bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different
Authors: Rimoldi Monica , Chieppa Marcello , Larghi Paola , Vulcano Marisa , Allavena Paola , Rescigno Maria
Published: July 2005

Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are “noninflammatory” as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs. (Blood. 2005;106:2818-2826)
Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2
Authors: Oshima Takashi , Abe Masahiro , Asano Jin , Hara Tomoko , Kitazoe Kenichi , Sekimoto Etsuko , Tanaka Yoichi , Shibata Hironobu , Hashimoto Toshihiro , Ozaki Shuji , Kido Shinsuke , Inoue Daisuke , Matsumoto Toshio
Published: July 2005

Multiple myeloma (MM) develops devastating bone destruction with enhanced bone resorption and suppressed bone formation. In contrast to enhanced osteoclastogenesis, little is known about the mechanism of impaired bone formation in MM. Because a canonical Wingless-type (Wnt) signaling pathway has recently been shown to play an important role in osteoblast differentiation, we examined whether MM cells affect a canonical Wnt pathway to suppress bone formation. Conditioned media from RPMI8226 and U266 MM cell lines and primary MM cells suppressed in vitro mineralization as well as alkaline phosphatase activity in osteoblasts induced by bone morphogenetic protein 2 (BMP-2). These cell lines constitutively produced a soluble Wnt inhibitor, secreted Frizzled-related protein 2 (sFRP-2), but not other Wnt inhibitors including sFRP-1, sFRP-3, and dickkopf 1 (DKK-1) at the protein level. Most MM cells from patients with advanced bone destructive lesions also expressed sFRP-2. Furthermore, exogenous sFRP-2 suppressed osteoblast differentiation induced by BMP-2, and immunodepletion of sFRP-2 significantly restored mineralized nodule formation in vitro, suggesting a predominant role for MM cell-derived sFRP-2 in the impairment of bone formation by MM. Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2.
Soluble factor cross-talk between human bone marrow-derived hematopoietic and mesenchymal cells enhances in vitro CFU-F and CFU-O growth and reveals heterogeneity in the mesenchymal progenitor cell compartment
Authors: Baksh Dolores , Davies John E. , Zandstra Peter W.
Published: July 2005

The homeostatic adult bone marrow (BM) is a complex tissue wherein physical and biochemical interactions serve to maintain a balance between the hematopoietic and nonhematopoietic compartments. To focus on soluble factor interactions occurring between mesenchymal and hematopoietic cells, a serum-free adhesion-independent culture system was developed that allows manipulation of the growth of both mesenchymal and hematopoietic human BM-derived progenitors and the balance between these compartments. Factorial experiments demonstrated a role for stem cell factor (SCF) and interleukin 3 (IL-3) in the concomitant growth of hematopoietic (CD45+) and nonhematopoietic (CD45–) cells, as well as their derivatives. Kinetic tracking of IL-3α receptor (CD123) and SCF receptor (CD117) expression on a sorted CD45– cell population revealed the emergence of CD45–CD123+ cells capable of osteogenesis. Of the total fibroblast colony-forming units (CFU-Fs) and osteoblast colony-forming units (CFU-O), approximately 24% of CFU-Fs and about 22% of CFU-Os were recovered from this population. Cell-sorting experiments demonstrated that the CD45+ cell population secreted soluble factors that positively affect the survival and proliferation of CFU-Fs and CFU-Os generated from the CD45– cells. Together, our results provide insight into the intercellular cytokine network between hematopoietic and mesenchymal cells and provide a strategy to mutually culture both mesenchymal and hematopoietic cells in a defined scalable bioprocess.
Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells
Authors: Neumann Frank , Wagner Claudia , Preuss Klaus-Dieter , Kubuschok Boris , Schormann Claudia , Stevanovic Stefan , Pfreundschuh Michael
Published: July 2005

