cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative genomics of freshwater Fe-oxidizing bacteria: implications for physiology, ecology, and systematics.

The two microaerophilic, Fe-oxidizing bacteria Sideroxydans ES-1 and Gallionella ES-2 have single circular chromosomes of 3.00 and 3.16 Mb that encode 3049 and 3006 genes, respectively. Multi-locus sequence analysis confirmed the relationship of these two organisms to one another, and indicated they may form a novel order, the Gallionellalaes, within the Betaproteobacteria. Both are adapted for chemolithoautotropy, including pathways for CO2-fixation, and electron transport pathways adapted for growth at low O2-levels, an important adaptation for growing on Fe(II). Both genomes contain Mto-genes implicated in iron-oxidation, as well as other genes that could be involved in Fe-oxidation. Nearly 10% of their genomes are devoted to environmental sensing, signal transduction, and chemotaxis, consistent with their requirement for growing in narrow redox gradients of Fe(II) and O2. There are important differences as well. Sideroxydans ES-1 is more metabolically flexible, and can utilize reduced S-compounds, including thiosulfate, for lithotrophic growth. It has a suite of genes for nitrogen fixation. Gallionella ES-2 contains additional gene clusters for exopolysaccharide production, and has more capacity to resist heavy metals. Both strains contain genes for hemerythrins and globins, but ES-1 has an especially high numbers of these genes that may be involved in oxygen homeostasis, or storage. The two strains share homology with the marine FeOB Mariprofundus ferrooxydans PV-1 in CO2 fixation genes, and respiratory genes. In addition, ES-1 shares a suite of 20 potentially redox active genes with PV-1, as well as a large prophage. Combined these genetic, morphological, and physiological differences indicate that these are two novel species, Sideroxydans lithotrophicus ES-1T (ATCC 700298T; JCM 14762; DSMZ 22444; NCMA B100), and Gallionella capsiferriformans ES-2T (ATCC 700299T; JCM 14763; DSMZ 22445; NCMA B101).
Nitrogen fixation and growth response of Alnus Rubra following fertiliztion with urea or biosolids

A fertilizacao nitrogenada de florestas com biosolidos constitui um meio de aceleracao do crescimento das plantas potencialmente nao impactante ao meio. Os efeitos de fertilizacao de nitrogenio atmosferico na relacao simbiontica e de fixacao de nitrogenio Alnus rubra Bong. (amieiro vermelho) e Frankia foram avaliados em um estudo de campo. Biosolidos classe B digeridos anaerobicamente e ureia sintetica (46% N) foram aplicados a taxas de 140, 280 e 560 kg ha-1 de N disponivel em um solo tipo Areia Quartzosa. Ao contrario das plantas do grupo controle (17 µmol C2H4 g-1 hr-1) ou fertilizadas com biosolidos (26-45 µmol C2H4 g-1 hr-1), plantas fertilizadas com ureia nao apresentavam fixacao de nitrogenio apos um ano de cultivo. Ao final do segundo ano, todas as arvores em todos os tratamentos fixavam N (7 µmol C2H4 g-1 hr-1; 4-16 µmol C2H4 g-1 hr-1; e 20-29 µmol C2H4 g-1 hr-1 para controle, ureia e biosolidos, respectivamente). Plantas cultivadas sob remediacao com biosolidos apresentaram maior biomassa na parte aerea ao final do ano 2 (50 g; 51 g; e 190 g para controle, ureia, e biosolidos, respectivamente), e tambem maiores concentracoes de nitrogenio foliar em ambos os periodos analisados (N foliar no ano 1 26 g kg-1, 27 g kg-1, e 40 g kg-1; N foliar no ano 2 17 g kg-1, 19 g kg-1, and 23 g kg-1, respectivamente para controle, ureia e biosolidos). A maior taxa de crescimento de A. rubra pode ter resultado em maior exigencia em N e os biosolidos supriram quantidades adicionais de nutrientes capazes de sustentar o crescimento acelerado.
ExTool: an interactive object-oriented expert system toolkit for distributed decision-making

The objective of this project has been to develop a flexible, generic (which can be easily adapted to various application domains), and interactive decision support toolkit (called ExTool) with a friendly user interface and distributed decision-making capabilities. A hybrid methodology has been adopted in which features from Artificial Intelligence have been incorporated into an object-oriented environment (in this case Smalltalk-80), taking advantage of the benefits offered by both paradigms. >
Decomposition of complex microbial behaviors into resource-based stress responses

