cssi/SciSciGPT-SciSciNet huggingface dataset:
Use of MMV as a Single Worst-Case Model Virus in Viral Filter Validation Studies

Typical platform processes for biopharmaceutical products derived from animal cell lines include a parvovirus filtration unit operation to provide viral safety assurance of the drug product. The industry has adopted this platform unit operation and gained a wider understanding of its performance attributes, leading to the possibility of streamlined approaches to virus clearance validation. Here, the concept of virus validation on a parvovirus-grade filter with a single worst-case model virus is presented. Several lines of evidence, including published literature and Amgen9s own data, support the use of a parvovirus, such as mouse minute virus (MMV), as a worst-case model virus to assess virus removal by parvovirus filters. The evidence presented includes a discussion of the design and manufacture of virus filters with a size exclusion mechanism for removal. Next, the characteristics of different model viruses are compared and a risk assessment on the selection of the relevant model viruses for clearance studies is presented. Finally, a comprehensive summary of literature and Amgen data is provided, comparing the clearance of larger viruses against MMV. Together, this analysis provides a strong scientific rationale for the use of a single, worst-case model virus for assessing virus removal by parvovirus filters, which will ultimately allow for more efficient and streamlined viral clearance study designs. LAY ABSTRACT: Demonstrating the virus clearance capability of a purification process is an important aspect of biopharmaceutical process development. A key component of the viral safety of the process is the inclusion of a parvovirus-grade filter as an effective and robust virus removal step. Traditional methodologies for viral clearance studies have been based on a conservative, data-intensive approach, but recent trends in the field of virus clearance and process development show evolution towards streamlined and more efficient study designs that are based on understanding the mechanism of viral clearance by downstream unit operations. The publication of scientific datasets and awareness of the underlying mechanisms involved with these unit operations have fueled this trend. Here, the concept of virus validation on a parvovirus-grade filter using a parvovirus as single, worst-case model virus is presented. Multiple lines of evidence are provided to support this proposal, including a review of published literature and Amgen historical data. The adoption of this approach provides benefits in terms of cost savings for executing viral clearance studies, but it also simplifies the necessary dataset and focuses on only supplying value-added information to demonstrate the viral safety of the process.
Impairments in static standing balance are highly prevalent among older adults receiving home-based physical therapy.

BACKGROUND AND PURPOSE Measures of balance are an important component of the physical therapist examination. This study investigated the usefulness of timed static stance durations for identifying balance impairments among patients receiving home-based physical therapy. METHODS This study involved the retrospective retrieval of data from the records of 48 patients at least 60 years of age. Their balance was measured under 3 foot configurations; that is, feet apart, feet together, and on each foot. RESULTS Every patient demonstrated impaired standing balance. Most, but not all could balance 30 seconds with the feet apart or together. Only 19 could maintain balance on each of both feet. Of those who could so balance, none was able to achieve the average time of normal individuals of comparable age. DISCUSSION AND CONCLUSIONS Although not able to identify all aspects of balance, timed durations of stance under different configurations demonstrate a high prevalence of balance impairments among patients receiving home-based physical therapy. As the tests are objective, fast, and require little space, they can be advocated in such a setting.
Understanding scoping reviews: Definition, purpose, and process

Background/purpose Scoping review design represents a methodology that allows assessment of emerging evidence, as well as a first step in research development. Despite its increasing use, to date no article reflecting use of scoping review methodology has been submitted for review at JAANP. The purpose of this article is to provide detailed information on scoping reviews, including definition, related processes, and uses, and discuss the relationship to nurse practitioner (NP) practice, policy, education, and research. The longer-term goal is that NPs will understand the related techniques, consider the methodology as a viable one for NP scholarship, and bring related reports to the forefront of NP publications. Methods This manuscript represents a brief report. Processes to develop the brief include detailed search and review of scoping review literature in CINAHL and PubMed. Both methodologic reports and reviews were included. Definitions and uses of scoping reviews were reviewed. Conclusion The definition and process of scoping review are evolving. Although there is controversy regarding the methodology, there is increasing visibility of scoping review methodology in the published literature since the year 2000, with over 500 published reviews currently available. Implications for practice A well-executed scoping review has potential to inform NP practice, policy, education, and research.
Comparison of salicylate and D-phenylalanine for detection of hydroxyl radicals in chemical and biological reactions.

