cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.

Abstract The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.
Polyaniline: Pernigranile, an isolable intermediate in teh conventional chemical synthesis of emeraldine

Abstract The conventional chemical oxidative polymerization of aniline to polyaniline in the emeraldine oxidation state using acidic ammonium peroxydisulfate (aniline: peroxydisulfate ≈ 4:1; aq. 1. ON HCl; ≈0 °C) was found to proceed via the intermediacy of the fully oxidized pernigraniline oxidation state (readily isolable as the base form). The intermediacy of the pernigraniline oxidation state was first detected by using a novel potential profiling technique in which the oxidation potential of the system was continuously monitored as a function of polymerization time.
Histology of Rhodnius prolixus infected with Trypanosoma rangeli

Abstract Intracellular stages of Trypanosoma rangeli develop in most tissues of infected Rhodnius prolixus , but they show a predilection for gut musculature, fat body, epidermis, and salivary glands. Heavy hemocoelic infections often result in severe nerve damage and hypertrophy of tracheal cells, which finally rupture and release flagellates. T. rangeli may inhibit the reduviid symbiote Nocardia rhodnii , possibly resulting in molting deformities and death of infected bugs. Autointoxication, caused by damaged muscular, nervous, and tracheal systems, is the other prime cause of mortality.
POSSIBILITIES OF POLARIZED PROTONS IN SppS AND OTHER HIGH ENERGY HADRON COLLIDERS

The requirements for collisions with polarized protons in hadron colliders above 200 GeV are listed and briefly discussed. Particular attention is given to the use of the ''Siberan snake'' to eliminate depolarizing resonances, which occur when the spin precession frequency equals a frequency contained in the spectrum of the field seen by the beam. The Siberian snake is a device which makes the spin precession frequency essentially constant by using spin rotators, which precess the spin by 180/sup 0/ about either the longitudinal or transverse horizontal axis. It is concluded that operation with polarized protons should be possible at all the high energy hadron colliders. (LEW)
Nongovernmental organizations and genetically modified crops in Kenya: Understanding influence within a techno-civil society

Abstract Genetically modified (GM) crops in Kenya are situated in a highly networked and transnational environment, where technical decisions are tied to livelihoods, politics and culture. Within that environment, certain nongovernmental organizations (NGOs) have been extremely influential, driving local decisions about whether and how GM crops will be adopted, and creating a technocratic policy environment. Building on interdisciplinary frameworks that connect agency with place and identity, I argue that NGO influence stems from the creation and management of organizational identities that link two powerful ideologies: the notion that the advancement of technology is tightly coupled to societal progress, and the view that a strong civil society is necessary for an informed and representative democracy. Utilizing ethnographic data, the concept of techno-civil society is presented as a means to understand the merger of these two ideologies as NGOs negotiate their identities and frame their role in deciding Kenya’s future with GM crops. Especially during key regulatory and technological developments in 2004–2005, the creation of a techno-civil society helped produce a scientized decision-making system that was closed and polarized. Acknowledging, and not essentializing, the normative dimensions of civil society and the values associated with technological pathways may help de-polarize debates about GM crops in developing countries.
Chromosome preparations from hepatocytes and bone marrow of Chinese hamsters: A direct method

This report describes a method for the direct preparation of chromosomes from the hepatocytes and bone marrow of the same Chinese hamster (Cricetulus griseus). The technique is a modification of that described by Becker et al. (J. natl. Ca. Inst. 46: 1261–69, 1971) for rat hepatocytes, with the following significant differences: (1) a less extensive partial hepatectomy is employed to initiate hepatocyte regeneration, (2) the use of a larger initial dose of colchicine (4 mg/K) 46–48 hours after hepatectomy instead of 1 mg/K 24 hours after hepatectomy, (3) the use of 0.075 M KCl as hypotonic solution instead of fetal calf serum diluted 1 : 7 with distilled water and (4) flame or blaze drying of chromosome preparations instead of air drying. The combination of the above modifications gave abundant, clear and well-spread chromosomes.
Digital Line-Artifact Removal

A variety of imaging procedures generate artifacts which have the visual appearance of a set of parallel lines across the image. In this paper we present a simple frequency-domain algorithm which considerably reduces that type of artifact. It has been found to be effective in a number of applications, and its performance will be illustrated by way of examples.
Studies on the Role of Sex Steroids in the Feedback Control of Gonadotropin Concentrations in Men. II. Use of the Estrogen Antagonist, Clomiphene Citrate

Abstract To further evaluate the relative roles for androgen and estrogen in the feedback regulation of gonadotropin secretion in men, we studied the effects of sex steroids on serum LH and FSH concentrations, the pulsatile release of LH, and the responses of LH and FSH to LRH administration before and during chronic clomiphene administration. We theorized that this approach might provide an opportunity to evaluate the pure androgenic component of testosterone, independent of its aromatization to estradiol, since the estrogen antagonist, clomiphene, would block estrogen-mediated effects. Infusion of testosterone (T; 7.5 mg/day for 4 days) produced a 40% decline in serum LH and FSH concentrations. Estradiol (E) infusion in dosages equivalent to that derived from the infused T (45 μg/day) resulted in a decline in serum LH which was 60% of that seen with T, indicating that most of the Tmediated LH suppression could be attributed to its aromatization to E. Dihydrotestosterone infusion also resulted in a 35% d...
Rapid synthesis and size control of CuInS2 semi-conductor nanoparticles using microwave irradiation

