cssi/SciSciGPT-SciSciNet huggingface dataset:
Management of clinical stage IIIA primary lung cancers in the National Cancer Database.

Background Clinical stage IIIA (cStage IIIA) non-small cell lung cancer (NSCLC) resulting from mediastinal lymph node disease (stage IIIA–cN2) represents one of the more challenging lung cancer scenarios. Not only is the prognosis disappointing but the accuracy of mediastinal staging is uncertain, the optimal treatment approach is unclear, and the outcomes are variable. In attempt to assess the current state of clinical stage IIIA-cN2 NSCLC in the United States, we examined this controversial cohort in the largest clinical database resource available, the National Cancer Database (NCDB). Methods The NCDB was queried for patients diagnosed between 1999 and 2011 with NSCLC, clinically staged to have mediastinal lymph node metastases but not systemic metastases (T1-3, N2, M0, cStage IIIA). Results A total of 83,913 cSstage IIIA NSCLC patients with presumed or confirmed mediastinal lymph node metastases were identified. Clinical staging of the mediastinum was variable, as lymph nodes were only biopsied in 23% of patients who were treated without surgery, and in surgical patients clinical N2 status was pathologically confirmed in only 56% of treatment naive patients. The most common treatment approach was nonsurgical, involving chemotherapy, radiation, or both (69% of patients) followed by surgery (14%). The 5-year survival varied by treatment and was highest for patients treated with surgery in combination with chemotherapy, radiation, or both (38%), followed by surgery alone (30%), nonsurgical treatment (11%), and worst for untreated patients (5%). Conclusions There is cause for concern over the accuracy of the clinical staging of the mediastinum among cStage IIIA-cN2 patients in the United States. The use of surgery is relatively low but is associated with an encouraging 5-year survival. Further study is needed to clarify the accuracy of mediastinal staging in the United States for cStage IIIA-cN2 NSCLC.
The Loss of Adaptive Plasticity during Long Periods of Environmental Stasis

Abstract: Adaptive plasticity allows populations to adjust rapidly to environmental change. If this is useful only rarely, plasticity may undergo mutational degradation and be lost from a population. We consider a population of constant size N undergoing loss of plasticity at functional mutation rate m and with selective advantage s associated with loss. Environmental change events occur at rate θ per generation, killing all individuals that lack plasticity. The expected time until loss of plasticity in a fluctuating environment is always at least \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackage[OT2,OT1]{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle...
A Case Report of Eosinophilic Esophagitis Accompanying Hypereosinophilic Syndrome

Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide. To date, HES presenting with esophagus involvement has only been reported once. Here, we present a 39-year-old Hispanic female patient with history of HES presenting with complaints of dysphagia and generalized pruritus.
Fluorescein Angiographic Findings after Intra-arterial Chemotherapy for Retinoblastoma

Purpose To evaluate fluorescein angiography (FA) findings after intra-arterial chemotherapy (IAC) for retinoblastoma. Design Retrospective case series. Participants Twenty-four eyes of 24 patients. Intervention Fifty-five IAC procedures for delivery of melphalan 5 mg and possible carboplatin 30 mg. Main Outcome Measures Vascular flow of iris, retina, and choroid after IAC. Results All patients received melphalan 5 mg, whereas the first 6 patients also were treated with additional carboplatin 30 mg. The IAC was performed as primary treatment in 17 eyes and as secondary treatment (after systemic chemotherapy) in 7 eyes. Two patients also received external-beam radiotherapy before IAC. At presentation, FA revealed neovascularization of the iris (NVI) in 8 eyes, and after IAC, complete NVI regression was noted in 5 eyes (63%). After a mean follow-up of 13 months after IAC, FA depicted the main tumor with decreased fluorescence in 22 eyes (92%). After 55 ophthalmic artery catheterizations, retinal vascular abnormalities by FA were detected in 7 eyes (13%) and choroidal vascular abnormalities were detected in 6 eyes (11%). The retinal abnormalities included ophthalmic artery obstruction (n = 1), transient ophthalmic artery spasm (n = 1), central retinal artery obstruction (n = 1), branch retinal artery obstruction (n = 2), and peripheral retinal ischemia (n = 2). Additional retinal neovascularization was found in 1 patient. The choroidal abnormalities included sector (n = 5) or diffuse (n = 1) choroidal nonperfusion. New-onset iris neovascularization was found in 2 patients. Retinal vascular abnormalities were diagnosed after median of 1 month after the first IAC, whereas choroidal vascular abnormalities were found after median of 5 months after the first IAC. Conclusions Fluorescein angiography suggests that vascular perfusion to the retina and the choroid can be compromised after IAC for retinoblastoma. The most common vascular abnormality was choroidal sector or diffuse nonperfusion. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Non-yrast level structure of35Nd via beta decay of135Pm

