cssi/SciSciGPT-SciSciNet huggingface dataset:
Large Clinical Trials and Registries—Clinical Research Institutes

As medical practice enters the era of “evidence-based medicine,” there is a growing need for high-quality scientific evidence to inform decisions made by physicians and other health care providers. However, pressures on the existing clinical research enterprise are mounting. New diagnostic and therapeutic technologies continue to drive up health care costs, while at the same time, resources for evaluating such technologies are increasingly constrained. Clinician-researchers therefore must have a thorough grasp of the strengths and limitations of various research methods and must be able to critically evaluate and apply approaches both traditional and novel. In this chapter, we will explore the history, background, and general concepts of clinical research before moving on to address how the results of investigations are expressed. We will also examine clinical trial design; ethical, legal, and organizational aspects of conducting clinical research; the application of statistical methods, including meta-analyses and systematic reviews; and the integration of these concepts into practice. Finally, we will visit current controversies in clinical research and explore some possibilities for the future.
Abstract 107: Flow-Diversion for Ophthalmic Segment Aneurysms. Clinical/Angiographic Outcomes and the Fate of the Ophthalmic Artery

Introduction: Flow diverters have emerged as an important tool in the management of intracranial aneurysms. This study aims to assess the visual outcomes, the obliteration rate and the need for retreatment of ophthalmic segment aneurysms (OSA) treated by the pipeline embolization device (PED). The study also systematically assesses a crucial issue with the use of flow diverters namely the patency of the ophthalmic artery (OA). Methods: Forty-one patients harboring 44 OSA treated by flow-diversion and 95 patients with internal carotid artery (ICA) aneurysms who had one or more PEDs covering the OA and in whom angiographic follow-up was available were identified. Complication rates, the need for re-treatment, aneurysm occlusion rates, the evolution of visual symptoms, and the evolution of headache/retro-orbital pain were registered. The patency of the OA at follow-up was systematically evaluated by two investigators. Results: The technical success rate was 100% for OSA. The complication rate was 2.27% and the mortality rate was 0%. At final angiographic follow-up, 77.27% of patients with OSA had complete occlusion, 6.81% had near-complete occlusion, and 15.90% had incomplete occlusion. Of symptomatic OSA, complete resolution or significant improvement was noted in 72.72%, while worsening of symptoms occurred in 4.54%. Also, 22% of patients had no significant changes in their symptoms. Of 95 patients with ICA aneurysms, the OA was covered by 1 PED in 81 patients (85%) and by 2 PEDs in 14 patients (15%). Mean angiographic follow-up time was 7.5 months. At the latest follow-up, the OA remained patient in 85 patients (89%), showed diminished flow in 4 patients (4%), and was occluded in 6 patients (7%). Only one patient (1%) had clinical symptoms related to OA occlusion. In multivariable analysis, younger age, larger aneurysm size and coverage by more than 1 device predicted OA occlusion. Conclusion: Flow-diversion appears to be an appealing option for OSA. The PED also preserves the patency of the OA in most cases. The occlusion of the OA in the few cases where it occurs is usually a clinically irrelevant event. Minimizing the number of PEDs across the OA is a crucial factor to preserve its patency.
Optimal intertemporal supply of a public facility under uncertainty

Abstract This paper is concerned with the optimal scheduling of open space over a finite planning period. The analysis presented considers explicitly and systematically the stochastic nature of demand for open space and the penalties associated with ‘leads’ and ‘lags’ in its supply over time. — The Technique of probabilistic discrete dynamic programming is used to develop a mathematical model that permits the determination and evaluation of various open space policies. The conceptual approach adopted and illustrated herein is applicable to a broad general class of economic planning problems, namely, the optimal intertemporal provision of a public service that requires as an essential input a ‘limited’ resource whose supply characteristics are controlable, but determined by its previous use.
Industrialización y dinámicas espaciales en Bogotá: las urgencias de la gestión territorial

Las reformas estructurales e institucionales que debieron adecuar al pais, y en especial a Bogota, a los estandares mundiales de productividad y competitividad, han significado una alta concentracion de las actividades productivas en la ciudad capital, cuando se esperaba que fuesen los puertos y las fronteras las que cobraran un mayor dinamismo. Sin embargo, se ha presentado una perdida de dinamismo relativo y absoluto de la industria manufacturera, tanto de Bogota como de los centros industriales tradicionales. Esto ha implicado mantener la Ciudad como polo de atraccion y requerir una reconfiguracion de espacios, incluyendo procesos de conurbacion. Se ha convertido entonces en prioridad para la Ciudad, pensar su territorio y su dimension regional, y concordar un proceso de reindustrializacion que la conduzca a responder a las exigencias del pais y de la region. Este articulo presenta primero un debate teorico sobre la importancia de la comprension del espacio y del territorio como elementos necesarios para el diseno de estrategias de futuro. Posteriormente se analiza el caso del comportamiento de Bogota y sus tendencias espaciales y de la industria manufacturera. Finalmente se presentan las conclusiones del trabajo.
Large exon size does not limit splicing in vivo

