential of a virus into a new host species. IMPORTANCE We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible to other virus species. We present an algorithm that predicts which species have cell surface receptors that make them susceptible to Machupo virus, based on computational docking of protein structures. Few molecular models exist for predicting the risk of spillover of a particular animal virus into humans or new animal populations. Our results suggest that a combination of evolutionary analysis, structural modeling, and experimental verification may provide an efficient approach for screening and assessing the potential spillover risks of viruses circulating in animal populations.
Texture Measurement Techniques for Zircaloy Cladding: A Round-Robin Study

A round-robin study of the texture of zircaloy tubing was conducted. Experimental techniques and texture determination results from 14 independent laboratories are presented. Results are consistent and reproducible, as determined both qualitatively (pole figures) and quantitatively (f-parameters). It was concluded that reliable x-ray diffraction techniques exist which describe the texture and that results from the participating laboratories are comparable. A number of parameters which can affect texture results are also discussed. 22 refs.
Late-onset Ochrobactrum anthropi sepsis in a preterm neonate with congenital urinary tract abnormalities

Recent trends in late-onset neonatal sepsis have revealed an increase in Gram-negative organisms as causative agents. Ochrobactrum anthropi is an emerging human pathogen that has been reported primarily in immunocompromised hosts, especially those with indwelling catheters or other medical devices. We report the occurrence of late-onset urosepsis secondary to O. anthropi in a preterm neonate with posterior urethral valves and review the salient features of the pathogen and its management.
Richard Nixon: Rhetorical Strategist

Series Foreword Foreword by Halford R. Ryan Preface Critical Analysis Collected Speeches Index
A simple one-step HPLC procedure for the purification of the NH2-terminal plasmin-derived Bβ1–42 peptide of human fibrinogen

Abstract Simplified procedures were developed to produce and isolate the plasmin-derived Bβ1–42 fragment from human fibrinogen. Peptides generated from fibrinogen by plasmin were separated by reverse phase HPLC chromatography. Two distinct peaks were identified as having amino acid compositions identical to Bβ1–42. The average final yield of HPLC-purified Bβ1–42 was 1.2 mg per 100 mg of fibrinogen. Recovery of the peptide (40–45% when compared to the theoretical yield) was significantly higher than yields obtained by open column techniques demonstrating the advantages of this simple one-step HPLC procedure.
Breast cancer risks in individuals testing negative for a known family mutation in BRCA1 or BRCA2.

Genetic testing for BRCA1 and BRCA2 mutations in family members of individuals with known deleterious mutations can distinguish between patients at high risk of disease and those who are not. Some studies have suggested that individuals testing negative for known familial mutations (true negatives), may still have a higher risk of breast cancer (BC) than the general population. We have examined a prospectively followed cohort of true negative women in the US. Subjects were close relatives of known BRCA1 and BRCA2 mutation carriers who had undergone genetic testing, were negative for the known familial mutation, and were unaffected at the time of genetic testing. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using SEER incidence rates. Among 375 true negatives, two invasive and two in situ BC and no ovarian cancers were diagnosed with mean follow up of 4.9 years (total of 1,962 person-years). Four invasive BC were expected, whereas two were observed, for an age-adjusted SIR of 0.52 (95% CI 0.13–2.09). We observed more cases of in situ BC (n = 2) than were expected (n = 0.9; SIR = 2.30; 95% CI 0.57–9.19). There were no cases of ovarian cancer observed; 0.4 case was expected. In this prospective study of women who were unaffected at the time of genetic testing and who were negative for the known familial mutation in BRCA1/2, no excess risk of invasive BC was observed. Our data suggest that such women in the US should adhere to population-based guidelines for breast cancer screening.
Measuring the success of public participation on environmental restoration and waste management activities in the U.S. Department of Energy

