cssi/SciSciGPT-SciSciNet huggingface dataset:
Chapter 20. Biosynthesis and genetic engineering of lipopeptides in Streptomyces roseosporus.

Abstract Daptomycin is an acidic cyclic lipopeptide antibiotic approved for treatment of infections caused by Gram‐positive pathogens, including Staphylococcus aureus strains resistant to other antibiotics. Daptomycin biosynthesis is carried out by a giant multisubunit, multienzyme nonribosomal peptide synthetase (NRPS). The daptomycin ( dpt ) biosynthetic genes have been cloned in a bacterial artificial chromosome (BAC) vector, sequenced, and expressed in Streptomyces lividans . Several of the dpt genes, including the three NRPS genes, are transcribed as a lengthy polycistronic message. The daptomycin‐producing strain, Streptomyces roseosporus , can be genetically manipulated, and a number of deletion mutants encompassing one or more of the dpt genes have been constructed. Several of the dpt genes have been expressed from ectopic chromosomal loci (ϕC31 or IS 117 attB sites) under the transcriptional control of the strong constitutive ermEp * promoter, and recombinant strains produced high levels of lipopeptides, thus establishing a trans ‐complementation system for combinatorial biosynthesis. A number of hybrid NRPS subunits have been generated by λ‐Red‐mediated recombination, and combinatorial libraries of lipopeptides have been generated by NRPS subunit exchanges, module exchanges, multidomain exchanges, deletion mutagenesis, and multiple natural lipidations, using the ectopic trans ‐complementation system in S. roseosporus .
Therapeutic Options in Multiple Myeloma: Focus on Bortezomib

Myeloma is the most frequent malignancy to involve the bone. The bone microenvironment plays an important role in supporting tumor growth, bone destruction and resistance to chemotherapy. Until the advent of novel therapies such as bortezomib, the prognosis for patients with myeloma did not change significantly over 40 years. The median survival of patients until 1996 was approximately 30 months, and has now improved to almost 5 years. Bortezomib is the first-in-class proteasome antagonist approved for treatment of myeloma. It is active in newly diagnosed, relapsed and refractory patients and is now being used as a platform for combinations with other new agents for myeloma. Its major side effects include neuropathy and thrombocytopenia. In addition to its anti-myeloma effect, bortezomib also targets the bone microenvironment and can inhibit osteoclast formation, and stimulate osteoblast activity in patients with myeloma. Potentially, combination of bortezomib with other agents that stimulate bone formation or block bone resorption will further enhance the anti-myeloma effects of bortezomib and overcome the contribution of the tumor microenvironment to myeloma growth. Multiple myeloma (MM) is a primary plasma cell malignancy, which is the most frequent malignancy to involve the bone. Over 80% of patients with MM have bone involvement during the course of their disease. 1 The prognosis for patients with MM had not changed significantly over the last 40 years until the last 5 years. 2 The median survival of patients up to 1996 was approximately 30 months, and this has now improved to almost 5 years with the advent of newer therapies. The new therapies that have made a major impact on the survival and quality of life in MM patients have been the introduction of immunomodulatory drugs (IMiDs) and bortezomib, which is the first-in-class proteasome antagonist to come to the clinic. Both the IMiDs, thalidomide and lenalidomide, and bortezomib have been used alone and in combination with dexamethasone as well as with each other to treat MM patients. These agents have increased response rates and prolonged both progression free survival and overall survival of patients with relapsed and/or refractory MM from 12 months to 24 months and newly diagnosed MM from 30 months to 45 months. Further, these drugs also have effects on MM bone disease, either by suppressing osteoclast (OCL) activity or in the case of bortezomib enhancing osteoblast (OBL) activity. In this review, we will examine the mechanism of action of bortezomib and its capacity to target MM cells as well as the marrow microenvironment in patients with MM.
Diffusion, Drifts, and Modulation of Galactic Cosmic Rays in the Heliosphere

Abstract The role of particle drifts in the heliospheric transport of cosmic rays is reviewed. The basic transport-theory is outlined, the most profound effects of drifts are interpreted. Experimental material seems to be in favour of the drift concept. A new, more advanced 3-D model incorporating a non-uniform solar wind speed, rising away from the wavy neutral sheet is introduced and some preliminary results are presented. Among others, the model correctly predicts the negative latitudinal gradient of cosmic ray intensity that appeared during the last solar minimum, and disappeared as the tilt angle of the sheet increased. Also, radial gradients predicted for the two polarity cycles become closer to each other. Possible modulation effects beyond the solar wind termination shock are discussed. Preliminary results suggest that, at lower energies, a substantial part of modulation may occur beyond the shock.
Observation of bound-free transitions of the linear Ar⋯I 2 (X, v″ =0) complex in and above the I 2 B-X spectral region

