cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract PR08: Altered nucleolar trafficking of the Blm helicase in the mouse reduces size, increases DNA damage and tumor susceptibility, and facilitates premature aging

Bloom9s syndrome (BS) is a recessive human chromosome breakage disorder caused by mutations in the recQ-like helicase BLM, sometimes known as RECQL2. Its clinical phenotype invariably includes male infertility, dwarfism, cancer susceptibility, and growth defects related to now characterized biochemical functions in DNA repair and rDNA transcription. The BLM protein includes two serines within a highly conserved carboxy-terminal nuclear localization sequence (NLS) that are critical for dynamic nucleolar trafficking of BLM where it facilitates rRNA transcription through direct interactions with RNA polymerase I and topoisomerase 1. CRISPR/Cas9-directed gene editing techniques generated homozygous murine models with these two conserved amino acids substituted by aspartic acids or alanines, and Blm proteins that were invariably excluded (DD) or constitutively localized (AA) within the nucleolus. Both protein isoforms retain biochemical functions and nuclear localization; BLM-/- cells transfected with the DD transgene display increases in nucleolar DNA damage compared to those transfected with the wild-type gene. BlmDD/DD mice with excluded Blm, but not BlmAA/AA mice, are smaller than their wild-type littermates at 8, 12, and 16 weeks of age; BlmDD/DD mice develop significantly more adenomas than littermates when crossed to the ApcMin/+ model of intestinal tumor formation. Finally, BlmDD/DD mice, but not their wild-type littermates, display signs of premature aging by one year of age, with weight loss, changes in coat color and quality, and spontaneous tumor formation. Our studies demonstrate functions for dynamic Blm nucleolar localization in maintaining stability of both the nucleolar and non-nucleolar genomes. A role for Blm/BLM in the prevention of aging is also exposed by these mouse models as only RecqL4 (RECQL4 mutations lead to Rothmund-Thomson syndrome in the human), but not Wrn/RecqL3 (WRN mutations lead to Werner9s syndrome in the human), localizes to the murine nucleolus. Both Werner9s syndrome and Rothmund-Thomson syndrome are associated with DNA repair deficiency, tumor susceptibility, and premature aging in the human. Our murine models also permit the definition of amino acid sequences and mechanisms that target or exclude proteins from the nucleolus. This abstract is also being presented as Poster A30. Citation Format: Michael McIlhatton, Max Fernandez, Samir Acharya, Vincenzo Coppola, Joanna L. Groden. Altered nucleolar trafficking of the Blm helicase in the mouse reduces size, increases DNA damage and tumor susceptibility, and facilitates premature aging [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr PR08.
Reforming Natural Gas Fracking Regulations in 2017–2018: How Should States Enforce Regulations?

While much scholarly work has been published on hydraulic fracturing regulatory frameworks, there is little discussion on the enforcement mechanisms of these regulations and statutes. This article ...
Evaluating utility and compliance in a patient-based eHealth study using continuous-time heart rate and activity trackers.

Telemedicine has been used to remotely diagnose and treat patients, yet previously applied telemonitoring approaches have been fraught with adherence issues. The primary goal of this study was to evaluate the adherence rates using a consumer-grade continuous-time heart rate and activity tracker in a mid-risk cardiovascular patient population. As a secondary analysis, we show the ability to utilize the information provided by this device to identify information about a patient's state by correlating tracker information with patient-reported outcome survey scores. We showed that using continuous-time activity trackers with heart rate monitors can be effective in a telemonitoring application, as patients had a high level of adherence (90.0% median usage) and low attrition (0.09% decrease per day) over a 90-day period. Furthermore, data collected correlated significantly with clinically relevant patient surveys (r2=0.15 for PROMIS global health scores, p < .00001), and therefore might provide an effective signal for identifying patients in need of intervention.
The difference between desistance from sexual offending and not reoffending

Scholars have generally relied on a lack of sexual recidivism as an indicator of desistance, which can be misleading because desistance and the lack of recidivism are two distinct construct...
In vitro cytotoxicity of glyco-S-nitrosothiols : a novel class of nitric oxide donors

