cssi/SciSciGPT-SciSciNet huggingface dataset:
Polyps and Tumors of the Gastrointestinal Tract in Childhood

Although a wide variety of polyps and tumors occur in the pediatric gastrointestinal tract, the incidence and pathologic types encountered differ from those seen in adults. Some of them may have unique associations with developmental and syndromic disorders, the recognition of which may be critical in clinical management. This chapter begins with a summary of the epidemiology of pediatric gastrointestinal polyps and masses and continues with more detailed sections focusing on the etiology, clinical features, pathologic findings, and genetics of specific gastrointestinal polyposis syndromes and gastrointestinal tumors. Major entities covered in the section on polyps include juvenile polyposis, Peutz-Jeghers syndrome, PTN hamartoma tumor syndrome, familial adenomatous polyposis, and inflammatory polyps. The section on tumors summarizes the literature on the various tumors that have presented in the pediatric gastrointestinal tract, with emphasis on colorectal carcinoma, carcinoid tumors, lymphoproliferative disorders, stromal tumors, and inflammatory myofibroblastic tumors.
Watt-Level 100-nm Tunable 3- $\mu$ m Fiber Laser

Watt-level erbium-praseodymium codoped ZBLAN midinfrared fiber laser with 100-nm continuously wavelength-tunable range (2.7-2.8 m) is demonstrated. Continuous-wave output of 1 W with a linewidth of 1.8 GHz over the entire tuning range is affordable. Owing to relatively small residual populations in the lower laser level I of Er ions in the Er-Pr-codoped system, the wavelength-tunable range shrinking with increasing pump power, which always happens in tunable singly Er-doped ZBLAN fiber lasers, was not observed in this tunable Er-Pr-codoped fiber laser.
Interior Additivity and Subjective Probability Assessment of Continuous Variables

One of the goals of psychological research on subjective probability judgment is to develop prescriptive procedures that can improve such judgments. In this paper, our aim is to reduce partition dependence, a judgmental bias that arises from the particular way in which a state space is partitioned for the purposes of making probability judgments. We explore a property of subjective probabilities called interior additivity (IA). Our story begins with a psychological model of subjective probability judgment that exhibits IA. The model is a linear combination of underlying support for the event in question and a term that reflects a prior belief that all elements in the state space partition are equally likely. The model is consistent with known properties of subjective probabilities, such as binary complementarity, subadditivity, and partition dependence, and has several additional properties related to IA. We present experimental evidence to support our model. The model further suggests a simple prescriptive method based on IA that decision and risk analysts can use to reduce partition dependence, and we present preliminary empirical evidence demonstrating the effectiveness of the method.
The creation of super-excited electronic Feshbach resonances by EUV-induced dissociation of O 2

We resolve complex electron autoionization dynamics in molecules in real time for the first time, where a second electron cannot be ejected from O 2 until the internuclear separation of the fragments is ≫30A.
Tissue Mixture Characterization In The Presence of Mri Inhomogeneity by the Em Algorithm

This paper presents a model-based approach to correct for both partial volume effect and inhomogeneity in segmenting tissue mixtures inside each voxel of magnetic resonance images. A maximum a posteriori probability (MAP) solution is sought. In calculating the solution, the well-known expectation maximization (EM) algorithm is employed. The models of data likelihood and Markov priors for tissue mixture and bias field in establishing this MAP-EM framework are described in details. A preliminary test is presented
Ler Pessoa a luz de Pessoa: uma interpretacao das Odes de Álvaro de Campos

A imensa obra de Fernando Pessoa converge num ponto: a busca angustiada pelo conhecimento de si, do mundo e de Deus, em um universo em acelerada transformacao. Este trabalho propoe analisar os poemas "Ode triunfal" e "Ode maritima", a luz dos textos filosoficos e esteticos de Fernando Pessoa, especialmente os escritos sobre o Sensacionismo e os "Apontamentos para uma estetica nao-aristotelica", assinados por Alvaro de Campos, alem de outros poemas, tanto do Pessoa ortonimo quanto do heteronimo, no objetivo de observar essa busca e verificar como ela e expressa nos textos poeticos selecionados.
Strain transfer and partitioning between the Panamint Valley, Searles Valley, and Ash Hill fault zones, California

We report new geologic and geomorphic observations that bear on the interpretation of connectivity and strain transfer among the Panamint Valley, Searles Valley, and Ash Hill fault zones, southern Walker Lane belt of California. Although these faults partition strain regionally onto dominantly normal and strike-slip structures, strain transfer occurs in a complex way not typical of linked strike-slip and extensional faults. The Searles Valley fault (W-directed normal fault) transfers slip onto the Panamint Valley zone, which changes from dominantly NNW-trending dextral strike-slip to more normal motion where they join. The Ash Hill fault (mostly right-lateral strike slip) transfers strain into the northern continuation of the Searles Valley zone, via a complex array of hanging-wall normal and strike-slip faults. These complex interactions, based on the age of structurally offset markers, appear to be stable over ;10 5 years.
Primary Kaposi sarcoma of the subcutaneous tissue

