cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract LB-299: Cynomolgus monkey plasma cell gene signature to quantify the in vivo activity of a half-life extended anti-BCMA BiTE® for the treatment of multiple myeloma

Background: Multiple myeloma (MM) is a hematologic malignancy where abnormal plasma cells (PC) accumulate in the bone marrow (BM). Patients often develop relapsed/refractory disease leading to significant morbidity and mortality. Elimination of residual disease is required for curative treatments. Patient outcome can be improved by using T-cell engaging agents, such as bispecific T-cell engager (BiTE®) antibody constructs, to redirect T cells to tumor cells. B-cell maturation antigen (BCMA), a TNF receptor superfamily member, supports PC survival and is widely expressed on MM and normal PC. Methods: A half-life extended (HLE) anti-BCMA BiTE® (BCMA HLE-BiTE®) antibody construct was generated and characterized in vitro, and in vivo in a mouse xenograft model and in non-human primates (NHP). To quantify on-target activity of the BCMA HLE-BiTE® in NHP it was necessary to follow changes in PC numbers. Because PC are rare (0.1 - 3%) in the BM and blood, detection using traditional assays is not possible. To address this limitation, a PC gene signature was defined and used to develop a quantitative ddPCR assay (sensitivity = 0.01%) to assess the effect of the BCMA HLE-BiTE® in a 12-day repeat-dose NHP study. Results: A BCMA HLE-BiTE® was selected that demonstrated cytotoxic activity using human effector cells (EC50: 0.13 ± 0.07 pM in MM.1R cells) and comparable activity using NHP effector cells. In a sub-cutaneous mouse xenograft model in which BCMA-positive NCI-H929 cells and human PBMC were co-administered, the BCMA HLE-BiTE® completely inhibited tumor formation, in contrast to vehicle controls with/without PBMC. The serum half-life of the BCMA HLE-BiTE® in NHP was 112 hours following a single 15 µg/kg IV dose. The PK/PD relationship in NHP was next evaluated in a 12-day repeat-dose study. A dose-dependent PK behavior as well as depletion of PC in blood and BM was observed, reaching 93% depletion in the blood and 85% in the BM in the high-dose group on day 12. Conclusions: These results demonstrate that the BCMA HLE-BiTE® is potent and effective at inducing cytotoxicity of target cells in vitro and in vivo, and may be suitable for once-weekly dosing in MM patients. This molecule is being evaluated in humans: trial NCT03287908. Citation Format: Ana Goyos, Chi-Ming Li, Petra Deegen, Pamela Bogner, Oliver Thomas, Joachim Wahl, Rebecca Goldstein, Maththias Friedrich, Angela Coxon, Mercedesz Balazs, Tara Arvedson. Cynomolgus monkey plasma cell gene signature to quantify the in vivo activity of a half-life extended anti-BCMA BiTE® for the treatment of multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-299.
Information Systems Redesign in a State Social Services Agency: A Case Study

Successful implementation of information systems (IS) is an essential part of executing new business strategies. Yet, IS development projects are most susceptible to fail. According to a report by the Standish Group 42% of IS projects are canceled before completion. This case addresses many of the causes of IS project failure. It is based on an information system redesign project undertaken by a state social services agency. The Project aims at automating the welfare system and providing mission-critical applications to the social workers in the field and federal subsidies distribution. The case is written from the perspective of an actual participant on the project during the time that is documented. Although most of the players recognized that they needed automation to conduct their business in a radically different and superior way, the project failed, wasting $32 million of taxpayers money. A number of problems such as lack of proper planning, underestimating the size and complexity of the endeavor, and organizational and cultural issues surrounding government agencies contributed to the project failure.
Malignant Tracheal Tumors

Tracheal tumors are quite rare, and about 90 % are malignant. The two most common malignant tracheal tumors, squamous cell and adenoid cystic carcinomas, have an equal incidence. Less common tumors include mucoepidermoid carcinomas, sarcomas, carcinoids, lymphomas, and melanoma. Common symptoms include dyspnea, cough, hemoptysis, wheeze (or “asthma”), stridor, and hoarseness. Distant metastases are rare.
The Impact of Audit Employee Job Satisfaction on Audit Quality

I exploit a novel office-level dataset on employee job satisfaction from Glassdoor.com and a natural experiment based on local precipitation during the auditing time period to examine the effect of audit employee job satisfaction on audit quality. I find that a unit increase in job satisfaction (on a scale from 1 to 5) decreases absolute abnormal accruals by 0.7 standard deviations. Using AAERs, “Big R” and “Little r” restatements, I find that more satisfied audit employees are more likely to detect significant accounting irregularities, but not minor accounting errors. Among job satisfaction indicators, these effects are driven by management quality and career opportunities. Overall, this evidence demonstrates the importance of individual audit employees to the audit process and has practical implications for audit firms’ treatment of employees and audited firms’ information environment.
Optically pumped rare gas lasers (Conference Presentation)

