cssi/SciSciGPT-SciSciNet huggingface dataset:
Altered pharmacokinetics of indinavir by a novel nonnucleoside reverse transcriptase inhibitor (HBY-097): a pharmacokinetic evaluation in HIV-positive patients.

HBY-097 (HBY), an investigational nonnucleoside reverse transcriptase inhibitor (NNRTI), and indinavir (IDV) share a common metabolic pathway, cytochrome P4503A4 (CYP3A4), and may clinically be used together as well as with zidovudine (ZDV). Thus, the potential pharmacokinetic (PK) interaction between these drugs was evaluated. HBY (500 mg Q8H), IDV (800 mg Q8H), and ZDV (200 mg Q8H) were given to 8 HIV-infected subjects. Serial plasma samples were collected at baseline (ZDV and IDV alone) and day 11 (all 3 drugs) to determine PK parameters using noncompartmental analysis. PK parameters for ZDV in the presence and absence of HBY were not appreciably different. However, both the maximum (Cmax) and minimum (Cmin) concentrations of IDV were significantly reduced, from a mean of 7514 +/- 1636 and 146 +/- 81 mcg/L to 4725 +/- 2494 mcg/L and 54 +/- 24 mcg/L (p < .05) after addition of HBY. Furthermore, apparent clearance (CL/F) of IDV before and after 11 days of concomitant HBY administration was significantly higher, from 0.69 +/- 0.14 to 1.94 +/- 0.63 L/h/kg (p < .05) with an associated reduction in area under the curve (AUC0-8) from 16,034 +/- 4903 to 6134 +/- 2701 mg/L/h (p < .05). The increase in IDV CL/F is consistent with the observed metabolic induction effects of other NNRTIs. The results of this trial showed that HBY significantly alters the pharmacokinetic parameters of IDV at the dose studied.
Magnitude estimation of imagery

Magnitude estimates of imagery for 47 nouns correlated highly (r = .948) with the rating scale values of Paivio, Yuille, and Madigan (1968).
Bi-rich BiPbSrCaCuO (2-2-2-3) superconducting tapes

Abstract The microstructural and electrical properties of Ag clad Bi y Pb 0.4 Sr 2 Ca 2 Cu 3 O x ( y = 1.8, 2.0 and 2.3) powder-in-tube tapes were investigated. The highest J c values (2000 A/cm 2 at 77 K and 0 T) were obtained for tapes of powders y = 1.8 and 2.0 following a 150 h thermomechanical routine at 855°C. The presence of alkaline earth second phases was not diminished by the addition of bismuth. The phase equilibria were observed to shift from 2-2-2-3+ Sr 14− x Ca x Cu 24 O 48 + Sr x Ca 2− x CuO 3 to 2-2-2-3 + Sr x Ca 2− x CuO 3 + CuO as the Bi content was increased from y = 1.8 to 2.0. (Sr,Ca) 2 PbO 4 and 2-2-1-2 were present as by-product phases at temperatures above and below 855°C. Higher Bi content ( y = 2.3) caused formation of the 2-2-1-2 phase as the 2-2-2-3 became Bi-saturated.
Eruptive xanthomas in a child with the nephrotic syndrome.

In a 4-year-old boy with steroid-resistant nephrotic syndrome and extreme hyperlipidemia, an intense pruritic papular eruption developed on the trunk, buttocks, and extensor surface of the extremities. Findings from a skin biopsy specimen were consistent with an eruptive xanthoma. The patient was treated with gemfibrozil (Lopid), a low-fat diet, and antihistamines. Within 1 month pruritus diminished, the cutaneous lesions resolved, and serum lipid levels declined.
Uranyl bromides obtained from aqueous solution

Abstract Uranyl bromide can be crystallized from acid solution as the very hygroscopic trihydrate. Part of the water can be removed at 60°C without decomposition, but irreversible decomposition takes place at 115°C. Its saturated solution is 6·5 M, viscous, very dark red and on density 3·36 g/ml. Recrystallization from ether or isopropanol yields organic solvate-hydrates. The basic bromide, UO2(OH)Br·2H2O, has been crystallized from acid-deficient uranyl bromide solutions. It forms stable dilute aqueous solutions, but its concentrated solutions deposit hydrated uranium trioxide.
Molecular Detection of the Laurel Wilt Fungus, Raffaelea lauricola

The laurel wilt disease fungus, Raffaelea lauricola, is killing redbay trees, spreading rapidly in the U.S. southeastern coastal plain forest, and posing a serious threat to the avocado industry in Florida. A molecular tool is urgently required to facilitate detection of this pathogen. The 5' region of the large ribosomal RNA (28S) gene is highly variable among Raffaelea spp. and ideal for this purpose but amplification of this sequence from R. lauricola has been difficult. Different amplification conditions were tested and a high-fidelity polymerase chain reaction (PCR) procedure utilizing a dNTP mix containing 7-deaza-dGTP was found to reliably amplify 28S sequences from R. lauricola. Sequencing the amplified products or cloned inserts also turned out to be difficult and required using a custom-blended sequencing mix containing 1 M betaine, 5% dimethyl sulfoxide, and dGTP-BigDye v3.1. Three GC-rich stem and loop or cruciform secondary structures were discovered, which may have interfered with amplification. This improved protocol made it possible to partially characterize the internal transcribed spacers sequence from R. lauricola, which also has interfering secondary structures. A TaqMan real-time PCR assay was designed using the species-specific 28S sequences and this allowed detection of R. lauricola from wood tissues or cultures. Wood tissues from symptomatic redbay, avocado, and sassafras trees in Florida were screened using this TaqMan assay and several were found to test positive for R. lauricola. Results were further confirmed by performing Koch's postulates for avocado specimens collected from commercial grooves.
Femto-Cells: Problem or Solution? A Network Cost Analysis

