Analysis and classification of microprogrammed computers.

Massachusetts Institute of Technology. Dept. of Electrical Engineering. Thesis. 1972. M.S.MICROFICHE COPY ALSO AVAILABLE IN BARKER ENGINEERING LIBRARY.Includes bibliographical references.M.S

Characterizing and Prognosticating Heart Failure with Improved Ejection Fraction Using NT-proBNP, Growth Differentiation Factor 15 and Global Longitudinal Strain

Background: Heart failure with improved ejection fraction (HFiEF) is a novel heart failure (HF) subgroup. There are sparse data on using NT-proBNP, growth differentiation factor 15 (GDF15) and global longitudinal strain (GLS) to characterize and prognosticate HFiEF patients. Objectives: (1) To determine the level and correlation between NT-proBNP, GDF-15 and GLS in HFiEF patients. (2) To examine the correlation of each marker with NYHA, MAGGIC prognostic score, HF etiologies, comorbidities status, degree of LVEF/ LV end-diastolic diameter change from baseline and diastolic dysfunction. (3) To look for association of each marker with follow-up LVEF change and 1-year composite mortality or HF events outcome. Materials & Methods: This was a cross-sectional observational study in Sarawak Heart Centre HF clinic. 53 HfiEF patients who had NT-proBNP and GDF15 tests performed were selected. This cohort had no HF events in the past 6 months during the blood tests. Clinical characteristics, echocardiography parameters, and 1-year composite clinical outcome were analyzed retrospectively. Results: The mean age of the cohort was 52 years old and 81% were male. The cohort was highly comorbid (hypertension 71%; diabetes 45.3%; AF 17.3%). Most of the patients (87%) were asymptomatic by NYHA (I) and low rate of composite outcome was observed, 5.7%. The mean NT-proBNP, GDF-15, GLS were 357 pg/ml, 1572 pg/ml, and -12.1% respectively. There were significant moderate correlation between GDF15 with NT-proBNP (r=0.414) and NT-proBNP with GLS (r=-0.351). Higher NT-proBNP and GDF15 levels were associated with poorer MAGGIC prognostic scores (r=0.549, 0.41 respectively). NT-proBNP was the only marker associated with a higher degree of LVEF improvement compare to baseline echocardiography. NT-proBNP was also related to severe diastolic echo parameters. Hypertension and diabetes were strongly associated with higher elevated GDF15 levels. The lower mean GLS level was significantly associated with the presence of composite outcome (-6.45% vs -12.47%, p=0.0). Patients with NT-proBNP levels below the median cutoff had favourable follow-up LVEF improvement (+9.73%, p=0.035). Conclusion: In our HFiEF study cohort, NT-proBNP best correlate and prognosticate future LV remodelling. GDF15 was closely related to systemic illnesses such as diabetes. The role of GLS in our HFiEF cohort remains uncertain

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

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field