The cytotoxicities of the nitric oxide (NO) donors, S-nitroso-N-acetylpencillamine (SNAP) and three glyco-SNAPs, glucose-1-SNAP, glucose-2-SNAP, and fructose-1-SNAP, towards the human gingival epithelioid S-G cell line and three human carcinoma cell lines derived from tissues of the oral cavity were compared using the neutral red (NR) assay. In general, the glucose-SNAPs were more cytotoxic than SNAP, which, in turn, was more cytotoxic than fructose-1-SNAP. Further studies focused on the response of S-G cells to glucose-2-SNAP. The cytotoxicity of glucose-2-SNAP was attributed to NO, as glucose-2-SNAP (t1/2=20 h at 28 degrees C) aged for 4 days was nontoxic, toxicity was eliminated in the presence of hydroxocobalamin, a specific NO scavenger, and toxicity was not noted with glucose-2-AP (the parent compound used to construct glucose-2-SNAP). Exposure of cells to glucose-2-SNAP resulted in a lessening of the intracellular level of glutathione and cells pretreated with the glutathione-depleter, 1,3-bis-(chloroethyl)-1-nitrosourea, were more sensitive to a subsequent challenge with glucose-2-SNAP. Cytotoxicity of glucose-2-SNAP was lessened upon coexposure with the antioxidants, myricetin, N-acetyl-L-cysteine, and L-ascorbic acid. S-G cells exposed to glucose-2-SNAP exhibited bi- and multinucleation. Death of S-G cells exposed to glucose-2-SNAP apparently occurred by apoptosis, as demonstrated with fluorescence microscopy by the appearance of brightly stained, hypercondensed chromatin in spherical cells and of membrane blebbing and by the DNA-ladder of oligonucleosome-length fragments noted with gel electrophoresis. In comparison with other classes of NO donors the sequence of toxicity towards S-G cells was S-nitrosoglutathione>glucose-SNAPs>SNAP, sodium nitroprusside>spermine NONOate>DPTA NONOate>DETA NONOate>fructose-1-SNAP>>SIN-1.
Marine Geography in Support of “Reefs at Risk”

In the landmark publication, Reefs at Risk: A Map Based Indicator of Threats to the World’s Coral Reefs (Bryant et al. 1998) of the World Resources Institute report the following sobering facts regarding the state of the world’s coral reefs: Fifty-eight percent of the world’s reefs (including 80 percent in Southeast Asia) are potentially threatened by human activity — ranging from coastal development and destructive fishing practices to overexploitation of resources, marine pollution, and runoff from inland deforestation and farming. Nearly half a billion people — 8 percent of the total global population — live within 100 kilometers of a coral reef. At least 40 countries lack any marine protected areas for conserving their coral reef systems. Scientists still do not know the actual condition of the vast majority of the world’s reefs. In the Pacific, for example, 90 percent of them have never been mapped or assessed.
Antibiotic resistance analysis of fecal coliforms to determine fecal pollution sources in a mixed-use watershed.

Antibiotic resistance analysis was performed on fecal coliform(FC) bacteria from a mixed-use watershed to determine thesource, human or nonhuman, of fecal coliform contamination. The study consisted of discriminant analysis of antibioticresistance patterns generated by exposure to fourconcentrations of six antibiotics (ampicillin, gentamicinsulfate, kanamycin, spectinomycin dihydrochloride,streptomycin sulfate, and tetracycline hydrochloride). Areference database was constructed from 1125 fecal coliformisolates from the following sources: humans, domestic animals(cats and dogs), agricultural animals (chickens, cattle, andhorses), and wild animals. Based on similar antibioticresistance patterns, cat and dog isolates were grouped asdomestic animals and horse and cattle isolates were grouped aslivestock. The resulting average rate of correctclassification (ARCC) for human and nonhuman isolates was94%. A total of 800 FC isolates taken from the watershedduring either a dry event or a wet event were classifiedaccording to source. Human sources contribute a majority(>50%) of the baseflow FC isolates found in the watershed inurbanized areas. Chicken and livestock sources areresponsible for the majority of the baseflow FC isolates foundin the rural reaches of the watershed. Stormwater introducesFC isolates from domestic (∼16%) and wild (∼21%) sourcesthroughout the watershed and varying amounts (up to 60%) fromchicken and livestock sources. These results suggest thatantibiotic resistance patterns of FC may be used to determinesources of fecal contamination and aid in the direction ofwater quality improvement.
Challenges of massive parallelism

Artificial Intelligence has been the field of study for exploring the principles underlying thought, and utilizing their discovery to develop useful computers. Traditional AI models have been, consciously or subconsciously, optimized for available computing resources which has led AI in certain directions. The emergence of massively parallel computers liberates the way intelligence may be modeled. Although the AI community has yet to make a quantum leap, there are attempts to make use of the opportunities offered by massively parallel computers, such as memory-based reasoning, genetic algorithms, and other novel models. Even within the traditional AI approach, researchers have begun to realize that the needs for high performance computing and very large knowledge bases to develop intelligent systems requires massively parallel AI techniques. In this Computers and Thought Award lecture, I will argue that massively parallel artificial intelligence will add new dimensions to the ways that the AI goals are pursued, and demonstrate that massively parallel artificial intelligence is where AI meets the real world.
An action principle for the motion of particles

An action principle is set up for the motion of charged matter in the presence of the Einstein gravitational field. It can be applied to the motion of an extended particle and avoids the difficulties of a point particle arising from the singularities in the field.
Inverted solvatochromic Stokes shift in GFP-like chromophores with extended conjugation†

Chromophore structures inspired by natural green fluorescent protein (GFP) play an important role in the field of bio-imaging. In this work, photochemical properties of a new class of GFP-like chromophores are investigated using computational approaches. Thermo-dynamically stable isomers are identified in vacuum and in solvent. Spectral Stokes shifts are computed and compared to experiments. An inverted solvatochromic shift between absorption and emission emerging in this new class of GFP-like chromophores is observed, and attributed to the stabilized charge transfer and inhibited rotational structural reorganization in solvent.
Engaging patients in health care epidemiology research: A case example.