Next-generation wireless cellular networks are likely to be multi-tiered, consisting of a macro-cell tier based on the traditional operator-deployed macro-cell structure, and a lower tier of femto-cells that are arbitrarily deployed by end-users. The need for such architectures is driven by increasing demands for higher data rates as well as to provide capacity to serve increasing numbers of subscribers. This paradigm shift in cellular architecture may therefore imply changes in the way cellular networks are managed today. In this paper, we examine operation costs of a two-tier macro-femto-cellular network in a capacity-limited scenario. We identify the key parameters, including nomadic-to-mobile user ratio, non-linear femto-cell capacity growth, femto-cell subscription rate, and QoS provisioning costs, which will impact recurring annual management costs of these networks. We then identify a model which captures these cost components and key parameters, allowing an operator to characterize the management cost of their access networks. We also identify through evaluations key situations where adopting these femto-cells may in fact add to an operator's overall costs, and provide key insights into the financial feasibility of femto-cells.
Monitoring Therapy in Patients Taking Levothyroxine

Purpose: To evaluate the use of thyroid function tests to monitor therapy in patients taking levothyroxine. Data Identification: Studies published between 1966 and January 1990 were identified thro...
Protecting Privacy for Dual-Use Researchers

With the recent revelation that U.S. intelligence agencies have been broadly tracking electronic communications for years ([ 1 ][1], [ 2 ][2]), a public discussion regarding the appropriate balance between privacy and security is overdue. The science community, especially those involved in dual-use
GPU-Accelerated Interactive Visualization and Planning of Neurosurgical Interventions

Advances in computational methods and hardware platforms provide efficient processing of medical-imaging datasets for surgical planning. For neurosurgical interventions employing a straight access path, planning entails selecting a path from the scalp to the target area that's of minimal risk to the patient. A proposed GPU-accelerated method enables interactive quantitative estimation of the risk for a particular path. It exploits acceleration spatial data structures and efficient implementation of algorithms on GPUs. In evaluations of its computational efficiency and scalability, it achieved interactive rates even for high-resolution meshes. A user study and feedback from neurosurgeons identified this methods' potential benefits for preoperative planning and intraoperative replanning.
When expert advice works, and when it does not

Both experts and users of expertise fail to grasp the role of expertise in decision making. Of course, expert advice is essential in complex human activities, but those who follow that advice also sometimes regret it. Under what conditions does expert advice and action tend to produce satisfactory outcomes? Recent studies of technological controversies and governmental regulatory procedures reveal some of the conditions under which expert advice may work well, and conditions under which it does not. Before considering these situations, the authors review two mental models (simple and cynical) that obstruct clear thinking about what users of expertise should expect from professional knowledge and what professionals should seek to contribute to technological controversies and other situations requiring expertise.
In search of kinesiology's core journals: an elusive and potentially value-laden enterprise1

Abstract In this paper we raise concerns over the methodological approach employed by Knudson (2013a) in attempting to identify core journals in kinesiology. Philosophical concerns about the nature of his results and their meaning are also brought to bear. The authors argue for more consistent, explicit, and inclusive methodology in identifying the journals and the associated measures of impact and prestige, and raise questions about the nature and purpose of scholarship in kinesiology that must be considered more fully. Our intention in raising these concerns is meant to answer the call of Knudson, Morrow, and Thomas (2014), who observed that scholars in kinesiology rarely challenge one another through letters to the editor, replication, or by other means. In the spirit of such scholarly discourse, we offer several observations that we feel should be considered, particularly prior to individuals or institutions attempting to operationalize and/or apply his study results.
An adaptively RF-powered wireless batteryless in vivo EKG and core body temperature sensing microsystem for untethered genetically engineered mice real-time monitoring

An adaptively RF-powered, wireless, batteryless, and implantable electrocardiogram (EKG) and core body temperature sensing microsystem for untethered genetically engineered mice real-time monitoring is designed, implemented, and in vivo characterized. A packaged microsystem exhibits a total size of 9 mm × 7 mm × 3 mm and a weight of 400 mg including a pair of stainless steel EKG electrodes. A low power 2 mm × 2 mm ASIC consisting of an EKG amplifier, a proportional-to-absolute temperature (PTAT) temperature sensor, an RF power sensing circuit, an RF-DC power converter, an 8-bit analog-to-digital converter (ADC), digital control circuitry, and a wireless data transmitter is powered by an adaptively controlled external RF energy source at 4 MHz to ensure a stable on-chip 2V supply with 156μΑ DC current for the overall microsystem operation.
Sex and Consequences: Abortion, Public Policy and the Economics of Fertility

Sex and Consequences: Abortion, Public Policy and the Economics of Fertility. By Phillip B Levine. Princeton and Oxford: Princeton University Press. 2004. 240 pp. $35.00.From the title alone it appears that either the author and his editor know little about sex and gender research or they think that any book with “sex” in the title will sell, or both. Thus, it is fortunate that the subtitle does accurately describe the contents of the book: an economic analysis of the consequences of changes in abortion law and policy on fertility behavior.
Percutaneous pedicle screw placement in the thoracic spine: A cadaveric study.