There have been concerted efforts to develop high-energy diode-pumped alkali vapor lasers (DPAL). These hybrid gas phase / solid-state laser systems offer possibilities for constructing high-powered lasers that have high beam quality. DPAL's utilize excitation of the alkali metal 2P3/22S1/2 transition, followed by collisional relaxation and lasing on the 2P1/2-2S1/2 line. Considerable progress has been made, but there are technical challenges associated with the reactivity of the metal atoms. Rare gas atoms (Rg) excited to the np5(n+1)s 3P2 configuration are metastable and have spectral properties that are closely similar to those of the alkali metals. In principle, optically pumped lasers can be constructed using excitation of the np5(n+1)p  np5(n+1)s transitions. We have demonstrated gain and lasing for optically pumped Ne*, Ar*, Kr* and Xe*. Three-level lasing schemes were used, with He as the collisional energy transfer agent that established the population inversion. These laser systems have the advantage using inert reagents that are gases at room temperature, with excellent potential for closed-cycle, multi-wavelength operation. The primary technical difficulty for the rare gas laser is the discharge production of sufficient Rg* metastables in the presence of >200 Torr of He. We have developed a high frequency pulsed discharge that yields >10^13 /cm^3 Ar* in the presence of He at pressures up to 730 Torr. Using this discharge, a diode pumped Ar* laser providing 4.1 W of continuous wave output has been demonstrated, with an optical conversion efficiency of 31%. Further development of the pulsed discharge system, lasing demonstrations with Xe* and preliminary experiments with dielectric barrier discharges will be discussed.
Implications of current reference structures for authority work in online environments

Cette etude est consacree a la recherche du pourcentage d'entrees auteurs vides dans le fichier autorite de la Library of Congress. Les resultats qui denombrent 65% d'entrees auteurs individuels ne contenant pas de references, soulignent l'importance d'un controle du fichier autorite, notamment dans la perspective de l'automatisation d'un fichier manuel
Limitations of spectral measures and observations of the group structure of surface waves

Wave-group structure, which plays a significant role in flux processes and the mechanics of the transfer of wave energy and momentum to the mean current field, is studied. The origin of wave groups, in particular sideband instabilities, the effects of amplitude variations on wave frequency and of wave damping on isolated groups, and flow separation over waves, is discussed. The mechanisms that cause the group formation are compared to the dynamics that result in wave propagation. The bifurcation and shift in wave modulations, and the possible existence of a unique asymptotic statistical state for the wave-modulation field are examined.
Culture-Negative and Culture-Positive Sepsis: A Comparison of Characteristics and Outcomes

BACKGROUND:The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive
Poverty and survival in targeted immunotherapy clinical trials.

10034Background: Whether precision medicine trials—which tailor medical treatment to a patient’s individual tumor characteristics—should include poverty as an outcome predictor is unknown. In Child...
Neuropsychological test performance in depressed and nondepressed collegiate athletes following concussion.

OBJECTIVE To examine neuropsychological test differences following concussion between collegiate athletes screening positive and negative for depression. METHOD Participants included 113 (91 male) college athletes, who were assessed at baseline and following diagnosis of sport-related concussion (SRC). The Beck Depression Inventory-Fast Screen was used as a screener for depression. Athletes were categorized as either depressed (≥4) or nondepressed (<4) following injury and compared on composites for memory and attention-processing speed. Groups were also compared on reliable change index scores from baseline, as well as on proportion of impaired scores. RESULTS Depressed athletes performed significantly worse than did nondepressed athletes on the Memory Composite (p = .04, d = .51) but not on the Attention-Processing Speed Composite score (p = .15, d = .46). Chi-square tests indicated that, compared with nondepressed athletes, a significantly higher number of depressed athletes showed reliable decreases on the following test indices: Verbal Memory Composite of the Immediate Post-Concussion Assessment and Cognitive Testing (p = .03, φ = .21), Brief Visuospatial Memory Test-Revised Total (p = .02, φ = .22), and Hopkins Verbal Learning Test-Revised Total (p = .05, φ = .19). Chi-square test indicated that, compared with nondepressed athletes, a significantly higher proportion of depressed athletes met criteria for impairment (p = .02, φ = .23). CONCLUSION Whether examining the data at the intraindividual or group level, there are memory deficits associated with the combination of an SRC and depression. The results highlight the importance of screening for depression to provide a more complete picture of an individual's functioning postconcussion. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Basic Data Types

It is often an impulsive tendency among programming students to dismiss data types as a less than impactful topic. After all, Scala is inferring the type for each expression or variable for you, and since there are so many other topics to learn, why spend the upfront time on a seemingly minor topic, right? Not only that, but in many introductory computer science languages, the type system is neglected entirely. Why, then, is it important to understand the difference between data types?
A Notion of Optimal Packings of Subspaces with Mixed-Rank and Solutions

We resolve a longstanding open problem by reformulating the Grassmannian fusion frames to the case of mixed dimensions and show that this satisfies the proper properties for the problem. In order to compare elements of mixed dimension, we use a classical embedding to send all fusion frame elements to points on a higher dimensional Euclidean sphere, where they are given “equal footing.” Over the embedded images—a compact subset in the higher dimensional embedded sphere—we define optimality in terms of the corresponding restricted coding problem. We then construct infinite families of solutions to the problem by using maximal sets of mutually unbiased bases and block designs. Finally, we show that using Hadamard 3-designs in this construction leads to infinitely many examples of maximal orthoplectic fusion frames of constant-rank. Moreover, any such fusion frames constructed by this method must come from Hadamard 3-designs.
An integrated computational materials engineering-anchored closed-loop method for design of aluminum alloys for additive manufacturing