Because of their frequent expression in a wide spectrum of malignant tumors but not in normal tissue except testis, cancer testis antigens are promising targets. However, except for HOM-TES-14/SCP1, their expression in malignant lymphomas is rare. SCP1 (synaptonemal complex protein 1) has been shown to elicit antibody responses in the autologous host, but no T-cell responses against HOM-TES-14/SCP1 have been reported. Using the SYFPEITHI algorithm, we selected peptides with a high binding affinity to major histocompatibility complex class 2 (MHC 2) molecules. The pentadecamer epitope p635-649 induced specific CD4+ T-cell responses that were shown to be restricted by HLA-DRB1*1401. The responses could be blocked by preincubation of T cells with anti-CD4 and antigen-presenting cells with anti–HLA-DR, respectively, proving the HLA-DR–restricted presentation of p635-649 and a CD4+ T-cell–mediated effector response. Responding CD4+ cells did not secrete interleukin-5 (IL-5), indicating that they belong to the TH1 subtype. The natural processing and presentation of p635-649 were demonstrated by pulsing autologous and allogeneic dendritic cells with a protein fragment covering p635-649. Thus, p635-649 is the first HOM-TES-14/SCP1–derived epitope to fulfill all prerequisites for use as a peptide vaccine in patients with HOM-TES-14/SCP1–expressing tumors, which is the case in two thirds of peripheral T-cell lymphomas.
Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma
Authors: Dewald Gordon W. , Therneau Terry , Larson Dirk , Lee You Kyoung , Fink Stephanie , Smoley Stephanie , Paternoster Sarah , Adeyinka Adewale , Ketterling Rhett , Van Dyke Daniel L. , Fonseca Rafael , Kyle Robert
Published: July 2005

The clinical efficacy of evaluating genetic anomalies in metaphase cells versus interphase nuclei for multiple myeloma (MM) is poorly understood. Therefore, survival for 154 patients with newly diagnosed untreated MM was compared with results from analysis of metaphase and interphase cells. Metaphases were studied by conventional cytogenetics and fluorescent-labeled DNA probes (fluorescence in situ hybridization [FISH]), whereas inter-phase nuclei were evaluated only by FISH. All FISH studies were done using DNA probes to detect t(4;14)(p16;q32), t(11;14)(q13;q32), t(14;16)(q32;q23), del(17) (p13.1), and chromosome 13 anomalies. Metaphases were abnormal by cytogenetics and/or metaphase FISH in 61 (40%) patients. Abnormal interphase nuclei were observed in 133 (86%) patients, including each patient with abnormal metaphases. FISH was a necessary adjunct to cytogenetics to detect t(4;14) and t(14;16) in metaphase cells. Patient survival was especially poor for patients with greater than 50% abnormal interphase nuclei, although this result was more likely due to level of plasma cells than specific chromosome anomalies. For metaphase data, patients with t(4;14), t(14;16), del(17) (p13.1), and/or chromosome 13 anomalies (primarily monosomy 13) had poor survival. A different outcome was observed for interphase data as patients with t(4;14) or t(14;16) had poor survival, whereas patients with chromosome 13 anomalies had intermediate survival: interphase FISH did not substitute for metaphase analysis.
The Ubiquitin-Proteasome Pathway and Its Role in Cancer
Authors: Mani Aparna , Gelmann Edward P.
Published: July 2005

Critical cellular processes are regulated, in part, by maintaining the appropriate intracellular levels of proteins. Whereas de novo protein synthesis is a comparatively slow process, proteins are rapidly degraded at a rate compatible with the control of cell cycle transitions and cell death induction. A major pathway for protein degradation is initiated by the addition of multiple 76–amino acid ubiquitin monomers via a three-step process of ubiquitin activation and substrate recognition. Polyubiquitination targets proteins for recognition and processing by the 26S proteasome, a cylindrical organelle that recognizes ubiquitinated proteins, degrades the proteins, and recycles ubiquitin. The critical roles played by ubiquitin-mediated protein turnover in cell cycle regulation makes this process a target for oncogenic mutations. Oncogenes of several common malignancies, for example colon and renal cell cancer, code for ubiquitin ligase components. Cervical oncogenesis by human papillomavirus is also mediated by alteration of ubiquitin ligase pathways. Protein degradation pathways are also targets for cancer therapy, as shown by the successful introduction of bortezomib, an inhibitor of the 26S proteasome. Further work in this area holds great promise toward our understanding and treatment of a wide range of cancers.
Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer
Authors: von der Maase Hans , Sengelov Lisa , Roberts James T. , Ricci Sergio , Dogliotti Luigi , Oliver T. , Moore Malcolm J. , Zimmermann Annamaria , Arning Michael
Published: July 2005

Purpose

To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC).