Abstract The value added by public participation to decision-making in the Office of Environmental Management (EM) in the Department of Energy (DOE) can be enhanced through better organization, improved participation strategies and mechanisms, and integration with other aspects of decision-making (e.g., problem definition, mission development, identification and evaluation of decision alternatives, and decision implementation). The opportunity to improve the value added by public participation, however, is contingent on being able to demonstrate that the resources devoted to such activity is a sensible and worthwhile investment. This article summarizes research conducted to expand those savings and improvements and facilitate other improvements by developing a set of performance-based indicators, based on discrete attributes of successful public involvement, for use in evaluating public participation programs and activities in EM, with special emphasis on activities implemented in the field offices of DOE. The success attributes and indicators were developed through reviews of appropriate research literatures and through intensive interviews with and surveys administered to diverse stakeholders, including DOE project managers and public participation specialists, contractor project managers and public participation specialists, representatives of tribal, state, and local governments, federal and state regulatory authorities, environmental interest groups, and other interested parties, at nine DOE facilities in the United States.
From ‘Underclass’ to ‘Undercaste’: Some Observations about the Future of the Postindustrial Economy and its Major Victims

When in 1963 Gunnar Myrdal took an old-fashioned Swedish word for ‘lower class’ to describe a new American ‘underclass’, little did he know what immense effects his brief, seemingly offhand, new conceptualization would have on America’s view and treatment of the poor. Indeed, had he known, I am sure he would have chosen another term, if only because some subsequent distortions of his idea ignored his crucial insight into the future of the US economy and those whom he saw as its newest victims. My chapter is devoted to some observations about that insight 30 years after the publication of his new concept, and about two other topics: variations in how the victims of the post-industrial economy are chosen in different countries; and cross-national variations in the definitions and uses of the term ‘underclass’. But before discussing these topics, a brief history of what happened to Myrdal’s concept in America is in order.
Functional similarities between the cytoplasmic organelles of melanocytes and the mitochondria of hepatocytes.

IN an earlier communication1, it was reported that the cytoplasm of melanocytes, located in the liver of the amphibian Amphiuma, is packed with large organelles containing melanin granules in varying numbers. These melanocytes have few mitochondria and no visible ribosomes, in contrast to the hepatocytes which present the familiar organelles in large numbers. The sharp structural differences between the respective liver cells evoked our interest in comparing the functions of the organelles which abound in each. The insight to be gained from such investigations seemed to transcend the particular melanocytes under discussion: normal cells with similar structures are being seen in other organs2–4 and in other vertebrates5,6, while abnormal metabolism of melanins is being encountered in human diseases ranging from neoplasia7 to extrapyramidal disorders of the brain8,9.
Deficit analysis: service capacity assessment and planning in developing countries – case study in the Philippines

Current demand analysis methods do not formally cover the case of chronic deficits in quantity or quality of water and sanitation services. These services include drinking water supply (DWS), wastewater and sewage treatment (WST), and municipal solid waste management (MSW). Formal analysis of this case would, at minimum, define the deficit state and evaluate appropriate options for reducing it. This paper proposes for a formal analytical model for municipal sanitation systems (MSS) that operate with deficits in at least one of the constituent services of DWS, WST, or MSW. The model introduces definitions and notation for describing the deficit state for conducting demand analysis on municipal sanitation systems. This model of demand analysis for systems with chronic deficits will hereinafter be referred to as deficit analysis. A case study for Bacoor, Philippines is presented as an example.
Accumulation and decay of chlorothalonil and selected metabolites in surface soil following foliar application to peanuts.

One of the principal uses of the fungicide, chlorothalonil, is control of foliar peanut diseases. Recent assessments indicate its runoff from treated fields in southeastern states presents risks to aquatic life. Two factors that control its runoff are how much reaches soil surfaces and degradation rates. To address these questions and to evaluate accumulation and decay of key metabolites, soil samples (0−2 cm) were collected after seven chlorothalonil applications on experimental peanut plots in south central Georgia during the 1999 growing season. At the start of and during laboratory incubations, samples were analyzed for the parent and degradates by HPLC−PDA−APCI−MS. The maximum observed residue levels were after the second application, after which canopy closure reduced soil deposition from later applications to 5−10% of applied amounts. After the last spray, <5% of the cumulative chlorothalonil applied was detected in the soil. Foliar interception and dissipation and rapid soil degradation contribute...
The membrane associated kinases which phosphorylate bone and dentin extracellular matrix phosphoproteins are isoforms of cytosolic CKII

