cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessment of sea level rise impacts on human population and real property in the Florida Keys

The potential impacts of sea level rise (SLR) on 95% of the land areas of the Florida Keys were estimated through analysis of a digital elevation model (DEM) derived from airborne light detection and ranging (LiDAR) measurements in a geographic information system. The topographic detail of the LiDAR DEM allowed projections of land, population, and property inundation in 0.15 m increments across a broad range of SLR scenarios for the next century. The results showed that a 0.6 m SLR by 2100 would inundate about 70% of the total land surface, but smaller percentages of the population (17%) and real property (12%). A 1.5 m rise in sea level during the same period would inundate 91% of the land surface, 71% of the population and 68% of property in the study area. Comparison of inundation dynamics indicates that the Lower Florida Keys are more susceptible to SLR than the Upper Florida Keys. The inundation dynamics exhibit non-linear behavior and demonstrate tipping points in inundation processes beyond which the inundation of land, population, and property speeds up. Acceleration of SLR will amplify the non- linear inundation, causing tipping points to be reached sooner.
Reduction of gut hypoplasia and cachexia in tumor-bearing rats maintained on total parenteral nutrition and treated with peptide YY and clenbuterol

Prevention of gut hypoplasia associated with total parenteral nutrition (TPN) was investigated in 67 adult male Fisher 344 rats. Mass and protein content of the small intestine was reduced by 31% and 39%, respectively, after 7 d of TPN in tumor-bearing (TB) rats. Coinfusing peptide YY (PYY; 1 nmol.kg-1.h-1) and treating the rats with the anabolic beta-adrenergic agonist, clenbuterol (CLE; 2 mg.kg-1.d-1), resulted in significant savings in small intestine weight (26% increase) and protein (42% increase). Although the colon also exhibited a significant decrease in mass (31%), none of the treatment combinations were effective in this region of the gut. Histologic analysis of ileum suggested that the additive effects of PYY and CLE were due to differential effects of these compounds on mucosal and muscular tissues, respectively. This combination of treatments also resulted in significant savings (30% increase) in gastrocnemius protein, suggesting a reduction in the cachectic response. These results suggest that TPN-induced gut hypoplasia and cancer cachexia may be reduced by the proper combination of nutritional, hormonal, and pharmacologic treatments. In addition, the anabolic effects of various treatments may be additive to counteract TPN-induced gut atrophy.
Joking cultures: Humor themes as social regulation in group life

Every interacting social group develops, over time, a joking culture: a set of humorous references that are known to members of the group to which members can refer and that serve as the basis of further interaction. Joking, thus, has a historical, retrospective, and reflexive character. We argue that group joking is embedded, interactive, and referential, and these features give it power within the group context. Elements of the joking culture serve to smooth group interaction, share a‰liation, separate the group from outsiders, and secure the compliance of group members through social control. To demonstrate these processes we rely upon two detailed ethnographic examples of continuing joking: one from mushroom collectors and the second from professional meteorologists.
Calcium-dependent release of tyrosine in brain elicited by stimulation of neuropeptide receptors

: We sought to establish whether the endogenous opiate-receptor agonist Met-enkephalin (m-ENK) selectively modulates the release of endogenous tyrosine (Tyr) from brain slices prepared from the corpus striatum (CS). Amino acids (AAs) released from slices of CS and, for comparison, cerebral cortex (Cx) were measured by HPLC. Incubation of slices with m-ENK (1-10 μM) increased the basal release of Tyr (up to 293% of control) from CS, but not Cx, whereas other nonneurotransmitter AAs, phenylal-anine (Phe) and valine (Val), were unchanged. The release of the putative neurotransmitter AAs glutamate (Glu), tau-rine (Tau), and glycine (Gly) were similarly increased by 50–150% with m-ENK in slices of CS, but not Cx. The enhanced release of AAs by m-ENK was prevented by removal of extracellular Ca2+ or by preincubation with the opiate receptor antagonist naloxone. Neuronal depolarization by potassium (5–55 mM) in the presence of Ca2+ did not affect the release of Tyr, whereas release of neurotransmitter AAs such as γ-aminobutyric acid (GABA) were markedly increased. The increase in basal Tyr release by m-ENK was not the result of a decreased uptake of Tyr. Relative to slices, the basal release of Tyr, Phe, and Val from a synaptosomal (P2) preparation of CS was small (8–51%) compared to that of GABA, Gly, Glu, and Tau (49–123%). Nonetheless, m-ENK (10 μM) markedly increased the release of Tyr (to 833%), but not Glu, Gly, and Tau from the P2 fraction. Other neuropeptides including cholecystokinin octapeptide (CCK-8), thyrotropin-releasing hormone (TRH), and vaso-active intestinal peptide (VIP) facilitated the release of Tyr from brain slices in a regionally specific pattern. We conclude that: (1) Tyr is released from nerve terminal-enriched preparations of CS, but not Cx, by m-ENK via an opiate receptor-mediated, Ca2+-dependent process with regional selectivity; (2) neuronal depolarization alone, however, does not affect the release of Tyr; (3) CCK-8, TRH, and VIP also increase Tyr release with regional specificity, suggesting that receptors for other neuropeptides may also modulate Tyr release. The specific neuronal source and functional role of Tyr released from elements of CS via activation of opiate receptors remain to be elucidated.
A New Approach to Jacobian Formulation for a Class of Multi-Section Continuum Robots

