cssi/SciSciGPT-SciSciNet huggingface dataset:
Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli.

Lesions of parahippocampal structures impair perfor- mance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working mem- ory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to ex- amine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly famil- iar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pic- tures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent with- out hypothesis that the medial temporal lobe is recruited for the short- term maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and para- hippocampal recruitment in the target-matching task with familiar stim- uli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli. Hippocampus 2001;11: 337-346. © 2001 Wiley-Liss, Inc.
Pulmonary manifestations of immune deficiency diseases.

The defense of the respiratory system against infection involves a complex interplay of the humoral immune system and the cellular immune system with complement and phagocytic cells. The respiratory tract is an important portal of entry for infection, and it is therefore not surprising that many immune deficiencies present initially with a respiratory infection. Thus, pediatric pulmonologists must be familiar with the pulmonary manifestation of immune deficiency. In this article we review current concepts concerning pulmonary disease in children with primary immune deficiency diseases and acquired immune deficiency syndrome (AIDS).
The Role of the Multidrug Resistance Protein-1 in Modulation of Endothelial Cell Oxidative Stress

Glutathione (GSH) is the major source of intracellular sulfhydryl groups. Oxidized GSH (GSSG) can be recycled to GSH by the GSH reductase or exported from the cell. The mechanism by which GSSG is exported and the consequence of its export from endothelial cells has not been defined previously. We found that human endothelial cells express the multidrug resistance protein-1 (MRP1) and use this as their major exporter of GSSG. Oscillatory shear stress, which is known to stimulate endothelial cell production of reactive oxygen species, decreased intracellular GSH. In contrast, laminar shear significantly increased intracellular GSH. Oscillatory shear also caused a robust export of GSSG that was prevented by the MRP1 inhibitor MK571 and by MRP1 small interfering RNA. MRP1 inhibition prevented the decline in intracellular GSH, preserved the intracellular GSH Nernst potential, and reduced apoptosis caused by oscillatory shear. In aortas of hypertensive mice, endothelial disulfide export was doubled, and this was prevented by MK571 and was not observed in aortas of hypertensive MRP1-/- mice. Further, the altered endothelium-dependent vasodilatation caused by hypertension was ameliorated in MRP1-/- mice. GSSG export by MRP1 leads to a perturbation of endothelial redox state and ultimately endothelial cell apoptosis. Endothelial MRP1 may provide a novel therapeutic target for prevention of vascular disease.
Far-field patterns of electron-beam pumped semiconductor lasers

Laser action is described for total internal reflection modes such that the far-field pattern is a circular ring surrounding the crystal in a plane perpendicular to the rectangular cavity faces. A number of recent experiments have shown that this far-field pattern can be observed in GaAs samples as well as in ZnO and CdS. Experiments are reported for single crystals at a temperature of 77°K pumped by a low-voltage electron beam using 100-ns low-duty cycle pulses. Photographs of the far-field pattern show a narrow line extending 360° around the axis of the crystal and having an angular width of 5 to 10°. Photographs of the near-field pattern indicate that the laser light is emitted in quadrants at the four corners of the rectangular cavity, combining at large distances to produce a 360° pattern. Experimental results on a number of CdS crystals of various thicknesses show that the voltage threshold for lasing (at constant current density) for the total internal reflection mode varies approximately as the 0.7 power of the crystal thickness. Losses from total internal reflection are negligible, and for CdS and ZnO platelets absorption losses are also so small that lasing can occur when the penetration depth of the electrons is only 1/40 of the total crystal thickness. Because of these low losses, lasing has been observed in ZnO and CdS at 2.5 keV and a current density of about 5 A/cm2for crystal platelets approximatley 2 microns thick. Since the penetration of a 2.5 keV electron is only about 500 A, this indicates that surface losses in CdS and ZnO with as-grown surfaces are also small. A similar thickness dependence is reported for GaAs doped with 1.5 \times 10^{19} Zn atoms/cm3, but absorption losses appear to be higher. Thus a 2-micron-thick crystal of GaAs pumped with an electron beam of the same current density as above lases with a voltage threshold of 10 keV. The threshold voltages measured for ZnO, CdS, and GaAs are considerably lower than any previously reported for electron-beam pumped semiconductor lasers.
Shift length and on-duty rest patterns in rotor-wing air medical programs.

