cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessment of Availability, Clinical Testing, and US Food and Drug Administration Review of Biosimilar Biologic Products

Importance Biosimilar biologic products were authorized in 2010, after the US Congress established an expedited pathway for approval of clinically similar versions of approved biologic products. Unlike for most small-molecule generic drugs, approval requirements for a biosimilar included animal studies and a comparative efficacy clinical trial. Objective To analyze the evidence required to support a biosimilarity license application, examine the US Food and Drug Administration (FDA) evaluation process, and estimate the costs of the key clinical trial evidence. Design This study evaluated all biosimilar biologic products approved from January 2010 through October 2019, using the publicly available FDA review documents, disclosures from ClinicalTrials.gov, and the published peer-reviewed literature. The costs of efficacy clinical trials were estimated using licensed proprietary software. Main Outcomes and Measures The following elements of each approved biosimilar were evaluated: the extent of human clinical testing to establish that the biosimilar had no clinically meaningful differences with the reference product, results of comparative animal studies, and FDA-cited application deficiencies. The cited deficiencies included the following categories: (1) facility inspection, (2) manufacturing or product quality, (3) animal studies, (4) laboratory analytical studies, (5) phase 1 and/or immunogenicity studies, and (6) phase 3 comparative efficacy trials. Results As of October 2019, the FDA had approved 23 biosimilar biologics for 9 reference products. The 29 clinical trials that established that the efficacy of the biosimilar products was comparable to that of the reference products enrolled a median (interquartile range [IQR]) of 504 (258-612) patients, had a median (IQR) estimated cost of $20.8 ($13.8-$35.3) million, and had a median (IQR) treatment duration of 52 (28-68) weeks. Substantial deficiencies temporarily halted the review of 9 applications, and the most frequent deficits were failed facilities inspections (n = 5) and manufacturing process quality problems (n = 6). The approved biosimilar submissions included 51 animal studies on species that included mice, rats, rabbits, dogs, and cynomolgus monkeys. Negative outcomes in 2 animal studies were attributed to differences between human and test species. The FDA generally met the standard 12-month review deadlines or stopped the review clock when serious deficiencies were identified. Conclusions and Relevance This study found that most comparative efficacy trials supporting the FDA approval of biosimilars appeared to be as rigorous as and often larger, longer, and more costly than pivotal trials for new molecular entities. Further research is needed into whether less costly comparative efficacy trials could provide adequate evidence of biosimilarity and whether animal studies contribute useful scientific evidence.
Magnetically Linked Star-Disk Systems. I. Force-free Magnetospheres and Effects of Disk Resistivity

We consider the interaction between a magnetic star and its circumstellar disk under the assumption that the stellar magnetic field permeates the disk and that the system's magnetosphere is force-free. Using simplified axisymmetric models (both semianalytic and numerical), we study the time evolution of the magnetic field configuration induced by the relative rotation between the disk and the star. We show that if both the star and the magnetosphere are perfectly conducting, then there is a maximum disk surface conductivity Σmax for which a steady state field configuration can be established. For larger values of conductivity, no steady state is possible, and the field lines inflate and effectively open up when a critical twist angle (which for an initially dipolar field is on the order of a few radian) is attained. We argue that for thin astrophysical disks, surface conductivities are likely to exceed the local Σmax except in the immediate vicinity of the corotation radius in a Keplerian disk. If the disk conductivity is high enough, then the radial magnetic field at the disk surface will become large and induce radial migration of the field lines across the disk. We find, however, that the radial diffusion in the disk is generally much slower than the field-line expansion in the magnetosphere, which suggests that the opening of the magnetosphere is achieved before the diffusive outward expulsion of the field lines from the disk can occur. The effects of magnetospheric inertial effects and of field-line reconnection are considered in the companion paper.
The Projection Problem for Predicates of Taste

Utterances of simple sentences containing taste predicates (e.g. "delicious", "fun", "frightening") typically imply that the speaker has had a particular sort of first-hand experience with the object of predication. For example, an utterance of "The carrot cake is delicious" would typically imply that the speaker had actually tasted the cake in question, and is not, for example, merely basing her judgment on the testimony of others. According to one approach, this 'acquaintance inference' is essentially an implicature, one generated by the Maxim of Quality together with a certain principle concerning the epistemology of taste (Ninan 2014). We first discuss some problems for this approach, problems that arise in connection with disjunction and generalized quantifiers. Then, after stating a conjecture concerning which operators 'obviate' the acquaintance inference and which do not, we build on Anand and Korotkova 2018 and Willer and Kennedy Forthcoming by developing a theory that treats the acquaintance requirement as a presupposition, albeit one that can be obviated by certain operators.
Carpal Tunnel Syndrome