The properties of CuInS2 semi-conductor nanoparticles make them attractive materials for use in next-generation photovoltaics. We have prepared CuInS2 nanoparticles from single source precursors via microwave irradiation. Microwave irradiation methods have allowed us to increase the efficiency of preparation of these materials by providing uniform heating and rapid reaction times. The synergistic effect of varying thiol capping ligand concentrations as well as reaction temperatures and times resulted in fine control of nanoparticle growth in the 3–5 nm size range. Investigation of the photophysical properties of the colloidal nanoparticles were performed using electronic absorption and luminescence emission spectroscopy. Qualitative nanoparticles sizes were determined from the photoluminescence (PLE) data and compared to HRTEM images.
Foundation for Model Integration: Semantic Backplane

One of the primary goals of the Adaptive Vehicle Make (AVM) program of DARPA is the construction of a model-based design flow and tool chain, META, that will provide significant productivity increase in the development of complex cyber-physical systems. In model-based design, modeling languages and their underlying semantics play fundamental role in achieving compositionality. A significant challenge in the META design flow is the heterogeneity of the design space. This challenge is compounded by the need for rapidly evolving the design flow and the suite of modeling languages supporting it. Heterogeneity of models and modeling languages is addressed by the development of a model integration language – CyPhy – supporting constructs needed for modeling the interactions among different modeling domains. CyPhy targets simplicity: only those abstractions are imported from the individual modeling domains to CyPhy that are required for expressing relationships across sub-domains. This “semantic interface” between CyPhy and the modeling domains is formally defined, evolved as needed and verified for essential properties (such as well-formedness and invariance). Due to the need for rapid evolvability, defining semantics for CyPhy is not a “one-shot” activity; updates, revisions and extensions are ongoing and their correctness has significant implications on the overall consistency of the META tool chain. The focus of this paper is the methods and tools used for this purpose: the META Semantic Backplane. The Semantic Backplane is based on a mathematical framework provided by term algebra and logics, incorporates a tool suite for specifying, validating and using formal structural and behavioral semantics of modeling languages, and includes a library of metamodels and specifications of model transformations.Copyright © 2012 by ASME
Do Rocks Have Rights

Jacques Arnold has an interesting job within CNES, the French space agency. He has been a Space Ethicist with them since 1998. His job is to talk with people working at CNES about the ethical implications of their work. He does not believe that ethics is a matter of a set of rules of behavior that must be followed and enforced, but rather a way of thinking and acting reflectively and responsibly in everything one does. He helps people think through the ethical consequences of their work in many dimensions, perhaps leading them sometimes to do things differently from the way they otherwise might have done them.
Effect of iodine deficiency on iodine-containing compounds of rat tissues.

The distribution and quantitation of endogenously labeled iodine-containing compounds in normal and iodine-deficient rats were determined under steady state conditions. An isotope equilibrium method based on chronic feeding of 125I-labeled diet of known specific activity containing 0.06 μg 127I/g (experimental) and 0.22 fig 127I/g (control) was employed. Iodine deficiency was associated with the usually described rise in thyroid weight and MIT/DIT and T3/T4 ratios, even though there was a significant absolute decrease in all iodine compounds. Despite the iodine deficiency state the absolute concentration of T4 exceeded that of T3. Quantities found per g thyroid were 5.3 μg DIT, 5.7 μg MIT, 2.6 μg T4 and 1.7 μg T3. The T3/T4 ratio in plasma and tissues also rose, but for different reasons, as there was an absolute rise in T3 in plasma and most tissues and an absolute fall in T4 in plasma and all tissues. Despite these changes the absolute concentration of T4 still exceeded that of T3 in plasma and most tis...
Increased Accumulation of Tissue ACE in Human Atherosclerotic Coronary Artery Disease

Background Angiotensin may play a pathophysiological role in experimental and human cardiovascular disease. Clinical studies have shown that ACE inhibitors reduce mortality, recurrent myocardial infarction, and ischemic events in patients with left ventricular dysfunction. Animal studies suggest that tissue ACE, particularly within blood vessels, may be an important target. Methods and Results To study tissue ACE in human coronary artery disease and to identify potential mechanisms of ACE inhibitor action, we examined ACE expression immunohistochemically in nonatherosclerotic and diseased human coronary arteries. In nonatherosclerotic arteries, ACE immunoreactivity was found in luminal and adventitial vasa vasorum endothelium. In early- and intermediate-stage atherosclerotic lesions, ACE was detected prominently in regions of fat-laden macrophages and in association with T lymphocytes. In advanced lesions, ACE immunoreactivity was also localized to the endothelium of the microvasculature throughout the pl...
An efficient simulation procedure for point estimation of expected shortfall

