cssi/SciSciGPT-SciSciNet huggingface dataset:
Combinatorial immunotherapeutic approaches to restore the function of anergic tumor-reactive cytotoxic CD8(+) T cells.

Numerous preclinical studies have demonstrated that combination immunotherapy can significantly reduce tumor growth and improve overall survival as compared to monotherapy. Furthermore, dual CTLA-4/PD-1 checkpoint blockade recently received FDA-approval for patients with metastatic melanoma, becoming the first combination immunotherapy to garner this designation in a rapidly evolving field. Despite this progress, the majority of patients do not respond to treatment, underscoring the critical need for more effective therapies. We have been investigating the mechanisms by which combination immunotherapy with an OX40 agonist plus CTLA-4 checkpoint blockade augments effector T cell responses to elicit anti-tumor immunity. Surprisingly, this approach failed to eradicate well-established tumors, in part due to the induction of anergy in cytotoxic CD8+ T cells. Further work revealed that anergic CD8+ T cells could be rescued by combining a dendritic cell-targeted vaccine with combination immunotherapy. Taken together, these data suggest that novel combinatorial immunotherapeutic strategies incorporating a vaccination strategy may be needed to generate effective anti-tumor responses in the majority of patients with metastatic disease.
Directional well trajectory design: The theoritical development of Azimuth bends and turns in complex well trajectory designs

Most complex well trajectories usually have bends and turns. The design requires some considerations to be made from the structure of subsurface formations to be drilled, to the available technology and equipment, as well as economics. When a complex well trajectory is being worked on, the effect of bends/turns in the azimuth is highly critical and care is taken not to exceed a set maximum tolerable dogleg severity. In this work, several well trajectories with varying bends and turns were modelled mathematically, for an easy calculation and pre-survey record presentation of a desired complex directional well trajectory, also from which the overall angle change (dogleg) is observed not to exceed a set maximum tolerable dogleg. A scenario was considered with few assumptions using a specially developed application, WellTIT v. 1.0, which assisted in calculating and presenting survey records to express the need for carefully developed bends in a Complex well trajectory design. http://dx.doi.org/10.4314/njt.v35i4.18
COST-BENEFIT ANALYSIS OF SAFETY BELTS IN TEXAS SCHOOL BUSES

Although safety belts have been shown to reduce the risk of serious injury or death in automobile crashes, evidence of their effectiveness in school buses is uncertain. In this paper, the potential costs and benefits of mandatory safety belts in Texas school buses are estimated, based on the assumption that their effectiveness is less than or equal to rear seatbelt effectiveness in autos. Costs are based on both retrofitting old buses with belts and installing them in new buses. Benefits include the direct and indirect (forgone earnings) cost-savings from preventable injuries and fatalities. Results indicate that a law mandating safety belts in Texas school buses would not be cost-beneficial. Annual benefits would exceed the annual costs of installing belts in new school buses. However, the benefits would not be large enough to compensate for the five-year costs associated with retrofitting old buses.
Women and higher education: A bibliography

This bibliography focuses on women and higher education cross-nationally. It has its origins in a broader earlier annotated bibliography (Kelly and Kelly, 1989) which listed over 1800 works on women’s schooling in the Third World in general and a much smaller number on women and higher education. This bibliography differs in that it includes references on women’s higher education in North American, European, and industrialized Asian and African nations and has been updated to include materials published through 1989. The present bibliography contains studies appearing in the 1980s. It is a guide to recently published research rather than a comprehensive listing of research. The bibliography concentrates on published research and was drawn from standard reference works, including the National Union Catalog, The Education Index, the Social Science Index, the British Humanities Index, the British Education Index, the Canadian Education and Bulletin Signeltique. It contains scholarly books and articles. Excluded are popular materials, very short articles and reportage, most government documents, and dissertations. Works in English, French, Spanish, Portuguese and German are listed, but, given the guides consulted, the bibliography is most comprehensive for research in English.
Nigrosome 1 absence in de novo Parkinson disease

A 63-year-old man with 6 months of mild left hand rest tremor and bradykinesia and subtle left wrist cogwheel rigidity was diagnosed with idiopathic Parkinson disease (PD). The most profound neuronal degeneration in PD occurs in nigrosome 1, a lens-shaped substructure of the substantia nigra containing approximately 22,000 cell bodies in each hemi-midbrain, measuring 6 × 6 × 1 mm.1,2 A 7T MRI at the caudal level of red nucleus (figure, A) shows nigrosome 1 signal present in the left nigra and absent in the right, consistent with the clinically affected side. 7T MRI of a healthy 63-year-old with normal bilateral nigrosome 1 signal is shown for comparison (figure, B).
Treatment of Meningeal Leukemia With Pyrimethamine

