cssi/SciSciGPT-SciSciNet huggingface dataset:
Cdc2-mediated Inhibition of Epidermal Growth Factor Activation of the Extracellular Signal-regulated Kinase Pathway during Mitosis

Inhibition of general transcription and translation occurs during mitosis to preserve the high energy requirements needed for the dynamic structural changes that are occurring at this time of the cell cycle. Although the mitotic kinase Cdc2 appears to directly phosphorylate and inhibit key proteins directly involved in transcription and translation, the role of Cdc2 in regulating up-stream growth factor receptor-mediated signal transduction pathways is limited. In the present study, we examined mechanisms involved in uncoupling receptor-mediated activation of the extracellular signal-regulated (ERK) signaling pathway in mitotic cells. Treatment with epidermal growth factor (EGF) failed to activate the ERK pathway in mitotic cells, although partial activation of ERK could be achieved in mitotic cells treated with phorbol 12-myristate 13-acetate (PMA). The discrepancy between EGF and PMA-mediated ERK activation suggested that multiple events in the ERK pathway were regulated during mitosis. We show that Cdc2 inhibits EGF-mediated ERK activation through direct interaction and phosphorylation of several ERK pathway proteins, including the guanine nucleotide exchange factor, Sos-1, and Raf-1 kinase. Inhibition of Cdc2 activity with roscovitine in mitotic cells restored ERK activation by EGF and PMA. Similarly, mitotic inhibition of ERK activity in cells expressing active mutants of H-Ras and Raf-1 kinase could also be reversed following Cdc2 inhibition. In contrast, ERK activation in cells expressing active MEK1 was not inhibited during mitosis or affected by roscovitine. These data suggest that Cdc2 inhibits growth factor receptor-mediated ERK activation during mitosis by primarily targeting signaling proteins that are upstream of MEK1.
Barriers and facilitators to the incorporation of environmental health into public health nursing practice.

Objectives: To describe the environmental health (EH) demands placed on public health nurses (PHNs) as well as the barriers and facilitators to incorporating EH into PHN practice. Design and Sample: A cross-sectional multimode (Web and pencil/paper) survey was used to collect data from PHNs in 1 rural western state. Research participants included 141 PHNs from a total of 228 survey invitations (61% response). Measures: A 39-item questionnaire was developed to measure the frequency of EH demands experienced by PHNs as well as the barriers and facilitators to the incorporation of EH into PHN practice and standard demographics. Results: Significant numbers of PHNs reported less than baccalaureate preparation (29%), suggesting that EH competencies cannot be assumed. PHNs are often asked for basic EH information and cite lack of time and lack of interest on the part of the populations being cared for as barriers to incorporating EH into their practice. Facilitators included free or inexpensive continuing education programs offered via the Internet and additional Internet resources or staff resource people. Conclusion: PHNs represent a significant portion of the public health workforce and have implied and explicit mandates to address EH issues in their practice. Resources should be directed toward helping PHNs become better prepared to address the current and future EH needs of populations.
Schedule-dependent therapeutic gain from the combination of fractionated irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/Km mouse model systems.

Abstract Cytotoxic drugs were administered either in single or fractionated doses before, during, or after a standard course of 5 daily X ray exposures. SCCVII and RIF-1 tumors were grown from cells implanted in the gastrocnemius muscles of syngeneic C3H Km mice, and treatments were evaluated by regrowth delay (GD). Non-tumor-bearing mice were irradiated locally to the upper abdomen for analysis of intestinal crypt cell survival, an acute normal tissue effect; other non-tumor-bearing mice were irradiated locally to the thorax for analysis of early (pneumonitis) and late (fibrosis) effects on the lungs, as reflected in changes in breathing rates. In a series of experiments to test the combination of i.p. 5-FU, cis-DDP, and X ray, dose effect factors (DEF's) were computed so that therapeutic gain factors (TGF's) could be calculated from the ratio, DER (tumor)/DEF (normal tissue) . The highest TGF, 6.7 (tumor/duodenum), was obtained for the schedule in which 100 mg/kg 5-FU was given 24 hr before the simultaneous administration of 1.6 mg/kg cis-DDP and X ray for 5 consecutive days. The following summary refers only to tumor growth delay data. In confirmation of previous extensive experiments, the combination of cis-DDP + X ray showed supra-additivity, whether the drug was given in a single dose (abbreviated P ) or simultaneously with X ray (abbreviated px), that is, P x x x x x or px px px px px. For CY + X ray, the greatest supra-additivity was obtained for either C x x x x x or x x x x x C. 5-FU alone did not act supra-additively with fractionated irradiation, but the addition of 5-FU to cis-DDP + X ray was supra-additive for certain schedules, maximally for F px px px px px. CY combined to give greater than additivity with either cis-DDP or X ray alone, and the combination of CY + cis-DDP + X ray appeared to be supra-additive for five different schedules, maximally for C x x x x x P. Normal tissue effects are being evaluated for these same schedules so that TGF's might soon be obtained.
Translational studies on augmentation of intratubular renin-angiotensin system in hypertension.

