cssi/SciSciGPT-SciSciNet huggingface dataset:
Understanding iatrogenic effects for evidence-based policy: A review of crime and violence prevention programs

Abstract This article has two main objectives. The first is to advance primary research on intervention studies that report iatrogenic effects. In short, we need to know a great deal more about why interventions cause harm. The second objective is to make the case that a body of knowledge on iatrogenic effects can play an important role in informing evidence-based policy. We view this knowledge as another key input in the policymaking process. Some primary research has been conducted on interventions with iatrogenic effects, and several studies with crime and violence outcomes are reviewed. Building on a number of important advances from this work, as well as from prior reviews on the subject, a research agenda is proposed to help enrich our understanding of interventions that cause harm and contribute to evidence-based policy in the area of crime and violence prevention. Directions for future research include carrying out longer follow-up assessments of interventions with iatrogenic effects and investigating the role of theory failure and implementation failure as potential explanations. In the same way that immediate action is needed to end interventions that cause harm, using the knowledge base on iatrogenic effects has the potential to provide policymakers with an important tool to help avoid causing harm in the first instance.
Covering AAG’s Tracks

This chapter presents TAs as a group of workers uniquely positioned to resist AAG’s restructuring of the labor process. TAs’ work included tasks of increasing number and complexity even though their positions were low-paying and insecure. AAG leveraged TAs’ experience, which sometimes outpaced that of teachers, to cover vacant teaching positions and even surveil new teachers. TAs’ work literally kept Eclipse running, while they struggled to obtain autonomy and compensation from the network. TAs amassed small benefits that made everyday work more manageable. On a structural level, they also developed unique abilities to critique administrators’ control over the labor process. TAs accumulated vast institutional knowledge not only because they worked at Eclipse far longer than the average teacher, but also because their movement afforded them special insight into the realities underlying individuals’ reputations.
Real-time deep learning assisted skin layer delineation in dermal optical coherence tomography

We present deep learning assisted optical coherence tomography (OCT) imaging for quantitative tissue characterization and differentiation in dermatology. We utilize a manually scanned single fiber OCT (sfOCT) instrument to acquire OCT images from the skin. The focus of this study is to train a U-Net for automatic skin layer delineation. We demonstrate that U-Net allows quantitative assessment of epidermal thickness automatically. U-Net segmentation achieves high accuracy for epidermal thickness estimation for normal skin and leads to a clear differentiation between normal skin and skin lesions. Our results suggest that a single fiber OCT instrument with AI assisted skin delineation capability has the potential to become a cost-effective tool in clinical dermatology, for diagnosis and tumor margin detection.
Working memory moderates the relation between implicit alcohol associations and heavy episodic drinking in moderate-to-heavy drinking men who have sex with men.

Abstract Introduction Heavy episodic drinking poses a risk for HIV-infection, particularly among men who have sex with men (MSM). Previous research suggests implicit associations may play a role in heavy episodic drinking and that various executive functions (EF) may moderate the relation between implicit associations and heavy episodic drinking. This study investigated the role of two EF – working memory (maintaining and updating information) and response inhibition (inhibiting prepotent responses) – as moderators of the relation between implicit alcohol approach associations and heavy episodic drinking among moderate-to-heavy drinking MSM. Methods Two-hundred and fifty-one participants completed measures of implicit alcohol associations (the implicit alcohol approach association test - IAT), working memory, and response inhibition, as well as a self-report questionnaire assessing heavy episodic drinking. Regression analyses were conducted to examine whether the association between the IAT and heavy episodic drinking was moderated by working memory and response inhibition. Results Results showed that working memory moderated the relation between the alcohol IAT and heavy episodic drinking such that IAT alcohol approach scores were positively associated with heavy episodic drinking among those low in working memory but not those high in working memory. Response inhibition did not moderate the association between IAT scores and heavy episodic drinking. Conclusions Results suggest that the relation between implicit alcohol approach associations and heavy episodic drinking is stronger among moderate-to-heavy drinking MSM with lower working memory capacity compared to those with higher working memory capacity, and these individuals may particularly benefit from alcohol intervention approaches that target automatic alcohol responses.
Evaluating a Web-Based Adult ADHD Toolkit for Primary Care Clinicians.