Pyrimethamine, a substituted pyrimidine with potent folate antagonistic properties, was given orally to treat two episodes of meningeal leukemia in a longterm survivor with acute myeloblastic leukemia. Remissions of seven and at least 6 mo duration were obtained on the two occasions. Spinal fluid concentrations of pyrimethamine were 10-25% of the simultaneous plasma concentrations. Considerations regarding lipid solubility, body distribution, and easily reversible toxicity of pyrimethamine suggest that further therapeutic trials are warranted, especially in childhood lymphoblastic leukemia.
Hazard and Risk Reduction Strategies

This chapter discusses that in both proactive and reactive phases of emergency response planning, hazard and risk reduction are the central objectives. Hazard reduction strategies include any attempt to minimize the potential harm or injury associated with any substance, situation, or condition. Risk reduction strategies focus not on the source of potential hazards, but rather on the exposure of persons to those hazards. As coequal efforts to minimize the impact of emergencies, hazard and risk reduction are most often described as two aspects of the process of mitigation. The concept of mitigation is very broad, inclusive of both proactive and reactive actions taken by both response and non-response personnel, and by governmental as well as private organizations.
The Transformation of Governance and Public Affairs Education

Public affairs education faces a critical challenge in providing managers and analysts with the right knowledge and skills in a time when governance has been transformed. While government's traditi...
Radioactive iodine uptake in hyperthyroid cats after administration of recombinant human thyroid stimulating hormone.

Background Radioactive iodine therapy is considered the treatment of choice for hyperthyroidism in cats, but the availability of this modality is limited by costs and hospitalization requirements. Administration of recombinant human thyroid stimulating hormone (rh-TSH) to humans with thyroid neoplasia or nodular goiter can increase thyroidal iodine uptake, thereby allowing the use of lower radioactive iodine doses for treatment. Veterinary studies of this subject are limited, and results are conflicting. Objective To investigate the effects of rh-TSH administration on thyroidal iodine uptake in hyperthyroid cats. Animals Ten client-owned hyperthyroid cats. Methods In this prospective clinical study, cats were administered saline (placebo), 50 μg rh-TSH (low-dose), and 100 μg rh-TSH (high-dose) in randomized crossover design with treatments separated by 7-10 days. After each treatment, thyroid scintigraphy was performed by administering 300 μCi 123 I and assessing radionuclide uptake 8 and 24 hours later. Serum thyroid hormone concentrations were measured at each visit. Results Thyroidal percent iodine uptakes (mean ± SD at 8 and 24 hours) in cats treated with placebo (25.2 ± 13.4%, 30.0 ± 12.8%), low-dose (24.1 ± 12.5%, 29.4 ± 13.7%), and high-dose rh-TSH (24.2 ± 16.3%, 30.8 ± 15.3%) were not different (P = .76). Independent of rh-TSH administration, percent iodine uptakes were positively correlated with serum thyroid hormone concentrations. Conclusions and clinical importance One-time administration of rh-TSH, even at high doses, would not be expected to lower radioactive iodine doses needed for treatment of hyperthyroidism in cats. Investigations of alternate strategies to increase thyroidal uptake of radioactive iodine are warranted.
Preliminary Design of Nutrient Removal Basins in the Fisheating Creek Watershed in Florida, USA Subject to Drought Conditions and Low Water Availability

The Fisheating Creek watershed located in Florida, United States of America (USA) is the focus of intense efforts to reduce nutrient transport into Lake Okeechobee which is located downstream. Public agencies and private land owners proposed constructing large nutrient removal basins in the watershed to reduce the overall nutrient load into Lake Okeechobee. This is challenging given the nature of the watershed with its low water availability and sensitivity to drought. This study evaluates the feasibility of implementing nutrient removal systems in such a watershed, including the overall risk and uncertainty of system performance. The study uses statistical evaluations of available water resources data and model simulations using Hydrologic Engineering Center Hydrologic Modeling System (HEC-HMS) to evaluate watershed flow conditions. Then, the study outlines alternatives for nutrient removal system implementation. The study revealed that considerable nutrient reduction is feasible but not optimal due to low overall water availability. The primary conclusion is that, while nutrient removal projects as large as 294 hectares can be constructed, the overall system operation will have to be very flexible to account for widely ranging inflows, including very low flows during drought situations.
In Vivo -Relevant Transwell Dish-Based Dissolution Testing for Orally Inhaled Corticosteroid Products

To establish an in vivo-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products. “Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane. While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (kdiss) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection. The in vivo-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.
Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department