Laser-induced fluorescence and action spectroscopy experiments were performed to identify the origin of the Ar...I(2) continuum signals observed in and above the I(2) B-X spectral region. We have verified that these signals arise from transitions of the linear Ar...I(2) (X,v"=0) complex. The data provides no evidence that the excited state complexes undergo a one-atom caging mechanism when prepared above the I(2)(B) dissociation limit, Ar...I(2) (B)*-->Ar+I+I*-->Ar+I(2)(B,v'). Instead, our results indicate that the continuum signals result from bound-free transitions of the linear Ar...I(2) X,v(")=0) complex to the inner repulsive walls of numerous Ar+I(2)(B,v') intermolecular potentials. The bound-free continuum signal associated with transitions to each Ar+I(2)(B,v') potential spans an energy region >700 cm(-1). We have found that the continuum signals turn-on 250(2)cm(-1) above the corresponding I(2) B-X,v'-0 band origin, and this energy represents the binding energy of the linear Ar...I(2) (X,v"=0) conformer, D(0) (")(L)=250(2)cm(-1).
Genetic Variations in the Serotonergic System Mediate a Combined, Weakened Response to SSRI Treatment: A Proposed Model

Abstract Individuals with the short (S) allele in the promoter region of the serotonin transporter gene (5-HTTLPR) show a less favorable response to selective serotonin reuptake inhibitor (SSRI) treatment than individuals with the long (L) allele. Similarly, individuals with the C(-1019)G allele for the mutation found in the promoter region of the serotonin 1A receptor gene (5-HTR1A) have shown blunted responses to SSRI treatment when compared with individuals lacking this polymorphism. While these findings have been replicated across multiple studies, only two studies to date have reported data for a gene-gene interaction associated with response to SSRI treatment. Both of these studies reported a combined effect for these genotypes, with individuals homozygous for the L allele and the C allele (5-HTT L/L – 1A C/C ) reporting the most favorable response to SSRI treatment and individuals homozygous for the S allele and the G allele (5-HTT S/S – 1A G/G ) reporting the least favorable response to SSRI treatment. Additionally, no neural mechanisms have been proposed to explain why this gene-gene interaction has been observed. To that end, this article provides a review of the relevant literature associated with these polymorphisms and proposes a feasible model that describes a genotype-dependent modulation of postsynaptic serotonin signaling associated with the 5-HTT and 5HTR1A gene. Significance Statement: Approximately forty percent of individuals that seek pharmacological treatment for depression do not initially respond to selective serotonin reuptake inhibitor (SSRI) antidepressants. Past research has attempted to determine if specific mutations in genes associated with the serotonergic system can help to predict response to antidepressant treatment; however, results have been inconclusive. Additionally, very little research has examined how multiple mutations can cause a combined, reduced response to SSRI antidepressant treatment. This article provides a review of the relevant literature, offers a model for why individuals with multiple mutations in the serotonergic system show a blunted response to SSRIs, and provides a basis for further research regarding genotype-dependent response to antidepressant treatment.
Incidence of the ponticulus posticus of the first cervical vertebra between ages six to seventeen.

Lateral cephalometric radiographs of 353 young caucasoid orthodontic patients from 6 years to 17 years were examined for the presence of ponticulus posticus of the first cervical vertebra. Visualization of the posterior fossa was not obstructed and in each case the squamous occipital and posterior arch of the atlas could be clearly defined. Of the 353 subjects, 56 (15.8%) showed some degree of a ponticulus posticus. Of these, 24 (14.6%) of 164 were males and 32 (16.9%) of 189 were females, with no apparent sex differences in the occurrence of this anomaly. Those showing a ponticulus were divided on the basis of bilateral complete or incomplete and unilateral complete or incomplete. There were numerous variations in the size and location of the ossification centers in the atlanto-occipital membrane. The youngest female with a ponticulus was six years seven months and the oldest 16 years 11 months, while the youngest male was six years four months and the oldest 16 years five months. Two females with a unilateral partial ponticulus were observed over a one to two year period. During this time a complete unilateral radiopaque ponticulus had developed.
Interaction-based Runtime Verification for Systems of Systems Integration

Complex distributed systems pose great challenges for quality assurance. Size, complexity and concurrency of these systems often render traditional verification techniques impractical. In particular, this is true for systems integration efforts, where additional challenges arise from the independent evolution of the composed systems. Runtime verification provides a systematic strategy for analytical quality assurance of such systems. Key elements of runtime verification are system models, ways to inject these models into the observed system and a framework for analysing and monitoring the runtime behaviour against the models. The approach we present in this article is based on interaction models. We specify expected system interactions using Message Sequence Charts (MSC), from which we generate distributed runtime monitors for each of the components. We use aspect-oriented programming (AOP) techniques to inject the monitors into the implementation of the components. Thereby, we verify the adherence of the distributed system interactions with the MSC model. The focus of this article is the runtime verification in the systems integration domain; here, Enterprise Service Buses (ESB) have emerged as a powerful infrastructure for integrating complex distributed systems. In the context of an ESB we leverage the Spring AOP framework to inject the runtime monitors. As a result we obtain a comprehensive, tool-supported approach for model-based runtime verification of interactions. We demonstrate our approach using the Central Locking System as running example of an integrated embedded system.
Bilateral attritional rupture of the ulnar nerve at the elbow

In a 56-year-old woman with severely deforming rheumatoid arthritis, surgical exploration demonstrated partial rupture of one ulnar nerve and complete rupture of the other.
Pressure Modulation of Exciton Fission in Tetracene