Introduction: Approximately 5% of the US adult population has Attention Deficient Hyperactivity Disorder (ADHD) that can negatively impact quality of life. Health care professionals report a need to increase their knowledge of and confidence in treating adult ADHD. The American Academy of Family Physicians National Research Network (AAFP NRN) collaborated with a panel of experts to create a web-based AAFP Adult ADHD Toolkit composed of resources to aid in the diagnosis, management, and treatment of adults with ADHD. Objectives: Assess the impact of using an AAFP Adult ADHD Toolkit in a practice setting. Methods: Ninety-seven primary and behavioral health care professionals from AAFP NRN practices (n=6) used the Toolkit for 17 weeks. Data on Toolkit use, usefulness, implementation, impact, and changes in knowledge and confidence were collected via pre-post and weekly surveys. Mixed methods, regression analyses, t-tests, and mixed ANOVA were used to assess change over time. Results: Use of the Toolkit improved health care providers9 knowledge by midpoint relative to baseline in areas related to treatment effects, side effects, and outcomes (3.6 vs 3.0; P = .004); existing ADHD resources (3.3 vs 2.9; P = .03); and management of ADHD in patients with comorbid conditions (3.2 vs 2.7; P = .01). By the end of the study, Toolkit use was associated with increased confidence in mental health and life history interview techniques (3.5 vs 3.0; P = .03); treatment options for ADHD with comorbid mental health disorders (3.2 vs 2.3; P ≤ .001); and treatment options for ADHD with coexisting substance use disorders (3.0 vs 2.3; P = .003). By the end of the study, most participants (n=47, 87%) reported the Toolkit addressed most of their needs related to diagnosis, treatment, and management of adult ADHD. Conclusion: Availability and adoption of the Toolkit into the routine care of adults with ADHD measurably increased health care professionals9 knowledge especially in those providers who regularly see adult patients with ADHD.
Contracting on Aggregated Accounting Estimates

Using a principal-agent framework in which the agent chooses the joint distribution over all contractible and non-contractible signals, we provide a theoretical justification for contracting on aggregated accounting estimates. The optimal contracting process can be decomposed into three stages: estimating individual items that the principal values, aggregating those estimates using the weights in the principal's objective (as opposed to weighting by sensitivity or precision), and compensating the agent based on the aggregated estimate. In a highly tractable specification of our model in which normal distributions arise endogenously, we show that optimal measurement rules are conservative yet produce unbiased estimates. Furthermore, we show that a weaker link between investment and future returns warrants more conservative treatment of expected future benefits, providing a contracting rationale for the immediate expensing of R&D, the capitalization of PP&E and the accrual of credit sales.
CFD using virtual shared memory

Publisher Summary High-performance computing is fundamentally governed by three issues: performance, affordability, and scalability. The overall goal of high-performance computing is to develop an evolutionary platform with unlimited computing potential. The Uncached Store Coherent Memory (USC) model is quite straightforward. Because there is only one valid memory region available at any given time, the regions are moved around to the appropriate processor when needed. USC does not suffer the consistency problems associated with replicated data, but does not always perform well. In the Cached Store Coherent. Memory (CSC) model, the function allows the simultaneous broadcast of updated memory regions to all appropriate processors. In both cases, there is a larger than necessary quantity of data that is communicated among the processors because of the fundamental memory unit being a page. Because the USC and CSC models provide the most straightforward implementation of the algorithm at hand, they are used to measure this benchmark. The Loop Coherent Memory model resolves the above problems by allowing replicated read/write memory regions. Jitter is completely eliminated because there can be more than one writable region.
Studies on the electron transport system: XXXIX. Assay of cytochrome oxidase. Effect of phospholipids and other factors

Abstract Various phospholipid sols increase the specific activity of cytochrome oxidase when added to the assay medium and act primarily by retarding or preventing the aggregation of cytochrome oxidase particles. Aggregates of the enzyme cannot be dispersed by phospholipids although bile salts and sonic oscillation are effective. Reaction velocities obtained with the manometric, polarographic, and spectrophotometric assays can be brought into agreement by including phospholipid sols in the assay media and by extrapolating the specific activities to infinite concentration of cytochrome c. Inhibition of the reaction by cytochrome c is discussed.
Scalable Synchrophasors Communication Network Design and Implementation for Real-Time Distributed Generation Grid

There has been a growing interest in the deployment of phasor measurement units (PMUs) not only in high-voltage transmission, but in lower-voltage distribution systems. For a distributed generation (DG) grid, this would require deployment of PMUs at critical locations, which implies accurate phase measurement with the support of a low delay, highly reliable network infrastructure. In the absence of such a network, the most cost-effective solution would be to consider a wireless network to support centralized control for situational awareness in the transmission, as well as the DG grid environment. Therefore, the main objective in this paper is to design and implement a scalable synchrophasor network using wireless LAN technology to assess network performance and requirements under real-world conditions. To achieve this, we have designed an emulation platform that can support physical and medium access control layers. The data communication at the application is based on the IEEE C37.118-2011-2 Standard. By considering a hierarchical network architecture for our testbed implementation, we propose an efficient method to reduce bandwidth, as well as provide capabilities for control and management at each hierarchical level. In addition, an efficient tree-based multihop routing protocol has been designed to match a specific distribution feeder structure. The testbed is then used to access different network configurations under various test conditions.
Imaging of Diffuse and Inflammatory Liver Disease