Study Design: A cadaveric study to determine the accuracy of percutaneous screw placement in the thoracic spine using standard fluoroscopic guidance. Summary of Background Data: While use of percutaneous pedicle screws in the lumbar spine has increased rapidly, its acceptance in the thoracic spine has been slower. As indications for pedicle screw fixation increase in the thoracic spine so will the need to perform accurate and safe placement of percutaneous screws with or without image navigation. To date, no study has determined the accuracy of percutaneous thoracic pedicle screw placement without use of stereotactic imaging guidance. Materials and Methods: Eighty-six thoracic pedicle screw placements were performed in four cadaveric thoracic spines from T1 to T12. At each level, Ferguson anterior-posterior fluoroscopy was used to localize the pedicle and define the entry point. Screw placement was attempted unless the borders of the pedicle could not be delineated solely using intraoperative fluoroscopic guidance. The cadavers were assessed using pre- and postprocedural computed tomography (CT) scans as well as dissected and visually inspected in order to determine the medial breach rate. Results: Ninety pedicles were attempted and 86 screws were placed. CT analysis of screw placement accuracy revealed that only one screw (1.2%) breached the medial aspect of the pedicle by more than 2 mm. A total of four screws (4.7%) were found to have breached medially by visual inspection (three Grade 1 and one Grade 2). One (1.2%) lateral breach was greater than 2 mm and no screw violated the neural foramen. The correlation coefficient of pedicle screw violations and pedicle diameter was found to be 0.96. Conclusions: This cadaveric study shows that percutaneous pedicle screw placement can be performed in the thoracic spine without a significant increase in the pedicle breach rate as compared with standard open techniques. A small percentage (4.4%) of pedicles, especially high in the thoracic spine, may not be safely visualized.
Solution of linear dynamic systems with uncertain properties by stochastic reduced order models

Abstract A novel method, referred to as the stochastic reduced order model (SROM) method, is proposed for finding statistics of the state of linear dynamic systems with random properties subjected to random noise. The method is conceptually simple, accurate, computationally efficient, and non-intrusive in the sense that it uses existing solvers for deterministic differential equations to find state properties. Bounds are developed on the discrepancy between the exact and the SROM solutions under some assumptions on system properties. The bounds show that the SROM solutions converge to the exact solutions as the SROM representation of the vector of random system parameters is refined. Numerical examples are presented to illustrate the implementation of the SROM method and demonstrate its accuracy and efficiency.
Kinematics of Recovery From a Stumble

BACKGROUND. Injuries most frequently related to accidents in elderly persons are falls during locomotion and stair ascent and descent. Although numerous risk factors have been related to falling behavior, effective strategies to predict and prevent falls have not evolved. The rationale underlying this study was that systematic experimental and analytical investigation of the effects of perturbations during locomotion and the subsequent requisites for recovery could lead to the development of clinically relevant evaluation(s) capable of identifying a predisposition to falling. The present study is the first biomechanical investigation of recovery from an anteriorly directed stumble. METHODS. Seven healthy, young males participated in this study. While the subjects walked along a walkway in the laboratory, stumbles were unexpectedly induced using a mechanical obstacle. Videotape records of these trials were analyzed and selected sagittal plane kinematics extracted. RESULTS. The perturbation caused an increase in the maximum trunk flexion angle from 4.3 degrees (control) to 18.3 degrees (p = .057), and this change was significantly associated with preperturbation walking velocity (p = .036). The maximum hip and knee flexion angles increased from 26 to 47 degrees (p = .039) and from 60 to 89 degrees (p = .009), respectively. The increases in maximum hip flexion velocity (79%) and maximum knee extension velocity (36%) were not significant. CONCLUSIONS. Identification of the principal elements of control during perturbed locomotion can contribute to understanding the relationship between specific age-related performance deficits and some types of falling behavior. The results suggest that recovery from a stumble is dependent upon lower extremity muscular power and the ability to restore control of the flexing trunk. Language: en
Features of sepsis caused by pulmonary infection with Francisella tularensis Type A strain.

