cssi/SciSciGPT-SciSciNet huggingface dataset:
Expression of a Dominant-Negative Mutant Inhibitor-κBα of Nuclear Factor-κB in Human Head and Neck Squamous Cell Carcinoma Inhibits Survival, Proinflammatory Cytokine Expression, and Tumor Growth in Vivo

We demonstrated recently that constitutive expression of proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in head and neck squamous cell carcinoma is correlated with activation of transcription factor nuclear factor (NF)-kappaB/Rel A (p50/p65), which binds the promoter region within each of the genes encoding this repertoire of cytokines. NF-kappaB can be activated after signal-dependent phosphorylation and degradation of inhibitor-kappaBalpha and has been reported to promote cell survival and growth. In the present study, we expressed a phosphorylation site mutant of inhibitor-kappaBalpha (IkappaBalphaM) in head and neck squamous cell carcinoma lines UM-SCC-9, -11B, and -38 to determine the effect of inhibition of NF-kappaB on cytokine expression, cell survival in vitro, and growth in vivo. After transfection with IKBalphaM, only a few UM-SCC-9 clones were obtained that stably expressed the mutant IkappaB, suggesting that expression of a mutant IkappaBalpha may affect survival of the transfected UM-SCC cell lines. After cotransfection of IkappaBalphaM with a Lac-Z reporter, we found that the number of surviving beta-galactosidase-positive cells in the three cell lines was reduced by 70-90% when compared with controls transfected with vector lacking the insert. In UM-SCC-9 cells that stably expressed IkappaBalphaM, inhibition of constitutive and tumor necrosis factor-a induced NF-kappaB activation, and production of all four cytokines was observed. Although UM-SCC-9 IkappaBalphaM-transfected cells proliferated at the same rate as vector-transfected cells in vitro, a significant reduction in growth of tumor xenografts was observed in SCID mice in vivo. The decreased growth of UM-SCC-9 IkappaBalphaM-transfected tumor cells accompanied decreased immunohistochemical detection of the activated form of NF-kappaB in situ. These results provide evidence that NF-KB and IkappaBalpha play an important role in survival, constitutive and inducible expression of proinflammatory cytokines, and growth of squamous cell carcinoma. NF-kappaB could serve as a potential target for therapeutic intervention against cytokine and other immediate-early gene responses that contribute to the survival, growth, and pathogenesis of these cancers.
Aerodynamic Design of a Land Speed Record Car

Over-all aerodynamic design considerations of The Blue Flame, a car which holds the world land-speed record, are discussed. Lift, drag, acceleration and deceleration characteristics are presented. Estimated drag coefficients and wind-tunnel results on a J^th scale model are compared with data measured during an actual speed run of The Blue Flame. Actual subsonic drag was found to be slightly lower than predicted.
THE LEFT ATRIAL APPENDAGE: TARGET FOR STROKE REDUCTION IN ATRIAL FIBRILLATION

A patient with atrial fibrillation (AF) has a greater than 5% annual risk of major stroke, a 5-fold increase compared to the general population. While anticoagulation remains the standard stroke prevention strategy, the nature of lifelong anticoagulation inevitably carries an increased risk of bleeding, increased stroke during periods of interruption, increased cost, and significant lifestyle modification. Many patients with atrial fibrillation have had their left atrial appendage (LAA) ligated or excised by surgeons during cardiac surgery, a decision based largely on intuition and with no clear evidence of efficacy in stroke risk reduction. The observation that 90% of the thrombi found in nonvalvular AF patients and 57% found in valvular AF are in the LAA, triggered significant interest in the LAA as a potential therapeutic target. Until recently, the results were inconsistent, and high rates of incomplete occlusions precluded the medical community from confirming a definite relationship between LAA and stroke. As a result, anticoagulation is still the recommended first-line stroke risk reduction in AF, and the American College of Cardiology/ American Heart Association guidelines recommend LAA exclusion only with surgical ablation of AF or in the context of concomitant mitral valve surgery. A handful of devices have been developed for LAA exclusion. This includes percutaneous options such as WATCHMAN™ Left Atrial Appendage Closure Device (Boston Scientific Corporation, Marlborough, MA), hybrid epicardial devices such as the LARIAT Suture Delivery Device (SentreHEART, Inc., Redwood City, CA), and epicardial surgical devices such as AtriClip® LAA Occlusion System (AtriCure, Inc., West Chester, OH). Studies of the Watchman device have shown noninferiority to Warfarin in stroke prevention and this device has recently gained approval from the U.S. Food and Drug Administration (FDA) following lengthy delays due to safety concerns. The Lariat device, which received 510K clearance by the FDA for tissue approximation but not LAA exclusion, has been the target of significant criticism due to serious procedural safety concerns and high incomplete closure rates. The surgical AtriClip has been FDA approved since 2009 and is currently the most widely used LAA exclusion device placed through an epicardial approach. Small studies have shown excellent reliability and success of complete LAA closure with the AtriClip device, which is implanted through an epicardial approach. Currently, we are conducting a multicenter trial to demonstrate the stroke prevention potential of this epicardial device through a short (45 minute), stand-alone, minimally invasive procedure in lieu of lifelong anticoagulation in patients at high risk of bleeding.
Measuring rDNA Diversity in Eukaryotic Microbial Systems: How Intragenomic Variation, Pseudogenes, and PCR Artifacts Confound Biodiversity Estimates