We introduce a new method for synthesizing kinematics and Jacobian relationships for an important class of continuous backbone “continuum” robots. The resulting Jacobians enable task and shape control by relating work space (Cartesian) coordinates to actuator inputs (tendon lengths, pneumatic pressures, etc.), via robot shape coordinates. The approach, which is applicable to a wide class of existing continuum robots, also features the capability of including extension, as well as bending, of individual sections. The approach is also shown to produce correct results for orientation, in contrast to previously published approaches. Results of a real-time implementation of the method on a multisection continuum manipulator are reported.
Measuring the elastic modulus of microgels using microdrops

Two microgel particles are encapsulated in a microdrop having a spherical diameter smaller than the sum of the diameters of the microgels; this causes the microgels to be squeezed together by the oil–water interface of the drop, in turn, making the drop ellipsoidal in shape. By modeling the force applied to the microgels by the drop and equating this to the Hertz contact force of their deformation, we are able to estimate their elastic modulus. By varying the surface tension and shape of the drops, we are able to measure the modulus of the microgels under different loads. This provides a simple technique for quantifying the elasticity of small, deformable objects, including liquid drops, microgels, and cells.
Adrenergically Mediated Ventricular Fibrillation in Probucol‐Treated Dogs: Roles of Alpha and Beta Adrenergic Receptors

A high incidence of sudden death due to ventricular fibrillation (VF) has been observed in dogs under chronic treatment with probucol, a new hypocholesterolemic agent. The present study describes the cardiac electrophysiologic properties of probucol-treated dogs and characterizes the electrophysiological response of these animals to manipulation of the autonomic nervous system. There was no significant difference in the spontaneous sinus cycle length, the QT interval, refractory period of the atrium, ventricle or A-V junction between normal and probucol-treated dogs. Epinephrine produced VF with few and sometimes no preceding premature ventricular extrasystoles. Electrical stimulation of the stellate ganglion induced VF in 16/19 dogs whereas stimulation of the right stellate ganglion induced VF in 1/19 dogs. Phenylephrine induced VF in 0/19 dogs, isoproterenol in 5/19 dogs, but phenylephrine + isoproterenol induced VF in 9/11 dogs in which isoproterenol did not produce VF. alpha (phentolamine) or beta (propranolol) blockade prevented initiation of VF by epinephrine, phenylephrine + is isoproterenol, and left stellate stimulation but alpha blockade did not prevent induction of VF by isoproterenol when isoproterenol alone produced VF. In this nonischemic model, we conclude that left stellate stimulation is a far more potent initiator of VF than right stellate stimulation and that induction of VF appears to require both alpha and beta adrenergic receptor stimulation.
The Computation of Second Vertical Derivatives of Geomagnetic Fields

Second vertical derivatives of magnetic fields, because of their high resolving power, are often very useful in interpreting magnetic anomalies. Formulas are developed which permit their ready numerical computation. Comparisons are made between the resulting approximate values and the rigorous values obtained for simple idealized fields. The similarity between maps of second vertical derivatives of fields and those of certain types of residual fields is discussed.
Promoting cultural competence in HIV/AIDS care

The importance of cultural competence in providing health care to a diverse patient population is well-recognized throughout the health professions, though there is as yet no widely accepted set of criteria for establishing and maintaining cultural competence. In HIV/AIDS, where behavioral factors figure so prominently in transmission, prevention, and treatment, cultural appropriateness is crucial to providing patient education and nursing care. This article suggests some specific cultural competence training strategies and offers a broad conceptual framework for teaching and learning about the issues involved in cultural competence, with specific illustrations relating to HIV/AIDS.
Overexpression of Ref-1 Inhibits Hypoxia and Tumor Necrosis Factor–Induced Endothelial Cell Apoptosis Through Nuclear Factor-κB–Independent and –Dependent Pathways