We present a computationally efficient simulation procedure for point estimation of expected shortfall. The procedure applies tools for ranking and selection to allocate more computational resources to estimation of the largest losses, which are those that affect expected shortfall. Given a fixed computational budget, our procedure estimates expected shortfall with a much lower mean squared error than a standard simulation procedure and much more precisely than an existing interval estimation procedure.
Effects of levels of human exposure on flight initiation distance and distance to refuge in foraging eastern gray squirrels (Sciurus carolinensis)

Flight initiation distance (FID), the distance at which an organism begins to flee from an approaching predator or threat, is associated to prey escape decision-making processes with benefit and cost trade-offs to remaining in a patch. Fac- tors that may affect FID can be altered by human-stimulated predation risk, although the magnitude of response may depend on human exposure. We investigated how FID and distance to refuge of foraging eastern gray squirrels (Sciurus carolinensis Gmelin, 1788), vary in seven sites corresponding to three levels of human exposure. We predicted that both FID and dis- tance to refuge increase as exposure to human stimuli decreases; FID increases with the starting distance of the approaching human; and FID increases with distance to refuge. We found that FID increased with decreasing human exposure and that FID increased with increasing starting distance. We found no difference in distance to refuge between exposure levels. Our results suggest that risk posed to gray squirrels in areas frequently visited by humans is minimized or reduced, leading to differences in FID between exposure levels and may be attributed to habituation to increased nonlethal stimuli in the form of exposure to humans.
“Some Queer Freak of Taste”: Gender, Authorship, and the “Rock Me to Sleep” Controversy

Published in 1860 under the pseudonym "Florence Percy," "Rock Me to Sleep" quickly became one of the most popular and widely circulated poems of the nineteenth century. It also became the subject of a heated literary controversy, with multiple claimants coming forward to insist that they had authored the lyric; the most committed imposter was Alexander McWhorter Ball, a New Jersey legislator whose wealthy and powerful friends mounted a national campaign to prove his authorship. The poem's actual author, Elizabeth Akers Allen, found herself in danger of losing her reputation and therefore her ability to place her work within the literary marketplace. Putzi argues that the poem's sentimentality rendered it eminently reprintable but also distanced the text from its author, thus causing pretenders to imagine themselves in her place. The gendered implications of this sort of aggressive read ing were revealed most clearly in Ball's claim to authorship, which was based on this middle-class gentleman's emotional legitimacy as evidenced by the private circulation of (what he claimed as) his poetry. Rather than asserting her own femininity, however, Akers Allen exposed the gender and class privilege underlying Ball's argument, claiming her own professionalism and disparaging Ball as a "poetaster" or a hopeless amateur. With publications across the United States taking sides on either side, the "Rock Me to Sleep" controversy became an important marker of the status of professional women writers in the post-Civil War era; more specifically, and perhaps more importantly, it positions one woman's composition, publication, and circulation practices within a literary marketplace that paradoxically asked women poets to be simultaneously of and beyond the market-amateurs in a professional world.
Nonlinear Dynamic Model Evaluation from Disturbance Measurements

The nonlinear nonsmooth nature of power system dynamics complicates the process of validating system models from disturbance measurements. This paper uses a Gauss-Newton method to compute a set of model parameters that provide the best fit between measurements and model response. Trajectory sensitivities are used to identify parameters that can be reliably estimated from available measurements. An overview of trajectory sensitivity analysis is provided. An example based on the Nordel system is used throughout the paper to illustrate the various concepts. This example exhibits both soft and hard nonlinearities.
Multiple dimensions of integrating development technology

Studies have shown that errors are most likely to be introduced in the requirements phase of a development effort. This problem is largely due to prose descriptions that are ambiguous or inconsistent. One potential solution to this problem is to capture requirements information in the form of formal specifications that can be checked for consistency and completeness using automated techniques. However; during the initial phases of a project, it may be difficult to construct formal specifications directly. In contrast, many developers find it more intuitive to create diagram to model their systems. As a means to bridge the gap between formal and informal approaches to software development, we have investigated the formalization of a commonly used object-oriented modeling notation, Object Modeling Technique (OMT). The formalization of OMT enables the automated generation of formal specifications of the diagrams that can then be analyzed using simulation and model checking, and other types of verification techniques. Lessons from this integration effort can assist in the development of strategies for integrating techniques from the assurance, fault tolerance, and security fields. One key factor to this type of collaboration will be the use of a specific problem domain to focus the integration efforts. Another issue to be addressed is a common framework upon which the researchers from the three fields can build their integrated techniques.
Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Connecticut