Molecular approaches have revolutionized our ability to study the ecology and evolution of micro-organisms. Among the most widely used genetic markers for these studies are genes and spacers of the rDNA operon. However, the presence of intragenomic rDNA variation, especially among eukaryotes, can potentially confound estimates of microbial diversity. To test this hypothesis, bacterially cloned PCR products of the internal transcribed spacer (ITS) region from clonal isolates of Symbiodinium, a large genus of dinoflagellates that live in symbiosis with many marine protists and invertebrate metazoa, were sequenced and analysed. We found widely differing levels of intragenomic sequence variation and divergence in representatives of Symbiodinium clades A to E, with only a small number of variants attributed to Taq polymerase/bacterial cloning error or PCR chimeras. Analyses of 5.8S-rDNA and ITS2 secondary structure revealed that some variants possessed base substitutions and/or indels that destabilized the folded form of these molecules; given the vital nature of secondary structure to the function of these molecules, these likely represent pseudogenes. When similar controls were applied to bacterially cloned ITS sequences from a recent survey of Symbiodinium diversity in Hawaiian Porites spp., most variants (~87.5%) possessed unstable secondary structures, had unprecedented mutations, and/or were PCR chimeras. Thus, data obtained from sequencing of bacterially cloned rDNA genes can substantially exaggerate the level of eukaryotic microbial diversity inferred from natural samples if appropriate controls are not applied. These considerations must be taken into account when interpreting sequence data generated by bacterial cloning of multicopy genes such as rDNA.
Prospective evaluation of metabolic bone disease after jejunoileal bypass.

Abstract Twenty-eight patients undergoing jejunoileal bypass for morbid obesity were studied prospectively for alterations in mineral metabolism and the development of metabolic bone disease. Eleven additional patients were examined for long-term complications. Serum 25-hydroxyvitamin D and fractional calcium absorption were depressed during the first 2 yr after bypass but normalized after this period. Serum parathormone remained normal. Mild osteomalacia was identified in 12% of subjects by histomorphometric analysis of undecalcified biopsy specimens. Osteomalacia was asymptomatic and could not be reliably diagnosed by noninvasive tests. Repeat biopsies demonstrated histologic improvement in 2 individuals followed serially. Improvement was not clearly related to vitamin D therapy. Abnormalities in mineral appositional rates and mineral maturation were identified in several additional patients. Studies in the long-term group did not indicate inexorable progression of metabolic bone disease. Although intestinal bypass produced several abnormalities in mineral metabolism during the first 2 yr after surgery, a trend toward normalization was evident after the period, possibly related to adaptive responses in the intestine.
Vibration of point-supported rectangular composite plates

Abstract A general approach is presented to study the free vibrations of rectangular symmetrically laminated composite plates with point supports by using the Rayleigh-Ritz method and the Lagrange multiplier technique for enforcing the zero displacement constraints at the support locations. Polynomial approximation functions are used and the constitutive relationships are written in terms of four lamination parameters. With these lamination parameters, the number of design variables is reduced to a minimum, which is useful for design optimization purposes, while all symmetric lay-ups are considered. This paper illustrates how the lamination parameters can be used for optimal design of vibrating plates. Results are presented for several cases and the effect of aspect ratio, material properties and lay-up are fully investigated. Plates on point supports and with straight and curved internal line supports are considered. For each case, the lay-up that maximizes the first natural frequency of the plate is determined.
Automatic alignment of myocardial perfusion images with contrast cardiac Tomography

Explicit fusion of perfusion data from Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy from Computed Tomographic Coronary Angiography (CTCA) has been shown to improve the diagnostic yield for coronary artery disease (CAD) compared to either modality alone. However, most clinically available methods were developed for multimodal scanners or require interactive alignment prior to display and analysis. A new approach was developed to register and display the two distributions obtained either from a single multimodal imager or from separate scanners, and a preliminary validation was undertaken using interactive alignment by experts.
Genetic algorithm optimization for small antenna design

Small antenna design is a complex balance of trade-offs imposed by geometry, volume, manufacturability, materials, and the operating environment. Experience and intuition are essential in the antenna design process, however, once design complexity reaches a certain level, the use of design optimization tools becomes extremely valuable if not a necessity. This paper demonstrates the use of genetic algorithm optimization applied to a proprietary field solver interfaced with a commercial CAD system.
Robotic transaxillary parathyroidectomy: surgical technique and pearls