Abstract Objectives This study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography–derived fractional flow reserve (FFRCT) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)–based triage program. Background FFRCT is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied. Methods ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFRCT were studied. FFRCT ≤0.80 was considered positive for hemodynamically significant stenosis. Results Among 555 patients, 297 underwent coronary CTA and FFRCT (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFRCT was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFRCT groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFRCT results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFRCT when revascularization was deferred. Negative FFRCT was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFRCT (8.0%) and coronary CTA (22.9%) (p Conclusions In ACP, FFRCT is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFRCT, which is associated with higher nonobstructive disease on invasive angiography.
KSOS—The design of a secure operating system *

This paper discusses the design of the Department of Defense (DoD) Kemelized Secure Operating System (KSOS, formerly called Secure UNIX). ** KSOS is intended to provide a provably secure operating system for larger minicomputers. KSOS will provide a system call interface closely compatible with the UNIX operating system. The initial implementation of KSOS will be on a Digital Equipment Corporation PDP-11/70 computer system. A group from Honeywell is also proceeding with an implementation for a modified version of the Honeywell Level 6 computer system.
Acute renal failure in adult horses

Renal disease can be pre-, intrinsic or post-renal in origin, with pre-renal disease being the most common and generally straightforward to correct if the primary problem can be addressed. Intrinsi...
4-Cyanoindole-based fluorophores for biological spectroscopy and microscopy.

Abstract Most biological molecules are intrinsically non- or weakly-fluorescent, hence requiring labeling with an external fluorophore(s) to be studied via fluorescence-based techniques. However, such labeling could perturb the native property of the system in question. One effective strategy to minimize such undesirable perturbation is to use fluorophores that are simple analogs of natural amino acids. In this chapter, we describe the synthesis and spectroscopic utility of two indole-based fluorophores, 4-cynaotryprophan (4CN-Trp) and 4-cyanoindole-2′-deoxyribonucleoside (4CNI-NS), with a focus on 4CN-Trp. This unnatural amino acid, which is only slightly larger than its natural counterpart, tryptophan (Trp), exhibits unique photophysical properties, making it a versatile fluorophore in biological spectroscopic and imaging applications. Through several specific examples, we highlight its broad utility in the study of various biological problems and processes.
Clinical Performance of Two SARS-CoV-2 Serologic Assays.

BACKGROUND: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid proliferation of serologic assays. However, little is known about their clinical performance. Here, we compared two commercial SARS-CoV-2 IgG assays. METHODS: 103 specimens from 48 patients with PCR-confirmed SARS-CoV-2 infections and 153 control specimens were analyzed using SARS-CoV-2 serologic assays by Abbott and EUROIMMUN (EI). Duration from symptom onset was determined by medical record review. Diagnostic sensitivity, specificity, and concordance were calculated. RESULTS: The Abbott SARS-CoV-2 assay had a diagnostic specificity of 99.4% (95% CI; 96.41-99.98%), and sensitivity of 0.0% (95% CI; 0.00-26.47%) at <3 days post symptom onset, 30.0% (95% CI; 11.89-54.28) at 3-7d, 47.8% (95% CI; 26.82-69.41) at 8-13d and 93.8% (95% CI; 82.80-98.69) at ≥14d. Diagnostic specificity on the EI assay was 94.8% (95% CI; 89.96-97.72) if borderline results were considered positive and 96.7% (95% CI; 92.54-98.93) if borderline results were considered negative. The diagnostic sensitivity was 0.0% (95% CI; 0.00-26.47%) at <3d, 25.0% (95% CI; 8.66-49.10) at 3-7d, 56.5% (95% CI; 34.49-76.81) at 3-7d and 85.4% (95% CI; 72.24-93.93) at ≥14d if borderline results were considered positive. The qualitative concordance between the assays was 0.83 (95% CI; 0.75-0.91). CONCLUSION: The Abbott SARS-CoV-2 assay had fewer false positive and false negative results than the EI assay. However, diagnostic sensitivity was poor in both assays during the first 14 days of symptoms.
Case Series of Botulinum Toxin Administered to Pregnant Patients and Review of the Literature

Objective: To evaluate a case series of patients who received medically necessary botulinum toxin during pregnancy. Materials and Methods: Retrospective chart review of three patients who underwent repeated intralaryngeal injections of botulinum toxin during pregnancy. Chart reviews were also conducted on the children to further evaluate the safety. Results: No evidence of harm to the mothers or fetuses were found in our series, including data from pregnancy and birth records using standard measures of gestation, APGAR scores, neonatal intensive care unit stay, and time until discharge. Clinical data for 3-5 years were available for the children. No evidence of muscular weakness was noted and all diagnoses were listed. Conclusion: Botulinum toxin injection for functional airway issues was not associated with any adverse effects to the mother or fetus during pregnancy in any of the cases reviewed. We recommend further investigation to evaluate the current contraindication of elective botulinum toxin use in pregnancy.
Colossoma macropomum-A tropical fish model for biology and aquaculture.