SummaryHydroxylation of salicylate and D-phenylalanine was measured to test the usefulness of these compounds for hydroxyl radical (HO•) detection in chemical and biological systems. When HO• were produced by the photolytic decomposition of hydrogen peroxide, nearly equal amounts of 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were produced from salicylate, with catechol as a minor product. In the photolytic reaction, nearly equal concentrations of p-,m-, and o-tyrosine were formed from D-phenylalanine. When salicylate or D-phenylalanine was present with Fenton reagents or in iron(II) autoxidation systems, the relative proportions of hydroxylated products were similar to those observed after photolysis, although less total products were usually detected. In contrast, when similar experiments were conducted with isolated hepatic microsomes and perfused livers, 2,5-DHBA was the primary product from salicylate, and p-tyrosine was the major product from D-phenylalanine. Cytochrome P-450 enzymes can hydroxylate s...
Femtosecond Studies of Electrons in Water

We have measured the dynamics of an electron photoionized from a neutral water molecule. Our results suggest that the electron solvation dynamics can be viewed as an internal conversion process.
EZH2 inhibition promotes epithelial-to-mesenchymal transition in ovarian cancer cells.

// Horacio Cardenas 1 , Janice Zhao 2 , Edyta Vieth 3 , Kenneth P. Nephew 4 , Daniela Matei 1, 5, 6 1 Northwestern University Feinberg School of Medicine, Department of Obstetrics and Gynecology, Chicago, IL, USA 2 Oakland University William Beaumont School of Medicine, Rochester, MI, USA 3 Indiana University Department of Medicine, Indianapolis, IN, USA 4 Medical Sciences, Indiana University, Bloomington, IN, USA 5 Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA 6 Robert Lurie Cancer Center, Northwestern University, Chicago, IL, USA Correspondence to: Daniela Matei, email: daniela.matei@northwestern.edu Horacio Cardenas, email: horacio.cardenas@northwestern.edu Keywords: ovarian cancer, EZH2, EMT, H3K27me3, GSK126 Received: March 24, 2016 Accepted: August 09, 2016 Published: August 22, 2016 ABSTRACT Cancer cells acquire essential characteristics for metastatic dissemination through the process of epithelial-to-mesenchymal transition (EMT), which is regulated by gene expression and chromatin remodeling changes. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3) to repress gene transcription. Here we report the functional roles of EZH2-catalyzed H3K27me3 during EMT in ovarian cancer (OC) cells. TGF-β-induced EMT in SKOV3 OC cells was associated with decreased levels of EZH2 and H3K27me3 ( P 15-fold) expression of EMT-associated transcription factors ZEB2 and SNAI2 . EZH2 knockdown (using siRNA) or enzymatic inhibition (by GSK126) induced EMT-like changes in OC cells. The EMT regulator ZEB2 was upregulated in cells treated with either approach. Furthermore, TGF-β enhanced expression of ZEB2 in EZH2 siRNA- or GSK126-treated cells ( P <0.01), suggesting that H3K27me3 plays a role in TGF-β-stimulated ZEB2 induction. Chromatin immunoprecipitation assays confirmed that TGF-β treatment decreased binding of EZH2 and H3K27me3 to the ZEB2 promoter ( P <0.05). In all, these results demonstrate that EZH2, by repressing ZEB2, is required for the maintenance of an epithelial phenotype in OC cells.
Transdisciplinary approaches enhance the production of translational knowledge.

The primary goal of translational research is to generate and apply knowledge that can improve human health. Although research conducted within the confines of a single discipline has helped us to achieve this goal in many settings, this unidisciplinary approach may not be optimal when disease causation is complex and health decisions are pressing. To address these issues, we suggest that transdisciplinary approaches can facilitate the progress of translational research, and we review publications that demonstrate what these approaches can look like. These examples serve to (1) demonstrate why transdisciplinary research is useful, and (2) stimulate a conversation about how it can be further promoted. While we note that open-minded communication is a prerequisite for germinating any transdisciplinary work and that epidemiologists can play a key role in promoting it, we do not propose a rigid protocol for conducting transdisciplinary research, as one really does not exist. These achievements were developed in settings where typical disciplinary and institutional barriers were surmountable, but they were not accomplished with a single predetermined plan. The benefits of cross-disciplinary communication are hard to predict a priori and a detailed research protocol or process may impede the realization of novel and important insights. Overall, these examples demonstrate that enhanced cross-disciplinary information exchange can serve as a starting point that helps researchers frame better questions, integrate more relevant evidence, and advance translational knowledge more effectively. Specifically, we discuss examples where transdisciplinary approaches are helping us to better explore, assess, and intervene to improve human health.
Abstract 654: Overexpression Of Class I Histone Deacetylases Repress Npr1 Gene Transcription In Mouse Mesangial Cells