In a previous investigation, statistical modelling was used to examine the relationship between large-bowel-cancer incidence and age, time period and birth cohort by anatomic sub-site and sex, using data from the Connecticut Tumor Registry (CTR) for the period 1950 to 1984. This analysis revealed differences in age-period-cohort patterns that suggested etiologic distinctions among sub-site groupings and between the sexes. To test the generalizability of the Connecticut findings, we have conducted a similar age-period-cohort analysis using data from the Danish Cancer Registry (DCR) for the period 1953 to 1987. Cancers of the large bowel were classified into 6 anatomic sub-sites: cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum. Data were fitted to log-linear age-period-cohort models. If we interpret differences in age-period-cohort patterns as reflecting etiologic distinctions, the Denmark analysis, in conjunction with the Connecticut findings, was consistent with there being etiologic distinctions between cancers of the colon vs. the rectum in both males and females, between cancers of the cecum and the ascending colon vs. the remainder of the colon in females and between males vs. females for cancers of the sigmoid colon and rectum. Cancers of the cecum and the ascending colon were the most similar between males and females. Due to the ambiguities of age-period-cohort modelling, these should be considered only tentative conclusions that can be tested by analytical epidemiologic studies.
Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells

Cyclic strain regulates many vascular smooth muscle cell (VSMC) functions through changing gene expression. This study investigated the effects of cyclic strain on protease-activated receptor-1 (PAR-1) expression in VSMCs and the possible signaling pathways involved, on the basis of the hypothesis that cyclic strain would enhance PAR-1 expression, reflecting increased thrombin activity. Uniaxial cyclic strain (1 Hz, 20%) of cells cultured on elastic membranes induced a 2-fold increase in both PAR-1 mRNA and protein levels. Functional activity of PAR-1, as assessed by cell proliferation in response to thrombin, was also increased by cyclic strain. In addition, treatment of cells with antioxidants or an NADPH oxidase inhibitor blocked strain-induced PAR-1 expression. Preincubation of cells with protein kinase inhibitors (staurosporine or Ro 31-8220) enhanced strain-increased PAR-1 expression, whereas inhibitors of NO synthase, tyrosine kinase, and mitogen-activated protein kinases had no effect. Cyclic strain in the presence of basic fibroblast growth factor induced PAR-1 mRNA levels beyond the effect of cyclic strain alone, whereas no additive effect was observed between cyclic strain and platelet-derived growth factor-AB. Our findings that cyclic strain upregulates PAR-1 mRNA expression but that shear stress downregulates this gene in VSMCs provide an opportunity to elucidate signaling differences by which VSMCs respond to different mechanical forces.
On Insulin Action in Vivo: The Single Gateway Hypothesis

It has become increasingly clear that insulin resistance plays an important role in the pathogenesis of chronic diseases of Westernized societies. Compelling evidence exists not only that insulin resistance is a risk factor for diabetes mellitus (1,2) but this metabolic characteristic is also associated with hypertension and atherosclerosis (3,4). In addition, there is evidence from the Pima Indians (5) and from high-risk offspring of two NIDDM parents (6) that insulin resistance is an inherited trait. Given that there must be one or more specific underlying mechanistic defects which are responsible for insulin resistance, and given its potential importance in the pathogenesis of chronic disease, it is incumbent upon us to continue to try to identify the cellular or molecular defects which underlie this condition.
The Internet and Education: Forces at War?

This note discusses the impact of electronic communication on education. I argue that we humans have very little real comprehension of the changes that modem computers have wrought to our system of life in general, and to the delivery of education in particular. I believe that automated learning (in all of its many and various forms) is on balance rather bad than good, that it stifles the imagination, that it does not inculcate creativity, and that many students, untrained by computers in the art of thinking, are already finding their niches in an “AynRandian” world [1]. What does this have to do with Soft Computing? Nothing, and Everything. Nothing, because none of you will, after reading this paper, crush your computers and look for the closet abacus. And everything, because I believe that the next generation of scientists, including those being cultivated right now in your elementary school back home, will be largely unable to formulate and solve new problems. When this happens, science will stagnate, and technology will no longer be the panacea that humans count on when problems they create for themselves become irresolvable by methods based on current knowledge.
A Study of Crosstalk in a $256 \times 256$ Photon Counting Imager Based on Silicon Geiger-Mode Avalanche Photodiodes

We demonstrate a $256 \times 256$ passive photon counting imager based on hybridization of back-illuminated silicon Geiger-mode avalanche photodiodes to an all-digital CMOS counting chip. Photon detection efficiencies in the 10%–20% are observed at visible wavelengths. The detection efficiency is currently limited by optical crosstalk that leads to elevation of dark count rates as the bias voltage on the photodiodes is increased. Both the time dependence of dark count activity during a gate time and the spatial structure of dark images were successfully explained using crosstalk-based models.
The Flagellar System of Pseudomonas aeruginosa