Background: Involvement of the subcutis by Kaposi sarcoma (KS) occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. Case presentation: We present a unique case of acquired immune deficiency syndrome (AIDS)associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh in a 43-yearold male, which occurred without overlying visible skin changes or concomitant KS disease elsewhere. Radiological imaging and tissue biopsy confirmed the diagnosis of KS. Conclusion: This is the first documented case of primary subcutaneous KS occurring in the setting of AIDS. The differential diagnosis of an isolated subcutaneous lesion in an human immunodeficiency virus (HIV)-infected individual is broad, and requires both imaging and a histopathological diagnosis to guide appropriate therapy.
Grb2 is required for the development of neointima in response to vascular injury

Objective— Neointima formation occurs in arteries in response to mechanical or chemical injury and is responsible for substantial morbidity. In this work, the role of the intracellular linker protein Grb2 in the pathogenesis of neointima formation was examined. Grb2 is a critical signaling protein that facilitates the activation of the small GTPase ras by receptor tyrosine kinases. Methods and Results— Cultured rat aortic smooth muscle cells were treated with an antisense morpholino to Grb2 and these cells showed a reduced proliferative response to platelet-derived growth factor stimulation. Grb2 −/− mice do not survive embryonic development. Grb2 +/− mice appear normal at birth and are fertile but have defective signaling in several tissues. Cultured smooth muscle cells derived from Grb2 +/− mice grew at a much slower rate than cells derived from Grb2 +/+ mice. Grb2 +/− and Grb2 +/+ mice were subjected to carotid injury. After 21 days, Grb2 +/+ mice developed robust neointima formation that, in some cases, resulted in an occlusive lesion. In contrast, Grb2 +/− mice were resistant to the development of neointima Conclusions— Grb2 is an essential component of the signaling cascade resulting in neointima formation after arterial injury.
Shoulder postural fatigue and discomfort: A preliminary finding of no relationship with isometric strength capability in a light-weight manual assembly task

Does greater strength capacity in the shoulder-complex afford increased protection against regionalized fatigue and discomfort induced by sustained awkward arm postures in light-weight manual assembly environments? This question was addressed by testing the relationship between differences in shoulder complex strength capacity, produced by variations in arm posture within a subject, and among subjects assuming equivalent arm postures, and severity of fatigue and discomfort sensed during a low-exertion manual performance task. Experimental findings showed that: (a) awkward arm postures produced substantial and rapid onset of postural fatigue and discomfort during a light-weight manual performance task where strength demands were low (i.e., less than 15 percent of maximum voluntary contraction (MVC)), (b) variations in strength capability found among arm postures within an individual subject, or 3mong subjects assuming the same arm posture, did not affect onset of substantial fatigue or discomfort when hands are postured near or above shoulder level, and (c) postures which simply appeared to be awkward, or which compromised strength capacity (e.g., working with the arm to the side of the body, or aligned in the coronal plane), did not necessarily increase discomfort of fatigue. Our findings suggest caution against sole reliance upon population or individual worker upper-extremity strength capabilities as predictors of fatigue and discomfort in the shoulder complex when manual exertions are small (e.g., light-weight manual assembly activities involving small parts or small hand-tools) and hands are postured at or above shoulder level.
Hashimot's encephalopathy-response to intravenous immunoglobulin.

Background: Hashimoto's encephalopathy is an unusual brain disorder consisting of focal and diffuse cerebral dysfunction that may present in a stroke-like fashion. Treatment has consisted of steroids and immunosuppression. Treatment with a potentially less toxic modality such as intravenous immunoglobulin (IVIG), if found to be effective, might offer an alternative approach to these patients. Case Description : We present an 82-year-old woman who developed headache, changes in mental status, and multifocal neurological deficits. Investigation revealed significantly elevated titers of antithyroid antibodies. Treatment with prednisone and methotrexate was unsuccessful. Treatment with monthly courses of IVIG resulted in marked clinical improvement. Conclusion : Hashimoto's encephalopathy may be more common than is generally recognized. A trial of IVIG should be considered for patients with this devastating condition
Aerobic exercise training improves whole muscle and single myofiber size and function in older women

To comprehensively assess the influence of aerobic training on muscle size and function, we examined seven older women (71 ± 2 yr) before and after 12 wk of cycle ergometer training. The training p...
Complexes from Trypanosoma brucei that exhibit deletion editing and other editing-associated properties.