The fluorescence quantum efficiency of tetracene crystals is found to increase rapidly with pressure. This behavior is interpreted as a reduction in the singlet exciton fission rate due to an increase in the energy separation between the singlet exciton state and the triplet exciton pair state. A red shift in the energy of the S0 T1 transition by 15 ± 7 cm−1/kbar is used to explain the experimental results. This shift is discussed in terms of the interactions which control the transition energy. Es wird gefunden, das die Fluoreszenzquantenausbeute von Tetrazen-Kristallen stark mit dem Druck ansteigt, was mit einer Abnahme der Zerfallsrate der Singulett-Exzitonen durch Zunahme der Energiedifferenz zwischen dem Zustand des Singulett-Exzitons und dem Paarzustand des Triplett-Exzitons erklart wird. Es wird eine Rotverschiebung der Energie des S0 T1-ubergangs um 15 ± 7 cm−1/kbar gefunden. Diese Verschiebung wird unter Berucksichtigung der die ubergangsenergie bestimmenden Wechselwirkungen diskutiert.
The Future: The Drive for Shareholder Value and Implications for HRD

The problem and the solution. Increasing shareholder pressure for short-term profits was identified as the number one business trend affecting the human resource development (HRD) profession during the ASTD/AHRD (Academy of Human Resource Development) future search conference and the issue most in conflict with HRD values. Subsequent events have thrown the concept of managing businesses based solely on shareholder value into a state of flux. This article examines the concept of shareholder value and suggests ways HRD professionals can and must influence the debate.
Current Status of Endovascular Devices to Treat Abdominal Aortic Aneurysms

The introduction of endovascular abdominal aortic aneurysm (AAA) repair has revolutionized the therapeutic approach to patients with AAA. Due to an on-going and prolific collaboration between vascular interventionalists and biomedical engineers, the devices used to perform endovascular AAA repair have also changed dramatically. The purpose of this publication is to provide an overview of the currently available and upcoming options for endovascular AAA repair.
Stimulated Actin Polymerization Induces Force Potentiation in Swine Carotid Artery

The phenomenon of post-tetanic potentiation, in which a single submaximal contraction or series of submaximal contractions strengthens a subsequent contraction, has been observed in both skeletal and cardiac muscle.In this study, we describe a similar phenomenon in swine carotid arterial smooth muscle. We find that a submaximal K+ depolarization increases the force generation of a subsequent maximal K+ depolarization - we term this “force potentiation.”Force potentiation was not associated with a significant increase in crossbridge phosphorylation or shortening velocity during the maximal K+ depolarization, suggesting that the potentiated force was not caused by higher crossbridge cycling.We found that measures of stimulated actin polymerization (higher prior Y118 paxillin phosphorylation, higher prior F actin, and transition to a more solid rheology evidenced by lower noise temperature and phase angle) present prior to the maximal K+ depolarization predicted the degree of force potentiation.Increased prior contraction alone did not induce force potentiation since readdition of Ca2+ to Ca2+-depleted tissues induced a partial contraction that was not associated with changes in noise temperature or with subsequent force potentiation.These data suggest that stimulated actin polymerization may produce a substrate for increased crossbridge mediated force, a process we observe as force potentiation.
Monolithic integration of silicon nanophotonics with CMOS

Monolithic integration of deeply-scaled silicon optical components with CMOS analog and mixed signal circuits has high potential to provide cost-effective and low-power optical interconnects for various applications spanning from Ethernet links in new generation datacenters, to optical backplanes in servers, and extensive parallelism in high-performance computing systems by connecting together racks, modules, and chips [1].
phases in human perception/conception/symbolization processes: cognitive anthropology and symbolic classification

The immediate goal of this paper is to compare and contrast two approaches in anthropology that are concerned with the role of culture in ordering a people's universe – cognitive anthropology and symbolic classification. A larger aim is to propose a schema of human perception, conception, and symbolization, delineating different phases in these processes that represent distinct levels of abstraction in our concept formation. I argue that cognitive anthropology focuses upon the phases in which memory codes are established, whereas symbolic classification deals with the phases in which analogy codes are formulated. Each may thereby be seen to complement the other in our effort to understand the role of culture in the ordering of the universe. [symbolic anthropology, cognitive anthropology, culture and classification, anthropological theory, memory versus analogy codes]
The calcium content of gastric juice

1. The calcium content of gastric juice with a Ph between 1.49 and 1.91 averaged 2.06 mg. per cent (36 patients). The calcium content of gastric juice with a Ph between 2 and 2.94 averaged 2.12 mg. per cent (17 patients). 'The calcium content of gastric juice with a Ph between 3.05 and 8.38 averaged 4.54 mg. per cent (12 patients). 2. Ewald test meal and fasting gastric juice contains more calcium than histamine stimulated secretion. 3. The gastric juice calcium in one pregnant dog was considerably higher than in man, while the calcium content of fundic pouch juice in four dogs was comparable to that in human gastric juice. 4. The calcium in human gastric juice, in these studies, was fairly well correlated with the Ph; usually the higher the Ph values, the higher was the amount of calcium. 5. The practical significance of these observations requires further study.
Consumer Virtual Reality for Collaborative Review of Power Plant Boiler Operation