Patients and Methods

Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival.

Results

A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (≤ three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively.

Conclusion

Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.
Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer
Authors: Rydén Lisa , Jirström Karin , Bendahl Pär-Ola , Fernö Mårten , Nordenskjöld Bo , Stål Olle , Thorstenson Sten , Jönsson Per-Ebbe , Landberg Göran
Published: July 2005

Purpose

Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance.

Patients and Methods

Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors.

Results

VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status.

Conclusion

Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.
Effects of Excess Weight on Cancer Incidences Depending on Cancer Sites and Histologic Findings Among Men: Korea National Health Insurance Corporation Study
Authors: Oh Sang Woo , Yoon Yeong Sook , Shin Soon-Ae
Published: July 2005

Purpose

The effects of excess weight on the development of cancers are controversial, and little is known for populations outside the United States and Europe. We conducted this study to assess the effects of excess weight with a large cohort of Koreans.

Methods

We assessed the relationship between body mass index (BMI) and various cancers in a 10-year follow-up cohort of 781,283 Korean men who were free of prior cancer at baseline. Weight and height were measured, and questionnaires related to health behaviors and medical history were completed. Data on newly developed cancers were obtained from two organizations in Korea. A proportional hazards model was used to examine the relationship between BMI and cancer.

Results

Adenocarcinoma in the colon and rectosigmoid, hepatocellular carcinoma, cholangiocarcinoma, adenocarcinoma in the prostate, renal cell carcinoma, papillary carcinoma in the thyroid, small-cell carcinoma in the lung, non-Hodgkin's lymphoma, and melanoma had positive dose-dependent relationships with BMI (all P < .05). Although no linear trend was found (P = .267), obese men who never smoked with a BMI of ≥ 30 kg/m2 had an increased risk of developing gastric adenocarcinoma (relative risk = 1.73). Other cancers, such as leukemia, multiple myeloma, and gallbladder and pancreatic cancer, did not show significant associations.

Conclusion

These findings show that, even in Koreans, obesity clearly increases the risk of many types of cancers and the strength of the associations varies with the organ and histologic type. Because these obesity-related cancers are reported to be rapidly increasing in Korea and many other Asian countries, controlling obesity epidemics could be an effective tool for preventing these cancers in these areas.
Enrolling Older Persons in Cancer Trials: The Effect of Sociodemographic, Protocol, and Recruitment Center Characteristics
Authors: Gross Cary P. , Herrin Jeph , Wong Natalie , Krumholz Harlan M.
Published: July 2005

Purpose

To determine the effect of patient, protocol, geographic, and institutional factors on enrollment of older persons onto cancer trials.

Methods

We conducted a cross-sectional analysis of patients enrolled onto National Cancer Institute–sponsored lung, breast, colorectal, and prostate cancer trials during 1996 to 2002. We used a cross-classified logistic multilevel model to examine the associations between patient, hospital, county, and protocol characteristics, and the likelihood of participants being elderly (≥ 65 years old).

Results

The final study sample consisted of 36,167 patients enrolled onto 33 trials. After accounting for cancer type, only 6% of the variation in elderly enrollment onto cancer trials was at the protocol level. In contrast, more than 55% of the variation in elderly enrollment was attributable to patient level variation. In multivariate analysis, nonwhite patients were significantly less likely to be elderly than whites (odds ratio [OR] for blacks, 0.51; 95% CI, 0.44 to 0.58; and OR for Hispanics, 0.49; 95% CI, 0.40 to 0.59 v whites). Participants living less than 7 miles from their recruitment center were significantly more likely to be elderly (OR, 1.31; 95% CI, 1.24 to 1.38). Among the 910 recruitment centers, the median adjusted proportion of patients who were elderly was 24.9% (interquartile range, 24.0% to 26.9%). There were a significantly higher number of outlier centers (≤ 20.8% or ≥ 29.3% elderly) than would be expected by a normal distribution (68 observed v six expected; P < .0001).