Abstract Introduction Air medical teams provide around-the-clock critical care, a pattern at risk of inducing performance-altering fatigue from circadian disruption and sleep deprivation. Safety is an essential issue in the air medical industry, but little data are available on shift length and on-duty rest practices. We report the results of a survey concerning those practices and analyze the relationships to crew duty practices by program model (hospital-operated, vendor-operated, independent, or public safety), base location, flight volume, and job requirements. Methods A survey was mailed to 182 Association of Air Medical Services-member rotor-wing air medical programs in the United States that complete scene flights with a flight nurse. One-hundred-twenty-nine programs (70.9%) returned anonymous surveys, all of which were used for data analysis. Results were analyzed with descriptive and nonparametric statistics. Results All pilots work shifts between 10 and 14 hours. For medical team members the shift distribution is: ≤ 8 hours, 0.4%; 9 to 12 hours, 44.2%; 12 to 16 hours, 7.0%; 17 to 24 hours, 45%; > 24 hours, 3.5%. An independent association exists between shift length greater than 12 hours and each of the following: flight volume per-aircraft under 731 flights/year, program model other than hospital operated, and nonhospital base (Fisher's exact test with Bonferroni correction, P All pilots are allowed on-duty rest on both day and night shifts. On-duty rest is permitted for 67.4% of medical team members: 18.2% only at night, and 49.2% at any time of day. The presence of any period of on-duty crew rest is significantly associated with nonhospital base, program model other than hospital-operated, and shift length exceeding 12 hours (Fisher's exact test with Bonferroni correction, P P Conclusion Notable differences arose between on-duty work and rest patterns for pilots and medical team members. Medical team members generally work longer shifts than pilots do, with shifts exceeding 12 hours as the most common staffing pattern. Medical team members also have less access to on-duty rest than do pilots. Traditional hospital-operated programs are more likely to use shorter shifts and prohibit on-duty rest for the medical teams, whereas vendor-operated, independent, or public safety programs are more likely to use longer shifts and permit on-duty rest. As the industry works toward a unified approach to mitigating the impact of fatigue on safe operation, variable practices based on job description and program style may be a factor.
A Novel Sorting Motif in the Glutamate Transporter Excitatory Amino Acid Transporter 3 Directs Its Targeting in Madin–Darby Canine Kidney Cells and Hippocampal Neurons

The glutamate transporter excitatory amino acid transporter 3 (EAAT3) is polarized to the apical surface in epithelial cells and localized to the dendritic compartment in hippocampal neurons, where it is clustered adjacent to postsynaptic sites. In this study, we analyzed the sequences in EAAT3 that are responsible for its polarized localization in Madin-Darby canine kidney (MDCK) cells and neurons. Confocal microscopy and cell surface biotinylation assays demonstrated that deletion of the EAAT3 C terminus or replacement of the C terminus of EAAT3 with the analogous region in EAAT1 eliminated apical localization in MDCK cells. The C terminus of EAAT3 was sufficient to redirect the basolateral-preferring EAAT1 and the nonpolarized EAAT2 to the apical surface. Using alanine substitution mutants, we identified a short peptide motif in the cytoplasmic C-terminal region of EAAT3 that directs its apical localization in MDCK cells. Mutation of this sequence also impairs dendritic targeting of EAAT3 in hippocampal neurons but does not interfere with the clustering of EAAT3 on dendritic spines and filopodia. These data provide the first evidence that an identical cytoplasmic motif can direct apical targeting in epithelia and somatodendritic targeting in neurons. Moreover, our results demonstrate that the two fundamental features of the localization of EAAT3 in neurons, its restriction to the somatodendritic domain and its clustering near postsynaptic sites, are mediated by distinct molecular mechanisms.
The future: taking veterinary laparoscopy to the next level.

Practical relevance:Laparoscopic surgery minimizes tissue trauma and speeds recovery, but its uptake into veterinary clinical practice has been slow.Clinical challenges:Laparoscopy is distinctly different from traditional open surgery and a reduced working area and loss of depth perception are among the challenges that the surgeon must get to grips with. Indeed, it is often lack of the necessary skills, rather than the cost of equipment, that presents the greatest obstacle.Audience:This article is aimed at practitioners keen to embrace minimally invasive surgery and advises on how to develop excellence in laparoscopic skills. It makes the case for simulation training and outlines methods that can be instituted in practice at low cost and with comparatively little time expenditure. It also describes technological advances that have already increased the success of veterinary ‘keyhole’ surgery, as well as those that look promising for the future.Evidence base:Simulation training has been an intense area of ...
Comparison of historic Grübler dyes with modern counterparts.