Pseudomonas aeruginosa typically possesses a single unsheathed polar flagellum that plays a variety of roles in the virulence in addition to its central role in swimming motility. The polar location of the flagellum of this organism (Figure 1A) contrasts with the peritrichously located flagella of enteric bacteria and the polar and lateral flagella found in some Vibrio spp. This polar placement is similar to that seen in some other monoflagellates, for example, V. cholerae, Helicobacter spp., Campylobacter spp., and a number of other pseudomonads. Besides the differences in the number and the location of the flagella from the well-described multiflagellated enteric bacteria, Escherichia coli and Salmonella typhimurium var. typhimurium44, the regulation of the assembly of this complex structure in P. aeruginosa differs considerably from that seen in these organisms. These differences are the main focus of this chapter. General details of flagellar assembly can be found elsewhere2, 44.
Occupational Exposures Associated with Male Breast Cancer

The role of occupational exposure to heat and electromagnetic fields was investigated in a case-control study of male breast cancer. Seventy-one cases reported to the New York State Tumor Registry between 1979 and 1988 were compared with 256 healthy male controls. Controls were frequency matched to cases by race, year of diagnosis, and age in 5-year intervals. Unconditional logistic regression modeling indicated that males with occupations that involved heat exposure had an elevated risk for the disease. The age- and county-adjusted odds ratio was 2.3 (95% confidence interval (CI) 0.95-5.3). Exposure to heat on the job could influence testicular function. No increase in disease risk was observed for males believed to have occupational exposure to electromagnetic fields (odds ratio = 0.7, 95% CI 0.3-1.9).
MUzECS: Block-based Arduino Programming for Exploring Computer Science (Abstract Only)

The inexpensive Arduino makes for an attractive embedded platform in introductory courses. Its many variants, open source tools, and well-established hobbyist community support a staggering breadth of possible uses. In this workshop, we concentrate on block-based programming of the Arduino, providing a smooth path for Scratch programmers to expand into the wider world of sensors, actuators, and embedded systems. The MUzECS curriculum is designed to be an inexpensive replacement for the costly final robotics module of Exploring Computer Science (ECS), but also has clear applicability to Advanced Placement Computer Science Principles (AP CSP) and even college undergraduate courses. The session will introduce the Arduino Leonardo board, detail various "shield" extensions that are available, and present the tools and resources needed for high school or college instructors to get started. Demonstration activities will focus on ECS-style lessons that build programmable musical instruments. Laptop required.
Abstract P2-02-04: MRI Findings and Outcomes in an Underserved Breast Cancer Population Screened withBRCATesting

Background: Patients with breast cancer and a familial risk and/or BRCA 1 or 2 mutations are at high risk of contralateral breast cancer and ipsilateral recurrence. While MRI screening is recommended for patients with BRCA mutations, and MRI staging for breast cancer is being increasingly used, the outcomes of such testing are not well described, especially in underserved populations. At Los Angeles County Hospital (LAC) for the last 3 years, we have enacted a program of genetic counseling and testing based standard guidelines as well as MRI evaluation of all patients newly diagnosed with breast cancer. LAC serves a population that includes a high number of indigent patients, primarily Hispanic (60%) and Asian (15%). Methods: We undertook a retrospective evaluation of all patients seen at LAC from March 2008 to March 2010 who underwent genetic counseling/testing and MRI as preoperative assessment for histologically documented breast cancer or followup after cancer treatment. IRB approval was obtained to extract data for this analysis. Demographic information along with clinical presentation, MRI and mammography results, additional imaging results, biopsy and surgical procedure and corresponding pathology data were obtained through the review of electronic medical records and clinic charts. Results: A total of 90 patients had both genetic testing and MRI reports available. The median age of all tested patients was 41 years. Ethnicity was 78% Hispanic, 9% Asian, 7% African American, 2% Caucasian and 4% other. BRCA mutation was seen in 20 cases (22%), 12 BRCA-1, 8 BRCA-2, 4 variants of unknown significance, and 66 had no mutation. Breast mass or other symptoms were the mode of detection in 89% of the overall cohort, and 81% in mutation carriers. The index lesion was visible on MRI in 78% and by mammogram in 82% of all patients. Ipsilateral MRI showed 7 abnormal non-index findings in 6 patients (7%); 6 of 7 lesions biopsied showed cancer. In the contralateral breast, 7 abnormalities were noted on MRI, but only 5 were amenable to biopsy as 2 could not be visualized by any means on follow up, and 1 showed cancer. Interestingly, only one of the 13 patients with abnormal findings carried a mutation (BRCA-1) and this patient did not have cancer on contralateral lesion biopsy. Mastectomy was performed in 91% and 78% of patients with and without mutation. Conclusions: Screening, counseling and testing for BRCA mutations is feasible in an underserved population, with a 22% mutation identification rate. MRI detected 5 non-index ipsilateral cancers and one contralateral cancer among 90 patients, with none of the detected cancers among the 20 mutation carriers. While MRI staging may be effective at detecting additional cancers in this underserved and high familial risk population, this appears to be independent of BRCA status. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-04.
Utilization and Role of Adjuvant Radiotherapy and Chemotherapy for Uterine Clear Cell Carcinoma: A National Cancer Data Base Analysis

