cssi/SciSciGPT-SciSciNet huggingface dataset:
Production and Persistence of Antibodies in Chickens to Sheep Erythrocytes. 1. Directional Selection

Abstract Two bidirectional selection experiments were conducted to measure antibody response to sheep red blood cells. Selection in one pair of lines was for high and low 5-day antibody titers to antigen(s), and in another pair of lines for persistence and nonpersistence of antibody titers between 5 and 21 days after the antigen(s) was given. Response to selection demonstrated additive genetic variation for high and low antibody titers at 5 days and for the persistence of titers. There was no response to selection for nonpersistence of titers. Crosses of the selected populations indicated a heterotic effect for both selected traits and reciprocal effects for the persistence/nonpersistence of the antibody titers.
Energy Expenditure and Enjoyment of Common Children's Games in a Simulated Free-Play Environment

Objective To measure the energy expenditure and enjoyment of children's games to be used in developing a school-based intervention for preventing excessive weight gain. Study design Healthy weight (body mass index [BMI] Results The games elicited a moderate intensity effort (mean ± standard deviation = 5.0 ±1.3 metabolic equivalents, 123 ±36 kcal/30 min). PAEE was higher for boys than for girls (0.12 ±0.04 versus 0.11 ±0.04 kcal/kg/min) and for healthy weight compared with overweight children (0.13 ±0.04 versus 0.11 ±0.03 kcal/kg/min). Twenty-two of the 30 games elicited a sufficiently high PAEE (≥100 kcal/30 min) and enjoyment (≥ neutral expression) for inclusion in future school-based interventions. Conclusions Not all children's games are perceived as enjoyable or resulted in an energy expenditure that was sufficiently high for inclusion in future physical activity interventions to prevent the excess weight gain associated with childhood obesity.
On algebraic construction of Gallager low density parity check codes

This paper presents two classes of low density parity check codes. Codes in these two classes perform well with iterative decoding.
The importance of early nutritional management of low-birthweight infants.

1. William C. Heird, MD* 1. 2. *Professor of Pediatrics, Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX. A number of reasons for concern about early nutritional management of very low birthweight (VLBW) infants, particularly extremely low birthweight (ELBW) infants, are enumerated by the authors of the articles in this issue. These include the possibilities that current management practices result in excessive losses of limited endogenous nutrient stores, fail to preserve host defense mechanisms, and do not promote normal growth and development of the central nervous system. An additional related concern is that these practices result in growth deficits of sufficient magnitude to prevent or hinder achievement of the infants’ growth potential. As Thureen notes, a number of studies have shown that reasonably stable infants who receive no protein or amino acid intake during the initial 7 to 10 days of life lose at least 1% of endogenous protein stores daily. Further, Premer and Georgieff suggest that sick infants may lose even more protein stores. Clearly, this loss cannot continue for long without severely depleting muscle mass that, in turn, results in muscle fatigue, failure, or both. Acute and chronic malnutrition also can compromise host defense mechanisms, thereby decreasing the ability to resist infection. Both results clearly are undesirable, and many believe that poor early nutritional management of ELBW and VLBW infants may contribute to this population’s high incidence …
Differential Expression of BCL-2 Family Proteins in ALK-Positive and ALK-Negative Anaplastic Large Cell Lymphoma of T/Null-Cell Lineage

Anaplastic large-cell lymphoma (ALCL) of T- or null-cell lineage, as defined in the revised European-American lymphoma classification, includes a subset of tumors that carry the t(2;5)(p23;q35) resulting in overexpression of anaplastic lymphoma kinase (ALK). Patients with ALK+ ALCL are reported to have a better prognosis than patients with ALK− ALCL. Because the mechanisms for this survival difference are unknown, we investigated the hypothesis that apoptotic pathways may be involved. We therefore assessed expression levels of the anti-apoptotic proteins BCL-2 and BCL-XL and the pro-apoptotic proteins BAX and BCL-XS in T/null-cell ALCL using immunohistochemical methods and correlated the findings with ALK expression and apoptotic rate (AR), the latter assessed by a modified Tdt-mediated dUTP nick-end labeling assay. ALK was detected in 21 of 66 (31.8%) ALCLs. BCL-2 was not detected in 21 ALK+ ALCLs but was present in 26 of 45 (57.8%) ALK− ALCLs (P < 0.0001). ALK+ and ALK− ALCLs also showed significant differences in expression of BCL-XL, BAX, and BCL-XS. ALK+ tumors less commonly had a high level of BCL-XL (1 of 17 versus 14 of 35, P = 0.01), and more commonly had high levels of BAX (13 of 18 versus 15 of 36, P = 0.05), and BCL-XS (11 of 16 versus 12 of 31, P = 0.05) compared with ALK− tumors. ALK+ tumors also had a higher mean AR than ALK− tumors (3.4% versus 1.1%, P = 0.0002). Differential expression of BCL-2 family proteins may be responsible for the higher AR observed in ALK+ ALCL and provides a possible biological explanation for the better prognosis reported for patients with ALK+ ALCL.
The Ca2+ channel β subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current