Various models of experimental hypertension and clinical examples of increased renin formation from a stenotic kidney or a juxtaglomerular cell tumor have shown that increased circulating angiotensin II (Ang II) stimulates the intrarenal/intratubular renin–angiotensin system (RAS) that elicits renal vasoconstriction, enhanced tubular sodium reabsorption, and progressive development of hypertension and renal injury. The enhanced intrarenal Ang II activity is due to both receptor-mediated Ang II uptake and Ang II type 1 (AT1) receptor–mediated stimulation of renal angiotensinogen (AGT) mRNA and protein by proximal tubule cells. The increased AGT secretion leads to local formation of Ang II and spillover of AGT into the distal nephron segments as reflected by increased AGT excretion in the urine, which provides an index of intrarenal RAS activity. In clinical studies, increased urinary excretion of AGT has been demonstrated in hypertension, type 1 and type 2 diabetes mellitus, and several types of chronic kidney diseases. In addition, renin secretion from principal cells of the collecting ducts is increased by AT1 receptor activation and acts on AGT from the proximal tubule to form more Ang I. Renin and/or (pro)renin activity is enhanced by binding to the (pro)renin receptor (PRR) on intercalated cells or secreted as soluble PRR contributing further to AGT cleavage, thus making more substrate available for Ang II conversion by local angiotensin-converting enzyme. The augmented intratubular Ang II concentrations together with elevated renal interstitial Ang II concentrations contribute to sustained stimulation of sodium reabsorption, vasoconstriction, development of hypertension, and progressive renal injury and fibrosis.
ESCUDO: A Fine-Grained Protection Model for Web Browsers

Web applications are no longer simple hyperlinked documents. They have progressively evolved to become highly complex—web pages combine content from several sources (with varying levels of trustworthiness), and incorporate significant portions of client-side code. However, the prevailing web protection model, the same-origin policy, has not adequately evolved to manage the security consequences of this additional complexity. As a result, web applications have become attractive targets of exploitation. We argue that this disconnection between the protection needs of modern web applications and the protection models used by web browsers that manage those applications amounts to a failure of access control. In this paper, we present Escudo, a new web browser protection model designed based on established principles of mandatory access control. We describe our implementation of a prototype of Escudo in the Lobo web browser, and illustrate how web applications can use Escudo for securing their resources. Our evaluation results indicate that Escudo incurs low overhead. To support backwards compatibility, Escudo defaults to the same-origin policy for legacy applications.
Named entity mining from click-through data using weakly supervised latent dirichlet allocation

This paper addresses Named Entity Mining (NEM), in which we mine knowledge about named entities such as movies, games, and books from a huge amount of data. NEM is potentially useful in many applications including web search, online advertisement, and recommender system. There are three challenges for the task: finding suitable data source, coping with the ambiguities of named entity classes, and incorporating necessary human supervision into the mining process. This paper proposes conducting NEM by using click-through data collected at a web search engine, employing a topic model that generates the click-through data, and learning the topic model by weak supervision from humans. Specifically, it characterizes each named entity by its associated queries and URLs in the click-through data. It uses the topic model to resolve ambiguities of named entity classes by representing the classes as topics. It employs a method, referred to as Weakly Supervised Latent Dirichlet Allocation (WS-LDA), to accurately learn the topic model with partially labeled named entities. Experiments on a large scale click-through data containing over 1.5 billion query-URL pairs show that the proposed approach can conduct very accurate NEM and significantly outperforms the baseline.
Biotechnology and molecular computing

Abstract Carbon-based molecular machines are in sight for the next-generation electronics industry. In that nature has been producing and maintaining molecular machines for millions of years, the biological sciences may hold the keys to tomorrow's computer science disciplines. This article reviews some contributions that natural systems may make, and some general concerns that have yet to be resolved in realizing molecule-based devices.
Arabidopsis Separase AESP Is Essential for Embryo Development and the Release of Cohesin during Meiosis

To investigate how and when sister chromatid cohesion is released from chromosomes in plants, we isolated the Arabidopsis thaliana homolog of separase (AESP) and investigated its role in somatic and meiotic cells. AESP is similar to separase proteins identified in other organisms but contains several additional structural motifs. The characterization of two Arabidopsis T-DNA insertion alleles for AESP demonstrated that it is an essential gene. Seeds homozygous for T-DNA insertions in AESP exhibited embryo arrest at the globular stage. The endosperm also exhibited a weak titan-like phenotype. Transgenic plants expressing AESP RNA interference (RNAi) from the meiosis-specific DMC1 promoter exhibited alterations in chromosome segregation during meiosis I and II that resulted in polyads containing from one to eight microspores. Consistent with its predicted role in the release of sister chromatid cohesion, immunolocalization studies showed that the removal of SYN1 from chromosome arms and the centromeres is inhibited in the RNAi mutants. However, the release of SYN1 during diplotene occurred normally, indicating that this process is independent of AESP. Therefore, our results demonstrate that AESP plays an essential role in embryo development and provide direct evidence that AESP is required for the removal of cohesin from meiotic chromosomes.
Evidence for the inherent unsteadiness of a river plume : Satellite observations of the Niagara River discharge