The incidence of diffuse liver disease, including all causes, is increasing worldwide. On one side this is due to trends in population towards aging and obesity resulting in a higher prevalence of steatosis/steatohepatitis, fibrosis, and cirrhosis. On the other side, inflammatory origin, especially due to viral hepatitis, is one of the primary reasons for diffuse liver disease. This chapter will describe the most common imaging features of hepatic metabolic and storage diseases, including overload with fat, iron, copper, and amyloid and diffuse neoplastic diseases. We also discuss focal and diffuse infectious and inflammatory hepatic diseases. Key imaging manifestations of fungal, granulomatous, parasitic, viral, and bacterial as well as the less common hepatic infections such as cat-scratch disease, bacillary angiomatosis, and amebic disease are reviewed to avoid pitfalls in image interpretation. Although magnetic resonance imaging (MRI) provides unique capabilities for noninvasive and quantitative characterization of liver tissue that rival the diagnostic utility of liver biopsies, also characteristic imaging findings with computed tomography (CT) that are useful in daily clinical routine will be discussed.
Complexity from precipitation reactions

A key challenge for modern molecular sciences is to bridge the gap between the nanoscopic world and macroscopic devices. The underlying question is whether one can control chemical reactions to produce directly macroscopic complexity, hierarchical order, and ultimately entirely new types of materials. If viewed as a form of complicated chemistry, biology unambiguously answers this question with a resounding “yes” and, furthermore, demonstrates the powerful potential of this approach. However, this fundamental reassurance does not provide significant help in developing nonbiological model systems and leaves us with seemingly insurmountable hurdles. The PNAS article by Haudin et al. (1) is an important step to overcome some of these hurdles, as it provides just such an experimental model.
Extended X‐Ray Absorption Fluorescence Spectroscopy (EXAFS)

This article has no abstract. Keywords: extended X-ray absorption fluorescence spectroscopy (EXAFS)
Cobra: contentbased filtering and aggregation of blogs and RSS feeds

Blogs and RSS feeds are becoming increasingly popular. The blogging site LiveJournal has over 11 million user accounts, and according to one report, over 1.6 million postings are made to blogs every day. The "Blogosphere" is a new hotbed of Internet-based media that represents a shift from mostly static content to dynamic, continuously-updated discussions. The problem is that finding and tracking blogs with interesting content is an extremely cumbersome process. In this paper, we present Cobra (Content-Based RSS Aggregator), a system that crawls, filters, and aggregates vast numbers of RSS feeds, delivering to each user a personalized feed based on their interests. Cobra consists of a three-tiered network of crawlers that scan web feeds, filters that match crawled articles to user subscriptions, and reflectors that provide recently-matching articles on each subscription as an RSS feed, which can be browsed using a standard RSS reader. We present the design, implementation, and evaluation of Cobra in three settings: a dedicated cluster, the Emulab testbed, and on PlanetLab. We present a detailed performance study of the Cobra system, demonstrating that the system is able to scale well to support a large number of source feeds and users; that the mean update detection latency is low (bounded by the crawler rate); and that an offline service provisioning step combined with several performance optimizations are effective at reducing memory usage and network load.
Chemistry of the Solar Nebula

We review theoretical models of thermochemical processes in the solar nebula which consider the effects of nebular dynamics on the chemistry of the abundant, chemically reactive volatile elements H, O, C, N, and S. Specific, testable predictions of these models are described. We also use the theoretical models to interpret the latest available data on the abundances and molecular speciation of volatiles in comet P/Halley.
Approximation algorithms for solving cost observable Markov decision processes

Partial observability is a result of noisy or imperfect sensors that are not able to reveal the real state of the world. Problems that suffer from partial observability have been modelled as Partially Observable Markov Decision Processes (POMDPs). They have been studied by researchers in Operations Research and Artificial Intelligence for the past 30 years. Nevertheless, solving for the optimal solution or for close approximations to the optimal solution is known to be NP-hard. Current algorithms are very expensive and do not scale well. Many applications can be modelled as POMDPs: quality control, autonomous robots, weapon allocation, medical diagnosis. Designing approximation algorithms to solve problems that have partial observability is the focus of this research. The model we propose (Cost Observable Markov Decision Processes or COMDPs) associates costs with obtaining information about the current state (Bayer 1998). The COMDP’s actions are of two kinds: world actions and observation actions. World actions change the state of the world, but return no observation information. Observation actions return observation information, but the state of the world does not change while performing them. COMDPs are intended to model situations that arise in diagnosis and active vision where there are many observation actions that do not change the world and relatively few world-changing actions. We are particularly interested in problems where there are many alternative sensing actions (including, especially, no sensing at all) and where, if all observation actions are performed, the entire state of the world is observable (but presumably at very great cost). Hence, COMDPs can also be viewed as a form of fully observable Markov Decision Processes (MDPs) where the agent must pay to receive state information (they are "cost-observable"). Any POMDP can be modeled as a COMDP and vice versa. We want to approximately solve COMDPs and determine what POMDP classes these approximations are good for. There are two fundamental problems that any POMDP approximation algorithm must address: how to act when "lost" and how to avoid getting "lost".
3-Methyl-1,5-pentanediol †

