cssi/SciSciGPT-SciSciNet huggingface dataset:
The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats.

Chemotherapy-induced pain is the most common treatment-limiting complication encountered by cancer patients receiving taxane-, vinca alkaloid- or platin-based chemotherapy. Several lines of evidence indicate that activation of pro-inflammatory cascades involving the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) as well as various growth factors are key events in the pathogenesis of many types of nerve-injury related pain. Similar mechanisms might also be involved in the etiology of chemotherapy-induced pain. Thalidomide and minocycline have profound immunomodulatory actions in addition to their originally intended pharmacological actions. These compounds were evaluated here for effects in preventing the development of taxol-induced mechanical and thermal hyperalgesia in rats. Thalidomide (50.0 mg/kg) reduced taxol-induced mechanical allodynia and hyperalgesia whereas minocycline (20.0 mg/kg) reduced taxol-induced mechanical hyperalgesia and allodynia as well as taxol-induced thermal hyperalgesia. These results suggest that immunomodulatory agents may provide a treatment option for the protection or reversal of chemotherapy-related pain.
Inhalant allergy and Meniere's disease: Use of electrocochleography and intranasal allergen challenge as investigational tools.

INTRODUCTION: In an earlier study, we demonstrated the feasibility of using electrocochleography (ECoG) to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and Meniere's disease, using the antigen to which they were most sensitive.OBJECTIVE: We expand on this earlier study and continue to investigate the feasibility of this model in a subset of patients with inhalant allergy and Meniere's disease after immunotherapy.STUDY DESIGN: Prospective study of 11 patients identified with both Meniere's disease and inhalant allergy in the practices of 2 neurotologists at our institution. Patients underwent a baseline ECoG, followed by intranasal challenge with the allergen to which they were most sensitive. This was followed by a second ECoG.RESULTS: Six of 11 patients had at least 1 year of immunotherapy (group 1), and 5 of 11 had had 0 to 6 months of immunotherapy (group 2). Four of 6 group 1 patients had a >15% increase i...
Influence of prion strain on prion protein adsorption to soil in a competitive matrix.

It is likely that the soil environment serves as a stable reservoir of infectious chronic wasting disease (CWD) and scrapie prions, as well as a potential reservoir of bovine spongiform encephalopathy (BSE, or “mad cow” disease). Prion adsorption to soil may play an important role in prion mobility, proteolysis, and infectivity. Differences in PrP environmental fate are possible due to the strain- and species-dependent structure of PrPSc. Kinetic and isothermal studies of PrP adsorption to sand and two whole soils were conducted using HY and DY TME-infected hamster, uninfected hamster, and CWD-infected elk brain homogenates as competitive PrP sources. The role of the N-terminus in PrP adsorption was also investigated. We report strain and species differences in PrP adsorption to soil over time and as a function of aqueous concentration, indicating that the fate of prions in the environment may vary with the prion strain and species infected. Our data also provide evidence that the N-terminal region of PrP...
Magnetic resonance (MR) evaluation of dilated pelvic veins: what the vascular and interventional radiologist needs to know

Learning Objectives 1. Identify various clinical conditions which cause pelvic venous dilatation and/or obstruction. 2. Describe the anatomic abnormality associated with each clinical condition and provide MR and correlative conventional angiographic examples of each abnormality. 3. Discuss the utility of MR angiography in planning potential endovascular interventions for such venous abnormalities, with a specific focus on the use of blood pool contrast agents in MR angiography. Background Recently developed MR blood pool contrast agents, such as gadofoscecet (Ablavar™), have markedly less extracellular distribution than their predecessors, a property that allows for steady-state high-resolution imaging of veins and complex venous lesions. In this presentation, we will illustrate how gadofoscecet use enhances the MR characterization of venous anomalies and abnormalities. Improved MR characterization facilitates not only proper diagnosis of but also the appropriate planning for endovascular interventions which treat pelvic vein obstruction. Clinical Findings/Procedure Details We will present MR and correlative conventional angiography examples of venous anomalies and abnormalities resulting in pelvic venous dilatation and/or obstruction, including: congenital caval anomalies, inferior vena cava stenosis stenosis from chronic iliocaval thrombosis, May-Thurner (Cockett) syndrome, nutcracker syndrome, gonadal vein reflux, venous obstruction secondary to mass effect from extrinsic anatomic structures. Conclusion and/or Teaching Points (1) Pelvic venous dilation is commonly caused by venous anomalies or abnormalities which can be diagnosed noninvasively using MR angiography. (2) MR blood pool contrast agents, such as gadofoscecet (Ablavar™), enhance MR characterization of venous anomalies and abnormalities by opacifying their full geographic extent as well as providing information regarding directionality of venous flow. (3) MR angiography is a useful, if not critical, tool in pre-procedure planning of endovascular treatment of pelvic vein obstruction.
Radar Mapping, Archeology, and Ancient Maya Land Use