We present satellite data from the Niagara River plume showing that a large eddy, or bulge, forms and grows in the plume near the mouth of the river. The plume consists of a semicircular bulge region immediately offshore of the mouth and a narrow current that propagates east along the shoreline. During the low-wind period from 27 to 29 May 1999, the width of the bulge more than doubled and the current width increased only slightly. Approximately one-third of the Niagara River water accumulated in the bulge near the mouth during this period, implying that the transport rate in the shore-parallel current was reduced to two-thirds of the river discharge rate. The effective radius and the growth rate of the bulge computed from the satellite images was in good agreement with previous laboratory results and a numerical model of the Niagara River plume. This is the first field evidence of the unsteadiness of the bulge.
Kein Ende für Totalsynthesen von Strychnin in Sicht? Lektionen für Strategien und Methoden in der Totalsynthese

Von Beginn des 19. Jahrhunderts an bis in die Gegenwart hinein haben sich Chemiker mit dem komplexen Indol-Alkaloid Strychnin beschaftigt. In diesem Aufsatz wollen wir untersuchen, weshalb Strychnin bis zum heutigen Tag eine bedeutende Zielstruktur fur direkte Syntheseversuche ist. Wir werden eine Reihe von Syntheserouten zu Strychnin diskutieren, um so letztlich ihren Einfluss auf die Entwicklung von Strategien und Methoden in der organischen Synthese aufzuklaren.
TOWARD A THEORY OF THE POLITICAL ENTREPRENEUR: EVIDENCE FROM LOCAL GOVERNMENT

Political scientists have been increasingly interested in entrepreneurs—individuals who change the direction and flow of politics. In this research note, we synthesize aspects of an economic approach to entrepreneurship with concepts used in political science. We then tie these theoretical observations to the emergence of entrepreneurs in local governments and test components of our theory using observations from a large set of suburban municipal governments. Empirically, we identify several conditions that affect the probability that an entrepreneur will emerge in a local government, especially slack budgetary resources that the political entrepreneur can reallocate. We also find that the probability with which an entrepreneur is found in local government is a function of the difficulty of overcoming collective action problems in a community.
Premarket Safety and Efficacy Studies for ADHD Medications in Children

Background: Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing. Methods: We identified all ADHD medications approved by the Food and Drug Administration (FDA) and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug’s clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials. Results: A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419). Eleven drugs (55%) were approved after ,100 participants were studied and 14 (70%) after ,300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9), with 5 (38%) drugs approved after participants were studied ,4 weeks and 10 (77%) after ,6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed. Conclusions: Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.
Making the invisible visible: verbal but not visual cues enhance visual detection.

Background: Can hearing a word change what one sees? Although visual sensitivity is known to be enhanced by attending to the location of the target, perceptual enhancements of following cues to the identity of an object have been difficult to find. Here, we show that perceptual sensitivity is enhanced by verbal, but not visual cues. Methodology/Principal Findings: Participants completed an object detection task in which they made an object-presence or -absence decision to briefly-presented letters. Hearing the letter name prior to the detection task increased perceptual sensitivity (d9). A visual cue in the form of a preview of the to-be-detected letter did not. Follow-up experiments found that the auditory cuing effect was specific to validly cued stimuli. The magnitude of the cuing effect positively correlated with an individual measure of vividness of mental imagery; introducing uncertainty into the position of the stimulus did not reduce the magnitude of the cuing effect, but eliminated the correlation with mental imagery. Conclusions/Significance: Hearing a word made otherwise invisible objects visible. Interestingly, seeing a preview of the target stimulus did not similarly enhance detection of the target. These results are compatible with an account in which auditory verbal labels modulate lower-level visual processing. The findings show that a verbal cue in the form of hearing a word can influence even the most elementary visual processing and inform our understanding of how language affects perception.
Testing for faults, looking for defects