Exon sizes in vertebrate genes are, with a few exceptions, limited to less than 300 bases. It has been proposed that this limitation may derive from the exon definition model of splice site recognition. In this model, a downstream donor site enhances splicing at the upstream acceptor site of the same exon. This enhancement may require contact between factors bound to each end of the exon; an exon size limitation would promote such contact. To test the idea that proximity was required for exon definition, we inserted random DNA fragments from Escherichia coli into a central exon in a three-exon dihydrofolate reductase minigene and tested whether the expanded exons were efficiently spliced. DNA from a plasmid library of expanded minigenes was used to transfect a CHO cell deletion mutant lacking the dhfr locus. PCR analysis of DNA isolated from the pooled stable cotransfectant populations displayed a range of DNA insert sizes from 50 to 1,500 nucleotides. A parallel analysis of the RNA from this population by reverse transcription followed by PCR showed a similar size distribution. Central exons as large as 1,400 bases could be spliced into mRNA. We also tested individual plasmid clones containing exon inserts of defined sizes. The largest exon included in mRNA was 1,200 bases in length, well above the 300-base limit implied by the survey of naturally occurring exons. We conclude that a limitation in exon size is not part of the exon definition mechanism.
Percolation in inhomogeneous superconducting composite wires

Abstract We report the initial results of SQUID voltmeter measurements on Cu-alloy wires which contain elongated μm-scale inclusions of superconducting Nb. Below the transition temperature T c of the Nb inclusions the wires have a temperature-dependent resistance which can be fit to R ∝ (T - T cl ) s where s = 1.06 ± 0.04. We develop a simple model employing percolation theory to explain this behavior.
Helium and lower oxygen concentration do not prolong tracheal tube ignition time during potassium titanyl phosphate laser use.

BACKGROUND: Tracheal tube fire is a well recognized complication of airway laser procedures. The use of helium in the anesthetic gas mixture delays the ignition time of polyvinyl chloride tracheal tubes when a carbon dioxide laser is used. The effects of helium gas mixtures on potassium titanyl phosphate (KTP) laser-induced tracheal tube ignition have not been studied. METHODS: One hundred forty unmarked polyvinyl chloride tracheal tube segments were exposed to KTP or carbon dioxide laser beams. Each tube segment was suspended in a burn chamber with varying mixtures of oxygen in either nitrogen or helium. The gas mixtures were 21%, 30%, and 40% O2 in N2 or 30% and 40% O2 in helium. Fourteen tube segments were tested for each gas mixture. The ignition time was recorded for each segment. The laser beam was turned off at 60 s if ignition did not occur. RESULTS: At 30% O2/N2, mean ignition time with the carbon dioxide laser was 41.3 +/- 10.8 s (mean +/- standard deviation), whereas at 30% O2/He, the mean ignition time was 60 +/- 0 s. Increasing the oxygen concentration to 40% significantly shortened the ignition time with both helium and nitrogen for the carbon dioxide laser. With the KTP laser, ignition time varied greatly at any oxygen concentration. At 30% O2/N2, median ignition time with the KTP laser was 6.9 s (mean time 15.6 +/- 19.5 s), whereas at 30% O2/He, median time was 8.6 s, (mean time 9.9 +/- 5.33 s). No statistically significant differences were found for the ignition times in the KTP laser groups. CONCLUSIONS: Using helium instead of nitrogen with oxygen delays unmarked polyvinyl chloride tracheal tube ignition time when the tube segments are exposed to a carbon dioxide laser beam as compared to a KTP laser. The different laser wavelengths and penetration properties may produce this difference. The helium protocol previously described has been proven safe only with the carbon dioxide laser and should be tested with other laser types before being used clinically with these lasers.
Spectrophotometric and polarographic analysis for phenobarbital, n-methylphenobarbital and n-methoxymethylphenobarbital in a mixture

Abstract Measurements of absorbance at 230 nm at pH 6.3 5 ,242 nm at pH 9.4 and at 273 nm at pH 13 are used to determine phenobarbital, N -methylphenobarbital and N -methoxy-methylphenobarbital in mixtures, in the presence of other drugs administered in epilepsy treatment and in the presence of serum components. The accuracy of the analysis is increased when phenobarbital is determined separately by differential pulse polarography.
Racial disparities in length of stay in hospice care by tumor stage in a large elderly cohort with non-small cell lung cancer