A severe incongruity has long existed between the well-known complexity of ancient Maya civilization and the relatively feeble economic base that could be reconstructed for it. Recent fieldwork has ihdicated that much more intensive cultivation patterns were used than was previously thought. Data from the use of synthetic aperture radar in aerial surveys of the southern Maya lowlands suggest that large areas were drained by ancient canals that may have been used for intensive cultivation. Ground checks in several limited areas have confirmed the existence of canals, and excavations and ground surveys have provided valuable comparative information. Taken together, the new data suggest that Late Class period Maya civilization was firmly grounded in large-scale and intensive cultivation of swampy zones.
Electrical Protection of Superconducting Magnet Systems

The problem of dissipating the energy stored in the field of a superconducting magnet when a quench occurs has received considerable study. However, when the magnet becomes a system 4 miles in length whose normal operation is an ac mode, some re-examination of standard techniques for dissipating energy outside the magnets is in order. Data accumulated in the Fermilab Energy Doubler magnet development program shows that heating associated with the temporal and spatial development of quenches is highly localized and can result in temperatures damaging to the superconducting wire. This paper reviews the design and operation of several energy dumping schemes, compatible with the operation of ac superconducting magnets, wherein more than 70% of the stored energy can be dissipated outside the magnet. Instrumentation to detect quenches early in their development and circuits for dumping the field energy are described, and representative operating performance data for the dump circuits and data showing temporal development of quenches are presented.
Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia

Summary Three siblings with onset of diabetes mellitus infancy are reported. Two (and possibly all three) of the children also had multiple epiphyseal dysplasia. Demineralization of the bone with multiple fractures, tooth discoloration, and skin abnormalities were also observed. A unifying biochemical or physiologic mechanism for the simultaneous appearance of diabetes, epiphyseal dysplasia, and possible ectodermal dysplasia has not suggested itself, but this may represent a new syndrome.
Directional running in mice: effects of cocaine and chlorpromazine.

Mice ran in a circular runway. Some received milk at every third circuit in a designated direction, clockwise or counterclockwise, in daily 1000-s sessions. Under control conditions, about 10 times as many circuits were made in the reinforced direction as in the non-reinforced direction. Cocaine (10, 30, 100 µM/kg) had little effect on the total number of circuits, but progressively increased the number in the non-reinforced direction. Chlorpromazine (1, 3, 10, 30 µM/kg) caused a monotonic decrease in total number of circuits and in number in non-reinforced direction. At the highest doses the proportion in the non-reinforced direction was increased. Mice, untrained in the runway and with no reinforcement of circuits in either direction, made many fewer total circuits than when running was reinforced and about equal numbers were in clockwise and in counterclockwise directions. Cocaine greatly increased the total number of circuits. As in the subjects whose running was reinforced, cocaine led to a much higher tendency for mice to run in a single direction. The similarities between the tendency to run in one direction after cocaine and the rotational behavior of rodents seen after cocaine and amphetamine suggest a common mechanism.
THE SICKLE CELL PAINFUL CRISIS IN ADULTS: PHASES AND OBJECTIVE SIGNS

The severe sickle cell painful crisis that requires hospitalization in adults typically seems to evolve along four distinct phases: Prodromal, initial, established, and resolving. Each phase may to be associated with certain clinical and laboratory findings. Objective clinical and laboratory signs may not be evident in the initial phase of the crisis especially in the absence of reliable base line steady state data. Several clinical, hematological, biochemical, and rheological changes emerge as the crisis progresses. This sequence of events creates several logistic issues in the care of these patients. The absence of objective findings early in the crisis usually discourages health care providers from repeating such tests and makes some of them suspicious of the authenticity of the painful episode in question. Consequently, an atmosphere of mistrust may develop between the patients and their care providers. This review puts the sickle cell painful crisis in perspective and, based on available data in the literature, shows that it is a dynamic process characterized by several changes during its evolution. It is hoped that this review will dispel some misconceptions about the painful crisis, elucidate its clinical course, and encourage further research to answer the questions it raises.
A prediction of heat generation in a thermoviscoplastic uniaxial bar

Abstract A thermodynamic model is presented for predicting the thermomechanical response, including temperature change, in a uniaxial bar composed of a thermoviscoplastic metallic medium. The model is constructed using the concept of internal state variables, and it is shown that this general framework is capable of encompassing several constitutive models currently used to predict the response of rate-sensitive metals in the inelastic range. Results are obtained for monotonic loading which agree with predicted results previously obtained by Cernocky and Krempl for mild steel at room temperature. The model is then utilized in conjunction with Bodner and Partom's constitutive equations to predict temperature change in Inconel (IN) 100 subjected to both monotonic and cyclic loading at 1005 K (1350°F).
LayTracks3D: A new approach for meshing general solids using medial axis transform