The isotope135Nd has been studied through the β-decay of mass-separated135pm. He-jet transported samples without mass-separation were also studied. The parent135Pm has isomers with β-decay half-lives of 40±3 s and 49±3 s. The low-lying non-yrast structure of135Nd is shown to consist of a group of levels which decay to a 65.1-keV isomeric level which is not reached in the yrast cascades.
Introduction to the Special Issue on Operations Research in Health Care

It is widely recognized that health-care systems both in the United States (U.S.) and in most other nations are in crisis. For example, the U.S. has the highest healthcare spending per capita in the world, its annual health expenditures exceed $2 trillion annually, and yet it lags behind several other developed nations in significant healthcare outcomes such as life expectancy or infant mortality. European health-care systems are also facing their own challenges, especially as they relate to the treatment of patients with very expensive conditions. At the same time, health-care systems in developing nations are still in their infancy and plagued by inefficiencies and inequities. Several factors contribute to the health-care systems crisis. Two of them are limited health-care budgets and innovative medical technologies that prolong life but at a very high cost. In this environment, it is natural to expect that the field of operations research (OR) has something to contribute. When resources are limited, OR models can highlight trade-offs, identify good solutions, and inform decision making. This special issue aims to showcase innovative applications of OR in the domain of health care. We received more than 60 excellent submissions that have undergone the normal review process. The papers appearing in this issue passed a dual threshold: they make a significant contribution to the field of OR by examining a health-care application, and each of them was reviewed by at least one health-care expert reviewer to verify the face validity of the health-care application and model assumptions. Three broad problem categories are reflected in the special issue papers: Health Care Policy, Treatment Optimization, and Health Care Operations Management.
Half-cycle pulse acting on a one-dimensional Rydberg atom: Semiclassical transition amplitudes in action and angle variables.

In this paper we derive the expression for the transition coefficient used in the preceding paper [C. D. Schwieters and J. B. Delos, Phys. Rev. A 51, 1023 (1995)] for principal-quantum-number transitions in one-dimensional hydrogen caused by half-cycle pulses. We briefly review the methods of Miller [Adv. Chem. Phys. 25, 69 (1974)] and Marcus [Chem. Phys. Lett. 7, 525 (1970); J. Chem. Phys. 54, 3965 (1971)], and then derive the result using the methods of Maslov and Fedoriuk [[ital Semi]-[ital Classical] [ital Approximation] [ital in] [ital Quantum] [ital Mechanics], (Reidel, Dordrecht, 1981)]. Also, we examine the approximate reduction of hydrogen from three to one dimension and we find a hitherto unknown correction due to the residual motion of one of the ignored degrees of freedom. We discuss the regime of validity of this one-dimensional approximation.
Efficient replication between non-hydrogen-bonded nucleoside shape analogs

DNA polymerase enzymes make an error only once per 10(4)-10(5) initial nucleotide insertions during DNA replication. Most currently held models of this high fidelity cite the hydrogen bonds between complementary pyrimidines and purines as a critical controlling factor. Testing this has been difficult, however, since standard molecular strategies for blocking or removing polar hydrogen-bonding groups cause changes to size and shape as well as hydrogen bonding ability. One answer to this problem is the use of nonpolar molecules that mimic the shape of natural DNA bases. Here we show that a non-hydrogen-bonding shape mimic for adenine is replicated efficiently and selectively against a nonpolar shape mimic for thymine. The results establish that hydrogen bonds in a base pair are not absolutely required for efficient nucleotide insertion. This adds support to the idea that shape complementarity may play as important a role in replication as base-base hydrogen bonds.
Energy-Efficient and Fault-Tolerant Distributed Mobile Execution

Although battery capacities keep increasing, the execution demands of modern mobile devices continue to outstrip their battery lives. As a result, battery life is bound to remain a key constraining factor in the design of mobile applications. To save battery power, mobile applications are often partitioned to offload parts of their execution to a remote server. However, partitioning an application renders it unusable in the face of network outages. In this paper, we present a novel approach that reduces the energy consumption of mobile applications through server offloading without partitioning. The functionality that consumes energy heavily is executed in the cloud, with the program's state check pointed and transferred across the mobile device and the cloud. Our approach is portable, as it introduces the offloading functionality through byte code enhancement, without any changes to the runtime system. The check pointed state's size is minimized through program analysis. In the case of a network outage, the offloading interrupts and the application reverts to executing locally from the latest checkpoint. Our case studies demonstrate how our approach can reduce energy consumption for third-party Android applications. Transformed through our approach, the applications consume between 30% and 60% fewer Joules than their original versions. Our results indicate that portable offloading can improve the battery life of modern mobile applications while maintaining their resilience to network outages.
Normative distribution of complete blood count from early childhood through adolescence: the Bogalusa Heart Study