Activation of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) by cardiac hormones atrial and brain natriuretic peptides (ANP and BNP) produces the second messenger cGMP, which plays a pivotal role in maintaining blood pressure and cardiovascular homeostasis. The objective of the present study was to gain insight into the epigenetic signaling mechanism in the regulation of Npr1 (coding for GC-A/NPRA) gene transcription and expression. The mouse mesangial cells were cultured in Dulbecco’s modified Eagles medium containing 10% fetal bovine serum and ITS (insulin, transferrin, and sodium selenite). The results showed that class I and II histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBu) significantly induced Npr1 promoter activity by 5- and 7-fold (TSA-treated, 2160.3 ± 32.4 and NaBu-treated, 3024.89 ± 25.03 vs. untreated control 432.2 ± 23.2, p Npr1 mRNA levels by 3.5-fold and NaBu by 5-fold (TSA-treated, 9.7 ± 0.89 and NaBu-treated, 13.8 ± 1.9 vs. control 2.68 ± 0.5; p Npr1 promoter activity by 6-fold (1955.4 ± 47.32 vs. control 325.9 ± 23.4, p Npr1 promoter activity by 50% (234.8 ± 9.5 and 265.4 ± 10.32, respectively vs. control 543.23 ± 7.8, p Npr1 gene transcription via inhibition of HDAC activity and histone acetylation. The identification of epigenetic signaling as a regulator of Npr1 gene expression will have important implications in prevention of hypertension and cardiac remodeling.
Inferring ascending auction participation from observed bidders

Abstract Participation in internet auctions goes well beyond those who place a bid. Participants arrive in random order, and if the auction’s standing price has already exceeded a participant’s valuation, she will not bid. Even so, her unreported valuation is a relevant part of demand for the item, and in an alternate random order, her bid would have been registered. I provide a method to estimate the average number of participants from the average number of bidders per auction. This enables estimation of the distribution of participant valuations from either the distribution of closing prices or the distribution of all observed bids.
Hysteretic Characteristics of Piezoelectric Materials

This chapter presents a brief but self-contained discussion on the origin of hysteresis in piezoelectric materials, some select modeling frameworks and effective compensation techniques. The materials given in this chapter shall prepare the readers for vibration-control systems using piezoelectric actuators and sensors discussed in Chaps. 9 and 3.
Hashtag Activism as a Form of Political Action: A Qualitative Analysis of the #BringBackOurGirls Campaign in Nigerian, UK, and U.S. Press

Researchers have argued that social media such as Twitter redistribute news media’s power over how issues are framed to scattered networks of activists and citizens. But what happens when an online campaign such as #BringBackOurGirls against Boko Haram’s kidnapping of Nigerian schoolgirls garners global media coverage? Using qualitative frame analysis, this study assesses how news media in Nigeria, the United Kingdom, and the United States framed the #BBOG activism campaign and finds key differences in news coverage. Despite Twitter’s potential for “networked framing” and diffusing news media’s power over discourses, the differential framing and localization of #BBOG in the United Kingdom and the United States vis-a-vis Nigeria demonstrates how institutional norms, local politics, and contextual realities can constrain social media activists’ preferred framing of important issues. Thus, despite Twitter’s promise for activism, online activists need to grapple with ways to maintain control over their issue discourses in the Twittersphere locally and (especially) internationally. We provide some recommendations on how to do this.
Inflammasome Activation by Pathogenic Crystals and Particles

The NLRP3 inflammasome is a multiprotein complex that controls processing and secretion of bioactive IL-1β and IL-18, powerful proinflammatory cytokines involved in several human diseases. The NLRP3 inflammasome is activated by pathogens, danger signals released by necrotic cells, and crystals and particles of varied size and structure. These inflammasome-activating particles have a causative role in human diseases such as gout, asbestosis, silicosis, and Alzheimer’s, or are useful as vaccine adjuvants, like in the case of alum. The molecular aspects involved in activation of the NLRP3 inflammasome by particles are being rapidly elucidated and emphasize the importance of phagocytosis, K+ efflux, and generation of reactive oxygen species in this process. Here, the recent literature is reviewed and important questions to be answered in the future are identified.
Optimizing Activity Detection via Sensor Fusion

Internet of Things (IoT) has enabled several applications related to data analytics. In this paper, an intuitive method for optimizing activity detection data is presented. Further applications include exploring detection accuracies of physical activities such as walking intensity and movement on stairs. This method utilizes different Microcontroller Units (MCUs) with embedded sensors which are used for activity detection. Additionally, this method also incorporates supervised learning - more specifically the Fine Gaussian SVM, to generate a predictive model for activity optimization.
CHAPTER 24 – Writing a Protocol

Publisher Summary A protocol is a complete written description of, and scientific rationale for, a research activity involving human subjects. Although an idea for a clinical study may be very good, the challenge is putting it into a format and structure that has a good chance of yielding clinically valid information. The process of converting an idea into an infrastructure, which results in clinically valid information, is in essence creating a clinical protocol. This chapter discusses the general guidelines of protocol writing in the United States. There are two major categories of clinical protocols. The first category is natural history protocols, which can be retrospective reviews of cases/histories. The second major protocol category is an interventional study or clinical trial designed to change the course of a disease through a therapy or the use of instrumentation. The elements to a clinical protocol may vary to some degree between academic institutions, and what differ are the added features required by an institution. An interventional trial usually requires more information and is scrutinized very carefully. It usually makes sense to include all persons, who are involved in the protocol, as associate investigators on the protocol. This has become more important as concerns about conflict of interest in clinical research are being concretized in a more formalized evaluation. The principal investigator should use the associate investigators' expertise in the development of the protocol. Each associate investigator should review the protocol, with special attention to the part related to his or her expertise. The principal investigator must collect the comments of her or his associate investigators and create the final protocol, which is then submitted for review.
Emeritus Attorney Pro Bono: From Rules, to Programs, to Law School Clinics

