cssi/SciSciGPT-SciSciNet huggingface dataset:
Developmental manganese neurotoxicity in rats: Cognitive deficits in allocentric and egocentric learning and memory

Manganese (Mn) is an essential element but neurotoxic at higher exposure levels. The effects of Mn overexposure (MnOE) on hippocampal and striatal-dependent learning and memory in rats were tested in combination with iron deficiency (FeD) and developmental stress that often co-occur with MnOE. Moderate FeD affects up to 15% of U.S. children and developmental stress is common in lower socio-economic areas where MnOE occurs. Pregnant Sprague-Dawley rats and their litters were housed in cages with or without (barren cage (BAR)) standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% FeD or iron sufficient (FeS) diet from E15-P28. Within each litter, separate offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage on alternate days from P4-28. Offspring were tested as adults in the Morris and Cincinnati water mazes. FeD and developmental stress interactively impaired spatial learning in the Morris water maze. Developmental stress and MnOE impaired learning and memory in both mazes. MnOE resulted in reduced CA1 hippocampal long-term potentiation (LTP) and increased levels of α-synuclein. Preweaning MnOE resulted in cognitive deficits on multiple domains of learning and memory accompanied by impaired LTP and α-synuclein changes, effects worsened by developmental stress.
VZV Neurovasculitis in the Setting of a Novel Adult-Onset Immunocompromised State with Autoantibodies to Interferon alpha (anti-IFNα) (S53.001)

OBJECTIVE: We report a previously healthy man who presented with profound neurological dysfunction due to varicella zoster virus (VZV) vasculitis, in the setting of autoantibodies to anti-IFNα. BACKGROUND: VZV vasculitis resulting in nervous system damage is rare in the immunocompetent host. Humoral immunity protects against acquiring VZV but T-cell mediated immunity shields against reactivation of the latent virus. Individuals who are immunocompromised due to T-cell mediated defects can present with severe systemic VZV. METHODS: Case report RESULTS: A previously healthy 64 year old man developed an acute T3 Brown-Sequard syndrome, following a spinal cord infarct. Symptoms progressed to include bilateral lower extremity weakness, ptosis, ophthalmoplegia, and encephalopathy. Magnetic resonance imaging (MRI), showed diffuse T2 hyperintensities with enhancement throughout the spine and brain, including enhancement of his meninges, roots, and cranial nerves. Successive cerebrospinal fluid (CSF) studies revealed increasing B-cell lymphocytosis, (maximum 661 cells/mcl), and CSF protein (maximum 242 mg/dL). CSF PCR was positive for VZV and IgM antibodies were detected. Further testing showed anti-IFNα autoantibodies in the plasma and CSF. Serum anti-IFNα fluorescence intensity was 30 times normal, and his plasma blocked IFNα-induced STAT-1 phosphorylation in normal monocytes. Treatment with acyclovir and methylprednisolone resulted in improvement of his encephalopathy and cranial neuropathies. Repeat LP revealed 32 WBC/mcl with normal protein. Follow up MRI showed no new lesions. CONCLUSION: This is the first identified case of CNS VZV neurovasculitis in the setting of binding and blocking autoantibodies to IFNα in the serum and CSF. Elevated serum and CSF levels of anti-INFα may impair natural killer, T-cell and neuronal antiviral activity. Disruption of T-cell mediated immunity due to anti-IFNα could result in an adult-onset immunocompromised state with severe VZV reactivation. The association of high-titer neutralizing autoantibodies to INFα with an adult-onset immunocompromised state is a novel and likely clinically significant finding. Disclosure: Dr. Ansari has nothing to disclose. Dr. Mittal has nothing to disclose. Dr. Christa has nothing to disclose. Dr. Rosen has nothing to disclose. Dr. Holland has nothing to disclose. Dr. Bonomo has nothing to disclose.
High magnitude unidirectional haptic force display using a motor/brake pair and a cable

Clever electromechanical design is required to make the force feedback delivered by a kinesthetic haptic interface both strong and safe. This paper explores a onedimensional haptic force display that combines a DC motor and a magnetic particle brake on the same shaft. Rather than a rigid linkage, a spooled cable connects the user to the actuators to enable a large workspace, reduce the moving mass, and eliminate the sticky residual force from the brake. This design combines the high torque/power ratio of the brake and the active output capabilities of the motor to provide a wider range of forces than can be achieved with either actuator alone. A prototype of this device was built, its performance was characterized, and it was used to simulate constant force sources and virtual springs and dampers. Compared to the conventional design of using only a motor, the hybrid device can output higher unidirectional forces at the expense of free space feeling less free.
Unintended Laboratory-Driven Evolution Reveals Genetic Requirements for Biofilm Formation by Desulfovibrio vulgaris Hildenborough.