Background We describe stakeholder engagement from a Patient-Centered Outcomes Research Institute–funded project to identify patients’ research priorities for health care–associated infections (HAI). We summarize insights from these activities to highlight feasibility and benefits of stakeholder engagement in health care epidemiology research.Patients and caregivers who had an HAI experience were involved in a patient and caregiver stakeholder group. We engaged clinicians, infection prevention experts, state public health professionals, and quality improvement experts in an institutional stakeholder (IS) group in an academic tertiary care medical center. Methods Through individual and combined group activities, we identified stakeholders’ HAI research priorities. Existing engagement resources from the Wisconsin Network for Research Support (WINRS) guided the process. Results Given the patients’ and caregivers’ experiences with HAIs, their perspectives broadened IS understanding of the impact of HAIs and the relevance of proposed research topics. After introductory activities described here, the patient and caregiver stakeholder group actively engaged with researchers and the IS group in discussing complex systems-level topics to reduce HAIs. We have sustained this engagement through continued collaboration. Conclusions Our engagement experience provides one example of how patients can be engaged in health care epidemiology research. Our experiences and lessons learned may be helpful to others interested in stakeholder engagement.
Topics in Functional Differential Equations

In this paper, we provide a concise presentation of the book "Functional Differential Equations: Advances and Applications" by Constantin Corduneanu, Yizeng Li, and Mehran Mahdavi, a research monograph, published by Wiley, 2016. The book contains five chapters, an Appendix, and a bibliography which includes more than five hundred fifty references. In each chapter, except the first one, there is a section, bibliographical notes, in which numerous references and their relationships to our work are provided. The book presents only part of the results available in the literature, mainly mathematical ones, without any claim related to the coverage of the whole field of functional differential equations or functional equations. The book also includes many applications of the results.
Black Men Who Have Sex with Men and Lifetime HIV Testing: Characterizing the Reasons and Consequences of Having Never Tested for HIV

HIV testing remains a critical point of entry to HIV treatment services and now biomedical prevention as well. Yet despite the high HIV prevalence among Black men who have sex with men (MSM), insufficient attention has been given to factors associated with those Black MSM in the United States who have never received an HIV test in their lifetime. Promoting Our Worth, Equality, & Resilience (POWER) is a cross-sectional observational study that recruited Black MSM at Black Pride events across six cities in the United States from 2014 to 2017. Participants completed an anonymous questionnaire and were offered free, confidential HIV testing. Of the 4174 Black MSM without a prior HIV diagnosis, 404 (9.68%) had never tested for HIV (mean age = 31.03 years). Lower education and greater internalized homophobia were associated with never having tested for HIV. Higher age (AOR = 1.05, 95%, 1.02–1.07) and assumption of HIV-positivity (AOR = 3.24, 95% CI 1.53–6.84) were both associated with increased odds of an HIV-positive test result (n = 119; 36%). To compare, HIV prevalence among Black MSM who had received at least one HIV test before study participation was 23%. While a minority of Black MSM had never received an HIV test, this group had a significantly higher likelihood of HIV infection. Alternative HIV testing strategies are needed to facilitate HIV testing initiation among Black MSM for whom conventional HIV testing modalities are insufficient.
A quantitative understanding of the role of co-composted biochar in plant growth using meta-analysis.

Abstract The combined use of biochar and compost as a soil amendment presents benefits to crops and nutrient cycling. Although there are literature reviews regarding biochar and biochar-compost mixtures, a quantitative literature review on the role of co-composted biochar (hereby called COMBI) in plant productivity is currently missing. The goal of this review paper is to find evidence-based measures of the effects of application rates, soil pH, plant types, biochar feedstock, and compost materials, on plant productivity. Plant productivity covers a variety of measurements but mostly refers to grain yield and above-ground biomass. Response ratio was selected as the effect size. Funnel plot showed that the studies were reasonably symmetrically distributed around the mean effect size. Results showed that application rates of 30 t/ha significantly increased plant productivity by 48.3 and 15.7%, respectively, while no significant yield increases were found for the application rates between 20 and 30 t/ha. When data was grouped based on the soil pH, the greatest increase in plant productivity was found to be at acidic soil pH values (pH 4–5), which was expected because the liming effect of biochar is often reported as one of the main mechanisms behind the increased crop yields. When different plant species were compared, cereal grasses grown with COMBI yielded significantly higher grain yields (39.7%). Rice husk biochar yielded the highest increase in productivity but this result was based on only one study. The second highest increase was obtained with wood-based biochars (29.4%) based on ten studies. The effect sizes found with our meta-analyses are based on 14 research works worldwide and represent the most updated information regarding the effects of COMBI on plant production. As more data on COMBI become available, data analyses can be updated to make more robust comparisons.
A Dynamic Systems Approach to Understanding Mindfulness in Interpersonal Relationships