Background. Noting the distribution of blood values in a biracial southern community according to age, sex, and race variations will help in understanding the normative developmental changes in early life and provides background information. Methods. Complete blood counts were obtained from 3,018 free-living children ages 5-17 years from a well-defined black-white community as part of a cardiovascular risk factor screening. Results. For children ages 5-17 years, hemoglobin levels, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and red blood count increased (P < 0.01) with age. Levels of platelet count and white blood count decreased (P < 0.0005) with age. Compared with females, males between ages 12 and 17 years have (P < 0.05) 0.4 × 1012/liter higher red blood count. 1 g/dl higher hemoglobin, 2% higher hematocrit, 0.2 g/dl higher mean corpuscular hemoglobin concentration, 0.5 × 109/liter lower white blood count. 1.4 fl lower mean corpuscular volume, 0.3 pg lower mean corpuscular hemoglobin, and 14 × 1O9/liter lower platelet count. Compared with blacks, whites have (P < 0.05) 0.5 109/liter higher white blood count, 0.05 1012/liter higher red blood count, 0.7 g/dl higher hemoglobin, 1.7% higher hematocrit, 2.4 fl higher mean corpuscular volume, 1 pg higher mean corpuscular hemoglobin, and 0.5 g/dl higher mean corpuscular hemoglobin concentration. A positive association was noted among blood count variables and hemoglobin with blood pressure similar to that in adults. Conclusion. Blood values differ by age, sex, and race. These differences change at maturation and should be considered when defining normal and "abnormal" blood values.
Renewable fecundity of male Aedes aegypti following replenishment of seminal vesicles and accessory glands

Abstract Secretion accumulated in the accessory glands and sperm in the seminal vesicles in male Aedes aegypti during the first 2 to 3 days after emergence. These two components of semen became depleted when 3-day-old males copulated in rapid succession with a series of 8 females in free flight, and each male was able to inseminate an averge of only 5·8 females. However, as early as 1 day after loss of fecundity, some males were again able to fully inseminate females, and males which were allowed 7 day periods of sexual inactivity between mating series were still fecund by the fourth successive series. Cycles of depletion and replenishment of accessory secretion and vesicle sperm correspond to each of these periods of mating and inactivity. Beyond the first series of matings males were sometimes less sexually responsive and less able to copulate and inseminate. But after the fourth mating series, surviving males that remained responsive and fecund had inseminated an average of 17·6 females per male; the maximum was 21 females by 1 male.
Targeting the motor regulator Klar to lipid droplets

In Drosophila, the transport regulator Klar displays tissue-specific localization: In photoreceptors, it is abundant on the nuclear envelope; in early embryos, it is absent from nuclei, but instead present on lipid droplets. Differential targeting of Klar appears to be due to isoform variation. Droplet targeting, in particular, has been suggested to occur via a variant C-terminal region, the LD domain. Although the LD domain is necessary and sufficient for droplet targeting in cultured cells, lack of specific reagents had made it previously impossible to analyze its role in vivo. Here we describe a new mutant allele of klar with a lesion specifically in the LD domain; this lesion abolishes both droplet localization of Klar and the ability of Klar to regulate droplet motion. It does not disrupt Klar's function for nuclear migration in photoreceptors. Using a GFP-LD fusion, we show that the LD domain is not only necessary but also sufficient for droplet targeting in vivo; it mediates droplet targeting in embryos, in ovaries, and in a number of somatic tissues. Our analysis demonstrates that droplet targeting of Klar occurs via a cis-acting sequence and generates a new tool for monitoring lipid droplets in living tissues of Drosophila.
The effect of tacrine and leupeptin on the secretion of the beta-amyloid precursor protein in HeLa cells.

Abstract The senile plaque in Alzheimer's disease (AD) consists mainly of the amyloid β-peptide (Aβ) derived from a larger beta-amyloid precursor protein (βAPP). The majority of βAPP is processed by either a secretory or lysosomal/endosomal pathway. Soluble derivatives of βAPP (sAPP) and Aβ generated by the proteolytic processing of full-length βAPP are normally secreted into the conditioned medium of cultured cells. Tacrine, a centrally active potent cholinesterase inhibitor that has been shown to improve cognitive functions in some patients with AD, inhibits the secretion of sAPP. Here we have investigated whether leupeptin, a lysosomal protease inhibitor, could influence this effect of tacrine. We analyzed levels of βAPP derivatives in cultured HeLa cells by immunoblotting cell lysates and conditioned media using the monoclonal antibody 22C11. Levels of sAPP normally present in conditioned media were severely reduced by treating cells with tacrine. The treatment of cells with tacrine resulted in a small decrease in the intracellular levels of βAPP. The effect of treating the cells with tacrine did not depend upon the growing state of the cells as a similar effect was observed when the drug was added either during initial plating of the cells or after the attachment of the cells. The effect of tacrine was not affected by preincubating the cells with low serum in the culture medium. The treatment of cells with tacrine plus leupeptin reduced the secretion of sAPP in the medium to the same degree as did the treatment with tacrine alone, suggesting that the tacrine-mediated inhibition of sAPP release may not involve leupeptin-sensitive proteolytic pathways. The results suggest that the inhibitory effect of tacrine on sAPP secretion is not due to the proteolytic cleavage of the holoprotein in the medium.
Recent Trends in Soviet Research on the Developing Countries