Biofilms of sulfate-reducing bacteria (SRB) are of particular interest as members of this group are culprits in corrosion of industrial metal and concrete pipelines as well as being key players in subsurface metal cycling. Yet the mechanism of biofilm formation by these bacteria has not been determined. Here we show that two supposedly identical wild-type cultures of the SRB Desulfovibrio vulgaris Hildenborough maintained in different laboratories have diverged in biofilm formation. From genome resequencing and subsequent mutant analyses, we discovered that a single nucleotide change within DVU1017, the ABC transporter of a type I secretion system (T1SS), was sufficient to eliminate biofilm formation in D. vulgaris Hildenborough. Two T1SS cargo proteins were identified as likely biofilm structural proteins, and the presence of at least one (with either being sufficient) was shown to be required for biofilm formation. Antibodies specific to these biofilm structural proteins confirmed that DVU1017, and thus the T1SS, is essential for localization of these adhesion proteins on the cell surface. We propose that DVU1017 is a member of the lapB category of microbial surface proteins because of its phenotypic similarity to the adhesin export system described for biofilm formation in the environmental pseudomonads. These findings have led to the identification of two functions required for biofilm formation in D. vulgaris Hildenborough and focus attention on the importance of monitoring laboratory-driven evolution, as phenotypes as fundamental as biofilm formation can be altered.IMPORTANCE The growth of bacteria attached to a surface (i.e., biofilm), specifically biofilms of sulfate-reducing bacteria, has a profound impact on the economy of developed nations due to steel and concrete corrosion in industrial pipelines and processing facilities. Furthermore, the presence of sulfate-reducing bacteria in oil wells causes oil souring from sulfide production, resulting in product loss, a health hazard to workers, and ultimately abandonment of wells. Identification of the required genes is a critical step for determining the mechanism of biofilm formation by sulfate reducers. Here, the transporter by which putative biofilm structural proteins are exported from sulfate-reducing Desulfovibrio vulgaris Hildenborough cells was discovered, and a single nucleotide change within the gene coding for this transporter was found to be sufficient to completely stop formation of biofilm.
The Mitophagy Receptor FUNDC-1 Contributes to Hypoxia-Reoxygenation Stress in C. elegans

Mitochondrial are central to hypoxia-reoxygenation (H/R) injury in both mammals and the nematode C. elegans and mitochondrial quality control (MQC) mechanisms including the mitochondrial unfolded protein response (UPR mt ), the production of anti-oxidants, and mitophagy are important for adapting to H/R stress. FUNDC1 (FUN14 domain containing 1) is a hypoxia-induced mitophagy mediator that has been characterized in mammalian cells. FUNDC1 is located on the mitochondrial outer-membrane and directly binds to LC3 and Drp1. However, the contribution of FUNDC1 to MQC and its interaction with other signaling pathways is currently unknown. We have identified a putative C. elegans FUNDC1 ortholog T06D8.7 (here after referred to as fundc-1 ) and begun to analyze its role in MQC during H/R. Fundc-1 is in an operon together with three other genes that are involved in mitochondria or proteasome function. Here, we demonstrate that transcription of fundc-1 is activated by hypoxia through HIF1 binding sites in both intragenic and operon promoters. We have generated fundc-1 mutant worms using CRISPR-Cas9 mutagenesis and find that loss-of-function worms are protected against hypoxic injury and death. Atfs-1 codes for a central regulator of UPR mt that we have recently shown is both necessary and sufficient to protect against H/R injury in C. elegans. Atfs-1 loss-of-function suppresses the T06D8.7 hypoxic-protected phenotype. This suggests that disrupting mitophagy elicits an UPR mt and subsequent adaptation to hypoxia. Use of the C. elegans model will facilitate dissecting interactions between fundc-1 and other hypoxia-relevant signaling pathways implicated in MQC.
Charter schools, parent choice, and segregation: A longitudinal study of the growth of charters and changing enrollment patterns in five school districts over 26 years

In 1975, a court-ordered busing program was launched to desegregate the schools of New Castle County, Delaware. It was by many accounts one of the most significant and successful desegregation programs in the nation (Armor & Rossell, 2002; Orfield, 2014; Raffel, 1980). In 1995, the districts of the county were declared “unitary” and the court order was lifted. Shortly thereafter, new policies were enacted allowing school choice, charter schools, and neighborhood attendance zoning. This study draws on primary and secondary data, including geographic, census, and enrollment data, and provides an account of the policy changes and a 26-year longitudinal analysis of changing enrollment trends and patterns. Segregation by race and income among schools accelerated after the policy changes. While the policy changes created greater segregation, enrollment trends varied by district and over time; segregation growth was moderate in two of the districts, small in the others. Our study illuminates the complexity of explaining segregation patterns and disentangling the contributing role of choice, charters, attendance zones, and residential demographics in explaining segregation patterns in school systems.
The Stereotype Content of Sexual Orientation

The stereotype content model provides a powerful tool to examine influential societal stereotypes associated with social groups. We theorize how stereotypes of gender, sexuality, and a group’s stat...
De novo atrial fibrillation after mitral valve surgery