We hypothesized that a redox-sensitive transcription factor, redox factor-1 (Ref-1) (HAP1, APE, and APEX), was critical in the regulation of endothelial cell survival in response to hypoxia and cytokines, including tumor necrosis factor (TNF)-alpha. Hypoxia resulted in a significant decrease in Ref-1 protein expression in both human umbilical vein endothelial cells and calf pulmonary artery endothelial cells. The hypoxia-induced decrease in Ref-1 expression was followed by a significant induction of apoptosis as measured by caspase 3 activity and nuclear morphology. Transient upregulation of Ref-1 significantly inhibited hypoxia-induced apoptosis. However, deletion of the redox-sensitive domain of Ref-1 abolished the antiapoptotic effect. We postulated that the antiapoptotic effects of Ref-1 were mediated through nuclear factor-kappaB (NF-kappaB). However, blockade of NF-kappaB with a dominant-negative IkappaB (S32A/S36A) expression vector had no effect on Ref-1-mediated survival under hypoxic conditions. The second aim of this study was to test the cytoprotective ability of Ref-1 upregulation in response to TNF-induced apoptosis. Ref-1 inhibition of TNF-induced death was associated with a significant potentiation of NF-kappaB activity. Deletion of the redox-sensitive domain of Ref-1 significantly inhibited TNF-induced NF-kappaB activation. Moreover, loss of the redox-sensitive domain also abolished the antiapoptotic effect of Ref-1 in response to TNF. To test whether Ref-1 induced activation of NF-kappaB was necessary to promote survival, we blocked NF-kappaB activity with a dominant-negative IkappaB (S32A/S36A). Indeed, blockade of NF-kappaB activity abolished the ability of Ref-1 to rescue TNF-induced apoptosis. In conclusion, upregulation of Ref-1 promotes endothelial cell survival in response to hypoxia and TNF through NF-kappaB-independent and NF-kappaB-dependent signaling cascades, respectively. Moreover, it seems that Ref-1 may act as a critical cofactor, mediating the TNF-induced NF-kappaB response in the vascular endothelium.
Design and performance evaluation of a two-stage resistively-heated thermal modulator for GC × GC

The design and performance evaluation of a two-stage resistively-heated thermal modulator that does not use any cryogenic consumables is described. A commercially available piece of stainless-steel wall coated capillary column is used as the modulator. Cooling of the modulator is provided by a two-stage refrigeration unit with an external heat exchanger and a closed-loop recirculating air system. The modulator is resistively heated by sending a current pulse through each stage of the modulator tube. Studies evaluating the modulator trapping efficiency, cooling efficiency, desorption efficiency, and resultant peak shape are presented and discussed. Performance evaluation of this modulator is compared to similar single-stage modulators, both qualitatively and quantitatively, and has exceeded the previous data reported for the single stage versions. GC × GC chromatograms of a C6-C20 n-alkane mixture, a petroleum sample, and a 38-component mixture of aliphatic, aromatic, and halogenated volatile organic compounds are provided. This two-stage modulator proves to be a viable alternative to commercially available modulators which require large amounts of cryogenic fluids.
Time series modeling of reactive ion etching using neural networks

Neural networks have been used to model the behavior of real-time tool data in a reactive ion etch (RIE) process. An etch monitoring and data acquisition system for transferring data from the RIE chamber to a remote workstation was designed and implemented on a Plasma Therm Series 700 Dual Chamber etcher. This system monitors gas flow rates, RF power, temperature, pressure, and dc bias voltage. A neural network was trained on the monitored data using the feed-forward, error backpropagation algorithm. This network was used to perform three distinct modeling tasks. First, the network was trained on a subset of ten samples of the time series representing a single process run, and subsequently used to forecast the next data point. In the second task, the network was trained as in the first task, but used to predict the next ten values of the data sequence. In each of the first two tasks, the trained network yielded errors of less than 5%. In the final task, a neural net was used to generate a malfunction alarm when the sampled data did not conform to its previously established pattern. >
Affine designs and linear orthogonal arrays

It is proved that the collection of blocks of an affine 1-design that yields a linear orthogonal array is a union of parallel classes of hyperplanes in a finite affine space. In particular, for every prime power q and every m>=2 there exists a unique (up to equivalence) complete linear orthogonal array of strength two associated with the classical design of points and hyperplanes in AG(m,q).
The Wild, Wild Web: The Mythic American West and the Electronic Frontier

This essay explores the ways in which the electronic frontier builds upon the mythology of frontier expansion generally and the western American frontier in particular, including economic opportunity, danger/uncertainty, individualism, outlaw behavior, vigilantism, and nostalgia.
Exploitation of intraspecific communication systems: illicit signalers and receivers.

We review exploitation of intraspecific communication by illicit signalers or receivers, restricting coverage to examples in which the exploiter or exploited, or both, is an arthropod. Illicit signalers aggressively mimic the chemical, acoustical, or visual signals normally used by their victims in sexual or social communication. Cited examples include bolas spiders that mimic pheromone blends to attract male moths as prey and femme fatale fireflies that mimic the flashing pattern of other species of fireflies to prey upon the responding males. Illicit receivers gain access to resources by eavesdropping on intraspecific signals. For example, several species of predatory beetles respond to the aggregation pheromones of bark beetles to feed on them or their offspring, and some parasitic flies orient to the stridulation songs of orthopteran species. In some cases, functional intraspecific communication systems may have evolved to reduce exploitation by illicit receivers; for example, changes in signal characteristics could make the signaler less apparent to potential exploiters. With rare exceptions, both illicit signalers and receivers tend to exploit the intraspecific communication systems of a limited number of taxa, probably because the production or detection of species-specific signals often requires the evolution of specialized signaling mechanisms or sensitive receptors. To convincingly demonstrate exploitation of intraspecific communication, one must first decipher the signals and responses that are part of the communication system. To date, the intraspecific communication systems of a few taxa (e.g., Lepidoptera, fireflies, crickets) are reasonably well understood, but those of many other groups are unknown or poorly understood. Even with this limitation, it is clear that exploitation of these systems by illicit signalers and receivers is widespread and diverse.
Nanoscale “Curtain Rods”: High-Throughput Tools for Studying DNA-Protein Interactions