This research describes the motivations and technical approach for the development of a collaborative environment of a coal-fired power plant operation. The system was developed using Unity 3D to interact with power plant models and computational fluid dynamics (CFD) simulation results. The system was developed for multiple remote users to interact using the Oculus Rift and Razer Hydra for 3D display, and hand tracking. Discussion of the power plant simulation and features of the interactive system are described.Copyright © 2014 by ASME
Family Distancing following a Fatal Farm Accident

Interviews in twenty-one farm families following a fatal accident identified factors involved in bereaved family members becoming more distant from one another. This article explores five of the di...
Acting Like a Physicist: Student Approach Study to Experimental Design.

National studies of science education have unanimously concluded that preparing our students for the demands of the 21st century workplace is one of the major goals. This paper describes a study of student activities in introductory college physics labs, which were designed to help students acquire abilities that are valuable in the workplace. In these labs [called Investigative Science Learning Environment (ISLE) labs], students design their own experiments. Our previous studies have shown that students in these labs acquire scientific abilities such as the ability to design an experiment to solve a problem, the ability to collect and analyze data, the ability to evaluate assumptions and uncertainties, and the ability to communicate. These studies mostly concentrated on analyzing students' writing, evaluated by specially designed scientific ability rubrics. Recently, we started to study whether the ISLE labs make students not only write like scientists but also engage in discussions and act like scientists while doing the labs. For example, do students plan an experiment, validate assumptions, evaluate results, and revise the experiment if necessary? A brief report of some of our findings that came from monitoring students' activity during ISLE and nondesign labs was presented in the Physics Education Research Conference Proceedings. We found differences in student behavior and discussions that indicated that ISLE labs do in fact encourage a scientistlike approach to experimental design and promote high-quality discussions. This paper presents a full description of the study.
Improved prostate cancer detection with anterior apical prostate biopsies

Abstract Purpose Research to improve prostate cancer detection with transrectal ultrasound-guided prostate biopsies has focused on increasing the number of cores and the directing of biopsies laterally. In this study, we describe our experience with the addition of anterior apical biopsies. Materials and Methods A total of 164 consecutive patients with an increased or increasing prostate-specific antigen and/or abnormal digital rectal examination underwent transrectal ultrasound and systematic biopsy. We performed our standard laterally directed sextant biopsies plus additional mid parasagittal plane biopsies at the base and mid-gland, and an anteriorly directed biopsy at the apex. Site-specific detection and tumor characteristics are reported. Results Prostate cancer was detected in 71 patients (43.3%). The most commonly unique site was the anterior apex. Excluding these biopsies would have missed 17% of the cancers detected. The cancers limited to the anterior apex had tumor characteristics similar to all other cancers detected. Conclusion In our experience, the anterior apical biopsies increase the detection of prostate cancer on transrectal ultrasound-guided biopsies. Further study on incorporating this site into the biopsy scheme is indicated.
Synthetic fluid inclusions: XVI. PVTX properties in the system H2O-NaCl-CO2 at elevated temperatures, pressures, and salinities

Abstract The ternary system H2O-NaCl-CO2 is one of the most important fluid systems in geochemistry and petrology. However, there is little information on the phase equilibrium and PVT properties in this system at salinities above 6 wt.% NaCl. In this study, PVTX data were obtained experimentally by using the synthetic fluid inclusion technique in conjunction with conventional microthermometry and a hydrothermal diamond–anvil cell. Solvi (liquid-vapor boundaries) and lines of equal homogenization temperature (approximating lines of constant density) were determined for pressures between about 100 and 500 MPa, temperatures of 300°C to 800°C, and compositions up to 40 wt.% NaCl and 20 mol.% CO2, both relative to water. Critical temperatures were obtained for ternary compositions ≤ 20 wt.% NaCl and ≤ 20 mol.% CO2, both relative to water. For a constant homogenization temperature, the dP/dT slopes of lines of equal homogenization temperature become steeper along pseudobinaries with both increasing carbon dioxide concentration and increasing NaCl. At constant salinity, the high-pressure portion of the solvus shifts to higher pressures and temperatures with increasing CO2 concentration. Addition of carbon dioxide causes the critical point to migrate towards higher pressures and slightly lower temperatures. For concentrations less than 20 wt.% NaCl and less than 20 mol.% CO2, the main effect of an increase in salinity at a fixed H2O/CO2 ratio is a sharp rise in the critical temperature, coupled with a moderate shift of the critical point towards higher pressures. The addition of CO2 and NaCl causes the solvus to migrate to high temperatures and pressures, reaching granulite–facies conditions for moderate to high concentrations of CO2 and NaCl. The results of this study are combined with literature data to construct P-T sections, with lines of constant homogenization temperature, for various compositions in the H2O-NaCl-CO2 ternary, and the results are compared with results predicted by a recently published equation of state.
Internationale organische stickstoffdauerdüngungs‐versuche (IOSDV). Standortvergleich Berlin ‐ Tartu (DORPAT)