Meeting the legal needs of low-income Americans continues to be a challenge for this country and the legal profession. In an effort to address the nation’s growing “Justice Gap,” 44 jurisdictions have adopted Emeritus Attorney Pro Bono Programs. Senior attorneys who opt for this bar status agree to provide pro bono representation through a legal services program, in return for free or reduced annual bar fees and continuing education requirements. This article argues that law schools should consider adding emeritus pro bono attorneys to their legal clinics. The article traces the provision of legal services within the United States through both federally-funded legal service providers and private pro bono. While private pro bono has grown in recent years, so has the Justice Gap. In reaction to this growing inability to meet the legal needs of low-income Americans, almost all states have created Emeritus Attorney Pro Bono Programs. The article discusses the growth of such programs, the differences among these programs, and the best and most effective program practices. The article then describes the development of law school clinical programs, including recent calls for schools to expand clinics to enhance student experiential learning opportunities. The advantages of adding emeritus attorneys to law school clinical programs are discussed, as well as potential accreditation, logistical, and ethical issues presented by such a strategy. While the article concludes that law schools should seriously consider emeritus attorneys as a potential clinic resource, schools must be careful to match the individual skills and experience of potential emeritus pro bono attorneys with the dual teaching and service missions of specific law school clinics.
Leveraging Women’s Leadership Talent to Promote a Social Justice Agenda in Ethiopian Schools:

Background:Research that identifies and celebrates the positive attributes of women educational leaders advancing a social justice agenda in traditionally male-dominated, Sub-Saharan African (SSA) ...
Opportunities for bipartisanship: Comparing water and energy policy in the Great Lakes region

Abstract The Great Lakes contain most of the United States’ surface freshwater and provide deep personal and economic connections for the residents of the region. These connections create an opportunity for bipartisanship in environmental policies with the potential to permeate energy policies. To explore that possibility, this paper examines how party affiliation affects support for water policy and energy policy in the Great Lakes region of the United States. Data from the Great Lakes Region Public Opinion Survey asked 696 Republicans, Independents, and Democrats from the Great Lakes region to respond to a range of environmental policy prompts. Responses to the policy prompts are grouped into four components: Water Quality, Water Diversions, Traditional Fuels, and Renewables. The results find that there is bipartisan support for the Water Quality and Water Diversions components. Energy policies do not receive the same bipartisan support, with Democrats and Independents having more support for the Renewables component while Republicans have more support for the Traditional Fuels component. However, when the fuel source is tied to its pollutants of the Great Lakes, then reactions to that fuel source receive a bipartisan response. The results of this research suggest that embedding water policy in energy policy may allow those policies to receive more bipartisan support. Combining water policy and energy policy can depolarize some of the politics surrounding environmental policy broadly.
EFFECTS OF DOMESTIC VIOLENCE EXPOSURE IN COLOMBIAN ADOLESCENTS: PATHWAYS TO VIOLENT AND PROSOCIAL BEHAVIOR

reasoning), which is frequently seen among substance abusers (Dawes, Tarter, & Kirisci, 1997; Giancola, & Tarter, 1999). This pattern of dysregulation may have exacerbated the risk of substance use problems among juvenile offenders; or may have prompted youths in the school sample to heightened levels of aggressiveness. The next step in the Crick and Dodge (1994) model involves response access or construction (e.g., previous successful coping strategies as well as
‘They wasn't makin’ my kinda music’: a hip-hop musician's perspective on school, schooling, and school music

ABSTRACTThis article focuses on a hip-hop perspective of school, schooling, and school music. The study involves applications of ethnographic (including autoethnographic) techniques within the framework of a holistic multiple case study. One case is an adult amateur hip-hop musician named Terrence (pseudonym), and the other is myself (a traditionally trained American music educator and scholar). My history as a professional educator and scholar juxtaposed with Terrence's perspective as a high school dropout offers a valuable contrast of beliefs, values, and assumptions about school and education. Exploring Terrence's experiences and perceptions helps us to understand him as a musician and learner and also allows for a critical investigation of my own perspectives. Recognising my assumption-laden perspectives offers meaningful layers of nuance towards complicating the relationships between schools, those who school, and those who are schooled. Implications for teachers and researchers include expanding con...
Transcriptome Analysis of HER2 Reveals a Molecular Connection to Fatty Acid Synthesis