Motivation: Highly redundant metabolic networks and experimental data from cultures likely adapting simultaneously to multiple stresses can complicate the analysis of cellular behaviors. It is proposed that the explicit consideration of these factors is critical to understanding the competitive basis of microbial strategies. Results: Wide ranging, seemingly unrelated Escherichia coli physiological fluxes can be simply and accurately described as linear combinations of a few ecologically relevant stress adaptations. These strategies were identified by decomposing the central metabolism of E.coli into elementary modes (mathematically defined biochemical pathways) and assessing the resource investment cost–benefit properties for each pathway. The approach capitalizes on the inherent tradeoffs related to investing finite resources like nitrogen into different pathway enzymes when the pathways have varying metabolic efficiencies. The subset of ecologically competitive pathways represented 0.02% of the total permissible pathways. The biological relevance of the assembled strategies was tested against 10 000 randomly constructed pathway subsets. None of the randomly assembled collections were able to describe all of the considered experimental data as accurately as the cost-based subset. The results suggest these metabolic strategies are biologically significant. The current descriptions were compared with linear programming (LP)-based flux descriptions using the Euclidean distance metric. The current study's pathway subset described the experimental fluxes with better accuracy than the LP results without having to test multiple objective functions or constraints and while providing additional ecological insight into microbial behavior. The assembled pathways seem to represent a generalized set of strategies that can describe a wide range of microbial responses and hint at evolutionary processes where a handful of successful metabolic strategies are utilized simultaneously in different combinations to adapt to diverse conditions. Contact: rossc@biofilms.montana.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Estrogen facilitates fear conditioning and increases corticotropin-releasing hormone mRNA expression in the central amygdala in female mice

Estrogens exert important actions on fear and anxiety-like behavior both in humans and non-human animals. Currently, the mechanisms underlying estrogenic modulation of fear are not known. However, evidence suggests that estrogens may exert their influence on fear within the amygdala. The purpose of the present study was to examine effects of estrogen on fear conditioning. Specifically, the present study examined whether long-term estrogen treatment in ovariectomized female mice via Silastic capsule implantation would facilitate both contextual and cued fear conditioning. In a separate set of experiments, we then examined whether estrogen treatment in ovariectomized female mice would modulate corticotropin-releasing hormone (CRH) gene expression within the amygdala. Long-term estrogen treatment facilitated both contextual and cued fear. Ovariectomized mice treated with estrogen froze significantly more to a context as well as to a discrete auditory cue. In addition, estrogen treatment significantly increased CRH mRNA expression within the central nucleus of the amygdala as measured by in situ hybridization and quantitative PCR. These data raise the possibility that estrogens could influence fear responses in females through their actions in the amygdala.
CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis

Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APCMIN/+ mice) to generate APCMIN/+ mice with CCR6 knocked out (CCR6KO-APCMIN/+ mice). CCR6KO-APCMIN/+ mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APCMIN/+ also had normal sized spleens as compared to the enlarged spleens found in APCMIN/+ mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APCMIN/+ as compared to APCMIN/+ mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy.
Compatibility of Vancomycin and Oxacillin during Simulated Y-Site Delivery:

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) in an evacuated intravenous (IV) bag. One oxacillin sodium 2 g vial was reconstituted with 11.5 mL sterile water for injection and diluted with 88 mL sterile water for injection in an evacuated IV bag. Three mL of each vancomycin and oxacillin were mixed in 4 test tubes to simulate Y-site delivery. Spectrometry, pH evaluation, and visual examination were performed...
Some Reflections on the Habsburg Empire and Its Legacy in the Nationalities Question

The startling events of the last five years in Eastern Europe have led to a surprising nostalgia for the Austro-Hungarian monarchy and Emperor Francis Joseph in the lands of the former Habsburg Empire. Politicians and journalists in Europe and America now compare the old empire to the disoriented East Central Europe of today and hold up the former as a positive model for a supranational organization. The current wave of nostalgia has been helped along by some recent historical works that certainly were not written for that purpose, but that contain generous assessments of the monarchy's positive qualities. For example, Istvan Deak, in his highly acclaimed book, Beyond Nationalism: A Social and Political History of the Habsburg Officer Corps, 1848–1918, strongly recommends that the “Habsburg experiment” in supranational organization be reexamined: “I am convinced that we can find here a positive lesson while the post-1918 history of the central and east central European nation-states can only show US what to avoid.” Similar positive statements can be found in the recently published works of Alan Sked, Barbara Jelavich, and F. R. Bridge.
A Morphological Test of the Monophyly of the Cardueline Finches (Aves: Fringillidae, Carduelinae)