With the advances in preoperative localization studies and greater demand for minimally invasive procedures, novel targeted approaches to the parathyroid glands have been described and practiced over the past 2 decades. Despite these various surgical options, no single technique has been established as superior to another. Recently, robotic surgery has evolved from a novel technique with an anticipated potential to overcome the limitations associated with endoscopic techniques, to the preferred surgical procedure in multiple surgical disciplines. Their application in head and neck surgery has gained wide popularity in Asia and recently in European and North American practice. This article reviews the application of robotic technology to further assist surgeons in accomplishing parathyroidectomy.
Mechanistic Studies on the Reaction between Cob(II)alamin and Peroxynitrite: Evidence for a Dual Role for Cob(II)alamin as a Scavenger of Peroxynitrous Acid and Nitrogen Dioxide

Peroxynitrite/peroxynitrous acid (ONOO(-)/ONOOH; pK(a(ONOOH)) =6.8) is implicated in multiple chronic inflammatory and neurodegenerative diseases. Both mammalian B(12)-dependent enzymes are inactivated under oxidative stress conditions. We report studies on the kinetics of the reaction between peroxynitrite/peroxynitrous acid and a major intracellular vitamin B(12) form, cob(II)alamin (Cbl(II)), using stopped-flow spectroscopy. The pH dependence of the reaction is consistent with peroxynitrous acid reacting directly with Cbl(II) to give cob(III)alamin (Cbl(III)) and (.)NO(2) , followed by a subsequent rapid reaction between (.)NO(2) and a second molecule of Cbl(II) to primarily form nitrocobalamin. In support of this mechanism, a Cbl(II)/ONOO(H) stoichiometry of 2:1 is observed at pH 7.35 and 12.0. The final major Cbl(III) product observed (nitrocobalamin or hydroxycobalamin) depends on the solution pH. Analysis of the reaction products in the presence of tyrosine-a well-established (.)NO(2) scavenger-reveals that Cbl(II) reacts with (.)NO(2) at least an order of magnitude faster than tyrosine itself. Given that protein-bound Cbl is accessible to small molecules, it is likely that enzyme-bound and free intracellular Cbl(II) molecules are rapidly oxidized to inactive Cbl(III) upon exposure to peroxynitrite or (.)NO(2).
Feeding hens during alternating a.m. and p.m. time blocks to induce zero egg production during the molt

Abstract There is a need to evaluate the position paper and guidelines set forth by the United Egg Producers (Washington, DC) and the American Veterinary Medical Association (Schaumburg, IL) on feeding practices and nutrient levels provided during a molt. This pilot study was undertaken to learn if a complete cessation of lay could be achieved with daily feeding while using an alternate morning and evening feeding schedule. This was an effort to mimic the fast that a bird experiences in a natural setting. The hens were fed the amount they would eat in 4 h during the morning one day and again the evening of the next day. Some hens ceased production in the third week and others in the fourth week, with zero production for all hens occurring during the fifth week. The return to 50% egg production was achieved from wk 7 to 8. Peak egg production occurred from the eleventh to twelfth weeks postmolt, reaching a level only 5 to 6 percentage points below the first cycle. This feeding protocol resulted in complete cessation of lay, allowing for a more uniform and complete restoration of the ovarian and oviductal tissues. This restoration is necessary for an effective economical postmolt period of egg production.
Seeing bodies in pain: from Hippocrates to Freud.

The study of pain has a history as long as that of Western medicine. In the 20th and 21st centuries much has been made about the epistemological problem of seeing somatic as well as psychic pain in...
STUDIES ON THE SOMATIC C POLYSACCHARIDE OF PNEUMOCOCCUS I. CUTANEOUS AND SEROLOGICAL REACTIONS IN PNEUMONIA

A study of 46 cases of pneumococcus pneumonia has shown that a characteristic response may be elicited by the intracutaneous injection of 0.1 mg. of the somatic C polysaccharide of pneumococcus. During the acute febrile period in patients who recover, the response consists of a delayed erythema which reaches its maximum intensity in 18 to 24 hours. During convalescence the reaction is not demonstrable. In patients in whom the disease is prolonged by complications the capacity of the skin to react persists. In 7 fatal cases the skin failed to react to C polysaccharide. Parallel studies of the reaction of the patients' serum with C have confirmed and extended the observations of Tillett and Francis on the appearance of the precipitation phenomenon during the acute stages and its disappearance in recovery. That the cutaneous and serological reactions are not specific for pneumococcus infection is shown by the results in 29 control cases. 8 patients with infectious febrile diseases not of pneumococcus origin gave responses similar to those noted in pneumonia. 2 patients with non-infectious fevers and 18 of 19 normal individuals failed to give either skin or serum reactions. These observations emphasize the importance of using separate components of the bacterial cell in the interpretation of cutaneous and serological reactions in pneumonia. The parallelism in results of the skin and serum tests in pneumococcus pneumonia with the somatic carbohydrate C, the significance of the reactions in relation to the clinical course and outcome of the disease, and the frequency of occurrence of both reactions in bacterial infections other than those of pneumococcal origin, are discussed.
The developmental decrease in REM sleep