Seventeen Grubler dyes produced in Germany between 1880 and 1939 were examined in this study. These dyes were: fuchsin-bacillus, diamond fuchsin, fuchsin S acid, rubin S, safranin O water soluble, safranin yellowish water soluble, methyl eosin, Sudan III, scarlet R, auramine, orange G, aniline blue, pyronin, carmine, lithium carmine, hematein and aurantia. Spectrophotometry and staining characteristics were used to determine the maximum absorbance and efficacy of each dye in common staining techniques. The spectral curves and staining characteristics of these dyes compared well with modern dyes used as controls. Fuchsin bacillus and diamond fuchsin are synonyms for basic fuchsin. Fuchsin S acid and rubin S are synonyms for acid fuchsin. The scarlet R sample was the same as the Sudan III. The two safranins were the same. The basic fuchsin samples were unsuitable for preparation of Schiff's reagent. Both basic fuchsin and pyronin samples were less concentrated than modern counterparts. It is noteworthy that...
Automated classification of EEG signals in brain tumor diagnostics

In brain tumor diagnostics, EEG is most relevant in assessing how basic functionality is affected by the lesion and how the brain responds to treatments (e.g. post-operative). This paper focuses on developing an automated system to identify space-occupying lesions in the brain using EEG signals. We discuss major complications in relating EEG to different tumor classes and suggest an approach of feature extraction using wavelet techniques and classification by self-organizing maps. Initial tests show improvement over conventional frequency band features common in the EEG community. The tests also highlight the need to obtain efficient physically-motivated features as to how EEG is affected by various tumors.
Accuracy and limitations of second-order many-body perturbation theory for predicting vertical detachment energies of solvated-electron clusters

Vertical electron detachment energies (VDEs) are calculated for a variety of (H2O)n− and (HF)n− isomers, using different electronic structure methodologies but focusing in particular on a comparison between second-order Moller–Plesset perturbation theory (MP2) and coupled-cluster theory with noniterative triples, CCSD(T). For the surface-bound electrons that characterize small (H2O)n− clusters (n ≤ 7), the correlation energy associated with the unpaired electron grows linearly as a function of the VDE but is unrelated to the number of monomers, n. In every example considered here, including strongly-bound “cavity” isomers of (H2O)24−, the correlation energy associated with the unpaired electron is significantly smaller than that associated with typical valence electrons. As a result, the error in the MP2 detachment energy, as a fraction of the CCSD(T) value, approaches a limit of about −7% for (H2O)n− clusters with VDEs larger than about 0.4 eV. CCSD(T) detachment energies are bounded from below by MP2 values and from above by VDEs calculated using second-order many-body perturbation theory with molecular orbitals obtained from density functional theory. For a variety of both strongly- and weakly-bound isomers of (H2O)20− and (H2O)24−, including both surface states and cavity states, these bounds afford typical error bars of ±0.1 eV. We have found only one case where the Hartree–Fock and density functional orbitals differ qualitatively; in this case the aforementioned bounds lie 0.4 eV apart, and second-order perturbation theory may not be reliable.
Elementary Properties and Examples of Analytic Functions

In this section the definition and basic properties of a power series will be given. The power series will then be used to give examples of analytic functions. Before doing this it is necessary to give some elementary facts on infinite series in ℂ whose statements for infinite series in ℝ should be well known to the reader. If a n is in ℂ for every n ≥ 0 then the series \(\sum\limits_{n = 0}^\infty {{a_n}} \) converges to z iff for every e > 0 there is an integer N such that \(|\sum\limits_{n = 0}^m {{a_n} - | < \in } \) whenever m ≥ N. The series ∑ a n converges absolutely if ∑ |a n | converges.
Approximations to the reliability of phased missions

supported by the Office of Naval Research (NR 042-300) and the Strategic Systems Project Office (TA 19422)
Validation of novel promoter sequences derived from two endogenous ubiquitin genes in transgenic Aedes aegypti

To date, only a limited number of promoter sequences have been described to drive transgene expression in the disease vector Aedes aegypti. We sought to increase this repertoire by characterizing the ability of upstream sequences derived from the Ae. aegypti Ub(L40) and polyubiquitin genes to drive the expression of marker proteins. Both genomic fragments were able to drive robust expression of luciferase in cultured mosquito cells. Following Mos1-transformation, the Ub(L40) promoter drove strong expression of a fluorescent marker in early larvae and in ovaries, while the polyubiquitin promoter drove robust EGFP expression in all stages of development, including constitutive expression throughout the midgut. These promoter fragments provide two new expression profiles for future Ae. aegypti genetic experiments.
Lightweight Remote Image Management for Secure Code Dissemination in Wireless Sensor Networks