Carpal tunnel syndrome affects millions of people each year. The most common cause is idiopathic although it is associated with trauma and several medical comorbidities. Treatment depends on many patient factors and often results in surgical management.
Modalities and Bribe Offers: Making Sense of Post-Soviet Corruption

Why villagers in Azerbaijan prefer to invest in building mosques and cemeteries rather than schools and kindergartens? Why the Azerbaijani government's sudden decision to outlaw food or other treat in funeral ceremonies is important? Why insurance is not perceived as a sphere of business by the Azerbaijani population? This article is able to pose and asnwers the questions through a novel methodology of political culture analysis - the concept of modalities. Focusing on the analysis of attitudes toward and practice of bribe offers by the population in the post-Soviet states, we argue that corruption is associated with imbalance within pairs of psychological modalities of Symbol and Content, Local and Global, Passive and Active. Government's selective focus on bureaucratic graft neglects formidable argument that the problem of corruption is tightly woven into political culture of a post-Soviet society. Simple administrative measures cannot overcome fundamental value orientations within a society.
A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers.

Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.
Signal processing quantification of changes in the blood volume pulse (BVP) waveform due to exercise

Observations made in the past by our group confirmed that the blood volume pulse (BVP) waveform recorded using an infrared finger photoplethysmograph (PPG) undergoes changes as the subject performs physical exercise. In particular, the Dicrotic Notch of the BVP waveform has been observed to become less prominent in connection with the performance of exercise. There is an interest in characterizing those changes through a single parameter to measure the level of exercise the subject has reached, at any time during an exercise session. This paper reports on the comparison of three Digital Signal Processing approaches designed to reflect the BVP waveform changes through a single parameter, which could be obtained automatically from the digitized BVP signal. For this study BVP measurements were taken from 10 subjects, as they engaged in upper-body exercises and rested afterwards.
United States, Business Ethics in the

This article provides an overview of the development of business ethics in the United States, including the cultural context, how regulation has pushed its development, and its current status as an academic field. This article also provides an overview of three major business ethics cases in the United States: Johnson and Johnson and the Tylenol Crisis, Enron, and Nike and Sweatshop Labor. Keywords: business ethics; corporate social responsibility; ethics education; codes of ethics; regulation; compliance programs
An efficient threshold public key cryptosystem secure against adaptive chosen ciphertext attack

This paper proposes a simple threshold Public-Key Cryptosystem (PKC) which is secure against adaptive chosen ciphertext attack, under the Decisional Diffie-Hellman (DDH) intractability assumption. Previously, it was shown how to design non-interactive threshold PKC secure under chosen ciphertext attack, in the random-oracle model and under the DDH intractability assumption [25]. The random-oracle was used both in the proof of security and to eliminate interaction. General completeness results for multi-party computations [6,13] enable in principle converting any single server PKC secure against CCA (e.g., [19,17]) into a threshold one, but the conversions are inefficient and require much interaction among the servers for each ciphertext decrypted. The recent work by Cramer and Shoup [17] on single server PKC secure against adaptive CCA is the starting point for the new proposal.
Concurrent constraint-based memory machines: a framework for java memory models (summary)

A central problem in extending the von Neumann architecture to petaflop computers with a shared memory and millions of hardware threads is defining the memory model [1, 2, 3]. Such a model must specify the behavior of concurrent (conditional) reads and writes to the same memory locations. We present a simple, general framework for the specification of memory models based on an abstract machine that uses sets of order and value constraints to communicate between threads and main memory. Memory is permitted to specify exactly those linkings (mappings from read events to write events) which result in a unique solution for the constraints, and hence forces a unique patterns of bits to flow from writes to reads. We show that this single principle accounts for almost all the “causality test cases” proposed for the java memory model. It may be used as the basis for developing a formal memory model for the java programming language. An implementation of CCMs in a Prolog-based constraint language has been developed by Tom Schrijvers and Bart Demoen [4]. This paper is a summary of [5].
BACTERIAL METABOLISM OF 2-METHYLALANINE

Aaslestad, H. G. (Louisiana State University, Baton Rouge), and A. D. Larson. Bacterial metabolism of 2-methylalanine. J. Bacteriol. 88: 1296–1303. 1964.—A bacterium isolated from soil was found to oxidize 2-methylalanine to 65% of the theoretical value by an adaptive enzyme system. Manometric experiments with whole cells indicated that acetone but not isopropylamine was an intermediate. Cellular extracts produced carbon dioxide from 2-methylalanine when pyruvate was added to the reaction mixture. Dialysis stimulated the 2-methylalanine metabolizing system, providing pyridoxal phosphate and pyruvate were supplied. A study of the stoichiometry of this pyridoxal phosphate-dependent reaction indicated that acetone and carbon dioxide were principal products. The formation of carbon dioxide from 2-methylalanine seemed dependent upon transfer of the amino group to pyridoxal phosphate. Other 2-methyl amino acids were found to be decarboxylated by this system, thus indicating a lack of absolute specificity.
The Common Law of the Labor Agreement: Vacations