Major components of mindfulness, such as the development of empathy and compassion and the sharing of experience between people, necessitate a consideration of interpersonal relationships. The purpose of this paper is to review the literature on interpersonal mindfulness to-date and present a new way to conceptualize and measure mindfulness as it is cultivated and developed in interpersonal relationships. We reviewed empirical literature on mindfulness in relationships and current conceptualizations and measures of mindfulness. Specifically, we focused attention on mindfulness in parenting and how cultivation of mindfulness impacts the parent–child interactions. Empirical investigations of mindfulness have largely centered on the intrapersonal and have rarely involved both intra- and interpersonal components of human experience. Further, although mindfulness is thought to involve the moment-to-moment awareness of human experience as it unfolds over time, empirical studies rarely measure mindfulness as a dynamic construct. We suggest that dynamic systems theory can provide a useful framework in understanding how mindfulness both organizes and is organized by interpersonal interactions. We discuss several ways in which dynamic systems theory can inform the conceptualization of mindfulness as a process that takes place both within and between individuals. Finally, we present examples of how fine-grained and time-varying methods rooted in dynamic systems theory and currently utilized in human development research can be applied to understanding how mindfulness is manifested within close interpersonal relationships.
Undergraduate nursing students' pharmacology knowledge and risk of error estimate.

Abstract Background In the United States alone, medication error causes injury to approximately 1.3 million people every year. Frequently, nurses have been blamed for the high rates of medication administration errors. Factors associated with medication error by nurses are categorized as personal, contextual and knowledge-based. There is evidence in the literature that showed nurses have insufficient knowledge in pharmacology. Purpose The overall purpose of this study was to estimate the risk of error based on the combined scores on pharmacology knowledge and self-rated certainty scores of undergraduate nursing students. Method A cross-sectional and correlational study was conducted. Students enrolled in an undergraduate nursing program who completed or were currently taking the pharmacology course were eligible for the study. Based on power analysis, a sample of 156 students was needed to reach 80% power with a level of significance of 0.05. A 42-item Pharmacology Knowledge Questionnaire (PKQ) test was administered, and students were asked to provide their level of certainty for each of their answers. Risk of error was calculated based on the combined scores in PKQ and self-rated certainty scores. Results 147 nursing students, 83% females with a mean age of 24 (SD = 5) years, participated in the study. Mean score in the PKQ was 25 (SD = 3.51) out of 42 items, which is equivalent to a grade of 60% (with a calculated weighted mean grade of 56%). Drug calculation was the subject area where students had the lowest mean score. Mean overall risk of error for all 42 items in the PKQ was 1.7 (SD = 0.14), on a scale of 0–3. This means that, on average, high risk of error was noted in 14% of the students who rated incorrect answers with high certainty. Positive correlations were noted between age and pharmacology score, and between when pharmacology course was last taken and risk of error. A negative correlation was noted between when pharmacology course was last taken and pharmacology score.
Improved Performance Guarantees for Orthogonal Group Synchronization via Generalized Power Method.

Given the noisy pairwise measurements among a set of unknown group elements, how to recover them efficiently and robustly? This problem, known as group synchronization, has drawn tremendous attention in the scientific community. In this work, we focus on orthogonal group synchronization that has found many applications, including computer vision, robotics, and cryo-electron microscopy. One commonly used approach is the least squares estimation that requires solving a highly nonconvex optimization program. The past few years have witnessed considerable advances in tackling this challenging problem by convex relaxation and efficient first-order methods. However, one fundamental theoretical question remains to be answered: how does the recovery performance depend on the noise strength? To answer this question, we study a benchmark model: recovering orthogonal group elements from their pairwise measurements corrupted by Gaussian noise. We investigate the performance of convex relaxation and the generalized power method (GPM). By applying the novel~\emph{leave-one-out} technique, we prove that the GPM with spectral initialization enjoys linear convergence to the global optima to the convex relaxation that also matches the maximum likelihood estimator. Our result achieves a near-optimal performance bound on the convergence of the GPM and improves the state-of-the-art theoretical guarantees on the tightness of convex relaxation by a large margin.
Space Technology and Africa's Development: The Strategic Role of Small Satellites

In 2014 the African Union adopted a 10-year Science, Technology and Innovation Strategy for Africa (STISA-2024). The strategy provides a flexible framework for adopting flagship programs that involve a number of countries based on their needs, capabilities and long-term development objectives. Some areas of technological endeavor, however, represent foundations upon which economic activities are constructed. One of those areas is building geospatial data infrastructure. This can be achieved through a variety of data-collecting measures ranging from large satellites to unmanned aerial vehicles. The opportunity to use remote sensing technology for development has never been greater. There are over 100 remote sensing satellites currently in orbit, with over half designed to gather imagery that could be used for development. The industry is also growing: the OECD estimates that over 250 satellites will be launched during this decade alone, compared to half that amount during the last decade. Recent innovations around satellite technologies have also driven down costs and made it viable for low-income countries to develop cost-effective satellite programs. This paper examines small satellite programs as windows of opportunity for countries to achieve their development goals. First, it locates the potential socioeconomic benefits of satellites in low-income countries. Next, it explores the recent history of, and lessons learned by, South Africa, Brazil, and South Korea. While tens of other countries have developed satellite programs, these case studies offer insights into how and why countries have created successful programs. Next, this chapter examines the latest technologies and focuses on emerging opportunities for current and future space programs. Lastly, it develops concrete options and a clear strategy for policymakers in emerging markets to consider when designing future programs.
Policy Spotlight: Women's Housing Precarity During and Beyond Covid-19