Tambaqui, a species native to the Amazon and Orinoco Basins and their tributaries, has a history marked by biological resilience that makes this species a model for studies focused on ecology, physiology, and fish farming. In addition, it is of economic interest, due to its favorable characteristics for production in farms and its unique flavor. As the tambaqui responds in a unique way to several environmental disturbances of natural origin, the species is often used in environmental studies. Some of these studies have been revisited in this review. We revised aspects related to its natural history, habitats and geographic distribution, physiological and biochemical adaptations, and zootechnical performance. The extraordinary adaptation of the tambaqui is the fast expansion of its lower lip when exposed to low oxygen availability that is improved simultaneously with other adjustments. The resilience of this species to significant alterations in water pH is also surprising, and is incomparable with that of other species, as only when it is exposed to pH 3.5, does the tambaqui begin to present physiological-biochemical disturbances. The analysis of the gene expression of tambaqui specimens under different experimental conditions has shed light on the adaptive mechanisms used by this unique Amazonian species. In this sense, this review sought to gather information regarding the tambaqui, and its many biological features employed to survive environmental challenges.
Management of Infants Born with Disorders of Sex Development

The aims of this chapter are the following: (1) provide a concise update on the mechanisms controlling normal and abnormal sexual differentiation, (2) provide a protocol used at our institution for practical management of infants born with DSD, (3) provide information to guide the physician on making a DSD diagnosis and its medical management, (4) provide new behavioral information on DSD, and (5) highlight current differences of opinions about the care of infants born with DSD. A discussion of infants who are born with DSD with normal-appearing genitalia is also included.
Beyond Affirmative Action

(1999). Beyond Affirmative Action. Administration in Social Work: Vol. 23, No. 3-4, pp. 47-68.
The fusion of parametric and non-parametric hypothesis tests

This paper considers the hypothesis testing problem when two sets of data having significantly different types of prior information are fused. The probability density function of the data in the first set is assumed to be known to within a finite set of parameters so that aparometric test can be used to test the hypothesis. The probability density function of the second set of data, possibly collected with a different sensor, is unknown and the detection hypothesis must be tested with a non- parametric method. The testsperjormed on the twa sets of data will be very different, parametric versus non- parametric, and depend upon significantly different test statistics which are likely to defne two drfferent rejection regions. Other than being measuredfrom the same object, the two sets of data and their corresponding test statistics have lirt/e in common. The absence of a common scale of measurement makes direct comparison meaningless. The parametric test will generally be the superior test when the correctprobabiliry density function of the data is assumed. If the probability densityfunction of the data differs from the probability densityfunction assumed when the test was designed then, if is likely that the power of the non- parametric test will be greater than that of the parametric test. In the absence of the probabilistic information required to fuze the data, the results of the two hypothesis tests will be fuzed using the only common probabilistic measure which is generally available, the statistical level of significance. The critical level is the smallest level of significance at which the hypothesis is rejected given the measured data. The level of significance can be calculated because it is based upon the assumption that the hypothesis is true. The greaier the critical level, the more confidence there is that the decision is correct.
OXIDATIVE STRESS RESPONSE AND CHARACTERIZATION OF THE OXYR-AHPC AND FURA-KATG LOCI IN MYCOBACTERIUM MARINUM

Oxidative stress response in pathogenic mycobacteria is believed to be of significance for host-pathogen interactions at various stages of infection. It also plays a role in determining the intrinsic susceptibility to isoniazid in mycobacterial species. In this work, we characterized the oxyR-ahpC and furA-katG loci in the nontuberculous pathogen Mycobacterium marinum. In contrast to Mycobacterium smegmatis and like Mycobacterium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and divergently oriented equivalents of the regulator of peroxide stress response oxyR and its subordinate gene ahpC, encoding a homolog of alkyl hydroperoxide reductase. Purified mycobacterial OxyR was found to bind to the oxyR-ahpC promoter region from M. marinum and additional mycobacterial species. Mobility shift DNA binding analyses using OxyR binding sites from several mycobacteria and a panel of in vitro-generated mutants validated the proposed consensus mycobacterial recognition sequence. M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region of ahpC. In contrast, OxyR did not bind to the sequences upstream of the katG structural gene, and katG expression did not follow the pattern seen with ahpC. Instead, a new open reading frame encoding a homolog of the ferric uptake regulator Fur was identified immediately upstream of katG in M. marinum. The furA-katG linkage and arrangement are ubiquitous in mycobacteria, suggesting the presence of additional regulators of oxidative stress response and potentially explaining the observed differences in ahpC and katG expression. Collectively, these findings broaden our understanding of oxidative stress response in mycobacteria. They also suggest that M. marinum will be useful as a model system for studying the role of oxidative stress response in mycobacterial physiology, intracellular survival, and other host-pathogen interactions associated with mycobacterial diseases.
Income Inequality and Population Health in Geographic Perspective