In superior cervical ganglion (SCG) neurons, stimulation of M(1) receptors (M(1)Rs) produces a distinct pattern of modulation of N-type calcium (N-) channel activity, enhancing currents elicited with negative test potentials and inhibiting currents elicited with positive test potentials. Exogenously applied arachidonic acid (AA) reproduces this profile of modulation, suggesting AA functions as a downstream messenger of M(1)Rs. In addition, techniques that diminish AA's concentration during M(1)R stimulation minimize N-current modulation. However, other studies suggest depletion of phosphatidylinositol-4,5-bisphosphate during M(1)R stimulation suffices to elicit modulation. In this study, we used an expression system to examine the physiological mechanisms regulating modulation. We found the beta subunit (Ca(V)beta) acts as a molecular switch regulating whether modulation results in enhancement or inhibition. In human embryonic kidney 293 cells, stimulation of M(1)Rs or neurokinin-1 receptors (NK-1Rs) inhibited activity of N channels formed by Ca(V)2.2 and coexpressed with Ca(V)beta1b, Ca(V)beta3, or Ca(V)beta4 but enhanced activity of N channels containing Ca(V)beta2a. Exogenously applied AA produced the same pattern of modulation. Coexpression of Ca(V)beta2a, Ca(V)beta3, and Ca(V)beta4 recapitulated the modulatory response previously seen in SCG neurons, implying heterogeneous association of Ca(V)beta with Ca(V)2.2. Further experiments with mutated, chimeric Ca(V)beta subunits and free palmitic acid revealed that palmitoylation of Ca(V)beta2a is essential for loss of inhibition. The data presented here fit a model in which Ca(V)beta2a blocks inhibition, thus unmasking enhancement. Our discovery that the presence or absence of palmitoylated Ca(V)beta2a toggles M(1)R- or NK-1R-mediated modulation of N current between enhancement and inhibition identifies a novel role for palmitoylation. Moreover, these findings predict that at synapses, modulation of N-channel activity by M(1)Rs or NK-1Rs will fluctuate between enhancement and inhibition based on the presence of palmitoylated Ca(V)beta2a.
Long noncoding RNA-microRNA-mRNA: a novel tripartite axis in the regulation of cardiac hypertrophy.

A large fraction of mammalian genomes is transcribed into noncoding RNAs.1 Despite the prevalence in the genome, up until recently, noncoding RNAs were regarded as junk RNAs that do not code for protein and, thereby, have no biological purpose. However, over the past decade, it has become increasingly evident that noncoding RNAs can and do serve important regulatory functions in pathophysiological processes.1 Short noncoding RNAs called microRNAs, typically 20 to 24 nucleotides in length, have been widely reported to post-transcriptionally regulate gene expression by binding to partially complementary sequences in target mRNAs or promoting mRNA degradation and translational repression.2 Another class of noncoding RNAs, typically >200 nucleotides in length, called long noncoding RNAs (lncRNAs) have been recently discovered to regulate gene expression not only at the post-transcriptional level, but also at transcriptional and epigenetic levels.3 Notably, lncRNAs have also been reported to function as microRNA sponges, altering microRNA expression levels by binding to and sequestering microRNAs.4,5 In the present study, Wang et al6 present evidence that a lncRNA modulates the ability of a microRNA to target an mRNA, which plays a role in the development of cardiac hypertrophy. To identify microRNAs whose expression is altered by hypertrophic stimulation, the authors6 performed microRNA microarray analysis and quantitative reverse transcription–polymerase chain reaction (qRT-PCR) on neonatal mouse cardiomyocytes treated with or without angiotensin II (Ang-II). In particular, microRNA-489 (miR-489) was found to be most downregulated microRNA in response to Ang-II treatment. The authors used several methods to study the role of miR-489 in cardiac hypertrophy. First, they infected cardiomyocytes with adenoviruses encoding miR-489 to overexpress miR-489 and subsequently treated the cardiomyocytes with Ang-II. Second, they transfected cardiomyocytes with miR-489 antagomirs (anta-489) to knockdown the expression of miR-489, followed by treatment of the cardiomyocytes with …
Primary ophthalmic rhabdomyosarcoma in 33 patients.