Conclusion

Race and proximity to trial enrollment centers were significantly related to age of trial participants after adjusting for protocol factors. Additional work should explore why some recruitment centers were outliers regarding enrollment of older persons.
Regulation ofArabidopsisshoot apical meristem and lateral organ formation by microRNAmiR166gand itsAtHD-ZIPtarget genes
Authors: Williams Leor , Grigg Stephen P. , Xie Mingtang , Christensen Sioux , Fletcher Jennifer C.
Published: July 2005

Plant development is characterized by precise control of gene regulation,leading to the correct spatial and temporal tissue patterning. We have characterized the Arabidopsis jabba-1D (jba-1D) mutant,which displays multiple enlarged shoot meristems, radialized leaves, reduced gynoecia and vascular defects. The jba-1D meristem phenotypes require WUSCHEL (WUS) activity, and correlate with a dramatic increase in WUS expression levels. We demonstrate that the jba-1D phenotypes are caused by over-expression of miR166g,and require the activity of the RNase III helicase DCL1. miR166gover-expression in jba-1D plants affects the transcripts of several class III homeodomain-leucine zipper (AtHD-ZIP) family target genes. The expression of PHABULOSA (PHB), PHAVOLUTA(PHV) and CORONA (CNA) is significantly reduced in a jba-1D background, while REVOLUTA (REV)expression is elevated and ATHB8 is unchanged. In addition, we show that miR166 has a dynamic expression pattern in wild-type and jba-1D embryos. Our analysis demonstrates an indirect role for miRNAs in controlling meristem formation via regulation of WUSexpression, and reveals complex regulation of the class III AtHD-ZIPgene family.
On the feasibility of constrained linear control problems with application to the ALSTOM gasifier
Authors: Kookos I K
Published: July 2005

In 1997 the ALSTOM Power Technology Centre issued an open challenge to the academic control community, which addressed the control of a gasifier plant at three different production levels. Despite the numerous attempts and control methodologies that have been applied to the ALSTOM benchmark case study no satisfactory solution has yet been presented. This work aims to study the feasibility of the gasifier control problem. It is shown that the problem formulation corresponds to an infeasible problem. More specifically, operation at nominal conditions (100 per cent load) is shown to be easy and minimum control effort is required to satisfy process specifications. Operation, on the other hand, at the 0 per cent load conditions is infeasible and as a result no control law can be found that satisfies all process constraints. In the light of the findings of this study it is recommended that the ALSTOM benchmark gasifier problem should be modified to alleviate the infeasibility problem.
Non-linear control of a series direct current motor via flatness and decomposition in the bond graph domain
Authors: Junco S , Donaire A , Achir A , Sueur C , Dauphin-Tanguy G
Published: July 2005

A bond graph (BG) based methodology for non-linear control system synthesis is presented through its application to a speed-tracking problem stated on a series direct current motor. After a global flatness analysis of the motor BG model, a two-loop cascade control structure is decided and developed on the basis of a physical system decomposition in electrical, mechanical, and coupling submodels. Each loop of the cascade tracks a reference for a flat output that is local to a subsystem of the decomposition. Bond graph techniques are given for the three main components of the design methodology: system decomposition, flatness analysis, and tracking controller design. Theoretical and practical properties of the resulting control system are discussed, and its performance is demonstrated through simulation experiments. The methodology is applicable to the broader class of non-linear BG models where input-output system inversion is well defined.
Tiotropium: A Bronchodilator for Chronic Obstructive Pulmonary Disease
Authors: Somand Heather , Remington Tami L
Published: July 2005

OBJECTIVE:

To review the scientific literature evaluating the efficacy and tolerability of tiotropium bromide, a new bronchodilator indicated for treatment of chronic obstructive pulmonary disease (COPD).

DATA SOURCES:

Articles were identified through searches of MEDLINE (1966–January 2005) using the key words tiotropium, BA 679 BR, chronic obstructive pulmonary disease, and anticholinergic agents. Additional citations were identified from bibliographies of publications cited.

STUDY SELECTION AND DATA EXTRACTION:

Experimental and observational studies of tiotropium bromide were selected. Trials of the efficacy of the drug in humans were the focus of the review.