As state and federal eviction moratoriums expire, millions of people across the country face the possibility of losing their homes, and the disparate impact of COVID-19 on women's economic prospects makes them especially vulnerable to eviction. This Policy Spotlight illustrates how everyday gender disparities contribute to housing instability for women and describes how COVID-19 amplified these disparities. The authors offer suggestions for policymakers looking to not only stem the coming wave of evictions but also to help women and families find long-term stability.
U.S. Family Forest Owners' Forest Management for Climate Adaptation: Perspectives From Extension and Outreach Specialists

In the United States (US), family forest owners, a group that includes individuals, families, trusts, and estates, are the largest single landowner category, owning approximately one-third of the nation’s forests. These landowners’ individualized decision-making on forest management has a profound impact on US forest cover and function at both local and regional scales. We sought to understand perceptions among family forest specialists of: climate impacts and adaptation options across different forested US regions; how family forest owners are taking climate adaptation into consideration in their forest management, if at all; and major barriers to more active management for adaptation among family forest owners. We conducted semi-structured interviews with 48 forest experts across the US who work with family forest owners, including extension specialists, state forestry agency employees, and consulting foresters who focus on family forest engagement. Our interviewees shared details on how both climate change impacts and forest management for climate adaptation vary across the US, and they perceived lack of active forest management by family forest owners. They explained that western forest landowners confronting the imminent threat of catastrophic wildfires are more likely to see a need for active forest management. By contrast, in the east, where most forestland is privately owned, interviewees said that landowners see relatively fewer climate impacts on their forests and less need for forest management to respond to climate change. Perceived barriers to more active family forest management for climate adaptation include the lack of more robust markets for a wide range of forest products, a higher capacity forestry workforce, education and assistance in planning forest management, and addressing the issue of increased parcelization of family forest lands. We situate these perceptions in conversations on the role of boundary organizations in climate adaptation, how individual adaptation occurs, and how governing methods frame adaptation possibilities.
Concentration of land holdings: An empirical exploration of Kuznets' conjecture

Abstract According to Kuznets (1963), the dynamics of the maldistribution process starts from an initial unequal income distribution, then through a cumulative effect, a high concentration of asset holdings is induced which in turn contributes to a high concentration of income. In other words, unequal income distribution tends to be self-perpetuated and unequal asset holdings is a medium of such process. The literature on rural income distribution seems to suggest a different emphasis by assigning a more crucial role to asset holdings, i.e., land, in the explanation of unequal income distribution. This study shows, via a simultaneous equation model and a multi-nation cross-sectional set of data, that both the land and income concentration ratios are positively related. Of the two rival conjectures of emphasis, the empirical evidence lends support in the general case to Kuznets, that is, over the entire range of countries, developed and less-developed, inequality in income seems to cause inequality in land holdings rather than vice-versa In the specific case of less developed countries, it is the high concentration of land holdings that influences the unequal distribution of income.
Silicon bipolar transistor design and modeling for microwave integrated circuit applications

This paper summarizes the recent progress in the fabrication, design, and modeling of silicon and Si/SiGe bipolar transistors for high-frequency microwave integrated circuit applications. These devices are now capable of performance levels that were only achievable with GaAs technology just a few years ago. The specific device requirements for low-noise signal and power amplifiers are discussed, as well as required improvements in device modeling for these applications.
Automatic creation of web services from extraction ontologies

The Semantic Web promises to provide timely, targeted access to user-specified information online. Though standardized services exist for performing this work, specifying these services is too complex for most people. Annotating these services is also problematic. A similar situation exists for traditional information extraction, where ontologies are increasingly used to specify information used by various extraction methods. The approach we introduce in this paper involves converting such ontologies into executable Java code. These APIs act individually or compositionally as services for Semantic Web extraction.
Paths to the Assembly in British North America: New Brunswick, 1786-1837