Abstract Objectives We sought to determine the incidence and risk factors for de novo atrial fibrillation (>90 days after surgery) in patients without pre-operative atrial fibrillation. Methods From 2004-2014, 2261 patients had mitral valve surgery; 1288 (57%) did not have a history of atrial fibrillation and 930 patient had rhythm information > 90 days after surgery. De novo atrial fibrillation, and death probabilities were estimated using a semi-competing risks, multi-state model. Univariable and multivariable risk factors for developing atrial fibrillation were identified using the Fine-Gray model. Results The 5- and 10-year incidence of de novo atrial fibrillation was 14% and 23%, respectively. Univariable risk factors were older age, more complex operations, more tricuspid regurgitation, and congestive heart failure (all p de novo atrial fibrillation were tricuspid valve surgery (1.80 [1.22, 2.65], p=0.003), aortic valve surgery (1.49 [1.03, 2.17], p=0.035), and older age (1.03 [1.02, 1.05], p De novo atrial fibrillation did not affect overall survival (p=0.41). Among patients who developed de novo atrial fibrillation, we observed increased use of warfarin (p Conclusions De novo atrial fibrillation develops progressively after mitral surgery and is associated with a strong trend towards stroke. Patients at high risk could be studied in a trial to reduce atrial fibrillation.
Further Understanding of Agglomeration Mechanisms in Spherical Crystallization Systems: Benzoic Acid Case Study

Spherical crystallization is a particle size enlargement technique that can provide significant process and micromeritic benefits to the production of active pharmaceutical ingredients. To this poi...
Applying participatory action approach to integrating professional librarians into open source software communities

This article theoretically explores how participatory action research might support integration of library professionals into open source software development communities. The author makes a case f...
Exploring Emotional Intelligence and IQ as Predictors of Success of Foster Care Alumni

The most common reason for foster care placement is child maltreatment. Sadly, once in the foster care system over 17% of children in the United States continue to experience multiple forms of maltreatment. After they “age out”, these alumni are particularly vulnerable to a host of adverse situations, such as low educational success and homelessness. The primary aim of this study was to explore individual characteristics that could predict the quality of life and level of distress of foster care alumni. Specifically, we were interested in the predictive ability of emotional intelligence (EI) and general intelligence (IQ) on quality of life and distress. Two multiple regression models were evaluated for the primary analyses. Both models included general intelligence and emotional intelligence as predictors, with one model containing quality of life and the other model level of distress as the criterion variables. The analyses demonstrated that general intelligence was not a significant predictor of quality of life or level of distress when controlling for emotional intelligence. In contrast, emotional intelligence was a significant predictor of improved quality of life and decreased level of distress when controlling for general intelligence. Emotional intelligence appears to be a characteristic that is amenable to change and a predictor of positive outcome among foster care alumni. Moreover, emotional intelligence may bolster resiliency against the higher levels of instability and stress experienced by foster care children.
The Postoperative Pancreas Imaging

Recent advances in the surgical techniques and postoperative intensive care have led to a decrease in the mortality rates after major pancreatic procedures, which now ranges from 1 to 3%. However, the morbidity rates are still high, resulting in longer hospital stays and greater cost. Imaging plays a fundamental role in the postoperative assessment. Specially, multidetector computed tomography scans (MDCT) is the modality of choice in the postoperative settings. Early diagnosis of the postoperative complications and differentiating them from being normal or expected postoperative findings is crucial to offer the best possible care for patients and to decrease the morbidity and mortality associated with surgery. In this article, we will briefly review the normal pancreatic anatomy, discuss the main types of pancreatic surgeries, and illustrate the imaging findings during the early postoperative period and of the main postsurgical complications in both acute and chronic postoperative settings.
Structural basis of elongation factor 2 switching.

Abstract Archaebacterial and eukaryotic elongation factor 2 (EF-2) and bacterial elongation factor G (EF-G) are five domain GTPases that catalyze the ribosomal translocation of tRNA and mRNA. In the classical mechanism of activation, GTPases are switched on through GDP/GTP exchange, which is accompanied by the ordering of two flexible segments called switch I and II. However, crystal structures of EF-2 and EF-G have thus far not revealed the conformations required by the classical mechanism. Here, we describe crystal structures of Methanoperedens nitroreducens EF-2 (MnEF-2) and MnEF-2-H595N bound to GMPPCP (GppCp) and magnesium displaying previously unreported compact conformations. Domain III forms interfaces with the other four domains and the overall conformations resemble that of SNU114, the eukaryotic spliceosomal GTPase. The gamma phosphate of GMPPCP is detected through interactions with switch I and a P-loop structural element. Switch II is highly ordered whereas switch I shows a variable degree of ordering. The ordered state results in a tight interdomain arrangement of domains I-III and the formation of a portion of a predicted monovalent cation site involving the P-loop and switch I. The side chain of an essential histidine residue in switch II is placed in the inactive conformation observed for the “on” state of elongation factor EF-Tu. The compact conformations of MnEF-2 and MnEF-2-H595N suggest an “on” ribosome-free conformational state.
New-Onset Delusions Heralding an Underlying Neurodegenerative Condition: A Case Report and Review of the Literature.