DATA SYNTHESIS:

Tiotropium bromide is an effective bronchodilator for patients with COPD. It produces clinically important improvements in lung function, symptoms of dyspnea, quality of life, and exacerbation rates compared with placebo. In comparative studies, tiotropium does not appear to be more efficacious than salmeterol or ipratropium.

CONCLUSIONS:

Tiotropium is an effective inhaled anticholinergic agent that is recommended among preferred long-acting bronchodilators for the chronic management of moderate to very severe COPD. Although similar to ipratropium in efficacy and tolerability, it has the advantage of once-daily dosing.
Supratherapeutic Response to Ezetimibe Administered with Cyclosporine
Authors: Koshman Sheri L , Lalonde Lucille D , Burton Ilene , Tymchak Wayne J , Pearson Glen J
Published: July 2005

OBJECTIVE:

To report the case of a patient who underwent orthotopic heart transplant (OHT) and demonstrated a supratherapeutic response to ezetimibe when administered with cyclosporine.

CASE SUMMARY:

Ezetimibe 10 mg/day was added to the lipid-lowering regimen (atorvastatin 40 mg/day) of a 64-year-old male patient after OHT to achieve a target low-density lipoprotein cholesterol (LDL-C) level ≤97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patient's LDL-C level had decreased by 60% to 51 mg/dL. Subsequently, the dose of ezetimibe was reduced to 5 mg/day and, after another 2 months, a repeat lipid panel revealed LDL-C 57 mg/dL.

DISCUSSION:

Hyperlipidemia is a common problem among heart transplant recipients. Combination therapy using a statin plus ezetimibe appears to be an attractive option to achieve target lipid levels in this population. However, the manufacturer warns that ezetimibe should be administered cautiously in patients concomitantly receiving cyclosporine. Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total ezetimibe. An objective causality assessment in this case revealed that this supratherapeutic LDL-C reduction was probably related to coadministration of ezetimibe and cyclosporine. A potential mechanism to explain this interaction might be an alteration in glucuronidation induced by cyclosporine.

CONCLUSIONS:

When ezetimibe is prescribed for patients concomitantly receiving cyclosporine, it should be initiated at a lower than recommended dose (≤5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.
The Effects of Work Pace on Within-Participant and Between-Participant Keying Force, Electromyography, and Fatigue
Authors: Gerard Michael J. , Armstrong Thomas J. , Martin Bernard J. , Rempel David A.
Published: July 2005

A laboratory study was conducted to determine the effects of work pace on typing force, electromyographic (EMG) activity, and subjective discomfort. We found that as participants typed faster, their typing force and finger flexor and extensor EMG activity increased linearly. There was also an increase in subjective discomfort, with a sharp threshold between participants' self-selected pace and their maximum typing speed. The results suggest that participants self-select a typing pace that maximizes typing speed and minimizes discomfort. The fastest typists did not produce significantly more finger flexor EMG activity but did produce proportionately less finger extensor EMG activity compared with the slower typists. We hypothesize that fast typists may use different muscle recruitment patterns that allow them to be more efficient than slower typists at striking the keys. In addition, faster typists do not experience more discomfort than slow typists. These findings show that the relative pace of typing is more important than actual typing speed with regard to discomfort and muscle activity. These results suggest that typists may benefit from skill training to increase maximum typing speed. Potential applications of this research includes skill training for typists.
Surface Textures Improve the Robustness of Stereoscopic Depth Cues
Authors: Thomas Geb , Goldberg Joseph H. , Cannon David J. , Hillis Steven L.
Published: July 2005

This research develops design recommendations for surface textures (patterns of color on object surfaces) rendered with stereoscopic displays. In 3 method-of-adjustment procedure experiments, 8 participants matched the disparity of a circular probe and a planar stimulus rendered using a single visible edge. The experiments varied stimulus orientation and surface texture. Participants more accurately matched the depth of vertical stimuli than that of horizontal stimuli, consistent with previous studies and existing theory. Participants matched the depth of surfaces with large pixel-to-pixel luminance variations more accurately than they did surfaces with a small pixel-to-pixel luminance variation. Finally, they matched the depth of surfaces with vertical line patterns more accurately than they did surfaces with horizontal-striped texture patterns. These results suggest that designers can enhance depth perception in stereoscopic displays, and also reduce undesirable sensitivity to orientation, by rendering objects with surface textures using large pixel-to-pixel luminance variations.
Agreeing with Automated Diagnostic Aids: A Study of Users' Concurrence Strategies
Authors: Wiegmann Douglas A.
Published: July 2005