Abstract This mini-review considers certain factors related to the developmental decrease in rapid eye movement (REM) sleep, including its timing, its relationship to other developmental changes, factors that may influence its progress and its potential role in brain development. Specifically, we discuss some of the theories proposed for its occurrence and agree with the classic notion that REM sleep is, at least, an active mechanism that may play a role in the maturation of the central nervous system (CNS), specifically contributing to the maturation of thalamocortical pathways. The developmental decrease in REM sleep occurs gradually from birth until after puberty in the human, but in other mammals it is brief and coincides with eye and ear opening and the beginning of massive exogenous activation. This purported role for REM sleep may change to involve a number of other functions with age. We describe recent findings showing that intrinsic morphological and physiological properties as well as serotonergic, n-methyl- d -aspartic acid (NMDA) and kainic acid (KA) synaptic inputs to mesopontine cholinergic neurons change dramatically at this critical period in development, perhaps driving what has been proposed as a REM sleep inhibitory process (RIP). We hypothesize that a dysregulation of this process could result in life-long disturbances in REM sleep drive, leading to hypervigilance or hypovigilance such as that observed in a number of disorders which have a mostly postpubertal age of onset. Finally, we also hypothesize that the role of normal cyclic increases in vigilance, observable during both sleep and waking, may be related, at least in part, to cortical blood flow.
Recommendations For Comparing Electronic Prescribing Systems: Results Of An Expert Consensus Process

Commercially available electronic prescribing systems may differ in their ef- fects on patients' health outcomes and on patients' ability to manage costs. An expert panel convened to recommend specific features that would enable electronic prescribing systems to advance these goals. The panel authored sixty recommendations and rated each using a modified Delphi process. Ratings identified fifty-two recommendations as clearly positive for patient safety and health outcomes and forty-three recommendations as achievable in the average clinician's office within three years. Overall, these recommenda- tions offer a synthesis of evidence and expert opinion that can help guide the development of electronic prescribing policy.
Southern Ocean Climate and Sea Ice Anomalies Associated with the Southern Oscillation

The anomalies in the climate and sea ice cover of the Southern Ocean and their relationships with the Southern Oscillation (SO) are investigated using a 17-year of data set from 1982 through 1998. We correlate the polar climate anomalies with the Southern Oscillation index (SOI) and examine the composites of these anomalies under the positive (SOI > 0), neutral (0 > SOI > -1), and negative (SOI < -1) phases of SOL The climate data set consists of sea-level pressure, wind, surface air temperature, and sea surface temperature fields, while the sea ice data set describes its extent, concentration, motion, and surface temperature. The analysis depicts, for the first time, the spatial variability in the relationship of the above variables and the SOL The strongest correlation between the SOI and the polar climate anomalies are found in the Bellingshausen, Amundsen and Ross sea sectors. The composite fields reveal anomalies that are organized in distinct large-scale spatial patterns with opposing polarities at the two extremes of SOI, and suggest oscillating climate anomalies that are closely linked to the SO. Within these sectors, positive (negative) phases of the SOI are generally associated with lower (higher) sea-level pressure, cooler (warmer) surface air temperature, and cooler (warmer) sea surface temperature in these sectors. Associations between these climate anomalies and the behavior of the Antarctic sea ice cover are clearly evident. Recent anomalies in the sea ice cover that are apparently associated with the SOI include: the record decrease in the sea ice extent in the Bellingshausen Sea from mid- 1988 through early 199 1; the relationship between Ross Sea SST and ENSO signal, and reduced sea ice concentration in the Ross Sea; and, the shortening of the ice season in the eastern Ross Sea, Amundsen Sea, far western Weddell Sea, and the lengthening of the ice season in the western Ross Sea, Bellingshausen Sea and central Weddell Sea gyre over the period 1988-1994. Four ENSO episodes over the last 17 years contributed to a negative mean in the SOI (-0.5). In each of these episodes, significant retreats in the Bellingshausen/Amundsen Sea were observed providing direct confirmation of the impact of SO on the Antarctic sea ice cover.
The Azolla-Anabaena azzolae symbiosis.

Free-living, nitrogen fixing blue-green algae occur in soils and in both fresh water and marine habitats from the tropics to the antarctic.l–3 Moreover, symbiotic relationships with nitrogen-fixing blue-green algae encompass members of a relatively large and diverse segment of the plant kingdom. In particular, blue-green algae in the Nostoc-Anabaena group exist in symbiotic associations as lichens and with liverworts, water-ferns, cycads and the angiosperm, Gunnera.3,4
Field-theoretic treatment of the 2d planar model with random p-fold symmetry-breaking field