In this article, Professor Abrams and Nolan continue their review of the common topics addressed by labor arbitrators. Vacations are a particularly challenging matter involving work qualification requirements and calculations of benefits issues. Abrams and Nolan suggest ways labor and management can design their vacation systems to avoid later problems in arbitration.
Lost in Translation: Law, Economics, and Subjective Standards of Care in Negligence Law

The Law & Economics movement has occasionally been a victim of its own success. Over the past four decades, it has generated an enormous specialist literature, often explicitly intended for other specialists. As is so often the case with increased specialization, the result has been escalating technical complexity accompanied by forbiddingly formal mathematics and a tendency to retreat into abstraction. As a result, Law & Economics has often failed to provide general legal audiences with insight into important legal questions, even where the tools of economics would be appropriate and useful. This Article examines – and rectifies – just such a failure. In particular, this Article examines departures from a uniform reasonable person standard in negligence law. From an economic standpoint, individuals might be held to different standards of care because: 1) they differ in their cost of taking precautions (e.g., a good driver can take additional precautions more cheaply than a bad driver); or 2) they differ in the accident costs they generate when exercising a given amount of care (e.g., a good driver causes fewer accidents than a bad driver that is exercising the same precautions). Though the two possibilities lead to sharply different prescriptions, the abstract nature of the Law & Economics literature has led scholars to focus almost entirely on the former scenario, while neglecting the latter. By examining both possibilities, I provide a new and superior explanation of how tort law treats disabilities and professional skill. In doing so, I also demonstrate the extent to which important legal insights can remain unappreciated when buried in an overly abstract mathematical literature.
Prior Inoculation with Type B Strains of Francisella tularensis Provides Partial Protection against Virulent Type A Strains in Cottontail Rabbits.

Francisella tularensis is a highly virulent bacterium that is capable of causing severe disease (tularemia) in a wide range of species. This organism is characterized into two distinct subspecies: tularensis (type A) and holarctica (type B) which vary in several crucial ways, with some type A strains having been found to be considerably more virulent in humans and laboratory animals. Cottontail rabbits have been widely implicated as a reservoir species for this subspecies; however, experimental inoculation in our laboratory revealed type A organisms to be highly virulent, resulting in 100% mortality following challenge with 50–100 organisms. Inoculation of cottontail rabbits with the same number of organisms from type B strains of bacteria was found to be rarely lethal and to result in a robust humoral immune response. The objective of this study was to characterize the protection afforded by a prior challenge with type B strains against a later inoculation with a type A strain in North American cottontail rabbits (Sylvilagus spp). Previous infection with a type B strain of organism was found to lengthen survival time and in some cases prevent death following inoculation with a type A2 strain of F. tularensis. In contrast, inoculation of a type A1b strain was uniformly lethal in cottontail rabbits irrespective of a prior type B inoculation. These findings provide important insight about the role cottontail rabbits may play in environmental maintenance and transmission of this organism.
Focus of Attention and Employee Reactions to Job Change1

Two hundred and five telecommunications field-service technicians underwent a job change and responded to our questionnaire. The amount of time since experiencing the job change was measured for each technician. We found support for the hypothesis that the more an employee focuses on his or her job, the stronger that employee will react to a job change. Technicians who focused highly on their jobs reported fewer excused absences and were more job involved as time passed after the change, compared to technicians who focused little on their jobs. Moreover, high off-job focused technicians became less committed, less job involved, less satisfied, and more likely to leave over time. Focus also was related to perceptions of job complexity, and moderated the relationship between complexity and employee responses. These findings provide further support for hypotheses posited by Gardner, Dunham, Cummings, and Pierce (1987a, 1989) regarding employee focus of attention.
High-Resolution Mapping of Infrared Photoluminescence

We report preliminary results of high-resolution scanning photoluminescence (PL) experiments in the near- and mid-infrared (IR) portions of the spectrum. The samples investigated were Hg0.7Cd0.3Te epilayers grown on Cd0.96Zn0.04Te and CdTe/Si substrates used in IR detectors and focal-plane arrays. To measure mid-IR PL, we modified a commercial, Fourier transform infrared (FTIR) spectrometer and designed a confocal microscope attachment. For near-IR PL mapping, we used a confocal microscope coupled to a grating spectrometer and a charge-couple device (CCD) camera. Diffraction-limited resolution was achieved in the near-IR setup (0.5 µm) and 22-µm resolution for the mid-IR setup.
Zebrafish (Danio rerio) Endomembrane Antiporter Similar to a Yeast Cation/H+ Transporter Is Required for Neural Crest Development