The virulence mechanisms of Francisella tularensis, the causative agent of severe pneumonia in humans and a CDC category A bioterrorism agent, are not fully defined. As sepsis is the leading cause of mortality associated with respiratory infections, we determined whether, in the absence of any known bacterial toxins, a deregulated host response resulting in sepsis syndrome is associated with lethality of respiratory infection with the virulent human Type A strain SchuS4 of F. tularensis. The C57BL/6 mice infected intranasally with a lethal dose of SchuS4 exhibited high bacterial burden in systemic organs and blood indicative of bacteremia. In correlation, infected mice displayed severe tissue pathology and associated cell death in lungs, liver and spleen. Consistent with our studies with murine model strain Francisella novicida, infection with SchuS4 caused an initial delay in upregulation of inflammatory mediators followed by development of severe sepsis characterized by exaggerated cytokine release, upregulation of cardiovascular injury markers and sepsis mediator alarmins S100A9 and HMGB1. This study shows that pulmonary tularemia caused by the Type A strain of F. tularensis results in a deregulated host response leading to severe sepsis and likely represents the major cause of mortality associated with this virulent pathogen.
Vibrational Corrections to Nuclear Magnetic Resonance Second Moments

The effect of rapid nuclear motions on the observable second moments of nuclear-magnetic resonance-absorption lines is considered by the method of lattice harmonics. An explicit formula is given in terms of time-averaged values of lattice harmonics. In the case of lattice vibrations in a cubic solid with a cubic point group at the nuclear site, the observable correction to the rigid lattice second moment is zero up to and including the second order in the relative nuclear amplitudes of vibration. In general, only the anisotropic vibrations contribute in second order to the observable second moment. (auth)
Distribution and Molecular Characterization of Resistance-Breaking Isolates of Beet necrotic yellow vein virus in the United States

ABSTRACT Beet necrotic yellow vein virus (BNYVV) is the causal agent of rhizomania in sugar beet (Beta vulgaris). The virus is transmitted by the plasmodiophorid Polymyxa betae. The disease is cont...
Pollen Characteristics and Genetics of Induced and Spontaneous Genetic Male‐Sterile Mutants in Rice

Pollen characteristics, inheritance and allelism of 23 genetic male-sterile (ms) mutants of rice (Oryza sativa L.) were investigated. Ten of the mutants were induced by ethyl methane sulfonate, one induced by ethyleneimine, seven induced by gamma rays, one induced by streptomycin, one derived from tissue culture and three were spontaneous mutants found in the field. Four pollen abortion types were observed among these ms mutants: 3 no-pollen (NP) type, 6 complete pollen abortion (CPA) type, 13 partial pollen abortion (PPA) type, and 1 stainable pollen abortion (SPA) type. Progeny tests over two years indicated that each of the mutants was inherited as a monogenic recessive. A partial diallel cross among the 23 ms mutants indicated that mutant E2 was allelic to G4, E5 was allelic to E9, N2 was allelic to N3, and that three other mutants, E3, G6 and T1, shared the same ms locus. Gene symbols ms-46 (t) through ms-63 (t) were assigned to these mutants.
Difficulties in Treating Steroid Withdrawal: Intermittent ACTH and Low Dose Systemic Cyclosporin Used to Treat a Senile Erythroderma Patient

The tapering or termination of prolonged strong topical and/or systemic corticosteroid application for extensive generalized eczema has adverse effects on the body and thus presents a very difficult situation. The present case is that of a 68-year-old man with erythroderma following eczema, whose steroid withdrawal was successfully treated with intermittent ACTH and low dose systemic cyclosporin administration over a period of one year.
The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras domain plasticity in Gαi1

Heterotrimeric G proteins are activated by exchange of GDP for GTP at the G protein alpha subunit (Gα), most notably by G protein-coupled transmembrane receptors. Ric-8A is a soluble cytoplasmic protein essential for embryonic development that acts as both a guanine nucleotide exchange factor (GEF) and a chaperone for Gα subunits of the i, q, and 12/13 classes. Previous studies demonstrated that Ric-8A stabilizes a dynamically disordered state of nucleotide-free Gα as the catalytic intermediate for nucleotide exchange, but no information was obtained on the structures involved or the magnitude of the structural fluctuations. In the present study, site-directed spin labeling (SDSL) together with double electron-electron resonance (DEER) spectroscopy is used to provide global distance constraints that identify discrete members of a conformational ensemble in the Gαi1:Ric-8A complex and the magnitude of structural differences between them. In the complex, the helical and Ras-like nucleotide-binding domains of Gαi1 pivot apart to occupy multiple resolved states with displacements as large as 25 A. The domain displacement appears to be distinct from that observed in Gαs upon binding of Gs to the β2 adrenergic receptor. Moreover, the Ras-like domain exhibits structural plasticity within and around the nucleotide-binding cavity, and the switch I and switch II regions, which are known to adopt different conformations in the GDP- and GTP-bound states of Gα, undergo structural rearrangements. Collectively, the data show that Ric-8A induces a conformationally heterogeneous state of Gαi and provide insight into the mechanism of action of a nonreceptor Gα GEF.
Resistivity studies on polymer semiconductors

Eighteen polyacene polymers were synthesized, and their resistivities were found to be of the order of 104–105 ohm-cm. The resistivity of these polymer semiconductors was found to be sensitive to changes in the conditions of synthesis, changes in the structure of the polymers, and variations of pressure and temperature during experimentation. The forbidden energy gap for these polymers was about 0.5 e.v. Although the formalism of the simple intrinsic semiconductor band model was not strictly applicable to the data on these polymers, such a treatment was found instructive.
ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma

Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative effect of erlotinib (an EGFR-specific tyrosine kinase inhibitor), and transient knockdown of ErbB3 expression results in acquired resistance to EGFR-targeted therapy. In this study, we develop a stable isogenic model of ErbB3 expression in an attempt to decipher ErbB3's true contribution to pancreatic cancer tumorigenesis and to examine how this receptor affects cellular sensitivity to EGFR-targeted therapy. Analysis of the EGFR-ErbB3 heterodimer demonstrates that ligand-induced PI3K-AKT signaling is limited to ErbB3-expressing cells and that this signaling cascade can be partially abrogated by inhibiting EGFR function with erlotinib. Using our model of exogenous ErbB3 expression we showed a di...
Buschke-Ollendorff syndrome presenting as a painful nodule

First reported in 1928, Buschke-Ollendorff syndrome (BOS) is an autosomal dominant genodermatosis with high penetrance and variable expressivity. It is characterized by skin-colored or yellow smooth papules, plaques, and nodules up to 2 cm consisting of elastomas or collagenomas, known as dermatofibrosis lenticularis disseminata.1 This syndrome also has nearly pathognomonic radiographic findings of 1- to 10-mm spherical, radiopaque osteosclerotic foci with uneven contours at the epiphysis and metaphysis of the long bones, pelvis, carpi, and tarsi, with rare inclusion of the spine. These foci are known as osteopoikilosis or osteopathia condensans.2 This syndrome may have cutaneous manifestations during early childhood, with most findings developing by puberty. Radiographically, it generally manifests during adolescence and appears most commonly in the phalanges, carpi, and metacarpi but may appear as early as age 2.3 BOS is present equally in males and females, with an estimated prevalence of 1:20,000 in the general population.4 Patients may only have bone or dermatologic findings, but dermatologic manifestations are more commonly present and may include variations of grouped papules and nodules.3, 5 Debilitating symptoms are rare, but radiographic findings may be confused for primary osteoblastic or metastatic disease.6 We present a case of BOS incidentally diagnosed in a 20-year-old white man, with both radiologic and cutaneous findings discovered after complaints of a painful enlarging nodule on the right lower extremity.
A53: Natural History of Pediatric Class V Membranous Lupus Nephritis—A Serial Biopsy Study

Background/Purpose: In 1998, Sorof et al. reported 28% of 60 pediatric SLE patients had class V lesions on their first biopsy and 37% had class V lesions on their most recent biopsy. Although 19% of patients with LN transformed from other classes to class V, there were no patients with repeat biopsies who showed complete resolution of their class V lesions. The prognosis of the patients with class V LN was better than those with non-class V LN (only 5% vs. 21% developed renal dysfunction or died). Methods: We retrospectively reviewed pathology records of pediatric lupus nephritis patients who underwent renal biopsies at Texas Children's Hospital between 1990 and 2013. Results: A total of 321 biopsies were performed on 174 patients with SLE. The cumulative incidence of class V histopathology was 50% (160/321). Upon initial biopsy, 93/174 (53%) patients had Class II, III or IV LN without class V lesions, and 81/174 (47%) patients had class V lesions, either alone (n = 38), or associated with class II, III or IV LN (n = 43). Repeat biopsies were obtained in 97 cases. The median interval between first and second biopsies was 11 months (IQR 9–19m, range 3–110 m). Of the 97 patients with at least 2 renal biopsies, 36 (37%) had class V lesions on the initial biopsy, and 61 (63%) did not have class V lesions on the initial biopsy. Although transformation between classes was common, the initially non-class V LN patients frequently remained free of class V lesions at follow up (n = 42, 70%). Of the 18/61 initially non-class V LN patients who did later develop class V lesions, 6% initially had pure class II LN, 61% pure class III, and 33% pure class IV. Repeat biopsies revealed mixed class V LN in 16/18 patients, with subsequent resolution of class V lesions or transformation to pure class V in 4. Six (17%) of the 36 patients with class V lesions on the initial biopsy had pure class V lesions, and 30 (83%) had mixed class II, III or IV LNThree (50%) of the 6 patients with initially pure class V lesions showed evolution to mixed class III/V LN, and evolution to class IV with sustained absence of class V lesions in 1 (17%). Of the 30 patients with initially mixed class V LN, repeat biopsies revealed persistent mixed class V LN in 22 (73%), transformation to pure class V in 4 (13%) and sustained resolution of class V lesions in 4 (13%). Conclusion: A comparison of the WHO classification of initial and repeat biopsies showed evolution to pure class V LN, or more commonly, development of a mixed class including class V LN. Although the vast majority of patients with class V LN showed persistence of this histopathology, sustained resolution of class V lesions may be possible.
Primed allospecific T cells prevent the effects of costimulatory blockade on prolonged cardiac allograft survival in mice