Wireless sensor networks are considered ideal candidates for a wide range of applications. It is desirable and sometimes necessary to reprogram sensor nodes through wireless links after they are deployed to remove bugs or add new functionalities. Several approaches (e.g., Seluge, Sluice) have been proposed recently for secure code dissemination in wireless sensor networks, all as security extensions to the state-of-the- art code dissemination system named Deluge. However, existing approaches all focused on securing the propagation of code images, but overlooked the security vulnerabilities in other image management aspects such as rebooting and erasing code images. In this paper, we identify the security vulnerabilities in epidemic image management in all existing solutions to secure code dissemination in wireless sensor networks. Such vulnerabilities allow an attacker to reboot a sensor network to undesirable images or erase critical images, exposing the network to security risks. We then develop a sequence of lightweight techniques to address these vulnerabilities. Our approach takes into consideration the limited resources on current sensor platforms, and removes the security vulnerabilities without introducing significant overhead. To evaluate the feasibility of our approach, we implement the proposed approach as a remote image management system named Seluge-ImageMan, which is intended to work with Seluge, a security extension to Deluge for injecting new code images. We perform a substantial set of experiments in the WiSeNeT sensor testbed, which consists of 72 MicaZ motes, to assess the performance overhead of Seluge-ImageMan. The experimental results indicate that our approach introduces very light overhead while completing the secure remote code image management solution for wireless sensor networks.
Eddies in the Stream The Prevalence of Uncertain Plans for Retirement

OBJECTIVE This study examined an assumption of retirement theory that typifies older workers as preretirees who are planfully engaged in paths toward retirement. METHODS Using survey responses among workers in the 1992 and 1994 waves of the Health and Retirement Study, we described the prevalence of nonsubstantive answers to questions about the expected form and timing of retirement (e.g., "don't know," "haven't thought about it"). We tested explanations for this uncertainty as an artifact of the survey process, but also as an outcome of the opportunity structure for retirement planning. RESULTS Survey procedure did generate some of these noncommittal responses. Depending on question type, approximately 10% to 40% of workers did not state when or how they would retire, and such responses were less prevalent across age and time. In addition, categorical uncertainty about form and timing was theoretically predictable in a framework that supposed that workers less subject to a socially attended life--at work or away--would be more undecided about the future. DISCUSSION Uncertainty is an authentic, meaningful stance toward retirement that theory and research design should not ignore. Just as actual transitions to retirement can be ambiguous or blurred, the expectation of retirement, as well, can be untidy.
Epigenomic and Noncoding RNA Regulation in Addictive Processes

The phenotypic effects of drugs of abuse are partially mediated by transcriptional and epigenetic regulatory mechanisms. This chapter will provide a brief overview of substance abuse and then focus on the roles of three epigenetic regulatory mechanisms in addictive processes: histone modifications, DNA modifications, and noncoding RNAs. This chapter will conclude with a focus on three other important areas: (1) the potential for long-lasting epigenetic effects due to drugs of abuse, (2) obstacles and opportunities in this scientific area as they pertain to addiction biology, and (3) the potential for translating epigenomic and noncoding RNA discoveries into improvements in human health and the treatment of substance use disorders.
Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double‐Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease

Background We hypothesized that nebivolol, a β‐blocker with nitric oxide–mediated activity, compared with atenolol, a β‐blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. Methods and Results In this pilot double‐blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow‐up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low‐WSS segments in the nebivolol cohort ( P =0.06). Low‐WSS regions were associated with greater plaque progression ( P <0.0001) and constrictive remodeling ( P =0.04); conversely, high‐WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling ( P =0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin‐capped fibroatheromas per vessel. Importantly, after adjusting for β‐blocker, low‐WSS segments remained significantly associated with lumen loss and plaque progression. Conclusion Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low‐WSS segments in the nebivolol arm. Both β‐blockers had similar effects on oxidative stress, microvascular function, and endothelial function. Clinical Trial Registration URL: . Unique identifier: [NCT01230892][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01230892&atom=%2Fahaoa%2F5%2F1%2Fe002764.atom
Correlating thyroid cytology and histopathology: Implications for molecular testing