CAtion/H+ eXchangers (CAXs) are integral membrane proteins that transport Ca2+ or other cations by exchange with protons. While several yeast and plant CAX proteins have been characterized, no functional analysis of a vertebrate CAX homologue has yet been reported. In this study, we further characterize a CAX from yeast, VNX1, and initiate characterization of a zebrafish CAX (Cax1). Localization studies indicated that both Vnx1 and Cax1 proteins are found in endomembrane compartments. Biochemical characterization of endomembrane fractions from vnx1 mutant cells and zebrafish Cax1-expressing yeast cells suggested that both yeast and fish CAXs have Ca2+/H+ antiport activities. Additionally, the vnx1 mutation was associated with heightened pH-sensitivity. In zebrafish embryos, cax1 was specifically expressed in neural crest cells. Morpholino knockdown of cax1 caused defects in neural crest development, including alterations in pigmentation, defects in jaw development, and reduction in expression of the neura...
Keeping the pirates at bay-lor: waves of blackberry, sailing through mac support, and navigating the filemaker seas

Although we came over on different ships, we are all in the same boat now. But sailing in the same boat and tying the same knots are two different things. The three of us would like to show, in a poster, the different ways in which each of us approaches customer service.BlackBerry support can be a choppy, windy sea of support. Supporting both a Blackberry Enterprise Server (BES) and over 230 individual BlackBerry clients can make the support seas rough at times. Many clients arrive on the shores of our ITS support desk pleading for help and mercy with their smart phone. To keep the clients at Bay(lor) from mutiny or from commandeering our ship of support we have new procedures in place for dealing with ornery pirates. Let us share a few suggestions with you as we reveal to you how we manage to swab the decks with our BlackBerry support.Macintosh clients are a different breed. They think that because using the Mac is easy, that fixing it when it breaks should be easy and FAST, too. Keeping in touch with clients, giving them a fairly accurate accounting for how long things are going to take, and using a checklist to make sure that nothing is forgotten provide a rudder to steer the experience and make for smooth sailing.When supporting an ever-changing software environment such as FileMaker, the seas can get stormy at times. Having to support both short term and long term projects can often be overwhelming. Existing databases inevitably need minor adjustment. User error can cause minor problems that constantly need attention. New database projects can take months of preparation. We will share with you some detailed support conventions and other tips that will help calm the raging seas.
A Model for Partnering with Not-for-Profits to Develop Socially Responsible Businesses in a Global Environment.

Corporate social responsibility (CSR) is increasingly important in the global environment. Businesses that want to be socially responsible, but do not have the resources of multinational corporations, can partner with non-governmental (NGO), not-for-profit (NFP), and religious organizations to access information about the culture, customs, and needs of the people in areas where they wish to do business. Without such information, CSR projects can have unintended consequences that are not beneficial for the community. Suggesting that local farmers sell corn to ethanol producers may increase the farmers’ income but also increase the cost of a food staple to the community. Providing food aid may result in local farmers being unable to sell their crops for enough money to buy seed for the next harvest. Donating cheaper cinder blocks instead of adobe bricks may result in more available housing, but the housing may be unlivable in the summer heat. This paper presents a three-part model for businesses to follow to develop socially responsible projects. The first strategy is to use electronic sources of information about a country and area for background information. The second strategy is to gather on-the-ground information about important issues from the people who are already operating in a community as part of NGO, NFP and missionary initiatives. The third strategy is to develop scenarios that will help identify possible negative consequences of socially responsible projects so that the project implementation can be monitored for such consequences and interventions designed to decrease or counter the impact of negative consequences.
Regiospecific cleavage of 1,3-dioxanes by organoaluminum compounds

Organoaluminum compounds react with 4-methyl-2-phenyl-1,3-dioxane with cleavage of the O1-C2 bond to give monoethers with a primary alcohol group.
A method of sequencing without subcloning and its application to the identification of a novel ORF with a sequence suggestive of a transcriptional regulator in the water mold Achlya ambisexualis.