Bone and dentin contain many phosphoproteins in their extracellular matrix. It has been postulated that the anionic character of these proteins, and the presence of phosphate groups in particular, is important for various functions related to biomineralization. Phosphophoryns (PP), are the most highly phosphorylated dentin matrix components. However, the tissue form of PP can be further phosphorylated in vitro by cytosolic and membrane associated-endogenous messenger-independent kinases from osteoblast-like cells. To examine the kinases, a 2-dimensional zymogram technique has been developed for the detection of casein kinase II (CKII) activity of purified kinases using intact PP as the substrate. After isolation by subcellular fractionation and ion-exchange chromatographic techniques, the enzymes are electrophoresed on an isoelectric focusing gel in the absence of SDS and disulfide bond breaking reagents. This first dimension gel is then layered on the zymogram gel containing PP + SDS. After electrophores...
Excision of Tumors in the Nasal Vestibule of Two Dogs

Two dogs with tumors in the left nasal vestibule were treated by surgical excision of the affected part of the nose. Radiation and chemopotentiation were used in one dog, which remained tumor-free after 12 months. When recovering from anesthesia, the second dog developed respiratory distress associated with upper airway obstruction and failure to mouth breathe. The dog was successfully treated by temporary tracheostomy and remained tumor-free after 3 months. Surgery preserved the function of the right nostril and gave an acceptable cosmetic result in both cases.
Access Control and Authentication for Converged Wireless Networks

This paper presents a novel AAA architecture featuring the use of role-based access control and authentication for a converged wireless network where a single operator, as in one of the North American operators who offer both cellular and DSL service, provides the converged services and broadband access. Important features, such as mutual authentication, fast roaming and NAT traversal issues in heterogeneous wireless networks, are discussed. In addition, the paper proposes a modeling approach to address converged network security in a systematic and cost efficient manner.
Teaching Phonological Recoding to Young Children with Phonological Processing Deficits: The Effect on Sight-Vocabulary Acquisition

This training study combines within-subjects comparisons of several literacy tasks with individual case studies of children with dyslexia over a five-month reading intervention. It was hypothesized...
Converting color values using stochastic interpolation

A major task in processing scanned images is converting the color values from the non-colorimetric color space used by the scanner to a device-independent color space or the color space of an output device. For example, typical color scanners produce 24-bit RGB values for each color pixel, while most printers use color spaces such as CMY or CMYK. While this conversion can be accomplished using a lookup table, the 16 million entries required makes the direct lookup table prohibitively large. This suggests use of a sparse lookup table, where only certain values are directly mapped. For all color values that are not directly mapped, the unknown values may be calculated from the nearest table entries via trilinear interpolation, a computationally intensive process. This paper presents a method of efficiently converting from a set of noisy color values to a set of device colorants. Using a deterministic process, 24-bit scanned color values are reduced to dithered 12-bit RGB table indices. After the reduction, a small but complete lookup table with 4096 entries converts the RGB values directly to the output color space. This stochastic interpolation process, while minimizing banding and abrupt color transitions, eliminates the need for trilinear interpolation of the data and significantly reduces the size of the lookup table.
Process control of polymer extrusion. Part I: Feedback control

On-line computer control of extrudate thickness was carried out using a 2–1/2 Inch single screw plasticating extruder. Predried poly(methyl methacrylate) (PMMA) was extruded through a slit die. Two feedback control methods, a conventional PI controller and a Smith predictor dead time compensation, were tried for both set point changes (i. e., extrudate thickness changes) and load changes (i. e., screw speed changes). Results showed that both the PI feedback control and the Smith predictor were satisfactory for long term set point changes but not for load changes. Since the Smith predictor may compensate the process dead time, it would be useful for regulating short term set point changes such as barrel temperature settings.
Hard‐sphere theory for correlation of tracer diffusion of gases and liquids in alkanes