3-Methyl-1,5-pentanediol product: 3-methyl-1,5-pentanediol byproduct: β-methylglutaraldehyde Keywords: hydrolysis, acetals and ketals; hydrolysis, miscellaneous; reduction, CO CHOH; catalysts, metal, Raney nickel W-6; filter aids; hydrogenation apparatus
Complexity and Transdisciplinarity: Reflections on Theory and Practice

Systems and complexity theories are transversal approaches that provide a new way of thinking as a response to the traditional reductionist approach that emerged with modernity. Complexity and transdisciplinarity are particularly relevant in an increasingly diverse, networked, uncertain, and fast-changing world. Examples are drawn from personal experience in academia, cross-cultural experiences, and the arts.
Dynamic Bundling: Less Effort for More Solutions

Bundling of the values of variables in a Constraint Satisfaction Problem (CSP) as the search proceeds is an abstraction mechanism that yields a compact representation of the solution space. We have previously established that, in spite of the effort of recomputing the bundles, dynamic bundling is never less effective than static bundling and nonbundling search strategies. Objections were raised that bundling mechanisms (whether static or dynamic) are too costly and not worthwhile when one is not seeking all solutions to the CSP. In this paper, we dispel these doubts and empirically show that (1) dynamic bundling remains superior in this context, (2) it does not require a full lookahead strategy, and (3) it dramatically reduces the cost of solving problems at the phase transition while yielding a bundle of multiple, robust solutions.
Anidulafungin in the treatment of invasive fungal infections.

More antifungal agents have reached clinical use in the past two decades than at any other time. The echinocandins have been a welcome addition to this group, with the latest being anidulafungin. There are several lines of evidence to support anidulafungin’s role as primary therapy for the treatment of invasive candidiasis in non-neutropenic patients, and as alternative therapy to fluconazole in patients with esophageal candidiasis with azole intolerance or triazole-resistant Candida. Pharmacokinetic–pharmacodynamic studies in animals have demonstrated superior efficacy, defined as maximal microbial kill, when compared to fluconazole, regardless of the fluconazole susceptibility of the Candida species. These studies, as well as dose-effect studies in patients, also support the currently recommended dose of anidulafungin. A well designed randomized controlled trial has demonstrated anidulafungin’s efficacy in patients with invasive candidiasis. In this paper, we argue that anidulafungin may be preferable to fluconazole for the treatment of candidemia. However, as of yet, the difference between anidulafungin and the other two licensed echinocandins as first-line therapy for invasive candidiasis is unclear. On the other hand, there is insufficient evidence as of yet to support first-line use of anidulafungin in patients with neutropenia or aspergillosis.
The water tank technique: Avoidance conditioning as a function of water level and pedestal size

Abstract Using the water tank technique, 45 male rats were confined for 5 days on either 7 cm, 11.5 cm, or 15 cm pedestals which were surrounded by water. Variations in the water levels which surrounded the tops of the pedestals had no effect on the acquisition of a shuttle-box active avoidance task. However, the size of the platforms on which the rats were confined did influence the acquisition process. Confinement on small platforms facilitated acquisition of the task. This facilitation was significant only when the smallest and largest pedestal groups were compared. The water tank apparatus is widely utilized in REM sleep deprivation experiments. The results from the present study indicate that the size of the large pedestal is critical as to its applicability as a control technique in these experiments.
1-Tetradecanol Complex Reduces Progression of Porphyromonas gingivalis–Induced Experimental Periodontitis in Rabbits

Background: It has been recently shown that monounsaturated fatty acids inhibit endothelial activation and reduce tissue responsiveness to cytokines. The present study has been planned to investigate topical application of a novel monounsaturated fatty acid complex (1-tetradecanol complex) for prevention of Porphyromonas gingivalis–induced periodontitis in rabbits.Methods: Experimental periodontitis was induced in New Zealand white rabbits with silk sutures tied around the mandibular second premolars bilaterally, followed by the topical application of 109 colony forming units (CFU) of P. gingivalis. 1-Tetradecanol complex (1-TDC) was topically applied at 1- and 10-mg/ml concentrations in five animals in each group, whereas control animals received olive oil vehicle (five animals) three times per week for 6 weeks. Negative controls included ligature alone (14 animals) or ligature + P. gingivalis (non-treatment; 15 animals). Rabbits were sacrificed after 6 weeks, and mandibular block sections were obtained;...
The effects of phospholipid unsaturation and alcohol perturbation at the protein/lipid interface probed using fluorophore lifetime heterogeneity