This study examined whether there are racial disparities for length of stay in hospice for patients with non-small cell lung cancer (NSCLC).We studied 53,626 deceased patients aged ≥66 years diagnosed with American Joint Committee on Cancer stages I-IV NSCLC identified from the Surveillance, Epidemiology, and End Results-Medicare linked data who used hospice services in the last six months before death, and died between 1 January 1991 and 31 December 2005. Median time (days) and percent length of stay in hospice, and multivariate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) using zero-truncated negative binomial regression described relationships. In 2000-2005, most patients (64.1%) had <30 days, including those (30.2%) with <7 days length of stay in hospice care. After adjusting for confounders, the IRR for length of stay in hospice compared to whites was 38% increased for blacks (IRR = 1.38; 95% CI: 1.01-1.89), and almost three-fold increased for Hispanics (IRR = 2.91;95% CI: 1.15-7.37) at stages I-II. However, blacks at stages III-IV had slightly decreased use of hospice services (IRR = 0.91; 95% CI: 0.85-0.97). Length of stay decreased slightly among blacks diagnosed with late stage (III-IV) NSCLC in 2000-2005.The gap in disparity for length of stay in hospice has narrowed for ethnic minorities compared to whites, while some ethnic minorities had greater length of stay at early disease stage.
Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies

Accurate DNA replication and repair is essential for proper development, growth and tumor-free survival in all multicellular organisms. A key requirement for the maintenance of genomic integrity is the availability of adequate and balanced pools of deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Notably, dNTP pool alterations lead to genomic instability and have been linked to multiple human diseases, including mitochondrial disorders, susceptibility to viral infection and cancer. In this review, we discuss how a key regulator of dNTP biosynthesis in mammals, the enzyme ribonucleotide reductase (RNR), impacts cancer susceptibility and serves as a target for anti-cancer therapies. Because RNR-regulated dNTP production can influence DNA replication fidelity while also supporting genome-protecting DNA repair, RNR has complex and stage-specific roles in carcinogenesis. Nevertheless, cancer cells are dependent on RNR for de novo dNTP biosynthesis. Therefore, elevated RNR expression is a characteristic of many cancers, and an array of mechanistically distinct RNR inhibitors serve as effective agents for cancer treatment. The dNTP metabolism machinery, including RNR, has been exploited for therapeutic benefit for decades and remains an important target for cancer drug development.
A comprehensive flow regime map for microchannel flow boiling with quantitative transition criteria

Due to the critical role of vapor confinement in establishing distinct flow and heat transfer characteristics in microchannels (as distinct from those in larger channels), the conditions under which such confinement occurs in microchannels are of great interest. It is shown in the present work that channel dimensions and flow properties alone, as proposed in past studies, are insufficient for determining confinement effects in microchannel boiling. Hence, a new criterion for physical confinement in microchannel flow boiling, termed the convective confinement number, that incorporates the effects of mass flux, as well as channel cross-sectional area and fluid properties, is proposed. This criterion helps determine the conditions under which a channel qualifies as a microchannel for two-phase flow, needing special treatment, and when a macroscale treatment is adequate. In addition, based on previous work by the authors, a new comprehensive flow regime map is developed for a wide range of experimental parameters and channel dimensions, along with quantitative transition criteria based on nondimensional boiling parameters.
Use of Optical Density of Fluorescent Conjugates for Analysis of Co-Precipitating Antibody.∗

SummaryThe O.D. of fluorescein isothiocyanate permits determination of quantity of protein derived from a conjugated precipitin serum when this is added to an unconjugated precipitin serum. This permits one to distinguish in a specific precipitate the antibodies of the 2 sera. This finding could have practical application in co-precipitation technics.
Transport of Nordic Seas Overflow Water Into and Within the Irminger Sea: An Eddy-Resolving Simulation and Observations

[1] Results from a climatologically forced, eddy-resolving (1/12°) Atlantic simulation using the Hybrid Coordinate Ocean Model help clarify some presently unresolved connections between volume transports of Nordic Seas overflow water at key locations in the northernmost North Atlantic Ocean. The model results demonstrate that, in addition to the known westward flow through the Charlie Gibbs Fracture Zone (CGFZ), some Iceland Scotland overflow water (ISOW) flows westward through gaps in the Reykjanes Ridge north of the CGFZ into the Irminger Sea, and some flows southward along the eastern flank of the Mid-Atlantic Ridge into the West European Basin. These results provide insights into the well-known inconsistency between observed westward transport of ISOW through the CGFZ (2.4 Sv) and the transports upstream at Southeast of Iceland section (3.2 Sv) and downstream in the western Irminger Sea (4.5 Sv). Although the portion of the simulated ISOW that flows through CGFZ is about 500 m deeper than observed, the model results also show two ISOW pathways of this flow into the Irminger Sea, one northward along the western flank of the Reykjanes Ridge and the other westward before turning north-eastward on the western side of the Irminger Basin. Comparisons with the long-term moored instrument database in the Irminger Sea show that the model-based mean circulation is in reasonable agreement with observed volume transports of overflow water and that it gives approximately correct temperature and salinity characteristics.
Visually Evoked Potentials: Amplitude Changes with Age