HER2 (erbB2/neu) is a member of the erbB family of receptor tyrosine kinases and is involved in regulating the growth of several types of human carcinomas. HER2 represents a successful therapeutic target of the biotechnology era as exemplified by the drug Herceptin (trastuzumab), which has clinical activity in a subset of breast cancer patients. Using DNA microarrays, we identified a cohort of genes that are differentially regulated by HER2 in breast epithelial cells. One of the HER2-regulated genes discovered was fatty acid synthase (FAS), which has been shown to be overexpressed in breast cancer as well as other cancers. FAS is implicated in tumorigenesis through its role in cell proliferation and membrane lipid incorporation of neoplastic cells. Here, we demonstrate that HER2-mediated induction of FAS is inhibitable by Herceptin and tyrosine kinase inhibitors of HER2. Through a phosphatidylinositol 3'-kinase-dependent pathway, HER2 stimulates the FAS promoter and ultimately mediates increased fatty acid synthesis. Interestingly, pharmacological inhibition of FAS preferentially induced apoptosis of HER2-overexpressing breast epithelial cells relative to matched vector control cells. These studies characterize a molecular connection between two genes individually implicated in tumorigenesis but never linked together.
Sensing under Uncertainty for Mobile Robots

In this work we present a control strategy under uncertainty for mobile robot navigation. In particular, we implement a server-client model, where the server executes the commands and the clients run in parallel, each performing its tasks. Tolerance analysis is performed to incorporate sensing uncertainties into the proposed model. The sensory system is depicted with a framework that allows different levels of data representation, based on the robust modeling of the sensing uncertainties.
Preliminary Statistical Survey of Plasmaspheric Ion Properties from Observations by De 1/RIMS

The paper presents mean temperatures and densities of plasmaspheric H(+) ions obtained from observations by the retarding ion mass spectrometer on Dynamics Explorer 1. Composition is shown in terms of ratios of densities of the various ion species to those of H(+). The spatial variations are indicated in terms of L shell profiles, with separate profiles for local morning and evening sides.
Temporal Separation of Transcription and Translation in Neurospora

Cells of Neurospora accumulated capacity for synthesis of kynureninase in the presence of cycloheximide and a suitable inducer. The capacity was expressed only when the cells were returned to a medium which allowed net synthesis of protein to resume. Subsequent expression did not require synthesis of ribonucleic acid (i.e., was not inhibited by actinomycin D) or the presence of inducer. The relative level of capacity, as judged by the initial rate of appearance of enzyme, increased linearly for 70 min in cells incubated in the presence of inducer plus antibiotic.
Efficient static timing analysis and applications using edge masks

Static timing analysis (STA) with multiple clock domains and complicated exception conditions is a complex practical problem that can dramatically increase compilation time, both for back-end analysis and during place and route. In FPGA placement, timing analysis with many constraints can dominate placement run-time.In this paper we introduce a simple binary edge-mask data structure on arcs in a timing netlist which allows for efficient timing analysis in the presence of many such constraints. The technique applies to either BFS or DFS-based timing analysis. Preliminary implementations on just the basic concept show a 59% decrease in STA run-time for multi-clock designs, indicating that significant benefit is to be gained from a complete implementation. On a set of heavily constrained designs this benefit improved to 80% run-time decrease.Further applications of the edge-mask concept are shown to efficiently deal with thru-x constraints, enumerating the k-longest paths in a timing graph, and partial/incremental timing analysis aimed at significant improvements in placement time.
Variables in photodynamic therapy for Barrett's esophagus

Photodynamic therapy with porfimer sodium (PS) is a treatment option for high grade dysplasia associated with Barrett's esophagus. This study sought to investigate the optical properties of Barrett's dysplasia that may be useful in light dosimetry planning and to determine the effect of PS on tissue absorption and scattering. Fiber optic reflectance spectra were collected before and 48 hours after administration of 2 mg/kg PS. Mucosal biopsies were collected at the same locations. According to Monte Carlo analysis, the fiber optic probe sampled only the mucosal layer. A mathematical fit of the reflectance spectra was performed as a function of blood volume fraction, oxygen saturation and scattering. The average calculated blood volume was 100% higher in Barrett's tissue than normal esophageal tissue. The average scattering slope from 620 to 750 nm was 26% higher for Barrett's dysplasia than normal esophageal tissue, indicating an increase in the size of scattering particles. The difference in the scattering amplitude was not statistically significant, suggesting no significant increase in the number of scattering particles. PS tissue content was determined with extraction methods. Changes in the scattering slope due to PS sensitization were observed; however they were not proportional to the extracted PS concentration.
Planned obsolescence and monopoly undersupply

Abstract This paper examines the welfare implications of planned obsolescence in situations where the traditional monopoly undersupply exists. We find that the monopolist’s introduction of incompatibility between successive generations of products alleviates the monopoly undersupply problem and may therefore generate higher social welfare than compatibility. Paradoxically, the stronger the network effects, the more likely welfare will increase as a result of incompatibility. Our result also extends to two-sided markets characterized by indirect network effects.
Downstream Conditions in a Constricted ARC with Radial Injection