Purpose: To review the findings, management, and outcome in 33 cases of primary ophthalmic rhabdomyosarcoma. Methods: The records of 33 consecutive patients from a single ocular oncology center were analyzed retrospectively for outcomes of final visual acuity, local recurrence, and distant metastasis. Results: Rhabdomyosarcoma was primarily located in the orbit in 25 cases (76%), conjunctiva in 4 (12%), eyelid in 1 (3%), and uveal tract in 3 (9%). Findings had been present for a mean of 5 weeks and included proptosis in 10 patients (30%), eyelid swelling in 7 (21%), and blepharoptosis in 6 (18%). The initial diagnoses before referral to us included primarily rhabdomyosarcoma in 8 cases (24%), conjunctivitis in 5 (15%), cellulitis in 5 (15%), and pseudotumor in 4 (12%). Tumors were classified according to the Intergroup Rhabdomyosarcoma Study Group staging and treatment protocols as group I in 4 cases (12%), group II in 12 (36%), group III in 16 (48%), and group IV in 1 case (3%). Treatment included surgical debulking, chemotherapy, and radiotherapy. Local tumor recurrence was detected in 6 patients (18%), lymph node spread in 2 (6%), and distant metastasis in 2 (6%). Long-term visual outcome of the 28 patients who maintained their globe was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 (18%), and 20/200 or worse in 12 (43%). Mean follow-up was 8.3 years; tumor-related death occurred in 1 patient (3%). Conclusions: Rhabdomyosarcoma can present in the orbit, eyelid, conjunctiva, and uveal tract. Following treatment, local tumor recurrence occurs in 18% of cases, metastasis in 6%, and death in 3%.
Cognitive Belief Systems and Their Persistence: Test-Retest Reliability of the Rational Behavior Inventory

It is a basic tenet of rational emotive and other cognitive restructuring psychotherapies that irrational belief systems are relatively stable constructs. The present study investigated this premise by examining the 10-wk. test-retest reliability of the Rational Behavior Inventory, a well-documented measure of irrational beliefs, employing a sample of 74 undergraduates. Correlations between scores for the first and second administrations of the inventory were moderate to high, and significant. There were no significant differences in scores taken at the beginning and end of 10 wk. These data confirm that irrational beliefs exhibit temporal stability.
Recovery-driven design: a power minimization methodology for error-tolerant processor modules

Conventional CAD methodologies optimize a processor module for correct operation, and prohibit timing violations during nominal operation. In this paper, we propose recovery-driven design, a design approach that optimizes a processor module for a target timing error rate instead of correct operation. We show that significant power benefits are possible from a recovery-driven design flow that deliberately allows errors caused by voltage overscaling ([10],[3]) to occur during nominal operation, while relying on an error recovery technique to tolerate these errors. We present a detailed evaluation and analysis of such a CAD methodology that minimizes the power of a processor module for a target error rate. We demonstrate power benefits of up to 25%, 19%, 22%, 24%, 20%, 28%, and 20% versus traditional P&R at error rates of 0.125%, 0.25%, 0.5%, 1%, 2%, 4%, and 8%, respectively. Coupling recovery-driven design with an error recovery technique enables increased efficiency and additional power savings.
Elektronenstoß‐induzierte Umlagerungen organischer Moleküle

Massenspektrometrische Fragmentierungen sind haufig von Wasserstoffwanderungen begleitet. Eine eingehende Untersuchung dieser Reaktionen, vorwiegend mit Deuteriummarkierung, hat wesentlich zum Verstandnis elektronenstos-induzierter Bindungsspaltungen beigetragen. Spater wurde gefunden, das auch andere Gruppen wie Alkyl, Aryl, Hydroxyl usw. nach einem Elektronenbeschus wandern konnen. Im vorliegenden Aufsatz werden derartige Umlagerungen organischer Verbindungen diskutiert. Diese Beobachtungen sind nicht nur von spezifisch mechanistischem Interesse, sondern die genaue Kenntnis uber das Eintreten solcher Wanderungsreaktionen ist entscheidend fur die richtige Deutung von Massenspektren und zur Vermeidung von Fehlinterpretationen bei der „Element-Kartographie”.
Fusion Imaging for TAVR

Accurate patient selection, pre-procedural planning, and intra-procedural guidance are paramount for procedural success in transcatheter aortic valve replacement (TAVR). Multimodality imaging plays a pivotal role in each of these steps and is essential for TAVR. Fluoroscopy remains the foundation for imaging guidance of transcatheter therapy; however, it does not provide the spatial information of 3D cardiac anatomy necessary for complex interventional procedures. With recent technologic improvements, the integration of multimodality imaging with fluoroscopy in the catheterization laboratory, also known as fusion imaging, now provides an alternative to traditional fluoroscopically guided catheterization. Multidetector computed tomography and rotational angiography (RA) are currently being utilized. This chapter will describe in detail the current use of fusion imaging in TAVR revealing the technical features, methodology, and potential utility, along with a better understanding of the limitations of this technology and future directions.
Report on the OCPA8 Conference

Many events have happened in 2014. In this newsletter I am pleased to report that the OCPA8 Conference held in Singapore this June has been successfully concluded, with some of the highlights summarized below. I am also happy to announce the site and hosting organizations of the OCPA9 Conference, the 2014 OCPA Award winners, and various honors and recognitions recently received by the OCPA members.
Abstract P382: Fried Food Consumption is Associated with a Higher Risk of Heart Failure among US Male Physicians