Abstract This paper presents an extension of the all-quad meshing algorithm called LayTracks to generate high quality hex-dominant meshes of general solids. LayTracks3D uses the mapping between the Medial Axis (MA) and the boundary of the 3D domain to decompose complex 3D domains into simpler domains called Tracks. Tracks in 3D have no branches and are symmetric, non-intersecting, orthogonal to the boundary, and the shortest path from the MA to the boundary. These properties of tracks result in desired meshes with near cube shape elements at the boundary, structured mesh along the boundary normal with any irregular nodes restricted to the MA, and sharp boundary feature preservation. The algorithm has been tested on a few industrial CAD models and hex-dominant meshes are shown in the Results section. Work is underway to extend LayTracks3D to generate all-hex meshes.
Solution delivery for copper CVD using Cu(hfac) 2 reduction

We have developed a solution delivery technique for performing copper CVD using the reduction of Cu(hfac)2 [where H(hfac) = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionel. We have obtained deposition rates of up to 3.6 mg cm−2 hr−1 (ca. 60 nm min−1) for a deposition temperature of 300 °C and reactor conditions of 40 Torr H2, 12 Torr isopropanol, and 1 Torr Cu(hfac)2. The increased rates are several times faster than growth rates observed using conventional Cu(hfac)2 sublimation with pure H2 as the carrier gas. We compare growth rates and film microstructure using TiN- and WNx-coated substrates. We also give preliminary results showing how the partial pressures of H2, i-PrOH, and Cu(hfac)2 each influence the deposition rate.
Allergic Rhizomucor sinusitis

Summary Dr. Marc F. Goldstein : In conclusion, AFS is a benign noninvasive disease of the paranasal sinuses that can be caused by a variety of fungal organisms. This report highlights the first case of AFS caused by Rhizomucor . Recognition of AFS as a distinct clinicopathologic entity separate from other causes of clinical and radiographic sinusitis, especially invasive fungal sinusitis and neoplasm, is important. The clinical diagnosis of AFS needs to be considered in the differential diagnosis of chronic refractory sinusitis if surgical specimens are to be properly analyzed both histologically and microbiologically. Proper diagnosis is important to ensure optimal therapy, including surgical debridement and oral corticosterois. In addition, accurate diagnosis avoids the unnecessary use of antifungal drugs or radical surgical procedures or both.
Identification of Long Intergenic Repeat Sequences Associated with DNA Methylation Sites in Caulobacter crescentus and Other α-Proteobacteria

A systematic search for motifs associated with CcrM DNA methylation sites revealed four long (>100-bp) motifs (CIR sequences) present in up to 21 copies in Caulobacter crescentus. The CIR1 and CIR2 motifs exhibit a conserved inverted repeat organization, with a CcrM site in the center of one of the repeats.
Embracing new technology and techniques in foot and ankle surgery.

The bulk of our surgical practices involves treating a handful of very common conditions. For the most part, surgeons treat each condition in a rather algorithmic cookie-cutter fashion. There is a tendency to treat most things the same way. Surgeons may choose “new” procedures that may be considered controversial. But what makes a procedure or technique controversial? New procedures and techniques are often labeled “controversial” because of a lack of follow-up. Interestingly, surgeons adopting newprocedures and/or implants are not necessarily considered controversial; rather, they may be seen as contemporary and innovative by patients and their peers. There are some surgeons who are early adopters of technology and new techniques. Others prefer a “wait-and-see” approach. And there are those surgeons that have their “bags of tricks” and will not modify their practice habits whatsoever. There is a natural progression for new technology/procedures to become mainstreamed. Changemay not be easily accepted, and this sparks controversy anddebate. With growing acceptance of new technology, research and medical papers emerge either validating or discrediting the concepts. This Clinics in Podiatric Medicine and Surgeryhighlightsseveral clinical controversies thatexist in foot andankle surgery today.
Cluster analysis: unsupervised learning via supervised learning with a non-convex penalty

Clustering analysis is widely used in many fields. Traditionally clustering is regarded as unsupervised learning for its lack of a class label or a quantitative response variable, which in contrast is present in supervised learning such as classification and regression. Here we formulate clustering as penalized regression with grouping pursuit. In addition to the novel use of a non-convex group penalty and its associated unique operating characteristics in the proposed clustering method, a main advantage of this formulation is its allowing borrowing some well established results in classification and regression, such as model selection criteria to select the number of clusters, a difficult problem in clustering analysis. In particular, we propose using the generalized cross-validation (GCV) based on generalized degrees of freedom (GDF) to select the number of clusters. We use a few simple numerical examples to compare our proposed method with some existing approaches, demonstrating our method's promising performance.
Heartbeat: Highlights from this issue