A commonly used criterion for evaluating tests for a VLSI chip is the coverage of modeled stuck-at faults. This coverage is deterministic, is easy to measure and has become an established standard. However, an often-asked question is: can the fault coverage tell us the defect level? Or, do we know how many defective chips will escape testing? This talk explains how thirty years of research provides some answers. An analysis of the test data for a Sematech chip gives a defect level of 1, 000 defective parts per million (DPM) for 99% fault coverage. It further calculates the fault coverage requirement as 99.9% to lower the defect level to 100 DPM. For today's large chips and system-on-chip (SOC) devices tests with such high coverage, if at all possible, are expensive to derive and expensive to apply. So, we pose a second question: how good are the stuck-fault coverage tests at detecting the presence of “real” defects, such as, to name a few, bridges, opens, shorts, or delays? Further analysis of the Sematech test data indicates that the stuck-at fault coverage may be a pessimistic indicator of the defect coverage. In other words, in trying to blindly increase the stuck-at fault coverage we may be chasing wrong targets. We summarize with thoughts on directions the industry is taking.
Efficient implementation of neighborhood logic for cellular automata via the Cellular Neural Network Universal Machine

The main difficulty in implementing cellular automata on the Cellular Neural Network Universal Machine (CNNUM) is the need to perform arbitrary logic functions of the input neighborhood. Since the architecture computes weighted sums of this neighborhood, by using a "B-template," it is limited to threshold logic, i.e., a logical operation to be computed by a single transient must be in the class of linearly separable Boolean functions. It was shown previously how a general logic function can be implemented on the CNNUM by cascading component functions from this class-namely by the direct implementation of the minterm or maxterm formulation of the desired function. However, for functions of a 3/spl times/3 input neighborhood this method may require up to 256 stages. We propose a more efficient method for implementing general logic functions on the CNNUM and other hardwares capable of performing a threshold logic function of an input neighborhood. The class of considered component functions is a superset of the minterms and maxterms but, for purposes of searchability, ease of implementation, and robustness, a subset of the general linearly separable Boolean functions. We have formulated an algorithm that will find a sequence of weight-restricted threshold logic functions (B-templates with weights from {-1, 0, +1} and a bias) that, when cascaded together using two-input logical operations, will result in the desired Boolean function. Two examples are given to exhibit the algorithm.
HUMANITARIAN MILITARY INTERVENTION: WARS FOR THE END OF HISTORY?

A current topic of global justice is the debate over the right of humanitarian military intervention or, as some style it, the “responsibility to protect” the “human security” of all, especially where that security is threatened by the very sovereign power charged to defend it. Such intervention came into its own only in the decade of the Nineties. This essay analyzes the factors that favored that outcome and sketches the difficulties to which humanitarian intervention proved to be exposed. There can be no doubt that the rhetoric supporting such a policy has expanded greatly during the past generation. But what of the reality? Is the “responsibility to protect” likely to prove the wave of the future, or merely that of the (still very recent) past?
Structural changes in the brain in depression and relationship to symptom recurrence

Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.
Hybrid Intrusion Detection Algorithm for Private Cloud

Detection and Prevention of Intrusion in the cloud environment is a tedious process. The main objective of this research work is to propose a Hybrid Intrusion Detection algorithm for private cloud environment which is efficient interms of security and performance. A detailed study has been carried out on the existing Intrusion detection systems, which gives a clear view that existing system cannot detect intrusion effectively. Artificial Intelligence has been incorporated in the research work to detect any type of intrusion in private cloud environment. Incorporating Artificial Intelligence technique resulted in self adapative Intrusion Detection System, which has been tested using the real time data collected using the network speed. Implementation of the research work gives a clear view about the efficiency of the algorithm in terms of security and performance, which has not been considered in the earlier research work. Detailed statistical analysis has been carried out as a part of the research work to prove the correctness of the proposed algorithm. The result of the implementation and analaysis gives a clear scope for further research work on Intrusion Detection System for cloud based environment. The proposed algorithm can be implemented for highly secured private cloud which are built for Military purpose and Banking sector to monitor the activities of the network efficiently.
Rating Environmental Performance in the Building Industry: Leadership in Energy and Environmental Design (Leed)

Environmentally preferable, or "green," building uses optimal and innovative design to provide economic, health, environmental, and social benefits. In 1993, the U.S. Green Building Council (USGBC) was formed by a broad range of building-industry stakeholders from the public, private, and nonprofit sectors. It is a committee-based, member-driven, and consensus-focused nonprofit coalition leading a national effort to promote high-performance buildings that are environmentally responsible, profitable, and healthy places to live and work. In 2000, USGBC created the Leadership in Energy and Environmental Design (LEED(tm)) rating system, which this case explores. This voluntary standard is intended to transform the building market by providing guidelines, certification, and education for green building. LEED is a comprehensive, transparent, and market-driven framework for assessing buildings' environmental performance. Compared with standard practice, green buildings can provide greater economic and social benefits over the life of the structures, reduce or eliminate adverse human health effects, and even contribute to improved air and water quality. Opportunities for reducing both costs and environmental impact include low-disturbance land-use techniques, improved lighting design, high-performance water fixtures, careful selection of materials, energy-efficient appliances and heating and cooling systems, and on-site water treatment and recycling. Less familiar innovations include natural ventilation and cooling without fans and air conditioners, vegetative roofing systems that provide wildlife habitat and reduce storm-water runoff, and constructed wetlands that help preserve water quality while reducing water-treatment costs.
Predictors of caregiver satisfaction with visiting nurse home visits after NICU discharge.