Visually evoked potentials of 215 subjects, aged 1 month to 81 years, were studied. Amplitudes of waves in the first 250 milliseconds of the response changed markedly with age. In responses recorded from the occiput, there was a rapid increase in amplitude reaching a maximum in the 5- to 6-year-old group, with means of amplitudes at this age being about twice as large as means of some older age groups. With children 7 years and older there was a rapid decline in amplitude until ages 13 to 14, when an abrupt increase in amplitude appeared. Amplitude appeared to stabilize at about age 16. In older subjects, mean age 60 and beyond, significant changes were noted in the earlier components of the response.
Cis-trans isomerism in (trpy)(PPh3)RuC12. Comparisons between the chemical and physical properties of a cis-trans isomeric pair

The syntheses of complexes derived from the planar, tridentate ligand 2,2',2''-terpyridine (trpy) of the type (trpy)Ru/sup II/(L)Cl/sub 2/ where L = PPh/sub 3/, P(p-C/sub 6/H/sub 4/Me)/sub 3/, or pyridine are described. Some rather striking differences in the properties of the cis and trans-isomers of the phosphine derivatives are reported. (BLM).
Role of molecular biology in identifying individuals at risk for sudden cardiac death

Cardiology has participated in the new developments in molecular biology and the impact of the Human Genome Project. In these last few years, we have observed how the research in human physiology and journal publications have been focusing on the most basic molecular level. Clinicians have likely been having trouble keeping up with the new developments and, more importantly, with the highly publicized discoveries trying to discern what is research and what can already be applied at the bedside. Molecular biology has just started, and there is no doubt that it will have a tremendous impact in the diagnosis, prevention, and therapy of most diseases, including sudden death and cardiac arrhythmia. In the last few years, we have seen new data in the field of genetics and arrhythmia that are already shaping our approach to an inherited disease. Routine clinical tests are not yet available, mainly due to the lack of sufficiently powerful technology, but with the pace of evolution at this turn of the millennium, we can certainly assume that such testing is just a matter of time.
Sliding charge-density waves as rough growth surfaces

Using high-resolution x-ray scattering techniques we have measured the transverse structure of the sliding charge-density wave (CDW) in NbSe 3 . For temperatures between 70 K and 120 K and for applied currents up to 40x the threshold current for sliding, the scattering peak for the sliding CDW is significantly broader than that for the pinned CDW, indicating that the sliding state is less correlated than the pinned state. Using scaling analysis, we show that the CDW phase roughness exponent α rises from 0.60 ± 0.01 in the pinned state to 0.80 ± 0.01 in the sliding state.
Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum.

Abstract Background & Aims: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile , the causative agent of antibiotic-associated colitis. Methods: Ileal loops were injected with 10 μg of toxin A, and enterotoxic responses were measured at various time points. Results: Pretreatment of mice with 2.5 μg/kg of the CRH receptor antagonist α-helical CRH (9–41) that blocks both CRH receptor subtypes reduced toxin A–mediated ileal secretion, epithelial cell damage, mucosal edema, neutrophil infiltration, and mucosal content of interleukin 1β and tumor necrosis factor α. Pretreatment with the specific CRH 1 receptor antagonist antalarmin (20 mg/kg, IP) also inhibited toxin A–induced fluid secretion and toxin A–associated histologic changes. CRH messenger RNA and protein were increased in mouse ileum 30 minutes after intraluminal toxin A administration. In situ hybridization and immunohistochemistry demonstrated that toxin A at 1 hour caused a substantial increase in the expression of both CRH receptor subtypes in the ileal mucosa. Conclusions: Peripheral CRH may play a proinflammatory role in toxin A–induced intestinal secretion and inflammation and that CRH 1 receptor, at least in part, is important in the mediation of these responses. GASTROENTEROLOGY 2002;123:505-515
CpG-rich sequences close to the site of duplication within the human IGH constant region

Human immunoglobulin heavy chains are encoded by a highly complex locus, IGH, which encompasses many transcriptional units, including nine alternative constant region genes. Much of the constant region gene cluster was duplicated during hominoid evolution. In rodents, IGH is known to be regulated by multiple elements, including several enhancers 3' of the alpha chain-encoding A constant region gene, CA, the last transcribed region. Sequences downstream of the two human CA genes, possibly containing homologous enhancer elements, have not yet been reported. By long-range mapping of genomic DNA, a cluster of unmethylated rare restriction sites, representing a potential CpG island, was previously reported downstream of each CA gene, close to the 3' end of the duplicated region. Such potential CpG islands are candidates for additional IGH regulatory elements. We isolated bacteriophage clones containing these clusters of methylation-sensitive restriction sites, which lie within short CpG-rich stretches. Some of these sites showed tissue-specific methylation. 3' of the unmethylated CpG-rich sequences, clones derived from the 5' (telomeric) copy of the duplicated region, contained, in order, endogenous retroviral sequences, a processed ELK1 pseudogene, and the pseudogene IGHGP. Comparison with the presumed 3' (centromeric) copy of the duplicated region showed that similarity was lost exactly at the end of the retroviral long terminal repeat sequences. These results imply that an endogenous retroviral integration was present immediately 3' of IGH in the common hominoid ancestor and suggest models for the duplication of the region.
Stability of voids in neutron irradiated nickel