URING I954-I955 the Kremlin initiated a radical change in its DJ policies toward the newly independent countries. The rigid emphasis on the "inevitability" of Communist takeovers gave way to the acceptance of non-Communist regimes as potential political allies. A comparable shift in Soviet Asian studies from a narrowly conceived ideological basis to a more pragmatic and tolerant approach took almost ten years to evolve. While the Soviet state busily courted the middle-class nationalist governments with diplomatic moves and economic aid, the academic community neglected the serious study of non-Communist forces. Not surprisingly, Anastas Mikoyan charged at the Twentieth Congress of the CPSU in i956 that the learned institutions concerned with research on the East "slumbered" while the contemporary world passed them by.
Testing the neutral theory of molecular evolution with genomic data from Drosophila

Although positive selection has been detected in many genes, its overall contribution to protein evolution is debatable. If the bulk of molecular evolution is neutral, then the ratio of amino-acid (A) to synonymous (S) polymorphism should, on average, equal that of divergence. A comparison of the A/S ratio of polymorphism in Drosophila melanogaster with that of divergence from Drosophila simulans shows that the A/S ratio of divergence is twice as high---a difference that is often attributed to positive selection. But an increase in selective constraint owing to an increase in effective population size could also explain this observation, and, if so, all genes should be affected similarly. Here we show that the difference between polymorphism and divergence is limited to only a fraction of the genes, which are also evolving more rapidly, and this implies that positive selection is responsible. A higher A/S ratio of divergence than of polymorphism is also observed in other species, which suggests a rate of adaptive evolution that is far higher than permitted by the neutral theory of molecular evolution.
Sobre cáscaras y blobs: Superficies estructurales de la era digital

Resumen es: Las nuevas tecnicas de representacion en arquitectura han ampliado las posibilidades de exploracion formal hacia lo que algunos interpretan como un mayor...
The Appointments Dilemma

In a separation of powers political system, effective bureaucratic control may be undermined by the fact that the power to appoint bureaucrats is controlled by a different set of principals from those that may control them through statutory or budgetary means. In particular, executives have proposal power over bureaucratic appointments and removals while legislators have proposal power over laws. In this article, I explore the consequences of this division of authority for bureaucratic outcomes. I argue that this pattern of authority often produces outcomes inferior to those generated when appointment, removal, and legislative powers are centralized as is the case in many parliamentary systems. The model reveals that restricting executive removal power can mitigate these problems. Finally, I discuss the relevance of thisappointments dilemmafor bargaining over bureaucratic structures with a focus on removal powers, independent commissions, and civil service rules.
Studies in fetal wound healing. VII, Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid

Fetal wound healing occurs rapidly and without inflammation, fibrosis, or scar formation. It is a process fundamentally different from adult wound healing. The mechanisms that underlie such unique healing properties are unknown. However, hyaluronic acid, a glycosaminoglycan component of the extracellular matrix, is prominent throughout the course of fetal wound healing, and is thought to play a major role in the healing process. Amniotic fluid contains high levels of hyaluronic acid. Amniotic fluid also contains a number of potent growth factors that are critical for fetal development. In this report, a new factor in amniotic fluid that stimulates deposition of hyaluronic acid is described. This activity is measured in an in vitro assay system in which cultured fibrosarcoma cells are used as indicator cells. Amniotic fluid thus provides two separate mechanisms for the deposition of hyaluronic acid. One is by exogenous application directly onto fetal skin wounds; the second is by providing a factor to increase the production of hyaluronic acid endogenously, by stimulating cells around the wound site. The resulting hyaluronic acid-rich area may support the ability of the fetal wound to heal with its unique properties.
Transient Fueling Controller Identification for Spark Ignition Engines

Presented in this paper is a feedforward fueling controller identification methodology for the transient fueling control of spark ignition (SI) engines. The hypothesis of this work is that the feedforward fueling control of SI engines can be separated into steady state and transient phenomena and that the majority of the nonlinear behavior associated with engine fueling can be captured with nonlinear steady state models. The proposed transient controller identification process is built from standard nonparametric identification techniques followed by parametric model recovery. Crank angle serves as the independent variable for these models. Two separate system identification problems are solved to identify the air path dynamics and the fueling path dynamics. The transient feedforward controller is then calculated as the ratio of the air path-over-the fueling path dynamics thereby coordinating the engine fueling with the air path dynamics. It will be shown that a linear transient feedforward-fueling controller operating in tandem with a nonlinear steady state fueling controller can achieve air-fuel ratio regulation comparable to the production fueling controller without the extensive controller calibration process. The engine used in this investigation is a 1999 Ford 4.6L V-8 fuel injected engine.
Deep-Sea Drilling for Landlubber Geologists — The Southwest Pacific, an Accordion Plate Tectonics Analog for the Cordilleran Geosyncline