Background: While previous studies have reported a positive relation of fried food consumption with type 2 diabetes, hypertension, and obesity, no previous study has examined the relation of total fried food intake with risk of heart failure (HF) in a prospective cohort. Objective: To test the hypothesis that fried food consumption is positively associated with risk of HF in male physicians. Methods: A prospective cohort of 19,968 participants from the Physicians’ Health Study. Frequency of fried food consumption was assessed between 1999 and 2002 using a food frequency questionnaire and HF was ascertained through annual follow-up questionnaires with validation in a subsample. We used Cox regression to estimate multivariable adjusted hazard ratios of HF. Results: During a median follow-up of 10.6 years, 862 cases of HF occurred. The mean age at baseline was 66.4 ± 9.2 years. Median frequency of fried food consumption was <1 time per week. Multivariable adjusted hazard ratios (95% CI) were: 1.0 (ref), 1.18...
Overcoming Barriers to Customer Co-Design: The Role of Product Lines

A key barrier to companies successfully engaging customers in the design of new products is customers fearing that they will be forced to pay much more for the custom products they help design. This fear is justified by the fact that once the customer has invested significant time and effort in co-designing a product, the firm can extract all the resulting consumer surplus through higher prices. At the same time, the firm allowing its customers to co-design products would be unlikely to commit to a price up front before knowing the complete design of the custom product, since it would then face significant risk of losing money. In this paper, we develop analytical models for this problem, and show how a firm can motivate its customers to engage in co-design. We also show how offering co-design can impact the firm's product (line) strategies and the quality of its products, including motivating the firm to increase the quality of its standard product, sometimes even beyond the efficient quality level. The effect of market and firm characteristics on the value of engaging customers in the co-design process is also examined. In addition, we show that the presence of information asymmetry about the firm's co-design capability may lead to even higher levels of co-design effort by the customer. These results provide valuable insights for managers regarding the potential value of supporting customer co-design.
42INMOLECULAR CLASSIFICATION OF KIDNEY CANCER

ABSTRACT Insight into the somatic genetics of clear cell renal cell carcinoma (ccRCC) has seen considerable advance in the past few years. Leveraging DNA sequencing approaches we have now begun to elaborate the picture of ccRCC, expanding from that dominated by VHL mutation into a more nuanced and complex view of this disease. Perhaps most striking is the contribution of mutations in the chromatin machinery. We and others have documented recurrent, frequent mutations in histone demethylases/methylases (SETD2, JARID1C, KDM6A) and a major role of chromatin remodeling machinery mutations (PBRM1, BAP1). Further, we have demonstrated marked intra-tumor heterogeneity for this disease, lending further insight into its development. This talk will provide an overview of these key insights and put them into context of a more comprehensive view of ccRCC. Disclosure: The author has declared no conflicts of interest.
Neighborhood Affluence, School-Achievement Scores, and Housing Prices: Cross-Classified Hierarchies and HLM

The housing literature has traditionally employed hedonic price models to investigate the impact of house and neighborhood characteristics on housing prices. These models, however, are not necessar...
P1-S4.04 Biases in the design of studies assessing the role of sexually transmitted infections as HIV risk factors

Background For over 20 yearss sexually transmitted infections (STIs) have been studied as risk factors for HIV infection. We show how the design of studies in this field has inherent biases due to inappropriate confounder definition, coinfection, and heterogeneity in exposure to HIV. We use herpes simplex virus 2 (HSV2) to illustrate these biases and show that use of a serodiscordant couple design can remove them. Such findings are timely given the interest in using HPV vaccination for HIV prevention based on similar data. Methods We developed an individual based model (IBM) using published data from an existing STI IBM (STDSIM). This model permits simulation of multiple cohort studies to show the direction and magnitude of these biases. The model is written in Matlab. Analyses were performed using Cox regression in SAS. Results We identified four causes of bias. (1) While confounding by sexual behaviour is widely appreciated it is less well understood that perfect measurement of sexual behaviour will not permit adequate control of confounding as data on the frequency of HIV exposure is missing. We show that this bias can result in upward confounding. 2) As HSV2 is more infectious than HIV we expect HSV2 to be acquired from coinfected partners first followed by HIV. 3) As coinfection increases HIV viral load HSV2 infection may act as a proxy for a partner9s elevated infectiousness with HIV. Both of these mechanisms result in upward bias, the magnitude of which depends on the prevalence of coinfection. 4) Between subject heterogeneity in the risk of disease has been shown to attenuate estimates for any risk factor. We show that this bias can result in significant attenuation of the HR and that it depends on the prevalence of HIV among subjects9 partners and their sexual behaviour. We show that if HIV serodiscordant couples are enrolled all four biases can be removed see Abstract P1-S4.04 Table 1. Conclusions The standard design is affected by at least four biases that preclude causal interpretations of all such HSV2-HIV studies performed to date. Use of a serodiscordant couple study design can remove these biases. It is impossible to correct previous results as the biases are not all in the same direction and their magnitudes depend on the unknown prevalence and transmissibility of both HSV2 and HIV among partners. These findings are expected to generalise to other STI-HIV risk factor studies and can help inform the decision to test HPV vaccination as an HIV prevention measure.
Concession Bargaining: The Meaning of Union Gains

The article reports on a study which measured the indirect impact of union gains or concession bargaining on the economic interests of firms. A discussion is presented about various categories and ...
Empirical Approach to Understanding the Fatigue Behavior of Metals Made Using Additive Manufacturing