Objective Because of the rarity of uterine clear cell carcinoma (UCCC), a National Cancer Data Base analysis was conducted to evaluate practice patterns and implications of adjuvant therapy. Methods The National Cancer Data Base was queried for UCCC patients diagnosed from 1998 to 2011. Patients receiving neoadjuvant therapy, lacking surgical staging, or having follow-up time shorter than 6 months were excluded. Factors associated with utilization were assessed using logistic regression. To define the probability of receiving chemotherapy and radiotherapy (CT + RT), propensity scores with inverse probability of treatment weighting (IPTW) were calculated using multivariable logistic regression. Log-rank test and multivariable IPTW-adjusted Cox proportional hazards modeling were then conducted. Results A total of 2504 patients were identified, with a median follow-up of 65.5 months. Most patients had FIGO (International Federation of Gynecology and Obstetrics) stage I to II UCCC (71.4%). Adjuvant RT alone, CT alone, or CT + RT was given in 35.3%, 9.5%, and 11.7%, respectively. Among those receiving RT, external beam was the most common modality (69.4%). Later year of diagnosis (>2005: odds ratio [OR], 4.42; 95% confidence interval [95% CI], 2.44–8.01), higher FIGO stage (IIIA-IIIC2: OR, 6.34; 95% CI, 3.93–10.24), larger tumor size (3.6–5.0 cm: OR, 3.40; 95% CI, 1.76–6.55), and lymph node dissection (OR, 4.22; 95% CI, 1.60–11.15) were associated with a higher chance of receiving CT + RT. With IPTW-adjusted multivariable analysis, CT + RT significantly decreased mortality risk in stage III to IVA patients (hazards ratio, 0.41; 95% CI, 0.22–0.77), trending toward benefit in stage I to II patients (hazards ratio, 0.53; 95% CI, 0.27–1.07). Conclusions In this hospital-based registry analysis of UCCC, adjuvant CT + RT significantly reduced the risk of death, reaching statistical significance for stage III to IVA patients.
GE-37INTEGRATED GENOMIC ANALYSIS OF LOW GRADE GLIOMA AND GLIOBLASTOMA REVEALS MOLECULAR STRATIFICATION BY IDH STATUS ACROSS GRADES AND HISTOLOGIES

TCGA has performed comprehensive molecular characterization of glioblastoma (GBM) and diffuse low grade glioma (LGG), which suggested heterogeneity in clinical diagnosis: GBM with isocitrate dehydrogenase (IDH) gene mutations corresponded with a hypermethylator/G-CIMP phenotype and relatively favorable outcome, while IDH-wildtype LGG were associated with GBM-like genomic and methylation features and poor survival. By integrating the GBM and LGG datasets, the TCGA LGG-GBM working group aims to classify them in a clinically relevant manner and to shed light on potential targets for therapy. Unsupervised clustering of 289 LGG and 398 GBM using methylation profiles resulted into six major groups, mainly driven by IDH status and age. G-CIMP/IDH mutant GBM clustered with IDH mutant LGGs and IDHwt LGG grouped with IDHwt GBM. Some but not all LGG with 1p/19q co-deletion, a hallmark of oligodendroglioma, clustered separate from other LGGs and associated with less favorable outcome, suggesting clinical value of methylation based patient stratification. IDH-wildtype LGG and GBM clustered into a classical-mesenchymal class and a proneural-mesenchymal subtype, the latter with normal-like methylation features. Unsupervised transcriptome clustering of 282 LGGs and 152 GBMs was again driven by IDH status, followed by strong associations with mutations in TP53/ATRX. Supervised comparison of IDH wildtype LGG and GBM suggested upregulation of oxidative phosphorylation gene sets in GBM which may provide an intriguing possibility of pathogenetic differences between histologically different but genomically similar gliomas. We evaluated the distribution of genomic alterations in glioma disease pathways and found that G-CIMP GBM uniquely associated with abnormalities in the MYC pathway, revealing a possible explanation for the aggressive behavior of IDH-mutant GBM relative to IDH-mutant LGG. In this first of its kind study, we improve our understanding of gliomagenesis by identifying shared and subtype-unique disease pathways and provide new modalities towards integrated classification of diffuse low and high grade glioma.
499 REACTIVATION OF PERIPHERAL BLOOD MONONUCLEAR CELLS IN WEST NILE FEVER SURVIVORS: FEASIBILITY OF USING CYTOKINE EXPRESSION PROFILES FROM MICROARRAYS TO EXPLAIN DISEASE SEQUELAE.