Abstract The formation and stability of voids introduced in high purity nickel by irradiation with neutrons in the temperature range 50 to 575 °C has been studied. Octahedral shaped voids form during irradiation at temperatures ⩾ 260 °C (0.30 T m ). The size of the voids increases and the density decreases with increasing irradiation temperature, but the volume fraction of voids is relatively temperature independent. If nickel is irradiated at a low temperature (50 °C) and subsequently annealed at an elevated temperature, stacking fault tetrahedra are formed; voids do not develop. The voids present in the nickel irradiated at temperatures > 260 °C coarsen during isothermal annealing at 600 °C by the process of large voids growing at the expense of smaller voids. At higher annealing temperatures, the voids anneal heterogeneously and are completely annealed at 800 °C. The configuration and density of voids in the nickel is compared to that in copper, aluminum and molybdenum.
Bayesian Quantitative Trait Loci Mapping for Multiple Traits

Most quantitative trait loci (QTL) mapping experiments typically collect phenotypic data on multiple correlated complex traits. However, there is a lack of a comprehensive genomewide mapping strategy for correlated traits in the literature. We develop Bayesian multiple-QTL mapping methods for correlated continuous traits using two multivariate models: one that assumes the same genetic model for all traits, the traditional multivariate model, and the other known as the seemingly unrelated regression (SUR) model that allows different genetic models for different traits. We develop computationally efficient Markov chain Monte Carlo (MCMC) algorithms for performing joint analysis. We conduct extensive simulation studies to assess the performance of the proposed methods and to compare with the conventional single-trait model. Our methods have been implemented in the freely available package R/qtlbim (http://www.qtlbim.org), which greatly facilitates the general usage of the Bayesian methodology for unraveling the genetic architecture of complex traits.
Tachyphylaxis to inhaled isoproterenol and the effect of methylprednisolone in dogs

Abstract Acute tachyphylaxis can be induced to inhaled isoproterenol (ISO) in anesthetized, closed-chested mongrel dogs. The responsiveness to ISO measured as the percent reduction in methacholine-induced bronchoconstriction was decreased significantly (p
The effect of inducers of mixed-function oxidases on hepatic microsome-mediated aflatoxin B1 transformation in C3H10T12 cells

Abstract The potent hepatotoxin and hepatocarcinogen aflatoxin B1 (AFB1) is metabolized by different forms of cytochrome P450 associated with the hepatic mixed-function oxidase system. C3H 10T 1 2 (10 T 1 2 ) cells, which have limited inherent capacity to metabolize AFB1, were treated with AFB1 in the presence of hepatic microsomes isolated from chemically treated rats to investigate the effects of the induction of specific cytochromes P450 on AFB1-mediated toxicity and transformation. Relative to uninduced microsomes, phenobarbital (PB) treatment induced AFB1-DNA binding (essentially representing the formation of AFB1-8,9-oxide bound to DNA) 3.2-fold, while pretreatment with Aroclor 1254, 3-methylcholanthrene (3-MC), or 5,6-benzoflavone (β-NF) preferentially induced aflatoxin M1 (AFM1) formation from 2- to 5-fold. 10 T 1 2 cells were exposed to a multiple treatment regimen with 4 μ m AFB1 and hepatic microsomes from uninduced, PB-, Aroclor 1254-, 3-MC-, or β-NF-treated rats; respective cumulative toxicities of approximately 90, 95, 70, 60, and 40% control (no microsomes) values resulted. An enhanced AFB1 transformation response correlated with the increasing toxicities observed for the different treatments, with uninduced or PB-induced microsomes yielding approximately four foci/dish, while treatments with Aroclor 1254-, 3-MC-, or β-NF-induced microsomes resulted in only one to two foci/dish. These results demonstrate that AFB1 is a complete carcinogen in the 10 T 1 2 system when repetitive incubations are used in conjunction with an appropriate hepatic microsomal activation system. These data also correlate the induction of AFB1-4-hydroxylase with a decrease in AFB1-mediated toxicity and transformation of 10 T 1 2 cells, and support the hypothesis that the Phase I metabolic conversion of AFB1 to AFM1 in the liver represents an effective detoxication pathway per se.
Numerical analysis of heat transfer due to confined slot-jet impingement on a moving plate

Abstract Convective heat transfer from a moving isothermal hot plate due to confined slot-jet impingement is investigated numerically. Two-dimensional turbulent flow is considered. The rectangular flow geometry consists of a confining adiabatic wall placed parallel to the moving impingement surface with the slot-jet located in the middle of the confining wall. The k − e turbulence model with enhanced wall treatment is used for the turbulence computations. The problem parameters are the jet exit Reynolds number, ranging from 5000 to 20,000, the normalized plate velocity, ranging from 0 to 2, and the normalized distance of separation between the impingement plate and the jet exit, ranging from 6 to 8. The computed flow patterns and isotherms for various combinations of these parameters are analysed to qualitatively understand the effect of the plate motion on the heat transfer phenomena. The distribution of the local and average Nusselt numbers and the skin friction coefficients at the hot moving surface for above combinations of the flow parameters are presented. Results are compared against corresponding cases for heat transfer from a stationary plate. The analysis reveals that the average Nusselt number increases considerably with the jet exit Reynolds number as well as with the plate velocity. The average skin friction coefficient, on the other hand, is relatively insensitive to the Reynolds number but increases significantly with the plate velocity.
Total Syntheses of (+)-Zampanolide and (+)-Dactylolide Exploiting a Unified Strategy