High-cycle fatigue measurements were performed on alloys prepared by powder-bed fusion additive manufacturing techniques. Selective laser melted (SLM) nickel-based superalloy 625 and electron beam melted (EBM) Ti-6Al-4V specimens were prepared as round fatigue specimens and tested with as-built surfaces at stress ratios of −1, 0.1 and 0.5. Data collected at R = −1 were used to construct Goodman diagrams that correspond closely to measured experimental data collected at R > 0. A second way to interpret the HCF data is based on the influence of surface roughness on fatigue, and approximate the surface feature size as a notch. On this basis, the data were interpreted using the fatigue notch factor kf and average stress models relating kf and stress concentration factor Kt. The depth and root radius of surface features associated with fatigue crack initiation were used to estimate a Kt of 2.8 for SLM 625. For Ti-6Al-4V, a direct estimate of Kt from HCF data was not possible, but approximate values of kf based on HCF data and Kt from crack initiation site geometry are found to explain other published EBM Ti-6Al-4V.
The design of a computer-based management system of the medical measurement units

This system is an application database coded in Microsoft Visual Foxpro 6.0. The fields of the database include serial number, department, equipment name, specification, factory name, product serial number, product date, classification, check time, check verdict, next check time and remark. The main menu of the system includes the data maintenance menu, the data inquiry menu, the printing menu, the statistics menu, the help menu and the exit menu. The data maintenance menu includes the add/delete data menu and the database management menu. The data inquiry menu included the classification inquire and the department inquire. The printing menu included the classification printing, the department printing and the forms printing..
The effect of Vasovasostomy Upon the Structure of the Vas Deferens in Rats

The reasons for the discrepancy between reappearance of sperm in the ejaculate following vasovasostomy and pregnancy rates remain obscure. To determine the possible adverse effects of reanastomosis upon the structure of the vas deferens, immediate microsurgical vasovasostomy was performed on 60 adult Sprague-Dawley rats. The fine structure of the mucosa, as seen by scanning electron microscopy: showed only subtle, transient changes with return to normal architecture within 3 months. Luminal dilatation, rather than stenosis, was a constant late finding. It is concluded that microsurgical reanastomosis has little, if any, permanent deleterious effect upon the structure of the vas deferens.
Determining the prevalence of Escherichia coli O157 in cattle and beef from the feedlot to the cooler.

Prevalence of Esche,'ichia co/i 0157 on cattle entering the slaughter floor may range from 10 to >70%. This study was conducted to determine the effect of E. co/i 0157 prevalence in fecal pats collected from feedlot pen floors on subsequent E. co/i 0157 prevalence on carcasses at various points in the slaughter process. Fecal pats from the feedlot pen floor were collected within 3 days before slaughter. During cattle processing at the slau ghter facilit y. additional samples were collected from the hide, from the colon, and from the carcasses before and after evisceration and alter final decontamination. Of 15 lots (a group of cattle from the same pen from a feedlot) sampled. 81 1 /( had at least one positive fecal pat from the feedlot floot 47% had a positive hide sample. 73%, had a positive colon/fecal sample. and 47% had it carcass sample prcevisceration; however, only 8% of lots had a positive carcass sample postevisceration (Sr alter final intervention. Of the total samples tested (a = 1.328). 24.7, 14.7. 27.6, 10.1. 1.4. and 0.3% of fecal pats from the feedlot floor, hide, colon. preevisceration, postevisceration, and final intervention samples, respectivel y, were positive for F. colt 0157. Pens with greater than 20C /r positive fecal pats from the feedlot floor had 25.5% hide. SI.47e colon, and 14.3. 2.9. and 0.7% carcass samples positive at preevisceration, at postevisceration, and after final intervention, respectively. However, fecal Pats from feedlot floor samples that contained less than 20% positive fecal samples showed lower pathogen prevalence, with 5.01 /( hide. 7.51 7c colon, and 6.3. 0. and 0% carcass positive samples at prcevisceratiun, postevisceratiun, and post—final intervention, respectively. Data from this study can be used as part of risk assessment processes in order to identify mitigation strategies to minimize prevalence of F. co/i 0157 on fresh beef carcasses.
Effects of the Wardill-Kilner (V/W-Y) Palatoplasty on Facial Growth

Abstract No Abstract Available. This investigation was supported in part by P.H.S. Research Grant DE-00853, National Institute of Dental Research.
Membrane Lipids and Modulation of Vascular Smooth Muscle Ion Channels

In vascular smooth muscle (VSM), lipids regulate the function of many cellular proteins, including ion channels. Lipids can directly target ion channels or regulate ion channels indirectly, that is, through interactions with cell signalling molecules that eventually target the ion channel. We summarize current knowledge on VSM ion channel regulation by lipids, whether lipids are originated in the smooth muscle itself, vascular endothelium, or paracrine or circulation sources, with a focus on possible direct interaction between lipid molecules and the proteins that constitute the VSM ion channel complex. We also describe the contribution of such lipid-VSM ion channel interaction to VSM physiology and pathophysiology. However, more than one mechanism or type of interaction may be involved in lipid-induced regulation of VSM ion channels and some mechanisms are not mutually exclusive, which adds significant complexity to the field. Understanding the mechanisms that underlie lipid modulation of VSM ion channels, however, is necessary for developing novel therapeutic approaches to improve vascular function and prevent or counteract widespread cardio/cerebrovascular disorders.
Causal Decision Theory