Abstract Genomic amplification with transcript sequencing (GAWTS) is a method of direct sequencing that involves amplification with PCR using primers containing phage promoters, transcription of the amplified product, and sequencing with reverse transcriptase. GAWTS requires the generation of PCR primers that are specific for the sequences on both sides of a region. Here we describe promoter ligation and transcript sequencing (PLATS), a direct method for rapidly obtaining novel sequences that utilizes generic primers and only requires knowledge of the sequence on one side of a region. PLATS involves restriction digestion of the amplified vector insert, ligation with a phage promoter, and then GAWTS using phage promoter sequences as the PCR primers. The method is rapid and economical because it uses a limited set of oligonucleotides, and it potentially amenable to automation because it does not require in vivo manipulations. PLATS facilitates the determination of a genomic sequence responsible for cross-hybridization in a Southern blot. Using PLATS, sequence has been obtained from a 1.1-kb segment in Achlya ambisexualis, which cross-hybridizes to the DNA-binding region of the chicken and Xenopus estrogen receptors. To our knowledge, this represents the first sequence reported from the Oomycetes, a large and widely distributed group of fungi. The sequence reveals a large, transcribed open reading frame that is markedly deficient in the dinucleotide TpA. A putative zinc finger containing three cysteines and one histidine (C-X2-C-X12-H-X3-C) and an acidic segment hint that this clone may be a member of a novel class of transcriptional regulators.
Synthesis and Crystal Structure Determination of Bifunctional Phosphine-Linked Triplatinum Double-Cluster Complexes.

Reactions of [Pt3(μ-CO)3(PCy3)3] (1) and [Pt3(μ-CNXyl)2(μ-CO)(CNXyl)(PCy3)2] (2) (Cy = C6H11, Xyl = C8H9) with 1/2 equiv of a bifunctional metal phosphine cation [(MPR‘2)2(R)]2+ (M = Cu, Ag, Au; R ...
Filtering and condensation tasks with integral and separable dimensions

Speed of classification was measured with a filtering task (only one dimension relevant) and a condensation task (two dimensions relevant) with integral dimensions of Munsell value and chroma and separable dimensions of value and size. The filtering task was easier with separable than with integral dimensions, but the condensation task was easier with integral than with separable dimensions. The results emphasize the importance of dimensional structure with separable dimensions and similarity or distance structure with integral dimensions.
Stereocontrol in Asymmetric γ-Lactam Syntheses from Imines and Cyanosuccinic Anhydrides

Computations (SCS-MP2//B3LYP) reveal that the asymmetric synthesis of highly substituted γ-lactams with three stereogenic centers, including one quaternary center, proceeds through a Mannich reaction between the enol form of the anhydride and the E-imine, followed by a transannular acylation. This new mechanistic picture accounts for both the observed reactivity and stereoselectivity. CH-O and hydrogen bonding interactions in the Mannich step and torsional steering effects in the acylation step are responsible for stereocontrol. It is demonstrated that this new mechanistic picture applies to the related reactions of homophthalic anhydrides with imines and presents new vistas for the design of a new reaction to access complex molecular architectures.
Effect of Clamping Pressure on PEM Fuel Cell Stack Performance

A two-dimensional mathematical model of a Proton Exchange Membrane fuel cell stack is developed. Taking advantage of the geometrical periodicity within the stack, the model is used to predict the detailed thermal, humidity, and electrochemical behavior of the fuel cell. Using recently-reported experimental results, the electrical and thermal contact resistances that develop within the stack, in response to the compressive force used to assemble the stack, are accounted for. The fuel cell performance, reported in terms of its power output and internal temperature distributions, is predicted to be very sensitive to the compressive load applied to the stack.Copyright © 2005 by ASME
Here today – not gone tomorrow: Roles for activating receptors in sustaining NK cells during viral infections

The conclusive evidence supporting a role for NK cells in defense against viruses has been obtained under conditions of NK cell deficiencies prior to infections. NK cell proliferation can be induced during infections, but the advantages of resulting expansion have been unclear because NK cell basal frequency is already high. However, NK cell decreases are also observed during certain conditions of viral infection. Given the range of potent antiviral and immunoregulatory functions of NK cells, such “disappearance” dramatically changes the resources available to the host. New studies demonstrate that proliferation dependent on activating receptors for virus-induced ligands is key for NK cell maintenance, and allows their continued availability for control of adaptive immune responses and immunopathology. This pathway for sustaining NK cells may represent a system used generally to select subsets for rescue during homeostatic purging. In the case of NK cells, though, nonselection limits continued access to the many beneficial functions of NK cells. The observations resolve the long-standing conundrum of reported NK cell increases and decreases during viral infections. Moreover, they demonstrate a previously unappreciated role for activating receptors, i.e. to keep NK cells here today and also tomorrow.
Study of mental iteration in different design situations

Mental iteration in engineering design is a repetition of cognitive activities occurring in designers' thinking process. While the importance of mental iteration has been recognized, the current understanding about it is still very limited. In this paper, we propose a framework to study mental iteration in different design situations. A cognitive activity model of conceptual design is developed to identify and capture various loops of cognitive activities. An experiment is conducted to study the effect of design problems and constraints on the behavior of mental iteration. The results indicate differences of iterative behaviors in response to different problem types and constraint conditions.
A Minisonicator To Rapidly Disrupt Bacterial Spores for DNA Analysis

