bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors
Authors: Chosdol Kunzang , Misra Anjan , Puri Sachin , Srivastava Tapasya , Chattopadhyay Parthaprasad , Sarkar Chitra , Mahapatra Ashok K , Sinha Subrata 
Published: January 2009

Abstract

Background
We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus.

Methods
In this study we used RAPD-PCR to identify novel genomic alterations in the astrocytic tumors of WHO grade II (Low Grade Diffuse Astrocytoma) and WHO Grade IV (Glioblastoma Multiforme). Loss of heterozygosity (LOH) of the altered region was studied by microsatellite and Single Nucleotide Polymorphism (SNP) markers. Expression study of the gene identified at the altered locus was done by semi-quantitative reverse-transcriptase-PCR (RT-PCR).

Results
Bands consistently altered in the RAPD profile of tumor DNA in a significant proportion of tumors were identified. One such 500 bp band, that was absent in the RAPD profile of 33% (4/12) of the grade II astrocytic tumors, was selected for further study. Its sequence corresponded with a region of FAT, a putative tumor suppressor gene initially identified in Drosophila. Fifty percent of a set of 40 tumors, both grade II and IV, were shown to have Loss of Heterozygosity (LOH) at this locus by microsatellite (intragenic) and by SNP markers. Semi-quantitative RT-PCR showed low FAT mRNA levels in a major subset of tumors.

Conclusion
These results point to a role of the FAT in astrocytic tumorigenesis and demonstrate the use of RAPD analysis in identifying specific alterations in astrocytic tumors.
Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats
Authors: Sathyanarayana Bangalore K , Hahn Yoonsoo , Patankar Manish S , Pastan Ira , Lee Byungkook 
Published: January 2009

Abstract

Background
Mesothelin is a 40 kDa protein present on the surface of normal mesothelial cells and overexpressed in many human tumours, including mesothelioma and ovarian and pancreatic adenocarcinoma. It forms a strong and specific complex with MUC16, which is also highly expressed on the surface of mesothelioma and ovarian cancer cells. This binding has been suggested to be the basis of ovarian cancer metastasis. Knowledge of the structure of this protein will be useful, for example, in building a structural model of the MUC16-mesothelin complex. Mesothelin is produced as a precursor, which is cleaved by furin to produce the N-terminal half, which is called the megakaryocyte potentiating factor (MPF), and the C-terminal half, which is mesothelin. Little is known about the function of mesothelin and there is no information on its possible three-dimensional structure. Mesothelin has been reported to be homologous to the deafness-related inner ear proteins otoancorin and stereocilin, for neither of which the three-dimensional structure is known.

Results
The BLAST and PSI-BLAST searches confirmed that mesothelin and mesothelin precursor proteins are remotely homologous to stereocilin and otoancorin and more closely homologous to the hypothetical protein MPFL (MPF-like). Secondary structure prediction servers predicted a predominantly helical structure for both mesothelin and mesothelin precursor proteins and also for stereocilin and otoancorin. Three-dimensional structure prediction servers INHUB and I-TASSER produced structural models for mesothelin, which consisted of superhelical structures with ARM-type repeats in conformity with the secondary structure predictions. Similar ARM-type superhelical repeat structures were predicted by 3D-PSSM server for mesothelin precursor and for stereocilin and otoancorin proteins.

Conclusion
The mesothelin superfamily of proteins, which includes mesothelin, mesothelin precursor, megakaryocyte potentiating factor, MPFL, stereocilin and otoancorin, are predicted to have superhelical structures with ARM-type repeats. We suggest that all of these function as superhelical lectins to bind the carbohydrate moieties of extracellular glycoproteins.
Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
Authors: Lee Jun Hyoung , Sung Bong Hyun , Kim Mi Sun , Blattner Frederick R , Yoon Byoung Hoon , Kim Jung Hoe , Kim Sun Chang 
Published: January 2009

Abstract

Background
Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-genome Escherichia coli strain MDS42 that lacks 14.3% of its chromosome.

Results
Here we describe the reengineering of the MDS42 genome to increase the production of the essential amino acid L-threonine. To this end, we over-expressed a feedback-resistant threonine operon (thrA*BC), deleted the genes that encode threonine dehydrogenase (tdh) and threonine transporters (tdcC and sstT), and introduced a mutant threonine exporter (rhtA23) in MDS42. The resulting strain, MDS-205, shows an ~83% increase in L-threonine production when cells are grown by flask fermentation, compared to a wild-type E. coli strain MG1655 engineered with the same threonine-specific modifications described above. And transcriptional analysis revealed the effect of the deletion of non-essential genes on the central metabolism and threonine pathways in MDS-205.