In this work, we combine nanoscale engineering with single-molecule biology to probe the biochemical interactions between individual proteins and DNA. This approach, a vast improvement over previous methods, constructs a platform to observe thousands of protein-DNA interactions in real time with unprecedented detail. A key challenge in these experiments involves collecting enough statistically relevant data in order to analyze reactions which are designed to be probed individually. “DNA curtains” are formed by flowing the DNA tethered to a lipid bilayer across nanopatterned barriers, facilitating massively parallel data acquisition.
Effects of field fertilizer practices on labeled ammonium-nitrogen transformations and its utilization by winter wheat

Field experiments with winter wheat (Triticum aestivum L.) were conducted in two years at two locations using15N-enriched (NH4)2SO4 on Smolan silt loam (Pachic Argiustoll) and Ost loam (Typic Arguistoll) soils. The objective was to relate differences in crop utilization of fertilizer to movement and transformations of the N in a complete factorial experiment having fall and spring applications, banded and broadcast, with and without nitrapyrin. Plant uptake of the 60 kg N/ha applied varied from 31% to 62% with greatest uptake when fertilizer was banded in the spring without nitrapyrin and least uptake from fall and spring broadcast treatments using nitrapyrin. Analysis of single factor effects showed greater crop contents of fertilizer N for spring than fall applications. That was related to immobilization of the applied N. Much more fertilizer N was in inorganic forms during the period of rapid wheat growth with spring applications than with fall. Banding the fertilizer at a depth of 0.05 m resulted in greater plant uptake than broadcasting or banding it on the soil surface. A significant portion of the applied N was immobilized near the point of application. That limited the downward movement of the N placed on the surface, making it less available to plant roots than the N placed 0.05 m deep where soil moisture was more favorable. Use of nitrapyrin resulted in lowered amounts of fertilizer N as NO3-until mid-May for fall treatments and until harvest with spring treatments. That appeared to be the reason for lowered plant uptake when nitrapyrin was used.
The Splenic Hemogram of the Unanesthetized Dog.

SummarySplenic and venous blood samples were obtained in unanesthetized dogs whose spleens had previously been placed subcutaneously with their vascular supply essentially intact. Erythrocyte and reticulocyte levels are elevated in the spleen. Under pentobarbital, the relocated spleen has less of those cells than does the normal organ. Evidence was presented that diverse splenic functions such as sequestration of formed elements and distensibility are interfered with by placing the spleen between the relatively rigid skin and abdominal musculature of the dog.
Western News Media & Democratic Politics

The Western news media and the democratic politics are of depending on each other and promoting with each other. The capitalist class promoted the progress of democracy in the process of fighting for freedom of press. The news media plays an important part in supervising the government, participating the government and political affairs, correcting wrong doings. Meanwhile, the progress of democracy is the guarantee of news media's development.
Communication Aspects of Dyadic Social Influence in Organizations: A Review and Integration of Conceptual and Empirical Developments

This chapter presents a review and synthesis of research on dyadic social influence in organizations, defined as the communication processes through which an individual participant within a complex organization elicits cognitive, emotional, and behavioral change from another individual in the pursuit of social objectives. Distinct streams of dyadic influence research have developed in various literatures and rely on divergent methods; this analysis crosses disciplinary boundaries to include work in communication theory, social and industrial/organizational psychology, and sociology, among others. The review considers (a) conceptual models of the process of dyadic influence, (b) efforts to identify and catalog influence-seeking methods, and (c) empirical studies of the antecedents, correlates, and consequences of influence method selection. Within each section, research issues, trends, and limitations that are specifically relevant to understanding influence in organizations are discussed. The authors intr...
A Single Surgeon's Experience with Enhanced Recovery after Surgery: An Army of One.

The benefits of enhanced recovery after surgery (ERAS) have been demonstrated for multiple surgical procedures in high-volume programs. However, resources required for its implementation may be daunting to individual surgeons. Patients undergoing elective abdominal procedures from June 2013 to April 2015 by a surgical oncologist before and after the implementation of an ERAS protocol were reviewed. A total of 179 patients were included. The mean age of the patients was 63 years, and a majority of them were females (53.6%), white (61.5%), had a Charlson score of 0 to 2 (45.8%), and a Clavien complication grade of 0 to I (60.1%). The univariate analysis revealed that the ERAS protocol was associated with shorter length of stay (LOS) (6.2 vs 9.6 days), lower cost ($21,674 vs $30,380), and lower mortality (0 vs 3.3%); P 0.05. An ERAS program can be instituted by an individual surgeon with the benefits of decreased LOS, cost, and mortality.
7Be(p, γ)8B and the high-energy solar neutrino flux

The importance of the7Be(p, γ)8B reaction in predicting the high-energy solar neutrino flux is discussed. I present a microscopic eight-body model and a potential model for the calculation of the7Be(p, γ)8B cross section.
A Sociological Consideration of Prayer and Agency