High-risk infants are commonly referred to Visiting Nurse Association (VNA) agencies for post-hospitalization services after discharge from the neonatal intensive care unit (NICU). Little is known about the effectiveness and perceived benefits of routine VNA services for these infants. The objective of this study was to identify factors predictive of family satisfaction with VNA services after NICU discharge. This is an observational study using data collected from routine quality assurance phone calls to families after NICU discharge. The setting is a single NICU at a large, urban academic medical center in Boston, MA, USA. We included all hospitalized infants discharged from the NICU from 1 January 2008 to 31 July 2014. Predictors included markers of infant biological and social risk and a survey measure of parent and nurse perceptions of parents’ preparedness at discharge. The outcome was parent response to the question, ‘Did you find the VNA visit helpful?’ at 2 weeks post discharge. Bivariate analyses showed perceived helpfulness of VNA visits associated with low maternal parity, lower 1-min Apgar score, lower birth weight and gestational age, diagnosis of respiratory distress syndrome and intraventricular hemorrhage and low discharge readiness scores. Only low maternal parity (odds ratio (OR) 1.82, 95% confidence interval (CI) 1.35, 2.46) and birth <35 weeks’ gestation (OR 1.45, 95% CI 1.15, 1.83) were significant predictors in multivariable analysis. Low maternal parity and gestational age <35 weeks predicted parent satisfaction with VNA services. Referral for VNA services is common after NICU discharge. There are currently no guidelines indicating which infants and families stand to benefit most from such services. Our findings may help in developing and streamlining processes for post-hospitalization VNA service referrals for high-risk infants.
"Uncontrolled desires": the response to the sexual psychopath, 1920-1960.

In the 1931 German film M, Peter Lorre portrayed a former mental patient who stalked innocent school girls, lured them with candy and balloons, and then, offscreen, murdered them in order to satiate his abnormal erotic desires. Two years later, when the film opened in the United States, the New York Times criticized director Fritz Lang for wasting his talents on a crime "too hideous to contemplate." Despite the reviewer's distaste for the public discussion of sexual crimes, the American media soon began to cater to a growing popular interest in stories of violent, sexual murders committed by men like "M." In 1937 the New York Times itself created a new index category, "Sex Crimes," to encompass the 143 articles it published on the subject that year. Cleveland, Detroit, and Los Angeles newspapers also ran stories about sexual criminals, while national magazines published articles by legal and psychiatric authorities who debated whether a "sex-crime wave" had hit America., The sex crime panic soon extended beyond the media and into the realm of politics and law. Between 1935 and 1965, city, state, and federal officials established commissions to investigate sexual crime, passed statutes to transfer authority over sex offenders from courts to psychiatrists, and funded specialized institutions for the treatment of sex offenders. As a result, in most states, a man accused of rape, sodomy, child molestation, indecent exposure, or corrupting the morals of a
An epizootic of unknown etiology in guinea pigs.

Summary and conclusionsBecause of the inconsistency obtained in attempted passage of the etiological agent to susceptible guinea pigs, it is postulated that the etiological agent was not being passed at all. It appeared that many of the inoculations merely served to prematurely hasten an unknown etiological agent on its way, culminating in the disease pattern and the epizootic which has been described.An epizootic of unknown etiology has been observed in guinea pigs. The disease was highly fatal. The symptoms and pathology were unlike any previously described disease of guinea pigs.
A Hormone Which Induces Pupation in the Common House Fly, Musca Domestica Linn.

Within the past few years a small group of workers in experimental entomology have been developing the new field of insect endocrinology . Most of this research has been in connection with hormones which initiate the processes of moulting and pupation, although hormonal activity has been shown to be present in the adult insect (Wigglesworth, 1936; Weed, 1936 and 1937). Questions have arisen concerning the application to insects of the term hormone, but it may be used in the true sense of the word since these secretions are produced in ductless glands, comparable to vertebrate endocrine organs which discharge directly into the blood.
Transmission of Type II (Marek’s) Leukosis with Semen from Infected Roosters

Abstract Type II (Marek’s) leukosis has been reported to be caused by a filterable virus (Sevoian et al., 1962) and more recently a herpes-like virus (Churchill and Biggs, 1967; Nazerian et al., 1968). Transmission of this infection among chickens has been demonstrated with oral washings and feces (Witter and Burmester, 1967) and by the air borne route (Sevoian et al., 1963) from infected chickens. A more recent report gave data indicating egg transmission (Sevoian, 1968) in support of earlier observation by Gibbs (1936) who found leukotic cells in the ovule of the ovary, in the tubes of the testes, and in the seminal and follicular fluids of infected roosters and hens respectively. Trials reported herein indicate the infective status of semen from roosters infected with Type II leukosis. MATERIALS AND METHODS Donors of artificially collected semen were eight-month-old cross-bred roosters kept at the University farm under natural conditions. Approximately 0.5 cc.…
Forbidden word entropy of cerebral oximetric values predicts postoperative neurocognitive decline in patients undergoing aortic arch surgery under deep hypothermic circulatory arrest.