Transcripts from many mitochondrial genes in kinetoplastids undergo RNA editing, a posttranscriptional process which inserts and deletes uridines. By assaying for deletion editing in vitro, we found that the editing activity from Trypanosoma brucei mitochondrial lysates (S.D. Seiwert and K.D. Stuart), Science 266:114-117,1994) sediments with a peak of approximately 20S. RNA helicase, terminal uridylyl transferase, RNA ligase, and adenylation activities, which may have a role in editing, cosediment in a broad distribution, with most of each activity at 35 to 40S. Most ATPase 6 (A6) guide RNA and unedited A6 mRNA sediments at 20 to 30S, with some sedimenting further into the gradient, while most edited A6 mRNA sediments at >35S. Several mitochondrial proteins which cross-link specifically with guide RNA upon UV treatment also sediment in glycerol gradients. Notably, a 65-kDa protein sediments primarily at approximately 20S, a 90-kDa protein sediments at 35 to 40S, and a 25-kDa protein is present at <10S. Most ribonucleoprotein complexes that form with gRNA in vitro sediment at 10 to 20S, except for one, which sediments at 30 to 45S. These results suggest that RNA editing takes place within a multicomponent complex. The potential functions of and relationships between the 20S and 35 to 40S complexes are discussed.
Legal Discrimination Against Lesbian, Gay, and Bisexual Employees: A Multi-Theoretical Model to Explain an Elusive Civil Rights Law

Using insights from historical, institutional (political-economic pluralism), critical, and values approaches to policy analysis, this manuscript seeks to explain why lesbians, gay men, and bisexuals, perhaps the most stigmatized populations in the United States, have not been awarded a very basic right: legal protection from workplace discrimination on the basis of sexual orientation. A detailed overview of the policy problem, its scope, and its significance is provided, followed by an in-depth explanation and application of the multi-theoretical model.
Culture of Honor and Violence Against the Self

Cultures of honor facilitate certain forms of interpersonal violence. The authors suggest that these cultures might also promote values and expectations that could heighten suicide risk, such as strict gender-role standards and hypersensitivity to reputational threats, which could lead people living in such cultures to consider death as an option when failure occurs or reputation is threatened sufficiently. Study 1 shows that, controlling for a host of statewide covariates, honor states in the United States have significantly higher male and female suicide rates than do nonhonor states, particularly in nonmetropolitan areas among Whites. Study 2 shows that statewide levels of antidepressant prescriptions (an indicator of mental health resource utilization) are lower in honor states, whereas levels of major depression are higher, and statewide levels of depression are associated with suicide rates only among honor states. Finally, Study 3 shows that individual endorsement of honor ideology is positively associated with depression.
Rigidification of a Flexible Protease Inhibitor Variant Upon Binding to Trypsin

The Tyr35→Gly replacement in bovine pancreatic trypsin inhibitor (BPTI) has previously been shown to dramatically enhance the flexibility of the trypsin-binding region of the free inhibitor and to destabilize the interaction with the protease by about 3 kcal/mol. The effects of this replacement on the enzyme-inhibitor interaction were further studied here by x-ray crystallography and isothermal titration calorimetry. The co-crystal structure of Y35G BPTI bound to trypsin was determined using 1.65 Å resolution x-ray diffraction data collected from cryopreserved crystals, and a new structure of the complex with wild-type BPTI under the same conditions was determined using 1.62 Å data. These structures reveal that, in contrast to the free protein, Y35G BPTI adopts a conformation nearly identical to that of the wild-type protein, with a water-filled cavity in place of the missing Tyr side chain. The crystallographic temperature factors for the two complexes indicate that the mutant inhibitor is nearly as rigid as the wild-type protein when bound to trypsin. Calorimetric measurements show that the change in enthalpy upon dissociation of the complex is 2.5 kcal/mol less favorable for the complex containing Y35G BPTI than for the complex with the wild-type inhibitor. Thus, the destabilization of the complex resulting from the Y35G replacement is due to a more favorable change in entropy upon dissociation. The heat capacity changes for dissociation of the mutant and wild-type complexes were very similar, suggesting that the entropic effects probably do not arise from solvation effects, but are more likely due to an increase in protein conformational entropy upon dissociation of the mutant inhibitor. These results define the biophysical role of a highly conserved core residue located outside of a protein-binding interface, demonstrating that Tyr35 has little impact on the trypsin-bound BPTI structure and acts primarily to define the structure of the free protein so as to maximize binding affinity.
Macromolecular transport through arterial wall: elastic barrier permeabilities

Injury of the arterial wall induces the synthesis of gene products that stimulate smooth muscle cell migration and proliferation, leading to intimal hyperplasia. This process contributes to the pathogenesis of atherosclerosis. To evaluate barriers to transport in the arterial wall of macromolecular transport into the arterial wall, we have developed mathematical models. These are based on experimental studies using HRP as a surrogate macromolecule for potential agents. Based on these data, we find that the media can be represented as a series of compartments bounded by elastic lamina. We further propose to model the thickened intima of an atherosclerotic artery as a distributed system juxtaposed to the compartmentalized media.
Injury prevention policy forum.