Background A gene expression classifier (GEC) has been advocated in management of some indeterminate nodules without surgery. We assessed the potential negative predictive value (NPV) of the GEC at our academic center. Methods Retrospectively, all cytologically indeterminate fine-needle aspirates (FNAs) diagnosed by University of Iowa cytopathologists over a 3-year period were identified. Histopathologic findings were recorded. Using published sensitivity and specificity, NPVs were calculated. Results Of 178 nodules (17, 135, and 26 in classes III, IV, and V, respectively), 71 (40%) were malignant. Prevalence of malignancy was 41%, 29%, and 96% for classes III, IV, and V, respectively. Using sensitivities and specificities for the GEC, NPVs were 91% for the cohort: 88%, 92%, and 26% for classes III, IV, and V, respectively. Conclusion Molecular testing should be associated with an NPV no lower than that from clinical criteria alone. With the prevalences reported, GEC use may result in more missed cancer diagnoses. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
PHYSIOLOGICAL STRESS AND COLOR POLYMORPHISM IN THE INTERTIDAL SNAIL NUCELLA LAPILLUS.

The intertidal snail Nucella lapillus exhibits considerable variation in shell color both within and between populations differentially exposed to wave action. Populations from high-wave-energy shores tended to be highly polymorphic and were dominated by pigmented morphs (especially brown), while those at more sheltered locations exhibited less polymorphism and were predominantly white. Field and laboratory experiments were conducted to determine the role of physiological stress and selective predation in maintaining the observed distribution of color morphs. The results demonstrated that 1) physiological stress from high temperature and desiccation during periods of tidal emersion was greater on protected shores, 2) under similar natural conditions, brown morphs heated up faster, attained higher temperatures, desiccated more rapidly, and suffered greater mortality than did white morphs, and 3) when pairs of brown and white morphs were tethered intertidally there was virtually no mortality of either morph on the exposed shore or in shaded microhabitats on the protected shore, but brown morphs suffered much greater mortality in sunny microhabitats on the protected shore. These findings demonstrate that the interpopulation variation in shell color of N. lapillus is in part a response to a selective gradient in physiological stress. Selection for crypsis by visually hunting predators did not appear to play a prominent role; however, only adults were considered, and the predation experiments were conducted in the fall before shorebirds that prey on whelks had arrived from their summer feeding grounds. Further experimentation to quantify the effects of visual predators such as birds and fish, particularly on juvenile snails, is necessary to assess adequately the importance of predation.
Elevation of gamma-aminobutyric acid in rat brain with hydroxylamine.

Summary1. Intraperitoneal injection of hydroxylamine resulted in elevation of levels of γ-aminobutyric acid in 8 brain areas of the rat. 2. These elevated levels of γ-aminobutyric acid were attained even after rats were pretreated with methylene blue to reduce methemoglobin formation. 3. The effect of a single injection of hydroxylamine persisted for at least 5 hours. 4. The potential value of this procedure for physiological study has been discussed.
p-Thiophenylalanine-induced DNA cleavage and religation activity of a modified vaccinia topoisomerase IB.

Vaccinia DNA topoisomerase IB is the smallest of the type IB topoisomerases. Because of its small size (314 amino acids) and target site specificity (5′(C/T)CCTTp↓ sites), it constitutes an excellent model for studying the interaction of type IB enzymes with duplex DNA. In this study, p-thiophenylalanine was incorporated into the enzyme active site (position 274) by in vitro translation in the presence of a chemically misacylated tRNA. The modification, which resulted in replacement of the nucleophilic tyrosine OH group with SH, retained DNA topoisomerase activity and did not alter the DNA cleavage site. However, the modified topoisomerase effected relaxation of supercoiled plasmid DNA at a rate about 16-fold slower than the wild-type enzyme. The thiophenylalanine-induced DNA cleavage rate (kcl = 1 × 10–4 s–1) was 30 times lower than for the wild-type enzyme (kcl = 3 × 10–3 s–1). In contrast, thiophenylalanine-induced DNA religation was faster than that of the wild-type enzyme. We propose that the change ...
Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1–1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 µg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (µg/g or µg/m2) and dermal wipes (Pearson=0.055 µg/g and 0.015 µg/m2; Spearman=0.644 µg/g and 0.578 µg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.
PEDIATRIC CARDIOMYOPATHY MUTATIONS IN A HIGHLY CONSANGUINEOUS POPULATION

Pediatric-onset cardiomyopathy is more common in inbred and highly consanguineous populations that are enriched for familial and recessive disease. The genetic causes of pediatric cardiomyopathy remain poorly understood. Nearly one quarter of marriages in Turkey are consanguineous. Studying this
Photodynamic Therapy and Cell Death Pathways