Since its initial outbreak in 1999, West Nile virus has become endemic across most of the United States. Although many patients will be asymptomatic after infection, approximately 40% of reported cases of West Nile fever through 2005 had some form of neuroinvasive disease. Of the survivors, there is varying disease sequelae, including fatigue, myalgias, paresthesias, and other neurologic symptoms. Of interest, patients who have similarly severe disease requiring hospitalization have varying degrees of disease sequelae on recovery. There may be a difference in the immune response between survivors. One approach would be to study the cytokine expression profile of reactivated peripheral blood mononuclear cells in patients with neuroinvasive disease using microarray techniques. Currently, there is a lack of published research looking at the immunology of infection in these patients. The aim of this study is to determine the feasibility of reactivating peripheral blood mononuclear cells of West Nile fever survivors in preparation for further studies looking at specific cytokine profiles of survivors. This approach could reveal patterns of immune response and regulation that could one day be instituted into new therapies to help alleviate the symptoms of this increasingly prevalent viral infection.
A Research on the Short Circuit Current Attenuation Characteristic of Short Circuit Generator with Large Capacity

This paper first briefly introduces the operational principals of short circuit generators.Then from the point of view of high-power laboratory,the attenuation characteristics of the short-circuit current of China-made 6 500 MV·A generator is studied and its MATLAB-based simulation mode is established.Based on the simulations of the attenuation characteristics of short-circuit current,the best choices of force excitation multiples to meet the requirements of relevant testing standards for three typical external impedance conditions are identified.The results of this paper provide a valuable reference for future operation of high-power laboratory.
How Do Family-Focused Prevention Programs Work? A Review of Mediating Mechanisms Associated with Reductions in Youth Antisocial Behaviors

The development and evaluation of family-focused preventive interventions has grown significantly in recent decades, but the degree to which these interventions produce anticipated improvements in the family environment, and the extent to which such changes are associated with reductions in youth antisocial behaviors (ASB), is unclear. This article seeks to answer these questions by reviewing evidence from tests of mediation conducted in evaluations of family-focused interventions. Interventions are drawn from family-focused interventions rated as Model Plus, Model, or Promising on the Blueprints for Healthy Youth Development Web site ( http://www.colorado.edu/cspv/blueprints/ ) based on evidence of their effectiveness in reducing child externalizing behaviors, substance use, and/or delinquency. Of the 19 such interventions listed on Blueprints, seven programs (37 %) were evaluated using mediation analyses which met study criteria. Two-thirds (67 %) of these analyses indicated significant improvements in the targeted family processes for intervention versus control group participants. Over half (62 %) of all tests of mediation were statistically significant and indicated that improvements in the family environment were associated with reductions in ASB. The results support prior theoretical and empirical literature identifying the family as an important context for preventing ASB and promoting healthy youth development. The findings also provide information that can be used to refine current family-focused interventions in order to increase their efficiency and potency, and to develop new interventions in order to expand the number and types of families who can benefit from such services.
Nutritional supplements modulate fluorescent protein-bound advanced glycation endproducts and digestive enzymes related to type 2 diabetes mellitus

Chronic hyperglycemia enhances the formation of advanced glycation endproducts (AGEs) and reactive oxygen species (ROS), contributing to diabetic complications. Thus, controlling blood glucose levels, inhibiting the formation of AGEs and reducing ROS are key therapeutic targets in early stage type 2 diabetes. The inhibitory effects of seven commercial liquid nutritional supplements against carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase, was determined by dinitrosalicylic (DNS) reagent and p-nitrophenyl-α-D-glucopyranoside solution, respectively. Antiglycation activity was determined using the formation of fluorescent protein-bound AGEs. Total phenolic and flavonoid content and antioxidant properties (1,1-diphenyl-2-picrylhydrazyl antioxidant activity (DPPH) and ferric reducing antioxidant power (FRAP)) were determined for correlation among these components and inhibitory activities. Samoan noni juice showed the greatest inhibitory effects against α-amylase, whereas chlorophyll extracts showed the greatest inhibitory effect against α-glucosidase. Inhibition of α-glucosidase correlated with TFC (r2 = 0.766; p < 0.01) and FRAP (r2 = 0.750; p < 0.01) whereas no correlation was observed for α-amylase inhibition. All supplements inhibited fluorescent protein-bound AGEs, with the greatest effect exerted by Olive Leaf Extract, Blood Sugar Support (IC50 = 0.5 mg/ml). The IC50 values negatively correlated with TPC (r2 = −0.707; p < 0.001) and DPPH scavenging activities (r2 = 0.515; p < 0.05). The findings of this study highlight the potential of liquid nutritional supplements in managing and treating type 2 diabetes mellitus.
Discipline Disparities for LGBTQ Youth: Challenges that Perpetuate Disparities and Strategies to Overcome Them

Snapp and Russell identify factors that give rise to and perpetuate discipline disparities towards LGBTQ youth, as well as put forth strategies to reduce them. Challenges include an overly punitive approach to discipline and security in schools; untrained and overextended school staff; explicit and implicit bias towards against LGBTQ students; and a lack of school support for LGBTQ students. The authors suggest non-punitive discipline practices and the creation of safe and affirming spaces for LGBTQ students, with properly trained school personnel. Although specific to LGBTQ students, these policies have the potential to improve safety and learning for all students due to their emphasis on inclusion and respect for diversity. These cross-constituency alliances identify, advocate for, and implement school practices and policies that will reduce discipline disparities for all students.
Radon Measurement Techniques