Prayer may be seen as one of the most individual forms of action. Yet, like suicide, another supposedly individualistic action performed by a solitary individual, prayer is a dynamic, reflexive, intersubjective social action, and the sociality of prayer may transform the agency of the actor who is committed to this action over time.
Climate Changes and Sustainability of Small Islands

Global climate changes on the surrounding sea surface and sea temperature appear to be more significant around islands and low-lying sea ports rather than land-locked states. Subject to the global rate of sea level rise, presently circa 3.1mm/year by the Intergovernmental Panel on Climate Change Fourth Assessment, the consequences of the combination of rises in sea level, sea temperature and increases in the frequency of unexpected climate extreme events - storms, hurricanes, tsunami may cause widespread destruction of mangroves, increasing beach erosion, damage to the health of coral reefs and make coastlines more vulnerable to flooding. There is an urgent need for more detailed information from systematic surveys on the identification and progress of climate changes on the sea level and surface and land movement at risk. Small islands in particular should review building and utility planning methods for coastal development and necessary economic diversification in a re-examination of their preparedness for sea level rise and extreme climates. This paper proposes a model - an ‘overlapping-phases-synchronisation (OPS)’ for long run sustainable economic development under climate change, and theoretically illustrate why synchronized processes of adaptation - the OPS model to climate changes is the way to minimise the costs of the loss and damages and to maximise the preservationism of bio-system for future sustainability.
Abstract Title Submitted by Hollie Pegram to the 2012 ASH Annual Meeting: Expansion and Modification of Umbilical Cord Blood T Cells with a Chimeric Antigen Receptor and IL-12

Abstract 1907 Transplantation of unrelated umbilical cord blood (CB) derived stem cells is often used to treat adult patients with B-cell acute lymphoblastic leukemia (B-ALL). However, patients can relapse post transplant and prognosis of those with advanced or refractory disease is poor. We hypothesize that additional therapy involving adoptive transfer of CB derived T cells modified to express a CD19-specific chimeric antigen receptor (CAR) could improve patient outcome following CB transplantation in this population. We have previously demonstrated that human T cells which express the anti-CD19 1928z CAR, containing the signaling domains of the co-stimulatory CD28 receptor and CD3z chain, effectively eradicate CD19 + tumors in SCID-Beige mice, and have shown promise in early clinical trials. In this study, we demonstrate the ability to effectively isolate and expand T cells from CB, necessary for application of adoptive CB T cell therapy. We compared T cell expansion in in vitro cultures with the addition of exogenous stimulatory cytokines, including IL-2, IL-7, IL-12, IL-15 or combinations thereof. We demonstrate that in vitro culture in the context of exogenous IL-12 combined with IL-15 resulted in optimal expansion of CB T cells (over 150-fold). In addition, expansion of T cells in the context of exogenous IL-12 and IL-15 resulted in a favorable phenotype, with maximal expression of memory T cell markers, CD62L and CCR7. Furthermore, these cells were shown to produce high levels of IFNγ and express high levels of CD107a following stimulation with PHA. CB T cells expanded in IL-12 and IL-15 were therefore shown to have a unique memory cell phenotype combined with effector T cell function. Previous studies in our laboratory have demonstrated that expression of IL-12 in tumor targeted T cells resulted in increased anti-tumor function. Given these studies and the favorable effect of IL-12 on CB T cell expansion we used retroviral modification to express both 1928z CAR and IL-12 in CB T cells. CB T cells modified with both IL-12 and 1928z were shown to have increased cytokine secretion when cultured with CD19 + tumor cells, compared to UCB T cells modified with a CAR alone. Additionally, these cells were demonstrated to have increased lytic function, resulting in increased specific lysis of CD19 + tumor cells in a 51 Cr release assay. Our data suggest that CB T cells modified to express both CAR and IL-12 will have improved anti-tumor function, and could therefore decrease relapse and improve overall survival following CB transplant for the treatment of B-ALL. Disclosures: Giralt: Millenium: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity9s Board of Directors or advisory committees, Research Funding.
Synthetic Route Development for the Laboratory Preparation of Eupalinilide E

Following the discovery that the guaianolide natural product eupalinilide E promotes the expansion of hematopoietic stem and progenitor cells; the development of a synthetic route to provide laboratory access to the natural product became a priority. Exploration of multiple synthetic routes yielded an approach that has permitted a scalable synthesis of the natural product. Two routes that failed to access eupalinilide E were triaged either as a result of providing an incorrect diastereomer or due to lack of synthetic efficiency. The successful strategy relied on late-stage allylic oxidations at two separate positions of the molecule, which significantly increased the breadth of reactions that could be used to this point. Subsequent to C–H bond oxidation, adaptations of existing chemical transformations were required to permit chemoselective reduction and oxidation reactions. These transformations included a modified Luche reduction and a selective homoallylic alcohol epoxidation.
Abstract MIP-061: RAC 1 AND CDC42 GTPASES AS REGULATORS OF OVARIAN CANCER PROGRESSION AND NICHE INTERACTIONS