Injury prevention researchers, advocates and practitioners have made extraordinary progress in identifying the risk factors for injury and in proposing interventions to tackle those risks. In several fields, however, we have been less successful at actually formulating, enacting, implementing or enforcing some of those interventions. For example, failure to store firearms in the home so that children are unable to gain access to them has been identified as a risk factor for suicide and unintentional injury.1–4 But laws requiring safe gun storage have been enacted in only 18 US states, and most of these laws provide only modest sanctions.5,6 More generally, both the Centers for Disease Control and Prevention (Atlanta, Georgia, US) and the National Institutes of Health (Bethesda, Maryland, US) have increasingly recognized the importance of improving the translation of research findings into practical interventions.7,8 There are, of course, many different categories of injury interventions, including efforts to modify behavior, products, the physical environment or the social environment to reduce risks.9,10 One important way to achieve any of these intervention goals is through policy change. Policies may be particularly effective because they can be designed to affect large numbers of individuals or institutions at once. What do we mean by “policy”? Different definitions of policy have been proposed depending on the context. One broad definition from the health politics literature is “a series of more or less related activities and their intended and unintended consequences for those concerned”.11 In its influential report The Future of Public Health , the Institute of Medicine identified the three core functions of public health as “assessment, policy development and assurance”. The Institute of Medicine defined policy development as “the process by which society makes decisions about problems, chooses goals and the proper means to …
Rainforests at the Margins: Regional Profiles

While this book used a global model for delineating the temperate rainforests of the world as presented in Chapter 1, there were some regions that appeared on closer inspection to qualify as rainforest even though they did not make the cut in the global model. The authors of regional profiles in this chapter make a compelling case for inclusion of these areas as “outliers” or “rainforests at the margins.” These are regions where local climates—especially the presence of fog—appear to compensate for climatic conditions otherwise atypical of more-definitive rainforests. For instance, in the Colchic and Hyrcanic forests of the Western Eurasian Caucasus, fog provides ample conditions for oceanic lichens and humidity-dependent vegetation despite temperatures considered too warm for most temperate rainforests.
Modulation of frontoparietal neurovascular dynamics in working memory

Our perception of the world is represented in widespread, overlapping, and interactive neuronal networks of the cerebral cortex. A majority of physiological studies on the subject have focused on oscillatory synchrony as the binding mechanism for representation and transmission of neural information. Little is known, however, about the stability of that synchrony during prolonged cognitive operations that span more than just a few seconds. The present research, in primates, investigated the dynamic patterns of oscillatory synchrony by two complementary recording methods, surface field potentials SFPs and near-infrared spectroscopy NIRS. The signals were first recorded during the resting state to examine intrinsic functional connectivity. The temporal modulation of coactivation was then examined on both signals during performance of working memory WM tasks with long delays memory retention epochs. In both signals, the peristimulus period exhibited characteristic features in frontal and parietal regions. Examination of SFP signals over delays lasting tens of seconds, however, revealed alternations of synchronization and desynchronization. These alternations occurred within the same frequency bands observed in the peristimulus epoch, without a specific correspondence between any definite cognitive process e.g., WM and synchrony within a given frequency band. What emerged instead was a correlation between the degree of SFP signal fragmentation in time, frequency, and brain space and the complexity and efficiency of the task being performed. In other words, the incidence and extent of SFP transitions between synchronization and desynchronization-rather than the absolute degree of synchrony-augmented in correct task performance compared with incorrect performance or in a control task without WM demand. An opposite relationship was found in NIRS: increasing task complexity induced more uniform, rather than fragmented, NIRS coactivations. These findings indicate that the particular features of neural oscillations cannot be linearly mapped to cognitive functions. Rather, information and the cognitive operations performed on it are primarily reflected in their modulations over time. The increased complexity and fragmentation of electrical frequencies in WM may reflect the activation of hierarchically diverse cognits cognitive networks in that condition. Conversely, the homogeneity in coherence of NIRS responses may reflect the cumulative vascular reactions that accompany that neuroelectrical proliferation of frequencies and the longer time constant of the NIRS signal. These findings are directly relevant to the mechanisms mediating cognitive processes and to physiologically based interpretations of functional brain imaging.
Gastrointestinal stromal tumor associated with other primaries: A study of 154 patients

10567 Background: The objective of this study is to investigate the characteristics and survival rate of patients with Gastrointestinal Stromal Tumor (GIST) associated with other primary malignancies. Methods: 783 patients with GIST were treated at M. D. Anderson Cancer Center from 1995 to 2007. Multiple primaries included tumors that were not considered to be a metastasis, invasion or recurrence of GIST excluding non-melanoma skin cancer. Data on gender, age at diagnosis of cancer, follow-up time after diagnosis, and death rate were collected. Results: Of the 783 patients, 154 (20%) were identified with at least one other primary other than GIST (GIST+). The ratio of men and women was 1.5 and 1.3 in patients with GIST+ compared to those with GIST only, respectively. Median age at diagnosis of GIST was 57 for patients with GIST only whereas it was 68 in patients with GIST+. The stomach was the frequent site of occurrence in GIST only and GIST+. The total numbers of other primaries developed before the dia...
Specificational Copular Sentences in Russian and English