The rough hard‐sphere (RHS) theory for transport properties has substantially improved understanding of diffusion, viscosity, and thermal conductivity. At present, however, quantitative predictions for polyatomic species are hampered by uncertainties in assigning the hard‐sphere diameter and the roughness factor, and by lack of molecular dynamics calculations. Because the qualitative features of the theory have proven correct for a variety of chemical systems, methods have been proposed for using rough hard‐sphere theory even when the exact parameters needed to apply the theory are unknown. One such approach is examined for tracer diffusion in alkane solvents for solutes ranging in size from hydrogen to hexadecane. Useful relations are shown which are simple, yet entirely consistent with hard‐sphere theory. The approach circumvents the difficulties in assigning roughness factor, diameter, and molecular dynamics results.
Effects of cold acclimation and 6-OHDA sympathectomy on cold tolerance of rats

Abstract 1. 1.|Cold tolerance (−10°C) of cold-acclimated (5°C) and non-cold-acclimated (23°C) rats, with and without 6-OHDA sympathectomy, was evaluated. 2. 2.|Cold acclimation enhanced the rats' tolerance to cold. 3. 3.|Cold-acclimated 6-OHDA-treated animals were able to maintain their colonic temperature better than saline-treated rats. 4. 4.|Non-cold-acclimated 6-OHDA-treated rats were unable to maintain their colonic temperature to the same extent as the saline-treated rats.
Intuitive confidence: choosing between intuitive and nonintuitive alternatives.

People often choose intuitive rather than equally valid nonintuitive alternatives. The authors suggest that these intuitive biases arise because intuitions often spring to mind with subjective ease, and the subjective ease leads people to hold their intuitions with high confidence. An investigation of predictions against point spreads found that people predicted intuitive options (favorites) more often than equally valid (or even more valid) nonintuitive alternatives (underdogs). Critically, though, this effect was largely determined by people’s confidence in their intuitions (intuitive confidence). Across naturalistic, expert, and laboratory samples (Studies 1–3), against personally determined point spreads (Studies 4 –11), and even when intuitive confidence was manipulated by altering irrelevant aspects of the decision context (e.g., font; Studies 12 and 13), the authors found that decreasing intuitive confidence reduced or eliminated intuitive biases. These findings indicate that intuitive biases are not inevitable but rather predictably determined by contextual variables that affect intuitive confidence.
MERLIN...and the geneticist's stone?

This MERLIN is not a wizard, but a new software package offering more rapid calculation of multipoint linkage likelihoods in larger pedigrees than has been possible. The practical advances provided by MERLIN are certainly welcome, but perhaps we need a little magic as well.
Recombinant tissue plasminogen activator infusion for hemodialysis catheter clearance

Hemodialysis (HD) catheter occlusion is a common cause of poor blood flow and inadequate dialysis. In order to address this problem in our pediatric dialysis unit, we elected to use short (2-h) infusions of low-dose recombinant tissue plasminogen activator (rtPA) for thrombolysis of occluded catheters. Catheters meeting diagnostic criteria for thrombosis were infused with 2.5 mg rtPA in 25 ml 0.9 normal saline over 2 h prior to dialysis. Retrospective data collection was carried out to assess the success of this procedure. Variables assessed included blood flow (Qb), transmembrane pressure (TMP) and venous pressure (VP) before and after rtPA infusion. Seven catheter thromboses in six patients were successfully treated with rtPA; there were significant improvements in Qb ( p 200 ml/min. No adverse events were observed. Low-dose rtPA infusion is safe and effective for catheter thrombolysis in outpatient pediatric HD patients. It may serve as an alternative method of administration to local instillation and may be used to restore patency before resorting to surgical revisions.
Uncertainty Analysis of Structural Dynamics by Using Two-Level Gaussian Processes