Randomized controlled trials increasingly recruit patients globally to facilitate recruitment and to improve validity and applicability. However, patients from countries with different developmental status may differ in terms of clinical profiles, adherence to prescribed therapy and access to health care facilities. Further, these differences may impact patient outcomes. In this issue of Heart Professor Prabhakaran and colleagues ( see page 279 ) (figure 1) report the influence of developmental status of individual countries, as defined by the United Nations' Human Development Index (HDI), on clinical outcomes of patients with Acute Coronary Syndrome (ACS) in a multinational study, the Trilogy ACS. Despite uniform study eligibility criteria, baseline characteristics differed significantly among patients from different HDI-classified countries. These baseline differences in turn were associated with differential outcomes. The authors conclude that geographical and other country-level factors variations in study populations need to be taken into account when designing, conducting and analyzing trials. In the companion editorial, Dr Banerjee ( see page 245 ) systematizes how this heterogeneity in developmental status can influence both internal and …
CONDITIONED REINFORCEMENT AND RESPONSE STRENGTH

Stimuli associated with primary reinforcers appear themselves to acquire the capacity to strengthen behavior. This paper reviews research on the strengthening effects of conditioned reinforcers within the context of contemporary quantitative choice theories and behavioral momentum theory. Based partially on the finding that variations in parameters of conditioned reinforcement appear not to affect response strength as measured by resistance to change, long-standing assertions that conditioned reinforcers do not strengthen behavior in a reinforcement-like fashion are considered. A signposts or means-to-an-end account is explored and appears to provide a plausible alternative interpretation of the effects of stimuli associated with primary reinforcers. Related suggestions that primary reinforcers also might not have their effects via a strengthening process are explored and found to be worthy of serious consideration.
Parenting dimensions and adolescents' internalisation of moral values

This study examined relations between parenting dimensions (involvement, autonomy support and structure) and adolescents’ moral values internalisation. A sample of 101 adolescents (71% female; 76% white; M age516.10, SD51.17) reported on the parenting behaviour of one of their parents and on their own moral values. Four forms of values regulation were assessed (external, introjected, identified and integrated), as well as overall internalisation. Structure was positively linked to external and introjected regulation, involvement was positively associated with identified and integrated regulation and structure was negatively linked to overall internalisation. Additionally, positive interactions were found for autonomy support and involvement predicting identified and integrated regulation. Implications for parenting and moral education are discussed.
Computerized Simulation in the Social Sciences

After years at the periphery of the social sciences, simulation is now emerging as an important and widely used tool for understanding social phenomena. Through simulation, researchers can identify causal effects, specify critical parameter estimates, and clarify the state of the art with respect to what is understood about how processes evolve over time. Moreover, simulation methods are often the most time-effective and cost-effective means of doing so and sometimes are the only means. This essay outlines current developments in the four main branches of social science simulation: systems dynamics models, network models (including neural network models), spatial models, and agent-based models. The limitations of simulation modeling are also discussed, along with methods for evaluating the validity of social science computer simulations.
Approximation algorithms for deadline-TSP and vehicle routing with time-windows

Given a metric space G on n nodes, with a start node r and deadlines D(v) for each vertex v, we consider the Deadline-TSP problem of finding a path starting at r that visits as many nodes as possible by their deadlines. We also consider the more general Vehicle Routing with Time-Windows problem, in which each node v also has a release-time R(v) and the goal is to visit as many nodes as possible within their "time-windows" [R(v),D(v)]. No good approximations were known previously for these problems on general metric spaces. We give an O(logn) approximation algorithm for Deadline-TSP, and extend this algorithm to an O(log2n) approximation for the Time-Window problem. We also give a bicriteria approximation algorithm for both problems: Given an e>0, our algorithm produces a (1/e) approximation, while exceeding the deadlines by a factor of 1+e. We use as a subroutine for these results a constant-factor approximation that we develop for a generalization of the orienteering problem in which both the start and the end nodes of the path are fixed. In the process, we give a 3-approximation to the orienteering problem, improving on the previously best known 4-approximation of [6].
The Preschool/Primary Gifted Child.

This manuscript provides an adaptation of the presentation given by Merle B. Karnes at the Richardson North Carolina Association for the Gifted and Talented Policy Conference. An overview of historical trends with regard to providing services to young gifted children with particular emphasis on inhibiting factors that have prevented greater services is provided. The work of Karnes and her associates at the University of Illinois with young gifted children from upper and middle class backgrounds is summarized. These two sections provide foundation for the concluding section in which we present our interpretation of “What we know for sure,” “What we think we know,” and “What we do not know” with regard to providing services to young gifted children.
Rare-Variant Association Testing for Sequencing Data with the Sequence Kernel Association Test