The Russian sentence (1), from Paduceva and Uspensky (1979), and English (2) are examples of specificational copular sentences: NP2 provides the ‘specification’, or ‘value’ of the description given by NP1. (1) Vladelec etogo osobnjaka – juvelir Fužere. owner-NOM this-GEN mansion-GEN jeweler-NOM Fuzhere ‘The owner of this mansion is the jeweler Fuzhere.’ (2) The biggest problem is the recent budget cuts. Williams (1983) and Partee (1986) argued that specificational sentences like (2) result from “inversion around the copula”: that NP1 is a predicate (type ) and NP2 is the subject, a referential expression of type e. Partee (1999) argued that such an analysis is right for Russian, citing arguments from Paduceva and Uspensky (1979) that NP2 is the subject of sentence (1). But in that paper I argued that differences between Russian and English suggest that in English there is no such inversion, contra Williams (1983) and Partee (1986): the subject of (2) is NP1, and both NPs are of type e, but with NP1 less referential than NP2, perhaps “attributive”. Now, based on classic work by Roger Higgins on English and by Paducheva and Uspensky on Russian, and on a wealth of recent work by Mikkelsen, Geist, Romero, Schlenker, and others, a reexamination the semantics and structure of specificational copular sentences in Russian and English in a typological perspective supports a partly different set of conclusions: (i) NP1 is of type and NP2 is of type e in both English and Russian; (ii) but NP1 is subject in English, while NP2 is subject in Russian; and (iii) NP1 in specificational sentences is universally topical (discourse-old), but only in some languages (like English) is that accomplished by putting NP1 into canonical subject position. In other words, both English (2) and Russian (1) move the -type NP1 into some sentence-initial position for information-structure reasons, but in English NP1 ends up as syntactic subject, whereas in Russian, it’s inverted into some other left-periphery position.
Does Research on Evaluation Matter? Findings From a Survey of American Evaluation Association Members and Prominent Evaluation Theorists and Scholars

Research on evaluation theories, methods, and practices has increased considerably in the past decade. Even so, little is known about whether published findings from research on evaluation are read by evaluators and whether such findings influence evaluators’ thinking about evaluation or their evaluation practice. To address these questions, and others, a random sample of American Evaluation Association (AEA) members and a purposive sample of prominent evaluation theorists and scholars were surveyed. A majority of AEA members (80.95% ± 7.60%) and sampled theorists and scholars (84.21%) regularly read research on evaluation and indicate that research on evaluation has influenced their thinking about evaluation and their evaluation practice (97.00% ± 3.38% and 94.00% ± 4.79%, for AEA members, and 100% and 100%, for prominent theorists and scholars, respectively).
New Proposals Relating to the Genera of the Boletaceae

A short time ago (Snell, 1941), a modification of Gilbert's arrangement of the genera of the Boletaceae (1931) was presented as an improvement upon the one most commonly used on this continent -the tri-generic scheme of Peck (1889), which used as tribes of the genus Boletus the subgroups of Fries (1863 & 1874) with minor modifications and additions. Recently, Rogers (1941) demonstrated that S. F. Gray's Natural Arrangement of British Plants (1821) is post-Friesian, at least as far as the first volume of the Systema is concerned. Accordingly, Gray's generic names must be given the consideration that has been denied them by recent mycologists in the uncertainty that has prevailed concerning the priority status of the Natural Arrangement. In Gray's family Hymenotheceae, two of the subfamilies (or tribes?) are the Boletideae and the Suillideae. The Boletideae contain species that are present-day Polyporaceae. The laterally attached species, whether corky, coriaceous or woody, are placed in the genus Boletus, but obviously this use of the name is of no interest to us because in the first volume of the Systema a few months before, Fries had established that genus in the present-day Boletaceae. The Suillideae include the forms that are fleshy and have long tubes separable from the cap and either united or distinct from each other, in the four following genera: Suillus Micheli, Pinuzza Micheli,1 Leccinum Micheli,1 and Fistulina Persoon. Fistulina is obviously 6f no concern in this discussion.
Risk perception for diabetes in Appalachian women.

ABSTRACTThe social and economic burden of diabetes is large and growing. Diabetes is a significant public health issue in the Appalachian region; women constitute approximately 50% of those diagnosed with diabetes. This cross-sectional study examined the relationship among sociodemographic, anthropometric, lifestyle, and psychosocial factors (cognitive and affective representations) and perceived risk of diabetes in non-diabetic, non-elderly (21–50 years) Appalachian women residing in West Virginia (N = 202). Participants were recruited through social media, flyers, and a newsletter from the West Virginia University Extension. The final survey was conducted from March 2015 to June 2015. Bivariate analyses were used to examine unadjusted relations among sociodemographic, anthropometric, lifestyle, and psychosocial factors and comparative perceived risk of diabetes. In a multivariable logistic regression model, we found that younger age, higher body mass index, non-White race, greater diabetes knowledge, pe...
Leukocyte cyclic adenosine monophosphate in asthmatic children Effects of adrenergic therapy

Blood specimens for measurement of leukocyte cyclic adenosine monophosphate (AMP) were obtained at weekly intervals from asthmatic children who were participating in a double-blind, crossover study to compare the effects of two adrenergic agents and a placebo. When patients were treated with the placebo, the basal measurements and the cyclic AMP responses of leukocytes to in vitro stimulation with epinephrine (10(-4) M) were similar to those of normal subjects but within one week after initiation of treatment with an adrenergic bronchodilator, leukocyte cyclic AMP responses to adrenergic stimulation in vitro decreased and remained low during the remainder of the treatment period. Within one week after discontinuation of adrenergic therapy, leukocyte cyclic AMP responses returned to the control level. Our results indicate that the alterations in leukocyte cyclic AMP metabolism which have been observed previously in asthmatic patients may result from medications used for treatment of asthma.
Onset of Normal Field Instability in a Ferrofluid in Microgravity