The thermal, flow and electrical conditions are presented for the downstream portion of an argon arc with local fluid constriction. The arc is initially wall-stabilized in a 10 mm diameter water-cooled constrictor and at some point after flow becomes fully developed the arc is constricted by a radial inward jet. The redevelopment of the flow downstream of the injection slot is investigated by measurements of the pressure drop, wall heat flux and electric field. It is observed that redevelopment proceeds roughly as predicted by classical theory. Measurements of the electric field indicate that the region of maximum constriction is limited in extent.
pSearch: information retrieval in structured overlays

We describe an efficient peer-to-peer information retrieval system, pSearch; that supports state-of-the-art content- and semantic-based full-text searches. pSearch avoids the scalability problem of existing systems that employ centralized indexing, or index/query flooding. It also avoids the nondeterminism that is exhibited by heuristic-based approaches. In pSearch; documents in the network are organized around their vector representations (based on modern document ranking algorithms) such that the search space for a given query is organized around related documents, achieving both efficiency and accuracy.
Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: effects on reproductive function.

The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to gonadal steroids. For decades it has been known that androgens, estrogens and progestins, acting through nuclear hormone receptors, elicit both organizational and activational effects in the hypothalamus and basal forebrain that are essential for reproductive function. While changes in gene expression mediated by these classical hormone pathways are paramount in governing both sexual differentiation and the neural control of reproduction, it is also clear that steroids impart critical control of neuroendocrine functions through non-genomic mechanisms. Specifically, endogenous neurosteroid derivatives of deoxycorticosterone, progesterone and testosterone, as well and synthetic anabolic androgenic steroids that are self-administered as drugs of abuse, elicit acute effects via allosteric modulation of γ-aminobutyric acid type A receptors. GABAergic transmission within the hypothalamus and basal forebrain is a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy and parturition. Summarized here are the known actions of steroid modulators on GABAergic transmission within the hypothalamus/basal forebrain, with a focus on the medial preoptic area and the supraoptic/paraventricular nuclei that are known to be central players in the control of reproduction.
Decomposing the structural identification of non-market values

Abstract This paper addresses the issue of transparency in structural modeling by investigating how the assumptions of a structural model contribute to its identification of non-market values. Assumptions about the form of the utility function, the depiction of preference heterogeneity, and the definition for the choice set are shown to jointly identify a partition of preference space which explains observed behavior. The borders of the partition reflect substitution patterns. The regions in the partition set-identify preferences. Assumptions about the distribution of preferences within each region point-identify partial equilibrium welfare measures. Together, these observations provide a framework for decomposing the structural identification of non-market values. The new framework allows analysts to explain how their modeling assumptions influence estimates for benefits and costs. This addresses federal guidelines for quantifying uncertainty in the modeling assumptions which enter benefit-cost analysis. The framework is demonstrated by decomposing estimates of the MWTP for air quality.
Localization of neurons supplying the extraocular muscles in the kitten using horseradish peroxidase.

Abstract The neurons supplying extraocular muscles were studied in sixteen newborn kittens, utilizing horseradish peroxidase to trace retrograde neuronal protein transport. In the third cranial nerve nuclear complex, the subgroups for the medial rectus, inferior rectus and inferior oblique muscles were distinctly separate neuron aggregates located ipsilaterally. The superior rectus muscle was supplied by a subgroup located contralaterally in the complex. The neurons of the fourth and sixth cranial nerve nuclei were also studied with this technique. Hitherto undisclosed details concerning these nuclei were demonstrated.
Tumor Necrosis Factor-α and Fas Activate Complementary Fas-associated Death Domain-dependent Pathways That Enhance Apoptosis Induced by γ-Irradiation

Activation of either tumor necrosis factor receptor 1 or Fas induces a low level of programmed cell death in LNCaP human prostate cancer cells. We have shown that LNCaP cells are entirely resistant to γ-radiation-induced apoptosis, but can be sensitized to irradiation by TNF-α. Fas activation also sensitized LNCaP cells to irradiation, causing nearly 40% cell death 72 h after irradiation. Caspase-8 was cleaved and activated after exposure to tumor necrosis factor (TNF)-α. However, after exposure to anti-Fas antibody caspase-8 cleavage occurred only between the 26-kDa N-terminal prodomain and the 28-kDa C-terminal region that contains the protease components. Although anti-Fas antibody plus irradiation induced apoptosis that could be blocked by the pancaspase inhibitor zVAD, there was no measurable caspase-8 activity after exposure to anti-Fas antibody. The effector caspases-6 and -7, and to a lesser extent caspase-3, were activated by TNF-α, but not by anti-Fas antibody. Anti-Fas antibody, like TNF-α also activated serine proteases that contributed to cell death. Exposure of LNCaP cells simultaneously to TNF-α and anti-Fas antibody CH-11 resulted in marked enhancement of apoptosis that occurred very rapidly and was still further augmented by irradiation. Rapid apoptosis that ensued from combined treatment with TNF-α, anti-Fas antibody, and irradiation was completely blocked either by zVAD or expression of dominant negative Fas-associated death domain. Our data shows that there are qualitative differences in caspase activation resulting from either TNF receptor 1 or Fas. Simultaneous activation of these receptors was synergistic and caused rapid epithelial cell apoptosis mediated by the caspase cascade.
The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements

Abstract We report that the thyroid hormone (T 3 ) receptor binds to DNA recognition sequences that are variations of the palindromic motif 5′-TCAGGTCA·TGACCT-GA-3′, resulting in transcriptional activation in vivo. This sequence is identical to the vitellogenin A2 estrogen response element except for the absence of 3 bp at the center of dyad symmetry, which we have termed a "gap." The T 3 receptor binds to estrogen response elements with high affinity in vitro, as well as to variations of the same sequence containing gaps of 1–6 bp. The T 3 receptor not only fails to activate transcription from estrogen response elements in vivo, but inhibits estrogen-dependent transactivation. We propose that the T 3 receptor binds to estrogen response elements in a transcriptionally inactive form and competes for estrogen receptor binding, resulting in a net decrease in gene expression. These data reveal that only a subset of T 3 receptor DNA-binding elements function as T 3 response elements.
Angioedema Associated with Candesartan

Most large clinical trials report that the frequency of angioedema caused by angiotensin-converting enzyme (ACE) inhibitors is 0.1-0.2%. The most common theory for this rare but potentially fatal adverse drug reaction cites ACE inhibitor-mediated accumulation of bradykinin as the culprit. Because angiotensin II receptor blockers (ARBs) do not exert their effects on ACE, they are not expected to cause bradykinin accumulation and therefore angioedema. Recently, several cases of angioedema related to the administration of ARBs have been documented in the literature. The existence of ARB-induced angioedema suggests that additional or alternate mechanisms not involving bradykinin are present in drug-induced angioedema. While taking candesartan for hypertension, a 53-year-old woman with known ACE inhibitor intolerance developed angioedema. During her hospitalization, candesartan was stopped and immunosuppressive therapy was administered. Within 24 hours, the angioedema had resolved completely and the patient was discharged. In light of the recent literature on ARB-induced angioedema, ACE inhibitor-intolerant patients who begin ARB therapy should receive appropriate counseling and be monitored closely for this adverse reaction.
Classification of essential amino acids for the weanling pig.

Abstract Feeding experiments with mixtures of purified amino acids show that arginine, leucine, phenylalanine, and valine are required for good growth of weanling pigs. The pig resembles the rat in its ability to synthesize part, but not all of the arginine required. It is now possible to tentatively classify the known amino acids with respect to major growth effects in weanling pigs. The amino acids which must be present in the diet for good growth are arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine . The remaining amino acids may be tentatively classed as dispensable.
Miroslav Volf on Living One’s Faith

In this essay the author reflects on Miroslav Volf’s discussion, in A Public Faith, of Christianity as properly a prophetic religion. The author focuses especially on the two main malfunctions that Volf cites as accounting for the fact that the faith of individual Christians is often not prophetic, namely, what he calls “idleness of faith” and what he calls “coerciveness of faith.”
Fibroblast growth factor pretreatment reduces epidermal growth factor- induced proliferation in rat astrocytes

Abstract Epidermal Growth Factor (EGF) is mitogenic for purified rat astrocytes in primary tissue culture. A combined concomitant treatment by EGF and Fibroblast Growth Factor (FGF) does not reduce the proliferation effect of EGF, however when the astrocytes are pretreated with EGF, their response to an EGF stimulation is reduced by 70%. This inhibition of EGF stimulation by FGF pretreatment is consistent across the EGF dose response curve and perhaps represents a mechanism for local modulation of astrocyte mitogenic effects.
Contribution of the vibrational free energy to phase stability in substitutional alloys: Methods and trends

Recent studies show that the effect of the lattice vibrations on predictions of phase stability can be important. Because complete computations of the phonon density of states from first principles are difficult, simpler models for the vibrational free energy have been used to incorporate these effects into phase diagram calculations. In this paper, we systematically investigate the accuracy of these approximations by studying model systems for which the vibrational free energy can be computed exactly in the harmonic approximation. We found that the Debye approximation, usually used in first-principles studies, fails to capture the configuration dependence of the vibrational free energy. We explain the reason for this failure. With the same model systems, we analyzed the effect of the lattice vibrations on the predicted phase diagrams as a function of size mismatch and chemical affinity. By fitting our results to the available experimental information, we find that the effect of vibrations on phase transition temperatures may be significant.
Donor Corneal Endothelial Striae