Abstract It is shown that the effects of a random p-fold symmetry-breaking field on the two-dimensional planar model can be studied systematically using field-theoretic methods within the context of the replica scheme. In the absence of vortices we show that the model is renormalizable in a double expansion in a temperature difference variable δ and in g02: the strength of the disorder. The spin—spin and spin—glass correlation functions are calculated and their behavior under the renormalization group is analyzed. The spin—glass correlation function exhibits power-law behavior at any temperature but the power law is gaussian at high temperatures and controlled by a non-zero field fixed line at low temperature. Although our results agree substantially with previous work we can now point out situations in which the expansion breaks down and higher order terms must be retained. Adding vortices we can show that for p > 2 2 an XY phase exists at intermediate values of temperature and for small values of g02 for which our expansion is valid, vortices are irrelevant perturbations. However, in the low-temperature phase our expansion breaks down and we can no longer conclude that vortices are irrelevant. The nature of the low-temperature phase remains unresolved.
Constructal Design of High-Conductivity Inserts

Bejan presented the Constructal Theory by solving an optimization problem for the cooling of a heat generating volume [1]. The proposed problem was “how to collect and channel to one point the heat generated volumetrically in a low conductivity volume of given size.” The proposed approach defined an elemental construct for which the geometry was optimized. The elemental construct had rectangular shape and consisted of two regions: one region with a low-conductivity material and heat generation and a second region with high-conductivity material that was used to conduct the generated heat to the exterior through one end (Fig. 6.1a). The fraction of high-conductivity material was fixed. More complex forms (assemblies) were obtained by combining the optimized elemental form as shown in Fig. 6.1b–d.
Building a Bridge from Research to the Market: IBM’s Industry Solutions Labs

Following the vision of creating synergy between customers’ future needs and emerging technologies, IBM Research established the first Research Client Center in 1997 – an instrument to create a bridge from research to the market. From that time onwards, IBM Research has opened up to the external world and entered into a true dialog with its clients. Today, open and collaborative innovation is imperative for IBM Research to drive innovation. In IBM’s innovation process, the Client Centers at IBM’s Research sites – the so-called Industry Solutions Labs (ISL) – are regarded as forums, knowledge hubs, and enablers. They have direct access to the scientists and benefit from the inspiring and creative atmosphere in the labs. The ISLs’ goal is to pose the right questions to stimulate valuable discussions and generate insightful answers to complex challenges. One of the core elements in ISL workshops is the discussion of key technology trends based on the Global Technology Outlook – IBM Research’s annual look into the future with regard to technology trends. These key trends identified are used to define areas of focus and future investment in the company.
The Effect of Annealing Conditions on Magnetron Sputtered Superconducting Tl-Based Thin Films

The annealing steps have been shown to be a crucial determinant of the quality of Tl-based superconducting films. In this study, we discuss the formation of the superconducting Tl2Ba2CaCu2O8 and Tl2Ba2Ca2Cu3O10 phases with varied post-annealing temperature and fixed annealing time. A x-ray, electron micro-probe, and scanning electron microscopy were carried out to evaluate the structure of superconducting phases formed for each annealing condition. For films deposited on SrTiO3 substrates and heat-treated at 870°C for 15 min, the lower Tc phase Tl2Ba2CaCu2O8 becomes a major phase. The films consist of nearly pure Tl2Ba2Ca2Cu3O10 phase with Tc (R=0) in the range of 100K to 118K and c-axis perpendicular to the film plane were obtained after annealing 880-890°C for 15 min. These films were epitaxy growth on SrTi03 substrates.
Adirondack Voices: Woodsmen and WoodsLore. By Robert D. Bethke. Urbana: University of Illinois Press, 1981. 148 pp. Hardbound, $12.50.

(1982). Adirondack Voices: Woodsmen and WoodsLore. The Oral History Review: Vol. 10, No. 1, pp. 192-194.
Mathematical Proof and the Reliability of DNA Evidence

.Leonard Adleman recently found the solution to a problem in graph theory using DNA technology. (See [Adleman].) However, once the solution was obtained, Adleman checked that the solution was correct by hand. As a result, DNA evidence served no justificatory function in this case. Perhaps this is fortunate since "the mathematical establishment has often expressed its displeasure with certain types of 'proof' visual, mechanical, experimental, probabilistic" [Davis 1995, p. 212]. At the risk of displeasing the mathematical establishment, I will suggest in this paper how DNA evidence might legitimately stand in for a mathematical proof. THE DIRECTED HAMILTONIAN PATH PROBLEM. The problem in graph theory that Adleman solved is an instance of the directed Hamiltonian path problem (DHPP). A directed graph is a group of towns connected in various ways by one-way roads. One of the towns is designated the start town and another town is designated the destination town. A path is a sequence of towns such that each town in the sequence is connected by a one-way road to the next town in the sequence. A Hamiltonian path (HP) is a path from the start town to the destination town that visits every other town exactly one time. The DHPP asks if a given directed graph contains an HP and if so what the HP is. The DHPP is an example of an NP-complete problem. A distinguishing feature of NP-complete problems is that while it is easy to check that a solution is correct, it is difficult to find a solution in the first place. In the case of the DHPP, it is easy to check whether or not any particular path is an HP, but it is difficult to find a path that is an HP.
ATC Perspectives of UAS Integration in Controlled Airspace