A ferrofluid is a magnetic liquid composed of nanoscale ferrous particles sus- pended in a low-viscosity carrier fluid. When subjected to a magnetic field, the surface of a ferrofluid deforms into peaks and valleys along the magnetic field lines. The onset of surface deformation is called the Normal Field Instability, and the theory describing the NFI identifies a critical magnetic field below which no magnetically driven surface deformations occur. This critical field depends on the gravitational acceleration and, according to the theory, should disappear as local gravitational acceleration approaches zero. Previous studies have been inconclusive on the existence of a critical magnetic field in reduced gravity. For our work, we designed a payload for a suborbital rocket mission which launched through the RockSat-C program. Our experiment incorporated a ferrofluid sam- ple and a uniform magnetic field which could be varied across a discrete range of value. During the microgravity portion of the rocket’s flight, we obtained video of the ferrofluid’s behavior to compare it to data taken in Earth’s gravity.
Abstract 2514: Second generation HDAC inhibitor, Quisinostat reinstates RD3 in neuroblastoma CSCs and promotes stem cell differentiation

Recently, we characterized the adaptive stemness and extreme plasticity of neuroblastoma (NB) cancer stem cells (CSCs). Further, new to science, we defined the loss of retinal degeneration protein 3 (RD3) in high-risk NB and identified its novel tumor evolution stabilization function. Moreover our studies identified definitive contribution of HDACs in the evolution of progressive NB. Herein, we investigated the potential of pyrimidyl-hydroxamic acid HDAC inhibitor, Quisinostat in restoring RD3 and NB-CSCs differentiation. Well characterized CD133+-CD34+ human NB CSCs exposed to increasing concentrations (2.5, 5, 10, 100, 200nM, 1, 2, 4, 8μM) of quisinostat were examined for inhibition of HDACs (HDACs 1-11, QPCR analysis), transcriptional (QPCR) and translational (immunoblotting) restoration of RD3, CSCs cell viability (automated trypan exclusion assay) differentiation (real-time live cell imaging) and formation of organized tumorospheres (tumorosphere formation assay). Quisinostat inflicted complete inhibition of NB-CSCs cell viability at 100nM concentration and beyond. QPCR analysis revealed a dose-dependent inhibition of HDACs in NB CSCs with quisinostat. We observed a significant transcriptional/translational restoration of RD3 selectively at 100nM and above of quisinostat treatment. Live-cell imaging demonstrated a dose-dependent -loss of stemness behavior and -increased differentiation of NB CSCs with quisinostat treatment. Tumorosphere formation assay demonstrated complete inhibition of organized tumorospheres at/after 100nM treatment. These results imply that Quisinostat restores RD3 and promotes NB-CSCs differentiation. More importantly, selective dose-dependent specificity of HDAC inhibition by Quisinostatnt and, restoration of RD3 and regulation of stemness physiognomies at/above 100nM concentrations identifies that HDAC 7 could serve as a critical player in this setting. Taken together, these results for the first time identify the potential of quisinostat in the regulation of NB evolution and with further studies may serve as a potential drug deliverable in the treatment and cure of high-risk NB. Acknowledgements: Stephenson Cancer Center - Experimental Therapeutics Program, NIH COBRE 1P20GM103639-01. Citation Format: DINESH BABU SOMASUNDARAM, Natarajan Aravindan. Second generation HDAC inhibitor, Quisinostat reinstates RD3 in neuroblastoma CSCs and promotes stem cell differentiation. [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 2514.
Authorization in Multimedia Conferencing Systems

Multimedia conferencing has been making significant progress in recent years. In the application of multimedia conferencing there are many situations that pose some intricate security problems; for example, a secret meeting of the defense department, a negotiating conference among different commercial groups, etc.. However, there are few studies that address the security of multimedia applications. Good solutions to these critical aspects will increase with the popularity of multimedia, since these systems may handle an enormous amount of information with a large variety of users. We present an authorization model for a multimedia conferencing system. The Object Modeling Technique (OMT) is used here to describe the static aspects of this model, where the authorization model is represented by a set of classes and their relationships. We also discuss some aspects of security administration and a possible implementation.
In Vivo Evaluation of Immunomodulating Effects of Lenalidomide (L) on Tumor Cell Microenvironment as a Possible Underlying Mechanism of the Antitumor Effects Observed in Patients (pts) with Chronic Lymphocytic Leukemia (CLL).