The first total syntheses of (+)-zampanolide (1) and (+)-dactylolide (2), members of a new class of tumor cell growth inhibitory macrolides, have been achieved. Key features of the unified syntheti...
A Symmetric Multiprocessor Architecture for Multi-Agent Temporal Difference Learning

Temporal difference learning methods have been successfully applied to a wide range of stochastic learning and control problems. In addition to correctness, one metric of a technique's performance is its learning rate - the number of iterations required to converge to an optimal solution. The learning rate can be increased by using multiple agents that can share experience. In a software environment, the potential speedup from additional agents is limited, since adding agents significantly increases the burden of computation and/or hinders real-time processing. To address this problem, this paper presents a parameterized hardware model of a multi-agent system based on a shared-memory Symmetric Multiprocessor (SMP). To the author's knowledge, this is the first application of an SMP architecture to a multi-agent reinforcement learning system. The control model employed is a multi-agent variation of the Sarsa(?) algorithm. Several hardware optimizations schemes are investigated with respect to feasibility and expected performance. The system is modeled using a cycle-accurate simulation in SystemC. The results indicate that real-time learning rates can be significantly improved by employing the proposed parallel hardware implementation.
Running and the Development of Disability with Age

Objective: To determine, by longitudinal study, whether regular vigorous running activity is associated with accelerated, unchanged, or postponed development of disability with increasing age. Stud...
Proctocolectomy with ileoanal anastomosis.

Ileoanal anastomosis has evolved through many phases before arriving at the highly successful procedure currently used at major centers. Interesting, in reviewing the world’s literature, those series that report patient outcomes stratified by year show significant improvements in function and quality of life in patients who have received the operation more recently when compared with patients receiving the operation in the earlier years. Continued technical advances and greater surgeon experience can only further improve function, outcome, and patient satisfaction. Despite some opposition,31 under elective conditions, IPAA remains an excellent option for patients with CUC and FAP once the decision for surgery has been mutually reached by the patient and surgeon.32 With technical modifications and with experience, mucosal proctectomy and IPAA can now be performed with a low rate of complications, with good functional results and quality of life and excellent long-term outcome. As these patients, especially those with CUC, experience more frequent inflammatory episodes or become refractory to medical management, their medical and surgical management will require a closely coordinated effort by their gastroenterologists and their surgeons. Unless the colectomy is urgent, these patients typically tend to get referred earlier and therefore have more favorable outcomes. Optimal results are obtained by careful patient selection, appropriate preoperative management, meticulous standardized surgical technique, appropriate postoperative education, and rigorous follow-up.
Three-Dimensional Transitory Control of Flow Separation over a 2-D Airfoil

The dynamics of controlled transitory 3-D flow attachment within a separated flow domain over a stationary and pitching 2-D airfoil is investigated in wind tunnel experiments using a spanwise-compact pulsed actuation having a characteristic time scale that is an order of magnitude shorter than the convective time scale. It is shown that spanwise spreading of the induced transitory 3-D flow attachment beyond the spanwise edges of the actuator can amplify the aerodynamic performance of the airfoil compared to 2-D, spanwise-bounded actuation. The dynamics of the 3D attachment domain and some features of its spanwise structure above the airfoil and in its near wake are investigated using PIV. The temporal and spanwise variations of the 3-D attached domain result in corresponding variations of the vorticity over the both surfaces of the airfoil and consequently in significant changes in the time-dependent sectional circulation. Coupling of the pulsed actuation to the airfoil’s motion by sequenced actuation during the pitch cycle enhances the control authority of 3-D unsteady separation and can significantly mitigate the effects of dynamic stall and improve the unsteady aerodynamic lift and pitching moment.
Fractional Factorial Design for the Identification of Important Instrumental Factors Affecting the Quality of Gas Chromatographic Separation of Whiskey Volatiles

A fractional-factorial screening experiment that helps students identify important factors in gas chromatographic method development is described. The experiment gives practical experience in relating chromatographic theory to practice. The results of sixteen gas chromatography runs of a single whiskey sample enable students to deduce that mobile-phase flow rate has the major effect on the quality of the separation of this complex mixture. Three other individual factors and an interaction of two factors exert a minor influence on the quality of the separation.
Measurement of Force Curve due to Electrostatic Charge on a Single Particle using Atomic Force Microscope [Translated]†