Purpose: Up to 53% of cardiac surgery patients experience postoperative neurocognitive decline. Cerebral oximetry is designed to detect changes in cerebral tissue saturation and therefore may be useful to predict which patients are at risk of developing neurocognitive decline. Methods: This is a retrospective analysis of a prospective study originally designed to determine if treatment of cerebral oximetry desaturation is associated with improvement in postoperative cognitive dysfunction in patients undergoing aortic reconstruction under deep hypothermic circulatory arrest. Cognitive function was measured, preoperatively and 3 months postoperatively, with 15 neuropsychologic tests administered by a psychologist; the individual test scores were summed and normalized. Bilateral cerebral oximetry data were stored and analyzed using measures of entropy. Cognitive decline was defined as any decrease in the summed normalized score from baseline to 3 months. Results: Seven of 17 (41%) patients suffered cognitive decline. There was no association between baseline cerebral oximetry and postoperative cognitive dysfunction. Nor were changes in oximetry values associated with cognitive decline. However, cognitive decline was associated with loss of forbidden word entropy (FwEn) (correlation: Rho ρ = 0.51, P = 0.037 for left cerebral oximetry FwEn and ρ = 0.54, P = 0.025 for right cerebral oximetry FwEn). Conclusion: Postoperative cognitive decline was associated with loss of complexity of the time series as shown by a decrease in FwEn from beginning to end of the case. This suggests that regulation of cerebral oximetry is different between those who do and those who do not develop cognitive decline.
STUDIES IN IRON ABSORPTION. III. BODY RADIOACTIVITY MEASUREMENTS OF PATIENTS WITH LIVER DISEASE.

Summary The range of iron absorption, determined by measurement of body radioactivity after ingestion of a standard test dose of Fe 59 labeled ferrous sulfate, was 1.0 to 44.7 per cent in a group of 24 patients with cirrhosis of the liver as compared with a range of 1.7 to 9.5 per cent in 6 hematologically normal subjects without cirrhosis. In 3 iron deficient patients the range was 4.0 to 18.3 per cent. There was no significant correlation between iron absorption and any of the following indices of iron metabolism: degree of anemia, bone marrow hemosiderin, liver hemosiderin, serum iron concentration, unsaturated serum iron binding capacity, or halftime of disappearance of transferrin bound Fe 59 in the plasma. Arterial oxygen saturation measured in 6 of the cirrhotic subjects was normal. Iron absorption was measured after surgical portacaval anastomosis in 3 patients with cirrhosis. The range in this group (3.0 to 44.7 per cent) paralleled that of the entire group of cirrhotics, suggesting either that enhanced iron absorption after such surgery may be a reflection of the liver disease itself, or that the formation of spontaneous collateral circulation bypassing the liver in unoperated cirrhotics may be the factor leading to enhanced iron absorption. This enhanced absorption of iron in patients with cirrhosis lends support to the concept that in some patients with hemochromatosis liver disease may be the primary factor and may precede the accumulation of iron in the tissues.
Interleukin-12 armored chimeric antigen receptor (CAR) T cells for heterogeneous antigen-expressing ovarian cancer.