Abstract Monophyly of the cardueline finches (Aves: Fringillidae, Carduelinae), an assemblage of 119 species of seed-eating songbirds, has not yet been rigorously tested. To test the hypothesis of cardueline monophyly I examined 37 taxa, among them 1 or 2 representatives from 16 of the 19 cardueline-finch genera as well as 4 Hawaiian honeycreepers. Each taxon was scored for 225 morphological characters, 148 from the skeleton and 77 from the integument. Cladistic analysis of these data found the carduelines to be monophyletic, so long as the honeycreeper Telespiza cantans is considered to be cardueline; as for the other honeycreepers, they form a clade but do not group with either Telespiza or the carduelines. Both cardueline monophyly and the nonmonophyly of honeycreepers have comparatively strong support, with support for cardueline monophyly coming primarily from evolutionary modifications to the head skeleton.
Native and alien species diversity at the local and regional scales in a grazed California grassland

Serpentine meadows in Northern California supported higher species richness at the 1-m2 scale than adjacent nonserpentine meadows, and had a considerably higher proportion of native species. Within each soil type, total species richness (natives plus aliens) was unrelated to biomass, cover, soil depth, or soil characteristics (N, P, Ca++, Mg++, water-holding capacity). However, the proportion of native species on serpentine was higher in meadows with lower levels of phosphorus and a lower calcium/magnesium ratio; the proportion of native species in nonserpentine meadows was higher on cool (north to northeast facing) slopes. At a regional scale, some of these effects were partly reversed; the rate at which new species accumulated with the addition of new sites, or beta diversity, was highest for native plant species in nonserpentine meadows. All of the above effects were independent of whether grazing by cattle was absent (removed 13 years ago) or present. The status of low-productivity serpentine soils as a refuge for native grassland species appears to be the result of their abiotic resistance to alien species, but not of a negative relationship between productivity and total species richness.
Performance analysis of space-time transmitter diversity techniques for WCDMA using long range prediction

Transmitter diversity in the downlink of code-division multiple-access (CDMA) systems achieves similar performance gains to the mobile-station receiver diversity without the complexity of a mobile-station receiver antenna array. Pre-RAKE precoding at the transmitter can be employed to achieve the multipath diversity without the need of the RAKE receiver at the mobile station. We examine feasibility of several transmitter diversity techniques and precoding for the third-generation wideband CDMA (WCDMA) systems. In particular, selective transmit diversity, transmit adaptive array and space-time pre-RAKE (STPR) techniques are compared. It is demonstrated that the STPR method is the optimal method to combine antenna diversity and temporal precoding. This method achieves the gain of maximum ratio combining of all space and frequency diversity branches when perfect channel state information is available at the transmitter. We employ the long range fading prediction algorithm to enable transmitter diversity techniques for rapidly time varying multipath fading channels.
Low-Power Low-Noise Neural Amplifier in 0.18μm FD-SOI Technology

For recording of neural signals from large population of neurons, stringent constraints are imposed on the design of neural amplifiers. We have designed neural amplifier in FD-SOI technology in order to achieve lower power consumption, smaller area, and better noise efficiency factor compared to the standard bulk processes. A symmetric pseudo resistor was realized with resistances on the order of 1015Ω, enabling a low cut-off frequency of 0.6mHz. The designed neural amplifier occupies an area of 0.004mm2, with simulated performance demonstrating an input-referred noise of 3.07μVrms and a power consumption of 6μW.
Real-time multichannel neural spike recognition with DSPs

Data acquisition technology that uses relatively inexpensive digital signal processors (DSPs) for the rapid acquisition of neuronal action potential (spike) data was investigated. Three spike sorting techniques were considered. The simplest classification routine tested was peak windowing. Spikes were considered to belong to the same class when their peak amplitude fell within a user-specified interval. Another approach required computing the RMS error between stored templates of each unit's spike waveform and the spike most recently detected. The new spike was classified according to the minimum of the RMS errors computed. In the third algorithm, two optimal coefficient vectors, called principal components, were computed from previously acquired template waveforms and stored. These principal components were used to compute two vector products for each newly detected spike waveform vector. The resulting two values were features that were used to classify the waveform. The test system that was constructed is described, and results obtained with each of the algorithms are compared and evaluated. >
OBSERVATIONS ON ‘PREDIABETES’

Abnormal blood sugar curves indicating ‘low sugar tolerance’ may be found in normal persons at times of emotional upset (1) or while they are living on low carbohydrate diets (2). Advanced age (3), high blood pressure (4), liver or kidney insufficiency (5, 6) tend to decrease the glucose tolerance. In addition, there are some persons, young or in middle age, in apparently good health, with blood pressure normal or slightly higher, without demonstrable liver or kidney disturbance, living on unrestricted normal diet who upon glucose tolerance tests consistently respond with markedly abnormal blood sugar time curves approaching those found in the diabetic. Such persons are almost invariably obese. Paullin and Souls (7) first called attention to this condition; John (8) called it ‘prediabetes.’ Rony (9) found it in 16 of 70 unselected cases of adult obesity. The frequent occurrence of this condition in obesity deserves attention for several reasons. In the first place there is the question whether or not obes...
A varactor diode based predistortion circuit