Photodynamic therapy (PDT) is the term used to describe the irradiation of photosensitized cells or tissue with phototoxic consequences. This process can result in the rapid initiation of not only apoptosis, an irreversible death pathway, but also autophagy. The procedures described here are designed to characterize the correlation between the PDT dose vs. survival of cells in vitro, the apoptotic effects of photodamage, and the extent of an autophagic response. These are assessed by clonogenic assays, observation of condensed chromatin characteristic of apoptosis, activation of “executioner” caspases, and the autophagic flux as indicated by comparing accumulation of the LC3-II protein under conditions where processing of autophagosomes is retarded vs. is not retarded.
Default Correlation Pricing and Trading

This chapter discusses the beginning of index and index tranche modeling. Correlation impacts risk assessment and valuation of CDO tranches. Each tranche value reflects correlation in a different way. Perhaps the most interesting correlation relationship shows in the equity (0–3%) tranche. This may first appear counterintuitive. It turns out that higher the correlation, lower is the equity tranche risk, and the value of the tranche is also correspondingly higher. Higher correlation makes extreme cases of very few defaults more likely. Everything else being the same, more the correlation, lower is the risk the investor takes on, and the premium the investor is going to receive over the lifetime of the tranche is also lower.
Mineralocorticoid Receptor (MR) trans-Activation of Inflammatory AP-1 Signaling: DEPENDENCE ON DNA SEQUENCE, MR CONFORMATION, AND AP-1 FAMILY MEMBER EXPRESSION *

Glucocorticoids are commonly used to treat inflammatory disorders. The glucocorticoid receptor (GR) can tether to inflammatory transcription factor complexes, such as NFκB and AP-1, and trans-repress the transcription of cytokines, chemokines, and adhesion molecules. In contrast, aldosterone and the mineralocorticoid receptor (MR) primarily promote cardiovascular inflammation by incompletely understood mechanisms. Although MR has been shown to weakly repress NFκB, its role in modulating AP-1 has not been established. Here, the effects of GR and MR on NFκB and AP-1 signaling were directly compared using a variety of ligands, two different AP-1 consensus sequences, GR and MR DNA-binding domain mutants, and siRNA knockdown or overexpression of core AP-1 family members. Both GR and MR repressed an NFκB reporter without influencing p65 or p50 binding to DNA. Likewise, neither GR nor MR affected AP-1 binding, but repression or activation of AP-1 reporters occurred in a ligand-, AP-1 consensus sequence-, and AP-1 family member-specific manner. Notably, aldosterone interactions with both GR and MR demonstrated a potential to activate AP-1. DNA-binding domain mutations that eliminated the ability of GR and MR to cis-activate a hormone response element-driven reporter variably affected the strength and polarity of these responses. Importantly, MR modulation of NFκB and AP-1 signaling was consistent with a trans-mechanism, and AP-1 effects were confirmed for specific gene targets in primary human cells. Steroid nuclear receptor trans-effects on inflammatory signaling are context-dependent and influenced by nuclear receptor conformation, DNA sequence, and the expression of heterologous binding partners. Aldosterone activation of AP-1 may contribute to its proinflammatory effects in the vasculature.
The Molecular Mechanism of Cellular Sensing of Acidity

Acidic conditions, which might be of physiologic or pathologic origin, are sensed by a variety of cellular mechanisms. In the brain and other central nervous system (CNS) areas, the foremost acid-sensing molecule most responsive to changes in pH is the acid-sensing ion channel (ASIC). In the peripheral nervous system (PNS), detection of acid is mostly moderated by ASICs along with other channels like the transient receptor potential (TRP) family which play a critical role in the transmission of the pain, tissue inflammation, and other pathologic conditions. Still, there are a variety of other ion channels and transporters responsive to pH changes, for example N-methyl-D-aspartate (NMDA) channels, outwardly rectifying Cl- channels and adenosine triphosphate (ATP)-sensitive K+ channels. The molecular mechanism of pH sensing is due in part to the biochemical structure of these membrane proteins which confers functionality. Recently solved ASIC crystal structure has been helpful to determine how this ion channel works. Functional ASIC proteins are composed of three subunits, each with two transmembrane domains. Minor distinctions between subunits give the channel unique physiologic properties. The most striking features of ASIC proteins are the large extracellular portion where proton interaction takes place and the pore region through which ions are conducted. Structural anomalies, defects in expression, are conditions in which ASICs or other acid-sensing molecules contribute to disease. Dysregulated pH homeostasis is involved in glutamate-independent acidosis-mediated neuronal injury where injury results from rapid and large intracellular Ca2+ increase. This principle is a hallmark characteristic of ischemic stroke. A detailed understanding of underlying cellular mechanisms to sensing acidity is absolutely required so that new therapies and curative medicines can be developed.
The Splicing History of an mRNA Affects Its Level of Translation and Sensitivity to Cleavage by the Virion Host Shutoff Endonuclease during Herpes Simplex Virus Infections.