Abstract A closed-loop approach based on integrated computational material engineering was used to design, fabricate and characterize an Al–1.5Cu–0.8Sc–0.4Zr (wt%) alloy for laser powder bed fusion additive manufacturing (AM). Finalization of composition and prediction of solidification behavior and mechanical properties were done using calculation of phase diagrams (CALPHAD) and analytical tools. The microstructure of the printed alloy in as-built condition consisted of crack-free regions with fine-equiaxed grains which was consistent with CALPHAD results. Yield strength (YS) of ~349 ± 8 MPa was also in more than 90% agreement with predicted YS. The findings demonstrate an efficient methodology for application-based alloy design for AM.
Effect of crypto currency on the government backed currency

Abstract. As international financial systems are becoming political tools to manipulate the exchange of money for good, cryptocurrency, and its potential to avoid the international banking system becomes more popular. Thus, the question becomes what happens to the nation’s monitory system if cryptocurrency’s electronic payment transaction and system replace the current system? Most nation’s central bank controls the financial systems, which affect institutions, rules, regulations, and laws of the land that affect this system. Robinson (2016) suggests money as a commodity in the national scope. International banks use BIC for transferring money with each other. Cryptocurrency, so far, does not need BIC to transfer money from one location to another. Bitcoin, the system is a peer-to-peer internet currency allowing verified, and decentralized transfers of value between individuals and businesses. This article is a short introduction discussing the legacy money and cryptocurrency and the potential of cryptocurrency as a new currency and its possible implications. Keywords. Cryptocurrency, Blockchain, Currency, Money, Bitcoin, BIC, SWIFT. JEL. O30, O35, O36.
Identification and Treatment of Opioid Withdrawal and Opioid Use Disorder in the Emergency Department

Introduction Opioid addiction and misuse constitute a public health crisis in the United States. Recent research supports buprenorphine induction in the emergency department (ED) setting for patien...
Total Synthesis of Novel Skeleton Flavan-Alkaloids

The first total synthesis of novel skeleton natural compounds kinkeloids A and B, a group of newly discovered flavan alkaloids isolated from the African plant Combretum micranthum, are described in this study. The key and final step are achieved by Mannich reaction, through which the piperidine moiety couples to the flavan moiety. The identities of synthesized kinkeloids were further confirmed through a comparison with the ones in the plant leaves extract using LC/MS.
Commitment to Competition: An Assessment of Antitrust Agency Budgets since 1970

In these remarks to the Industrial Organization Society, I discuss the adequacy of antitrust enforcement resources in the U.S. Relevant resources are measured by the competition budgets of the Justice Department and the Federal Trade Commission. Since 1970 these have been influenced by the overall economy, its changing structure, and politics, but they have not kept up with the pace of mergers or other measures of the need for antitrust. Thus at present, the resources devoted to antitrust fall well short of what is required for continued vigilance over our growing and changing economy.
The lipid droplet—a well-connected organelle

Our knowledge of inter-organellar communication has grown exponentially in recent years. This review focuses on the interactions that cytoplasmic lipid droplets have with other organelles. Twenty-five years ago droplets were considered simply particles of coalesced fat. Ten years ago there were hints from proteomics studies that droplets might interact with other structures to share lipids and proteins. Now it is clear that the droplets interact with many if not most cellular structures to maintain cellular homeostasis and to buffer against insults such as starvation. The evidence for this statement, as well as probes to understand the nature and results of droplet interactions, are presented.
Diverse routing in WDM optical networks with shared risk link group (SRLG) failures

We study the diverse routing problem in WDM optical networks with SRLG failures. We consider a more general case of SRLG failures than those considered in Datta and Somani (2004) and Doucette and Grover (2002). All the optical links in an SRLG share a common endpoint. In addition, a link can belong to arbitrary number of SRLG groups and an SRLG may include more than two links. We develop a polynomial time optimal algorithm to find a pair of least cost SRLG-disjoint paths between a source and a destination. We prove the correctness of the algorithm which is also shown to be more time efficient than the graph transformation based algorithm of Datta and Somani (2004).
COMMON AGRICULTURAL POLICY: A EUROPEAN JOURNEY - THEN, NOW AND THE FUTURE

The reform process of the CAP has been, till now, driven by market and financial factors. The Mid Term Review, however, reveals that new important issues have emerged. The impact of the next main events, the ongoing WTO Round and the enlargement, on the CAP are examined. The analysis shows that the Mid Term Review is mainly inspired by an attempt to deliver a prompt political response to the concerns of EU citizens, although, on the market side, it goes beyond the line drawn by Agenda 2000 anticipating part of the reform supposed to be needed after 2006 in preparation of the CAP for the enlarged EU. The new tools introduced by the Proposal may be seen to contribute at restoring market conditions in the EU agricultural sector and at promoting higher level of positive externalities output. After a preliminary examination of the new reform Proposal, the document highlights the main difficulties it may encounter in the approval process, the questions that need to be explored and the inconsistencies with the main long term goal of the European model of agriculture.
Attacks on the Warren Court by State Officials: A Case Study of Why Court-Curbing Movements Fail

