The impacts and benefits of using CASE tools in the system development life cycle

The basic idea underlying computer-aided software engineering (CASE) technology is to increase a systems developer\u27s productivity by providing a set of well-integrated, labor-saving tools that transform computer-based information systems (CBIS) development into an automated process. Two major issues of interest are addressed by this article. The first issue includes subjects related to the corporate data processing environment when adopting CASE technology for developing CBIS applications. The second issue includes subjects related to examining the impacts and benefits of using CASE technology as an automated development CBIS application tool within the system development life cycle

Regulation of Stem Cell Metabolism by the Lin28/let-7 Axis

My PhD thesis is focused on two fundamental aspects of stem cell metabolism: (1) the role of Lin28 in programming stem cell metabolism, and (2) how metabolism in turn fuels and governs pluripotency. Our studies led us to discover that the stem cell factor Lin28a promotes gigantism by enhancing glucose metabolism in mice, coinciding with discoveries that LIN28B polymorphisms influence height variation in human GWAS. Subsequently, we discovered that the Lin28/let-7 pathway controls glucose metabolism by orchestrating the upregulation of multiple insulin-PI3K-mTOR components, particularly in skeletal muscle progenitors. Since let-7 accumulates with aging, our discoveries suggest that let-7 could represent a new drug target for treating insulin resistance and type 2 diabetes during aging. During these studies, we also observed that Lin28a enhances tissue regeneration in adulthood. Regeneration capacity has long been known to decline with aging, but why juvenile organisms show enhanced tissue repair had remained unexplained. We found that Lin28a reactivation improved the regrowth of skin, hair, cartilage, bone and mesenchyme after injuries. Let-7 repression was necessary but insufficient to explain these phenotypes. In parallel, Lin28a bound to and enhanced the translation of mRNAs for several oxidative enzymes, thereby increasing OxPhos. Lin28a-mediated tissue repair was negated by OxPhos inhibition, whereas a pharmacologically-induced increase in OxPhos promoted wound repair. Thus, Lin28a enhanced tissue regeneration in adults by reprogramming cellular bioenergetics. My interest in the central principles of stem cell metabolism also led us to map the metabolic pathways associated with pluripotency during iPS reprogramming and Lin28/let-7 perturbation. Surprisingly, we found that Thr-Gly-S-adenosylmethionine (SAM) metabolism consistently showed the best correlation with pluripotency. 13Carbon isotope metabolomics further revealed that Thr was catabolized to generate Gly and acetyl-CoA, and ultimately SAM - essential for all methylation reactions. Thr is required for SAM and histone H3K4 methylation in mouse ESCs, thus regulating the open euchromatin and pluripotency of ESCs. Our study shed light on a novel amino acid pathway in stem cells, and demonstrated that metabolic conditions can direct cell fate. In summary, my work has helped us to understand how we can reprogram and manipulate metabolic networks to regulate stem cell homeostasis

Performance Evaluation of Automated Static Analysis Tools

Automated static analysis tools can perform efficient thorough checking of important properties of, and extract and summarize critical information about, a source program. This paper evaluates three open-source static analysis tools; Flawfinder, Cppcheck and Yasca. Each tool is analyzed with regards to usability, IDE integration, performance, and accuracy. Special emphasis is placed on the integration of these tools into the development environment to enable analysis during all phases of development as well as to enable extension of rules and other improvements within the tools. It is shown that Flawfinder be the easiest to modify and extend, Cppcheck be inviting to novices, and Yasca be the most accurate and versatile

Trim25 is an RNA-specific activator of Lin28a/TuT4-mediated uridylation

SummaryRNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity

A self-evaluation system of quality planning for tourist attractions in Taiwan: an integrated AHP-Delphi approach from career professionals

This study seeks to identify a set of key indicators along with weightings for tourist attractions in Taiwan, and develop a quality management self-evaluation mechanism for tourism businesses, using an advanced integrated Analytic Hierarchy Process and Delphi (AHP-Delphi) approach derived from the supply side perspective. This research study comprises two phases: (1) Delphi method analysis that involves 17 experts, providing confirmation about the evaluation criteria; and (2) Analytical Hierarchical Process (AHP) method which aims to allocate weightings to the evaluation criteria from the experts. Findings from the Delphi method analysis revealed the acceptance of two dimensions, six sub-dimensions and 17 indicators as key evaluation criteria. The AHP method analysis indicated that the most significant dimension was managing quality, with tourism services and public sector facilities being the most important sub-dimension and indicator respectively. The self-evaluation mechanism proposed in this planning perspectives can assist tourism businesses and national/regional Destination Management Organization to identify quality management problems and possible ways of enhancing quality tourism, so that tourism experience, and tourist’s satisfaction can be further improved effectively between the conflicting views by career professionals