Uncertainty analysis is an important part of structural dynamic analysis in various applications. When a large complex structure is under consideration, component mode synthesis (CMS) is frequently used for reduced-order numerical analysis. But even so, in some situations the computational costs are still high for repeated running of a computer code which is required in uncertainty analysis. Gaussian processes offer an emulation approach to realization of fast sampling over a given parameter configuration space. However, both the low-fidelity data obtained by CMS and the corresponding sample obtained by Gaussian process emulation need to be assessed by comparing with high-fidelity data which can be obtained but are usually very expensive. When obvious bias exist in the low-fidelity data, two-level Gaussian processes are introduced for processing both the low- and high-fidelity data simultaneously to make more accurate predictions of quantities of interest. CMS can serve not only to provide low-fidelity data but also to locate problematic areas on complex structures. Comparisons of the results obtained by Monte Carlo sampling, which is performed using both a full finite element model and a CMS model, indicate that two-level Gaussian processes can be an efficient tool to emulate high-fidelity sampling with guaranteed accuracy.Copyright © 2011 by ASME
Semiconductor nanowire photovoltaics

The use of semiconductor nanowires for photovoltaic applications is advantageous for several reasons: 1) it permits interpenetrating networks of materials for semiconductor heterojunctions at the nanoscale, allowing efficient carrier extraction following light absorption, 2) long absorption paths are possible while maintaining short distances for carrier collection, even in imperfect materials, 3) single crystal materials can be grown in relatively thin films with little material, 4) strong light trapping is possible due to the geometry of the nanowires, and 5) manipulation of materials properties is possible by varying the size of the nanostructures. These advantages must be traded off against the difficulties of fabricating devices (particularly planarization of structures), issues with recombination centers at interfaces, and the requirement of making ohmic contacts with relatively low temperature processes. The optical and electronic properties of semiconductor nanowires, nanowire arrays, and heterojunction interfaces are discussed. Recent results for photovoltaic cells based on semiconductor nanorods and nanowires are summarized, and opportunities for improvement of device characteristics are presented.
Transcriptional Regulation of Heart Valve Progenitor Cells

The development and normal function of the heart valves requires complex interactions among signaling molecules, transcription factors and structural proteins that are tightly regulated in time and space. Here we review the roles of critical transcription factors that are required for specific aspects of normal valve development. The early progenitors of the heart valves are localized in endocardial cushions that express transcription factors characteristic of mesenchyme, including Twist1, Tbx20, Msx1 and Msx2. As the valve leaflets mature, they are composed of complex stratified extracellular matrix proteins that are regulated by the transcriptional functions of NFATc1, Sox9, and Scleraxis. Each of these factors has analogous functions in differentiation of related connective tissue lineages. Together, the precise timing and localized functions of specific transcription factors control cell proliferation, differentiation, elongation, and remodeling processes that are necessary for normal valve structure and function. In addition, there is increasing evidence that these same transcription factors contribute to congenital, as well as degenerative, valve disease.
Neuronal-Astrocyte Metabolic Interactions: Understanding the Transition into Abnormal Astrocytoma Metabolism

Brain function depends on complex metabolic interactions among only a few different cell types, with astrocytes providing critical support for neurons. Astrocyte functions include buffering the extracellular space, providing substrates to neurons, interchanging glutamate and glutamine for synaptic transmission with neurons, and facilitating access to blood vessels. Whereas neurons possess highly oxidative metabolism and easily succumb to ischemia, astrocytes rely more on glycolytic metabolism and hence are less susceptible tolack of oxygen. Astrocytoma cells seem to retain basic metabolic mechanisms of astrocytes; for example, they show a high glycolytic rate, lactate extrusion, ability to flourish under hypoxia, and opportunistic use of mechanisms to enhance cell division and maintain growth. Differences in metabolism between neurons and astrocytes may also extend to astrocytoma cells, providing therapeutic opportunities against astrocytomas, including sensitivity to acetate, a high rate of glycolysis and lactate extrusion, glutamate uptake transporters, differential sensitivities of monocarboxylate transporters, presence of glycogen, high interlinking with gap junctions, use of nicotinamide adenine dinucleotide phosphate for lipid synthesis, using different isoforms of synthetic enzymes (e.g. isocitrate dehydrogenase, pyruvate carboxylase, pyruvate kinase, lactate dehydrogenase), and different glucose uptake mechanisms. These unique metabolic susceptibilities may augment conventional therapeutic attacks based on cell division differences and surface receptors alone.
Cluster randomization trials: A simulation study