Many will find the answer easy—though they may disagree with each other on which the answer is. A standard line on the prisoner’s dilemma rests on dominance: What you do won’t affect what Twin does. Twin may rat or keep mum, but in either case, you yourself will do better to rat. Whichever Twin is doing, you would spend less time in jail if you were to rat than if you were to keep mum. Therefore the rational way to minimize your own time in jail is to rat.
Abstract 64: Identification and validation of novel therapeutic targets of osteosarcoma using cutting edge technologies

Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. The current treatment options have not changed over the last four decades and rely on tumor resection and nonspecific combination chemotherapy, resulting in a 5-year survival rate of 0-29% if clinically apparent metastases are present. Although these tumors are rare in humans, with ∼900 cases annually, they are highly prevalent in canines, with over 50,000 cases annually, and have seemingly similar genetics. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS- associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR, MAPK, and ERK5 signaling pathways. We identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma. We have now begun pre-clinical testing of inhibitors of our top actionable targets to treat osteosarcoma, namely SEMA4D and CSF1R. Further, we have begun to validate top candidate metastasis genes using the CRISPR nuclease system in immortalized osteoblasts and osteosarcoma cell lines. Preliminarily we have found that loss of candidate osteosarcoma metastasis genes ANAPC1 or TOAK1 increases the migration capacity of immortalized osteoblasts, while loss of EXOC1 or GRLF increases their ability for anchorage independent growth in soft agar assay. Results of these ongoing studies will be presented. Citation Format: Branden Smeester, Natalie Wolf, Branden S. Moriarity. Identification and validation of novel therapeutic targets of osteosarcoma using cutting edge technologies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 64.
GhostScope: Conceptual Mapping of Supernatural Phenomena in a Large Folklore Corpus

Since the inception of the field of folkloristics in the early nineteenth century, scholars have paid considerable attention to the relationship between place and folklore. An important yet largely overlooked question is how individuals in a tradition group, through their storytelling, negotiate the conceptualization of their local environment. In our work, we present a preliminary method for representing the conceptual mapping of the environment by storytellers or classes of storytellers. As opposed to our other geographically based methods for exploring the corpus, in which places are anchored in geography, GhostScope imagines all of the storytellers positioned at a conceptual “center.” Geographic locations are then calculated for direction and distance based on this zero-point. The work is based on a digitized subset of legends from Evald Tang Kristensen’s larger collection of Danish folklore.
Quantum statistical properties of stimulated Raman generation

Quantum fluctuations of pulse energy and shape are observed when stimulated Raman generation is pumped by temporally smooth or fluctuating laser pulses. In the case of smooth single-mode frequency-doubled Nd:YAG laser pulses, the generated Stokes pulse energy is seen to fluctuate by more than 100%, although the pulses are macroscopic in energy.1
Abstract MS2-1: MS2-1 Targeting the ATR checkpoint in cancer therapy

Remi Buisson1, Michael S. Lawrence2, Cyril H. Benes1 & Lee Zou1,3 1. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, MA. 2. Broad Institute of Harvard and MIT, Cambridge, MA. 3. Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, MA. Recent cancer genomics studies have revealed that the mutation signatures of APOBEC3A/B are commonly detected in several cancer types, such as bladder, breast, head and neck cancers, lung adenocarcinoma, and lung squamous cell carcinoma. APOBEC3A/B are members of the APOBEC family of cytosine deaminases. While APOBEC3 proteins are important for the innate immunity against viral infection, they are not expressed in normal tissues. When APOBEC3A/B are aberrantly expressed in cancer cells, they become potent “mutators”, which may promote genomic instability and contribute to tumor evolution. Interestingly, recent studies have suggested that APOBEC3A/B may act during DNA replication. However, whether the APOBEC3A/B activity in cancer cells induces DNA replication stress, and whether this activity creates a vulnerability in cancer cells that can be exploited therapeutically, remains unknown. In this study, we show that APOBEC3A imposes a unique type of mutator-driven DNA replication stress, and that the ATR kinase plays a crucial role in antagonizing this stress. APOBEC3A expression activates ATR during DNA replication through UNG2-generated abasic sites. Surprisingly, ATR inhibition in APOBEC3A-expressing cells results in a drastic surge of abasic sites at replication forks, revealing an ATR-mediated feedback loop countering the action of APOBEC3A during replication. Mechanistically, ATR inhibition unleashes APOBEC3A-driven ssDNA accumulation at replication forks, which propagates the substrate of APOBEC3A and ultimately drives cells into replication catastrophe. In a panel of cancer cell lines, ATR inhibitor selectively induces replication catastrophe in those harboring high APOBEC3A/B activity, showing that the APOBEC3A/B activity in cancer cells confers susceptibility to ATR inhibition. Together, these results suggest that the unique APOBEC-driven replication stress in cancer cells may offer a new opportunity for ATR-targeted therapy. Citation Format: Zou L. MS2-1 Targeting the ATR checkpoint in cancer therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr MS2-1.
Measuring clinically relevant endpoints in a serum-free, three-dimensional, primary cell culture system of human osteoarthritic articular chondrocytes

