Nauman Chaudhry

An extended database design methodology for uncertain data management

Abstract Many real world systems require the support of database management systems (DBMS) that can handle vague or imprecise data. Fuzzy theory has been shown to be particularly suitable for this purpose. Indeed there have been several proposals for extending the relational data model in order to represent and query fuzzy data. However, little work has been done in modeling uncertainty at the conceptual schema level or for mapping such a schema to a relational DBMS. To fill this gap, we propose fuzzy entity-relationship methodology (FERM), which is a comprehensive methodology for design and development of fuzzy relational databases. FERM includes an extended fuzzy entity-relationship model to capture imprecision at the schema level as well as generic rules for mapping this schema to relational databases. In this paper, we also show the application of FERM to build a prototype of a fuzzy database for a discrete control system for a semiconductor manufacturing process.

Adaptive extensions to a multibranch run‐to‐run controller for plasma etching

Fuzzy logic and database learning mechanisms have been incorporated into a generic plasma etching run‐to‐run controller, resulting in a very dynamic, adaptable, and robust system. The system features an Applied 8300 reactive ion etcher controlled by a Techware II equipment controller. A TCP/IP connection links this equipment controller to the run‐to‐run controller residing on a SUN. The run‐to‐run control environment is generic in that the basic control framework and controller development results are applicable to very large scale integrated manufacturing in general. The controller is multibranch as it utilizes multiple algorithms in complementary fashion to achieve process optimization and control. The current implementation utilizes three branches: (1) a linear approximation control algorithm, (2) an optimization algorithm that utilizes (real‐time) data collected in situ to determine optimal run‐to‐run process parameter settings, and (3) a statistical optimization algorithm that utilizes run‐to‐run dat...

A design methodology for databases with uncertain data

Many real world systems and applications require information management components that provide support for managing imprecise data. There have thus been several proposals for extending relational database systems in order to represent as well as query such imprecise data. Little work, however, has been done in modeling uncertainty at the conceptual schema level and in developing design methodologies for developing fuzzy relational databases (FRDBs). To fill this gap, a design methodology for FRDBs is proposed. This methodology contains extensions for representing the imprecision of data in the entity-relationship (ER) data model, and a set of steps for the derivation of a FRDB from this extended ER model. As a case study, this methodology has been applied to the design of a control database for semiconductor manufacturing.<<ETX>>

The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

A kinase that controls cell division also promotes the activity of the transforming growth factor–β pathway. Placing BUB1 in the TGF-β Pathway The transforming growth factor–β (TGF-β) pathway regulates cell proliferation and migration, processes involved in development, regeneration, and tumorigenesis. The kinase BUB1, which promotes proper chromosome alignment as cells prepare to divide, also regulates cell proliferation. Nyati et al. connected BUB1 to TGF-β signaling. They found that knocking down BUB1 impaired TGF-β–mediated proliferation of tumor cells—but not by acting at chromosomes. Instead, cytoplasmic BUB1 interacted with TGF-β receptor subunits at the cell surface, promoting the interaction between receptor subunits and between the receptor and downstream signaling proteins. Inhibiting the kinase activity of BUB1 suppressed TGF-β pathway activity in cells in culture and in xenografts. The findings suggest a possible point of crosstalk between the mitotic checkpoint and TGF-β signaling. Transforming growth factor–β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β–mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion.

Active Controller: utilizing active databases for implementing multistep control of semiconductor manufacturing

Whenever the fabrication process consists of several steps and the dynamic modification of individual steps or step sequences of the process is allowed, multistep feedback and feed-forward control can be utilized to improve the quality of the fabrication process. In this paper, we describe the Active Controller-an adaptable and portable software enabler for multistep control in manufacturing facilities. The Active Controller utilizes a recently emerging technology, called active databases, to define and automatically execute powerful and expressive rules for implementing multistep control algorithms. The conditions of Active Controller rules are defined to check for scenarios in which multistep control is needed. The Active Controller keeps track of relevant processing events and data, and when the conditions for multistep control hold, executes appropriate actions to compensate for the errors in processing. We show that the Active Controller, with its capability for the definition of complex rules over a history of processing events and its ability to invoke user-provided analysis routines, provides for a portable and adaptable system that can be used to implement different algorithms for multistep control.

A multilevel approach to the control of a chemical–mechanical planarization process

A multilevel hierarchical control system has been designed and is being applied to chemical–mechanical planarization (CMP) process control. The current implementation of the control system incorporates closed‐loop run‐to‐run (R2R) control and open‐loop real‐time monitoring, and can accommodate inter‐cell control. The R2R control element is enabled via a generic cell controller (GCC) implementation that provides flexible automated control of the process and equipment, multiple control algorithm branches and fuzzy logic decision capability among the branches, simulation capabilities, hardware and software independence, and extensive GUI support for control and data analysis. The R2R element utilizes a linear approximation multivariate control algorithm (branch) that supports individual exponential weighted moving average (EWMA) modeling of advices (outputs), weighting of inputs, granularity, and input bounding. The real‐time element of the control system utilizes a partial least squares (PLS) algorithm to identify real‐time equipment input trace patterns and relate these patterns to alarming conditions. The entire control system is designed to provide multivariate control of CMP process removal rate and uniformity. As a result of extensive design of experiments and testing, the R2R control level has been demonstrated to achieve good control of removal rate and fair control of uniformity. The addition of the real‐time element is expected to improve process control and reduce R2R process noise, thus leading to a more effective R2R control element.