The specific activities of 222Rn in environmental samples (atmospheric and soil air, surface and groundwater, etc) can vary over 5 orders of magnitude and hence the methods and instruments to measure radon activities vary widely. The measurement techniques are classified based three characteristics—i) whether measurement involves 222Rn or its progeny; ii) time resolution; and iii) detection of the type of emission, whether alpha or beta particle or gamma radiation resulting from radioactive decay. The three broad classes of time resolution, based on sampling and analysis, include i) grab-sample technique; ii) continuous technique and iii) integrating technique. The preferred technique is based on the purpose of the study and the research question addressed. Precise determination of radon activity in surface waters of the ocean and lakes for tracer studies requires careful sampling. A review of most commonly-used techniques for measuring radon in air and water samples along with quality control, precision and accuracy in radon measurements are presented in this chapter.
Cancer driver gene discovery through an integrative genomics approach in a non-parametric Bayesian framework.

Motivation Comprehensive catalogue of genes that drive tumor initiation and progression in cancer is key to advancing diagnostics, therapeutics and treatment. Given the complexity of cancer, the catalogue is far from complete yet. Increasing evidence shows that driver genes exhibit consistent aberration patterns across multiple-omics in tumors. In this study, we aim to leverage complementary information encoded in each of the omics data to identify novel driver genes through an integrative framework. Specifically, we integrated mutations, gene expression, DNA copy numbers, DNA methylation and protein abundance, all available in The Cancer Genome Atlas (TCGA) and developed iDriver, a non-parametric Bayesian framework based on multivariate statistical modeling to identify driver genes in an unsupervised fashion. iDriver captures the inherent clusters of gene aberrations and constructs the background distribution that is used to assess and calibrate the confidence of driver genes identified through multi-dimensional genomic data. Results We applied the method to 4 cancer types in TCGA and identified candidate driver genes that are highly enriched with known drivers. (e.g.: P < 3.40 × 10 -36 for breast cancer). We are particularly interested in novel genes and observed multiple lines of supporting evidence. Using systematic evaluation from multiple independent aspects, we identified 45 candidate driver genes that were not previously known across these 4 cancer types. The finding has important implications that integrating additional genomic data with multivariate statistics can help identify cancer drivers and guide the next stage of cancer genomics research. Availability and Implementation The C ++ source code is freely available at https://medschool.vanderbilt.edu/cgg/ . Contacts hai.yang@vanderbilt.edu or bingshan.li@Vanderbilt.Edu. Supplementary information Supplementary data are available at Bioinformatics online.
Epigenetic and Nongenomic Roles for Histone Deacetylases in Heart Failure

Heart failure due to systolic and/or diastolic ventricular dysfunction afflicts millions of people worldwide. Most heart failure drugs target signaling cascades that emanate from the cardiomyocyte cell surface. However, given the ability of numerous receptors to trigger adverse ventricular remodeling, it has been hypothesized that more efficacious therapeutic strategies would be based on inhibition of downstream “nodal” points that integrate upstream signals to convey a common pathway for heart failure pathogenesis. This chapter highlights data suggesting that a family of epigenetic regulatory enzymes, histone deacetylases (HDACs), represent such nodal points. We discuss recent findings that illustrate how HDACs not only control cardiac gene expression via epigenetic regulation, but also serve crucial non-genomic functions in the heart through deacetylation of non-histone proteins.
The usefulness of the video head impulse test in children and adults post-concussion.

OBJECTIVE Dizziness after concussion have been reported in both youths and adults. It is not clear if the dizziness experienced post-concussion is from peripheral or central etiology. New technology has been developed to quickly and easily quantify the magnitude of peripheral vestibular disorders that is non-invasive and acceptable to youths and adults. The purpose of this study was to determine if youths and adults' post-concussion have evidence of decreased horizontal semicircular canal vestibulo-ocular reflex (VOR) gains as measured with the video head impulse test (vHIT), which would indicate a peripheral vestibular disorder. An additional purpose was to determine if VOR gain scores correlate with functional performance measures. DESIGN Descriptive cross sectional. SETTING Large medical center out-patient concussion program. PARTICIPANTS Fifty-six subjects with concussion. MAIN OUTCOMES/MEASURES Subjects completed the vHIT testing, the Dizziness Handicap Inventory (DHI), the Vestibular Activities and Participation (VAP) scale, the Pediatric Vestibular Symptom Questionnaire, gait speed assessment, the Dynamic Gait Index (DGI) and a verbal analog scale of symptom provocation before and after the vHIT testing. RESULTS There were no abnormal vHIT findings in any subject. Headaches, dizziness and nausea were significantly worse post vHIT testing (p < 0.05). Youths had better DGI and DHI scores than subjects older than 20 (p < 0.05). CONCLUSION The vHIT did not detect horizontal semicircular canal weakness in any of the subjects tested. In addition, older adults reported more activity and participation limitations than the younger subjects with concussion.