The influence of phospholipid unsaturation and perturbation by alcohols, on the membrane protein/lipid interface, was probed using the fluorescence decay properties of 1,6-diphenyl-1,3,5-hexatriene (DPH) and DPH attached to the sn-2 chain of phosphatidylcholine (DPH-PC), in lipid bilayers and microsomal membranes. With microsomal membranes it was found that it was appropriate to describe the fluorescence decay of DPH-PC as a range of decay rates, accomplished by fitting the data to a bimodal fluorescence lifetime distribution. The major lifetime center had a broad distributional width, indicative of excited state fluorophore heterogeneity. The effect was attributable to protein, and by inference, the protein/lipid interface, since in vesicles made from total microsomal lipids (i.e., without protein) the fluorescence decay was homogeneous. Upon addition of ethanol or hexanol the width of the lifetime distribution of the major lifetime center increased, indicating increased environmental heterogeneity. It was confirmed that the effect was manifest at the protein/lipid interface, and not due to lipid-reorganizational factors, since it could also be obtained using a simple lipid bilayer vesicle system with apocytochrome c as a model membrane protein, and DPH instead of DPH-PC. Environmental heterogeneity was also found to increase with increased phosphatidylcholine (sn-2) unsaturation. The environmental heterogeneity at the protein/lipid interface could arise from a combination of varying polarities of amino acid side chains and of water that may intercalate in packing defects on the hydrophobic surface of the protein. Therefore the results could be explained on the basis of an increased degree of hydration at the protein/lipid interface. Such an effect offers a route whereby acyl chain perturbation and increased unsaturation might influence protein conformation and hence function.
IRON‐MEDIATED CHANGES IN THE GROWTH OF LAKE ERIE PHYTOPLANKTON AND AXENIC ALGAL CULTURES

The effect of iron enrichment on algal growth and photosynthesis was investigated using natural assemblages of Lake Erie phytoplankton and axenic cultures of Anabaena, Scenedesmus and Selenastrum. Cell yield and photosynthesis were frequently inhibited in the presence of unchelated iron over the range of 3.6 to 53.7 μM iron as FeCl3. In lake water and in a defined medium with low nutrient concentrations, the degree of inhibition by iron could be reduced by chelating the iron with EDTA or by enriching the cultures with phosphorus. Chemical analyses revealed that the EDTA efectively reduced the ability of the ferric iron to remove soluble phosphorus from the media. EDTA was also observed to reduce rather than enhance iron uptake by axenic cultures of A. flos-aquae. These data support the hypothesis that additions of EDTA to low-nutrient media may serve to stimulate algal growth in the presence of iron by preventing the iron from altering extracellular concentrations of soluble ions essential for algal metabolism. In medium with high nutrient concentrations, the soluble phosphorus concentration was not appreciably altered by either EDTA-chelated or unchelated iron enrichment (0.9 to 53.7 μM). Instead, the observed enhancement of cell yield by EDTA-chelated iron in nutrient-rich media appeared to be due to the direct effect of iron on intracellular metabolic processes.
PatchPeer: A scalable video-on-demand streaming system in hybrid wireless mobile peer-to-peer networks

Video-on-demand service in wireless networks is one important step to achieving the goal of providing video services anywhere anytime. Typically, carrier mobile networks are used to deliver videos wirelessly. Since every video stream comes from the base station, regardless of what bandwidth sharing techniques are being utilized, the media stream system is still limited by the network capacity of the base station. The key to overcome the scalability issue is to exploit resources available at mobile clients in a peer-to-peer setting. We observe that it is common to have a carrier mobile network and a mobile peer-to-peer network co-exist in a wireless environment. A feature of such hybrid environment is that the former offers high availability assurance, while the latter presents an opportunistic use of resources available at mobile clients. Our proposed video-on-demand technique, PatchPeer, leverages this network characteristic to allow the video-on-demand system scale beyond the bandwidth capacity of the server. Mobile clients in PatchPeer are no longer passive receivers, but also active senders of video streams to other mobile clients. Our extensive performance study shows that PatchPeer can accept more clients than the current state-of-the-art technique, while maintaining the same Quality-of-Service to clients.
Primary proteasome inhibition results in cardiac dysfunction.