Objective To present a striking case of new-onset psychosis in a middle-aged woman subsequently diagnosed with behavioral variant frontotemporal dementia (bvFTD). To review the data regarding key red-flag features that may suggest a diagnosis of a neurodegenerative process, and specifically bvFTD, rather than a primary psychotic disorder. To examine the role of genetics, especially mutations of the microtubule-associated protein tau (MAPT) gene, in familial cases of frontotemporal dementia (FTD). Data sources The pertinent literature was searched online (PubMed, Google Scholar) using the following search terms: frontotemporal dementia (FTD), Pick's disease, behavioral variant FTD (bvFTD), psychosis, delusions, MAPT, and genetics. No date or language limit was applied. Study selection The case report was generated through detailed assessment of clinical notes, imaging studies, and laboratory results. The brain autopsy was carried out and summarized by our neuropathology team. Previously published literature was selected for inclusion in the review section based on relevance to the topic. Results A neurodegenerative etiology for psychosis (and specifically bvFTD) should be suspected in patients with progressive deficits in executive function, language, or memory. Other key warning features include the presence of a strong family history of a late-life psychotic disorder (or institutional placement or suicide), loss of empathy, impaired recognition of facial expression, or the development of emotional blunting and apathy, abnormal movements, or seizures. Conclusions Neurodegenerative disease should be on the differential diagnosis for any patient presenting with new-onset psychosis and behavioral changes in mid to late adulthood. Should red-flag features be present, early referral to a clinic specializing in dementia is recommended for further evaluation. This case highlights that MAPT mutations can be associated with psychosis in FTD and should be considered in the genetic workup. Ongoing research into the cellular and neural circuit mechanisms of psychosis in neurodegenerative disease may shed light on pathologic processes underlying psychosis in primary psychiatric disorders.
Tissue-specific fatty acid composition of glandular trichomes of mite-resistant and -susceptible Pelargonium xhortorum

Anacardic acids, alkyl phenolic acids excreted by tall glandular trichomes of the garden geranium, Pelargonium xhortorum, confer small-pest resistance. Up to 90% of the trichome exudate from mite-resistant P. xhortorum inbreds consists of an unusual anacardic acid with an unsaturated omega-5 (ω5) alkyl chain. As fatty acids are biochemical precursors to anacardic acids, we examined by GC the fatty acid composition of leaves, pedicels, petals, sepals, mature seeds, and glandular trichomes from pest-resistant and pest-susceptible Pelargonium inbred lines to determine the localization of ω5-fatty acids within plant tissues. The fatty acid composition of lipid classes (galactolipids, phospholipids, and neutral lipids) extracted from glandular trichomes from mite-resistant pedicels were also examined. ω5-Fatty acids (16:1Δ11 and 18:1Δ13) were found only in the glandular trichomes from pest-resistant geraniums (27.2% in trichomes of pedicels) and were localized predominantly in the phospho- and galactolipids (phosphatidylinositol, 25.9%; phosphatidylcholine, 18.2%; monogalactosyldiglyceride, 15.5%; and diglactosyldiglyceride, 14.0%).
Severity of fetal growth restriction stratified according to maternal obesity.

Objective: The primary objective of this study was to ascertain if among women with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile) the frequency of severe FGR (sFGR;...
The Icing on the Cake: How Background Factors Affect Law Faculties’ Predictions in Masterpiece Cakeshop

In Craig v. Masterpiece Cakeshop, Inc., a Colorado cake shop and its owner sought review of the Colorado Civil Rights Commission’s issuance of a cease and desist order for refusing to make a custom wedding cake for a same-sex wedding. The case brings up issues involving compelled expressive speech and the Free Exercise Clause of the First Amendment. The Colorado Court of Appeals held that neither of these constitutional rights was violated by the Colorado Civil Rights Commission’s actions. The Supreme Court of the United States granted the shop owner’s petition to review the case. Supreme Court oral arguments were heard on December 5, 2017. This article provides the results of an online survey of U.S. law school faculty. Masterpiece Cakeshop was selected for this survey because it is likely to evoke emotion. Therefore, it is an ideal case to assess how background factors affect Supreme Court predictions among law school faculty.
Maternal Circulating MiRNAs That Predict Infant FASD Outcomes Influence Placental Maturation

Abstract Prenatal Alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, though the linking causal mechanisms are unclear. We previously identified 11 gestationally-elevated maternal circulating miRNAs that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time, that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intra-vascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited expression of pro-EMT transcripts in placenta. Our data suggests that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction. Summary Maternal gestational circulating microRNAs, predictive of adverse infant outcomes including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts.
Rates of remission, sustained remission, and recurrence in a randomized controlled trial of cognitive behavioral therapy versus supportive psychotherapy for body dysmorphic disorder