Osteoarthritis (OA) is characterized by degeneration of articular cartilage within the joint, inflammation and pain. The purpose of this study was to develop a primary, serum free cell culture system of human osteoarthritic articular chondrocytes (HOACs) with which to study manifestations of the disease process. Joint tissues were obtained from OA patients undergoing total knee arthroplasty (TKA). HOACs isolated from the femoral condyles and tibial plateau of the same side were combined, plated in three-dimensional, alginate beads and cultured for five days in serum, hormone and protein free medium. More living cells were obtained from the femoral condyles than the tibial plateau. The optimal plating density was 2.5 × 106 cells/ml of alginate. The amounts of DNA, RNA, proteoglycans and total collagen were similar in cultures prepared from the sides of least and greatest pathology. More type 1 than type 2 collagen was detected in the medium on days 2 and 5. A greater percentage of type 1 than type 2 collagen was degraded. The inflammatory cytokine interleukin-1 beta was present in the medium and alginate associated matrix. Although variation in the metabolic profiles between subjects was observed, HOACs from all patients continued to reflect the OA phenotype for five days in culture. This serum free, three-dimensional primary culture system of HOACs provides a platform with which to measure clinically relevant endpoints of OA and screen potential disease modifying OA therapeutics.
Horizon nulling helix antennas for GPS timing

Global Positioning System (GPS) antennas installed at fixed site infrastructure are susceptible to interference incident along the direction of the horizon. In this paper, a series of quadrifilar helical antennas are presented for the application of GPS timing. The first antenna employs a novel method of reactive loading along the length of the multi-turn helix. The phase distribution along the helix creates a deep null in the gain pattern at the horizon while maintaining sufficient beam width in the zenith direction. The horizon null minimizes ground based interference. The second antenna achieves similar performance by varying the pitch of the helix arms along the length of the antenna. The third antenna operates over L1 and L2 frequencies using concentric helices. A novel method is presented to decouple the concentric helices based on distributed trap circuits along the length of the helix arms, which preserves the horizon nulling patterns at both frequencies. The proposed antennas offer improved performance over previous horizon-nulling designs. Additionally, the proposed antennas can be manufactured at a lower cost compared to other interference mitigating antennas based on the simple architecture.
Patterns of failure in a phase II trial of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) for resectable and borderline resectable (BLR) pancreatic cancer.

482Background: There is emerging interest in the role of SBRT in locally advanced pancreas cancer, however little prospective data exists examining the safety, efficacy, and optimal target volumes for SBRT in the neoadjuvant setting for resectable or BLR pancreatic cancer. Methods: Eighteen patients were enrolled from 11/2014-6/2017. SBRT was delivered to the tumor and abutting vessel with fiducials/compression and a 3 mm PTV margin to 33 Gy (6.6 Gyx5fxn) with an optional elective PTV to 25 Gy (5 Gyx5fxn) customized to the nodal space and mesenteric vessels. Patients without progression underwent surgery 4-6 weeks following SBRT. The primary endpoint is ≥ Grade 3 acute and late GI toxicity. Secondary endpoints included overall survival (OS), progression-free survival (PFS),and cumulative incidence of local failure (LF). LF is defined as recurrence within conventional RT volumes from the time of resection to local failure or last CT with no progression. Local failures were fused to planning CTs for dose qu...
Field-varying aberration recovery in EUV microscopy using mask roughness

We derive and solve a simplified, self-calibrated inverse problem to characterize the field-dependent aberrations of an EUV synchrotron-based full-field microscope, using images of the surface roughness of an EUV photomask under several angles of illumination. We demonstrate diffraction-limited imaging performance at the center of its field-of-view.
How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults

Recommendations regarding how long isoniazid should be taken to prevent tuberculosis have gradually shifted from 12 to 6 months of treatment. These recommendations and the relevant evidence from controlled trials on duration of treatment are reviewed. The conclusions for immunocompetent adults are: 1) 6 months of preventive treatment does not give optimal protection; 2) more than 12 months of preventive treatment is not necessary; 3) 9-10 months appears to be the optimal duration; and 4) total duration of preventive treatment may be more important than its continuity.
Michael Balint then and now: a contemporary appraisal.