Aims The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. Methods and results Female domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P < 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P < 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P < 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. Conclusion The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic–restrictive cardiomyopathy phenotype.
The rejuvenated scenario of epithelial–mesenchymal transition (EMT) and cancer metastasis

The molecular mechanisms underlying cancer progression and metastasis are still poorly understood. In recent years, the epithelial-to-mesenchymal transition (EMT), a traditional phenomenon revealed in embryonic development, has been gradually accepted as a potential mechanism underlying cancer progression and metastasis. Many cell signaling pathways involved in development have been shown to contribute to EMT. An increasing number of genetic and epigenetic elements have been discovered, and their cross-talk relationship in EMT remains to be explored. In addition, accumulating experimental evidence suggests that EMT plays a critical role in different aspects of cancer progression, such as metastasis, stem cell traits, and chemoresistance. However, there are some disagreements and debate about these studies, which raise critical questions worthy of further investigation. Solving these questions will lead to a more complete understanding of cancer metastasis. Due to the close relationship of EMT to cancer metastasis and chemoresistance, targeting EMT or reversing EMT is likely to lead to novel therapeutic approaches for the treatment of human cancers.
Joint clustering of protein interaction networks by block modeling

Identification of functional modules in protein protein interaction (PPI) networks may help better understand cell functions. Many existing computational methods focus on identifying modules based on either individual PPI networks or protein sequence similarities within the species. As both interaction data and sequence similarities may not be either complete or accurate with respect to revealing protein functionalities, we propose a joint clustering framework based on block modeling to integrate the available information across different species to utilize both protein interaction data and sequence similarities. The motivation is to borrow strengths from multiple data sources for more accurate module identification as evolutionally different species may share similar cellular organization. Our blockmodel joint clustering enables the identification of not only densely connected modules but also those modules containing proteins with similar interaction patterns to the rest of the networks. We develop a simulated annealing (SA) algorithm based on Potts-Models for the blockmodel problem to solve the non-convex combinatorial optimization. Our method is validated using synthetic networks as well as yeast and fruit fly PPI networks. The experimental results conclude that joint clustering outperforms clustering of individual networks separately.
STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits

Clinically, HER2 proto-oncogene amplification is found in about 25-30% of human breast cancers, where it is correlated to a poor prognosis. Constitutive STAT3 activation is found in about 50-60% of the breast tumors and associated with tumorigenesis and drug resistance. In this study, we showed that STAT3 was phosphorylated in HER2-overexpressing, ER-positive human breast tumors and, furthermore, phosphorylated STAT3 promoted the stem-like cell phenotype. We examined the dysregulation of the stem cell markers (Oct-4, Sox-2 and CD44) and the tumorsphere formation in HER2-overexpressing human breast cancer cell lines. We demonstrated that the STAT3 inhibitor, Stattic, treatment abolished the cancer stem cell phenotype in HER2-positive breast cancers. Combined treatment of Herceptin and Stattic showed the synergistic effect on the cancer cell growth in vitro. In addition, when the STAT3 gene was knocked down, the expression of the stem cell markers Oct-4, Sox-2 and CD44 were downregulated and tumorsphere formation was abolished. HER2-elicited STAT3 signaling may provide a potential model for drug resistance induced by stem-like cell characteristics. This mechanism may be responsible for acquiring resistance to Herceptin in the treatment of HER2-overexpressing breast tumors. Based on our findings, targeting pSTAT3 could overcome Herceptin-induced resistance in HER2-overexpressing breast tumors.
Transport and EPR studies at ambient pressure in (TMTSF)2-PF6 —Pristine and doped with TMTTF

Abstract We report on transport and EPR studies of (TMTSF)2-PF6, both in its pristine form and when doped with the sulfur analog TMTTF. All samples undergo a single phase transition which can be seen in both the transport and magnetic data and which, in the undoped material, occurs at ∼11.5 K. The effects of a 3% dopant concentration are dramatic: a 40% rise in the transition temperature, a 130% rise in the room- temperature spin susceptibility and a 30% fall in the low-temperature g shift. Possible causes are discussed.
Pulverized coal combustion: NOx formation mechanisms under fuel rich and staged combustion conditions

A 2 Kg/h pulverized fuel one dimensional flame combustor was used to determine time resolved NO profiles under fuel rich and staged combustion conditions. Seven solid fuels, including two coal chars, were investigated. Results show that at all fuel rich conditions NO is formed rapidly and then is slowly destroyed. The peak NO value and the rate of destruction are strong functions of coal composition and stoichiometry. Under staged combustion conditions NO may increase or decrease at the staging point, depending on the fuel and on the quantity of NO formed in the first stage. Use of artificial oxidants confirmed that under most conditions examined, the NO formed in the first and second stages consisted primarily of Fuel NO. Heterogeneous formation and reduction of NO during FMC char combustion was modeled by a two-reaction scheme. For this char, heterogeneous reduction was less than first order in NO and had an activation energy of 47 kcal/mole. The roles of devolatilization and homogeneous reactions are discussed, in the light of the data presented.
Improved bounds on elastic and transport properties of fiber-reinforced composites: Effect of polydispersivity in fiber radius