Gegenstand der Untersuchung war der Einflus des Breitengrades (Standort Berlin 52° nB. Tartu 58ˆ nB.) auf die Ertragsbildung von Sommergerste und Kartoffeln im Rahmen der IOSD Versuchsreihe. Trotz der ungunstigeren Standortbedingungen in Tartu (niedrigere Temperaturen, kurzere Vegetationszeit) im Vergleich zu Berlin wurden in Tartu deutlich hohere Sommergersten Korn‐ und Gesamtertrage bei der zum Vergleich herangezogenen Stickstoffdungung von 120 kg/ha erziehlt. Es konnte aufgrund 5‐jahriger Versuchsergebnisse bei einer Analyse des Ertrages nachgewiesen werden, das der hohere Kornertrag der Sommergerste in Tartu im Vergleich zu Berlin allein auf das hohere Einzelahrengewicht zuruckzufuhren ist. Das hohere Ahrengewicht basiert auf einer erheblich hoheren Kornzahl je Ahre und auf einem geringfugig erhohten Tasusendkorngewicht (trotz erhohter Kornzahl je Ahre). Als Ursache fur die erhohte Kornzahl je Ahre konnte die in Tartu um 6 Wochen spatere Aussaat und die damit noch weiter verstarkten Unterschiede (Tage...
An improved function for fitting sedimentation velocity data for low-molecular-weight solutes

Many traditional approaches to the analysis of sedimentation velocity data work poorly with data for low-molecular-weight solutes, which have sedimentation boundaries that are severely broadened by diffusion. An approach that has previously had some success is to directly fit these broad boundaries to approximate solutions of the Lamm equation that directly account for the high diffusion. However, none of the available approximate solutions work well at times both early and late in the run, or give boundary shapes that are highly accurate, especially for species of molecular weight
EFFECTS OF PULSED LASER IRRADIATION OF THE FOREHEAD IN MICE.

Abstract 1. Non-focused or focused laser irradiation of the frontal area of mice produced neurological damage, followed by death in 75% within 24 hours of irradiation. These effects are attributed to other than thermal effects. 2. Initial studies with laser radiation delivered at high peak power (greater than 100 megawatts) appears to cause greater damage than at lower power levels. Consequently, power, and power density as well as energy delivered, may be of considerable importance in regard to the interaction with biological material, and radiation. 3. Attention should not be limited to the superficial area of interaction in personnel accidentally exposed to laser radiation. Deep effects may be of greater severity than the superficial lesion.
Laser action in a flowing mixture of formic acid, nitrogen, and helium

Laser action has been observed in an electrically excited mixture of formic acid, nitrogen, and helium. The source of population inversion is shown to be CO 2 molecules that are formed by the dissociation of formic acid.
Use of a general toxicity test to predict heavy metal concentrations in residential soils.

Significant clusters of developmental delay and mental retardation (DD/MR) were identified in children born in South Carolina. Although it is difficult to identify one factor that causes DD/MR, environmental insult including exposure of pregnant women to heavy metals can induce DD/MR in their children. Because it is expensive to measure the concentrations of individual metals in large numbers of environmental samples, the general Microtox® toxicity test was used to identify highly toxic soil samples. Approximately 100 soil samples were collected from residential areas and analyzed to determine an effective concentration (EC50) of soil required to inhibit 50% light emission of the luminescent bacterial test organism (Vibrio fischeri). The EC50 values were then transformed to relative toxicity units (RTU). A subset of 56 high and low toxicity soil samples was then analyzed by inductively coupled plasma–atomic emission spectrometry (EPA method 6010) for arsenic, lead, and chromium, which are known neurotoxins. The highest measured arsenic concentration was 30 times higher than the South Carolina residential soil limit. Significant correlations were found between the RTU and soil arsenic and chromium concentrations. Microtox® also identified some low arsenic and chromium samples as toxic, presumably because additional unidentified toxicants were present in the soil. In general, however, the Microtox® test was effective in identifying soils with elevated concentrations of arsenic and chromium, even in residential neighborhoods where limited soil toxicity was expected.
The utility of an improved readability short form of the MMPI with elderly male patients

Compared an improved readability short form of the MMPI (IRF) with the FAM and the MMPI-168 in a sample of 100 male veterans, aged 60 and over. The three forms were found to perform acceptably well in terms of measures commonly used to evaluate the statistical validity of MMPI short forms. Median correlations of short form estimates with the MMPI standard scales were .91, .90, and .89 for the FAM, MMPI-168, and the IRF, respectively. In comparison with the other two forms, the IRF was intermediate in the frequency of codetype matches, but was highest in rate of correct validity decisions. The IRF also showed the fewest significant differences between the means of the estimated MMPI scale scores and those that actually were obtained. It was concluded that although the results demonstrated no strong statistical advantage for any short form, the IRF, because of increased comprehensibility, might have a wider applicability, particularly among patients with whom short forms would be used most often.
On non-linear perturbations of stochastic Volterra integral equations