A single particle is brought into contact with a metal target, and the force acting on the particle is measured by using atomic force microscope (AFM). By focusing on measuring the force ‘curve’ , rather than looking only at the maximum adhesive force, electrostatic interaction was successfully observed by separating other interactions such as liquid bridge and intermolecular forces. To evaluate the force curve, the force curve with an approximation of disk-to-disk interaction based on image force was numerically calculated and a good analytical approximation was developed. The fact of successful agreement between the observed force curve and the theory revealed that the force curve observed can be surely attributed to the electrostatic interaction, and that the amount of charge on the particle and the radius of the charged (contact) area can be estimated from the analysis. The order of magnitude of the measured charge density was 10 -2 C/m 2 , which is much greater than that obtained with impact charging experiment as 10 -4 C/m 2 . From this it was concluded that the force curve measurement with AFM can capture the net amount of the charge generated before charge relaxation due to gas discharge taking place. In the experiment using 8 kinds of metal (Al, Au, Cr, Ni, Pt, Ti, Zn, and Zr) and polystyrene particle, the net charge generated was shown to be compared fairly well with the conventional simple condenser model based on metal-to-metal contact model in terms of contact potential difference in its order of magnitude. Although a clear correlation was not obtained between the measured charge density and the work functions of metal targets because of a large scatter in the data, a strong relationship between the charge density and contact area was found. The underlying mechanisms for the relationship is not known at this moment; however the finding gives a good hint for the next attempt.
Pollen and fungal spores indoor and outdoor of mobile homes

Background Allergenic diseases triggered by aeroallergens extract a health cost in quality of life and in economic impact. People generally spend 90% to 95% of their time indoors, so understanding the environmental factors that affect the presence of aeroallergens indoors are important in understanding health impact and potential intervention methods. Objective To describe the relationship of indoor airborne pollen and fungal spores in occupied mobile homes with outdoor concentrations and other environmental factors within geographically diverse areas of Texas. Methods Airborne pollen and fungal spores were collected during the daytime with RotoRod samplers indoor and outdoor of mobile homes in Houston and El Paso, Texas. Samples were counted simultaneously with a dual eyepiece microscope and identified morphologically and through staining techniques. Results Geometric mean concentrations (counts/m 3 ) indoors and outdoors for pollen, respectively, were Houston 7.1 and 196.4; and El Paso 17.5 and 71.5. Gometric mean concentrations (counts/m 3 ) indoors and outdoors for spore, respectively, were Houston 98.5 and 196.4; and El Paso 36.9 and 71.5. Indoor to outdoor ratios (I/O) for pollen and fungal spores were found to be higher on average than has been previously reported. Modeling of predictive factors in Houston demonstrate that 62% and 41% of indoor levels of pollen and fungal spores, respectively, can be explained by their corresponding outdoor levels. These data suggest that the many factors associated with individual exposure to airborne pollen and fungal spores indoors are under the control of the occupant, and may additionally be influenced by the physical characteristics of mobile homes, in particular the high surface area to volume ratio and restricted flow patterns.
Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases

Since the discovery of NAD-dependent deacetylase activity of the silent information regulator-2 (SIR2) family ('sirtuins'), many exciting connections between protein deacetylation and energy metabolism have been revealed. The importance of sirtuins in the regulation of many fundamental biological responses to various nutritional and environmental stimuli has been firmly established. Sirtuins have also emerged as critical regulators for aging and longevity in model organisms. Their absolute requirement of NAD has revived an enthusiasm in the study of mammalian biosynthesis of NAD. Sirtuin-targeted pharmaceutical and nutriceutical interventions against age-associated diseases are also on the horizon. This review summarizes the recent progress in sirtuin research (particularly in mammalian sirtuin biology) and re-evaluates the connection between sirtuins, metabolism, and age-associated diseases (e.g., type-2 diabetes) to set a basis for the next ten years of sirtuin research.
Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department.

Study Objective. To determine the value of fosphenytoin compared with phenytoin for treating patients admitted to an emergency department following a seizure. Design. Cost-minimization analysis performed from a hospital perspective. Setting. Hospital emergency department. Patients. Two hundred fifty-six patients participating in a comparative clinical trial. Intervention. Estimation of adverse event rates and resource use. Measurements and Main Results. In our base case, phenytoin was the preferred option, with an expected total treatment cost of $5.39 compared with $110.14 for fosphenytoin. One-way sensitivity analyses showed that the frequency and cost of treating purple glove syndrome (PGS) possibly could affect the decision. Monte Carlo simulation showed phenytoin to be the preferred option 97.3% of the time. Conclusion. When variable costs of care are used to calculate the value of phenytoin compared with fosphenytoin in the emergency department, phenytoin is preferred. The decision to administer phenytoin was very robust and changed only when both the frequency and cost of PGS was high.
Transit-Time Effects in Ultra-High-Frequency Class-C Operation