The Deep Sea Drilling Project offers the geologist who is not trained in marine geology an unparalleled opportunity to study deep-sea sediments and volcanic rocks in their environment of formation and an opportunity to evaluate concepts of plate tectonics theory. Results of deep-sea drilling in the southwest Pacific are useful in interpreting the early history of the Cordilleran geosyncline as a product of continental fragmentation and the growth of volcanic arc-marginal ocean basin systems.
Modelling the feasibility of intramolecular dehydrodiferulate formation in grass walls

Molecular modelling is a useful tool for predicting and visualising molecular interactions, eg providing a means of predicting the feasibility of covalent bond formation between macromolecules. Molecular modelling was used to evaluate the feasibility of intramolecular diferulate formation. Two ferulates were positioned at various locations along the backbone of an arabinoxylan (16 xylose residues) and the optimised structure generated using MM2 parameters. For ferulates separated by several xylose residues, diferulates could only form if the xylan backbone relaxed allowing chain folding to bring the two ferulates within spatial proximity for bonding. In positions that would allow overlap of ferulates, one or both of the ferulates would have to rotate along the xylan backbone for radical coupling. In both cases high-energy barriers prevented the complete rotation to allow bond formation. It therefore seems unlikely that intramolecular dehydrodiferulates form readily within grass cell walls. When two xylose residues separate two arabinose moieties containing ferulate units it is feasible for rotation to a position allowing the formation of the 5-5 linked diferulate with no relaxation of the backbone. This is the only diferulate that can form without bond strain when the ferulates are positioned three xylose residues apart on the same xylan backbone. This suggests restricted positioning of ferulates for 5-5 coupling.
Deformation potentials of bulk semiconductors

Abstract A theory of deformation potential electron-phonon scattering coefficients is presented for elemental and compound semiconductors. Expressions for the acoustical deformation potential constants at symmetry points are obtained in closed form for direct-gap bulk semiconductors. The deformation potential vs k is predicted for GaAs.
Plant tissue-based amperometric electrode for eliminating ascorbic acid interferences

Abstract An application of tissue-based electrodes aimed at eliminating interferences from co-existing electroactive constituents is described. The concept is illustrated using a zucchini-containing carbon paste electrode. The presence of the enzyme ascorbic acid oxidase (AAO) in the zucchini tissue effectively eliminates contributions from ascorbic acid, thus allowing selective measurement of dopamine or norepinephrine. In comparison with analogous enzyme-based AAO electrodes, the tissue “eliminator” electrode offers high biocatalytic stability and activity and extremely low cost. The effects of various experimental variables are studied using pulse voltammetry, chronoamperometry and flow-injection amperometry. The electrode has a useful lifetime of 4 weeks. Simultaneous elimination of uric acid interferences is obtained via the co-immobilization of uricase. Oxygen background currents are eliminated in the presence of ascorbic acid.
Homoclinic and Heteroclinic Bifurcations in an Overlapping Generations Model with Credit Market Imperfection

We analyze a nonlinear OLG model with credit market imperfection and endogenous labor supply. When the investors' protection is perfect, the model reduces to the standard one sector growth model proposed by Reichlin (JET 40:89---102, 1986), while the model reduces to the one studied by Matsuyama (Econometrica 72:853---884, 2004) when the agents' labor supply is exogenous. Our goal is to highlight that the local analysis of the perfect foresight equilibrium may lead to misleading conclusions because the local analysis neglects the occurrence of different global bifurcation scenarios. In particular, the existence of a heteroclinic connection or the occurrence of a homoclinic bifurcation may be associated with global indeterminacy even when all steady states are locally determinate.
Mapping Genetically Compensatory Pathways from Synthetic Lethal Interactions in Yeast

Background Synthetic lethal genetic interaction analysis has been successfully applied to predicting the functions of genes and their pathway identities. In the context of synthetic lethal interaction data alone, the global similarity of synthetic lethal interaction patterns between two genes is used to predict gene function. With physical interaction data, such as protein-protein interactions, the enrichment of physical interactions within subsets of genes and the enrichment of synthetic lethal interactions between those subsets of genes are used as an indication of compensatory pathways. Result In this paper, we propose a method of mapping genetically compensatory pathways from synthetic lethal interactions. Our method is designed to discover pairs of gene-sets in which synthetic lethal interactions are depleted among the genes in an individual set and where such gene-set pairs are connected by many synthetic lethal interactions. By its nature, our method could select compensatory pathway pairs that buffer the deleterious effect of the failure of either one, without the need of physical interaction data. By focusing on compensatory pathway pairs where genes in each individual pathway have a highly homogenous cellular function, we show that many cellular functions have genetically compensatory properties. Conclusion We conclude that synthetic lethal interaction data are a powerful source to map genetically compensatory pathways, especially in systems lacking physical interaction information, and that the cellular function network contains abundant compensatory properties.
In vivo gene transfer moves one step closer to success

Achieving sustained expression of clotting factors and achieving this expression at levels high enough to result in clinical improvement have been the two critical goals of efforts to treat hemophilia by gene transfer. In this issue Nathwani and colleagues (page [1662][1]) demonstrate that they have
Prostate cancer incidence in males with Lynch syndrome