PURPOSE OF THE STUDY: The Ras-homologous (Rho) family GTPases Rac1 and Cdc42 contribute to metastatic dissemination through regulation of actin reorganization, cell motility, cell-cell and cell-extracellular matrix adhesion. The purpose of the study was to investigate the contributions of these GTPases in ovarian cancer progression. EXPERIMENTAL PROCEDURES: GTPase target expression and activity was determined by analysis of The Cancer Genome Atlas (TCGA), immunohistochemistry of ovarian cancer tissues and enzymatic assays of patient samples. The effects Rac1 and Cdc42 expression were investigated by comparing cell behaviors in vitro and in vivo in engineered cell lines and use of inhibitors of Rac1, Cdc42 or dual inhibition by the R-enantiomer of ketorolac. SUMMARY OF THE DATA: Expression of the constitutively active Rac1 splice variant Rac1b and elevation of Cdc42 protein were detected in advanced ovarian cancer specimens thus providing the first evidence for dysregulation of these GTPase targets in ovarian cancer. To confirm the importance of Rac1, RNA-seq gene expression data from 305 Stage III or IV ovarian cancer samples were downloaded from The Cancer Genome Atlas (TCGA) and evaluated for RAC1 gene expression. The samples with the highest Rac1 RNA levels had significantly worse (p=0.039) age adjusted survival than the patients with the lowest Rac1 levels. Additional analyses identified more than 4,000 genes that were differentially expressed (FDR corrected p CONCLUSIONS: These findings indicate that high expression of Rac1 is associated with late stage disease and/or poor patient survival and with genes involved in extracellular matrix, cell proliferation and cell migration. These functions of Rac1 were confirmed in experimental models and inhibition of protein activity provided anti-tumor benefit in vivo. Together, these data suggest that Rac1 and/or Cdc42 function as drivers of ovarian cancer and may represent novel therapeutic targets to improve ovarian cancer outcome. Citation Format: Hudson LG, Kenney SR, Rivera, M., Weisend, J. Luo, L., Ness, S., Gillette, JM, Wandinger-Ness A. RAC 1 AND CDC42 GTPASES AS REGULATORS OF OVARIAN CANCER PROGRESSION AND NICHE INTERACTIONS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-061.
Intraglomerular gap junctions enhance interglomerular synchrony in a sparsely connected olfactory bulb network

KEY POINTS Despite sparse connectivity, population-level interactions between mitral cells (MCs) and granule cells (GCs) can generate synchronized oscillations in the rodent olfactory bulb. Intraglomerular gap junctions between MCs at the same glomerulus can greatly enhance synchronized activity of MCs at different glomeruli. The facilitating effect of intraglomerular gap junctions on interglomerular synchrony is through triggering of mutually synchronizing interactions between MCs and GCs. Divergent connections between MCs and GCs make minimal direct contribution to synchronous activity. ABSTRACT A dominant feature of the olfactory bulb response to odour is fast synchronized oscillations at beta (15-40 Hz) or gamma (40-90 Hz) frequencies, thought to be involved in integration of olfactory signals. Mechanistically, the bulb presents an interesting case study for understanding how beta/gamma oscillations arise. Fast oscillatory synchrony in the activity of output mitral cells (MCs) appears to result from interactions with GABAergic granule cells (GCs), yet the incidence of MC-GC connections is very low, around 4%. Here, we combined computational and experimental approaches to examine how oscillatory synchrony can nevertheless arise, focusing mainly on activity between 'non-sister' MCs affiliated with different glomeruli (interglomerular synchrony). In a sparsely connected model of MCs and GCs, we found first that interglomerular synchrony was generally quite low, but could be increased by a factor of 4 by physiological levels of gap junctional coupling between sister MCs at the same glomerulus. This effect was due to enhanced mutually synchronizing interactions between MC and GC populations. The potent role of gap junctions was confirmed in patch-clamp recordings in bulb slices from wild-type and connexin 36-knockout (KO) mice. KO reduced both beta and gamma local field potential oscillations as well as synchrony of inhibitory signals in pairs of non-sister MCs. These effects were independent of potential KO actions on network excitation. Divergent synaptic connections did not contribute directly to the vast majority of synchronized signals. Thus, in a sparsely connected network, gap junctions between a small subset of cells can, through population effects, greatly amplify oscillatory synchrony amongst unconnected cells.
Automated External Defibrillators in High Schools: Disparities Persist Despite Legislation.

OBJECTIVES Automated external defibrillators (AEDs) have demonstrated increased survival in out-of-hospital cardiac arrest, and their prevalence continues to rise. In 2009, Connecticut passed a legislation requiring all schools to have an AED, barring financial barriers. The objectives of this study were (1) to determine if this legislation was associated with an increase in Connecticut high school AEDs and (2) to detect disparities in the availability of AEDs based on school type, student demographics, and school size. STUDY DESIGN A single researcher conducted a scripted telephone survey of all 54 public and 13 private high schools in New Haven County, Connecticut. RESULTS A response rate of 100% was achieved. Forty-nine percent of high schools had an AED before the legislation, compared with 88% after (P < 0.001). Before legislation, private schools had a higher percentage of AEDs than public schools (69% vs 44%; P = 0.1). Postlegislation, the difference is less (92% vs 87%; P = 0.4). Small schools (<400 students) are significantly less likely to have an AED than larger schools (40% vs 100%; P < 0.001). Schools with a higher percentage of students with disabilities are also less likely to have an AED (P = 0.005), even when controlling for school size (P = 0.03). CONCLUSIONS State legislation requiring schools to have an AED, if financially feasible, was associated with a significant increase in AED presence among New Haven County high schools. Small high schools and those with a higher percentage of students with disabilities remain less likely to have an AED despite legislation.
cAMP Oscillations during Aggregation of Dictyostelium