Bridging knowledge translation gap in health in developing countries: visibility, impact and publishing standards in journals from the Eastern Mediterranean

BackgroundLocal and regional scientific journals are important factors in bridging gaps in health knowledge translation in low-and middle-income countries. We assessed indexing, citations and publishing standards of journals from the Eastern Mediterranean region.MethodsFor journals from 22 countries in the collection of the Index Medicus for the Eastern Mediterranean Region (IMEMR), we analyzed indexing in bibliographical databases and citations during 2006–2009 to published items in 2006 in Web of Science (WoS) and SCOPUS. Adherence to editorial and publishing standards was assessed using a special checklist.ResultsOut of 419 journals in IMEMR, 19 were indexed in MEDLINE, 23 in WoS and 46 in SCOPUS. Their impact factors ranged from 0.016 to 1.417. For a subset of 175 journals with available tables of contents from 2006, articles published in 2006 from 93 journals received 2068 citations in SCOPUS (23.5% self-citations) and articles in 86 journals received 1579 citations in WoS (24.3% self-citations) during 2006–2009. Citations to articles came mostly from outside of the Eastern Mediterranean region (76.8% in WoS and 75.4% in SCOPUS). Articles receiving highest number of citations presented topics specific for the region. Many journals did not follow editorial and publishing standards, such addressing requirements about the patient’s privacy rights (68.0% out of 244 analyzed), policy on managing conflicts of interest (66.4%), and ethical conduct in clinical and animal research (66.4%).ConclusionJournals from the Eastern Mediterranean are visible in and have impact on global scientific community. Coordinated effort of all stakeholders in journal publishing, including researchers, journal editors and owners, policy makers and citation databases, is needed to further promote local journals as windows to the research in the developing world and the doors for valuable regional research to the global scientific community.

A novel reporter for real-time, quantitative imaging of AKT-directed K63-poly-ubiquitination in living cells

Post-translational K63-linked poly-ubiquitination of AKT is required for its membrane recruitment and phosphorylation dependent activation in response to growth-factor stimulation. Current assays for target specific poly-ubiquitination involve cumbersome enzymatic preparations and semi-quantitative readouts. We have engineered a reporter that can quantitatively and in a target specific manner report on AKT-directed K63-polyubiquitination (K63UbR) in live cells. The reporter constitutes the AKT-derived poly-ubiquitination substrate peptide, a K63 poly-ubiquitin binding domain (UBD) as well as the split luciferase protein complementation domains. In cells, wherein signaling events upstream of AKT are activated (e.g. either EGFR or IGFR), poly-ubiquitination of the reporter leads to a stearic constraint that prevents luciferase complementation. However, upon inhibition of growth factor receptor signaling, loss of AKT poly-ubiquitination results in a decrease in interaction between the target peptide and the UBD, allowing for reconstitution of the split luciferase domains and therefore increased bioluminescence in a quantitative and dynamic manner. The K63UbR was confirmed to be suitable for high throughput screen (HTS), thus providing an excellent tool for small molecule or siRNA based HTS to discover new inhibitors or identify novel regulators of this key signaling node. Furthermore, the K63UbR platform could be adapted for non-invasive monitoring of additional target specific K63-polyubiquitination events in live cells.

Abstract 1137: Bub1 is a key regulator of TGF-β signaling

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The transforming growth factor-beta (TGF-β) family of cytokines regulates many processes such as immune suppression, angiogenesis, wound healing and epithelial to mesenchymal transition (EMT. Early in tumorigenesis, when epithelial cells retain exquisite growth sensitivity to this ligand, TGF-β signaling elicits a tumor suppressing activity. However, transformed cells become refractory to TGF-β-mediated growth inhibition and acquire a phenotype wherein the intracellular signaling circuitry of the cells is altered, leading to tumorigenic and metastatic effects in response to TGF-β exposure. Although TGF-β activating pathways have been studied, the molecular participants are poorly defined. Here we identify budding uninhibited by benzimidazoles-1 (Bub1) as an integral component of canonical and non-canonical TGF-β signaling pathways, where Bub1 is required for TGFBRI-TGFBRII complex formation and activation. Bub1-depleted cells exhibited reductions in TGF-β dependent Smad2/3 phosphorylation, recruitment of Smad2/3 to the TGFBRI-II complex, PI3K/Akt and p38MAPK activation, Smad binding element driven promoter activity (SBE4-Luc), and invasion and migration. Furthermore, a targeted small molecule inhibitor of Bub1 kinase activity (2OH-BNPP1), as well as an inactive kinase mutant of Bub1, abrogated ligand mediated TGF-β signaling and phenotypic response. These studies demonstrate a role for the Bub1 kinase in mediating TGF-β dependent signaling beyond its established function in cell-cycle regulation and chromosome cohesion and uncover the underlying basis for the pleiotropic cellular response commonly observed upon activation of the pathway. Citation Format: Shyam Nyati, Katrina Schinske-Sebolt, Sethuramasundaram Pitchiaya, Katerina Chekhovskiy, Areeb Chator, Nauman Chaudhry, Joseph Dosch, Marcian E. Van Dort, Varambally, Kumar-Sinha, Nyati, Ray, Walter, Sooryanarayana Varambally, Chandan Kumar-Sinha, Mukesh K. Nyati, Dipankar Ray, Nils G. Walter, Hongtao Yu, Brian D. Ross, Alnawaz Rehemtulla. Bub1 is a key regulator of TGF-β signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1137. doi:10.1158/1538-7445.AM2014-1137