A simulation study is conducted to compare several methods that test the common log odds ratio in multiple 2 x 2 tables when the data are correlated within clusters. Allowing cluster size to vary within each table, we evaluate the unadjusted Mantel-Haenszel chi-square statistic (X 2 MH ), the adjusted Mantel-Haenszel chi-square statistics of Rao and Scott using both an unpooled design effect (X 2 RSN ) and a pooled design effect (X 2 RSP ), the adjusted Mantel-Haenszel chi-square statistic of Donald and Donner (X 2 DD ), the chi-square statistic using the GEE approach (X 2 GEE ), the adjusted Mantel-Haenszel chi-square statistic of Begg (X 2 B ), the Wald (X 2 W ), the robust Wald (X 2 RW ), the score (X 2 S ), the robust score (X 2 RS ), and the adjusted Mantel-Haenszel chi-square statistics of Zhang and Boos (X 2 ZBP and X 2 ZBN ). The test statistics above are compared in terms of empirical significance levels and empirical power levels. The robust score statistic X 2 RS and the adjusted Mantel-Haenszel chi-square statistics of Zhang and Boos (X 2 ZBP and X 2 ZBN ) generally have empirical significance levels closer to the nominal value than the other statistics. These three statistics have similar empirical power levels when the intracluster correlation is zero or the cluster sizes are balanced. X 2 RS performs better in terms of empirical power levels when a positive intracluster correlation exists in the imbalance setting.
Physical map of chromosomal and plasmid DNA comprising the genome of Leptospira interrogans

The size and physical structure of the Leptospira interrogans genome was characterized using contour-clamped homogenous electric field (CHEF) gel electrophoresis. The L. interrogans genome is approximately 4750 kb in size and is composed of two molecular species of DNA: a 4400 kb chromosome; and a 350 kb plasmid, pLIN1. A physical map of the chromosome was constructed with the restriction enzymes NotI and SfiI. A physical map of pLIN1 was constructed with ApaI, NotI, Sse83871, SgrAI, and SmaI. Both the L. interrogans chromosome and pLIN1 are circular.
Trauma-induced alterations in macrophage function.

Background: The juxtaposition of immune suppression and a hyperactive inflammatory response after injury represents a paradox in immune function. The aim of this study was to evaluate the delayed macrophage hypersecretion of inflammatory mediators in relation to functional macrophage defects. Methods: BALB/c mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One and 7 days after injury, splenic macrophages were isolated and assayed for antigen presentation and the production of inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin (IL)-6, prostaglandin E2, H202, and nitric oxide. Results: One day after injury, there were significantly diminished macrophage antigen presentation and decreased mean production of TNF-α, IL-6, and H202. In contrast, 7 days after injury, splenic macrophages produced significantly increased mean amounts of TNF-α, IL-6, prostaglandin E2, H202, and nitric oxide, with a persistent functional defect in antigen presentation. Conclusions: This phasic response to trauma suggests a persistent state of macrophage dysregulation that may help explain the paradox of immune suppression, manifested by functional defects predisposing patients to increased infections, in the setting of inflammatory mediator hypersecretion, predisposing patients to the systemic inflammatory response syndrome/multiple organ dysfunction syndrome. (Surgery 1998;123:96-101.)
Relating nanomaterial properties and microbial toxicity

Metal and metal oxide nanoparticles are among the most commonly used nanomaterials and their potential for adversely affecting environmental systems raises concern. Complex microbial consortia underlie environmental processes, and the potential toxicity of nanoparticles to microbial systems, and the consequent impacts on trophic balances, is particularly worrisome. The diverse array of metal and metal oxides, the different sizes and shapes that can be prepared and the variety of possible surface coatings complicate assessments of toxicity. Further muddling biocidal interpretations are the diversity of microbes and their intrinsic tolerances to stresses. Here, we review a range of studies focused on nanoparticle–microbial interactions in an effort to correlate the physical–chemical properties of engineered metal and metal oxide nanoparticles to their biological response. General conclusions regarding the parent material of the nanoparticle and the nanoparticle's size and shape on potential toxicity can be made. However, the surface coating of the material, which can be altered significantly by environmental conditions, can ameliorate or promote microbial toxicity. Understanding nanoparticle transformations and how the nanoparticle surface can be designed to control toxicity represents a key area for further study. Additionally, the vast array of microbial species and the structuring of these species within communities complicate extrapolations of nanoparticle toxicity in real world settings. Ultimately, to interpret the effect and eventual fate of engineered materials in the environment, an understanding of the relationship between nanoparticle properties and responses at the molecular, cellular and community levels will be essential.
A microprocessor based feedback controller for mechanical ventilation