Concerns about the use of anthrax spores as a weapon of mass destruction have motivated the development of portable instruments capable of detecting and monitoring a suspected release of the agent. Optimal detection of bacterial spores by PCR requires that the spores be disrupted to make the endogenous DNA available for amplification. The entire process of spore lysis, PCR, and detection can take several hours using conventional methods and instruments. In this report, a minisonicator and prototype spore lysis cartridge were built to disrupt Bacillus spores in 30 s for rapid, real-time PCR analysis. Utilization of the minisonicator improved PCR analysis by decreasing the limit of detection, reducing the time of detection, and increasing the signal amplitude. Total time of spore disruption and detection using the minisonicator and a microchip PCR instrument was less than 15 min.
Value-based management of design reuse

ABSTRACT Effective design reuse in electronic products has the potential to provide very large cost savings, substantial time-to-market reduction, and extra sources of revenue. Unfortunately, critical reuse opportunities are often unused, because they provide clear value to the corporation but directly harm the business performance of one or more organizational partners involved. It is therefore crucial to provide tools to help reuse partners participate in a reuse transaction when the transaction provides value to the corporation as a whole. Value-based Reuse Management (VRM) addresses this challenge by (a) ensuring that all parties can quickly assess the impact of a reuse opportunity on their business performance, and (b) encouraging high-value reuse opportunities by supplying value-based rewards to potential parties. In this paper, we introduce the Value-Based Reuse Management approach and we describe key results on electronic designs that demonstrate its advantages. Our results indicate that Value-based Reuse Management has the potential to significantly increase the success probability of high-value electronic design reuse. Keywords: Reuse, cost, value, management, reward, electronic, design, automatic, return, economic.
Perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to angiotensin II-induced hypertension.

In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 μg/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/day) or pressor (0.7 mg/kg/day) dose of Ang II at 3.5 months and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickness during diastole and systole. While Ang II stimulated an increase in wall thickness, the degree of increase was equivalent between control and TCDD offspring. In contrast, perinatal TCDD exposure did not alter basal blood pressure. However, Ang II increased systolic blood pressure more rapidly and to a greater degree in TCDD offspring. Further, Ang II stimulated renal myofibroblast differentiation and collagen deposition to a greater degree, and tended to increase procollagen I mRNA in TCDD offspring, compared to controls. These data suggest that perinatal TCDD exposure increases the susceptibility of offspring to renal fibrosis and hypertension in adulthood.
A mutation in the Schizosaccharomyces pombe rae1 gene causes defects in poly(A)+ RNA export and in the cytoskeleton.

A collection of fission yeast Schizosaccharomyces pombe conditional mutants was screened for defective nucleocytoplasmic transport of poly(A)+ RNA by fluorescence in situ hybridization. We identified a temperature-sensitive mutant that accumulated poly(A)+ RNA in the nucleus and have named it rae1-1, for ribonucleic acid export. All rae1-1 cells exhibit the defect in poly(A)+ RNA export within 30 min following a shift to the nonpermissive temperature. In addition, in the rae1-1 mutant, actin and tubulin become disorganized, and cells undergo an irreversible cycle arrest. Results from experiments in which rae1-1 cells were arrested in various phases of the cell division cycle and then shifted to nonpermissive temperature suggest that cells are particularly vulnerable to loss of rae1 function during G2/M. However, the inability to export RNA from the nucleus to the cytoplasm was not limited to a particular phase of the cell division cycle. The rae1 gene was isolated by complementation and encodes a predicted protein of 352 amino acids with four β-transducin/WD40 repeats.
Epithelial giant cells in measles as an aid in diagnosis

Ascertainment of the presence of epithelial multinucleate giant cells, a relatively specific feature in the cytopathology of measles, is a simple and useful diagnostic tool. During the prodromal stage and the first day of the rash, these cells are recoverable from accessible epithelial surfaces, such as the pharynx, the lining cells of nasal and buccal cavities, and conjunctiva. In the next few days they disappear progressively. They may also be seen in sputum and in urinary deposits. Although their identification is of value mainly in the prodromal stage, it may also be useful in the differential diagnosis of a rash when measles is a questionable possibility. Epithelial giant cell formation was not observed in children vaccinated with Schwarz strain, live, attenuated measles virus.
Proceedings of the 45th Annual Simulation Symposium

SpringSim'12, sponsored by the Society for Modeling and Simulation (SCS) and in collaboration with the ACM SIGSIM, brings together scientists and scholars from a variety of disciplines to collaborate and exchange ideas. Featuring members of industry, academia, military, and government from all over the world, SpringSim continues its mission to offer a unique setting for the discussion and advancement of all aspects of modeling and simulation. SpringSim'12 features an exciting group of world-renowned experts giving presentations concerning a variety of topics. Many of the SpringSim symposiums will offer tutorials and panel discussions covering topics specific to those fields.
Effects of Ouabain on the Left Ventricular Response to Exercise in Patients with Angina Pectoris