Sequencing studies are increasingly being conducted to identify rare variants associated with complex traits. The limited power of classical single-marker association analysis for rare variants poses a central challenge in such studies. We propose the sequence kernel association test (SKAT), a supervised, flexible, computationally efficient regression method to test for association between genetic variants (common and rare) in a region and a continuous or dichotomous trait while easily adjusting for covariates. As a score-based variance-component test, SKAT can quickly calculate p values analytically by fitting the null model containing only the covariates, and so can easily be applied to genome-wide data. Using SKAT to analyze a genome-wide sequencing study of 1000 individuals, by segmenting the whole genome into 30 kb regions, requires only 7 hr on a laptop. Through analysis of simulated data across a wide range of practical scenarios and triglyceride data from the Dallas Heart Study, we show that SKAT can substantially outperform several alternative rare-variant association tests. We also provide analytic power and sample-size calculations to help design candidate-gene, whole-exome, and whole-genome sequence association studies.
Distinguishing feral and managed honeybees (Apis mellifera) using stable carbon isotopes

The ability to distinguish feral and managed honeybees (Apis mellifera) has applications in studies of population genetics, parasite transmission, pollination, interspecific interactions, and bee breeding. We evaluated a diagnostic test based on theoretical differences in stable carbon isotope ratios generated by supplemental feeding. We evaluated (1) if carbon isotope ratios can distinguish feral and managed honeybees and (2) the temporal persistence of the signal after discontinuation of supplemental feeding. We compared carbon isotope ratios from four types of experimental colonies: feral, managed with and without supplemental feed, and managed with 13C-labeled glucose added to supplemental feed. There was a significant difference between the isotopic signatures of colonies receiving supplemental feed and unfed feral colonies. This difference, however, only persisted for a few weeks after supplemental feeding was discontinued, suggesting that this method may work best under a narrow range of conditions. This work highlights the potential for exploiting temporal turnover of carbon in bee tissues as a tool for studying nutrient flow in honeybee colonies.
Parallel computing for chromosome reconstruction via ordering of DNA sequences

In this paper we present our practical experience with the design and implementation of a suite of parallel algorithms called PARODS, for chromosome reconstruction via ordering of DNA sequences. PARODS contains parallel algorithms based on an earlier serial algorithm ODS which is a physical mapping algorithm based on simulated annealing. The parallel simulated annealing (PSA) algorithms for physical mapping in PARODS are based on Markov chain decomposition. We propose and describe perturbation methods and problemspecific annealing heuristics in the context of the physical mapping problem. We describe implementations of parallel Single Instruction Multiple Data (SIMD) algorithms on a 2048processor MasPar MP-2 system and implementations of parallel Multiple Instruction Multiple Data (MIMD) algorithms on an 8-processor Intel iPSC/860 system and on a cluster of UNIX workstations using the Parallel Virtual Machine (PVM) system. We discuss and analyze the convergence, speedup and scalability characteristics of the aforementioned algorithms. We show the best SIMD algorithm to have a speedup of 1232 on the 2048 processor MasPar MP-2 system and the best MIMD algorithm to have a speedup of 5.35 on the 8-processor Intel iPSC/ 860 system and 3.40 on a 6-workstation cluster running PVM. ” 1998 Elsevier Science B.V. All rights reserved.
Could treatment with tamoxifen be superior to aromatase inhibitors in early-stage breast cancer after pharmacogenomic testing? A modeling analysis

502 Background: Adjuvant endocrine treatment with upfront aromatase inhibitors yields improved disease-free survival compared to tamoxifen in unselected women with estrogen receptor-positive breast cancer. However, levels of endoxifen, the active tamoxifen metabolite, are known to vary with the number of mutant alleles of the cytochrome P450 CYP2D6 enzyme. We created a Markov model to examine whether the optimal treatment strategy for patients with wild type genetics (wt/wt) might differ from that for patients with homozygous (*4/*4) or heterozygous (wt/*4) mutations. Methods: Annual recurrence risks with aromatase inhibitors and tamoxifen in unselected women were taken from the BIG 1–98 trial. Based on data from Goetz et al., we assumed that the percent of patients who are homozygous and heterozygous for mutations are 6.8% and 21.1%, respectively, and that the hazard ratio (HR) for increased cancer recurrence on tamoxifen among *4/*4 carriers is 1.86 relative to patients with wt/wt or wt/*4 genotypes. Be...
Planar textures in superfluid 3He-A

Making use of the Ginzburg-Landau free energy, singularities such as disgyrations and vortex lines and stable textures in the planar (or two-dimensional) texture are studied. Here both % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqaqpepeea0xe9qqVa0l% b9peea0lb9sq-JfrVkFHe9peea0dXdarVe0Fb9pgea0xa9pue9Fve9% Ffc8meGabaqaciGacaGaaeqabaWaaeaaeaaakeaaieqaceWFSbGbaK% aaaaa!3883!\[{\hat l}\] and % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqaqpepeea0xe9qqVa0l% b9peea0lb9sq-JfrVkFHe9peea0dXdarVe0Fb9pgea0xa9pue9Fve9% Ffc8meGabaqaciGacaGaaeqabaWaaeaaeaaakeaaieqaceWFKbGbaK% aaaaa!387B!\[{\hat d}\] vectors, characterizing the texture in 3He-A, are assumed parallel to each other and lie always in a plane. The dynamics of disgyrations is also considered.
CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver

Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. Previous studies from our laboratory showed that microRNA 107 (miR107) and microRNA 103 downregulate CYP2C8 post-transcriptionally. miR107 is located in intron 5 of the pantothenate kinase 1 (PANK1) gene. p53 has been reported to coregulate the induction of PANK1 and miR107. Here, we examine the possible downregulation of CYP2C8 by drugs capable of inducing miR107. Hypolipidemic drugs, such as bezafibrate, known activators of the peroxisome proliferator-activated receptor α (PPARα), induce both the PANK1 gene and miR107 (∼2.5-fold) in primary human hepatocytes. Surprisingly, CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPARα in HepG2 cells, with a further increase after bezafibrate (∼18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (∼10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. Promoter sequence analyses, deletion studies, mutagenesis studies, and electrophoretic mobility shift assays identified a PPARα response element located at position -2109 base pair relative to the translation start site of CYP2C8. Chromatin immunopreciptation assay analysis confirmed recruitment of PPARα to this PPARα response element after bezafibrate treatment of human hepatocytes. Thus, we show for the first time that CYP2C8 is transcriptionally regulated by PPARα, suggesting the potential for drug-drug interactions due to upregulation of CYP2C8 by PPAR activators.
Relationships Among Older Women Living in a Nursing Home

SUMMARY Literature suggests that women's skills in establishing close ties with other women help sustain them in old age by giving them a sense of control over their lives. This paper questions how such a notion may apply to women in a nursing home setting and contrasts women's experiences with those of men. It is a reanalysis of data from a previously reported study of institutionalized elders' social networks, this time with a specific focus on women residents' relationships with one another. Here, I consider the role of negative interaction in personal relationships, the meaning of intimacy and reciprocity in the nursing home context, and issues of age and gender. The final section, implications for practice and future research, includes a discussion of the opportunities for and constraints on relationship formation.
Fever, rash, and arthralgias in a male adolescent.

A previously healthy boy presents with a 6-week history of intermittent fever, diffuse erythematous rash, and polyarthralgias.
Perinatal Nutrition, Epigenetics, and Disease

Nutrition and growth during the perinatal period have long-term implications for neonates. The Developmental Origins of Disease Hypothesis states that molecular and cellular events initiated during this period have the potential to impart lifelong phenotypic changes to infants. Undernutrition resulting in intra- or extrauterine growth restriction is associated with an increased risk of neurodevelopmental impairment and lung disease as well as adult-onset diseases, including obesity, insulin resistance, and cardiovascular disease. A proposed molecular mechanism by which early events alter later health is epigenetic modifications to chromatin. One well-studied epigenetic modifier is nutrition. Much of the current evidence associating early nutritional status to epigenetic adaptations stems from animal models. This review summarizes known associations between perinatal nutrition and epigenetic alterations to chromatin. Much work remains in the field to identify how associated histone and DNA modifications contribute to changes in gene expression. It also is important to determine why a particular gene is targeted in the first place. Detailed understanding of these aspects of perinatal nutrition and epigenetics should allow development of specific, targeted interventions.
PO-0446 Parenteral Nutrition Compromises Neurodevelopment Of Preterm Pigs

Background and aims Advances in neonatal intensive care and nutrition support have increased survival of preterm infants, but the risk of compromised neurodevelopment is a concern. We evaluated parenteral nutrition (PN) as a heretofore unreported contributing factor to compromised neurodevelopment after preterm birth. Methods Neurodevelopment of preterm pigs delivered at 92% of gestation (representative of 32 week preterm infants) and provided PN or enteral nutrition (EN) for 10 days was assessed by observations of motor activity, sensory and cognitive skills, brain mass, magnetic resonance imaging, and cerebellar histology. Fluid volumes, energy, and nutrients were comparable. Results PN pigs grew slightly better than EN pigs, but had smaller brains (28 + 0.5 vs 32 + 0.6; p = 0.009), including the cerebellum, reduced motor activity (p = 0.005) and sensory responses (p Conclusions PN is essential for many preterm infant, and particularly those delivered earlier in gestation. The neurodevelopment delay caused by total PN independent of confounding variables (disease, inconsistent gestational ages,diverse genetics, different nutritional support and NICU protocols) is a novel and disturbing finding. The preterm pig is a translational animal model for investigating the relationship between nutrition support and neurodevelopment after preterm birth, improving PN solutions, and advancing neonatal intensive care.
Constitutive expression Of NGF And P75(NTR) affected by bladder distension and NGF antisense treatment.