The Warren Court's many decisions expanding federal power provoked a series of state-based Court-curbing proposals that would have reduced the Court's power over the states so radically as to transform the nation into a virtual confederation. In addition to reviving the doctrine of interposition, state officials developed and promoted constitutional amendments that would have excluded Congress from the amendment process and would have created a so-called "Court of the Union" composed of the fifty state chief justices, which could have overruled the Supreme Court on issues affecting the states. These amendments made considerable headway and generated much controversy but are now virtually forgotten. In addition to analyzing the origins, progress, and defeat of these and other measures, the article places this neo-confederate movement in the larger context of Court-curing movements through U.S. history, explaining that the efforts failed because the proposals were largely tactical rather than practical; even the state officials who opposed Warren Court decisions had reasons to wish to preserve the Court's power; organizational and institutional obstacles impeded the proposals; elites successfully rallied public opposition to the proposals; the Court's opinions were broadly consistent with public opinion; public respect for the Court remained resilient; and economic conditions discouraged Court-curbing.
Oxygen‐rich mass loss from carbon‐rich stars—some implications

We have evaluated the degree of dust to gas coupling in the atmospheres of red giant stars, and find non‐zero drift velocities. Chemical fractionation of the stellar atmosphere on an evolutionary timescale is implied.
The D/H Ratio in Molecular Clouds

This paper summarizes our understanding of the dominant D-reservoirs in molecular clouds and suggests possible direct determinations of the Dabundance. It is concluded that rotational HD lines from shock regions provide the best way to determine the gas phase Dabundance. In cold dense cores, the dominant gas phase D-reservoir is likely to be atomic D, because of expected inefficient HD formation on grain surfaces. The gas phase Dabundance derived from observations of dense cores is ≈5x10-6 /n4 (with n4 the total density in units of 104 cm-3). A large fraction of the D (≈50%) may be locked up in deuterated molecules in grain mantles. A small fraction (≈2%) may be locked up in the photolyzed residues of such grain mantles. PAHs will also be deuterated (PADs), containing ≈1% of the D. Finally, it is likely that all of these processes have contributed to the D-enrichment observed in solar system materials.
ISOTOPE SHIFT BETWEEN 209BI AND 6.3-DAY 206BI

The hyperfine structures of 206Bi (6.3 day) and 209Bi (1018 year) have been measured with the use of a 10-m focal-length Czerny–Turner grating monochromator, and the isotope shift between them was obtained. The radioactive isotope 206Bi was produced by proton bombardment of 208Pb. A radiochemical procedure was developed for separating the radioactive bismuth from the lead target and transferring it into an electrodeless lamp. The light source contained about 10 ng of 206Bi. From an analysis of the hfs in the 6p3 S412 and 6p27s P412 states, a value of 121±13 mK was obtained for the 206Bi–209Bi isotope shift in the 3067-A resonance line. The possible effect on this value of perturbations by other isotopes is discussed.
Free-flying Shuttle payloads - An extrapolation of sounding rocketry into the Shuttle era

A concept is described for flying scientific and other instruments on the Shuttle, using a free-flying payload. Low costs are maintained by minimizing interfaces with the Space Transportation System and by assembling the payload using modified sounding rocket hardware. This approach allows all Shuttle missions to be considered for scientific missions and gives the Spacelab program the freedom to concentrate on those missions which can take special advantage of supervision by the Orbiter crew.
Rivanol-ethanol fractionation of parotid fluid and colostrum.

Die Reihenfraktionierung durch Rivanol und athylalkohol wird mit Vorteil fur die Trennung von Speicheleiweisskorpern verwendet: Immunglobulin A des Speichels und der Vormilch erscheint in zwei Formen, von denen die eine gegenuber Rivanol widerstandsfahig ist, wahrend die andere durch Rivanol gefallt wird. Von der ursprunglich angesetzten Speichelamylase erscheinen 75% in hohem Reingehalt in der durch Rivanol und athylalkohol fallbaren Phase. Das gesamte Verfahren beansprucht 6 Stunden.
Stability of Choices about Life-Sustaining Treatments

Objective: To examine the stability of patients' choices for life-sustaining treatments. Design: A longitudinal cohort study. Setting: Primary care practices in central North Carolina. Patients: Me...
The Shropshire Schizoid and the Machines of Modernism

In “The Shropshire Schizoid and the Machines of Modernism” Edward P. Comentale considers the work of A. E. Housman, D. H. Lawrence, and Wyndham Lewis in order to engage with modernism from a perspective indebted to the theories of Deleuze and Guattari. Comentale thus intervenes polemically in recent attempts to rethink and revise scholarly conceptions of Modernism. “The Shropshire Schizoid” argues that critical understanding of Modernism should not be based on oedipal accounts of Modernist textuality that construe desire as founded upon lack. In his detailed readings of key works by Housman, Lawrence, and Lewis, Comentale seeks to elaborate a reading practice which returns us to Modernism's original generative power, its capacity to create new articulations of desiring-production within the circuits and flows of capitalist modernity. Contending that criticism is insufficiently attentive to the explosive impact of desire within Modernist art and writing, Comentale suggests that it should be more attuned to...
Energy balance of six common landscape surfaces and the influence of surface properties on gas exchange of four containerized tree species