The purpose of this paper is to investigate the existence and asymptotic mean square behaviour of random solutions of non-linear stochastic integral equations of the form fort≥o.A random solution of the equation is defined to he a second-order stochastic process x(t;ω) on {0, ∞) which satisfies the equation almost certainly. Conditions are given such that a unique random solution exists which is G-stable hi mean square. Finally, an application of the results to stochastic differential systems is presented. This paper extends the results of Tsokos and Hamdan (1972) to a more general class of stochastic integral equations and a more general concept of stability.
Techniques for deploying elliptically orbiting constellations in along-track formation

Abstract Two techniques to deploy four spacecraft in an along-track formation with 500 km separation distance in an elliptical orbit are developed and evaluated: (1) The deployment from the original (parking) circular orbit into the final elliptical orbit is based on the solution of the associated non-linear two-point boundary value problem (TPBVP) following Pontryagin's principle for each spacecraft in the constellation. The control energy is minimized subject to a terminal time which is sequentially shortened until at least one component of the control thrust vector exhibits bang-bang characteristics. (2) Deployment is also based on the sequential deployment of all the spacecraft from the original circular orbit to the final elliptical orbit based on the concept of the Hohmann transfer and incorporating the logic for two impulsive line of apsides shifting maneuvers. The mother satellite would be placed into a regular Hohmann transfer orbit, while the remaining (three) daughter satellites would be placed into modified Hohmann transfer orbits to account for the desired final spacing and small differences in transient orbital periods. The TPBVP approach can result in much shorter total deployment times, but at a greater propulsive cost than for the Hohmann transfer approach.
Internal optical loss and threshold characteristics of semiconductor lasers with a reduced-dimensionality active region

We develop a general approach to including the internal optical loss in the description of semiconductor lasers with a quantum-confined active region. We assume that the internal absorption loss coefficient is linear in the free-carrier density in the optical confinement layer and is characterized by two parameters, the constant component and the net cross-section for all absorption loss processes. We show that the free-carrier-density dependence of internal loss gives rise, in general, to the existence of a second lasing threshold above the conventional threshold. Above the second threshold, the light-current characteristic is two-valued up to a maximum current at which the lasing is quenched. We show that the presence of internal loss narrows considerably the region of tolerable structure parameters in which the lasing is attainable; for example, the minimum cavity length is significantly increased. Our approach is quite general but the numerical examples presented are specific for quantum dot (QD) lasers. Our calculations suggest that the internal loss is likely to be a major limiting factor to lasing in short-cavity QD structures.
Plant nematode resistance genes

Root-knot and cyst nematodes cause severe damage to crops throughout the world. Genes conferring resistance against nematodes have been identified in many plant species and several of these have been, or soon will be, cloned. Nematode biotypes that can infect resistant plants have been identified. Investigation of cloned resistance genes and of virulent nematodes is likely to lead to improved host resistance.
External Threats and Political Tolerance in Taiwan

Political tolerance is a significant issue for democracies under external threats. When imposed dangers are felt by citizens of the polity, competitors for political power are likely to believe that they are engaging in political battles of a zero-sum nature, having a life or death consequence. Because Taiwan is under constant military pressure from China, it is an excellent case for an analysis of political tolerance in a democracy that is threatened by external forces. Employing recently collected survey data, this study finds that the majority of Taiwanese residents show a willingness to extend rights of citizenship to others in the polity on the most salient issue that divides them. However, the perceived threats from Beijing’s claims to the island and from the Taiwan independence movement have had negative impacts on the citizens’ level of tolerance. The finding of this study will have important policy implications for Taiwan’s young democracy and will also hold significant theoretical implications f...
Platelet P2Y12 Receptor Inhibition

Antiplatelet therapy is the cornerstone of treatment for patients with coronary artery disease. Since adenosine diphosphate (ADP) represents one of the most important mediators of thrombosis, the inhibition of the platelet ADP receptor, in particular the P2Y12 subtype, plays a pivotal role in secondary prevention of recurrent atherothrombotic events in high-risk settings. Numerous clinical trials have shown the efficacy of clopidogrel, an inhibitor of the ADP P2Y12 receptor, in patients presenting with an acute coronary syndrome and undergoing percutaneous coronary intervention. However, laboratory and clinical experience with clopidogrel have led to understanding some of the limitations of this drug, the most important of which is its broad range in interindividual response variability, resulting in the development of novel ADP P2Y12 receptor-inhibiting strategies. This article provides an overview of ADP P2Y12 receptor-inhibiting strategies, including high clopidogrel dosing regimens and novel agents under advanced clinical development.
Scripting distributed agents

The TRUCE language and ACACIA distributed infrastructure extend common notions of scripting to the realm of distributed agents. This paper provides an overview of how TRUCE and ACACIA approach the issues of openness, concurrency, and decentralization encountered when trying to apply scripting to autonomous distributed components.
The Gender Gap in Internet Use: Why Men Use the Internet More Than Women—A Literature Review