A considerable amount of research indicates that relative income is related to health, or more specifically, that greater disparities in income are related to poorer health. Referred to as the relative income hypothesis, the causal mechanisms, social implications and general nature of this relationship continue to stimulate interesting and important research across several disciplines. One dimension of the association between income inequality and health that has yet to be explored or considered fully is the geographical. In an attempt to elucidate and evaluate how geography is implicated with the relative income hypothesis, the role and significance of geographic spillovers, regional effects and diffusion are theorized and explored. This research uses a geographic framework, spatial analytic techniques, and current and imputed data to revisit and re-examine the linkage between relative income and health at the global scale. Results indicate that the association between income inequality and health is somewhat tempered when examined within an explicitly spatial framework, and that regional and geographic effects need to be considered and treated carefully in cross-sectional, international studies of health.
STAT-1α and IFN-γ as Modulators of TNF-α Signaling in Macrophages: Regulation and Functional Implications of the TNF Receptor 1:STAT-1α Complex

TNF-alpha and IFN-gamma cooperate in the activation of macrophages. TNF-alpha-dependent activation of NF-kappaB is stronger in the presence of IFN-gamma. STAT-1alpha associates with TNFR1 in TNF-alpha-treated cells, and this association attenuates TNF-alpha-mediated NF-kappaB activation. We hypothesized that nuclear localization of STAT-1alpha due to IFN-gamma signaling would preclude it from being recruited to the TNFR1 and therefore enhance TNF-alpha-induced NF-kappaB activation. In the RAW264.7 macrophage cell line, TNF-alpha treatment indeed recruits STAT-1alpha to the TNFR1, and this association is abrogated when cells are exposed to IFN-gamma. TNF-alpha treatment induces a more robust activation of NF-kappaB in STAT-1alpha-deficient cells, and restoration of STAT-1alpha inhibits TNF-alpha-dependent NF-kappaB activation. Our results suggest that a receptor-proximal level of cross-talk exists between these two cytokine pathways: IFN-gamma limits STAT-1alpha availability to the TNFR1 by depleting STAT-1alpha from the cytoplasm, thus allowing for optimal NF-kappaB activation upon TNF-alpha ligation.
Proinflammatory Cytokine Genes are Constitutively Overexpressed in the Heart in Experimental Systemic Lupus Erythematosus: A Brief Communication

The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1beta and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6(lpr) (MRL-lpr/lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1beta, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.
Association of slugs with the fungal pathogen Epichloë typhina (Ascomycotina: Clavicipitaceae): potential role in stroma fertilisation and disease spread

Epichloe spp. are endophytes of grasses, and form epiphytic external stromata on flowering tillers. E. typhina was first noticed infecting Dactylis glomerata (= orchardgrass, cocksfoot) stands in the Willamette Valley in 1996, and soon became the primary factor limiting the longevity of seed production fields. Several species of slugs are present in these fields, and we investigated their role in E. typhina biology. Pre-dawn surveys of D. glomerata fields in 2009 and 2010 found Prophysaon andersoni and Arion subfuscus slugs feeding on the fungal stromata. When unfertilised and fertilised immature stromata predominated, approximately 80% of the individuals of these two species that were seen on plants were found on the stromata. As the majority of stromata reached maturity the presence of these species on stromata declined to between 20–40%. The common agricultural slug pest, Deroceras reticulatum, was on stromata only 20% of the time early in the season, and declined to <5% at stromata maturity. Observations of frass from slugs determined that the most common constituent was the food sources upon which the slug species was usually found during these surveys. Typically 100% of the frass from P. andersoni and A. subfuscus contained stroma material, compared to 25% for D. reticulatum. Spermatia, and ascospores later in the season, were commonly seen in the frass of slugs that consumed stromata. Some slugs that had no stroma material in their frass appeared to have consumed spermatia and ascospores from the leaf surface. A multiple-choice laboratory test confirmed the different proportional preferences of P. andersoni and D. reticulatum for stroma (0.72 vs 0.20) and leaf (0.07 vs 0.38), respectively. Two laboratory multiple-choice tests, and a field survey, found that P. andersoni preferred unfertilised and immature stroma over mature stroma. D. reticulatum is the most common and abundant slug in Willamette Valley grass seed fields, yet it is the least likely to move spermatia between unfertilised stromata, or ascospores to uninfected plants. P. andersoni and A. subfuscus are mycophagous, frequently transport viable spermatia and ascospores in their frass; yet they are generally confined to field edges. Data and observations suggest the role of slugs in the epidemiology of E. typhina is small compared to other factors.
Role of New Antifungal Agents in the Treatment of Invasive Fungal Infections in Transplant Recipients: Isavuconazole and New Posaconazole Formulations

Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Transplant patients are at risk for such invasive fungal infections. The most common invasive fungal infections are invasive candidiasis in the SOT and invasive aspergillosis in the HSCT. In this article, we will discuss the epidemiology of invasive fungal infections in the transplant recipients and susceptibility patterns of the fungi associated with these infections. Additionally, the pharmacology and clinical efficacy of the new antifungal, isavuconazole, and the new posaconazole formulations will be reviewed. Isavuconazole is a new extended-spectrum triazole that was recently approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. Posaconazole oral suspension solution has shown some limitations in the setting of fasting state absorption, elevated gastrointestinal pH, and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide additional treatment options by reducing interpatient variability and providing flexibility in these set of critically ill patients. This review will detail these most recent studies.
Drug-induced DNA Hypermethylation and Drug Resistance in Human Tumors

Drug-induced DNA hypermethylation was observed to constitute one component of the response of human tumor cells to toxic concentrations of commonly used cancer chemotherapy agents. In both human lung adenocarcinoma cells (HTB-54) and human rhabdomyosarcoma cells (CCl-136), pulse exposures to the topoisomerase II inhibitors etoposide and nalidixic acid; to the antibiotic doxorubicin; to the microtubule inhibitors vincristine, vinblastine, and colchicine; to the DNA cross-linking agent cisplatinum; to hydroxyurea; and to the antimetabolites 1-beta-D-arabinofuranosylcytosine, 5-fluorouracil, 5-fluorodeoxyuridine, and methotrexate were associated with profound drug-induced DNA hypermethylation. Exposure of human T-lymphocytes (MOLT-4) to toxic pulse doses of 3'-azidodideoxythymidine was associated with similar drug-induced DNA hypermethylation. In every case, drug-induced DNA hypermethylation was observed only when the degree of DNA synthesis inhibition caused by the drug exceeded 90% and when drug levels or duration of exposure was sufficient to kill 90-100% of exposed cells. Drug-induced DNA hypermethylation was shown not to represent a tissue culture phenomenon, since it occurred in vivo during high-dose 1-beta-D-arabinofuranosylcytosine and hydroxyurea treatments in two leukemic patients. Drug-induced alterations in DNA methylation were frequently biphasic, with hypomethylation occurring at drug concentrations which produced mild DNA synthesis inhibition and which killed less than 50% of exposed cells. Exposure to the alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cyclophosphamide and to the antimetabolites 5-azadeoxycytidine and 6-thioguanine was associated with DNA hypomethylation at all studied concentrations in HTB-54 cells. Drug-induced DNA hypermethylation could be blocked by preexposure to hypomethylating agents administered at nontoxic to mildly toxic concentrations. Drug-induced DNA hypermethylation may be capable of creating drug-resistant phenotypes by inactivating genes the products of which are required for drug cytotoxicity. Perhaps paradoxically, drug-induced DNA hypermethylation may also produce a second class of drug-resistant tumor cells, characterized by overexpression of particular gene products, by potentiating the process of gene amplification.
Determination of clemastine in human plasma by gas chromatography with nitrogen–phosphorus detection

A method for the quantitative determination of clemastine in human plasma has been developed and validated. The assay uses gas chromatography with nitrogen-phosphorus detection and a HP-1 capillary column (25 mx0.22 mm, film thickness 0.33 mm) coated with dimethylpolysiloxane. Clemastine (with orphenadrine as internal standard) was isolated from human plasma using liquid-liquid extraction. A linear relationship was observed between 0.1 and 12.8 ng/ml using the peak area ratio of clemastine to orphenadrine with a correlation coefficient greater than 0.99 (the detection limit for clemastine was 0.06 ng/ml). The intra- and inter-day coefficients of variation were less than 11%. The developed method was used for the analysis of plasma samples from healthy volunteers (n = 19) to examine the pharmacokinetics of the antihistamine clemastine after single and multiple oral doses of clemastine fumarate.
Urinary Tract Infections: What’s New?

