A Corona Discharge Initiated Electrochemical Electrospray Ionization Technique

We report here the development of a corona discharge (CD) initiated electrochemical (EC) electrospray ionization (ESI) technique using a standard electrospray ion source. This is a new ionization technique distinct from ESI, electrochemistry inherent to ESI, APCI, and techniques using hydroxyl radicals produced under atmospheric pressure conditions. By maximizing the observable CD at the tip of a stainless steel ESI capillary, efficient electrochemical oxidation of electrochemically active compounds is observed. For electrochemical oxidation to be observed, the ionization potential of the analyte must be lower than Fe. Ferrocene labeled compounds were chosen as the electrochemically active moiety. The electrochemical cell in the ESI source was robust, and generated ions with selectivity according to the ionization potential of the analytes and up to zeptomolar sensitivity. Our results indicate that CD initiated electrochemical ionization has the potential to become a powerful technique to increase the dynamic range, sensitivity, and selectivity of ESI experiments

Glucocorticoid-regulated localization of cell surface glycoproteins in rat hepatoma cells is mediated within the Golgi complex.

Glucocorticoid hormones regulate the post-translational maturation and sorting of cell surface and extracellular mouse mammary tumor virus (MMTV) glycoproteins in M1.54 cells, a stably infected rat hepatoma cell line. Exposure to monensin significantly reduced the proteolytic maturation and externalization of viral glycoproteins resulting in a stable cellular accumulation of a single 70,000-Mr glycosylated polyprotein (designated gp70). Cell surface- and intracellular-specific immunoprecipitations of monensin-treated cells revealed that gp70 can be localized to the cell surface only in the presence of 1 microM dexamethasone, while in uninduced cells gp70 is irreversibly sequestered in an intracellular compartment. Analysis of oligosaccharide processing kinetics demonstrated that gp70 acquired resistance to endoglycosidase H with a half-time of 65 min in the presence or absence of hormone. In contrast, gp70 was inefficiently galactosylated after a 60-min lag in uninduced cells while rapidly acquiring this carbohydrate modification in the presence of dexamethasone. Furthermore, in the absence or presence of monensin, MMTV glycoproteins failed to be galactosylated in hormone-induced CR4 cells, a complement-selected sorting variant defective in the glucocorticoid-regulated compartmentalization of viral glycoproteins to the cell surface. Since dexamethasone had no apparent global effects on organelle morphology or production of total cell surface-galactosylated species, we conclude that glucocorticoids induce the localization of cell surface MMTV glycoproteins by regulating a highly selective step within the Golgi apparatus after the acquisition of endoglycosidase H-resistant oligosaccharide side chains but before or at the site of galactose attachment

The District Court and the Ongoing Pursuit of Local Justice in North Carolina

The state of North Carolina’s system of district courts is a prominent example of the success of legal reform, but also of the difficulties that reform can encounter. From the earliest days of the Lords Proprietors, Old English law played a significant role in colonial judicial administration. As North Carolina expanded, however, growing pains emerged; among the most severe were the availability of courts for small matters, the qualifications of those appointed to serve as judges, and the challenges brought on by interference in the court system by the executive and legislative branches of government. This Article tracks North Carolina’s long journey from judicial pariah to a model of effective governance, including the influence of other states, legal scholars, and public opinion. It concludes that the establishment of a dedicated system of district courts in the state fundamentally improved and continues to maintain—despite recent changes—a robust administration of justice in North Carolina

Cognitive rigor: blending the strengths of Bloom's taxonomy and Webb's depth of knowledge to enhance classroom-level processes

To teach the rigorous skills and knowledge students need to succeed in future college entry courses and workforce training programs, education stakeholders have increasingly called for more rigorous curricula, instruction, and assessments. Identifying the critical attributes of rigor and measuring its appearance in curricular materials is therefore fundamental to progress in this area. By superposing two widely accepted models for describing rigor — Bloom's Taxonomy of Educational Objectives and Webb’s Depth-of Knowledge (DOK) model — this article defines cognitive rigor (CR) and introduces the CR matrix for analyzing instruction and enhancing teacher lesson planning. Two large-scale collections of student work samples analyzed using the CR matrix are presented, illustrating the preponderance of curricular items aligned to each cell in the matrix. Educators should use the cognitive rigor matrix to align the content in their curricular materials to the instructional techniques used in classroom delivery.Vice President for Researc

Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

ABSTRACT: INTRODUCTION: Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. METHODS: Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. RESULTS: Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay and increasing plasma fibrinogen levels. We found no fibrinogen concentrate comparator studies in patients with haemorrhage due to massive trauma, although efficacy across all assessed outcomes was reported in a number of noncomparator trauma studies. CONCLUSIONS: The weight of evidence does not appear to support the clinical effectiveness of FFP for surgical and/or massive trauma patients and suggests it can be detrimental. Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn

Blood transfusion in critical care

Blood transfusion is frequent in critical care. Transfusion raises the mass of transfused blood components and is lifesaving in acute hemorrhage. In massive transfusion (>10 units of red blood cells), early attempts to restore coagulation function appear helpful. Transfusion in non-bleeding patients is largely prophylactic, is seldom evidence-based, and may be deleterious. In hemodynamically stable critical care patients, level I evidence suggests that a hemoglobin of >7 g/dL and platelet counts of >10,000/μL are well tolerated

Satellite-Based Assessment of Grassland Conversion and Related Fire Disturbance in the Kenai Peninsula, Alaska

Spruce beetle-induced (Dendroctonus rufipennis (Kirby)) mortality on the Kenai Peninsula has been hypothesized by local ecologists to result in the conversion of forest to grassland and subsequent increased fire danger. This hypothesis stands in contrast to empirical studies in the continental US which suggested that beetle mortality has only a negligible effect on fire danger. In response, we conducted a study using Landsat data and modeling techniques to map land cover change in the Kenai Peninsula and to integrate change maps with other geospatial data to predictively map fire danger for the same region. We collected Landsat imagery to map land cover change at roughly five-year intervals following a severe, mid-1990s beetle infestation to the present. Land cover classification was performed at each time step and used to quantify grassland encroachment patterns over time. The maps of land cover change along with digital elevation models (DEMs), temperature, and historical fire data were used to map and assess wildfire danger across the study area. Results indicate the highest wildfire danger tended to occur in herbaceous and black spruce land cover types, suggesting that the relationship between spruce beetle damage and wildfire danger in costal Alaskan forested ecosystems differs from the relationship between the two in the forests of the coterminous United States. These change detection analyses and fire danger predictions provide the Kenai National Wildlife Refuge (KENWR) ecologists and other forest managers a better understanding of the extent and magnitude of grassland conversion and subsequent change in fire danger following the 1990s spruce beetle outbreak

Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum.

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus

Pt/SnO2-based CO-oxidation catalysts for long-life closed-cycle CO2 lasers

Noble-metal/tin-oxide based catalysts such as Pt/SnO2 have been shown to be good catalysts for the efficient oxidation of CO at or near room temperature. These catalysts require a reductive pretreatment and traces of hydrogen or water to exhibit their full activity. Addition of Palladium enhances the activity of these catalysts with about 15 to 20 percent Pt, 4 percent Pd, and the balance SnO2 being an optimum composition. Unfortunately, these catalysts presently exhibit significant decay due in part to CO2 retention, probably as a bicarbonate. Research on minimizing the decay in activity of these catalysts is currently in progress. A proposed mechanism of CO oxidation on Pt/SnO2-based catalysts has been developed and is discussed