Abstract Aims It is known that bladder exposure to noxious stimuli elicits nerve growth factor (NGF) expression with region wise differences. Here, we investigated the effect of bladder distension (cystometry) and bladder wall injection of NGF antisense oligonucleotide (ODN) together as well as separately on spontaneous (constitutive) expression of NGF and its cognate p75 neurotrophin receptor (p75NTR). Method Under isoflurane anesthesia, either 15 μg of protamine sulfate (vehicle) alone or complexed with 1.5 μg of NGF antisense or scrambled ODN was injected (10 μL) at 4 sites in bladder wall of 24 adult female Sprague-Dawley rats and 6 rats were left untreated (n = 30). Under urethane anesthesia, cystometry (CMG) was performed in treated and control rats. Fluorescent ODN and NGF/p75NTR expression was localized in harvested tissue. Key findings Complexation of ODN with protamine was essential for the retention of ODN in bladder tissue as the uncomplexed ODN was untraceable after injection. Bladder distension from CMG raised the expression of NGF and p75NTR relative to CMG naive rats. The groups treated with vehicle, scrambled and antisense ODN were indistinct with regard to CMG parameters, but the intense immunoreactivity of NGF and p75NTR seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense. Significance The constitutive expression of NGF and p75NTR is responsive to bladder distension and administration of NGF antisense. Complexation with protamine reduces the clearance of ODN and demonstrates the potential of ODN nanoparticles as an option for reducing the inducible NGF expression in OAB patients following intradetrusor injection.
Focused Ion Beam: Advanced Technique for Device Modification

Focused ion beam (FIB) technology is used to modify circuits for early-product design debug; it also has the capability to create probe points to underlying metallurgy, allowing device characterization while maintaining full functionality. These techniques provide critical feedback to designers for rapid verification of proposed design changes. Current FIB technology has its limitations because of redeposition of sputtered material; this phenomena may induce vertical electrical shorts and limit the achievable aspect ratio of a milled via to 6:1. Therefore, innovative enhancements are required to provide modification capability on planar chip technology which may utilize up to five levels of metallurgy. The ability to achieve high-aspect-ratio milling is required to access underlying circuitry. Vias with aspect ratios of 10:1 are necessary in some cases. This paper reviews a gas-assisted etching (GAE) process that enhances FIB milling by volatilizing the sputtered material, examines the results obtained from utilizing the GAE process for high-aspect-ratio milling, and discusses selectivity of semiconductor materials (silicon, aluminum, tungsten and silicon dioxide).
The use of neutrons in cancer therapy : A historical perspective through the modern era

The fields of boron neutron capture therapy (BNCT) and fast neutron radiotherapy are surveyed starting with the early clinical work that began shortly after the discovery of the neutron by Chadwick in 1932. The evolution of each field is described and the current status in regards to accepted clinical indications and ongoing research areas summarized. BNCT remains a research area but a discussion is given of current efforts to design and construct non-reactor-based epithermal neutron sources to deploy this technology to major medical centers if the clinical research proves successful. Fast neutron radiotherapy is a mature field with selected clinical indications for locally advanced salivary gland tumors and inoperable sarcomas of bone and soft tissue. The current status of clinical trials for locally advanced prostate cancer and other tumors is reviewed. Ongoing areas of research in the field of fast neutron radiotherapy are described.
Ovarian transplantation. Graft-host interactions in corneal encapsulated homografts.

Ovarian homografts encapsulated in corneal tissue may survive by the induction of specific immunologic tolerance in the host by the graft or the adaptation of the graft to the host. To test these hypotheses, these grafts were challenged in a series of experiments. Despite challenge grafts of ovarian tissue and skin from the original donor and of ovarian tissue from a “third party” donor, the ovarian tissue within the capsule remained viable for periods up to 30 weeks. A “backgraft” of encapsulated ovarian tissue removed from the recipient after 11 weeks and stripped of its capsule was not rejected after 6 weeks’ residence in the original donor. Rejection times for homografts of ear skin in animals with ovarian homografts were the same as controls. These data indicate that (a) survival was not due to immunologic tolerance and (b) the surviving ovarian tissue was nonantigenic in relation to the host but had not undergone adaptation. It is suggested that the less antigenic cells within the capsules had been “passively” selected for survival by prolonged incubation in an immunologically unfavorable environment.
Neutral amino acid transport systems of microvillous membrane of human placenta

Placental transport produces concentrations of amino acids in fetal blood greater than those of maternal blood. Competitive inhibition studies of zwitterionic amino acid transport in isolated vesicles from the microvillous (maternal facing) plasma membranes of syncytiotrophoblast defined three transport systems: 1) a sodium-dependent system that supports methylaminoisobutyric acid (MeAIB) transport and has the characteristics of an A system; 2) a sodium-independent system with a high affinity for leucine and other amino acids with branched or aromatic side chains; and 3) a sodium-independent system with a preference for alanine as a substrate. The two sodium-independent systems could be further discriminated by marked specificity for trans stimulation with alanine or with leucine. System ASC, known to be present in whole placenta, and the neutral brush-border or imino systems of other polarized epithelia were apparently absent. Kinetic characteristics of the A system make it the probable primary driving force for concentrative transfer of its substrate amino acids to the fetus. Characteristics of the high-affinity leucine system demonstrated that it is saturated by normal serum leucine concentrations. Regulation of either system has the potential to alter placental amino acid uptake and transfer to the fetus.
The Effects of Training in Combinatorial Reasoning and Propositional Logic on Formal Reasoning Ability in Junior High School Students