For many years it has been known that developing cells of Dictyostelium discoideum show periodic surges as they aggregate. When it was discovered that the cells were responding chemotactically to cAMP gradients produced within the populations, experiments were carried out that demonstrated similar periodic changes in the concentration of extracellular cAMP. Moreover, homogenous populations of developed cells held in suspension could be shown to respond to cAMP by changes in cell shape. Such suspensions showed spontaneous oscillations in light scattering as well as cAMP levels as the result of entrainment of the cells. The molecular components necessary for the pulsatile release of cAMP were uncovered by analyzing the behavior of a large number of strains with defined mutations isolated from saturation mutagenic screens. Subsequent genetic and biochemical studies established the connections between a dozen proteins essential for spontaneous oscillations. Computer simulations of a molecular circuit based on these results showed that it is able to account for the temporal and quantitative aspects of the oscillatory system. The circuit also appears to be coupled to the construction and dismantling of the actin/myosin cortical layer that ensures that pseudopods are restricted to the anterior of cells during chemotaxis and that the cells do not back-track when the natural wave is behind them. Since the same molecular clock controls both signal production and signal response, these behaviors are always kept strictly in phase.
Measurement of protein turnover in skeletal muscle strips.

Isolated porcine and bovine muscle strips were incubated in Krebs Ringer bicarbonate buffer to determine in vitro protein synthesis (PS) and protein degradation (PD) rates to validate the in vitro system for use with livestock species. The addition of 5X plasma concentrations of amino acids to the medium stimulated PS 30%. Addition of 3.5 mM leucine to a leucine-deficient buffer supplemented with amino acids decreased PD 37% and stimulated PS 24%. The addition of .1 U/ml insulin reduced PD 28% and increased PS 30%. Protein degradation was elevated in longitudinally split rat soleus and extensor digitorum longus muscles compared to their contralateral intact muscles. Muscle strips must be removed within 15 min of exsanguination because PD rates become greatly elevated thereafter. ATP concentrations declined during incubation, but the addition of ATP or creatine had no effect on either PD or PS. Neither PD nor PS was affected by the addition of transferrin, fetuin, ascorbate, dexamethasone or indomethacin to the incubation medium. However, muscle strips were sensitive to the addition of triiodothyronine (T3), PD was increased up to 75% as T3 concentration was increased, and PS rates doubled compared to controls. Serum from mature barrows or gilts had no effect on protein turnover, but the addition of 10% and 15% serum from boars increased both PD and PS. With fasted pigs a continual decline in PS occurred over 5 d, whereas PD was elevated at 3 d and then declined to rates comparable to the fed state after 5 d. These data suggest that the in vitro system has application for assessing relative changes that occur in vivo following nutritional, physiological and endocrinological manipulation.
Experimental Assessment of Pulsed Corona Discharge for Treatment of VOC Emissions

The application of the pulsed corona discharge was experimentally evaluated for the treatment of VOC mixtures typically present in the exhaust streams of wood processing industry. Methanol, acetone, dimethyl sulfide, and α-pinene were selected as representative VOC compounds. An experimental database for the destruction and removal efficiencies and energy costs was produced for individual VOCs and their mixtures valid for input concentrations (5 to 1000 ppm), temperatures (25 to 200°C) and relative humidity (0 to 100%). High removal efficiencies and destruction rates above 99% were obtained with power levels competitive with the present technologies for VOC removal. Energy cost of VOC removal increases in the species sequence: dimethyl sulfide, methanol, α-pinene, acetone. It was found that energy decomposition costs were reduced as temperature and moderate humidity increased.
Mouse hepatitis virus minus-strand templates are unstable and turnover during viral replication

During the first 6 hours after infection at 37°C, MHV-A59 infected cells accumulate seven species of minus strands, one equal in length to the viral genome RNA and six that are subgenomic and with sizes equal to those of the six subgenomic viral mRNA (Sawicki and Sawicki 1990). These templates are found in double-stranded replicative intermediates (RIs and RFs) that together with viral polymerases are active in transcription of the viral plus strand species. Thus, replication of MHV-A59 conforms to the general rules discovered for plus strand RNA viruses. It is unique in having a genome of ∼32 kb and in utilizing a novel discontinuous transcription mechanism to form the templates for its 3′ nest set of viral mRNA (Sawicki and Sawicki 1990, 1995, 1998;). Our studies have been verified by Schaad and Baric (1994) and Baric and Yount (2000).
Knowledge-Based Security of Dynamic Secrets for Reactive Programs