Background Little data exist on remission rates following psychotherapy for body dysmorphic disorder (BDD). Methods Using data from a large study of therapist-delivered cognitive behavior therapy (CBT) versus supportive psychotherapy (SPT) for BDD (N = 120), we estimated remission rates at treatment endpoint, and rates of delayed remission, sustained remission, and recurrence at 6-month follow-up. We also examined improvement in broader mental health outcomes among remitters. Results Full or partial remission rates at end-of-treatment were significantly higher following CBT (68%) than SPT (42%). At 6-month follow-up, an additional 10% (CBT) and 14% (SPT) experienced delayed remission, 52% (CBT) and 27% (SPT) experienced sustained remission, and 20% (CBT) and 14% (SPT) experienced recurrence. Remission was never achieved by 18% (CBT) and 45% (SPT). Participants in remission at end-of-treatment experienced significant improvements in functional impairment, depression severity, BDD-related insight, and quality of life compared to nonremitters. Conclusions Full or partial remission rates are high following CBT for BDD and higher than after SPT.
When Electoral Responsiveness Harms Voters: Evidence from Electoral Pollution Cycles in Mexican Municipalities

Can electoral responsiveness harm voters, and if so, when? Most of the literature on electoral responsiveness rightly argues that voters support policies that bring about immediate positive outcomes. In this paper, we theorize a set of circumstances under which politicians’ pursuit of voters’ preferred policy can also have immediate adverse consequences for voters. We provide evidence of the effect of electoral incentives on a critical type of public good—air quality—in a young, developing democracy—Mexico. By leveraging the exogeneity of the local electoral calendar, we find that state governors can be particularly incentivized to improve public welfare perceivable to the voters during the election, but sacrifice air quality and inadvertently harm public health in both the short and long terms. We call this phenomenon an “electoral pollution cycle.” We show that regulatory forbearance, rather than economic boom, around the election most likely explains the phenomenon. We argue that the electoral pollution cycle can impose significant human costs. This paper contributes to the study of the welfare consequences of electoral incentives in democracies. It also sheds light on how voters could fail to internalize the tradeoff between different forms of welfare improvement in the short run.
Price-Induced Technical Progress in 80 Years of US Agriculture

This paper presents a theory of technical progress that interprets the price-induced conjecture of Hicks. It provides also an exhaustive set of comparative statics conditions that constitute the scaffolding for an empirical test of the theory. A crucial assumption is that entrepreneurs make decisions about techniques on the basis of expected information about prices and quantities. Another assumption is that these decisions are made in order to fulfill a profitability objective. The novelty of our approach is that expected relative prices enter the production function as shifter of the technology frontier. The consequence of this assumption is an expansion of the traditional Shephard lemma that is useful for identifying the portion of input quantities that have been determined by the conjecture of price-induced technical progress (PITP). The theory is applied to a sample of 80 years of US agriculture. Three versions of the general model are presented. The first version deals only with expected relative prices. The empirical results do not reject the PITP hypothesis. The second and third versions introduce lagged expected relative prices, lagged R&D expenditures and lagged extension expenditures as explanatory variables of the portion of the input quantities that may be attributable to technical progress.
We will now resume our regular programming

In this commentary, I take up the opportunity to explore what educational change in this pandemic era involves. In the process, I draw particularly on the institutional theories that help me understand why large-scale reform efforts so often fail to live up to their ambitions (Meyer & Rowan, 1977;Tyack & Cuban, 1995);on the theories of situated and distributed cognition that informed my training as a developmental psychologist (Salomon, 1983);and on the systems and complexity theories that help explain why mechanistic, linear plans to implement changes have to give way to an understanding of the ever-changing conditions and an embrace of emergent possibilities that cannot be entirely anticipated (Fullan, 2015;Senge, 1990;Wheatley, 1999)
STRUCTURAL CHANGES IN THE WORLD AUTO COMPANIES: THE EMERGING JAPANESE ROLE

Japan's recent dominance of the international auto industry does not result from some major single factor, such as technological superiority or advanced automation. It derives from twenty years of building flexible, durable industrial systems - integrating assemblers, suppliers, and related companies. Current competitive advantages result from combinations of seemingly unrelated company, government, and labor practices. Japan's position of leadership will instigate major changes in international labor forces, corporate strategies, and government policies, as former auto powers adapt to new competition, and simultaneous shifts in energy and economics.
DNA damage and DNA replication stress in yeast models of aging.

DNA damage is an important factor in aging in all eukaryotes. Although connections between DNA damage and aging have been extensively investigated in complex organisms, only a relatively few studies have investigated DNA damage as an aging factor in the model organism S. cerevisiae. Several of these studies point to DNA replication stress as a cause of age-dependent DNA damage in the replicative model of aging, which measures how many times budding yeast cells divide before they senesce and die. Even fewer studies have investigated how DNA damage contributes to aging in the chronological aging model, which measures how long cells in stationary phase cultures retain reproductive capacity. DNA replication stress also has been implicated as a factor in chronological aging . Since cells in stationary phase are generally considered to be “post-mitotic” and to reside in a quiescent G0/G1 state, the notion that defects in DNA replication might contribute to chronological aging appears to be somewhat paradoxical. However, the results of recent studies suggest that a significant fraction of cells in stationary phase cultures are not quiescent, especially in experiments that employ defined medium, which is frequently employed to assess chronological lifespan. Most cells that fail to achieve quiescence remain in a viable, but non-dividing state until they eventually die, similar to the senescent state in mammalian cells. In this chapter we discuss the role of DNA damage and DNA replication stress in both replicative and chronological aging in S. cerevisiae. We also discuss the relevance of these findings to the emerging view that DNA damage and DNA replication stress are important components of the senescent state that occurs at early stages of cancer.
Tool support for production use of formal techniques