Costimulatory blockade can induce long-term allograft survival in naive animals, but may not be as effective in animals with previously primed immune repertoires. We attempted to induce long-term graft survival in B10.D2 recipients of B10.A cardiac allografts using donor-specific transfusion (DST) plus anti-CD40 ligand antibody (alphaCD40L). Recipients were either naive mice, or mice previously primed to B10.A or third party alloantigens through engraftment and rejection of skin transplants. Untreated naive mice rejected cardiac transplants by day 15 and contained a high frequency of primed, donor-reactive T cells. Donor-specific transfusion/alphaCD4OL treatment of naive animals induced long-term graft survival associated with low frequencies of donor-reactive T cells. Previous priming of donor-specific T cells through rejection of B10.A, but not third party, skin grafts prevented the effects of DST/alphaCD40L on prolonging survival of B10.A hearts. Moreover, adoptive transfer of CD3+, CD4+ or CD8+ T cells from B10.A skin-graft-primed animals prevented the effects of DST/alphaCD40L. The data demonstrate that animals with immune repertoires containing previously primed, donor-reactive T cells are resistant to the effects of costimulatory blockade. The findings have important implications for ongoing, costimulatory blockade-based trials in humans, whose T-cell repertoires are known to contain memory alloreactive T cells.
A CHARACTERISTIC DENSE ENVIRONMENT OR WIND SIGNATURE IN PROMPT GAMMA-RAY BURST AFTERGLOWS

We discuss the effects of synchrotron self-absorption in the prompt emission from the reverse shock of gamma-ray burst afterglows in a dense environment, such as the wind of a stellar progenitor or a dense interstellar medium in early galaxies. We point out that when synchrotron losses dominate over inverse Compton losses, the higher self-absorption frequency in a dense environment implies a bump in the reverse-shock emission spectrum, which can result in a more complex optical/IR light curve than previously thought. This bump is prominent especially if the burst ejecta is highly magnetized. In the opposite case of low magnetization, inverse Compton losses lead to a prompt X-ray flare. These effects give a possible new diagnostic for the magnetic energy density in the fireball and for the presence of a dense environment.
Double-Blind Study on the Effects of Topical Anesthesia on Laryngeal Secretions

Summary The application of topical anesthesia to the oropharynx is a common clinical practice during oral and nasal laryngoscopy. Clinically, questions have been raised about whether topical anesthesia alters laryngeal secretions, which distorts clinical impressions. A double-blind, placebo controlled design was employed to address this issue. Ten premenopausal women with healthy vocal folds and 10 premenopausal women with phonotraumatic lesions underwent oral videolaryngoscopic examinations on subsequent days under both anesthesia and placebo conditions, in counterbalanced order. Video segments were rated by three judges. Dependent variables were balling and pooling of secretions, as previously described in the literature. Statistical analyses failed to reveal any clear effect of topical anesthesia on either secretion balling or pooling for the collapsed data set, but one cannot exclude changes in individual cases. Moreover, there was no evidence that secretions were differentially affected by anesthesia across subject groups. Null results in this data set replicate and extend previously reported findings by other authors. 1 An incidental but potentially interesting finding was that the order of treatment condition (anesthesia versus placebo first) seemed relevant for secretions: Subjects who received the anesthesia condition first tended to show more secretion balling in general, as compared with subjects who received the placebo condition first. Speculation is entertained regarding possible physiological pathways for these incidental findings, which could be relevant for some clinical practice.
The sensitivity of fuel cycle performance to separation efficiency

Abstract Reprocessing separation efficiency is a major design variable in the implementation of advanced fuel cycles as it affects waste disposal requirements, fuel fabrication, system economics, and other fuel cycle system characteristics. Using a newly developed, physics-based integrated fuel cycle systems analysis model, this study investigated the impact of varying reprocessing separation efficiencies on fuel cycle cost (FCC), proliferation resistance and repository impact. Repository impact was captured by the disposal facility capacity governed by thermal output, the projected dose rate, mass inventory, and waste toxicity index. The coupled systems analysis model included fast reactor simulation tool to analyze the depletion in the fast reactor and the requirements for the fresh fuel in transient and equilibrium states. In this calculation, the feedback between separation efficiencies and fresh and discharged fuel compositions was dynamically accounted for. The new systems model was benchmarked against published results and used to investigate a single-tier nuclear fuel cycle scenario in which light water reactors (LWRs) and 0.5 transuranic (TRU) conversion ratio (CR) sodium-cooled fast reactors are deployed in an equilibrium that results in zero net TRU production. The results indicated that fuel cycle system performance is significantly affected by the changes in partitioning strategies and elemental separation efficiency in reprocessing plants. Moreover, the effect of varying separation efficiencies on reactor performance, fuel cycle mass balances and economic performance are discussed.
On the use of hybrid reinforcement learning for autonomic resource allocation