The response of the left ventricle to a level of supine bicycle exercise that induced angina, and the effects of ouabain (0.01 mg/kg) on this response were evaluated in 14 patients with coronary arterial disease. Before administration of ouabain, exercise was associated with depressed pumping performance of the left ventricle in four patients: stroke work fell with exercise while left ventricular end-diastolic pressure (LVEDP) increased. In five patients left ventricular (LV) performance was not frankly depressed, but nevertheless was abnormal: stroke work increased, but was accompanied by an inordinately large rise in LVEDP. In the remaining five patients LV function was essentially normal. Ouabain improved LV performance at rest in only a minority of patients, but during the stress of exercise, LV hemodynamics were improved by ouabain in 12 of the 14 patients. Five patients, however, continued to show either depressed or abnormal function with exercise after they were given ouabain. As judged by the relationship of LVEDP to LV peak dp/dt, left ventricular contractility was increased by ouabain in most patients both at rest and during exercise. Despite its beneficial effects on left ventricular performance, ouabain did not consistently alter either exercise tolerance or the LV tension-time index and pressure-rate product at which angina occurred.
Acupuncture-based modalities: novel alternative approaches in the treatment of gastrointestinal dysmotility in patients with systemic sclerosis.

Background The gastrointestinal (GI) dysmotility of systemic sclerosis (SSc, scleroderma) patients requires careful evaluation and intervention. The lack of effective prokinetic drugs motivate researchers to search for alternative treatments. Objectives We present an overview of the pathophysiology of SSc GI dysmotility and the advances in its management, with particular focus on acupuncture-related modalities and innovative therapies. Data sources Original research articles were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline methodology. We have searched the MEDLINE database using Medical Subject Heading (MeSH) for all English and non-English articles with an English abstract from 2005 to October 2012. Results Only four original articles of various study designs were found studying Complementary and Alternative Medicine (CAM) therapies for SSc patients. Despite the small patient study numbers, CAM treatments, acupressure, and transcutaneous electroacupuncture, showed self-reported and physiologic evidence of improvement of GI functioning and/or symptoms in SSc patients. Conclusions CAM therapies include experimental modalities with the potential to offer relief of symptoms from GI dysmotility. Larger studies are needed to investigate their optimal use in patient subsets to tailor therapies to patient needs.
Patterns of carbon flow from glucose to methane in a thermophilic anaerobic bioreactor

[U-14C]Glucose, added carrier-free to sludge from a thermophilic anaerobic bioreactor being fed a lignocellulose waste, was rapidly turned over with less than one-third of the original radiolabel remaining as glucose after 5 s of incubation. The primary labeled products found were [14C]acetate and 14CO2, which were in a ratio near 2:1. Further incubation resulted in the disappearance of [14C]acetate and the appearance of an equivalent amount of label as 14CH4 and 14CO2. No significant production of [14C]propionate, butyrate, lactate, or ethanol was detected from [14C]glucose, even if these potential intermediates (unlabeled) were added to the sludge at a concentration of 1 mM to trap any label entering their pools. Addition of 0.8 atm (80 kPa) of H2 to the headspace over sludge resulted in some accumulation of [14C]lactate and a corresponding decrease in [14C]acetate produced from [14C]glucose. Production of [14C]propionate, butyrate and ethanol were still not significant in the presence of H2. Incubation of sludge for 1 h in the presence of hydrogen resulted in increases in the lactate and formate concentrations, but not those of propionate, butyrate, or ethanol. These results demonstrate that glucose was metabolized directly to acetate, CO2, and H2 by the microbial populations in the bioreactor with little carbon from glucose flowing through other intermediates, indicating a high degree of coupling between glucose fermentation and hydrogen uptake. The short-term response of these microbial populations to elevated H2 partial pressures was to increase lactate production.
Binaural vs. monaural auditory evoked potentials in rat neocortex

High spatial resolution epicortical recording techniques and numerical modeling were used to investigate laterality effects on the middle latency auditory evoked potential (MAEP) complex. Our data confirm previous reports that auditory stimulus laterality has a consistent effect on the amplitude, timing, and spatial distribution of the MAEP complex. The earliest temporal components (P1a, P1b and N1) show the greatest sensitivity, and are absent during ipsilateral stimulation. The later positive slow wave (P2) is present at the same amplitude during all stimulation conditions. Generation of the P2 appears to be independent of prior activation of areas 36 and 41 reflected in the early components, suggesting its generation by a more diffuse thalamocortical pathway, possibly from the medial division of the medial geniculate. Serial vs. parallel activation of rodent auditory cortex is discussed in the context of laterality-sensitive MAEP components.
In vivo characterization of four types of opioid binding sites in rat brain