The relatively scant use of formal techniques in software development is the result, in part, of a lack of suitable support tools. Many tools have been developed that provide novel analysis capabilities but lack basic yet commonplace facilities which are essential in production software development. More importantly, many existing tools for the development of formal specifications fail to provide mechanisms for the manipulation of natural language despite the fact that natural language is essential to give meaning to the terms in the formal specification. In this paper, we describe a toolset that has been developed with the specific intent of providing comprehensive facilities for creating formal specifications in production software development. The toolset supports a powerful formal notation, Z but also provides comprehensive and fully integrated support for natural language. As well as describing the toolset we present a preliminary evaluation of its use on a commercial specification.
Case History: The First Drug-Specific FDA-Approved Pharmacogenetic Test: UGT1A1 Genotyping for Irinotecan

PL-15 Irinotecan, a camptothecin prodrug, has had a checkered past, as early clinical investigators reported that the drug9s administration was associated with severe and unpredictable diarrhea and myelosuppression. Furthermore, the initial pharmacokinetic studies of this agent were unable to demonstrate a consistent relationship between drug and metabolite (SN-38) disposition and toxicity. Thus, the 1994 Cancer Research paper by Gupta and colleagues, demonstrating an inverse relationship between glucuronidation of SN-38 and toxicity, was of great interest. Subsequent studies demonstrated that SN-38 was a substrate for UGT1A1, the same enzyme responsible for bilirubin glucuronidation. These findings led to the hypothesis that heritable genetic variability in the UGT1A1 promoter (a variable number of TA repeats), which had been recently associated with serum bilirubin concentrations, was responsible for much of the interindividual variability in irinotecan9s pharmacokinetics and toxicity. This hypothesis was tested by our group and others, using a combination of in vitro, prospective clinical, and retrospective clinical studies. In general, there was agreement that there was a relationship between UGT1A1 genotype and phenotype (toxicity and pharmacokinetics), which led to an FDA-initiated change in the irinotecan label in 2005. Subsequently, the FDA approved a 510(k) application from Third Wave Technologies for UGT1A1 genotyping in the context of planned irinotecan therapy. More recent studies have confirmed the relationship of genotype to toxicity, although the optimal clinical use of this test has not been established.
Implementing a CMOS boundary-scan architecture tutorial

This tutorial discusses the implementation of a boundary-scan architecture in CMOS. The boundary-scan testability features and principles, as discussed in the Institute of Electrical and Electronics Engineers (IEEE) Standard 1149.1, are reviewed. Next, we describe the necessary steps to convert those principles into a practical boundary-scan architecture implementation. Our implementation was for the MOSIS 2 /spl mu/m Scalable CMOS (SCMOS) p-well process. Design tactics and issues for the individual architecture components are treated as well. >
Abstract 2047: Molecular photoacoustic imaging and serum diagnostics rapidly detect response to angiopoietin 1 and 2 blockade in ovarian cancer

Introduction: There is an urgent clinical need to develop noninvasive biomarkers that early detect tumor responses to anti-angiogenic therapy. Treatment response in ovarian cancer patients is assessed with transvaginal ultrasound imaging of tumor size and CA125 screening. We hypothesized that combining photoacoustic (PA) imaging to non-invasively visualize tumor vascular architecture, with serum diagnostics using endothelial biomarkers, would yield a sensitive and readily translatable approach for monitoring response to anti-angiogenic therapy. Methods: Ovarian tumors were established in nude mice by orthotopic injection of OV2008 cells at day 0. At day 10 mice were randomized into groups of at least n = 10. Baseline PA imaging and submandibular blood draw were performed, then repeated 24h after dosing with a peptibody that prevents the interaction of secreted angiopoietin 1 (Ang1; agonist) and 2 (Ang2; antagonist) with the receptor tyrosine kinase Tie2, or vehicle, on days 13, 16 and 19. Mice were then sacrificed and tumors excised for histology. Results: PA imaging uses endogenous hemoglobin light absorption to generate contrast. At 797nm, we found a 1.5-fold increase in hemoglobin-weighted signal in vehicle mice by day 19, while treated mice remained close to the baseline (n=9; p=0.008). The oxyhemoglobin-weighted PA signal (837nm/797nm) was elevated by 20% in treated mice but decreased 15% in vehicle mice (n=9; p Conclusions: We have shown for the first time that PA imaging and serum angiopoietin levels measure complementary parameters that indicate response to angiopoietin blockade in ovarian cancer. PA imaging noninvasively detected drug-induced vessel regression and normalization, giving a functional readout of response. This modality can be readily combined with transvaginal ultrasound. The drug action was mediated by normalization of mAng1 levels, indicated by serum measures and IF. Importantly, this work supports the combined use of in vitro and in vivo diagnostics to monitor response to anti-angiogenic therapy in clinical trials. Citation Format: Sarah E. Bohndiek, Laura Sasportas, Steven Machtaler, Jesse V. Jokerst, Sharon Hori, Sanjiv S. Gambhir. Molecular photoacoustic imaging and serum diagnostics rapidly detect response to angiopoietin 1 and 2 blockade in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2047. doi:10.1158/1538-7445.AM2014-2047
Measurement of Cytochrome P‐450