Operation and performance of a varactor diode based linearizer is investigated. This novel predistortion topology employs a series resonant circuit with a reverse biased varactor diode acting as a power dependant capacitor. The linearizer itself is both simulated and tested to display its nonlinear properties. In addition, a 1.8 GHz power amplifier is linearized based on this technique. An improvement of 11 dB in ACPR and an increase in 1.8 dB for the compression point is measured for the linearized PA.
Inferior Vena Cava Filters: Recognizing Indications for Placement and Retrieval

Inferior vena cava (IVC) filter placement is indicated in patients with acute pulmonary embolism (PE) or deep vein thrombosis (PE) who have contraindications to anticoagulation or who have recurrent PE despite therapeutic anticoagulation. IVC filter insertion may be considered on a case-by-case basis for patients with acute PE who are able to receive therapeutic anticoagulation but who have limited cardiopulmonary reserve and in whom a subsequent PE would likely be fatal. Retrievable IVC filters are inserted to provide temporary protection from PE during such periods of increased vulnerability or when interruption of anticoagulation is necessary. IVC filters should be retrieved as soon as they are no longer necessary.
Parametric Resonance of Suspension Roofs in Wind

Since suspension roofs or curved membrane roofs are usually flexible, there are two important problems with regard to dynamic instability in wind-induced vibration of these roofs; one is flutter and the other is a resonance due to the periodical character of wind velocity fluctuations in atmospheric turbulence. The latter problem is undertaken here. If wind is assumed as inviscid potential flow, and if vorticities are introduced to represent the difference of velocities of wind and roofs in order to take into consideration wind-roof interaction effect, the latter problem can be analyzed as that of parametric resonance in antisymmetric deflection modes. Possibility of the occurrence of this resonance is confirmed under some conditions in atmospheric turbulence, where wind velocity fluctuation was revealed into spectral density function by Davenport. Analytic solution and numerical results, e.g., are presented concerning the several important factors which govern the prevention of parametric resonance.
Arch Dams: Theory, Methods, and Details of Joint Grouting

Procedure developed whereby contraction joints of arch dams are pressure-grouted, making structure monolithic; metal seals capable of expansion and contraction are installed around peripheries of joints or areas to be grouted so as to hold grout in joint; special systems of piping with outlets to faces of joint are used for conveying fluid grout into joints; abnormal stresses due to grout pressure can be controlled.
PARP-2 domain requirements for DNA damage-dependent activation and localization to sites of DNA damage

Poly(ADP-ribose) polymerase-2 (PARP-2) is one of three human PARP enzymes that are potently activated during the cellular DNA damage response (DDR). DDR-PARPs detect DNA strand breaks, leading to a dramatic increase in their catalytic production of the posttranslational modification poly(ADP-ribose) (PAR) to facilitate repair. There are limited biochemical and structural insights into the functional domains of PARP-2, which has restricted our understanding of how PARP-2 is specialized toward specific repair pathways. PARP-2 has a modular architecture composed of a C-terminal catalytic domain (CAT), a central Trp-Gly-Arg (WGR) domain and an N-terminal region (NTR). Although the NTR is generally considered the key DNA-binding domain of PARP-2, we report here that all three domains of PARP-2 collectively contribute to interaction with DNA damage. Biophysical, structural and biochemical analyses indicate that the NTR is natively disordered, and is only required for activation on specific types of DNA damage. Interestingly, the NTR is not essential for PARP-2 localization to sites of DNA damage. Rather, the WGR and CAT domains function together to recruit PARP-2 to sites of DNA breaks. Our study differentiates the functions of PARP-2 domains from those of PARP-1, the other major DDR-PARP, and highlights the specialization of the multi-domain architectures of DDR-PARPs.
Using an environmental justice approach to examine the relationships between park availability and quality indicators, neighborhood disadvantage, and racial/ethnic composition