Scripts on webpages could steal sensitive user data. Much work has been done, both in modeling and implementation, to enforce information flow control (IFC) of webpages to mitigate such attacks. It is common to model scripts running in an IFC mechanism as a reactive program. However, this model does not account for dynamic script behavior such as user action simulation, new DOM element generation, or new event handler registration, which could leak information. In this paper, we investigate how to secure sensitive user information, while maintaining the flexibility of declassification, even in the presence of active attackers---those who can perform the aforementioned actions. Our approach extends prior work on secure-multi-execution with stateful declassification by treating script-generated content specially to ensure that declassification policies cannot be manipulated by them. We use a knowledge-based progress-insensitive definition of security and prove that our enforcement mechanism is sound. We further prove that our enforcement mechanism is precise and has robust declassification (i.e. active attackers cannot learn more than their passive counterpart).
Platinum‐Catalyzed Desaturation of Lactams, Ketones, and Lactones

The development of a general platinum-catalyzed desaturation of N-protected lactams, ketones, and lactones to their conjugated α,β-unsaturated counterparts is reported. The reaction operates under mildly acidic conditions at room temperature or 50 °C. It is scalable and tolerates a wide range of functional groups. The complementary reactivity to the palladium-catalyzed desaturation is demonstrated in the efficient conversion of iodide, bromide, and sulfur-containing substrates.
Strontium isotopes reveal ephemeral streams used for spawning and rearing by an imperilled potamodromous cyprinid Clear Lake hitch Lavinia exilicauda chi

Identification of habitats responsible for the successful production and recruitment of rare migratory species is a challenge in conservation biology. Here, a tool was developed to assess life stage linkages for the threatened potamodromous cyprinid Clear Lake hitch Lavinia exilicauda chi. Clear Lake hitch undertake migrations from Clear Lake (Lake County, CA, USA) into ephemeral tributary streams for spawning. An aqueous isoscape of strontium isotopic ratios (87Sr/86Sr) was constructed for Clear Lake and its watershed to trace natal origins and migration histories of adult recruits. Aqueous 87Sr/86Sr differentiated Clear Lake from 8 of 10 key tributaries and clustered into 5 strontium isotope groups (SIGs) with 100% classification success. Otolith 87Sr/86Sr showed all five groups contributed variably to the population. The age at which juveniles migrated from natal streams to Clear Lake ranged from 11 to 152 days (mean±s.d., 43±34 days) and was positively associated with the permanency of natal habitat. This information can be used by resource managers to develop conservation actions for Clear Lake hitch. This study demonstrates the utility of strontium isotopes in otoliths as a tool to identify important freshwater habitats occupied over the lifespan of an individual that would otherwise be challenging or impossible to trace with other methods.A
Translating Animal Models of Obesity and Diabetes to the Clinic

Abstract Animal models of disease and drug action have played a vital role in the translation of the effects of CNS drugs from bench to bedside. Because of the limitations in our ability to understand the molecular mechanisms underlying the pathophysiology of disease in the human brain, we rely on animal models to provide insight into these mechanisms and identify promising targets for the development of therapeutics for various diseases. In this chapter, we discuss the key attributes of a valid animal model. We also elaborate on several examples of animal models used in preclinical research, including spontaneous, selectively bred, genetic, surgical, pharmacological, behavioral, or environmental models. Finally, we describe how these models have been used for the discovery and development of obesity therapeutics.
Paleopathology and children in the Andes: Local/situated biologies and future directions.

In the decades since Verano (1997) published his foundational piece on Andean paleopathology, scholars have recognized the importance of the bioarchaeology of childhood. Yet, scholarship on ancient childhood in the Andes deemphasizes paleopathology. Nonadult paleopathological data are often employed in large-scale, biocultural studies focused on environmental or political adaptations; however, they can also elucidate children's individual lived experiences and roles in society. To generate culturally-meaningful paleopathological data, we must take a contextualized approach to our analyses and interpretations. Disparate use of chronological age in published datasets makes synthesis across studies problematic, and ethnohistorical and ethnographic data on Andean children demonstrate that developmental age categories, rather than chronological age ranges, are most appropriate. Further, paleopathological data can best inform our investigations when they are combined with related datasets such as those on sex, diet, activity, and mobility. With that in mind, we use the theoretical framework of "local biologies" (and the related "situated biologies"), where biology is viewed as heavily contingent on culturally-specific beliefs and practices and local physical, sociocultural, and political environments (Lock, 1993, 2001; Niewohner and Lock, 2018). Local biologies approaches can enrich social bioarchaeology and paleopathology to by specifically situating children and their experiences within the ancient Andean world.
From Classical to Unconventional: The Immune Receptors Facilitating Platelet Responses to Infection and Inflammation

Platelets have long been recognized for their role in maintaining the balance between hemostasis and thrombosis. While their contributions to blood clotting have been well established, it has been increasingly evident that their roles extend to both innate and adaptive immune functions during infection and inflammation. In this comprehensive review, we describe the various ways in which platelets interact with different microbes and elicit immune responses either directly, or through modulation of leukocyte behaviors.