The family of cytochrome P-450 enzymes are involved in the metabolism of xenobiotics. This unit provides protocols for the three most common ways to measure cytochrome P-450. Spectrophotometric detection of the Soret band gives a quantitative measure of total cytochrome P-450 in microsomes, liver homogenate, or mitochondria, but lacks information about the specific P-450 forms. Immunochemical methods such as immunoblotting provide very sensitive semiquantitative identification of specific P-450 enzymes Finally, enzymatic assays depend on substrate specificity and also provide information about specific P-450 enzymes, although some members of this group of enzymes have broad and sometimes overlapping specificities.
A new type of cone-shaped high gain circularly polarized antenna for PCB integration

A new type of antenna having circularly polarization is developed and studied in this paper. The proposed structure consists of two cone-shaped radiators to construct a dipole antenna. One is simply fed by microstrip line and faced up on the top side. The other one is upside down and directly connected to the ground plane on the bottom side. In each identical cone-shaped radiator, by introducing a gap with appropriate size and specific position excites two orthogonal resonant modes with 90 degree phase deference that leads to good circular polarization. A reflector located at 9.4 mm over the antenna, which is capable of achieving large antenna gain (>8.84 dBi). At the operation frequency 5.8 GHz, the return loss is large than −18 dB and the main beam is toward to the direction at θ = 160° and ϕ = 130°. The other design results show the front-to-back ratio can reach to 13.12 dB, the circular polarization axial ratio in the main beam direction is less than 0.94dB, and the 3 dB circularly polarization axial ratio bandwidth is 375 MHz (5650 MHz to 6025 MHz). The sized of this proposed antenna is 4.5cm by 3cm and made out of FR4 (er = 4.3, tanδ = 0.02). Consequently, the antenna is very suitable for integration between different gears such as DVD player, AP, game console and so on.
Theoretical and experimental studies of shock-compressed benzene and polybutene

We report experimental and theoretical studies on shock pressure, volume, and temperature of liquid polybutene and benzene over the pressure ranges 19-210 GPa and 39-70 GPa, respectively. Analysis of the (P-V) Hugoniot data is consistent with a model which assumes hydrocarbons to be decomposed into a dense diamond-like phase and hydrogen in the molecular phase. The measured radiating temperatures of the shock front are substantially lower than the theoretical values and a possible reason is discussed. Chemical equilibrium calculations which include up to 12 species suggest the presence of small concentrations of several high-molecular-weight species.
An hypothesis: the same six polysaccharides are components of the primary cell walls of all higher plants.

Publisher Summary This chapter presents an overview of primary cell walls to reach consensus on the nomenclature of primary cell wall polysaccharides. The evidences are presented supporting the hypothesis that cellulose, xyloglucan, arabinoxylan, homogalacturonan, RG-I, and RG-II are the six polysaccharides common to all primary cell walls of higher plants. In many cells, these six polysaccharides account for all or nearly all of the primary wall polysaccharides. Like the physically interacting proteins that constitute the electron transport machinery of mitochondria, the structures of the six apparently ubiquitous polysaccharides of primary cell walls have been conserved during evolution. Indeed, it is hypothesized that the common set of six structural polysaccharides of primary cell walls have been structurally conserved because they physically interact while endowing the walls with closely related mechanisms for cell enlargement, cell differentiation, and resistance to pests.
Sarcomas of the prostate gland.

The prostate gland is an organ in which not only glandular elements may be involved by a neoplastic process but also contains numerous different types of mesenchymal elements that can develop into a primary neoplasm. This process may involve the neurogenic elements, the vascular compartment as wel1 as the supporting fibromuscular components of the prostate. We shall primarily discuss the fibromuscular tissue c0mpartment.l Even though it is composed mostly of fibrocytes and smooth muscle cells, there is also another type of muscular cel1 that gives rise to malignant neoplasms that develop primarily in the prostate. This is the skeletal muscle that can be seen readily in normal and benign prostatic tissue obtained after transurethral resection of a suprapubic prostatectomy.’ This is evidenced by the fact that rhabdomyosarcoma of the prostate is most commonly found in children whereas leiomyosarcoma and fibrosarcoma occur in a much older age group.
The Lived Experience of Self-Transcendence in Women With AIDS