Abstract Introduction: L is a more potent analogue of thalidomide with antitumor activity reported in MDS and multiple myeloma. Clinical anti-leukemic activity of L is reported for the first time by our group in pts with CLL. The underlying mechanism of its antitumor activity remains undetermined. We investigated the effect of L on the tumor microenvironment and studied the modulation of soluble cytokines and immune cells (T and NK cells) in pts receiving L. Patients and Methods: CLL pts enrolled on the clinical study with L were eligible. Pre and post (day 7) samples were obtained for evaluation of changes in serum cytokine and immune cell environment. Malignant cells were also obtained to investigate the in vitro antitumor activity of L prior to initiating treatment on clinical trial. Results: With Anexin V staining for evaluation of apoptosis induction, in vitro testing of pts samples (n=10) showed only a modest increase in apoptosis at 200mg of L - levels clinically not achievable. Yet same pts treated with L on clinical study showed significant antitumor response, suggesting the mechanism to be possibly related to modulation of the tumor microenvironment. In evaluation of the tumor cytokine microenvironment (n= 10) we noted significant L induced increase in IL-10 (n=6), IL-8 (n=8), IP-10 (n=10), IL-8 (n=8), TNF-alpha (n=4) and decrease in PDGF (n=5) and RANTES (n=5). While evaluation of the immune cell repertoire we observed an absolute increase in T-cell as well as NK-cell after treatment with L. Conclusion: Our in vitro evaluation does not suggest a direct apoptotic effect of L on the malignant CLL cells and thus support the hypothesis that the anti-leukemic effect noted in the clinical trial (reported separately) is most likely from in vivo modulation of the tumor microenvironment as is demonstrated from changes in the cytokine milieu and the cellular immune response. Collectively these changes may be responsible for the immune modulating properties of L and the resultant anti-CLL activity in pts.
Stress, Alcohol and Epigenetic Transmission

The stress system is a major neuroendocrine system with pivotal regulatory physiological functions. This system is regulated by intricate communication between the hypothalamus, pituitary, and adrenal glands. Stress axis function is often perturbed by alcohol abuse that lasts long and which is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. The cellular mechanism involved in the development of aberrant stress response to alcohol is multifactorial and partly controlled by epigenetic modifications of various genes of the stress regulatory system. One of these targeted genes is the stress response inhibitory proopiomelanocortin gene, which is hypermethylated and its transcription reduced by alcohol. Recent evidence that the alcohol epigenetic changes on the proopiomelanocortin gene are inherited provides a plausible explanation for transmission of alcohol-induced complex behavioral traits including aberrant stress responses across generations.
Isolated Liver Metastasis in Hürthle Cell Thyroid Cancer Treated with Microwave Ablation.

Hurthle cell thyroid cancer (HCTC) is a less common form of differentiated thyroid cancer. It rarely metastasizes to the liver, and when it does, the metastasis is almost never isolated. Here we report a 62-year-old male with widely invasive Hurthle cell thyroid cancer, who underwent total thyroidectomy and received adjuvant treatment with I-131 with posttreatment scan showing no evidence of metastatic disease. His thyroglobulin however continued to rise after that and eventually an isolated liver metastasis was identified. He underwent laparoscopic microwave ablation of the liver metastasis, with dramatic decline in thyroglobulin and no structural disease identified to date. This case highlights the rare occurrence of isolated liver metastasis from HCTC and also illustrates the utility of thermoablation as an alternative to surgical resection in the treatment of small isolated liver metastases from HCTC.
Investigating the Structure of the Drug Transporter EmrE

Multidrug resistance in bacteria is a critical challenge in public health and drug discovery. One of the primary mechanisms of resistance is efflux pumps, which couple an energetically favorable process with the export of a drug molecule against its concentration gradient.1 Efflux pumps from the small multidrug resistance protein family are ubiquitous among bacteria. These secondary active transporters couple the efflux of a wide variety of toxic compounds with the proton gradient of the inner membrane.2 To gain insight into this transport process we carried out a series of biophysical experiments, including solution and solid-state NMR spectroscopy using the multidrug transporter EmrE. EmrE is an asymmetric and antiparallel homodimer, which couples the efflux of cationic drugs with the import of protons. Previously, we revealed a large change in structure and dynamics due to the acid/base chemistry at a conserved glutamic acid residue.3 In this work we focus on describing the site-specific structural changes within the substrate binding pocket that drive the large conformational change in EmrE. Specifically, our oriented solid-state NMR and solution NMR experiments reveal backbone and side chain structural perturbations upon binding protons or drugs that reveal a specific mechanism involving aromatic residues in the binding pocket. Finally, we built on our previous findings 3 to show how conformationally biased mutants allow for the unambiguous determination of monomer-specific restraints for structural elucidation of EmrE in lipid bilayers.References1. Pu, Y.; Zhao, Z.; Li, Y.; Zou, J.; Ma, Q.; Zhao, Y.; Ke, Y.; Zhu, Y.; Chen, H.; Baker, Matthew A. B.; Ge, H.; Sun, Y.; Xie, Xiaoliang S.; Bai, F., Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells. Molecular Cell 2016, 62 (2), 284-294.2. Nikaido, H.; Pages, J. M., Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 2012, 36 (2), 340-63.3. Gayen, A.; Leninger, M.; Traaseth, N. J., Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE. Nat Chem Biol 2016, 12 (3), 141-145.
Neuroendocrine differentiation patterns in metastases from advanced prostate cancer.