Abstract Public parks are key community resources that can promote health. Some research has examined whether parks are equitably dispersed across neighborhoods of varying socioeconomic status and racial/ethnic composition, but few studies have examined the interaction of these characteristics. Additionally, the quality of park environments has received limited attention, but is considered integral to utilization of parks. This study examined the relationship between neighborhood disadvantage and park availability and quality and whether neighborhood racial/ethnic composition moderated these associations. A neighborhood disadvantage index was created for all block groups ( n = 255) in a southeastern U.S. county using Census Bureau data. Detailed audits of all public parks were conducted in 2013 ( n = 103). Park availability was determined using ArcGIS and four park quality indicators were examined: facilities, amenities, incivilities, and aesthetics. No significant differences were detected between neighborhood disadvantage and number of parks. However, high-disadvantaged neighborhoods had increased park incivilities compared to low-disadvantaged neighborhoods (IRR = 1.93, 95% CI = 1.24, 3.00). Further, neighborhood racial/ethnic composition moderated the associations between park incivilities and amenities and neighborhood disadvantage. Among low-disadvantaged neighborhoods, park incivilities increased as neighborhood minority concentration increased but remained constant in high-disadvantaged neighborhoods. Additionally, among low-disadvantaged neighborhoods, the number of park amenities decreased as neighborhood minority concentration increased but among high-disadvantaged neighborhoods, park amenities increased as neighborhood minority concentration increased. Identifying and rectifying disparities in park quality may be integral to creating equitable park environments across diverse neighborhoods.
Practicing engineering while building with blocks: identifying engineering thinking

Children's free play naturally enhances skills of observation, communication, experimentation, as well as development of rationale and construction skills. These domains, while synthesised, can lead to the development of certain process models regarding the way constructions could be designed, built and improved. The Design Process model constitutes a core concept of engineering. Blocks seem to be one of the best tools to use in order to work towards the development of such a model. This is a qualitative observational study in preschoolers’ free playing with blocks. Eighteen children aged three- to five-years-old were observed and videotaped for four months to examine whether young children can demonstrate instances of precursors to engineering behaviour while building, by demonstrating similarities to the Design Process. Analysis of the video data showed that children demonstrated and articulated goal-oriented design, problem-solving thinking, innovation stemming out of synthesis of multiple designs, pat...
Acute gastrointestinal bleeding in anticoagulated patients: a prospective evaluation.

Acute gastrointestinal hemorrhage is one of the most feared complications of anticoagulation therapy. We prospectively evaluated 18 episodes of acute gastrointestinal bleeding in 17 patients anticoagulated with coumadin or heparin. Endoscopic examination revealed significant lesions irrespective of age, duration of anticoagulation, level of anticoagulation or symptoms. The high frequency of objective findings (e.g., 44% ulcers) suggests that diagnostic endoscopy should be performed in patients with acute gastrointestinal bleeding associated with anticoagulant therapy.
High frequency of nonadherence to Clostridium difficile treatment guidelines.

OBJECTIVES The 2010 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America treatment guidelines for Clostridium difficile infections (CDI) recommend oral metronidazole for mild-to-moderate disease and oral vancomycin for severe disease. Given that disease severity is easily determined by the peripheral white blood cell count and serum creatinine level, a computerized decision support (CDS) pathway to guide treatment is inherently appealing. Because providers often override or ignore the computer-based alerts, the proposed CDS pathway should be justified before implementation. METHODS We undertook this study to ascertain the frequency of nonadherence to CDI guidelines. Between October 1, 2007 and September 30, 2008, a total of 229 cases were screened and 78 cases were included in the study, which took place at a 661-bed acute tertiary care teaching hospital. RESULTS During the year-long study of CDI cases at our tertiary care hospital, 61.5% (48/78) of the patients received an antibiotic regimen that was not recommended by the 2010 guidelines. Among the 35 patients with mild-to-moderate CDI, 85.7% (30/35) received the recommended treatment of oral metronidazole monotherapy; in contrast, among the 43 patients with severe disease, none (0/43) received the recommended treatment of oral vancomycin monotherapy (P < 0.01). Moreover, 17.9% (14/78) of patients received concurrent oral metronidazole and vancomycin, a regimen that is not recommended anywhere in the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines and which may be associated with a poor outcome. Patients who received combination oral metronidazole and vancomycin were not more likely to have comorbidities or severe CDI compared with those who received a single antibiotic agent. CONCLUSIONS As a result of this study, we plan to educate our providers on the treatment of CDI through a CDS pathway in an effort to increase guideline adherence, decrease inappropriate antibiotic use, and potentially improve patient outcomes.
Materialbeschreibung für die geburtshilfliche Regionalanästhesie

Die physiologischen Veranderungen der Schwangerschaft erhohen das Risiko der Allgemeinanasthesie. Die Pradisposition der Schwangeren fur Atemwegskomplikationen bei der Narkoseeinleitung hat in den letzten Jahrzehnten das Interesse an den Methoden der Regionalanasthesie aufleben lassen. Heute ist diese die Methode der Wahl fur geplante Eingriffe, vielerorts aber auch fur Notfalleingriffe bei der Schwangeren (z.B. Kaiserschnittgeburt). Der Fortschritt bei Fertigung und Design des Materials und die damit erzielte Senkung der Komplikationsrate ist ein entscheidender Faktor fur die weite Verbreitung dieser Verfahren. Wesentliche Voraussetzung fur den Erfolg eines Regionalverfahrens ist neben der Vertrautheit mit der Methode auch die Kenntnis der verwendeten Materialien.
SU-F-T-325: On the Use of Bolus in Dosimetry and Dose Reduction for Pacemaker and Defibrillator