Reinforcement Learning (RL) provides a promising new approach to systems performance management that differs radically from standard queuing-theoretic approaches making use of explicit system performance models. In principle, RL can automatically learn high-quality management policies without an explicit performance model or traffic model, and with little or no built-in system specific knowledge. In our original work (Das, R., Tesauro, G., Walsh, W.E.: IBM Research, Tech. Rep. RC23802 (2005), Tesauro, G.: In: Proc. of AAAI-05, pp. 886---891 (2005), Tesauro, G., Das, R., Walsh, W.E., Kephart, J.O.: In: Proc. of ICAC-05, pp. 342---343 (2005)) we showed the feasibility of using online RL to learn resource valuation estimates (in lookup table form) which can be used to make high-quality server allocation decisions in a multi-application prototype Data Center scenario. The present work shows how to combine the strengths of both RL and queuing models in a hybrid approach, in which RL trains offline on data collected while a queuing model policy controls the system. By training offline we avoid suffering potentially poor performance in live online training. We also now use RL to train nonlinear function approximators (e.g. multi-layer perceptrons) instead of lookup tables; this enables scaling to substantially larger state spaces. Our results now show that, in both open-loop and closed-loop traffic, hybrid RL training can achieve significant performance improvements over a variety of initial model-based policies. We also find that, as expected, RL can deal effectively with both transients and switching delays, which lie outside the scope of traditional steady-state queuing theory.
New Approaches and Tools for Grazing Management

Novel concepts and tools to promote progress in grazing science and management need to incorporate heterogeneity and nonlinear scaling of spatially and temporally distributed ecological interactions such as diet selection, defoliation, and plant growth. Traditional grazing management factors are number of animals, species and category of animals, spatial distribution of forage demand, and temporal distribution of forage demand. These traditional methods have been based on a paradigm that is static, assumes equilibrium conditions, and does not consider scaling issues, neither in time nor in space. Three related issues that can contribute to the progress in the understanding and management of grazing systems are spatial heterogeneity, event-driven dynamics, and scaling effects. Spatial heterogeneity of species and defoliation determine pasture stability by modulating competition and response to heterogeneous defoliation. When pasture species are well mixed, livestock are less able to select their preferred diet. When species are separated into larger and more easily identifiable patches, the selected diet approaches the preferred one. Simultaneously, patchiness in pasture components and redistribution of nutrients by grazing can lend global compositional stability to grass–clover pastures. Grazing at high animal density can be studied using the paradigm of event-driven dynamics. Several mechanisms suggest that grazing systems should have allometric spatial and temporal scaling in addition to the well-recognized allometric scaling of food requirements with body mass. Grazing system performance should scale allometrically with pasture size because both resource distribution and animal movements frequently have fractal properties. As pasture size increases, fewer hierarchical levels of grazing behavior are constrained, and the new spatial patterns introduce nonlinearity in the response to pasture size. Operant conditioning of foraging behavior, conditioned aversions, plant spatial pattern, pasture size and shape, timing and duration of grazing periods, and number of animals are discussed as precision tools to manage grazing systems.
Manifestations of Ictal Fear

Investigators from Okayama University and Medical Center report five pediatric patients with ictal fear followed from Jan 2003 to Dec 2012. The age of epilepsy onset ranged from 8 months to 9 years and 10 months.
Closing the “Great Divide”: New Social Theory on Society and Nature

Twenty years ago, two environmental sociologists made a bold call for a paradigmatic shift in the discipline of sociology—namely, one that would bring nature into the center of sociological inquiry and recognize the inseparability of nature and society. In this essay, we review recent scholarship that seeks to meet this challenge. The respective strands of this literature come from the margins of environmental sociology and border on other arenas of social theory production, including neo-Marxism, political ecology, materialist feminism, and social studies of science. Bringing together scholars from sociology, anthropology, geography, and history, each of these strands offers what we consider the most innovative new work trying to move sociology beyond the nature/society divide.
Legionella pneumophila feoAB Promotes Ferrous Iron Uptake and Intracellular Infection

In order to determine the role of ferrous iron transport in Legionella pathogenesis, we identified and mutated the feoB gene in virulent Legionella pneumophila strain 130b. As it is in Escherichia coli, the L. pneumophila feoB gene was contained within a putative feoAB operon. L. pneumophila feoB insertion mutants exhibited decreased ferrous but not ferric iron uptake compared to the wild type. Growth on standard buffered charcoal yeast extract agar or buffered yeast extract broth was unaffected by the loss of L. pneumophila FeoB. However, the L. pneumophila feoB mutant had a reduced ability to grow on buffered charcoal yeast extract agar with a reduced amount of its usual iron supplementation, a phenotype that could be complemented by the addition of feoB in trans. In unsupplemented buffered yeast extract broth, the feoB mutant also had a growth defect, which was further exacerbated by the addition of the ferrous iron chelator, 2,2′-dipyridyl. The feoB mutant was also 2.5 logs more resistant to streptonigrin than wild-type 130b, confirming its decreased ability to acquire iron during extracellular growth. Decreased replication of the feoB mutant was noted within iron-depleted Hartmannella vermiformis amoebae and human U937 cell macrophages. The reduced intracellular infectivity of the feoB mutant was complemented by the introduction of a plasmid containing feoAB. The L. pneumophila feoB gene conferred a modest growth advantage for the wild type over the mutant in a competition assay within the lungs of A/J mice. Taken together, these results indicate that L. pneumophila FeoB is a ferrous iron transporter that is important for extracellular and intracellular growth, especially in iron-limited environments. These data represent the first evidence for the importance of ferrous iron transport for intracellular replication by a human pathogen.
National pediatric cardiology quality improvement collaborative: Lessons from development and early years