Automated diagnostic aids that are less than perfectly reliable often produce unwarranted levels of disuse by operators. In the present study, users' tendencies to either agree or disagree with automated diagnostic aids were examined under conditions in which (a) the aids were less than perfectly reliable but aided-diagnosis was still more accurate that unaided diagnosis; and (b) the system was completely opaque, affording users no additional information upon which to base a diagnosis. The results revealed that some users adopted a strategy of always agreeing with the aids, thereby maximizing the number of correct diagnoses made over several trials. Other users, however, adopted a probability-matching strategy in which agreement and disagreement rates matched the rate of correct and incorrect diagnoses of the aids. The probability-matching strategy, therefore, resulted in diagnostic accuracy scores that were lower than was maximally possible. Users who adopted the maximization strategy had higher self-ratings of problem-solving and decisionmaking skills, were more accurate in estimating aid reliabilities, and were more confident in their diagnosis on trials in which they agreed with the aids. The potential applications of these findings include the design of interface and training solutions that facilitate the adoption of the most effective concurrence strategies by users of automated diagnostic aids.
Effect of a Concurrent Auditory Task on Visual Search Performance in a Driving-Related Image-Flicker Task
Authors: Richard Christian M. , Wright Richard D. , Ee Cheryl , Prime Steven L. , Shimizu Yujiro , Vavrik John
Published: July 2005

The effect of a concurrent auditory task on visual search was investigated using an image-flicker technique. Participants were undergraduate university students with normal or corrected-to-normal vision who searched for changes in images of driving scenes that involved either driving-related (e.g., traffic light) or driving-unrelated (e.g., mailbox) scene elements. The results indicated that response times were significantly slower if the search was accompanied by a concurrent auditory task. In addition, slower overall responses to scenes involving driving-unrelated changes suggest that the underlying process affected by the concurrent auditory task is strategic in nature. These results were interpreted in terms of their implications for using a cellular telephone while driving. Actual or potential applications of this research include the development of safer in-vehicle communication devices.
Concordance between Task and Interface Rotational and Translational Control Improves Ground Vehicle Performance
Authors: Beckman Paul A.
Published: July 2005

Research in various areas of human-system interaction suggests the importance of examining the similarities and dissimilarities between tasks and the interfaces used to complete them. Specifically, the theory of cognitive fit suggests that human problem solvers will perform better when the data and data displays they use to complete a task match some characteristic of that task. An experiment was performed that extends the theory of cognitive fit to the realm of human performance on motor tasks. Participants completed several virtual vehicle control motor tasks that consisted of rotational and translational control components. The tasks were performed with user interfaces that either combined or separated rotational and translational control. The tasks were of two types: control of either rotation or translation changes but not both concurrently, or simultaneous control of combined rotation and translation changes. The results indicate that task performance was better when the characteristics of the interface matched the characteristics of the task. Actual or potential applications of this research include constructing ground vehicle interface controls that are designed specifically based on the characteristics of the task for which they are to be used, such as primarily driving fast and in a straight line (e.g., on a highway) versus primarily driving slowly with much turning (e.g., on a city street).
Designing for Adaptation to Novelty and Change: Functional Information, Emergent Feature Graphics, and Higher-Level Control
Authors: Hajdukiewicz John R. , Vicente Kim J.
Published: July 2005