There is a gender gap in Internet use: Two thirds of users are males, and males account for 77% of on-line time. This article reviews related research to explain these differences. From childhood on, males are more experienced with computers and have more favorable attitudes toward computers than do females. These gender differences in computer experiences and attitudes as well as the masculinization of the computer culture may be transferred to Internet use and attitudes. In fact, the Internet culture was developed by its earliest users, primarily male scientists, mathematicians, and technologically sophisticated computer hackers. This culture can be discomforting and alien to females. For example, netiquette norms tolerate uncensored hostility and even harassment, which women may find offensive. Gendered linguistic differences also affect Internet discussion groups. Linguistic analysis of on-line academic discussion groups found males' postings were status enhancing and adversarial whereas females' post...
Luck, Mystery and Supremacy: D. Z. Phillips Reads Nagel and Williams on Morality

This paper critically examines D. Z. Phillips’ critical examination of Nagel's and Williams's famous exchange about moral luck. It argues that Phillips fails properly to identify the fundamental issues at stake in the exchange – particularly with respect to the role of scepticism, of the picture of the will as an extensionless point, and of the putative supremacy of morality – and so fails to recognise a certain commonality of interest between himself and those he criticises.
CW ultraviolet and visible laser action from ionized silver in an electron beam generated plasma

Continuous wave laser oscillation was obtained in the 318.1-nm and the 478.8-nm lines of Ag(II) in a neon-silver vapor mixture excited by glow discharge electron beams. Laser output powers of 14 and 60 mW were obtained in the ultraviolet and blue transitions, respectively, using nonoptimized optical cavities. The use of neon as a buffer gas significantly increases the number of possible laser lines that might be obtained with this type of excitation by means of selective energy transfer processes involving quasi-resonant collisions. >
The “Double‐Coller” Technique For EEG Electrode Preparation and Placement

For accurate and reliable EEG recording. electrode resistances must be kept relatively low and constant. To ensure that these conditions are met, a fixing agent, collodian, is usually used to fix the electrodes firmly to the scalp. Collodian, however, produces many unwanted side effects. A “double-cllar” method of electrode placement is described whereby electrodes may be firmly fixed to the scalp without the use of collodian. This technique is both faster and less troublesome than the use of collodian. Using this technique, electrode resistances at vertex and occiput were well below generally acceptable criteria (averaging under 5000 ohms) and there was no significant increase in resistance at either placement following nearly 2 hrs of continuous EEG recordings. It is concluded that, under certain laboratory conditions, the “double-collar” method of electrode preparation and placement is superior to the use of collodian.
Neural and mechanical response time for speech production.

The reaction time of 10 neurologically normal young adults was determined for a speech production task. The response was production of a CVC word following the offset of an auditory stimulus tone. ...
Spectral Broadening of Europium Ions in Glass

The fluorescence and absorption spectra of trivalent europium ions in glass were measured and compared with the spectra of single crystals of ${\mathrm{Gd}}_{2}$${\mathrm{O}}_{3}$: Eu. It was determined that there is a great similarity between the optical properties of the rare-earth glasses and rare-earth sesquioxide crystals. The spectral studies showed that the europium ions locate in two, and possibly three, average environment sites in glass, mirroring the three sites in which the ion locates in the monoclinical form of the sesquioxide. The primary broadening mechanism was found to be inhomogeneous as determined by the temperature independence of the spectral half width and peak wavelength in the range from 4 to 300\ifmmode^\circ\else\textdegree\fi{}K. This inhomogeneous broadening arises from the heterogeneity of the ion environment in glass.
Revised age of the Rockland tephra, northern California: Implications for climate and stratigraphic reconstructionsin the western United States

[Lanphere et al. (1999)][1] presented new data for the age of the Rockland pumice tuff breccia of [Wilson (1961)][2] using the incremental-heating 40Ar/39Ar technique. Their age, ∼610 ka, is ∼200 ka older than zircon fission-track ages obtained on this tuff by [Meyer et al. (1980][3]; [1991)][4
Morphology and properties of twisted polymeric fibers

Abstract The morphology and mechanical properties of four different fibers-polyethylene, polypropylene, nylon 66, and polyethylene terephthalate-under the influence of twisting, were investigated. It was found that a model for affine deformation of the fibers can be applied only for very low-twist levels. At high-twist levels the stress distribution and the deformation made in the fiber were very complex. A preferred radial orientation occurred in polyethylene, nylon 66, and polyethylene terephthalate giving rise to an ideal situation for chain tilting and kinking. Polymorphic transition, twinning, and yielding were also observed in the case of polyethylene. The fiber moduli decreased sharply with twist, and this was attributed to the effects of inhomogeneous stress distribution and fibril slippage.
Down-regulation of the RNA editing enzyme ADAR2 contributes to RGC death in a mouse model of glaucoma