Abstract There is a need to better understand the impacts unmanned aircraft systems (UAS) have on air traffic control (ATC) when they are integrated into the National Airspace System (NAS) in controlled airspace. An increasing number of UAS are requesting access to controlled airspace. Today, the larger UAS that are accessing busier controlled airspace consist mostly of Global Hawk and Predator-class aircraft. While these models of large UAS will continue to fly in the NAS, a small number of additional high-altitude long-endurance (HALE) UAS will be added to the traffic mix. Although the larger UAS flying in controlled airspace tend to fly in less congested areas, there is still an impact on ATC. Over the past several years, MITRE has been using a combination of techniques to determine the key impacts on controllers and the air traffic system. The analyses have shown that there are several areas where air traffic control is most affected by UAS flights. One of these areas is the filing of flight plans; especially for long-duration missions. Another difference is the flight profile of UAS. UAS flight profiles are frequently very different from traditional point-to-point routes that most manned aircraft fly. The impact on controllers is exacerbated by the fact that most of these UAS operating in controlled airspace use latitude/longitude waypoints to define their route instead of the more common named fixes or waypoints. The communications and control link for beyond visual line of sight operations can present additional challenges for controllers if there are delays in responses to clearances and maneuvering of aircraft. While these examples have some potential to exist for manned aircraft, they are more prevalent in UAS. One additional issue, unique to UAS, is the complete loss of the communications and control link. Throughout this research, MITRE has looked at potential ways of mitigating issues that arise from the different UAS challenges, and reviewed some of the pros and cons of these different approaches, including changes in procedures, automation, and policy.
Evidence for an hepatic role in the control of sodium excretion

Discussion and ConclusionsThe increased natriuresis found after a small hypertonic sodium chloride load was infused into anesthetized dogs was found to be greater when the stimulus was administered directly into the hepatic circulation than when it was infused systemically via the femoral vein. In addition, the response appears to be dose-related within limits. At 0.05 ml/kg/min a significant natriuresis was obtained only after portal loading. At double this rate, significant increases in sodium excretion occurred with both routes of administration, but the increase after portal loading was more than 50% greater. At a higher rate of infusion (0.4 ml/kg/min) no difference was observed between routes. It would appear that the liver exerts a modest influence on sodium excretion and that the modest contribution of an hepatic component is obscured by other components of the natriuretic response to saline loading when the load of saline is increased.Data obtained when 5% saline was infused distal to the hepatic...
Abstract LB-64: Selective estrogen receptor modulators (SERMs) act as breast cancer chemopreventive agents by attenuating oxidative estrogen metabolism

Possibility of developing hormone dependent cancer in women will increase with long term exposure to endogenous estrogens. Estrogen induced, estrogen receptor (ER) mediated cell proliferation (hormonal pathway) and formation of reactive estrogen metabolites (chemical pathway) are believed to contribute to estrogen carcinogenesis. Estrogens are oxidized to the catechols, 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ) by P450 1A1/1A2 and P450 1B1 respectively. Both catechols are further oxidized to form electrophilic o-quinones which can react with DNA and proteins, while 4 hydroxyestradiol O-quinone (4-OHE 2 -Q) is considered as the ultimate carcinogen. Selective Estrogen Receptor Modulators (SERMs) are used in cancer chemoprevention and in the treatment of post menopausal osteoporosis. The current study focuses on elucidating the influence of clinical and pre clinical benzothiophene SERMs on oxidative estrogen metabolism in ER negative non tumerigenic human breast epithelial cells (MCF-10A). Upon exposure to 17β-estradiol (E 2 ), MCF-10A cells transformed into a malignant phenotype and showed anchorage independent colony growth in soft agar. After treatment of MCF-10A cells with E 2 and SERMs, estrogen metabolites were analyzed using a sensitive LC-MS/MS method. Among the SERMs tested, raloxifene and desmethylarzoxifen (DMA) showed a significant reduction in catechol estrogen formation whereas 4′F-DMA had little effect. Furthermore, raloxifene and DMA significantly inhibited E 2 induced malignant transformation and reactive oxygen species formation in MCF-10A cells. These data suggest that raloxifene and DMA possess chemopreventive activity through inhibition of genotoxic estrogen quinone formation, in addition to their action via estrogen receptors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-64. doi:1538-7445.AM2012-LB-64
Molecular Basis of Embryo Implantation

Implantation following placentation is a unique system for mammals to reproduce. The initial attachment of the embryo to the uterus occurs via the apical cell membranes of two epithelial cells, trophoblast of the blastocyst and surface epithelial cells of the endometrium. Analysis of the implantation at the molecular level has been a difficult problem in reproductive biology. Recently, a major break through was made in this area: A discovery of a novel cell adhesion molecule complex mediating the initial attachment of trophoblast to the endometrial epithelium. This review provides a brief overview of cell adhesion molecules involved in implantation and introduces identification and characterization of trophinin and tastin.
Evaluation of Lung and Prostate Biospecimens at the Point-of-Acquisition with a Dual-Color Fluorescent H&E Analog