Opioid receptor multiplicity was studied in the brain of intact rats by two experimental approaches. The first involved in vivo labeling by administration of [3H] tracers s.c. to intact rats. The second method was based on ex vivo labeling by incubating fresh brain homogenates immediately after sacrifice with suitable receptor type-specific tracers. The ex vivo labeling approach thus can measure the in vivo receptor occupancy of unlabeled ligands, provided that these ligands do not equilibrate between bound and free form over the assay period. The results suggest the presence of four separate types of opioid binding sites that resemble the mu, delta, kappa, and the newly identified lambda sites.
Differential effects of PAK1-activating mutations reveal activity- dependent and -independent effects on cytoskeletal regulation

PAKs are serine/threonine protein kinases that are activated by binding to Rac or Cdc42hs. Different forms of activated PAK1 have been reported to either promote membrane ruffling and focal adhesion assembly or cause focal adhesion disassembly and stress fiber dissolution. To understand the basis for these distinct morphological effects, we have examined the mechanism of mutational activation of PAK1, and characterized the effects of different active PAK1 proteins on cytoskeletal structure in vivo. We find that PAK1 contains an autoinhibitory domain that overlaps with its small G protein binding domain and that two separate activating mutations within this regulatory region each decrease autoinhibitory activity. Because only one of these mutations affects Cdc42hs binding activity, this indicates that activation of PAK1 by these mutations results from interference with the function of the autoinhibitory domain and not with small G protein binding activity. When we examined the morphological effects of these different forms of PAK1 in vivo, we found that PAK1 kinase activity was associated with disassembly of focal adhesions and actin stress fibers and that this may require interaction with potential SH3 domain-containing proteins. Lamellipodia formation and membrane ruffling caused by active PAK1 expression, however, was independent of PAK1 catalytic activity and likely requires interaction among multiple proteins binding to the PAK1 regulatory domain.
Calculated properties of some possible vinyl chloride metabolites

There is considerable evidence indicating that the carcinogenic action of vinyl chloride involves metabolic conversion to the epoxide (chlorooxirane) as the initial step. In order to learn more about its subsequent behavior, we have computed structures, energies and other properties for two different protonated forms of the epoxide, and also for two possible rearrangement products, chloroacetaldehyde and acetyl chloride. An ab initioSCF-MO procedure (GAUSSIAN 70) was used. Oxygen protonation is found to weaken both CO bonds, the effect being greater for the bond involving the carbon bearing the chlorine. Chlorine protonation leads to a marked weakening of the CCl bond; this suggests a possible loss of HCl, leaving behind a carbonium ion (and possible alkylating agent or rearrangement precursor). Thus, while CO bond breaking is doubtless an important reaction pathway for chlorooxirane, our results indicate that attention should also be focused upon the CCl bond; its rupture may conceivably be a key step in the biological action of vinyl chloride.
The web in high school science teaching: constructing a technology in practice

The Internet is becoming omnipresent as a resource for K-12 education. Teachers are a diverse set of users who must incorporate this resource into ongoing practice. Research on using the Internet in classrooms is lagging far behind deployment, and teachers are left to their own devices to figure out what works. Using case studies of three teachers, this study considers the work of teaching with the Internet as a site for understanding the challenges and problems teachers experience as they incorporate the Internet into their high school science teaching. Challenges include figuring out how to fit the Internet into the curriculum and finding time to do so; managing a new kind of discourse around Web sites; and establishing ways to hold students accountable for their work and to evaluate what they do. This research is aimed at informing system designers who provide technologies for teachers and teacher educators who prepare teachers to meet these challenges.
The Effect of Winds and Tides on the Length of the Day

The seasonal variation in the zonal winds of the atmosphere are reexamined and estimated to account for a January to July change of 0,5 milliseconds in the length of the day. Thus only one third of the change in length of the day reported by the astronomers is explained by angular momentum transfers between the earth and atmosphere. The corresponding effect of the varying equilibrium body tide of the earth caused by changes in the sun's distance and longitude is negligible. DOI: 10.1111/j.2153-3490.1951.tb00787.x
Oral Atypical Cellular Blue Nevus: An Infiltrative Melanocytic Proliferation

The atypical cellular blue nevus is an extremely rare nevomelanocytic lesion which lacks precise histologic characterization in the current literature. Given the potential for significant architectural and cytologic overlap with melanoma, further study, including molecular analysis, is needed. This is the first description of an atypical cellular blue nevus of the oral cavity.