A microcomputer feedback system has been developed which adjusts the inspired minute volume of a ventilator based on the patient's end-tidal CO2 concentration. The feedback controlled ventilator was evaluated in 6 dogs (18-20 kg). Arterial PCO2 was monitored continuously while end-tidal CO2 concentration was controlled by the micro-computer system and the following perturbations introduced: [1] NaHCO3 was infused IV, [2] a pulmonary artery was occluded, [3] one lumen of a double lumen endobronchial tube was occluded, and [4] an air embolism was given. The end-tidal PCO2 controller kept PaCO2 within 1.2 mm Hg of the desired value when CO2 production increased by as much as 44%. Changing the ventilation/perfusion ratios caused differences as large as 22 mm Hg between the arterial and end-tidal PCO2 and the controller was not effective in keeping PaCO2 at the desired level. Closed loop control of ventilation based on end-tidal PCO2 measurements successfully compensated for increases in CO2 production keeping PaCO2 constant. The controller did not, however, keep PaCO2 at the desired level when significant changes occurred in the distribution of blood flow to ventilation.
A collaborative therapeutic relationship and risk of suicidal ideation in patients with bipolar disorder.

Abstract Background A diagnosis of Bipolar Disorder (BD) is among the strongest known risk factors for suicide. The present study examines the relative impact of current mood state (depressed, manic or mixed) and patient perceptions of the therapeutic relationship on suicidal ideation in veterans with BD. Methods We conducted analyses of the baseline data from a naturalistic cohort study of veterans receiving care for BD ( N = 432) at a large urban VA mental health clinic. Logistic regression was used to examine the relative impact of patient- and treatment-related factors on suicidal ideation within the two weeks prior to recruitment. Results Over 49% (213/432) of veterans receiving current outpatient treatment for BD reported at least some suicidal ideation within the two weeks prior to recruitment. After accounting for current mood state and other identified risk factors, even minimal increases (i.e., per point increase on a 0–60 rating scale) in the extent to which the therapeutic relationship is perceived as collaborative (OR = 0.97; p Limitations This study is cross sectional and relies exclusively on patient self-report. Conclusions Mental health treatment providers should be aware of the high rate of suicidal ideation in patients with BD. Successful management of suicidal ideation likely involves a focus on improving symptoms as well as establishing a collaborative therapeutic relationship.
Iterative Algorithms for Solving Mixed Model Equations

Abstract Iterative algorithms for obtaining solutions for sire effects and breeding value estimates from progeny with records in mixed model procedures were compared. Successive overrelaxation with adaptive acceleration and a Jacobi conjugate gradient method seem to be more generally useful for two general areas of interest: 1) sire evaluation models, where some effects are absorbed; and 2) reduced animal models, where no effects are absorbed. An inverse of the relationship matrix may be included as part of the coefficient matrix and its inclusion will not prevent convergence. Key features include: 1) scaling the equations so that all diagonal elements are 1 and the scaled coefficient matrix remains real, symmetric, and positive definite; 2) calculation of a new relaxation parameter during run time to approximate the value that will yield fastest convergence; 3) calculation of a new relaxation parameter after convergence begins to slow down; and 4) use of numerically accurate and efficient convergence criteria. The Jacobi conjugate gradient method was 55% more efficient than successive overrelaxation in solving reduced animal model equations of order 3356. Number of iterations and total execution times for all iterations were: 83, 2.89s and 169, 6.44s, respectively. Another reduced animal model application with equations of order 38,139 converged in 38s (50 iterations) using successive overrelaxation. Solutions for sire equations constrained to full rank converged more quickly than unconstrained equations.
Apolipoprotein A-I α-Helices 7 and 8 Modulate High Density Lipoprotein Subclass Distribution