Improved rigorous bounds were computed on the effective elastic and transport properties (including the effective axial shear modulus, effective transverse bulk modulus, and effective transverse shear modulus) of a transversely isotropic fiber-reinforced material composed of infinitely-long oriented multisized impenetrable circular cylinders distributed throughout a matrix. Results were used to study the effect of fiber-radius polydispersivity on the elastic and transport properties of such unidirectional composites. It was found that increasing the degree of polydispersivity increases the effective transverse conductivity (or axial shear modulus) and the effective transverse bulk modulus, and slightly decreases the effective transverse shear modulus for cases in which the fibers are more conducting or stiffer than the matrix.
1004 VACCINATION OF PEDIATRIC NURSES WITH TOWNE STRAIN CYTOMEGALOVIRUS (CMV)

A trial of live, attenuated Towne strain CMV vaccine was undertaken in 21-34 yr. old healthy female nurses seronegative by complement fixation (CF) and anticomplement immunofluorescence (ACIF). Thus far, 10 nurses have been vaccinated with 103.5 pfu subcutaneously and followed for 6 mos (3) to 1 yr (7). After vaccination, they had serial exams, CBCs and chemistry profiles, and viral cultures of the throat, urine, cervix, and blood. They were tested for CF, ACIF, and neutralizing antibodies (NT) and for cell mediated immunity (CMI) by the lymphocyte proliferation assay. Although 9 nurses developed erythema and/or edema at the vaccination site, none had temperature ≥38.5°C, systemic illness, or persistent laboratory abnormalities. Antibodies (CF, ACIF, NT) appeared in 2-4 wks and peaked by 8 wks. Peak geometric mean titers were 1:39 CF, 1:97 ACIF, and 1:34 NT. Two patterns were observed in the 9 nurses followed for CMI. Eight nurses had an early (2-4 wks) and, in most cases, a late (26-39 wks) peak; 1 nurse had only a late peak. None of the women excreted CMV from any site. Towne strain CMV vaccine appears safe and immunogenic in preliminary trials among healthy women of child bearing age who may be at increased risk of exposure. (Supported by a grant from Merck, Sharp and Dohme and the Hassel Foundation.)
Single-center experience with the HELEX septal occluder for closure of atrial septal defects in children.

Catheter closure of atrial septal defects (ASDs) is an accepted procedure among pediatric cardiologists. We report our early experience with the newest of these devices in clinical trials in the United States. Between April and October 2001, 14 patients were enrolled in an FDA phase II multicenter trial comparing the results of ASD closure using the HELEX™ Septal Occluder to a surgical control group. Of the 14 patients, devices were placed and left in 13, one being removed for an excessive residual leak despite placing the largest device available. Of the remaining 13 patients, all patients had successful closure of their defects. An average of 1.8 devices/patient were deployed, reflecting the learning curve for this new device and new delivery style. Six devices were replaced because of excessive residual leaks, three for premature lock release, and two for improper seating of the device. There were no procedural complications, however, one patient required device removal 4 months postimplant for possible allergic reaction to nickel. The same patient had removal of stainless steel sternal wires for the same reason. At the 6-month follow-up, 11 of 13 patients had complete closure of the ASD, the other two having small, hemodynamically insignificant left to right shunts. In one of these patients, there was complete closure at the 12-month follow-up, whereas the other patient awaits the 1-year evaluation. Early experience at our institution has demonstrated the ease of use of this device, its complete retrievability, and excellent closure of small to moderate ASDs in children. (J Interven Cardiol 2003;16:79–82)
Engineering Escherichia coli for odd straight medium chain free fatty acid production

Microbial biosynthesis of free fatty acids (FFAs) can be achieved by introducing an acyl–acyl carrier protein thioesterase gene into Escherichia coli. The engineered E. coli usually produced even chain FFAs. In this study, propionyl-CoA synthetase (prpE) from Salmonella enterica was overexpressed in two efficient even chain FFAs producers, ML103 (pXZM12) carrying the acyl-ACP thioesterase gene from Umbellularia californica and ML103 (pXZ18) carrying the acyl-ACP thioesterase gene from Ricinus communis combined with supplement of extracellular propionate. With these metabolically engineered E. coli, the odd straight chain FFAs, undecanoic acid (C11:0), tridecanoic acid (C13:0), and pentadecanoic acid (C15:0) were produced from glucose and propionate. The highest total odd straight chain FFAs produced by ML103 (pXZM12, pBAD-prpE) reached 276 mg/l with a ratio of 23.43 % of the total FFAs. In ML103 (pXZ18, pBAD-prpE), the highest total odd straight chain FFAs accumulated to 297 mg/l, and the ratio reached 17.68 % of the total FFAs. Due to the different substrate specificity of the acyl-ACP thioesterases, the major odd straight chain FFA components of ML103 (pXZM12, pBAD-prpE) were undecanoic acid and tridecanoic acid, while the ML103 (pXZ18, pBAD-prpE) preferred pentadecanoic acid.
Interferon-γ-independent CD8+ T cell-mediated protective anti-malaria immunity elicited by recombinant adenovirus