ABSTRACTPurpose: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems.Materials and Me...
Multiconfiguration Hartree-Fock calculation for the bound-free photodetachment cross section of H-

The photodetachment cross section of the H/sup -/ ion has been obtained with the multiconfiguration Hartree-Fock method extended to compute the multiconfiguration Hartree-Fock continuum wave function. The electron correlation and polarization effects that are very important for photodetachment cross-section calculation have been taken into account in an ab initio manner through the configuration-interaction procedure. Our results are compared with other accurate and elaborate theoretical calculations and with experiment. It is found that the present results are in excellent agreement with experiment throughout the range of energies considered. The theoretical results obtained by other accurate methods are also in very close agreement with the present results.
Effects of pollination timing on fruiting in Asclepias speciosa Torr. (Asclepiadaceae)

Etude de l'influence de l'âge du pollen et des ovaires, de l'ordre de la pollinisation des fleurs dans l'ombelle et de l'heure de la journee sur la fructification
Detection of high explosive detonation across material interfaces with chirped fiber Bragg gratings

Measuring detonation wavefront position and velocity changes across material interfaces has been demonstrated using an all-optical chirped fiber Bragg grating approach. An experiment was conducted with a cylindrical rate stick consisting of multiple high explosive (HE) segments. A measurement of detonation position across interfaces of different HE formulations was made for both low and high spatial resolution gratings. The results show the accuracy of measured velocities is increased with the higher resolution gratings. A decaying shock driven into the polymethyl methacrylate (PMMA) segment provided a measure of the minimum internal fiber pressure required for prompt grating destruction and accurate wavefront position measurement.
Spectral signatures of axially excited slabs of dielectric thin-film helicoidal bianisotropic mediums

Dielectric thin-film helicoidal bianisotropic mediums (TFHBMs) are rotationally nonhomogeneous nano-engineered materials of recent vintage. Here, optical signatures of axially excited TFHBM slabs are calculated after solving a boundary value problem, after assuming the chosen materials to have single-resonance Lorentzian dielectric response properties. The spectrum of co- and cross-polarized reflectances and transmittances, true and apparent circular dichroisms, true and apparent linear dichroisms, ellipticity transformation, and optical rotation are presented. The role of the structural period in the spectral location of the circular Bragg phenomenon is delineated, and measures to deepen that phenomenon are discussed. The effects of structural handedness on the spectrum are also identified.
Social moral epistemology.

The distinctive aim of applied ethics is to provide guidance as to how we ought to act, as individuals and as shapers of social policies. In this essay, I argue that applied ethics as currently practiced is inadequate and ought to be transformed to incorporate what I shall call social moral epistemology. This is a branch of social epistemology, the study of the social practices and institutions that promote (or impede) the formation, preservation, and transmission of true beliefs. For example, social epistemologists critically evaluate the comparative advantages of adversarial versus inquisitorial criminal proceedings as mechanisms for the discovery of truth.
Effects of temperature dependent spin wave damping in the two-dimensional Hubbard antiferromagnet☆

Abstract Effects of the temperature dependent damping energy for spin waves in the long-range antiferromagnetic (AF) state of the generalized N -orbital ( S = 1 2 ) Hubbard model at half filling is discussed. Thermally excited spin waves acquire a finite lifetime via (1) interactions between spin waves and (2) scattering due to AF domain boundaries. The damping energy Γ sw due to (1) and (2) increases with T as T 2 and e −2 πρ 3/ T ∝ ξ −1 (inverse spin-spin correlation length), respectively. These T dependences for Γ sw suggest that the contribution from the interaction between long wavelength spin waves is dominant for T T o , but the contribution from the domain boundary scattering becomes dominant for T > T o . Both ζ and Γ sw , respectively, provides a natural length and low energy cutoff scale for the macroscopic response of spins at intermediate temperatures. We discuss the consequence of the T dependent Γ sw in the high- T c copper oxides.
sRNA of phage φ29 of Bacillus subtilis mediates DNA packaging of φ29 proheads assembled in Escherichia coli

The structural genes of the prohead of phage phi 29 of Bacillus subtilis and a small phi 29 RNA (sRNA) were cloned and expressed in Escherichia coli individually or in combination to study the role of the sRNA in prohead assembly and the mechanism of prohead morphogenesis. The genes coding for the proteins of the scaffold (gp7), the capsid (gp8), the portal vertex (gp10), and the dispensable head fiber (gp8.5) were expressed in E. coli and the gene products were assembled, with and without the presence of the sRNA, into uniform and prolate particles that resembled the typical native phi 29 prohead. No differences in particle size and shape were found between the particles of 7-8-8.5-10 (scaffold-capsid-fiber-portal vertex) and 7-8-8.5-10-RNA (scaffold-capsid-fiber-portal vertex-RNA), suggesting that the phi 29 sRNA was not required for phi 29 prohead assembly. The 7-8-8.5-10 particles produced in E. coli in the absence of phi 29 sRNA were fully competent to package phi 29 DNA in the defined in vitro DNA packaging system by the addition of purified sRNA. Moreover, these DNA-filled heads were assembled into infectious virions in extracts. Without the addition of the sRNA, the 7-8-8.5-10 particles were incompetent while the 7-8-8.5-10-RNA particles were competent in DNA packaging. Bacterial sRNA present in E. coli cannot substitute for the phi 29 sRNA. The assembly of prohead particles in E. coli indicated that host factors unique to B. subtilis were not required. The evidence that the phi 29 sRNA was not required for phi 29 prohead assembly and was not a fixed structural component of the phi 29 prohead favors the conclusion that the phi 29 sRNA is a specific enzyme or morphogenetic factor in DNA packaging.
The partition function of a topological field theory