Conclusion
This result demonstrates that the elimination of genes unnecessary for cell growth can increase the productivity of an industrial strain, most likely by reducing the metabolic burden and improving the metabolic efficiency of cells.
Role of Acid-Sensing Ion Channel 3 in Sub-Acute-Phase Inflammation
Authors: Yen Yi-Tin , Tu Pan-Hsien , Chen Chien-Ju , Lin Yi-Wen , Hsieh Sung-Tsang , Chen Chih-Cheng 
Published: January 2009

Background Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout ( ASIC3−/−) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation. Results Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3−/− mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3+/+ controls, ASIC3−/− mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3−/− or ASIC3+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3−/− mice, as previously described. However, ASIC3−/− mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3+/+ mice. Conclusion We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.
Numerical simulation of embankment—structure transition design
Authors: Gallego Giner I , López Pita A 
Published: January 2009

The experience of several European railway systems has shown that problems occur frequently in zones with embankment—structure transitions, and these areas therefore require repeated maintenance. To date, no adequate solution for these zones has been demonstrated, and different European railway systems have adopted different design approaches. In this work, a finite-element model is developed to simulate the behaviour of embankment—structure transitions to improve the methods available for modelling railway track designs. The most distinctive characteristic of the model proposed here is its attempt to simulate the real behaviour of the diverse materials that make up the structure of the track in a transition. To achieve this, a three-dimensional model with boundary conditions that more closely resemble real conditions was used; the model assumes that the surface defining the embankment slope is free and it takes into account the elastoplastic behaviour of the soil. This model was tested by numerical calculations of several case studies created from different values of geotechnical and geometrical parameters of transition zones. The results from this analysis will help to define new criteria for improving the design of embankment—structure transitions.
Real-time simulation of a COGAG naval ship propulsion system
Authors: Altosole M , Benvenuto G , Figari M , Campora U 
Published: January 2009

Design and optimization of the propulsion system is a crucial task of the ship design process. The behaviour of the propulsion system, in transient conditions as well as in steady state, is greatly affected by the capability of the control system to manage the available power and to achieve the desired performance in the shortest time. The selection of a proper control scheme is a trade-off between different and conflicting needs. Two of the opposites are: increasing the ship operability by adding more functions and more controls; and reducing the control system development and installation time and cost. In this paper, the rapid prototyping and testing procedure for the development of the propulsion controller of the new Italian aircraft carrier Cavour is presented, using real-time hardware-in-the-loop (RT-HIL) simulation. The procedure is based on a wide use of simulation technology. First, a complete dynamical model of the ship propulsion plant was developed. Then, batch simulation was used to develop the best possible control scheme. Finally, RT-HIL simulation was used to debug the real controller software and to tune the controller parameters before sea trials. The application of the procedure led to a significant reduction in the development phase of the controller design. Furthermore, the adoption of the RT-HIL technology greatly reduced the time spent to tune the control system during the ship delivery phase.
Weight-Based Argatroban Dosing Nomogram for Treatment of Heparin-Induced Thrombocytopenia
Authors: Ansara Alexander J , Arif Sally , Warhurst Robert D 
Published: January 2009

BACKGROUND Manufacturer recommendations for argatroban use in the setting of heparin-induced thrombocytopenia (HIT) state that the dosage should be titrated to a goal activated partial thromboplastin time (aPTT) of 1.5–3 times the baseline aPTT. The lack of a clear dosing strategy with argatroban may result in delayed stabilization of aPTT. There are no published nomograms to guide the dosing of argatroban. OBJECTIVE To study the anticoagulant effect and incidence of bleeding and thrombotic events in patients receiving argatroban, with doses determined using a weight-based nomogram. METHODS Patients with suspected or documented HIT at an 800-bed teaching community hospital were prospectively treated, in a nonrandomized, nonblinded manner, with argatroban; dosage adjustments were made according to 1 of 2 variations of a dosing nomogram: standard or hepatic/critically ill. The primary outcomes were time to aPTT stabilization and percentage of patients whose aPTTs were within the therapeutic range of 45–90 seconds at 6, 12, 24, 48, 72, and 96 hours. Secondary outcomes were the percentage of patients whose aPTTs were subtherapeutic, supratherapeutic, or above the therapeutic threshold of 45 seconds at each time interval; incidence of thrombotic events; number of dosage adjustments to achieve stabilization; and number of major bleeding events. RESULTS Fifty-one patients were prospectively treated using the standard (n = 34) and hepatic/critically ill (n = 17) nomograms. Mean time to aPTT stabilization was 16.25 hours with the standard nomogram and 27.05 hours with the hepatic/critically ill nomogram. The percentages of patients with aPTTs within the therapeutic range at each time interval were 82.4%, 82.4%, 88.2%, 96.4%, 100%, and 100% with the standard nomogram and 58.8%, 82.4%, 76.5%, 93.3%, 100%, and 90.9% with the hepatic/critically ill nomogram. There were no thrombotic events after the initiation of argatroban. Three cases of major bleeding occurred. CONCLUSIONS The nomogram is an effective dosing tool for achieving and maintaining therapeutic levels of anticoagulation.
Increases in C-Reactive Protein May Predict Recurrence of Clozapine-Induced Fever
Authors: Kohen Izchak , Afzal Noman , Hussain Saira , Manu Peter 
Published: January 2009