Transit-time effects in ultra-high-frequency triodes and tetrodes used in class-C operation are analyzed. Effects discussed are electron-transit reactance; electron-transit phase-delay angle; cathode back-heating; use of a screen grid to improve efficiency; changes in optimum shunt impedance; secondary emission; and anode back-heating by secondary electrons. It is pointed out that by increasing voltage and current density simultaneously the frequency and power can be raised without sacrificing efficiency or bandwidth. An equivalent circuit is described which takes account of certain important transit-time effects.
Mesenchymal chondrosarcoma of the kidney

A case of mesenchymal chondrosarcoma of the kidney, with osseous metastases, is presented in this article, and the clinical, radiologic, and histopathologic features of this uncommon neoplasm are discussed. The addition of this case to those previously reported in the literature brings the total number of reported cases of mesenchymal chondrosarcoma of extraskeletal origin to 42. None of the previously reported cases originated from the kidney. The metastatic pattern of this case illustrates the propensity of mesenchymal chondrosarcoma to metastatize to unusual locations.
Shared distribution of digital products using multicast

Broadband connectivity enables effective distribution of interactive multimedia content over the Internet. The successful deployment of future multimedia applications with high bandwidth requirements will depend on business models that efficiently allocate network resources based on user demands and preferences. We present a market-based allocation framework to complement existing network protocols in a scalable and feasible manner. The model exploits the redundancy of the network to share digital products among hierarchies of communities that share common demand profiles. Quality of service-based multicast is used as the underlying network protocol. While significant advances have been made in terms of the technological protocols, corresponding business models have not been explored extensively. We outline such a model accounting for the current market structure. The highlights of the business model we propose are shared distribution, hierarchy of communities and bundling of products by local distributors. Our model leads to the NP-hard problem of computation of Steiner arborescences, and we outline feasible solution heuristics.
Successful in vitro growth of human respiratory epithelium on a tracheal prosthesis

Reconstruction of tracheal defects may be necessary following trauma or oncologic surgery. Defects up to 8 cm can often be repaired using end-to-end anastomosis. Use of a tracheal prosthesis for larger defects has been complicated by recurrent stenosis and infection. Recent animal studies, utilizing a Dacron® polyurethane prosthesis suggest that problems with anastomotic stenosis and infection can be controlled. Problems with a central stenosis within the prosthesis persist when used for defects greater than 6 cm. Establishment of a confluent lining of respiratory epithelium is believed to be necessary for successful prosthetic tracheal reconstruction. Using cell culture techniques, we report the first successful seeding and growth of human respiratory epithelium onto a Dacron polyurethane tracheal prosthesis.
Novel methods of sampling phase space in the simulation of biological systems

New advances in molecular dynamics and Monte Carlo simulations have led to impressive increases in the speed of sampling phase space for complex biological systems. These methods have been combined with new fast algorithms for computing long range electrostatic interactions for new polarizable force fields. In addition, new methods for sampling low energy molecular conformations allow the rapid determination of thermodynamically dominant regions on the potential-energy surface. Accurate measures of the rate of phase-space sampling should allow both the optimization and the comparison of methods for a particular problem of interest.
Protein Phosphatase 2Cβ Association with the IκB Kinase Complex Is Involved in Regulating NF-κB Activity

The NF-κB pathway is important in the control of the immune and inflammatory response. One of the critical events in the activation of this pathway is the stimulation of the IκB kinases (IKKs) by cytokines such as tumor necrosis factor-α and interleukin-1. Although the mechanisms that modulate IKK activation have been studied in detail, much less is known about the processes that down-regulate its activity following cytokine treatment. In this study, we utilized biochemical fractionation and mass spectrometry to demonstrate that protein phosphatase 2Cβ (PP2Cβ) can associate with the IKK complex. PP2Cβ association with the IKK complex led to the dephosphorylation of IKKβ and decreased its kinase activity. The binding of PP2Cβ to IKKβ was decreased at early times post-tumor necrosis factor-α treatment and was restored at later times following treatment with this cytokine. Experiments utilizing siRNA directed against PP2Cβ demonstrated an in vivo role for this phosphatase in decreasing IKK activity at late times following cytokine treatment. These studies are consistent with the ability of PP2Cβ to down-regulate cytokine-induced NF-κB activation by altering IKK activity.
Pressure solution deformation of conglomerates in shear zones, Narragansett Basin, Rhode Island

Abstract Pressure solution deformation in shear zones in a Pennsylvanian quartzite conglomerate from Narragansett Basin, Rhode Island, has resulted in 51–58% cobble volume reduction. Only 16–27% of this volume reduction is due to shearing; the rest is the result of an earlier constriction during folding. In the shear zones it is possible to demonstrate the effects of flattening and shearing. Pressure solution has had a flattening effect, whereas inter-cobble rotation has aligned the planes containing the long and intermediate axes of the cobbles parallel to the shear plane. The magnitude of the flattening and the degree of alignment increases with the intensity of shearing. In one shear zone internal penetrative deformation of the cobbles has occurred in addition to pressure solution and inter-cobble rotation. The magnitude of the additional strain produced by this internal penetrative deformation can be estimated, but the amounts of strain caused by flattening and shearing cannot be separated.