ABSTRACT During lytic herpes simplex virus (HSV) infections, the virion host shutoff (Vhs) (UL41) endoribonuclease degrades many cellular and viral mRNAs. In uninfected cells, spliced mRNAs emerge into the cytoplasm bound by exon junction complexes (EJCs) and are translated several times more efficiently than unspliced mRNAs that have the same sequence but lack EJCs. Notably, most cellular mRNAs are spliced, whereas most HSV mRNAs are not. To examine the effect of splicing on gene expression during HSV infection, cells were transfected with plasmids harboring an unspliced renilla luciferase (RLuc) reporter mRNA or RLuc constructs with introns near the 5′ or 3′ end of the gene. After splicing of intron-containing transcripts, all three RLuc mRNAs had the same primary sequence. Upon infection in the presence of actinomycin D, spliced mRNAs were much less sensitive to degradation by copies of Vhs from infecting virions than were unspliced mRNAs. During productive infections (in the absence of drugs), RLuc was expressed at substantially higher levels from spliced than from unspliced mRNAs. Interestingly, the stimulatory effect of splicing on RLuc expression was significantly greater in infected than in uninfected cells. The translational stimulatory effect of an intron during HSV-1 infections could be replicated by artificially tethering various EJC components to an unspliced RLuc transcript. Thus, the splicing history of an mRNA, and the consequent presence or absence of EJCs, affects its level of translation and sensitivity to Vhs cleavage during lytic HSV infections. IMPORTANCE Most mammalian mRNAs are spliced. In contrast, of the more than 80 mRNAs harbored by herpes simplex virus 1 (HSV-1), only 5 are spliced. In addition, synthesis of the immediate early protein ICP27 causes partial inhibition of pre-mRNA splicing, with the resultant accumulation of both spliced and unspliced versions of some mRNAs in the cytoplasm. A common perception is that HSV-1 infection necessarily inhibits the expression of spliced mRNAs. In contrast, this study demonstrates two instances in which pre-mRNA splicing actually enhances the synthesis of proteins from mRNAs during HSV-1 infections. Specifically, splicing stabilized an mRNA against degradation by copies of the Vhs endoribonuclease from infecting virions and greatly enhanced the amount of protein synthesized from spliced mRNAs at late times after infection. The data suggest that splicing, and the resultant presence of exon junction complexes on an mRNA, may play an important role in gene expression during HSV-1 infections.
Big Data and Deep Analytics Applied to the Common Tactical Air Picture (CTAP) and Combat Identification (CID)

Accurate combat identification (CID) enables warfighters to locate and identify critical airborne objects as friendly, hostile or neutral with high precision. The current CID processes include processing and analysing data from a vast network of sensors, platforms, and decision makers. CID plays an important role in generating the Common Tactical Air Picture (CTAP) which provides situational awareness to air warfare decision-makers. The Big âCIDâ Data and complexity of the problem pose challenges as well as opportunities. In this paper, we discuss CTAP and CID challenges and some Big Data and Deep Analytics solutions to address these challenges. We present a use case using a unique deep learning method, Lexical Link Analysis (LLA), which is able to associate heterogeneous data sources for object recognition and anomaly detection, both of which are critical for CTAP and CID applications.
SOX2 is required for inner ear neurogenesis

Neurons of the cochleovestibular ganglion (CVG) transmit hearing and balance information to the brain. During development, a select population of early otic progenitors express NEUROG1, delaminate from the otocyst, and coalesce to form the neurons that innervate all inner ear sensory regions. At present, the selection process that determines which otic progenitors activate NEUROG1 and adopt a neuroblast fate is incompletely understood. The transcription factor SOX2 has been implicated in otic neurogenesis, but its requirement in the specification of the CVG neurons has not been established. Here we tested SOX2’s requirement during inner ear neuronal specification using a conditional deletion paradigm in the mouse. SOX2 deficiency at otocyst stages caused a near-absence of NEUROG1-expressing neuroblasts, increased cell death in the neurosensory epithelium, and significantly reduced the CVG volume. Interestingly, a milder decrease in neurogenesis was observed in heterozygotes, indicating SOX2 levels are important. Moreover, fate-mapping experiments revealed that the timing of SOX2 expression did not parallel the established vestibular-then-auditory sequence. These results demonstrate that SOX2 is required for the initial events in otic neuronal specification including expression of NEUROG1, although fate-mapping results suggest SOX2 may be required as a competence factor rather than a direct initiator of the neural fate.
Initiation and Engagement with Methadone Treatment among Pregnant and Postpartum Women