OBJECTIVE To report a case of recurrent clozapine-induced fever that was associated with a rise in C-reactive protein (CRP). CASE SUMMARY A 73-year-old man with Lewy Body dementia was admitted for psychosis. He was treated with clozapine (initial dose 12.5 mg/day, titrated to 75 mg/day over 15 days). On day 15 of clozapine therapy, he developed a benign fever (maximum 38.4 °C) that was associated with a rise in the CRP level (3.96 mg/dL). The level normalized when clozapine was discontinued. However, when the patient was rechallenged with clozapine, the CRP level became elevated (4.36 mg/dL) after 3 days of therapy, with a subsequent recurrence of fever (38.7 °C). DISCUSSION We postulate that the elevation in CRP levels and the subsequent fever were caused by the effects of clozapine on the cytokine system via interleukin-6 and tumor necrosis factor-α, resulting in an inflammatory response with an acute phase reaction. This case is unique, as it is the first reported in the literature associating a recurrence of clozapine-induced fever with the known immunomodulatory effects of clozapine on cytokines and CRP level. According to the Naranjo probability scale, this adverse effect is probably associated with clozapine. CONCLUSIONS Clozapine-related fever is generally benign but difficult to assess and manage, as it can be confused with much more serious conditions. Further research is needed to study whether CRP is a useful tool in predicting and managing clozapine fever.
Risktaking and Driver Behaviors: A Laboratory Study
Authors: Shoptaugh Carol F. 
Published: January 2009

A number of variables have been implicated as predictors of actual risky driving behaviors. However, due to differing methodologies, the literature shows few consistent findings. The current study is an attempt to establish a more complete understanding of the relationship between risk related characteristics and actual risktaking decisions. It was predicted that individuals who had a greater propensity for taking risks would also be more prone to making risky decisions in a simulated driving task. Sixty subjects (30 male, 30 female) were selected based on their Kogan and Wallach Choice Dilemma risktaking scores (15 high and 15 low risktakers in each gender group). Subjects participated in two 1 1/2 hour experimental sessions. Session one was a video tape risk choice session and session two, a battery of demographic, driving and risktaking characteristic questionnaires were given. The most significant finding in this study involved the misuse of speed and distance in making turn decisions. All subjects adopted a safer criterion than the normative model for left turn gap distances, but for right turn merging gaps high risktaking subjects perceived significantly more gaps as safe than did low risktaking subjects. Further, as speed increased from 30mph to 55mph all subjects believed more gaps to be safe for right turn merging. This miscalculation could result in a rear end accident. Most demographic, driver and risktaking measures failed to correlated significantly with risky decision making. Only the Choice Dilemma and the Pelz-Schuman Impulsivity questionnaire correlated with each other and the risky driver decisions.
The Older Driver — A Challenge to the Design of Automotive Electronic Displays
Authors: Rockwell T.H. , Augsburger Arol , Smith Stanley W. , Freeman Scott 
Published: January 2009

Older drivers present unique challenges to the display designer. Approximately 30 percent of all drivers in the U.S. are over 50 years of age. Visual impairment, e.g., presbyopia, begins after 40. After age 55, approximately 91 percent of the population use bifocals. Unfortunately, bifocals with significant add power create zones of decreased acuity in the critical instrument panel viewing distances of 500–800 mm. In this paper, the demands for vision in driving are related to the special visual disabilities associated with the older driver, such as increased sensitivity to glare, high contrast ratio blurring of electronic displays and increased time for target recognition. A computer legibility model is presented to relate the principal factors in design, namely character height and width, viewing distance, contrast ratio and background luminance with legibility impairment associated with various age groups. Implications of model predictions to display design are discussed.
Reduced Keyboard Designs Using Disambiguation
Authors: Kreifeldt J. G. , Levine S. L. , Iyengar C. 
Published: January 2009