Objective: To describe the lived experience of self-transcendence in women with AIDS, associated with increased sense of meaning and purpose, well-being, self-esteem, and connectedness with self and/or others. Design: Exploratory-descriptive, using phenomenological research methods for the study approach, data collection, and data analysis. Setting: One written description and nine audiotaped interviews of self-transcendence experiences were provided by women with class IV HIV infection (AIDS). Participants: Ten women recruited by nurses at an AIDS family clinic and through a flyer at the AIDS Support Group House in Seattle. Outcomes: Participant descriptions indicated that women with AIDS continue to find meaning and purpose in their lives through experiences of receiving from others, giving to others, and maintaining hope. Results: The findings support the theory that self-transcendence views and behaviors are a source of mental health at the end of life. Conclusions: The findings suggest several ways nurses may help women with AIDS discover or make meaning and purpose in their lives.
Assessment of dispersion corrected atom centered pseudopotentials: application to energetic molecular crystals.

A comparative study of the structural features of molecular crystals 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX), cyclotrimethylenetrinitramine (RDX), 2,4,6-trinitro-1,3,5-benzenetriamine (TATB), and pentaerythritol tetranitrate (PETN) at ambient pressure were calculated using density functional theory (DFT) and dispersion corrected atom centered pseudopotentials (DCACPs). While the molecular structural parameters showed little dependence on the pseudopotential used, the overall volume and lattice vector lengths were substantially improved by the use of DCACPs. DCACP predictions of lattice vector lengths are within 1.3% of experiment, corresponding to an approximately 2% error in density. Conversely, DFT underestimates crystal densities by 5−10%. The results indicate that DCACPs substantially compensate for the inadequate description of van der Waals interactions in DFT. Additionally, comparison of DCACP predictions with analogous calculations using an alternate dispersion corrected DFT method in...
Academic deficits in emotionally disturbed children revisited.

While some evidence exists that children with emotional disorders are deficient in academic achievement compared to non-handicapped populations, the nature and extent of these deficits remain unclear. For a sample of children admitted to a psychiatric hospital, achievement scores in reading, arithmetic, and spelling were obtained; and underachievement was computed based on mental age. Findings suggested that only minimal academic deficits exist but that wide variability is evident. Implications for differential diagnosis are discussed.
Inflammatory biomarkers in airways of patients with severe asthma compared with non‐severe asthma

Summary Background About 5–10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy. Objective We determined whether there were any differences in inflammatory biomarkers between severe and non-severe asthma patients. Methods Nineteen severe and 20 non-severe asthma patients were recruited and underwent collection of induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies. Results Biopsy results showed no differences in eosinophils (major basic protein positive), neutrophils, macrophages, T cells and mast cells in the bronchial submucosa. However, subbasement membrane (SBM) thickness and smooth muscle area were increased in the biopsies. No significant differences were observed in the induced sputum inflammatory cells. In BAL fluid, there was a significant increase in neutrophils but a significant decrease in macrophages. Eosinophil counts were non-significantly increased threefold in both sputum and BAL in severe asthma. Levels of IL-8 and IL-13 in sputum supernatants were similar in both groups of asthma patients. There was a significant inverse correlation between post-bronchodilator forced expiratory volume in 1 s and provocative concentration of methacholine causing a 20% fall in FEV1 with SBM thickness. Conclusion Differences in inflammatory cells were observed mainly in terms of increased neutrophils and reduction in macrophage numbers in BAL fluid with a trend towards increased eosinophils in severe asthma compared with non-severe asthma. However, the most notable features are the increase in features of airway wall remodelling of SBM thickness and smooth muscle area.
Preservation of phenotype in an organotypic cell culture model of a recessive keratinization defect of Norfolk terrier dogs.

: The purpose of this study is to reproduce in vitro a recessive keratinization defect of Norfolk terrier dogs characterized by a lack of keratin 10 (K10) production. Keratinocytes from skin biopsy samples of four normal dogs and two affected dogs were cultured organotypically with growth factor-supplemented media in order to stimulate cornification. The cultured epidermis from the normal dogs closely resembled the normal epidermis in vivo and cornified. The cultured epidermis from the affected dogs displayed many phenotypic alterations identified in skin biopsies from dogs with this heritable defect. Immunohistochemistry and immunoblotting showed a marked decrease in K10 from the cultures of the affected keratinocytes, compared to that in K10 from the cultures of the normal keratinocytes. Real-time reverse transcription polymerase chain reaction quantitation showed a 31-fold decrease in K10, a 1.75-fold increase in K1 and a 136-fold increase in K2e between the affected and the normal epidermis. Organotypic keratinocytes showed a 241-fold decrease in K10, a 31-fold decrease in K1 and a 1467-fold decrease in K2e between the affected and normal cultures. Although in vitro keratin expression did not precisely simulate in vivo, the morphology of the normal and the affected epidermis was largely preserved; thus, this culture system may provide an alternative to in vivo investigations for cutaneous research involving cornification.