During the late 18th and early 19th centuries, New Brunswick assemblymen followed paths to the assembly that conformed to colonial British American standards. These paths included securing appointments to important local offices and accumulating wealth and economic influence. Because many first-generation assemblymen successfully transferred these assets to their political heirs, prominent social origins and the family connections that accompanied them had become important components of electoral success by the time that the colony’s second generation of elected political leaders entered the assembly during the 1810s and 1820s. This development signified the emergence of local oligarchies in numerous New Brunswick constituencies. Resume A la fin du 18e siecle et au debut du 19e siecle, les deputes du Nouveau-Brunswick emprunterent des voies menant a l’Assemblee qui etaient conformes aux normes de l’Amerique coloniale britannique. Ces voies comprenaient l’obtention de nominations a des postes importants sur la scene locale et l’accumulation de richesse et d’influence economique. De nombreux deputes de la premiere generation reussirent a transmettre ces atouts a leurs heritiers politiques, de sorte que les origines sociales distinguees et les liens familiaux qui les accompagnaient etaient devenus d’importants facteurs de succes electoral au moment ou la deuxieme generation de dirigeants politiques elus de la colonie firent leur entree a l’Assemblee, dans les annees 1810 et 1820. Cette situation entraina l’emergence d’oligarchies locales dans de nombreuses divisions electorales du Nouveau-Brunswick.
The changing face of post‐transplant lymphoproliferative disease in the era of molecular EBV monitoring

Pediatric PTLD is often associated with primary EBV infection and immunosuppression. The aim was to retrospectively review the spectrum of histologically documented PTLD for two time intervals differentiated by changes in use of molecular EBV monitoring. Eleven of 146 patients (7.5%) in 2001-2005 (Era A) and 10 of 92 (10.9%) in 1993-1997 (Era B) were diagnosed with PTLD. The median age at liver transplantation (0.8 and 0.9 yr, respectively) and the median duration between liver transplant and diagnosis of PTLD (0.6 and 0.7 yr, respectively) were similar in both eras. However, patients in Era A presented with significantly less advanced histological disease compared to patients in Era B (p=0.03). Specifically, nine patients (82%) in Era A had Pl hyperplasia/polymorphic PTLD, whereas in Era B, six had advanced histological disease (five monomorphic and one unclassified). Three transplant recipients in Era B died secondary to PTLD, whereas there were no PTLD-related deaths in Era A (p=0.03). Heightened awareness of risk for PTLD, alterations in baseline immunosuppression regimens, implementation of molecular EBV monitoring, pre-emptive reduction in immunosuppression and improved therapeutic options may have all contributed to a milder PTLD phenotype and improved clinical outcomes.
Development and characterization of a novel 177Lu-MeO-DOTA-7E11 antibody construct (CYT-500) for the treatment and imaging of prostate adenocarcinoma

4745 Background: The effective treatment of prostate cancer is a significant clinical problem. Prostate-specific membrane antigen (PSMA) is overexpressed by prostate cancer cells. The anti-PSMA monoclonal antibody 7E11 labelled with 111 In via the chelator GYK-DTPA (CYT-356) is currently FDA approved for clinical imaging. We have developed a stable methoxy-DOTA-linked conjugate to 7E11 (CYT-500), labelled with the beta and gamma emitter 177 Lu, and compared it to CYT-356 in a LNCaP-bearing mouse model. Compared to CYT-356, CYT-500 exhibits favorable biodistribution and may be an effective radioimmunotherapeutic for prostate cancer. Methods: DOTA-7E11 immunoconjugates were formed under various conditions and characterized using SDS-PAGE and HPSEC for purity and molecular weight and MALDI-MS for chelator:antibody ratio. Specificity and biological activity were evaluated with immunoaffinity binding ELISA targeting the PSMA N-terminal epitope recognized by 7E11. Optimal 177 Lu radiolabelling conditions were determined. PK studies were performed in mice. Acute and expanded acute toxicology studies were conducted in rats and dogs, and safety pharmacology studies in dogs. Pharmacokinetics and biodistribution studies of CYT-500 and CYT-356 were performed in LNCaP xenograft mice at 2, 8, 12, 24, 72 and 168 hrs. Studies of CYT-500 were performed in non-tumor-bearing controls at 8, 24 and 72 hrs. Optical imaging and single-photon emission computed tomography were performed, followed by autoradiography and tissue counting to assess the distribution of the agents in tumor and normal tissues. Results: Conjugation of me-O-DOTA to 7E11 (CYT-500) has been achieved using conditions that preserve the integrity of 7E11 and its PSMA binding ability. Molar ratios of linker to antibody range from 0.2 to 5.3. Radiolabelling to activities in excess of 20 mCi/mg is achieved in 10-20 minutes at room temperature. Purity is 96% to 98%. There is little radiolabel loss in vitro or in vivo . PK studies in mice show a favorable clearance pattern. Biodistribution and imaging studies demonstrate significant tumor uptake (injected radioactivity of 0.3% to 2.2% in 12 animals ranging from 6 hrs to 13 days). Acute and expanded acute toxicology studies in rats and dogs, respectively, and safety pharmacology studies in dogs showed no significant adverse reactions at doses up to 20 times the anticipated human dose. In the imaging studies, both 177 Lu- and 111 In-7E11 conjugates demonstrated an early blood pool phase with uptake dominated by the blood, lung, spleen and liver, followed by prominent tumor uptake and retention after 24 hours. Uptake of 177 Lu MAb in tumor was notably higher than that of 111 In MAb at 24 hours. Only the liver differed significantly, with the 111 In-7E11 demonstrating continued uptake after 72 hours. Conclusions: A 177 Lu-labeled radioimmunoconjugate has been developed. The biological and physical characteristics of this agent support its use for therapy and imaging of prostate cancer.
Measurement science and manufacturing science research