There are a number of important applications where the accuracy of typed copy is less important than other criteria, such as the speed of entry, ease of learning, reduced keyboard size, provision for innovative keyboard designs and work methods, etc. Some of these applications include communication devices for the motor handicapped and rough drafting. The applications in question still provide single finger typing as opposed to multifinger entries for chord keyboards. One approach to keyboard design for such applications involves using a multicharacter key set. Because there is more than one character on a key, the number of keys can be reduced to a point limited only by the required accuracy of the text produced which is itself limited by the ability of “disambiguation” algorithms to decode the ambiguous text strings. Reducing the number of keys increases text entry rates and reduces learning time. Experiments with keysets of 10, 12, 14, and 16 keys have produced keystroke rates of 3.3 to 1.7 characters per second and a 6% keying error while the disambiguation programs can produce an accuracy of 85 to 95%. Learning time in the experiments was about 9 to 12 minutes. The experiments demonstrate the feasibility of increasing text entry rates and freeing the keyboard from architectural constraints.
Riding Mower Control Placement Guideline Development
Authors: Heasly Christopher C. , Perse Randy M. , Malone Thomas B. , Fleger Stephen A. 
Published: January 2009

Accident investigations and subsequent hazard analysis studies of power mower accidents conducted by the Consumer Product Safety Commission (CPSC), indicated that the current version of the American National Standard for Turf Care Equipment - Power Lawn Mowers, Lawn and Garden Tractors, and Lawn Tractors - Safety Specifications (ANSI/OPEI B71.1-1986) might benefit from review and/or revision. The analyses indicated control activation, placement and/or operation may have contributed to a number of the accidents reviewed. Accordingly, special emphasis was to be focused on review of Part III: Ride-On Mowers, Lawn Tractors, and Lawn and Garden Tractors, paragraph 13., Controls. This paper describes the approach utilized in development of the inputs to update ANSI/OPEI B71.1-1986. Additionally, the paper describes a brief overview of the voluntary standard review/acceptance process.
Children's Human Factors in the Design of a Pre-School Educational Furnishings System
Authors: Wise Barbara K. , Wise James A. 
Published: January 2009

This paper describes the Human Factors design basis of an innovative educational furnishings system developed for the “Head Start Classroom of the Future”. The Human Factors contributions centered on: — the ergonomics of pre-school children, including sizing, reach, visual access and ability to manipulate the furnishings elements, — safety and hazards analyses for the construction of furnishings, materials and surface finishes selection, — design for children-computer interactions through a new type of computer furniture, — development of a ‘cognitive ergonomics’ for educational furnishings that assess how these support planned activities and opportunistic discovery play. The furnishings system is analogous to office landscaping systems that are flexible, modular in nature and adaptable to different facility settings. It is called a “Learning Landscape”, and it helps the classroom become a true active partner in the learning process
Tactical Symbology Standards
Authors: Kirkpatrick Mark , Dutra Lisa A. , Lyons Robert A. , Osga Glenn A. , Pucci John J. 
Published: January 2009

CRT displays aboard U.S. Navy ships use a standardized monochrome Naval Tactical Data System (NTDS) symbol set to represent properties of symbols such as platform type (e.g. Aircraft Carrier, Combat Air), environment (e.g. air, surface, subsurface), and identification (e.g. hostile, friendly). A color symbol set has been proposed in NATO Standardization Agreement 4420, Display Symbology and Colours for NATO Maritime Units (1990). The U.S. Navy is currently considering ratification of this Standardization Agreement (STANAG). Empirical comparisons of operator performance using the NTDS symbology versus those using the color-filled NATO STANAG symbology were conducted. Two additional experimental symbologies were also created. The first, called NTDS Equated, is a color version of the NTDS symbol set, and the second experimental symbol set, called NATO Outline, is a color outline version of the color filled NATO STANAG symbol set. Test subjects were asked to find (hook) specific symbols during a tactically relevant scenario. Time to the first correct hook and percentage of correct hooks were subjected to analyses of variance (ANOVA). Experimental results revealed that the NATO STANAG symbol set outperformed all other symbol sets in terms of symbol recognition time, and outperformed the NTDS Standard symbol set for symbol recognition accuracy as well. The results indicated that tactical information can be transferred more quickly and accurately to watch standers through effective use of symbol coding. Test subjects familiar with the NTDS symbology expressed a preference for the color symbol sets in opinion surveys administered after the experiment. General conclusions resulting from comparisons across symbol sets were that color fill was more effective than color outline, and that operator performance gains were achieved as a result of color coding and greater information content on the symbol. This paper presents the human performance assessment that was conducted, the results, and the implications of the findings for ratification of NATO STANAG 4420.