An increased risk of prostate cancer is currently not considered a part of the Lynch syndrome spectrum. The purpose of this study was to retrospectively examine prostate cancer incidence in the Lynch syndrome cohort at the Ohio State University in comparison with that in the general population. We included all males diagnosed with Lynch syndrome from June 1998 to June 2012 at the Ohio State University and obtained baseline information including cancer history. If patients had not been seen in the 12 months before June 2012, they were contacted to document changes in their cancer history. We compared prostate cancer incidence among the Lynch syndrome families with that of the general population by using the Surveillance, Epidemiology, and End Results registry 1999–2009. Of the 188 males identified with Lynch syndrome, 11 males were diagnosed with prostate cancer during the study period. The ratio of observed to expected numbers of prostate cancer cases resulted in a standardized rate ratio of 4.87 (95% confidence interval: 2.43–8.71). Impaired mismatch repair expression and microsatellite instability were seen in one out of two prostate cancer specimens available for testing. Males with Lynch syndrome had a nearly fivefold increased risk of developing prostate cancer but did not appear to have earlier onset or a more aggressive phenotype. Genet Med 16 7, 553–557.
Dissipation in few-photon waveguide transport [Invited]

We develop a formulation of few-photon Fock-space waveguide transport that includes dissipation in the form of reservoir coupling. We develop the formalism for the case of a two-level atom and then show that our formalism leads to a simple rule that allows one to obtain the dissipative description of a system from the nondissipative case.
A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain.

Objective. Assess efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, on the reduction of pain severity, in patients with diabetic peripheral neuropathic pain (DPNP). Methods. This was a multicenter, parallel, double-blind, randomized, placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Patients (N = 116 per group) were randomly assigned to receive duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo, for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale. Secondary outcome measures and safety were evaluated. Results. Compared with placebo-treated patients, both duloxetine-treated groups improved significantly more (P < 0.001) on the 24-hour average pain score. Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure. A significant treatment effect for duloxetine was observed in most secondary measures for pain. Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- (12.1%) versus the placebo- (2.6%) treated group. Duloxetine showed no adverse effects on diabetic control, and both doses were safely administered and well tolerated. Conclusions. In this clinical trial, duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP.
Intratubular Hydrostatic Pressure in Testis and Epididymis Before and After Long-Term Vasectomy in the Guinea Pig

In vivo measurements of intratubular hydrostatic pressure were taken in the testis caput epididymis and cauda epididymis of the guinea pig before and after vasectomy. A range of from 2 to 11 cm water pressure in these locations was observed in normal animals. A significantly greater (p less than .005) mean pressure was found in the caput epididymis than in the seminiferous tubules and the proximal cauda and in the distal cauda (p less than .0005) than in the proximal cauda. Present results and similar previous results warranted examination of the transport of sperm and fluid through the male reproductive system. The presence of a significantly greater (p less than .0001) hydrostatic pressure in the distal cauda epididymis 4 months and 1 year postvasectomy than normal is a reflection of the accumulation of sperm and fluid. However the pressures in the caput epididymis and proximal caudal tubules were insignificantly elevated. It is concluded that changes in spermatogenesis observed after long-term vasectomy in the guinea pig are unrelated to the direct transmission of the increased caudal pressure to the testis. (AUTHORS MODIFIED)
Calculation of the entropy of a fluid by a montecarlo simulation based on free volume

Abstract A method is proposed for calculating the free energy of a fluid by a Monte-Carlo (MC) simulation based on a modified free-volume theory. With this method, it is possible to calculate the excess entropy over that of the ideal gas, and the internal energy, separately with one simulation at a given density and temperature, without a reference system other than the ideal gas. A radial free-space distribution function (RFSDF), ζ( r ), is defined as the average of the Boltzmann probabilities of random displacements r of the molecules; this is a characteristic function for describing the nearest-neighbor molecular structure or the space in which a molecule can move. The function is obtained, effectively, as the ratio [(number of acceptances of displacement r )/(number of trials of displacement r ), in a Metropolis MC simulation. The free volume is then computed by integrating ζ( r ) with respect to the radial volume element 4π r 2 d r . While the partition function of the system is obtainable from the free volume, the excess entropy is calculated here directly from the ratio of the free volume of the fluid to that of an ideal gas. The internal energy is obtained in the same runs by the usual Metropolis MC procedure. The excess entropy and/or the excess free energy agree very well with the values obtained from the equations of state for both the hardsphere system and the Lennard-Jones fluid.
The heat transfer resistance of various heat exchanger tubing alloys in natural and synthetic seawaters

The heat transfer resistance due to fouling of various alloys as a result of exposure to natural and synthetic seawater environments was determined. It was found that the copper-base alloys had a lower fouling heat transfer resistance than noncopper-base alloys. In natural seawater, this lower heat transfer resistance due to fouling was attributed to the toxic nature of the copper alloys inhibiting biofouling which occurred on the noncopper-base alloy. In synthetic seawater, free of biological organisms, the copper alloys had lower fouling heat transfer resistance, due apparently to the higher thermal conductivity of the scale formed on the copper alloys relative to that on the noncopper alloys. Magnitudes of these effects are described.
Alterations of the corneo-fundal potential of the eye during sleep.