Scientific reasoning is an important skill for students. According to Piaget, students develop formal reasoning during their teens. Studies have shown, however, that some secondary students and adults are unable to reason formally. This study sought to determine three things: Can combinatorial and propositional reasoning be taught to junior high school students? Does moving from the familiar to nonfamiliar facilitate nonspecific transfer? Does gender influence the learning of reasoning skills? Subjects were concrete operational reasoners at pretest. With 20 ten minute instructional episodes, students were able to learn and use combinatorial reasoning and propositional logic, with specific transfer only. There were no significant effects for gender. Students who had received the treatments experienced less frustration and better achievement in their science classes as compared to their non treatment counterparts. The results suggested that reasoning instruction can be effective and should be includ...
Kroetz, Fassbinder and Drama for the Masses

Kroetz’s success in relatively small theatres with plays like Stallerhof and Ghost Train proved not to be enough for a playwright interested in touching a mass audience. His first plays were grouped with those by Fassbinder, Martin Sperr and Wolfgang Bauer because of common features such as attention to specific milieus, stress on local dialect and slang, and concentration on small excerpts from reality. Kroetz has more than once expressed the opinion that his early recognition owed something to the wave of ‘neo realist’ plays at the end of the sixties. While Peter Handke had become an outspoken literary phenomenon, Kroetz on several occasions provoked public outcry with his work, and achieved a notoriety which went beyond the plays themselves. (In July of 1973 an Austrian high school teacher was fired without notice for arranging to read Stallerhof with her class.) In the course of the seventies Kroetz also frequently made open critical statements on the state of the nation and partook in party politics. His attitudes toward his work as a playwright changed significantly, though his approach to structure (short simple scenes) and realistic dialogue remained largely unchanged.
The Development of Neural Circuits in the Limb Moving Segments of the Spinal Cord

The problem of how motoneurons in the vertebrate spinal cord establish appropriate peripheral and central connections during embryogenesis has been considered with emphasis on the chick. The sequence of synapse formation in the cord does not allow one to determine whether motoneurons are intrinsically specified, or specified by the muscles with which they synapse or by other mechanisms such as position in the cord. It was shown low-ever that motoneurons grow out very selectively to the appropriate muscles from the start and that from the time that spontaneous movement begins, it is co-ordinated with reciprocal activation of antagonists, possibly mediated by reciprocal inhibitory connections. Various models for bringing about the observed connectivity are reviewed and experimental manipulations utilizing transplanted supernumerary limbs proposed that might allow one to distinguish between the different possibilities.
High-Dose Melphalan and Autologous Stem Cell Transplantation in Unusual Non-Amyloid Light Chain Deposition Disorders.

Abstract Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains, usually with a kappa genotype, are deposited in various tissues in a globular form resulting in organ dysfunction. Crystal-storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystalline deposits. Both LCDD and CSH are uncommon diseases, for which there is limited treatment experience. However, conventional anti-plasma cell chemotherapy with oral melphalan as is used in multiple myeloma has been tried in LCDD with little benefit. Between 1999–2005, five patients with LCDD and one patient with CSH have been treated at Boston University Medical Center with high-dose intravenous melphalan (IVM) followed by autologous peripheral blood stem cell transplantation (SCT). Patients have been treated with either 200mg/m2 of IVM (n=5) or 140 mg/m2 (n=1) depending on age and clinical status and subsequently have been assessed for hematologic responses and for improvements in organ function at 3, 6 and 12 months, and annually thereafter. The median age of patients at the time of treatment has been 45 years (range 34–51). Four patients with LCDD had kappa light chain deposition involving the kidneys and 1 of these patients had extrarenal involvement of the heart on electron microscopy of endomyocardial biopsy as well. One patient with LCDD had lambda deposition involving kidneys only. The patient with CSH had only renal involvement, with kappa light chain plasma cell dyscrasia. All except 1 patient had impaired renal function with creatinine clearance ranging from 21 – 64 ml/min. All treated patients are alive and well at a median follow up of 13.6 months (range 5–24 months). Median survival has not yet been reached. No treatment-related deaths were noted, and treatment-related toxicities were manageable and reversible. All evaluable patients (n=4) have achieved a hematologic complete response of the underlying plasma cell dyscrasia after IVM/SCT. In conclusion, this experience indicates that IVM/SCT is a safe, feasible, and effective modality for the treatment of these unusual light chain deposition disorders.