Purpose: Special attention is required in planning and administering radiation therapy to patients with cardiac implantable electronic devices (CIEDs), such as pacemaker and defibrillator. The range of dose to CIEDs that can induce malfunction is very large among CIEDs. Significant defects have been reported at dose as low as 0.15Gy. Failures causing discomfort have been reported at dose as low as 0.05Gy. Therefore, accurate estimation of dose to CIED and dose reduction are both important even if the dose is expected to be less than the often-used 2Gy limit. We investigate the use of bolus in in vivo dosimetry for CIEDs. Methods: In our clinic, high-energy beams (>10MV) are not used for patients with CIED due to neutron production. Solid water phantom measurements of out-of-field dose for a 6MV beam were performed using parallel plate chamber at different depth with and without 2cm bolus covering the chamber. In vivo dosimetry at skin surface above the pacemaker was performed with and without bolus for 3 patients with pacemaker <5cm from the field edge. Results: Chamber measured dose at depth ∼1 to 1.5cm below the skin surface, where the CIED is normally located, was reduced by ∼6% – 20% with bolus. The dose reduction became smaller at deeper depth. In vivo dosimetry at skin surface also yielded ∼20% – 60% lower dose when using bolus for the 3 patients. In general, TPS calculation underestimated the dose. The dose measured with bolus is closer to the dose at the depth of the pacemaker and less affected by contaminant electrons and linac head leakage. Conclusion: In vivo CIED dose measurements should be performed with 1 to 2cm bolus covering the dosimeter on the skin above the CIED for more accurate CIED dose estimation. The use of bolus also reduces the dose delivered to CIED.
Force-Matching. A New Approach to Determine Action Forces for the Ergonomic Evaluation in Automotive Industry

The collection and analysis of applied forces is an essential part of the ergonomic evaluation of workplaces. In industrial companies, direct measurements and estimates are currently considered to be accepted methods. The present study identifies alternatives to the accepted procedures for the determination of action-forces and analysed one of these in detail: force-matching.
Cannabis and brain-stimulation reward.

Summary Effects of Δ9-tetrahydrocannabinol (Δ9-THC) were studied on self-stimulation (SS) behavior in rats with implanted electrodes at the posterior hypothalamus (PH) or area ventralis tegmentum (A 10 area). Its effects were also studied with respect to spontaneous motor activity (SMA), rectal temperature, barbiturate sleeping time, development of tolerance and brain neurotransmitter levels. Two patterns of Δ9-THC effects were observed in these experiments. In one type, there was a gradual drug-induced depression that persisted for a prolonged period. Decrease in SS responding in nonaroused subjects, hypothermia, potentiation of barbiturate-induced sleep are examples. These effects may be due to a nonspecific generalized depression of the central nervous system. The other type, a triphasic effect is characterised by an initial depression followed by a stimulation and then again depression, and is observed in SS in aroused subjects and SMA. The effects of the stimulants such as amphetamine and cocaine are antagonised during the initial depressant phase and unaffected or even potentiated during the subsequent stimulant phase. The neurochemical studies demonstrated an initial decrease in dopamine (DA) in the caudate nucleus and diencephalon-midbrain (DM) and increase of serotonin (5-HT) in DM and PM (pons-medulla) followed by increase in DA and decrease in 5-HT and then their reversal in respective brain areas. These effects can be well correlated to the triphasic behavioral effects. Development of tolerance to the behavioral depressant effect in SS on repeated administration of Δ9-THC in SS and lack of cross-tolerance to mescaline were also observed.
Activity Modulation by Photochromic Effectors

Although photochromic azobenzene molecules with the ability to modulate biological activity are not found in nature, they can be used to probe naturally occurring systems and to enable us to learn something about the mechanisms by which these systems function. Studies on their ability to mimic or to interfere with biochemical activity can provide information that can compliment data obtained by other methods, including physical (X-ray crystallography, NMR, circular dichroism), chemical, physiological or immunological procedures. Although no single methodology provides a complete, integrated picture of a biochemical process, each can contribute data that serve to clarify the overall system. Even such a powerful technique as X-ray crystallography shows the structure and configuration as it is in a crystal only; this structure can be different from the configuration that directly participate in the biological process.
Targeted Messages and Constituent Demographics: How Strategic Candidate Communication Leverages District Constituencies