Abstract The pattern of alteration of the corneo-fundal potential (CFP) of the human eye during the night of sleep was found to be similar in 15 subjects. During the first 30 min of entry into darkness and the onset of sleep CFP alterations were of large magnitude. A 28% decrease was followed by a 49% increase above the CFP level in standard illumination. These changes are probably a reflection of the process of dark adaptation of the retina. They are not influenced by the level of alertness. Throughout the remainder of the night of sleep the CFP changes are reliable and predictable. After the first hour the level of CFP is only slightly above that in bright illumination prior to sleep onset. Between 1.5 and 6 h the CFP increases in a linear manner. Once the level after 90 min is determined, the actual level after 6 h may be accurately predicted utilizing a linear model. Thus, for practical purposes the sensitivity of the amplifier of a DC recording system may be fixed after the initial pre-sleep calibration in standard room lighting and the level of elevation noted after 90 min.
Effects of sex hormones on mesangial cells.

. Male gender is associated with a more rapid progression of chronic renal disease. In various experimental models of renal injury, manipulation of the hormonal milieu can replicate the effects of gender on the course of renal disease. These observations suggest that sex hormones per se may be important determinants of the greater susceptibility of the male kidney to progressive renal injury. Sex hormones may influence many of the processes implicated in the pathogenesis of renal disease progression, including cell proliferation and the synthesis and degradation of collagen and proteoglycans. In addition, sex hormones may indirectly influence these processes by modulating the synthesis and release of vasoactive agents, cytokines, and other growth factors, which in turn are capable of altering mesangial cell function. Finally, estrogens also exert potent antioxidant effects that may contribute to the protective effect of female gender on the course of renal disease.
Nuclear translocation of p65 NF-κB is sufficient for VCAM-1, but not ICAM-1, expression in TNF-stimulated smooth muscle cells: Differential requirement for PARP-1 expression and interaction

Although nuclear translocation of NF-κB and subsequent binding to promoters of ICAM-1 and VCAM-1 have been shown to be decisive for their expression, a number of discrepancies in the expression patterns of these adhesion molecules have been reported in both cell culture systems and disease settings, including atherosclerosis, asthma, and autoimmune diseases. Here we show that while p65 NF-κB nuclear translocation in TNF-treated smooth muscle cells (SMCs) was sufficient for the expression of VCAM-1, expression of ICAM-1 showed a critical requirement for PARP-1. I-κBα phosphorylation and subsequent degradation were virtually identical in both TNF-treated wild-type and PARP-1−/− SMCs. VCAM-1 expression in TNF-treated PARP-1−/− SMCs was completely inhibited by the NF-κB inhibitor, pyrrolidine dithiocarbamate, confirming that VCAM-1 expression was indeed NF-κB-dependent. The expression of both VCAM-1 and ICAM-1 was associated with a transient interaction between PARP-1 and p65 NF-κB when examined in the fibroblastic cell line, COS-7, and in the airway epithelial cell line, A549. Such interactions were confirmed using florescence resonance energy transfer analysis. Protein acetylation activity, mediated by p300/CBP, was required for both VCAM-1 and ICAM-1 expression in TNF-treated SMCs; however, the interaction of PARP-1 with p300/CBP was dispensable for VCAM-1 expression. These findings indicate that p65 NF-κB nuclear translocation may be sufficient for certain genes (e.g., VCAM-1) while insufficient for others (e.g., ICAM-1), thus providing a novel insight into the role of NF-κB in driving target gene expression. Furthermore, the data suggest a differential requirement for PARP-1 expression in inflammatory processes.
Deaminating enzyme labels for potentiometric enzyme immunoassay

Abstract Adenosine deaminase, asparaginase, and urease are examined as possible enzyme labels for immunoassays using potentiometric detection with the ammonia gas-sensing membrane electrode. Considerations of binding ability, retained activity, and stability reveal asparaginase to be the most effective enzyme label for immunoassay purposes. The utility of the potentiometric approach with this enzyme label is demonstrated via model hapten assays for dinitrophenyl groups and for cortisol.
Structural refinements of praseodymium and neodymium orthophosphate

The crystal structures of PrPO4 and NdPO4 have been determined by single crystal X-ray diffraction techniques. The structures are isostructural with CePO4 and LaPO4, and are monoclinic in space group P21n. The cell constants are a = 6.741(3), b = 6.961(4), c = 6.416(3) A, and β = 103.63(3)° for PrPO4 and a = 6.722(1), b = 6.933(1), c = 6.390(2) A, and β = 103.72(2)° for NdPO4. The least-squares structural refinements of PrPO4 and NdPO4 yielded R values of 0.034 and 0.038 based on 810 and 947 unique reflections, respectively. The lanthanide metal atoms are coordinated with nine oxygens and are linked together by very slightly distorted tetrahedral phosphate groups. The nine oxygen atoms ligating the lanthanide atoms form a polyhedron that is best described as a pentagonal interpenetrating tetrahedron.
The yeast SRM1 protein and human RCC1 protein share analogous functions.