The research program of Semiconductor Research Corp. is managed as three overlapping areas: Manufacturing Sciences, Design Sciences and Microstructure Sciences. A total of 40 universities are participating in the performance of over 200 research tasks. The goals and direction of Manufacturing Sciences research became more clearly focused through the efforts of the Manufacturing Sciences Committee of the SRC Technical Advisory Board (TAB). The mission of the SRC Manufacturing Research is the quantification, control, and understanding of semiconductor manufacturing process necessary to achieve a predictable and profitable product output in the competitive environment of the next decade. The 1994 integrated circuit factory must demonstrate a three level hierarchy of control: (1) operation control, (2) process control, and (3) process design. These levels of control are briefly discussed.
Conjugate gradient method for adaptive nonlinear filtering

The application of the Conjugate Gradient (CG) method for the identification of a new class of non-linear discrete time systems, called "Generalized Bilinear System" is investigated. An algorithm based on the CG method is developed for adaptive generalized bilinear filtering with output error method. This algorithm outperforms the LMS and RLS methods in terms of speed of convergence. In this algorithm, the optimization is done over blocks of input and output data rather than a single pair of data. However, only one iteration and coefficient update is done for every sample of data. Some examples are given to illustrate the efficiency of the algorithm.
Towards a Theory of Galaxy Formation

The theories of star and galaxy formation are intimately related. Unfortunately, there is no accepted theory of star formation, despite the fact that laboratories where stars are currently forming exist within 200 pc of the sun. This may suggest that attempting to understand how galaxies formed would be a futile endeavor. However such a prospect has never deterred theoreticians, and this lecture is devoted to describing some aspects of how star formation processes are relevant to galaxy formation. I commence by discussing the formation of the first stars in the collapsing protogalactic gas cloud. I then examine the characteristic parameters of the old spheroidal components of galaxies, and show how important a role star formation processes must have played in their development and evolution.
Short-term wind forecasting using spatial and temporal wind measurements

Wind intermittency is the main obstacle to wider integration of wind generation. Jay Apt et. al. claim that wind power generation is so unreliable that 100% of scheduled wind generation must be backed up by spinning non-renewable generators. We believe that the requirements for spinning reserve can be reduced by effective short-term forecasting on both spatial and temporal information. Although similar work has been reported [1] in the past, we analyze the available information using different data sets and machine learning methods to provide a comparison of multiple statistical approaches. The training data includes historical wind speed and direction at locations close to the site of interest. The used machine learning methods are sequential minimal optimization (SMO) regression, linear regression, multilayer perceptron, and a Radial Basis Function (RBF) neural network.
In Vivo and In Vitro Action of Norethindrone on Staphylococci

Norethindrone has been examined in vitro for antibacterial activity against 10 microorganisms. Turbidimetric techniques were used to assay the antibacterial activity of norethindrone. The organisms tested included Staphylococcus aureus, S. epidermidis, Micrococcus conglomeratus, Listeria monocytogenes, Streptococcus faecalis, Salmonella typhosa, Shigella flexnerii, Klebsiella pneumoniae, Escherichia coli, and Proteus vulgaris. Bacteriostatic action was shown only against the gram-positive microorganisms when they were grown anaerobically in Tryptic Soy Broth containing 10 to 50 mug of norethindrone per ml. The bacteriostatic action of norethindrone was exerted primarily during the first 8 hr of incubation and it was reduced by the presence of oxygen. Mestranol at a concentration of 1 to 10 mug/ml failed to exert any significant action on S. aureus. However, incorporation of 5 mug of mestranol per ml in the culture medium enhanced the bacteriostatic action of norethindrone on staphylococci. Enhancement of the bacteriostatic action of norethindrone could not be obtained by the addition of a concentration of 5 mug/ml of testosterone, 17alpha-estradiol, and 17beta-estradiol. Progesterone and 4-pregnen-20beta-ol-3-one under similar conditions showed an additive bacteriostatic effect when they were incorporated into the culture medium containing norethindrone. In vivo studies indicated that female, adult New Zealand rabbits, injected subcutaneously with two injections of 10 to 20 mug of norethindrone, 24 hr apart, and challenged intradermally with S. aureus 4 hr after the second injection, had fewer lesions with smaller areas of swelling and erythema as compared to control, nontreated rabbits. The protective effect of norethindrone on the development of staphylococcal lesion seemed related to hormone concentration. Thus, it was demonstrated with doses of 20, 15, and 10 mug, but not with doses of 1 and 5 mug. When the lesions were excised 48 to 92 hr after infection and when viable cell counts were made, rabbits treated with norethindrone showed significantly lower staphylococcal counts than the control rabbits. During the 1st day after infection with S. aureus, leukocytic counts of the norethindrone-treated rabbits remained normal, whereas control animals showed elevated leukocytic counts.
Wingless can't fly so it hitches a ride with dynein