Micro targeting of messages occurs often in strategic campaigns, as candidates actively recruit constituencies through their claims, promises, and appeals. Targeted campaign communication may come in the form of either particularistic, or collective and broad-principled, messages (Hersh and Schaffner, 2013). I maintain that targeted campaign communication occurs primarily through use of policy claims and representative claims. Policy claims entail the communication of candidate issue positions and issue ownership, which increase in salience when interacted with constituent demographic identity (Petrocik 1996, Petrocik et al, 2003). Representative claims involve a candidate creating a representation of her constituency, making a claim about her connection to this portrayal, and arguing that this connection proves she is the best possible representative (Saward, 2010, 2008). Targeted messaging of policy or representative claims can be successful when a candidate successfully convinces diverse groups of voters that she is ideologically closer to their preferred positions (Somer-Topcu, 2014). And yet, which policy and representative claims do candidates use to increase support among voters? How do these targeted claims influence district satisfaction, electoral outcomes, and turnout? The small, but growing, literature on targeted campaign communication, would benefit from further study about to whom, and under what conditions, targeted messages are effectively delivered. I argue that the policy topics and representative claims communicated by candidates is directly a function of the demographic and political groups in the district. Furthermore, this targeting is conditional -- the greater the chance that individuals outside of the targeted group may view the message, the less likely it is that the candidate will deliver it (Nteta and Schaffner, nd). To test this I create a novel dataset using archived website texts of over 4,000 candidates from the 2014 and 2016 campaign cycles. Using Structural Topic Modeling and Latent Dirichlet Allocation, I identify the topics and claims communicated by candidates. I find evidence of strategic issue selection influenced by district demographics. First, I find that, in accordance with the literature, political alignment of a district determines claims made (Cormack, 2013). Second, I find that strategic issue selection is also governed by district demographics -- areas with a larger minority population focus on topics such as social issues, immigration, employment, health care, and education. Moreover, I find that non-policy topics, such as representative claims and symbolic appeals, are strategically selected based upon the race, gender, and age distribution of a district. Lastly, I analyze the intersection of targeted messages and candidate demographic identity.
Preface: physiopathology of vascular risk factors in Alzheimer's disease.

When one thinks of vascular risk factors to Alzheimer’s disease (VRF-AD), several things may come to mind. First, what are VRF-AD and why are they important? Second, why or what makes them a pathological risk to Alzheimer’s disease (AD)? Third, how can they be identified or diagnosed? Fourth, what interventions if any, can be used to manage VRF-AD and could they help reduce or reverse the prevalence of cognitive decline and AD? This special issue of the Journal of Alzheimer’s Disease titled “Physiopathology of Vascular Risk Factors in Alzheimer’s Disease” is dedicated to these four questions and many others which relate to their profile, pathophysiology, diagnosis, and intervention. A panel of international experts from 16 countries pooled their knowledge to provide clarity and insight into VRF-AD, one of the fastest growing fields in AD research. VRF-AD were rarely if ever mentioned in the medical literature prior to 1997. That year, several prospective epidemiological studies discovered what turned out to be a breakthrough in our limited understanding of AD. The studies reported how specific maladies that directly affected the cerebral vasculature could lead to the development of cognitive decline and AD onset. As more studies began evaluating large populations of middle age and elderly individuals with hypertension, atherosclerosis, diabetes type 2, hyperlipidemia, and heart disease, it became clear that a
Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.
Search-and-Match in a Rush: Investigating Reactive Licensing in the Pharmaceutical Industry

Large innovative firms routinely strengthen their new product pipelines by licensing developing technologies from other (typically startup) companies. Licensing is generally portrayed as a carefully planned and executed, "proactive" activity, used to implement the large firm's innovative strategy. We argue that these firms also use licensing in a different -"reactive"- way, when they seek to quickly fill the gap left by development setbacks of other products in their pipelines. In reactive circumstances, firms favor speedier dealmaking in detriment of time searching for candidate technologies that are compatible with the their capabilities. This haste hurts the "matching quality" of licensed technologies and, in turn, their post-licensing development performance. We study the problem in the context of the pharmaceutical industry, where this behavior can be rationalized by executive compensation tied to the firm's stock market returns. Exploiting quasi-experimental variation from clinical trial outcomes, we show that reactive licensing: (i) does occur, (ii) deteriorates matching quality, and (iii) creates significant productivity costs for firms that engage in it.
Oral anticoagulation and left atrial thrombi resolution in nonrheumatic atrial fibrillation or flutter: A systematic review and meta-analysis.

