Insulin depletion leads to adipose-specific cell death in obese but not lean mice

Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory "overexpression" of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.     

Binding and lysing of blood clots using MRX-408

RATIONALE AND OBJECTIVES: A thrombus-specific ultrasound contrast agent, MRX-408, has been developed recently. This agent consists of phospholipid-coated microbubbles with a ligand capable of targeting the GPIIb/IIIa receptor, thereby allowing the microbubbles to bind with thrombi rich in activated platelets. In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombolysis using this agent compared with a nontargeted agent. METHODS: For clot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope. Change in backscatter signals from the blood clots after binding was examined by both an ultrasound scanner and two single-element transducers arranged in a transmitter-receiver pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase. RESULTS: Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the "acoustic signature", or properties, of blood clots changed after binding. Clots became more echogenic and nonlinear. In vivo fundamental ultrasound imaging confirmed that as a result of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable. Under 1-MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 34% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION: The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.     

Auditory system plasticity in children after long periods of complete deafness

Separation and identification of proteins by two-dimensional (2-D) electrophoresis can be used for protein-based gene expression analysis. In this report single protein spots, from polyvinylidene difluoride blots of micropreparative E. coli 2-D gels, were rapidly and economically identified by matching their amino acid composition, estimated pI and molecular weight against all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2-D map were analyzed and identities assigned. Three of the proteins were unknown. By protein sequencing analysis, 20 of the 27 proteins were correctly identified. Importantly, correct identifications showed unambiguous "correct" score patterns. While incorrect protein identifications also showed distinctive score patterns, indicating that protein must be identified by other means. These techniques allow large-scale screening of the protein complement of simple organisms, or tissues in normal and disease states. The computer program described here is accessible via the World Wide Web at URL address (http:@expasy.hcuge.ch/).     

Laparoscopic versus open appendectomy

BACKGROUND: Clinical manifestations and course of sickle-cell anemia are variable. Knowledge about the factors, possibly geographic, that influence prognosis are still scanty. POPULATION AND METHODS: Data of hospitalization and management of children with sickle-cell disease were studied during two years (1992-1993) in the Pediatric Unit of Libreville Hospital. They concerned 205 admissions of 171 children and 131 outpatients. RESULTS: The main causes of hospitalization were: acute anemia (36 cases before the age of 5 years); painful crisis whose frequency increased with age (23% before 5 years, 35% between 5 and 10, 42% after 10 years); infections, essentially pulmonary occurring early, and bone infections at any age. Eight children died (because a complication of their disease). Among the 131 outpatients, half were detected because pyrexia, anemia and/or more often "hand-foot syndrome". More than 60% had hepatomegaly, one third still had splenomegaly after five years of age and more than one third was icteric. More than half children older than ten years had growth disorders. Mean hemoglobin level was 7 g/dL. 21 of the 83 tested children for HBsAg were positive and only one out of 79 was positive for HIV. CONCLUSIONS: Clinical manifestations and course of sickle-cell anemia in our patients are similar to those reported in Congolese children. Genetic and environmental factors may be responsible for differences with children from other, in particular French, cohorts.     

Metabolic role of glutamine and its importance in nutritional therapy

The advances in the field of nutritional support have made certain nutrients very relevant, which, although they have been known for a long time, at present represent an important chapter in nutrition, entering into what is known as "nutritional pharmacology". Among these nutrients is glutamine, an amino acid classified as non-essential, but which in certain circumstances may become to be considered as an "essential nutrient". In the present review, a review is made of its metabolic role, synthesis and degradation, metabolic routes and functions under normal conditions as well as under critical conditions. It is known that glutamine stimulates the synthesis and inhibits the degradation of proteins, it is an important vehicle for the transport of nitrogen and carbon within the tissues, it stimulates the synthesis of hepatic glycogen, it is an energy source for cell division, for the growth of different cells of rapid replication, such as enterocytes, colonocytes, and fibroblasts, as well as for other cells of the immune system, such as lymphocytes and macrophages. Thus its role in the maintenance of structure, in metabolism and function of the intestinal mucosa, and in dysfunctions of the immune system. In parenteral nutrition, at present there are no preparations which include it, given the stability problems which it presents, although attempts have been made to resolve this, using different possibilities, such as di-peptides. However, in enteral nutrition, the diets tend to include it, although in a small proportion. Nevertheless, having recognized its beneficial role in a certain type of patients, at present there are diets which contain glutamine in higher doses, with the object of attempting to cover the increased demands of glutamine which shall arise in these situations. The inclusion of glutamine in nutritional therapy is supported by multiple studies which reflect the beneficial effect of this nutrient, both in enteral nutrition as in parenteral nutrition.     