Abstract Gas exchange and growth of woody landscape plants is strongly affected by underlying surfaces. In urban areas, plants are subjected to energy balance characteristics of a variety of surfaces. We investigated energy balance properties of six urban surfaces: asphalt, gravel rock mulch, lava rock mulch, concrete, pine bark mulch, and turf. Each summer over a 3-year period, incoming global shortwave radiation, surface temperature, surface reflectivity (albedo), soil temperature below each surface, and soil heat flux were measured for each surface, and total incoming radiation, thermal conductivity, and longwave radiation emitted by each surface were calculated. Differences in surface properties were analyzed by regression analysis. Albedo was greatest for concrete and least for lava rock mulch, while thermal conductivity was greatest for asphalt and least for lava rock and pine bark mulches. Under maximum incoming total radiation, regression analysis indicated: soil heat flux was greatest under asphalt and concrete and least under lava rock and pine bark mulches; soil temperature below each surface was greatest for asphalt and concrete and least for pine bark mulch; surface temperature was greatest for pine bark mulch and least for turf; and longwave radiation flux of each surface was greatest for pine bark mulch and least for turf. This research revealed that more energy was conducted into the soil below asphalt and concrete, and that a greater portion of incoming radiation was prevented from entering the soil below pine bark and lava rock mulches than below other surfaces. Due to these effects, and the lack of evaporative cooling, surface temperatures were greater, and more longwave radiation was emitted from non-vegetative surfaces than from turf. In a concurrent study, we investigated if the energy balance of turf, pine bark mulch, and asphalt surfaces influenced gas exchange of four containerized tree species grown over each surface. On several occasions over a 2-year period, morning-to-evening measurements of stomatal conductance, leaf temperature, and plant water loss were made on containerized Bechtel crabapple (Malus ionensis ‘Plena’), Norway maple (Acer platanoides ‘Crimson King’), globe willow (Salix matsudana ‘Navajo’) and American plane tree (Platanus occidentalis). Leaves over pine bark mulch and asphalt intercepted more longwave radiation and generally had greater leaf temperature and leaf-to-air vapor difference than leaves over turf. As a result, trees over non-vegetative surfaces generally had lower stomatal conductance and water loss than trees over turf.
Pauli-Algebraic Operators in Polarization Optics*

Techniques for analysis and synthesis of linear optical systems involving polarization effects are related and extended through fuller exploitation of the algebra of complex 2 × 2 matrices.
Pathogenesis of osteopetrosis in the ia rat: reduced bone resorption due to reduced osteoclast function.

Osteopetrosis, a skeletal condition characterized by excessive accumulation of bone, is an inherited disease in man, rats and mice. In ia rats the condition undergoes spontaneous permanent remission beginning 30 to 50 days after birth, in contrast to the disease in mice and men. Thus, the ia rat offers a unique opportunity to analyze factors suspected of causing the skeletal condition. In the present investigation bone formation and bone resorption have been measured at various ages in ia rats and normal littermates. Bone matrix formation, measured by 3H-proline uptake, was decreased slightly during the first three postnatal weeks and elevated slightly thereafter. Bone resorption, stimulated by injection of parathyroid extract, was determined in vivo as the rate of release of 3H from bone after incorporation of 3H-proline. Bone resorption was reduced 20% at two weeks and elevated 20% by three weeks. Administration of parathyroid extract or thyroxine, or a deficiency of thyrocalcitonin produced by thyroidectomy (supplemented with thyroxine), did not hasten remission. An abnormally high cytoplasmic concentration of acid phosphatase activity was observed in ia osteoclasts during the first two weeks. The skeletal signs of spontaneous remission, appearing between 30 and 50 days after birth, were preceded by a normal response of the serum calcium to exogenous parathyroid extract, by increased bone resorption and by a more normal cytoplasmic distribution of acid phosphatase activity during the third postnatal week. These observations are interpreted to indicate that the osteopetrotic condition of ia rats is not due to deficiencies of parathyroid hormone or thyroxine or an excess of thyrocalcitonin but results from failure of osteoclasts to respond to stimuli promoting resorption. Specifically, these cells seem able to synthesize but not release normal amounts of the lysosomal enzyme acid phosphatase.
The clock in the mouse retina: melatonin synthesis and photoreceptor degeneration

Melatonin is synthesized rhythmically under control of circadian oscillators by the retinas of non-mammalian vertebrates. Here we report that the retinas of some strains of laboratory mice exhibit robust circadian rhythms of melatonin synthesis which can be entrained by light in vitro. The rd mutation results in progressive loss of the rod and later cone photoreceptors. In mice homozygous for rd retinal melatonin synthesis is rhythmic at postnatal day 28 but not in older animals. Apparently rod photoreceptors are necessary for the expression of the circadian rhythm of melatonin synthesis but not for the synthesis itself. The many genetic and molecular tools available in the mouse can now be applied to analysis of the retinal circadian oscillator.
Theory of a Thin-Ring Airfoil in an Incompressible Inviscid Source Flow Field