Abstract The Saccharomyces cerevisiae protein SRM1 and the mammalian protein RCC1 have amino acid sequence similarity throughout their lengths. SRM1 was defined by a recessive mutation in yeast that both activates the signal transduction pathway required for mating and leads to arrest in the G1 phase of the cell cycle. RCC1 was defined by a recessive mutation in hamster cells that causes premature chromosome condensation and other characteristics of entry into mitosis. Despite the seemingly different roles implied by these phenotypes, we suggest that RCC1 and SRM1 proteins have similar functions. In particular, we find that RCC1 can complement the temperature-sensitive growth phenotype of two independent srm1 mutations and also complements, at least partially, phenotypes associated with activation of the pheromone response pathway, such as transcription induction of FUS1. However, RCC1 fails to complement an srm1 null allele. Further characterization of the srm1 mutant phenotype reveals a defect in plasmid and chromosome stability, suggesting that the mutants have a defect in DNA replication, mitosis, or their coordination. Finally, like RCC1, SRM1 is a nuclear protein. Together, these data imply that SRM1 and RCC1 have a common role in their respective organisms.
Outcome of preterm infants with congenital heart disease.

Objectives and study design: To evaluate the morbidity and mortality of preterm infants with congenital heart disease (CHD), a chart review was performed for infants with CHD, excluding isolated patent ductus arteriosus, who were <37 weeks’ gestation, weighed <2500 g, and were admitted to our neonatal intensive care unit from 1976 to 1999 (N = 201). Results: Patients in the study represented 1.9% of the total neonatal intensive care unit population <37 weeks’ gestation and <2500 g. The median gestational age was 33 weeks, and the mean birth weight was 1852 g. CHD diagnosis frequencies were similar to those reported in other large incidence studies, except for a higher percentage of conotruncal defects. The risk of necrotizing enterocolitis was 1.7 times higher and the overall mortality twice as high in our patients compared with patients in the neonatal intensive care unit who did not have CHD. Cardiac surgery (n = 133) was performed on 108 patients. During the recent period of 1985 to 1999, compared with our institution’s overall results for CHD surgery, the operative mortality rate was 10.4% versus 5.4% for closed procedures and 25.4% versus 10.5% for open procedures. The actuarial survival rate is 51% at 10 years; survival improved as the study period progressed. Conclusions: Infants with both CHD and prematurity did significantly worse than either group alone. Such outcome data are required for proper allocation of resources to care for this high-risk pediatric population. (J Pediatr 2000;137:653-9)
2′,5′-Dideoxyadenosine 3′-Polyphosphates Are Potent Inhibitors of Adenylyl Cyclases

2',5'-Dideoxyadenosine 3'-di- and triphosphates were tested as inhibitors of brain adenylyl cyclases. With an IC50 approximately 40 nM, 2',5'-dideoxy-3'-ATP is the most potent nonprotein synthetic regulator of adenylyl cyclases thus far described. Neither 2',5'-dideoxy-3'-ADP nor 2',5'-dideoxy-3'-ATP inhibited activity by competition with substrate, and the linear noncompetitive inhibition observed was consistent with interaction via a distinct domain. The availability of this ligand will permit the development of a variety of probes that will be extremely useful in investigating adenylyl cyclase structure and the role(s) that this class of compound may play in physiologically regulating cell function.
Transcription promotes guanine to thymine mutations in the non-transcribed strand of an Escherichia coli gene

Transcription of DNA opens the chromatin, causes topological changes in DNA and transiently exposes the two strands to different biochemical environments. Consequently, it has long been argued that transcription may promote damage to DNA and there are data in Escherichia coli and yeast supporting a correlation between high transcription and mutations. We examined the transcription-dependence of the reversion of a nonsense codon (TGA) in E. coli and found that there was a strong dependence of mutations on transcription in strains defective in the repair of 8-oxoguanine in DNA. Under conditions of high transcription there was a three to five-fold increase in mutations that changed TGA in the non-transcribed strand to a sense codon. Furthermore, in both mutY and mutM mutY backgrounds the mutations were overwhelmingly G:C to T:A. In contrast, when the TGA was in the transcribed strand in relation with the inducible promoter, high transcription decreased the rate of reversion. Similar results were obtained in a strain defective in the transcription-repair coupling factor, Mfd, suggesting that transcription dependent increase in base substitutions does not require transcription-dependent DNA repair. However, Mfd does modulate the magnitude of the mutagenic effect of transcription. These data are consistent with a model in which the non-transcribed strand is more susceptible to oxidative damage during transcription than the transcribed strand. These results suggest that the magnitudes of individual base substitutions and their relative numbers in other studies of mutational spectra may also be affected by transcription.