Ultra‐fast‐switching flexoelectric liquid‐crystal display with high contrast

Abstract— The flexoelectro‐optic effect provides a fast‐switching mechanism (0.01–0.1 msec), suitable for use in field‐sequential‐color full‐motion‐video displays. An in‐plane electric field is applied to a short‐pitch chiral nematic liquid crystal aligned in the uniform standing helix (or Grandjean) texture. The switching mechanism is experimentally demonstrated in a single‐pixel test cell, and the display performance is investigated as a function of device parameters. A contrast ratio of 2000:1 is predicted.     

Individual characteristics and the intention to continue project escalation

The factors leading to the continuing problems with information system (IS) project failure are of importance to both the research and practitioner communities. The psychological factors that lead project managers to escalate troubled projects are investigated. Theoretical grounding is presented for a research model consisting of Need for Achievement as an antecedent trait for implementation mindset, internal locus of control, preference for consistency, and time urgency, which in turn predict the Intention to Continue a troubled IS project. Using responses from 232 IS project stakeholders, the model is tested using structural equation modeling. The results support Need for Achievement as an antecedent to the other independent variables. Implementation mindset and internal locus of control were found to be significant predictors of the project managers’ intention to continue the IS projects. Based on the findings, suggestions for project re-evaluation milestones (PRMs) are presented.     

Introducing the IA-64 architecture

Microprocessors continue on the relentless path to provide more performance. Every new innovation in computing-distributed computing on the Internet, data mining, Java programming, and multimedia data streams-requires more cycles and computing power. Even traditional applications such as databases and numerically intensive codes present increasing problem sizes that drive demand for higher performance. Design innovations, compiler technology, manufacturing process improvements, and integrated circuit advances have been driving exponential performance increases in microprocessors. To continue this growth in the future, Hewlett Packard and Intel architects examined barriers in contemporary designs and found that instruction-level parallelism (ILP) can be exploited for further performance increases. This article examines the motivation, operation, and benefits of the major features of IA-64. Intel's IA-64 manual provides a complete specification of the IA-64 architecture     

Pilot mental workload: how well do pilots really perform?

The purpose of this study was to investigate the effects of increasing mental demands on various aspects of aircrew performance. In particular, the robustness of the prioritization and allocation hierarchy of aviate-navigate-communicate was examined, a hierarchy commonly used within the aviation industry. A total of 42 trainee pilots were divided into three workload groups (low, medium, high) to complete a desktop, computer-based exercise that simulated combinations of generic flight deck activities: flight control manipulation, rule-based actions and higher level cognitive processing, in addition to Air Traffic Control instructions that varied in length from one chunk of auditory information to seven chunks. It was found that as mental workload and auditory input increased, participants experienced considerable difficulty in carrying out the primary manipulation task. A similar decline in prioritization was also observed. Moreover, when pilots were under a high mental workload their ability to comprehend more than two chunks of auditory data deteriorated rapidly.     

Software component certification

Although the stringent requirements of some critical applications may require independent certification, the authors see software developer self-certification as a viable alternative in many other cases. They accept that using software certification laboratories (SCLs) may work well for certain software distribution models, but they cannot be applied to all types of software development. The approach has several drawbacks. For example, an SCL may work well for larger software houses that ship mass-marketed software applications to the public, but it is less satisfactory for smaller developers who make reusable components or safety-critical software or for developers who belong to the freeware community