Ecological interface design (EID) is a theoretical framework that aims to support worker adaptation to change and novelty in complex systems. Previous evaluations of EID have emphasized representativeness to enhance generalizability of results to operational settings. The research presented here is complementary, emphasizing experimental control to enhance theory building. Two experiments were conducted to test the impact of functional information and emergent feature graphics on adaptation to novelty and change in a thermal-hydraulic process control micro-world. Presenting functional information in an interface using emergent features encouraged experienced participants to become perceptually coupled to the interface and thereby to exhibit higher-level control and more successful adaptation to unanticipated events. The absence of functional information or of emergent features generally led to lower-level control and less success at adaptation, the exception being a minority of participants who compensated by relying on analytical reasoning. These findings may have practical implications for shaping coordination in complex systems and fundamental implications for the development of a general unified theory of coordination for the technical, human, and social sciences. Actual or potential applications of this research include the design of human-computer interfaces that improve safety in complex sociotechnical systems.
Laser Projection versus a CRT Display in the Visual Perception of Aircraft Aspect
Authors: Niall Keith K.
Published: July 2005

High-resolution visual displays have been designed for flight simulation so that observers may judge the aspect angle of aircraft at far distances. The present experiment compares two display devices as untrained observers judge the spatial orientation of two target aircraft: F-15 and F-16 jets. The display devices are a prototype direct-write microlaser projector and an SXGA-format CRT display. Observers' accuracy of aircraft identification is better with the laser projector, and recognition response times are faster. A simple rule was found to fit the observers' response times; it is expressed in terms of a statistic on the autocorrelation of black-and-white silhouette images of aircraft. Observers' estimates of aspect are biased by the laser projector, whereas observers' estimates of aspect are accurate on average with the SXGA display. This bias in estimation of aspect may be attributable to variations in line brightness introduced by the laser projector. Actual or potential applications of this research include the evaluation of high-resolution visual displays for the training of basic fighter maneuvers with military jet pilots.
Using Tactile Features to Help Functionally Blind Individuals Denominate Banknotes
Authors: Lederman Susan J. , Hamilton Cheryl
Published: July 2005

This study, which was conducted for the Bank of Canada, assessed the feasibility of presenting a raised texture feature together with a tactile denomination code on the next Canadian banknote series ($5, $10, $20, $50, and $100). Adding information accessible by hand would permit functionally blind individuals to independently denominate banknotes. In Experiment 1, 20 blindfolded, sighted university students denominated a set of 8 alternate tactile feature designs. Across the 8 design series, the proportion of correct responses never fell below .97; the mean response time per banknote ranged from 11.4 to 13.1 s. In Experiment 2, 27 functionally blind participants denominated 4 of the previous 8 candidate sets of banknotes. The proportion of correct responses never fell below .92; the corresponding mean response time per banknote ranged from 11.7 to 13.0 s. The Bank of Canada selected one of the four raised-texture designs for inclusion on its new banknote series. Other potential applications include designing haptic displays for teleoperation and virtual environment systems.
Headway Feedback Improves Intervehicular Distance: A Field Study
Authors: Shinar David , Schechtman Edna
Published: July 2005

The effectiveness of a headway measuring and recording device was evaluated in terms of its ability to increase drivers' car-following distance. Forty-three drivers first drove for approximately 3 weeks without headway feedback and then for approximately 3 more weeks with immediate time headway (THW) feedback. Whenever the THW decreased to 1.2 s or less a red warning light came on, and whenever the THW decreased further to 0.8 s or less a buzzer was also sounded. The results showed that prior to receiving THW information, drivers drove at shorter headways than after they received that information. The effect of the feedback was to reduce the time spent in short headways (≤0.8 s) by approximately 25% (from 20% to 15% of the time) and to increase the time spent in safer longer headways (>1.2 s) by approximately 20% (from 57% to 65% of the time). The effect was similar for younger and older drivers, for male and female drivers, for urban and highway speeds, and for daytime and nighttime driving. An immediate application of these findings is to install headway feedback displays to drivers so that they may maintain safer headway distances than they do currently.
Aiding Planning in Air Traffic Control: An Experimental Investigation of the Effects of Perceptual Information Integration
Authors: Moertl Peter M. , Canning John M. , Gronlund Scott D. , Dougherty Michael R. P. , Johansson Joakim , Mills Scott H.
Published: July 2005