Asymmetric RNA localization is required for many developmental processes in a wide range of organisms. For example, wingless and pair-rule transcripts are localized to the apical membrane of polarized cells. It has been unclear, however, if this localization is important for biological activity and, in addition, how the transcripts are transported. Two recent studies(1,2) have identified cis-elements and trans-acting factors that are required for the asymmetric localization of mRNAs. Correct localization is shown to be required for biological activity, and a mechanism of RNA transport involving the microtubule motor dynein has been revealed. BioEssays 23:869–872, 2001. © 2001 John Wiley & Sons, Inc.
The second Sovietology

In his paper ‘Why Studies in Soviet Philosophy’1 Professor Bochenski advanced two premisses to substantiate the theoretical as well as practical import of philosophical Sovietology: “(i) not all Soviet philosophy is nonsense; on the contrary, much of it is philosophically interesting; (ii) Soviet philosophy is not irrelevant; it is an important factor in the phenomenon of Communism which, as everybody will agree, is important both theoretically and practically.”2 Among the additional reasons for engaging in Sovietology Bochenski gives overcoming that kind of philosophical sectarianism which makes Western thinkers unwilling to give serious consideration to the work of their Soviet colleagues.3
Work Status and Work Performance of People With Disabilities: An Empirical Study

As the U.S. economy is thrust into the global economy and meets global economic competition, the country needs to mobilize people with disabilities to participate in the labor force and enable them...
Tachycardia-induced cardiomyopathy

Systolic dysfunction associated with chronic tachyarrhythmias, known as tachycardia-induced cardiomyopathy, is a reversible form of heart failure characterized by left ventricular dilatation that is usually reversible once the tachyarrhythmia is controlled. Its development is related to both atrial and ventricular arrhythmias. The diagnosis is usually made following observation of a marked improvement in systolic function after normalization of heart rate. Clinicians should be aware that patients with unexplained systolic dysfunction may have tachycardia-induced cardiomyopathy, and that controlling the arrhythmia may result in improvement and even complete normalization of systolic function.
Hypertension and Healthy People 2020: The Role of Health Insurance Expansion

Hypertension remains one of the most prevalent and treatable risk factors for cardiovascular disease and is associated with an enormous public health burden in terms of morbidity, mortality, and healthcare spending.1 Both clinical and policy interventions have important roles to play in primary prevention, prompt diagnosis, and appropriate treatment. However, although the tools at clinicians’ disposal for managing hypertension have proliferated over the past decades, policy makers continue to struggle with a refractory set of social and economic determinants of health in this area. With nearly 50 million Americans lacking any health insurance2 and millions more underinsured and exposed to high out-of-pocket costs,3 financial barriers play an important role in preventing the appropriate management of chronic diseases such as hypertension, particularly in lower-income populations. The year 2014, with the full implementation of the Affordable Care Act (ACA), brings with it a dramatic change to the set of policies in place to help tackle these challenges. Article see p 1692 In this week’s issue of Circulation , Egan and colleagues4 present findings on the nation’s progress toward meeting Healthy People 2020 goals for the management of hypertension. Their careful analysis of nearly 15 years of data from the National Health and Nutrition Examination Surveys shows that although progress has been made since 1999 in some areas, most notably in the proportion of adults treated and the proportion with adequate control, there have been no changes in the prevalence of hypertension. Furthermore, the proportion of treated individuals under adequate control has plateaued in recent years and remains roughly 20 percentage points below the Healthy People goal of 88%. How, if at all, will the ACA affect these figures? The main mechanism by which the ACA …
Crystal Structure of Mycobacterium tuberculosis MenB, a Key Enzyme in Vitamin K2 Biosynthesis

Bacterial enzymes of the menaquinone (Vitamin K2) pathway are potential drug targets because they lack human homologs. MenB, 1,4-dihydroxy-2-naphthoyl-CoA synthase, the fourth enzyme in the biosynthetic pathway leading from chorismate to menaquinone, catalyzes the conversion of O-succinylbenzoyl-CoA (OSB-CoA) to 1,4-dihydroxy-2-naphthoyl-CoA (DHNA-CoA). Based on our interest in developing novel tuberculosis chemotherapeutics, we have solved the structures of MenB from Mycobacterium tuberculosis and its complex with acetoacetyl-coenzyme A at 1.8 and 2.3 A resolution, respectively. Like other members of the crotonase superfamily, MenB folds as an (α3)2 hexamer, but its fold is distinct in that the C terminus crosses the trimer-trimer interface, forming a flexible part of the active site within the opposing trimer. The highly conserved active site of MenB contains a deep pocket lined by Asp-192, Tyr-287, and hydrophobic residues. Mutagenesis shows that Asp-192 and Tyr-287 are essential for enzymatic catalysis. We postulate a catalytic mechanism in which MenB enables proton transfer within the substrate to yield an oxyanion as the initial step in catalysis. Knowledge of the active site geometry and characterization of the catalytic mechanism of MenB will aid in identifying new inhibitors for this potential drug target.