BACKGROUND Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and < 1 year, were selected. Study quality was assessed using recommendations adapted from the Agency for Healthcare Research and Quality. Pooled LAT resolution rates were evaluated for vitamin K antagonist (VKA) studies and low risk of bias warfarin studies. RESULTS The pooled LAT resolution rate of 619 subjects from 16 VKA studies was 63.7% (95% confidence interval [CI], 53.3%-72.9%). The pooled LAT resolution rate of 94 subjects from four studies that specified warfarin use, exclusion of prior long-term therapeutic OAC, and target international normalized ratio (INR) ≥ 2.0 and/or average achieved INR ≥ 2.0 was 79.3% (95% CI, 69.8%-86.4%). Two studies in direct-acting oral anticoagulants (DOACs) reported LAT resolution rates of 89.5% (17 of 19) for dabigatran and 41.5% (22 of 53) for rivaroxaban. CONCLUSIONS Warfarin is the most studied initial OAC agent for treating LAT in nonrheumatic AF and/or AFL with a resolution rate of nearly 80%. Further studies in DOACs are warranted.
Multiscale modeling of carbon fiber-reinforced polymer composites in low-temperature arctic conditions

Exploration of new frontiers within the Arctic region introduces new challenges for the structural materials used in naval applications. This compels research on the influence of Arctic temperatures (from room temperature to $$-~70\,\,^{\circ }\hbox {C}$$ ) on the mechanical behavior of composites. In the current investigation, the effects of low temperatures on the axial stiffness of graphite/epoxy composites with unidirectional, cross-ply, and quasi-isotropic layups are studied using MAC/GMC, a micromechanical simulation tool developed by the NASA Glenn Research Center. Parametric studies were conducted to understand how various constituent material properties of a graphite/epoxy laminate influence the global, homogenized, axial stiffness of the composite subjected to arctic conditions. MAC/GMC provided accurate simulation results as compared with published experimental data. Results revealed that the increase in axial stiffness of carbon fibers is the main mechanism responsible for the overall increase in the global axial stiffness of the laminated composites at low temperature. The current research effort expands the understanding of how composites respond and behave in such extreme, low-temperature environments.
Structural and enzymatic properties of Escherichia coli glutamine synthetase subjected to limited proteolysis.

Publisher Summary This chapter focuses on the structure of nicked glutamine synthetase. Glutamine synthetase is susceptible to limited proteolysis, termed nicking, under non-denaturing conditions by a variety of proteases. Proteolytic nicking occurs within a limited region of the enzyme and leads to a 97% reduction of enzymatic activity as measured by transferase and forward assays. Nicked glutamine synthetase retains its overall dodecameric structure, is still recognized by antibodies to intact enzyme, and is still adenylylated essentially normally. The chapter also describes the interactions of nicked glutamine synthetase with substrates and inhibitors using some experiments. The nicking of glutamine synthetase by protease under non-denaturing conditions does not completely inactivate the enzyme. Nicked glutamine synthetase catalyzes at least some of the same reactions as GS, but with a much lower efficiency than GS.
Does Switching to a New Antipsychotic Improve Outcomes? Data from the CATIE Trial

Purpose:Previous analysis of data from CATIE showed that patients randomly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to randomization. This study addresses additional outcomes measures evaluating symptoms, neurocognition, quality of life, neurological side effects, weight, and health costs. First, considering patients randomized to olanzapine or risperidone, outcomes among patients who had been on the drug to which they were randomized prior to CATIE (N = 129 “stayers”) were compared to outcomes of those who switched to either of these two drugs (N = 269 “switchers”). A second set of analyses considered patients on baseline monotherapy with olanzapine (N = 297); risperidone (N = 252) or quetiapine (n = 87) and compared those randomly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE. In mixed models of each outcome the in...
Inferences about Molecular Mechanisms through Fluctuation Analysis

Membrane channels operate in an inherently probabilistic fashion because the world at a molecular level is chaotic. As a consequence of this molecular chaos, the number of open channels in an excitable cell’s membrane varies incessantly around an average value and produces random fluctuations in membrane conductance. The statistical characteristics of these fluctuations are not identical for all channel types, but rather reflects those same physical processes that give rise to variety in behaviors between species of channels. Thus, one sort of channel may produce small and rapid fluctuations, whereas another may yield large, slow noise. The essence of fluctuation analysis —the study of a system’s inherent noise—is this: channel noise reflects underlying molecular mechanisms, so we can learn about these mechanisms by studying conductance fluctuations. In some situations, fluctuation analysis is simply an alternative to studying the average response to a perturbation, but in other instances we can gain information not otherwise available. For example, different molecular mechanisms can exhibit identical average behavior, but produce fluctuations with distinct characteristics.