We report a novel topical fluorescent staining method that closely replicates standard H&E, which combined with rapid ex vivo microscopy allows rapid nondestructive evaluation and diagnosis of intact tissue samples at the point-of-acquisition.
To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease

Despite similar components, the heterogeneity of skin characteristics across the human body is enormous. It is classically believed that site-specific fibroblasts in the dermis control postnatal skin identity by modulating the behavior of the surface-overlying keratinocytes in the epidermis. To begin testing this hypothesis, we characterized the gene expression differences between volar (ventral; palmoplantar) and nonvolar (dorsal) human skin. We show that KERATIN 9 (KRT9) is the most uniquely enriched transcript in volar skin, consistent with its etiology in genetic diseases of the palms and soles. In addition, ectopic KRT9 expression is selectively activated by volar fibroblasts. However, KRT9 expression occurs in the absence of all fibroblasts, although not to the maximal levels induced by fibroblasts. Through gain-of-function and loss-of-function experiments, we demonstrate that the mechanism is through overlapping paracrine or autocrine canonical WNT–β-catenin signaling in each respective context. Finally, as an in vivo example of ectopic expression of KRT9 independent of volar fibroblasts, we demonstrate that in the human skin disease lichen simplex chronicus, WNT5a and KRT9 are robustly activated outside of volar sites. These results highlight the complexities of site-specific gene expression and its disruption in skin disease.
Tendon Regeneration with Tendon Hydrogel-Based Cell Delivery: A Comparison of Fibroblasts and Adipose-Derived Stem Cells.

Background:Tendon hydrogel is a promising biomaterial for improving repair strength after tendon injury. This study compares the capacity of fibroblasts and adipose-derived stem cells to proliferate, survive, and acquire tenogenic properties when seeded into tendon hydrogel in vitro and in vivo.Meth
Neonatal Tissue Damage Promotes Spike Timing-Dependent Synaptic Long-Term Potentiation in Adult Spinal Projection Neurons.

Mounting evidence from both humans and rodents suggests that tissue damage during the neonatal period can “prime” developing nociceptive pathways such that a subsequent injury during adulthood causes an exacerbated degree of pain hypersensitivity. However, the cellular and molecular mechanisms that underlie this priming effect remain poorly understood. Here, we demonstrate that neonatal surgical injury relaxes the timing rules governing long-term potentiation (LTP) at mouse primary afferent synapses onto mature lamina I projection neurons, which serve as a major output of the spinal nociceptive network and are essential for pain perception. In addition, whereas LTP in naive mice was only observed if the presynaptic input preceded postsynaptic firing, early tissue injury removed this temporal requirement and LTP was observed regardless of the order in which the inputs were activated. Neonatal tissue damage also reduced the dependence of spike-timing-dependent LTP on NMDAR activation and unmasked a novel contribution of Ca2+-permeable AMPARs. These results suggest for the first time that transient tissue damage during early life creates a more permissive environment for the production of LTP within adult spinal nociceptive circuits. This persistent metaplasticity may promote the excessive amplification of ascending nociceptive transmission to the mature brain and thereby facilitate the generation of chronic pain after injury, thus representing a novel potential mechanism by which early trauma can prime adult pain pathways in the CNS. SIGNIFICANCE STATEMENT Tissue damage during early life can “prime” developing nociceptive pathways in the CNS, leading to greater pain severity after repeat injury via mechanisms that remain poorly understood. Here, we demonstrate that neonatal surgical injury widens the timing window during which correlated presynaptic and postsynaptic activity can evoke long-term potentiation (LTP) at sensory synapses onto adult lamina I projection neurons, which serve as a major output of the spinal nociceptive circuit and are essential for pain perception. This persistent increase in the likelihood of LTP induction after neonatal injury is predicted to favor the excessive amplification of ascending nociceptive transmission to the mature brain in response to subsequent injury and thereby exacerbate chronic pain.
Intravesical Bacillus Calmette-Guerin Therapy and Associated Granulomatous Renal Masses

We report a case of clinically symptomatic renal granulomas occurring during intravesical and intracutaneous bacillus Calmette-Guerin therapy for bladder cancer. The patient responded to antituberculous triple therapy. We emphasize the rarity of such extravesical infectious complications and discuss the possible routes of renal inoculation.
P08.06 Lactic acid isomers differentially reduce chlamydia trachomatis infection in a ph dependent manner