This analysis concerns itself with the loading calculation of a thin-ring airfoil symmetrically positioned in an unbounded spherical source flow field. A spherical source was used to replace the undisturbed, nonparallel, but axisymmetric, freestream. A ring vortex distribution was used to replace the thin-ring airfoil. The thin-airfoil theory not only limits the shape of the airfoil, but also applies only for a small angle σ, between the chord line and the relevant undisturbed source flow rays. With the latter restriction, the distance between the source origin and the midchord of the airfoil, roa of Fig. 2, is considered to be longer than the chord ca and the terms of 0 1roa/ca2 and higher-order terms were neglected in the analysis. The result of the analysis is a set of algebraic equations containing geometric parameters of the flow field. For a given geometry the strength of the ring vortex distribution can be calculated readily.
Dugin, Eurasianism, and Central Asia

Abstract Eurasianism as a concept emerged among Russian emigres in the 1920s, with the premise that Russia is a unique ethnic blend, primarily of Slavic and Turkic peoples. Its geopolitical implications for Russia include gravitation toward mostly Turkic Central Asia. Alexander Dugin, one of its best-known proponents, believes that the demise of the Soviet Union was simply a tragic incident. The people of the former USSR should again be united in a grand Eurasian empire, with Russia a benign and generous patron, providing its “younger brothers” clients economic largesse and defense, mostly against the predatory USA. The “orange revolutions” and the rise of Russian nationalism, for whose proponents a restored imperial presence is rather marginal, indicate that Eurasianism—along with the dream of the resurrection of the USSR—is becoming less viable.
Exact wavefunctions for the one-dimensional gravitational gas

Abstract An exact solution is exhibited for the Schrodinger equation for the one-dimensional gravitational gas. The boson ground state energy is also calculated.
Responses to 9/11 reveal opportunities— and barriers—for commercial ADR

The fallout for conflict resolution professionals from the terrorist attacks of Sept. 11, 2001, strikes at the core of their existence: What do they do? What do they provide? Maria R. Volpe and Staci Strobl, of New York, have been looking broadly at the question of “deliverables” since 9/11. They discuss the business ADR aspects of that research, and provide lessons the profession should have learned.
Effects of Esthetic Surroundings: II. Prolonged and Repeated Experience in a “Beautiful” and an “Ugly” Room

(1956). Effects of Esthetic Surroundings: II. Prolonged and Repeated Experience in a “Beautiful” and an “Ugly” Room. The Journal of Psychology: Vol. 41, No. 2, pp. 459-466.
Enhancement Of Dissolution Rates Of Poorly Water‐Soluble Drugs By Crystallization In Aqueous Surfactant Solutions I: Sulfathiazole, Prednisone, And Chloramphenicol

Effects of crystallization of poorly water-soluble drugs in aqueous surfactant solution on in vitro dissolution rates were investigated. Marked enhancement was observed for chloramphenicol, sulfathiazole, and prednisone. Differential thermal analysis studies indicated the presence of small amounts of surfactant in surfactant-treated crystals. Possible mechanisms of dissolution enhancement are discussed.
Ultrasound of Pediatric Musculoskeletal Disease: From Head to Toe

Ultrasound (US) can be used to evaluate a variety of musculoskeletal pathologies related to developmental anomalies, most commonly developmental dysplasia of the hip (DDH), infection, inflammation, and trauma. US has unique advantages in evaluation of the immature bone in children. It is possible to directly visualize the cartilaginous epiphyses that are not demonstrated on radiographs, joints, and soft tissues. US is safe and does not involve ionizing radiation or the need for sedation. US also has the advantage of real-time imaging, which can be useful in evaluation of subluxation or clicking syndromes.
Bioorthogonal Small Molecule Imaging Agents Allow Single-Cell Imaging of MET

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that has emerged as an important cancer target. Consequently, a number of different inhibitors varying in specificity are currently in clinical development. However, to date, it has been difficult to visualize MET expression, intracellular drug distribution and small molecule MET inhibition. Using a bioorthogonal approach, we have developed two companion imaging drugs based on both mono- and polypharmacological MET inhibitors. We show exquisite drug and target co-localization that can be visualized at single-cell resolution. The developed agents may be useful chemical biology tools to investigate single-cell pharmacokinetics and pharmacodynamics of MET inhibitors.
Polarized microtubule arrays in apical dendrites and axons

The polarization of microtubules within neurons in vivo is crucial in their role of determining the directions and speeds of intracellular transport. More than a decade ago, electron microscopy studies of mature hippocampal cultures indicated that their axons contained microtubules of uniform polarity and that dendrites contained microtubules of mixed polarity. Here, we evaluated polarity distributions in native brain tissues and in cultures by using multiphoton microscopy and second-harmonic generation from microtubules. We confirmed the expected polarized microtubule arrays in axons; however, we also unexpectedly found them ubiquitously in apical dendrites of mature hippocampal CA1 and cortical layer V pyramidal neurons. Some of these organized dendritic microtubule arrays extended for >270 μm with overall polarity of >80%. Our research indicates neurite-specific and age-dependent microtubule organizations that have direct implications for neuronal cargo transport.
A CASE STUDY OF A JAPANESE CHILD LEARNING ENGLISH AS A SECOND LANGUAGE1,2