Glaucoma is a progressive neurodegenerative disease of retinal ganglion cells (RGCs) associated with characteristic axon degeneration in the optic nerve. Excitotoxic damage due to increased Ca2+ influx, possibly through NMDA-type glutamate receptors, has been proposed to be a cause of RGC dysfunction and death in glaucoma. Recent work has found that expression of another potentially critical receptor, the Ca2+-permeable AMPA receptor (CP-AMPAR), is elevated during various pathological conditions (including ALS and ischemia), resulting in increased neuronal death. Here we test the hypothesis that CP-AMPARs contribute to RGC death due to elevated Ca2+ influx in glaucoma. AMPA receptors are impermeable to Ca2+ if the tetrameric receptor contains a GluA2 subunit that has undergone Q/R RNA editing at a site in the pore region. The activity of ADAR2, the enzyme responsible for this RNA editing, generally ensures that the vast majority of GluA2 proteins are edited. Here, we demonstrate that ADAR2 levels decrease in a mouse model of glaucoma in which IOP is chronically elevated. Furthermore, using an in vitro model of RGCs, we find that knockdown of ADAR2 using siRNA increased the accumulation of Co2+ in response to glutamate, and decreased the rectification index of AMPA currents detected electrophysiologically, indicating an increased Ca2+ permeability through AMPARs. The RGCs in primary culture also exhibited increased excitotoxic cell death following knock down of ADAR2. Furthermore, cell death was reversed by NASPM, a specific blocker for CP-AMPARs. Together, our data suggest that chronically elevated IOP in adult mice reduces expression of the ADAR2 enzyme, and the loss of ADAR2 editing and subsequent disruption of GluA2 RNA editing might potentially play a role in promoting RGC neuronal death as observed in glaucoma.
Quantification of Protoporphyrin IX Accumulation in Glioblastoma Cells: A New Technique

Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After treatment with a series of 5-ALA doses, both PpIX and YFP fluorescence were measured. The ratio of PpIX to YFP fluorescence was calculated. Results. YFP fluorescence permitted the quantification of cell numbers and did not interfere with 5-ALA metabolism. The PpIX/YFP fluorescence ratio provided accurate relative PpIX levels, allowing for the assessment of PpIX accumulation in tissue. Conclusion. Constitutive YFP expression strongly correlates with cell number and permits PpIX quantification. Absolute PpIX fluorescence alone does not provide information regarding PpIX accumulation within the cells. Our research indicates that our PpIX/YFP ratio assay may be a promising model for in vitro 5-ALA testing and its interactions with other compounds during FGR surgery.
Structure-activity relationships of steroid hormones on muscarinic receptor binding.

Abstract A total of fifty steroidal compounds were tested for their inhibition on the binding of muscarinic receptor antagonist, [3H]quinuclidinyl benzilate ([3H](−)QNB), to the hypothalamic membranes prepared from male rats. Among the compounds tested, the active structures (with IC50 values ⩽100 μM in parentheses) are: progesterone (40), 5β-pregnane-3,20-dione (40), deoxycorticosterone (50), 5β-pregnane-17α,21-diol-3,20-dione (30), 11-desoxy-17-hydroxycorticosterone (22), 17α-hydroxyprogesterone (20), 5β-pregnan-17α-ol-3,20-dione (24), 5β-androstane-3,17-dione (100), and 5β-dihydrotestosterone (100). By examining all the compounds tested, the following structure-activity relationship became apparent: (a) The ring A-reduced steroidal structures with a 5β -conformation were more potent than those with a 5α-conformation; (b) 17α-hydroxylation of the steroidal ring increased the steroid's inhibitory activity; (c) The C3 carbonyl group was essential for activity; (d) Reduction of the C3 carbonyl group or aromatization of the ring A abolished the steroid's inhibitory activity; (e) Oxidation of the C11 position of ring C resulted in a decrease or loss of inhibitory activity; and (f) Different modifications of the side chain of ring D by acetylation resulted in either an increase or a decrease in the inhibitory activity. The structure-activity relationship as revealed in this study might provide an insight for the synthesis of a steroidal molecule with a high affinity for the muscarinic receptor as well as for the search of a more potent and physiologically relevant steroidal metabolite possessing the ability to interact with the muscarinic receptor.
Comparative analysis of temozolomide (TMZ) versus 1,3-bis (2-chloroethyl)-1 nitrosourea (BCNU) in newly diagnosed glioblastoma multiforme (GBM) patients

Purpose Although TMZ replaced BCNU as the standard initial chemotherapy in the treatment of GBM, no studies have been reported comparing BCNU with TMZ. We therefore did a retrospective analysis comparing these agents as initial therapy in GBM. Patients and methods Eighty-one patients with GBM in our institution received both radiation and chemotherapy as initial treatment after surgery or biopsy; 49 receiving BCNU and 32 TMZ. These were analyzed for overall survival (OS) and progression-free survival (PFS) versus the type of chemotherapy used. The influence of salvage therapy on the outcome was investigated also. Results Median OS was superior in the TMZ versus the BCNU group (15.9 vs. 11.5 months) and the curves were judged to be significantly different by the log-rank test; P < 0.02. However, PFS was not significantly different between the two groups. Bevacizumab plus irinotecan (BI) was used as salvage therapy in one-third of the TMZ patients but in none of the BCNU patients. When patients receiving BI were omitted from the TMZ group the OS curve overlapped that of BCNU patients. Conclusion These data suggest that the superior OS of the TMZ-treated GBM patients was not due to better tumor control by TMZ but was possibly related to the newer salvage therapy that was available to them.