Abstract The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) was established by the Joint Council on Congenital Heart Disease to dramatically improve the outcomes of care for children with congenital heart disease (CHD) through a national collaborative network of multidisciplinary clinical teams and families, working together to collect longitudinal data, use improvement science methods and conduct research intended to accelerate the development and translation of new knowledge into practice. The initial project selected for this learning network is focused on care processes and outcomes of the initial interstage period for infants with hypoplastic left heart syndrome. A practice-based registry is being used to understand variation in care and outcomes of infants and children with complex CHD. The NPC-QIC has effectively recruited and engaged a large number of U.S. centers caring for infants with complex CHD and provides the infrastructure needed to support the implementation of practice changes across the collaborative that will ultimately improve outcomes in this high-risk group of patients. We describe here the development and early years of NPC-QIC as well as the challenges this collaborative faces moving forward.
Investigation of the weak interaction from general relativity

The flat—space-time limit of a generalized covariant field theory of electrodynamics in general relativity is explored. The generalized force, expressed in terms of Hermitian products of spinor functions, is a complex variable. Its real part corresponds to the standard (Lorentz) force in electrodynamics; its imaginary part corresponds to reflection nonsymmetric forces, some that can be identified with the weak interaction—particularly applied to neutron decay, within the context of this theory. To test the theory, the effective charge compared with the electron charge,ew/e, is computed, found to be the order 7.10−4. This result is compared with Fermi’s result for this ratio for the pseudoscalar, current-current interaction, which gave the order of 3.10−4.
Diagnostic strategies for the persistent sciatic artery

Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that leads to aneurysmal degeneration and atherosclerotic changes. A careful understanding of the embryology is mandatory as variations in vascular development determine the optimal treatment. We present a case of an 85-year-old female who was incidentally found to have a PSA aneurysm, and review the literature.
Using Medicare Payment Policy To Transform The Health System: A Framework For Improving Performance

As the largest payer for health services in the United States, Medicare has the potential to use its payment policies to stimulate change in the organization of care to improve quality and mitigate cost growth. This paper proposes a framework in which Medicare would offer an array of new bundled payment options for physician group practices, hospitals, and delivery systems, with incentives to encourage greater integration in the organization of health care delivery and the provision of more coordinated care to beneficiaries. These changes could also serve as a model for other payers to improve quality and efficiency throughout the health system.
Commentary: the importance of demonstrations in developing adolescent HIV care models.

Common knowledge among providers of care and outreach to HIV-positive youth supports the program characteristics identified by these projects. Future efforts now must use this knowledge as well as the knowledge gained from NIH and other youth-oriented HIV research to rigorously test best practices and apply them to the field. Returning to the basic epidemiology of HIV it is the success of youth-oriented HIV prevention outreach and treatment programs that will affect increases or decreases in HIV incidence and mortality within the United States. (excerpt)
A brief anti-stigma intervention for Chinese immigrant caregivers of individuals with psychosis: Adaptation and initial findings:

Mental illness stigma has adverse effects on both the caregivers' psychological well-being and the effectiveness of care that consumers receive. While anti-stigma interventions for family caregivers from Western settings have recently shown efficacy, these interventions may not be equally applicable across culturally diverse groups. Specifically, Chinese immigrant caregivers experience heightened internalized stigma, which predisposes the adoption of harmful coping strategies and reduced quality of social networks. We present an anti-stigma intervention based on a peer-family group format, co-led by a clinician and a trained family caregiver, to counter stigma among Chinese immigrants. Data are presented from a brief intervention administered to a pilot sample of 11 Chinese immigrant caregivers that provides: psychoeducation, strategies to counter experienced discrimination, and techniques to resist internalized stigma. Case vignettes illustrate implementation of this intervention, and how the peer-family format via interactive contact counteracts internalized stereotypes, encourages adaptive coping strategies, and reinvigorates social networks. Quantitative results further suggest preliminary efficacy in reducing internalized stigma for caregivers who evidenced at least some prior internalized stigma. This study constitutes an initial but important step towards reducing mental illness stigma among Asian Americans, for whom stigma has played a powerful role in the delay and underuse of treatment.
Deconvolution of target signature for a scene with bistatic impulse radiating antennas and a sphere

A model for an impulse radiating antenna (IRA) has been developed in WIPL-D. A scene using a bistatic pair of these IRAs is modeled with a sphere target and is simulated in the frequency domain. The input to the antenna is a Gaussian pulse, and the current on the receive antenna is plotted vs. frequency. This receiver response is proportional to the scattered field from the sphere. The frequency domain data are processed to give the time domain response. The objective of this work is to deconvolve the signature of the scatterer from the receiver transient response. Additional separate simulations for each scene component and electromagnetic interaction were needed and were performed using WIPL-D. The process is successful for this scene, which does not include a ground plane. The analysis of the simulated data and deconvolution of the target signature are done in Matlab.