Abstract Purpose The purpose of this study was to explore perceptions of experiences and challenges with methadone maintenance treatment (MMT) and obstetrical care among pregnant and postpartum women enrolled in a methadone maintenance program. Research Design The study featured a grounded theory approach including two focus groups with pregnant and postpartum methadone users at a methadone maintenance clinic in Worcester, Massachusetts. Two research team members conducted and recorded focus groups, which took approximately 45 minutes to 1 hour. Grounded theory was used to guide data analysis and open coding, where transcripts were reviewed line by line to create code definitions as concepts emerged inductively from the data. Results Five emergent themes were derived from the data: 1) guilt, coupled with fear of negative outcomes for their infant, dictates women's MMT treatment decisions; 2) finding obstetricians with experience treating pregnant women using methadone can be a challenge; 3) methadone clinic physicians are instrumental in helping women find the right methadone dose during pregnancy; 4) some women had strong preferences for methadone over buprenorphine; and 5) women face substantial substance abuse treatment challenges after delivery. Conclusions Women experience substantial challenges engaging in MMT during the perinatal period. Additional challenges arise from finding obstetrical providers who have experience with MMT and are willing to care for pregnant women. This study may provide a starting point for future interventions seeking to improve care coordination between substance abuse treatment and prenatal care programs.
Initial impacts of rain gardens’ application on water quality and quantity in combined sewer: field-scale experiment

Green infrastructures such as rain gardens can benefit onsite reduction of stormwater runoff, leading to reduced combined sewer overflows. A pilot project was conducted to evaluate the impact of rain gardens on the water quality and volume reduction of storm runoff from urban streets in a combined sewer area. The study took place in a six-block area on South Grand Boulevard in St. Louis, Missouri. The impact was assessed through a comparison between the pre-construction (2011/2012) and the post-construction (2014) phases. Shortly after the rain gardens were installed, the levels of total suspended solids, chloride, total nitrogen, total phosphorous, zinc, and copper increased. The level of mercury was lower than the detection level in both phases. E. coli was the only parameter that showed statistically significant decrease following the installation of rain gardens. The likely reason for initial increase in monitored water quality parameters is that the post-construction sampling began after the rain gardens were constructed but before planting, resulted from soil erosion and wash-out from the mulch. However, the levels of most of water quality parameters decreased in the following time period during the post-construction phase. The study found 76% volume reduction of stormwater runoff following the installation of rain gardens at one of studied sites. Statistical analysis is essential on collected data because of the encountered high variability of measured flows resulted from low flow conditions in studied sewers.
Site-Specific Glycan Heterogeneity Characterization by Hydrophilic Interaction Liquid Chromatography Solid-Phase Extraction, Reversed-Phase Liquid Chromatography Fractionation, and Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry.

Reversed-phase chromatographic separation of glycopeptides tends to be dominated by the peptide composition. In contrast, capillary zone electrophoresis separation of glycopeptides is particularly sensitive to the sialic acid composition of the glycan. In this paper, we combine the two techniques to achieve superior N-glycopeptide analysis. Glycopeptides were first isolated from a tryptic digest using hydrophilic interaction liquid chromatography (HILIC) solid-phase extraction. The glycopeptides were separated using reversed-phase ultra high-performance liquid chromatography (UHPLC) to generate four fractions corresponding to different peptide backbones. Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry (CZE-ESI-MS/MS) was used to analyze the fractions. We applied this method for the analysis of alpha-1-acid glycoprotein (AGP). A total of 268 site-specific N-glycopeptides were detected, representing eight different glycosylation sites from two isomers of AGP. Glycans included...
Getting by with a little help from our friends

We offer two kinds of constructive criticism in the spirit of support for Doris's socially scaffolded pluralism regarding agency. First: The skeptical force of potential "goofy influences" is not as straightforward as Doris argues. Second: Doris's positive theory must address more goofy influences due to social processes that appear to fall under his criteria for agency-promoting practices. Finally, we highlight "arms race" phenomena in Doris's social dynamics that invite closer attention in further development of his theory.