12Background: Immune escape via downregulation of tumor associated antigens (TAAs) is an important mechanism of resistance to Chimeric Antigen Receptor (CAR) T cell therapy. Particularly in solid tumor malignancies where antigen expression could be heterogeneous, the risk of antigen-low or antigen-negative relapse is significantly high. One strategy to overcome this limitation is to reengineer CAR T cells to engage other arms of the immune system such as endogenous cytotoxic T cells and dendritic cells (DC) to broaden the antitumor response beyond the TAA targeted by CAR T cells. This could be achieved by co-modifying CAR T cells with Interleukin-12 (IL-12). IL-12 is a proinflammatory cytokine produced by DCs, and macrophages, and has been shown to promote maturation of DCs and increase T-cell proliferation. We hypothesized that CAR T cells genetically engineered to constitutively secrete IL-12 will be efficacious against Muc16ecto low (MLo) and Muc16ecto high (MHi) heterogeneous tumors in a syngeneic mou...
The Diagnostic Odyssey of Autism Spectrum Disorder.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by challenges in social communication and interaction and restricted or repetitive behavior, interests, or activities. Although ASD symptoms generally manifest in early childhood, many individuals experience delays accessing an autism diagnosis and related services. In this study, we identify the individual, social, and structural factors that influence parents9 experiences of children9s ASD diagnosis. METHODS: Parents of 25 children with autism participated in 60- to 90-minute semistructured in-person interviews. Interviews were recorded and transcribed verbatim. Transcripts were analyzed using the method of grounded theory. This inductive method allowed analysts to identify key themes related to participants’ experiences of children9s ASD diagnosis. RESULTS: The process of ASD diagnosis reflects an odyssey that includes 3 key phases: the prediagnosis phase, in which “Making Sense of Child Difference” is a primary characteristic of participants’ experiences; the during-diagnosis phase, when “Navigating Diagnosis” suggests systematic barriers that influence the timing of ASD diagnosis; and the postdiagnosis phase, when participants’ experiences of “Connecting to Services” point to the important role that personal efforts play in gaining access to care. CONCLUSIONS: In this study, we highlight individual, social, and structural factors that influence parent experiences before, during, and after their child9s autism diagnosis. Our findings indicate the need for more consistent and continuous support for autistic individuals and their families during the diagnostic odyssey, as well as resources that better represent the diversity of experiences and symptoms associated with autism across the life course.
A combined positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner

The advent of hybrid scanners, combining complementary modalities, has revolutionized the application of advanced imaging technology to clinical practice and biomedical research. In this project, we investigated the melding of two complementary, functional imaging methods: positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI). PET radiotracers can provide important information about cellular parameters, such as glucose metabolism. While EPR probes can provide assessment of tissue microenvironment, measuring oxygenation and pH, for example. Therefore, a combined PET/EPRI scanner promises to provide new insights not attainable with current imagers by simultaneous acquisition of multiple components of tissue microenvironments. To explore the simultaneous acquisition of PET and EPR images, a prototype system was created by combining two existing scanners. Specifically, a silicon photomultiplier (SiPM)-based PET scanner ring designed as a portable scanner was combined with an EPRI scanner designed for the imaging of small animals. The ability of the system to obtain simultaneous images was assessed with a small phantom consisting of four cylinders containing both a PET tracer and EPR spin probe. The resulting images demonstrated the ability to obtain contemporaneous PET and EPR images without cross-modality interference. Given the promising results from this initial investigation, the next step in this project is the construction of the next generation pre-clinical PET/EPRI scanner for multi-parametric assessment of physiologically-important parameters of tissue microenvironments.
Mitochondrial Reactive Oxygen Species in Proapoptotic Effect of Promising Cancer Chemopreventive Phytochemicals

Cancer chemopreventive phytochemicals have been identified from multiple dietary plants as well as from components of alternative medicine. Preclinical studies using rodent cancer models have provided compelling experimental evidence for cancer chemopreventive effects of these phytochemicals. Mitochondria-derived reactive oxygen species (ROS) play a critical role in their prodeath and chemopreventive responses. These phytochemicals inhibit mitochondrial electron transport chains causing ROS production, thus triggering apoptotic and/or autophagic cancer cell death. Although normal epithelial cells are resistant to mitochondrial perturbations by many phytochemicals, underlying mechanisms of the differential response in cancer cells versus normal cells remain elusive. This chapter reviews experimental evidence linking mitochondrial reactive oxygen species in cancer chemopreventive effects of a few promising phytochemicals.
Negative regulation of rat hepatic aldehyde dehydrogenase 3 by glucocorticoids.

The alyde dehydroghenases are a family of proteins whose function is to catalyze the oxtion of a wide variety of aliphatic and aromatic aldehydes to their corresponding carboxc acids and are classified according to their sequence similarity (Linda 1994). One family member, aldehyde dehydrogenase 3, is induced by polycyclic aromathydrocarbons or chlorinated aromatic compounds, such as TCDD (Dunn et al., 1988).ese compounds are ligands for the Ah receptor, which functions as a transcription factorn concert with a dimerization partner, known as ARNT (Ah receptor nuclear transltor), Ah receptor binds to a canonical consensus sequence (TNGCGTC), denoted AhE. Binding facilitates gene transactivation (Whitlock et al., 1996). Two AhRE core sequences have b identified in the 5’ flanking region of the rat ALDH3 gene (Takimoto et al., 1;Xie et al., 1996).
Sensitivity studies of the effects of nuclear data uncertainties for the higher plutonium isotopes upon fast reactor design