Recombinant adenovirus, expressing the CS protein of Plasmodium yoelii, AdPyCS, was shown to induce a comparable degree of T cell-mediated protection against malaria as a single dose of irradiated P. yoelii sporozoites, causing inhibition of liver stage development. We now report that differently from sporozoite-induced immunity, interferon (IFN)-γ does not mediate the protective immunity induced by AdPyCS, since a similar degree of protection was observed in AdPyCS immunized mice lacking IFN-γ−/− and the IFN-γ receptor (IFN-γR−/−) compared to that in wild-type mice. Depletion of CD8+ T cells from these immunized mice almost completely abolished the AdPyCS-induced immunity, indicating that the immunization with AdPyCS induces CD8+ T cell-mediated protective anti-malaria immunity, which is independent of IFN-γ.
Current Density versus Potential Characteristics of Dye-Sensitized Nanostructured Semiconductor Photoelectrodes. 1. Analytical Expressions

A closed-form analytical model is developed to describe the steady-state current density−potential (J−E) characteristics of dye-sensitized nanostructured semiconductor photoelectrodes. The basic components of the model are a set of differential equations that describe the generation, recombination, and transport of charge carriers in mesoporous semiconductor electrode systems. Charge-carrier transport is treated as a diffusion process, and semiclassical Marcus theory is used to describe the kinetics at the interfaces between the semiconductor and the contacting phase as well as the kinetics at the interfaces with adsorbed dye. The model relates explicitly, within a single formalism, the rate constants for charge transfer of the mesoporous membrane electrode system to conventional intramolecular and intermolecular electron-transfer rate constant expressions and to interfacial electron-transfer processes at planar metal or semiconductor electrodes. The near-equilibrium situation is considered by including t...
Dominant Negative Transcriptional Regulation by a Mutant Thyroid Hormone Receptor-β in a Family with Generalized Resistance to Thyroid Hormone

An abnormal human thyroid hormone beta-receptor (hTR beta-Mf), which has a glycine to arginine substitution in the hormone-binding domain, has been identified in affected members of one family with generalized resistance to thyroid hormone. To better understand the mechanism by which this mutation produces the observed abnormality, expression vectors for the wild-type and mutant thyroid hormone receptors (TRs) were prepared to test hormone-binding activity and trans-activation function. Nuclear extracts of COS-7 cells transfected with wild-type TRs showed specific T3-binding activity, while mutant receptor-transfected COS-7 nuclear extract failed to bind T3. On the other hand, in a avidin-biotin complex DNA-binding assay, in vitro translated hTR beta-Mf showed high binding activity to the thyroid hormone response element, which was indistinguishable from that of wild-type TRs. In a transient expression study, only the wild-type TRs activated a rat GH gene promoter-chloramphenicol acetyltransferase fusion gene in a T3-dependent manner. Additionally, when wild-type TR and hTR beta-Mf were cotransfected, hTR beta-Mf inhibited gene activation regulated by wild-type TRs. From these results we conclude that 1) hTR beta-Mf has no demonstrable T3 binding and appears to have minimal, if any, ability to activate a thyroid hormone-responsive gene in spite of its preserved ability to bind to a TRE in DNA; 2) hTR beta-Mf inhibits the transcriptional activation of a thyroid hormone-responsive gene by the wild-type TRs in a dominant manner; and 3) the dominant negative regulatory function of hTR beta-Mf appears to explain the clinical manifestations of thyroid hormone resistance produced by this mutation when present in the heterozygous state.
Older male partners high rates of incarceration and marginal economic activities in the sexual networks of a random digit dial sample of 14-19 year old economically disadvantaged African American youth.

Conclusions: To the extent that incarceration is correlated with STD risk the presence of a large percentage of male sex partners with a history of incarceration suggests that improved screening and treatment of incarcerated adolescents and young adults could benefit the reproductive health of all youth in the community. The disproportionate rates of STDs among African American female adolescents cannot be explained by their rates of high-risk sexual behaviors. Geographic segregation and partner selection may be more important determinants of their STD risk. (excerpt)
Advances in Conditioning Regimens for Older Adults Undergoing Allogeneic Stem Cell Transplantation to Treat Hematologic Malignancies

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.