Miniature Ring-Shaped Peristaltic Pump

An experimental miniature peristaltic pump exploits piezoelectrically excited flexural waves that travel around a ring: A fluid is carried in the containers formed in the valleys between the peaks of the flexural waves, What sets the present pump apart from other pumps that exploit piezoelectrically excited flexural waves is the ring shape, which makes it possible to take advantage of some of the desirable characteristics of previously developed piezoelectric rotary motors. A major advantage of the circular (in contradistinction to a straight-line) wave path is that the flexural waves do not come to a stop and, instead, keep propagating around the ring. Hence, a significant portion of the excitation energy supplied during each cycle is reused during the next cycle, with the result that the pump operates more effectively than it otherwise would

lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development

BACKGROUND: Lin28 proteins are post-transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let-7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let-7 abundance. We have previously demonstrated that lin28 proteins have functions associated with the regulation of early cell lineage specification in Xenopus embryos, independent of a lin28/let-7 regulatory axis. However, the nature of lin28 targets in Xenopus development remains obscure. RESULTS: Here we show that mir-17∼92 and mir-106∼363 cluster miRNAs are down regulated in response to lin28 knockdown, and RNAs from these clusters are co-expressed with lin28 genes during germ layer specification. Mature miRNAs derived from pre-mir-363 are most sensitive to lin28 inhibition. We demonstrate that lin28a binds to the terminal loop of pre-mir-363 with an affinity similar to that of let-7, and that this high affinity interaction requires to conserved a GGAG motif. CONCLUSION: Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir-17∼92 family miRNAs. This article is protected by copyright. All rights reserved

Appropriate cut-off value for follicle-stimulating hormone in azoospermia to predict spermatogenesis

<p>Abstract</p> <p>Background</p> <p>This study was undertaken to determine the optimal cut-off value for FSH to predict the presence of spermatogenesis in patients with non-obstructive azoospermia.</p> <p>Methods</p> <p>A total of 206 non-obstructive azoospermic men were enrolled in this prospective study. By using receiver operating characteristic (ROC) curves, we determined the optimal cut-off value for FSH and evaluated whether the test could adequately predict successful sperm retrieval.</p> <p>Results</p> <p>There were 108 non-obstructive azoospermic patients who had evidence of spermatogenesis (group A) and achieved success in sperm retrieval. Another 98 non-obstructive azoospermic patients (group B) failed in sperm retrieval. The mean value of serum FSH in group B was significantly higher than in group A (28.03 +/- 14.56 mIU/mL vs 7.94 +/- 4.95 mIU/mL, p < 0.01; respectively). The area under the receiver operating characteristic curves were 0.939 +/- 0.02 and a cut-off value of 19.4 mIU/mL discriminated between group A and B with a sensitivity of 70%. The positive predictive value for failed sperm retrieval (group B) can reach 100%.</p> <p>Conclusions</p> <p>Elevated plasma levels of FSH of more than 19.4 mIU/mL could be used as a reliable criterion for a trial of sperm retrieval from testes in artificial reproductive techniques.</p

A novel framework for multilevel full-chip gridless routing

Abstract — Due to its great flexibility, gridless routing is desirable for nanometer circuit designs that use variable wire widths and spacings. Nevertheless, it is much more difficult than grid-based routing because of its larger solution space. In this paper, we present a novel “V-shaped ” multilevel framework (called VMF) for full-chip gridless routing. Unlike the traditional “Λ-shaped ” multilevel framework (inaccurately called the “Vcycle” framework in the literature), our VMF works in the V-shaped manner: top-down uncoarsening followed by bottom-up coarsening. Based on the novel framework, we develop a multilevel full-chip gridless router (called VMGR) for large-scale circuit designs. The top-down uncoarsening stage of VMGR starts from the coarsest regions and then processes down to finest ones level by level; at each level, it performs global pattern routing and detailed routing for local nets and then estimate the routing resource for the next level. Then, the bottom-up coarsening stage performs global maze routing and detailed routing to reroute failed connections and refine the solution level by level from the finest level to the coarsest one. We employ a dynamic congestion map to guide the global routing at all stages and propose a new cost function for congestion control. Experimental results show that VMGR achieves the best routability among all published gridless routers based on a set of commonly used MCNC benchmarks. Besides, VMGR can obtain significantly less wirelength, smaller critical path delay, and smaller average net delay than the previous works. In particular, VMF is general and thus can readily apply to other problems. I