The sensitivity of LMFBR design parameters to nuclear data uncertainties is investigated. Based on a review of the available cross section literature, the uncertainties in the cross sections of 240Pu, 241Pu, and 242Pu, as well as 239Pu and 238U, are evaluated. The effects of these cross section uncertainties upon reactor parameters are assessed by making uniform cross section adjustments within the range of uncertainties. The sensitivity calculations consider two methods of maintaining the system at critical: (1) by adjusting the core enrichment, and (2) by adjusting the amount of control in the core. The results of these sensitivity calculations are compared with target accuracies for calculation of reactor parameters. These sensitivities are further used to estimate the nuclear data uncertainties which would be allowable to meet the target accuracies.
Predictive modeling of broad wavelength light-harvesting performance in assemblies of multiple chromophores

Abstract Developing efficient panchromatic light harvesting systems that exploit the energy available from the entire solar spectrum in an economically feasible and scalable fashion is of great importance. Light harvesting by incorporating multiple chromophores into molecular assemblies such as micelles and vesicles is one method for accomplishing this result. In this paper, we describe panchromatic light harvesting in lipid-based vesicle bilayers that contain a random distribution of lipid-bound chromophores. Numerically exact modeling based on Forster theory is developed to establish the criteria for designing a highly efficient panchromatic light-harvesting unit. An approximate modeling method is also developed to greatly reduce the complexity of the modeling problem. Both the exact and approximate models are verified by designing and experimentally testing an efficient three-chromophore light-harvesting system. For the experiments, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (Rhod) as the lowest energy chromophore, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (NBD) as an intermediate acceptor, and Marina Blue® 1,2-Dihexadecanoyl-sn-Glycero-3-Phosphoethanolamine (MB) as the highest energy absorber (donor) are selected. From chromophore concentrations and R0 values, modeling predicts an overall efficiency of energy transfer to the terminal acceptor greater than ≈0.6 across a broad excitation wavelength range of ≈250 nm. The predicted transfer efficiency is verified by the experimental results. In addition, comparison of the approximate modeling method with both the numerically exact method and experimental results confirms that the computationally efficient approximate method is sufficiently accurate to guide choices of experimental parameters such as chromophore concentration. Overall, these results show predictive design of panchromatic light-harvesting performance can be performed rapidly and efficiently using an approximate kinetic model for randomly distributed assemblies of multiple chromophores.
New Boundary Condition for Decoupling Capacitance Selection in SiC Phase Legs Considering Short-Circuit Events

This paper presents a new boundary condition for designing phase legs when using the decoupling capacitance method. New SiC MOSFETs have much higher short-circuit currents—over 14X datasheet rating—then comparable Si IGBT devices. The energy draw on the decoupling capacitance due to this can be a large step input that over-voltages the device if not accounted for. Decoupling capacitance requirements have previously been based on switching conditions during normal operation and may not be sufficient for high current devices or modules. Furthermore, fast protection work has focused on lower current discrete devices whereas this issue becomes more prevalent in higher current configurations. Analysis of device over-voltage during short-circuit events is presented along with new sizing guidelines for DC link decoupling capacitance.
Evolution of post-pulmonary vein isolation atrial fibrillation inducibility at redo ablation: Electrophysiological evidence of extra-pulmonary vein substrate progression.

Background The electrophysiological substrate underlying atrial fibrillation (AF) progression remains difficult to identify. Objective The goals of this study were to study the evolution of post–pulmonary vein isolation (PVI) AF inducibility (AFI) after AF ablation and to compare patients with organized atrial tachycardia recurrence (OATr) versus those with paroxysmal or persistent AF recurrence. Methods We studied 99 patients who underwent de novo AF ablation (p1) and redo ablation (p2) for AF recurrence (AFr) or OATr. Stepwise AF ablation was performed at p1 and p2: (1) PVI, (2) coronary sinus defragmentation, and (3) left atrial (LA) defragmentation. Burst pacing followed each step, with AFI defined as sustained AF >5 minutes, triggering the next step. Patients with OATr underwent OAT ablation and inducibility testing post-redo PVI. Inducibility progression (IP) was defined as AFI at further steps of p2 compared to p1. Results Among patients with AFr, 34 of 72 patients (47%) exhibited post-PVI IP vs 2 of 27 (7.4%) patients with OATr (P = .0002). Stratification for persistent AF/paroxysmal AF/OATr showed a consistent association between recurrence phenotype and IP. Pulmonary vein (PV) reconnection incidence was 90%, without association with recurrence type or IP. LA volume was larger in patients with IP than in those without IP (86.7 ± 25.3 mL vs 72.0 ± 28.9 mL; P = .001). Right atrial dimensions increased between p1 and p2 in patients with IP vs no IP and in patients with AFr vs OATr. Conclusion Patients with AFr after first ablation exhibit IP more frequently at redo ablation than do patients with OATr. IP correlates with more advanced AFr type, larger LA volumes, and progressive right atrial enlargement. PV reconnection is not associated with AFr. Changes in post-PVI AFI may accurately indicate progression of extra-PV AF-maintaining substrate.