Excessive traction during excision of donor corneoscleral buttons can result in damage or death to corneal endothelial cells. This damage manifests as multiple peripheral and, less commonly, central striae or stretch marks that correspond to linear opacities at the level of the endothelium. The striae consist of parallel lines of degenerate endothelium, each line three to eight cells wide, and stain readily with trypan blue, which is indicative of cell damage or death. Light and electron microscopy demonstrates cell membrane lysis with abrupt demarcation between abnormal and normal endothelial cells. The number of these striae correlates with the degree of traction or stretch applied during corneoscleral excision. Careful slit-lamp biomicroscopy of corneoscleral buttons discloses endothelial striae in approximately 5% of specimens. Careful excisions of corneoscleral buttons are necessary to decrease the incidence and severity of endothelial striae.
Critical analysis of soft X-ray cross section data

Abstract A project is in progress in the national Bureau of Standards (NBS) Photon and Charged Particle Data Center to collect and evaluate photon cross section data in the X-ray region 100 eV to 100 keV. This project complements earlier NBS evaluations and compilations which focused primarily on energies above 10 keV. The NBS collection of experimental total attenuation coefficients (10 eV to above 10 GeV) abstracted from the literature is now computerized to facilitate use and for future updates. These experimental results have been compared systematically with a theoretical photoabsorption calculation by Scofield, and also with a semi-empirical compilation by Henke et al. Sample graphical comparisons of measured data with the Scofield theoretical results are presented here for silicon and uranium. Silicon data from an International Union of Crystallography project are also presented. Discrepancies and uncertainties in the various experimental data sets are typically 5 to 50% or more in the soft X-ray region. However, systematic trends can be seen which suggest that the Scofield theoretical values, taken as a whole, are not improved by the Hartree-Slater to Hartree-Fock renormalization in this photon energy region.
A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine.

Peroxynitrite reacts with 2‘,3‘,5‘-tri-O-acetyl-guanosine to yield a novel compound identified as 1-(2,3,5-tri-O-acetyl-β-d-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6). This characterization was achieved using a combination of UV/vis spectroscopy and ESI-MS. Additionally, 1-(β-d-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6a) was synthesized by an independent route, characterized by UV/vis spectroscopy, ESI-MS, and 1H- and 13C NMR, and shown to be identical to deacetylated 6. This product is extremely stable in aqueous solution at both pH extremes and is formed in significant yields. These characteristics suggest that this lesion may be useful as a specific biomarker of peroxynitrite-induced DNA damage. We also observed formation of 2‘,3‘,5‘-tri-O-acetyl-8-nitroguanosine (2‘,3‘,5‘-tri-O-acetyl-8-NO2Guo), 2-amino-5-[(2,3,5-tri-O-acetyl-β-d-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (2‘,3‘,5‘-tri-O-acetyl-Iz), and the peroxynitrite-induced oxidation products of 2‘,3‘,5‘-tri-O-ace...
Attribution of Responsibility Implied in a Notice of Acceptance or Rejection

200 college students reported which of 2 messages they would send, as representatives of a social club, to a person whose application to join the club had been accepted or rejected. One message had the effect of assigning less internal responsibility to the sender (S) for the decision than did the other. Ss were randomly assigned to send either an acceptance or a rejection notice and were randomly assigned to one of two message pairs which differed in the manner in which the locus of control for the decision was varied. When the results from both message conditions are combined, the difference between the proportion of “internal responsibility” messages in the accept versus the rejection conditions is significant (p < .06), indicating that Ss tend to imply more internal responsibility in the acceptance notices they send and more external responsibility in their rejection notices. There is a rather weak curvilinear relationship between the message chosen to send in the rejection condition and S‘s Machiavel...
Quantitative Determination of 1,4-Dioxane and Tetrahydrofuran in Groundwater by Solid Phase Extraction GC/MS/MS†

Groundwater contamination by cyclic ethers, 1,4-dioxane (dioxane), a probable human carcinogen, and tetrahydrofuran (THF), a co-contaminant at many chlorinated solvent release sites, are a growing concern. Cyclic ethers are readily transported in groundwater, yet little is known about their fate in environmental systems. High water solubility coupled with low Henry's law constants and octanol-water partition coefficients make their removal from groundwater problematic for both remedial and analytical purposes. A solid-phase extraction (SPE) method based on activated carbon disks was developed for the quantitative determination of dioxane and THF. The method requires 80 mL samples and a total of 1.2 mL of solvent (acetone). The number of steps is minimized due to the "in-vial" elution of the disks. Average recoveries for dioxane and THF were 98% and 95%, respectively, with precision, as indicated by the relative standard deviation of <2% to 6%. The method quantitation limits are 0.31 microg/L for dioxane and 3.1 microg/L for THF. The method was demonstrated by analyzing groundwater samples for dioxane and THF collected during a single sampling campaign at a TCA-impacted site. Dioxane concentrations and areal extent of dioxane in groundwater were greater than those of either TCA or THF.