Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells

Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-alpha, IFN-beta, IFN-gamma, IL-2 or tumor necrosis factor (TNF)-alpha and, unlike the induction of IFN-gamma production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.     

Vocal fatigue among teachers

Recordings were made at the beginning and end of workdays of teachers who experience vocal fatigue (n = 22) and those who do not experience fatigue (n = 17). Those who experienced fatigue were recorded on days in which they did and did not fatigue. Both groups evaluated their vocal characteristics, each time they made a recording. Subsequently, a listener panel evaluated the same characteristics from the recordings. Both groups estimated the amount and characteristics of their talking time, completed a psychological evaluation and provided medical histories. The authors interpret the data obtained as indicating that the vocal characteristics of teachers who fatigue and those who do not fatigue are similar on days the former group does not fatigue and that the two groups are similar in the amount and loudness of their talking time, at work and at home. However, teachers who fatigue tend to spend more time in activities that appear to be vocally demanding and are more likely to perceive situations as being anxiety producing. Teachers who fatigue tend to be in good health, but have had more hearing problems and allergies than their colleagues and more of their family members have had voice problems.     

The incidence of drug-related problems as a cause of hospital admissions in children

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.     

A test house study of pesticides and pesticide degradation products following an indoor application

Preexisting pesticide degradates are a concern for pesticide biomonitoring studies as exposure to them may result in overestimation of pesticide exposure. The purpose of this research was to determine whether there was significant formation and movement, of pesticide degradates over a 5‐week period in a controlled indoor setting after insecticide application. Movement of the pesticides during the study was also evaluated. In a simulated crack and crevice application, commercially available formulations of fipronil, propoxur, cis/trans‐permethrin, and cypermethrin were applied to a series of wooden slats affixed to the wall in one room of an unoccupied test house. Floor surface samples were collected through 35 days post‐application. Concentrations of the pesticides and the following degradates were determined: 2‐iso‐propoxyphenol, cis/trans 3‐(2,2‐dichlorovinyl)‐3‐3‐dimethyl‐(1‐cyclopropane) carboxylic acid, 3‐phenoxybenzoic acid, fipronil sulfone, fipronil sulfide, and fipronil desulfinyl. Deltamethrin, which had never been applied, and chlorpyrifos, which had been applied several years earlier, and their degradation products, cis‐3‐(2,2‐dibromovinyl)‐2,2‐dimethylcyclopropane‐1‐carboxylic acid, and, 3,5,6‐trichloro‐2‐pyridinol, respectively, were also measured. Propoxur was the only insecticide with mass movement away from the application site. There was no measurable formation or movement of the degradates. However, all degradates were present at low levels in the formulated product. These results indicate longitudinal repetitive sampling of indoor degradate levels during short‐term studies, is unnecessary.     

Quality certification and control of polymer laser sintering: layerwise temperature monitoring using thermal imaging

In additive manufacturing (3D printing) of products for aerospace, medical, or other critical applications, the quality of the manufactured part must be “certified” before it can be used. New methods are needed to certify the quality during the fabrication process. The digital 3D quality certificate (3DQC) assures that process monitor values were within specification during the entire fabrication process. This paper proposes an approach for using high resolution infrared thermal imaging to monitor the temperature of individual layers before, during, and after laser scanning. Temperature data is indexed to the part geometry using a binary template created from the sliced 3D model. This data provides a record of the process conditions during the creation of each volume element of the part. Two temperatures are discussed in this paper: the peak temperature achieved during laser scanning and the residual temperature in the layer just before adding the next powder layer. Both of these monitors show a relationship to the geometry of the part, the layer cross-sectional area, and the presence or absence of an underlying solid layer. While both of these temperatures likely relate to part quality, this relationship is not yet understood. Ultimately, this monitor data can be used to control the process, e.g., modify the laser scan or the wait time before recoating, in order to provide more uniform sintering of each volume element of the part.     

Concept maps as the first step in an ontology construction method

A method is proposed to be used as the first step in the ontology acquisition process. This method is based on the use of concept maps as a means of expression for the expert, followed by an application that assists the expert in detailing the structure of the knowledge represented in the map. This application analyses the concept map, taking into account the map topology and key words used by the expert. From this analysis a series of questions are presented to the expert that, when answered, reduce the map ambiguity and identify some common patterns in ontological representations, such as generalizations and mereologic relations. This information can be used by the knowledge engineer during further knowledge acquisition sessions or to direct the expert to a further improvement of the map. The method was tested by a group of volunteers, most of them engineers working at the aerospace sector, and the results suggest that both the use of concept mapping as well as the refining step are acceptable from the point of view of the end user, supporting the claim that this method is viable as an option to reduce some of the difficulties in large scale ontology construction.     

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.     

Model oxide-supported metal catalysts: energetics,particle thicknesses,chemisorption and catalytic properties

Many industrially important catalysts consist of late transition metal particles supported on the surfaces of oxide materials. Our studies of such systems using model catalysts consisting of metal films vapor deposited onto the surfaces of single-crystalline oxides are reviewed here. Systems studied include Cu on ZnO, Pt on ZnO, Au on TiO₂ and Cu, Ag and Pb on MgO. A unique adsorption microcalorimeter was developed to measure directly the energetic stability of the metal atoms on the oxide surfaces and the adhesion energy at the metal/oxide interface, which clarify the structural and chemisorption properties of the ultrathin metal particles. The structure of the oxide surface and the metal particles was elucidated by low-energy electron diffraction (LEED), low-energy ion scattering spectroscopy (ISS), angular-resolved X-ray photoelectron spectroscopy (XPS) and X-ray photoelectron diffraction (XPD). The electronic character of the metal particles was revealed by XPS, Auger electron spectroscopy (AES), band-bending and work function measurements. Sintering rates were measured by temperature-programmed ion scattering spectroscopy (TPISS). The chemisorption properties of these particles and their catalytic reactivity were monitored by mass spectroscopy and temperature-programmed desorption (TPD).