This paper pays tribute to Michael Balint's psychoanalytic contributions, thus far neglected in the United States. To assess the current relevance of some of Balint's pioneering ideas, the paper highlights some of Balint's core concepts. These gain in importance and enduring relevance when viewed from the perspective of Heinz Kohut's psychoanalytic self psychology. The “basic fault” and the unsurpassed depth and subtlety of Balint's description of the archaic transferences are examples of what are of lasting value in his work.
Mechanisms of Neuronal Degeneration in Huntington’s Disease

Two complementary research strategies have been undertaken to define the mechanisms of neuronal degeneration in Huntington’s disease (HD) (Kowall et al., 1987; Ferrante, 1991). Because HD is an autosomal dominant disease caused by a specific mutation localized to the telomeric region of the short arm of chromosome four, a great deal of effort has been directed to finding the gene locus responsible for the disease (Gusella et al., 1986). Although the gene has recently been identified, the specific biochemical abnormality that causes HD and the mechanism of neuronal degeneration has not yet been determined (Huntington’s Disease Collaborative Research Group, 1993). This strategy has made it possible to diagnose presymptomatic individuals and has contributed to mapping studies of the human genome. A second complementary strategy that we and others have used has been to define the specific changes that occur in HD brain and explore animal models that recreate these pathological alterations (Kowall et al., 1987; Beai et al., 1989a and b, 1991a and b; Albin et al., 1990; DiFiglia, 1990; Ferrante, 1991; Ferrante et al., 1992, 1993;).
Autophagy and Cell Death

Autophagy is an evolutionarily conserved biological phenomenon related to protein degradation and organelle turnover. Three types of autophagy have been defined: macroautophagy, microautophagy, and chaperone-mediated autophagy, which differ the way of in the delivery of substrates to the lysosome. In macroautophagy, substrates are wrapped in a double membrane structure, called the autophagosome. The formation of the autophagosome and its fusion with the lysosome are genetically controlled by a series of autophagy molecules and are activated in response to a number of environmental cues. Much has yet to be learned about the signaling pathway and the molecular mechanisms about this process. Autophagy is important to multiple cellular functions, particularly for nutrient and energy balance, and the turnover of cellular substances. The relationship of autophagy with cell death is complicated and may be context-dependent. Whereas the nature of autophagic death has yet to be carefully defined, it seems that autophagy may, in fact, be a key regulator of both apoptosis and necrosis. In this context, the roles of macroautophagy in both prosurvival and prodeath have been identified. Understanding the circumstance in which autophagy affects cell functions and therefore cell viability is critical for the future intervention of this process to control cancer, tissue injury, and other disease processes.
The Role of Connective Tissue in Atherosclerosis

In man atherosclerosis generally involves the large and medium sized arteries in which connective tissue proteins comprise more than half the dry weight. Connective tissue contributes to some of the most important alterations in the significant human lesion, the fibrous plaque. It is this lesion which poses the most serious threat to health and life. As recently reviewed by Smith and Smith (1), it is still open to debate whether or not fibrous plaques, or at least some of them, develop from fatty streaks. We, therefore, will restrict our discussion to fibrous lesions. Fibrous lesions begin to develop in the second to third decade of life in almost all individuals of our type of society. However, it takes decades of slow growth before they produce clinical symptoms.
Continuous-Time Flow-Limited Modeling by Convolution Area Property and Differentiation Product Rule in 4-Phase Liver Dynamic Contrast-Enhanced CT

Parametric-fitting approaches for tracer kinetic modeling depend on the capability of a computational method to describe underlying physiologic processes that cause temporal intensity changes in dynamic contrast-enhanced DCE images. Rapid scan techniques allow perfusion CT imaging with high temporal resolution. In clinical practice, however, the perfusion CT protocol is especially a trade-off between the number of data points and the total radiation dose. Considering availability and radiation exposure, use of DCE-CT imaging derived from 4 temporal phases, which include precontrast, arterial, portal, and delayed phases, is highly desirable for the liver. However, low-temporal- resolution images like 4-phase liver DCE-CT present several barriers to modeling of tracer kinetics because of the lack of temporal enhancement data, which limits obtaining reliable physiologic information. The major reason for the limited application of a tracer kinetic model in temporally sparse dynamic data is that general computational algorithms such as deconvolution techniques require discretizing of arterial or portal-vein and tissue curves for estimation of kinetic parameters, leading to an unstable computational solution. The numerical instability due to the discretization of the enhancement curves can be more pronounced in the low-temporal-resolution data like those gleaned from 4-phase DCE-CT. For this reason, we propose a novel dual-input continuous-time tracer kinetic modeling method based on a new mathematical approach that uses the convolution area property and the differentiation product rule, without any discretization of the enhancement curves. This model was applied to case studies of hepatocellular carcinoma in 4-phase DCE-CT to illustrate the potential effectiveness of continuous-time tracer kinetic modeling. The proposed analytic scheme was shown to be feasible for estimation of kinetic parameters even in 4-phase liver DCE-CT, potentially being a practical guide for tracer kinetic model-based curve-fitting in temporally sparse data.
Nonmarket Strategy in Poland

With almost 38 million citizens, Poland is one of the most populous nations in Eastern and Central Europe. Poland’s GDP of roughly $1.1 trillion makes it one of the largest economies in the region as well, and a per capita GDP approaching $28,000 makes it one of the wealthiest. Although Poland’s economy is relatively stable and prosperous, recent political developments, including clashes with the EU, challenge the nation’s upward trajectory (see Table 12.1) (Miller et al. 2018).