Abstract Mice have a monodisperse high density lipoprotein (HDL) profile, whereas humans have two major subfractions designated HDL2 and HDL3. Human apoA-I transgenic mice exhibit a human-like HDL profile, indicating that the amino acid sequence of apoA-I is a determinant of the HDL profile. Comparison of the primary sequence of mouse and human apoA-I and the previously designated “hinge” domain of apoA-I led us to hypothesize that α-helices 7 and 8 (7/8) are determinants of HDL subclass distribution. The following proteins were expressed inEscherichia coli: human apoA-I, T7-hAI; mouse apoA-I, T7-mAI; chimeric human apoA-I containing murine helices 7/8 in place of human helices 7/8, T7-hAI(m7/8); and the reciprocal chimera, T7-mAI(h7/8). The recombinant proteins were examined for their association with human plasma HDL subclasses. The results demonstrated that T7-hAI bound HDL2 and HDL3 equally well, whereas T7-mAI bound to HDL2 preferentially. T7-hAI(m7/8) behaved like T7-mAI, and T7-mAI(h7/8) behaved like T7-hAI. Thus, α-helices 7/8 are strong contributors to the pattern of HDL subclass association. Self-association, α-helicity, cholesterol efflux, and lecithin-cholesterol acyltransferase activity of the recombinant proteins were also assessed. Human apoA-I self-associates more and activates human lecithin-cholesterol acyltransferase better than mouse apoA-I. These differential characteristics of human and mouse apoA-I are not dependent on helices 7/8.
Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania major-infected mice.

BALB / c and anti-IL-12-treated C3H mice infected with Leishmania major develop a Th2 cell response. However, in contrast to BALB / c mice, C3H mice treated transiently with an anti-IL-12 monoclonal antibody switch from a Th2 to a Th1 response and resolve their lesions once treatment is terminated. We report here that the critical difference in the Th2 response between BALB / c and C3H mice is in their ability to respond to IL-12. Thus, C3H mice with a Th2 response maintain a CD4+ T cell population that expresses IL-12 receptor β1 and β2 mRNA and produces IFN-γ after exposure to IL-12. These results indicate that Th2 cell populations from different genetic backgrounds differ in their stability, and that this difference can be related to differential regulation of the IL-12 receptor.
Tritium Production and Permeation in High-Temperature Reactor Systems

Tritium (Display FormulaH13) is a radioactive isotope of hydrogen formed by ternary fission events (rare emissions of three nuclides rather than two during a fission) and neutron absorption (and subsequent decay) of predecessor radionuclides, particularly 6Li and 7Li. Also in fusion, the concept of breeding tritium during the fusion reaction is of significance for the future needs of a large-scale fusion power plant. Tritium is of special interest among the fission products created in next-generation nuclear reactors such as gas cooled reactors and molten salt reactors, because of the large quantities produced when compared with conventional light-water reactors (LWR) and the higher temperatures of operation for these systems enhances permeation. To prevent the tritium contamination of proposed reactor buildings and surrounding sites, this paper examines the root causes and potential solutions for mitigation of permeation of this radionuclide, including materials selection and inert gas sparging. A model is presented that can be used to predict permeation rates of hydrogen through metallic alloys at temperatures from 450–750°C. Results of the diffusion model are presented along with mitigation strategies for tritium permeation.Copyright © 2013 by ASME
Herman Melville: scepticism, cynicism, and the Memoirs of a Greek

The essay emphasizes the importance of Herman Melville's 1849/1850 visit to London and the Continent, paying particular attention to the books he purchased at this time (listed in his Journal). I argue that in the period leading up to the composition of Moby-Dick, Melville was particularly drawn to essayistic prose and that this provided for him a means of exploring his own intellectual scepticism. At the same time, he was clearly interested in the tradition of picaresque fiction that exhibited a more extreme form of cynicism. My essay charts this development in his thinking by exploring his reading of a forgotten picaresque novel by Thomas Hope, Anastasius, or the Memoirs of a Greek. I suggest that this work had a formative influence on Melville's last novel, The Confidence-Man.