This is the sequel to my paper ‘TCFTs and Calabi-Yau categories’, Advances in Mathematics 210 (2007) no. 1, 165-214. Here we extend the results of that paper to construct, for certain Calabi-Yau A ∞ categories, something playing the role of the Gromov-Witten potential. This is a state in the Fock space associated to periodic cyclic homology, which is a symplectic vector space. Applying this to a suitable A ∞ version of the derived category of sheaves on a Calabi-Yau yields the B model potential, at all genera. The construction does not go via the Deligne-Mumford spaces, but instead uses the Batalin-Vilkovisky algebra constructed from the uncompactified moduli spaces of curves by Sen and Zwiebach. The fundamental class of Deligne-Mumford space is replaced here by a certain solution to the quantum master equation, essentially the ‘string vertices’ of Zwiebach. On the field theory side, the BV operator has an interpretation as the quantized differential on the Fock space for periodic cyclic chains. Passing to homology, something satisfying the master equation yields an element of the Fock space.
Erwin Schrödinger's views on gravitational physics during his last years at the University of Vienna and some research ensuing from it

The author, who was Schrodinger's assistant during his last years in Vienna, gives an account of Schrodinger's views and activities during that time which lead him to a different approach to research on the relations between gravitation and quantum phenomena. Various features of past research are outlined in nontechnical terms. A heuristic argument is presented for the role of the zero-point energy of massive particles in counteracting gravitational collapse and the formation of horizons. Arguments are presented for the view that progress in describing extreme gravitational phenomena can be achieved by the new outlook obtained from the introduction of the analog of Maxwell's vacuum displacement term with a quasiconstant parameter, rather than from renormalization of special processes, even if this is successful. The results can be expected to be in accord with Schrodinger's conjectures.
A model for measuring the implementation of community support programs: results from three sites.

We present and test a model for measuring the implementation of Community Support Programs (CSPs) for persons with severe mental illnesses. The model is intended to facilitate the description and replication of these programs and the future study of their critical ingredients. The model defines important implementation variables in seven areas of program functioning; we then suggest instruments to measure each of these variables. Results of a study examining the application of the model and measures forthree conceptually distinct CSPs illustrate the utility of the model and measures for implementation analysis of CSPs. Importantly, findings revealed thata priori hypotheses about how the programs were expected to differ on the implementation variables were largely supported.
1655 THE ADVERSE EFFECT OF HYPOCALORIC UNDERNUTRITION ON OXYGEN TOLERANCE IN NEWBORN RATS

Because newborn infants who require intensive respiratory support and high O2 therapy are often less than adequately nourished during the early days of life, we tested the effect of hypocaloric undernutrition on newborn rat pups exposed to hyperoxia. Rat pups were randomized into groups of 11/dam (normally-nourished) (NN) or 18/dam (undernourished)(UN) and placed in >95% O2 (or 21% O2) for the 1st 7 days of life. Dams were switched daily to prevent O2 toxicity in the nurturing adult rats. In each of 4 experiments the UN pups tolerated hyperoxia more poorly than the NN pups. Composite survival rates at 7 days in O2 were: 47/108 (44%) (UN) vs. 56/77 (73%)(NN)(p<0.005). The UN pups had significantly reduced body wts and lung wts, but the lung wt/body wt ratios were normal (0.86 vs. 0.83). Lung maturation was markedly impaired by O2 exposure in both nutritional groups - alveoli per high power field = 11.1 ± 2.3 (NN in air) vs. 3.5 ± 0.7 (NN in O2) (68% inhibition); 11.4 ± 2.6 (UN in air) vs. 4.2 ± 0.7 (UN in O2) (64% inhibition). There were essentially equivalent increases in the protective lung antioxidant enzyme responses to hyperoxia in the NN and UN pups, respectively: superoxide dismutase (+80%, +85%); catalase (+90%, +75%); glutathione peroxidase (+275%, +230%); G-6-PD (+200%, +240%). Thus, tolerance to prolonged high O2 treatment is definitely impaired in UN pups; but the mechanism(s) for compromised tolerance in hypocaloric undernourished newborns needs further explication. (Supported in part by V.A.H. Research funds and NIH grant HL26029).