Major findings are reported here of a longitudinal, naturalistic study of the acquisition of English as a second language by a five-year old Japanese girl. The emphasis is on empirical findings based on careful distributional analyses performed on the data, rather than on any particular theoretical orientation. The major content areas discussed are 1) the problem of prefabricated patterns (Hakuta 1974b); 2) the order of acquisition of grammatical morphemes; and 3) the problem of language transfer. It is argued that there is still great need for a broader empirical data base before any serious attempts at theoretical formulations of the second language acquisition process are made.
A compact, 1-MV, 6-kA radiography source with a onemeter extension and right-angle bend

The Hybrid Radiation Source (HRS) is a compact pulsed power generator consisting of a commercial flash x-ray system that has been retrofitted with a custom front-end assembly, replacing a sealed glass tube1. A new high impedance (∼120 Ohm) space-charge-limited (SCL) diode was fielded on the HRS. This diode produces a ∼ 1.6 mm diameter x-ray spot suitable for high-resolution radiography2. This system has been modified by extending the diode from the generator with a one-meter-long vacuum transmission line. Also, the anode has been oriented to point perpendicular to the transmission-line axis. The extension and re-direction allow for the placement of the high-yield, small-spot-size, HRS radiographic source in previously unreachable locations. Parameters such as voltage, current, and source size have been measured and analyzed, allowing for optimization of the radiographic source. Discussion will also include circuit diagrams, simulation models, and diagnostic traces.
Photophysical behavior of transition metal complexes having interacting ligand localized and metal-to-ligand charge transfer states

Abstract Transition metal complexes having metal-to-ligand charge transfer (MLCT) excited states have been extensively investigated as sensitizers in light-induced electron transfer reactions. The photophysical behavior of the complexes is strongly dependent on the ligand serving as the electron acceptor. In systems where ligand localized triplet excited states are close in energy to the thermally equilibrated 3 MLCT state, strong interaction between the states is observed. This article provides an overview of the unique photophysical behavior observed in systems of this type.
Evaluation of Mitral Regurgitation by Doppler E chocar diogr aphy

The diagnosis and assessment of mitral regurgitation has been one of the main challenges for cardiac ultrasound. Imaging techniques (M-mode and two-dimensional echocardiography) provide direct morphologic and etiologic information of the evaluation of patients with suspected mitral regurgitation. The advent of cardiac Doppler increased tremendously the ability to evaluate mitral regurgitation noninvasively. Continuous-wave and pulsed Doppler have been found to be sensitive and specific in the detection of mitral regurgitation. The introduction of color flow Doppler simplified enormously the assessment of patients with suspected mitral regurgitation. The maximal regurgitant area and maximal regurgitant area corrected for left atrial size have become the most commonly used parameters to evaluate mitral regurgitation by color flow Doppler in the clinical setting. However, the color regurgitant jet area is highly dependent on anatomical, hemodynamic, and equipment factors. A new method, based on the proximal isovelocity surface area, is being evaluated and appears to be relatively independent of equipment factors. Transesophageal echocardiography has been shown to be exquisitely sensitive in the detection of mitral regurgitation. Quantitation of mitral regurgitation by transesophageal echocardiography is currently based on the maximal regurgitant area and this parameter appears to correlate closely with the angiographic degree of mitral regurgitation. Pulmonary venous flow analysis had been used in conjunction with color flow mapping for the evaluation of mitral regurgitation by transesophageal echocardiography. The presence of reversed systolic flow has been shown to be sensitive and specific for the diagnosis of severe mitral regurgitation. Patients with clinically difficult surface studies, flail mitral valve leaflets, and prosthetic mitral valve are best evaluated by the transesophageal approach with interrogation of pulmonary venous flow. (ECHOCARDIOGRAPHY, Volume 8, November 1991)
Behavioral organization is independent of locomotor activity in 129 and C57 mouse strains.

Assessing locomotor behavior is a standard methodology to characterize the behavioral phenotype of a genetic manipulation. Typically, levels of locomotor activity are measured using various methods that are based on the frequency of photobeam breaks or distance traveled as assessed by video-tracking systems. Locomotor behavior, however, is multi-dimensional and reflects the combined influences of multiple processes. Here, we examine the number of independent dimensions of locomotor behavior in mice based on measures derived from a video-tracking system. In addition, we test the hypothesis that locomotor behavior varies substantially across mouse strains. 84 mice were tested for 30 min in a 41 × 41 cm enclosure. Based on previous investigations in rats, we also assessed the spatial and dynamical aspects of locomotor behavior using the spatial scaling exponent, d, and the dynamical entropy, h. A principal component analysis and a one-way repeated measure ANOVA were conducted. C57 mouse strains differ substantially from 129 mouse strains on almost all measures of locomotor behavior. The principal component analysis revealed that two independent factors influence this set of measures. The first factor reflects the amount or level of locomotor activity, the second factor quantifies the degree of spatial and dynamical organization of behavior. These strain differences and the existence of at least two independent dimensions when measuring locomotor behavior may help to parse the effects of gene manipulations relative to strain differences in mutant mice.
Digestion of fibrin by thrombin.