5085 Background: Neuroendocrine differentiation (NED) in advanced prostate cancer (APC) is considered an aggressive phenotype with poor outcome and limited treatment options. Diagnosis depends on h...
Ultrafast Kerr-driven beam cleanup in graded-index multimode fiber

We observe a nonlinear spatial self-cleaning process with ultrashort pulses in multimode fiber. Experiments and simulations demonstrate its origin to be nonlinear interactions between the fiber spatial modes, due exclusively to the Kerr effect.
TP53 Mutations and Outcome in Patients with Myelodysplastic Syndromes (MDS)

Abstract Objectives: TP53, a tumor suppressor gene, is frequently mutated in myeloid malignancies. The negative impact of TP53 mutations in myelodysplastic syndromes (MDS) has been described previously but there is controversy regarding the prognostic impact of the mutation's characteristics (location, type, passenger vs. driver, and others). Methods: We sequenced DNA samples from 732 patients (pts) with MDS and related myeloid malignancies for the presence of TP53 mutations and 61 other genes that have been described as recurrently mutated in MDS. Overall survival (OS) was measured from the time of diagnosis to time of death or last follows up. Variant allele frequencies (VAFs) adjusted by zygosity were used to define clonal architecture of driver clones. Results: Of 80 mutations detected in 73 (10%) pts, 66 (88%) were missense, 7 (9%) were nonsense, and 7 (9%) were frame shift deletions/insertions. Pts with TP53 mutations had a higher WBC (4.6 vs. 3.9 X 109/L, p = .04), higher bone marrow blast % (median 9 vs. 3, p =0.1), and a higher risk category by revised International prognostic Scoring System (56% vs. 27%, p =.01) compared to pts with TP53 wild type. TP53 mutations were commonly occurred with TET2 (16%), PRPF8 (13%), ASXL1 (11%), DDX54 (8%), DNMT3A (8%), and IDH2 (8%). The mean VAF for TP53 was 41.9 (5-100). TP53 mutations were defined as drivers in 20% of samples, passengers in 40%, and mosaic in 40%. Mutation positions included: 19 (24%) in the DNA binding domain, 2 (3%) in the transactivation domain, 1 (1%) in the tetramerization domain and 58 (72%) other. With a median follow up of 16.4 months, the median OS for the entire group was 8.24 months. Patients with TP53 as driver mutations had a worse OS compared with patients with TP53 as passenger mutations (median, 2.2 vs. 13.0 months, respectively, p =.02). Similarly, OS by TP53 VAF categorized as low ( 50%) was 12.4, 8.5, and 3.4 months, respectively. Among patients with available treatment data, 29 patients were treated with the hypomethylating agents, azacitidine or decitabine, 17% responded (60% CR, and 40% PR), and OS was similar compared to patients treated with other therapies. Patients treated with Hematopoietic stem cell transplant (HCT) had superior OS compared to pts not receiving HCT (median, 14.9 vs. 8.9 months, respectively, p =.05). Conclusions: TP53 mutations are associated with poor outcome in MDS, but the outcome varies depending on the type of mutation and VAF. Treatment with HCT remains a valid treatment option in a subset of patients but novel treatment strategies are desperately needed. Disclosures Mukherjee: Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.
Accelerated estimation of corrosion rate in supercritical and ultra-supercritical water

This study explores a methodology for the determination of the accelerated corrosion rate of candidate materials to be used in advanced supercritical and ultra-supercritical water-based thermal reactors. Electrochemical impedance spectroscopy and electrochemical frequency modulation were used to evaluate the corrosion rates of SAE 316 stainless steel, Nitronic 50, Inconel 718, and Inconel 625 in supercritical water at 530 °C and in ultra-supercritical water at 600 °C. The results were compared to the results of gravimetric studies that were performed to determine the viability of the utilization of electrochemical analyses in supercritical and ultra-supercritical water. For all of the conditions that were tested, results showed that the corrosion rates during electrochemical testing had trends that were similar to the long-term gravimetric results. Thus, the hybrid methodology described in this manuscript can reduce testing times from >1000 h to ~ 10 h. Measurement of corrosion rates in ‘difficult’ environments is an ever-present challenge to corrosion engineers. An accelerated methodology to enable the corrosion rate of steel and nickel alloys in supercritical water under realistic conditions is presented. Supercritical water—a dense gaseous state at high temperature and pressure—is an attractive heat transfer medium for nuclear and coal-fired power stations, as it enables high heat transfer efficiency. Measuring corrosion rates for metals exposed to supercritical water is tricky to perform in situ however, necessitating long-term exposure tests. While accelerated tests have been reported, these did not use environments equivalent to those experienced in-service. However, David Rodriguez and Dev Chidambaram from the University of Nevada Reno in the USA now demonstrate the use of electrochemical analyses for assessing corrosion rate under realistic conditions, achieving results comparable to those from long-term gravimetric testing. This allows experiment times to be reduced from weeks or months, to less than a day.