Introduction Epidemiological studies indicate that the vaginal microbiota can significantly impact the risk of acquiring sexually transmitted infections, including chlamydia. Lactobacillus spp. are the most common commensal bacteria in the healthy human vagina; they produce lactic acid to create an acidic environment with pH ranging between 3.5 and 4, thought to reduce vaginal colonisation by STI agents. However, not all species of Lactobacillus are believed to perform this function equally, and we hypothesised that species that produce low amounts or no D-lactic acid, while achieving low pH do not fully protect women. Methods A 3D model of cervical epithelial cells (A2EN) developed in our lab was exposed to D(-), L(+) or a D/L racemic mixture of lactic acid at various concentrations to produce pH 7, 5.5 and 4 or to several Lactobacillus spp. conditioned media (LCM). Cells were infected with C. trachomatis serovar L2 for 48 h, stained and imaged by confocal microscopy. Analysis of the resultant IFUs was used to determine the number of infected host cells. Results We observed a reduction of Chlamydia trachomatis infectivity in a pH dependent manner. Further, at pH 4, D(-) lactic acid afforded maximal protection compared to L(+) lactic acid. Interestingly, 50% infectivity is still observed with HCL at pH 4, indicating that pH alone is not responsible for this protection. Exposure of cells to conditioned media from the various Lactobacillus spp. showed that high D(-) lactic acid producing bacteria ( Lactobacillus crispatus and Lactobacillus jensenii) afforded significantly greater protection against C. trachomatis than did Lactobacillus iners, which produces predominantly L(+) lactic acid. Conclusion These results suggest a differential role for specific species of Lactobacillus in driving resistance to C. trachomatis infections and potentially other STIs. Lactic acid isomers production should be considered when developing Lactobacillus vaginal probiotics. Disclosure of interest statement Project funded by NIH-NIAID-STI-CRC U19 AI084044 “Eco-Pathogenomics of Chlamydial Reproductive Tract Infection”. No pharmaceutical grants were received in the development of this study.
Paradoxes of moral reparation: Deontic foci vs. circumstances

The distinction between deontic focus and deontic circumstance is obvious and essential to the understanding of our reasonings about obligations, permissions, rights, and wrongs. Here we have dealt with the basics. These basics must be developed into a full deontic logic. Fortunately, such a comprehensive deontic logic that includes identity, quantification over individuals, and quantification over properties has already been proposed, and applied to the interpretation of legal texts. It should be an excellent basis for Feldman's intriguing and promising idea of world utilitarianism.
Functionalism in the lexicon: Where is it, and how did it get there?

Why do languages have the words they have, and not some other set of words? While certainly there is some arbitrariness in the lexicon (English ‘frog’ vs. Spanish ‘rana’), there is just as surely some systematicity or functionality in it as well. What exactly might the nature of this systematicity or functionality be? For example, might the lexicon be efficiently adapted for communication, learning, memory storage, retrieval, or other cognitive functions? This paper critically reviews evidence that natural language lexicons efficiently carve up semantic fields (e.g., color, space, kinship) and have phonological forms that are similarly efficient when the aggregate lexicon is considered. The paper also suggests additional ways functionalism in lexicons might be assessed, and speculates on how functional lexicons may have arisen.
Fluid Overload and Cumulative Thoracostomy Output Are Associated With Surgical Site Infection After Pediatric Cardiothoracic Surgery.

OBJECTIVES To determine the impact of cumulative, postoperative thoracostomy output, amount of bolus IV fluids and peak fluid overload on the incidence and odds of developing a deep surgical site infection following pediatric cardiothoracic surgery. DESIGN A single-center, nested, retrospective, matched case-control study. SETTING A 26-bed cardiac ICU in a 303-bed tertiary care pediatric hospital. PATIENTS Cases with deep surgical site infection following cardiothoracic surgery were identified retrospectively from January 2010 through December 2013 and individually matched to controls at a ratio of 1:2 by age, gender, Risk Adjustment for Congenital Heart Surgery score, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, primary cardiac diagnosis, and procedure. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Twelve cases with deep surgical site infection were identified and matched to 24 controls without detectable differences in perioperative clinical characteristics. Deep surgical site infection cases had larger thoracostomy output and bolus IV fluid volumes at 6, 24, and 48 hours postoperatively compared with controls. For every 1 mL/kg of thoracostomy output, the odds of developing a deep surgical site infection increase by 13%. By receiver operative characteristic curve analysis, a cutoff of 49 mL/kg of thoracostomy output at 48 hours best discriminates the development of deep surgical site infection (sensitivity 83%, specificity 83%). Peak fluid overload was greater in cases than matched controls (12.5% vs 6%; p < 0.01). On receiver operative characteristic curve analysis, a threshold value of 10% peak fluid overload was observed to identify deep surgical site infection (sensitivity 67%, specificity 79%). Conditional logistic regression of peak fluid overload greater than 10% on the development of deep surgical site infection yielded an odds ratio of 9.4 (95% CI, 2-46.2). CONCLUSIONS Increased postoperative peak fluid overload and cumulative thoracostomy output were associated with deep surgical site infection after pediatric cardiothoracic surgery. We suspect the observed increased thoracostomy output, fluid overload, and IV fluid boluses may have altered antimicrobial prophylaxis. Although analysis of additional pharmacokinetic data is warranted, providers may consider modification of antimicrobial prophylaxis dosing or alterations in fluid management and diuresis in response to assessment of peak fluid overload and fluid volume shifts in the immediate postoperative period.