Abstract Thrombin of high purity and free of plasmin clotted and then solubilized clots of fibrinogen free of plasminogen. Polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate and 1-chloro-3-tosylamido-7-amino-2-heptanone revealed fewer bands than in corresponding digests of fibrinogen by plasmin.
Abstract 1667: Pathway analysis of bladder cancer genome-wide association study identifies several novel pathways involved in bladder cancer development

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Recent genome-wide association studies (GWAS) have identified multiple genetic variants associated with bladder cancer risk but only explain a small fraction of the inherited variability. A recurring problem in traditional GWAS analysis (i.e., single-SNP analysis) is the lack of consideration of biological pathways that contains network of genes with subtle, undetectable effect at the single SNP or single gene level. Application of innovative secondary analyses focusing on genes and pathways will complement and expand traditional GWAS analysis and identify novel genes and pathways that are associated with bladder cancer risk. We used the genome-wide scan data from MD Anderson's bladder cancer case control study to identify cellular signaling pathways involved in bladder cancer tumorigenesis. Gene set enrichment analysis (GSEA) was applied as a secondary analysis of our previous bladder cancer GWAS data. GSEA can detect subtle effects of multiple SNPs in the same gene set, and multiple genes in the same biological pathway, which are often missed in traditional GWAS analysis. Using three GSEA approaches (Gen-Gen, Aligator, and SNP Ratio Test), we consistently identified 18 pathways significantly associated with bladder cancer risk. The top pathways included two cell cycle pathways involved in the G1/S transition (PGenGen: 0.001, PAligator: 0.001, PSRT: 0.002), neural cell adhesion molecule (NCAM) pathway (PGenGen:<0.001, PAligator: 0.020, PSRT: 0.014), platelet-derived growth factor (PDGF) induced intracellular pathway (PGenGen: <0.001, PAligator: 0.026, PSRT: 0.006) and unfolded protein response pathway (PGenGen: 0.007, PAligator: 0.001, PSRT: <0.001). We identified that CCNE1 rs8110447 and rs8102137 were the most significant SNPs and gene in the two cell cycle pathways. As previously reported in GWAS, CCNE1 at 19q12 is a hotspot for bladder cancer susceptibility. However, other pathways with known susceptibility genes, such as those containing GSTM1, were not significant in the GSEA analysis, suggesting that this approach has identified novel biological pathways involved in bladder cancer tumorigenesis. Future studies are needed to validate in independent population. Overall, these findings contribute to a coherent understanding of the overall gene networks involved in bladder cancer susceptibility as well as offer additional etiologic insights highlighting the specific genes and pathways involved. 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 1667. doi:1538-7445.AM2012-1667
New evidence on the origin of methane in hydrothermal gases

Abstract A 250°K difference between calculated hydrogen isotope temperatures and calculated carbon isotope temperatures, the presence of other aliphatic hydrocarbons, and negative radioactive data are collectively interpreted to mean that chemical reaction between carbon dioxide and molecular hydrogen is probably not the primary source of methane in these features.
Cell wall lipopolysaccharide damage in Escherichia coli due to freezing.

Abstract Freezing and thawing of Escherichia coli in water suspensions produce uninjured, nonlethally injured, and lethally injured cells as determined by their ability to multiply under different conditions. These treatments do not affect the microscope count or the optical density of the suspensions. The nonlethally injured cells develop extreme sensitivity to deoxycholate, lauryl sulfate, actinomycin D, and lysozyme. Lethally injured cells can be lysed by lysozyme as measured by the reduction in microscope count and optical density. These results have suggested that the outer membrane of the cell wall, which acts as a protective barrier in normal cells, has been damaged during freezing. In nonlethally injured cells, the damage can be repaired in K 2 HPO 4 solutions. Reduction in the adsorption efficiency of the T-series phages indicated that the lipopolysaccharide, and not the lipoprotein of the outer membrane of the cell wall, is damaged in the frozen cells.
Buoyancy effects on a turbulent shear flow

The effects of buoyancy on the structure of a turbulent flow with uniform velocity, temperature, and concentration gradients in the vertical direction are studied theoretically on the basis of a statistical turbulent-flow model. The study shows that the three components of the turbulent kinetic energy, the mean square temperature fluctuation, the Reynolds stress, the turbulent heat transfer, and the turbulent mass transfer are all enhanced under unstable conditions and suppressed under stable conditions. The turbulent heat transfer is more strongly affected by the buoyancy than the Reynolds stress, so that the ratio of the eddy conductivity to the eddy viscosity decreases at increasing Richardson numbers. The buoyancy affects the turbulent heat transfer and the turbulent mass transfer in the same manner. Comparison with experimental data shows satisfactory agreement for most of the turbulent properties.