Knowledge-based monitoring of the pointing control system on the Hubble space telescope

A knowledge-based system for the real time monitoring of telemetry data from the Pointing and Control System (PCS) of the Hubble Space Telescope (HST) that enables the retention of design expertise throughout the three decade project lifespan by means other than personnel and documentation is described. The system will monitor performance, vehicle status, success or failure of various maneuvers, and in some cases diagnose problems and recommend corrective actions using a knowledge base built using mission scenarios and the more than 4,500 telemetry monitors from the HST

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume Overload

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial–nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the ‘mitochondrial paradigm’ for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Blunt Splenic Injury in Adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (\u3e15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p \u3c 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) \u3c 15 and 46.6% of patients with ISS \u3e 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p \u3c 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p \u3c 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum

Blunt Splenic Injury in Adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (\u3e15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p \u3c 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) \u3c 15 and 46.6% of patients with ISS \u3e 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p \u3c 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p \u3c 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Contribution of Age and Gender to Outcome of Blunt Splenic Injury in Adults: Multicenter Study of the Eastern Association for the Surgery of Trauma

Background : The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. Methods : Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. Results : Fifteen percent of patients were 55 years of age or older. A similar proportion of patients \u3e= 55 went directly to the operating room compared with patients \u3c 55 (41% vs. 38%) but the mortality for patients \u3e= 55 was significantly greater than patients \u3c 55 (43% vs. 23%). Patients \u3e= 55 failed nonoperative management (NOM) more frequently than patients \u3c 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p \u3c 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women \u3e= 55 failed NOM more frequently than women \u3c 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p \u3c 0.05). Conclusion : Patients \u3e= 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients \u3c 55. Women \u3e= 55 had significantly greater mortality and failure of NOM than women \u3c 55