Prior research examined how controllers plan in their traditional environment and identified various information uncertainties as detriments to planning. A planning aid was designed to reduce this uncertainty by perceptually representing important constraints. This included integrating spatial information on the radar screen with discrete information (planned sequences of air traffic). Previous research reported improved planning performance and decreased workload in the planning aid condition. The purpose of this paper was to determine the source of these performance improvements. Analysis of computer interactions using loglinear modeling showed that the planning interface led to less repetitive - but more integrated - information retrieval compared with the traditional planning environment. Ecological interface design principles helped explain how the integrated information retrieval gave rise to the performance improvements. Actual or potential applications of this research include the design and evaluation of interface automation that keeps users in active control by modification of perceptual task characteristics.
Malleable Attentional Resources Theory: A New Explanation for the Effects of Mental Underload on Performance
Authors: Young Mark S. , Stanton Neville A.
Published: July 2005

This paper proposes a new theory to account for the effects of underload on performance. Malleable attentional resources theory posits that attentional capacity can change size in response to changes in task demands. As such, the performance decrements associated with mental underload can be explained by a lack of appropriate attentional resources. These proposals were explored in a driving simulator experiment. Vehicle automation was manipulated at 4 levels, and mental workload was assessed with a secondary task. Eye movements were also recorded to determine whether attentional capacity varied with mental workload. The results showed a clear decrease in mental workload associated with some levels of automation. Most striking, though, were the results derived from the eye movement recordings, which demonstrated that attentional capacity varies directly with level of mental workload. These data fully supported the predictions of the new theory. Malleable attentional resources theory suggests that future vehicle designers should employ their technology in driver support systems rather than in automation to replace the driver. The implications of this theory are discussed with regard to capacity models of attention as well as to the design of future vehicle systems.
Visually Induced Motion Sickness Predicted by Postural Instability
Authors: Smart L. James , Stoffregen Thomas A. , Bardy Benoît G.
Published: July 2005

We investigated whether postural instability can predict motion sickness and studied relations among instability, motion sickness, and vection. Nine men and 4 women (mean age = 19.85 years) were exposed, while standing, to an optical simulation of body sway. Head motion was recorded using a magnetic tracking system. Postural instabilities were observed prior to the onset of motion sickness. Vection was reported by most participants, including all who became ill. A discriminant analysis revealed that parameters of postural motion accurately predicted motion sickness. The results confirm that postural instability precedes motion sickness and suggest that measures of postural motion may serve as reliable predictors of motion sickness. Potential applications of this research include the development of on-line diagnostic tools that will allow for the prevention of motion sickness in operational and training settings.
Collision Warning Timing, Driver Distraction, and Driver Response to Imminent Rear-End Collisions in a High-Fidelity Driving Simulator
Authors: Lee John D. , McGehee Daniel V. , Brown Timothy L. , Reyes Michelle L.
Published: July 2005

Rear-end collisions account for almost 30% of automotive crashes. Rear-end collision avoidance systems (RECASs) may offer a promising approach to help drivers avoid these crashes. Two experiments performed using a high-fidelity motion-based driving simulator examined driver responses to evaluate the efficacy of a RECAS. The first experiment showed that early warnings helped distracted drivers react more quickly---and thereby avoid more collisions---than did late warnings or no warnings. Compared with the no-warning condition, an early RECAS warning reduced the number of collisions by 80.7%. Assuming collision severity is proportional to kinetic energy, the early warning reduced collision severity by 96.5%. In contrast, the late warning reduced collisions by 50.0 % and the corresponding severity by 87.5%. The second experiment showed that RECAS benefits even undistracted drivers. Analysis of the braking process showed that warnings provide a potential safety benefit by reducing the time required for drivers to release the accelerator. Warnings do not, however, speed application of the brake, increase maximum deceleration, or affect mean deceleration. These results provide the basis for a computational model of driver performance that was used to extrapolate the findings and identify the most promising parameter settings. Potential applications of these results include methods for evaluating collision warning systems, algorithm design guidance, and driver performance model input.
Intelligibility of Speech in a Virtual 3-D Environment
Authors: MacDonald Justin A. , Balakrishnan J. D. , Orosz Michael D. , Karplus Walter J.
Published: July 2005

In a simulated air traffic control task, improvement in the detection of auditory warnings when using virtual 3-D audio depended on the spatial configuration of the sounds. Performance improved substantially when two of four sources were placed to the left and the remaining two were placed to the right of the participant. Surprisingly, little or no benefits were observed for configurations involving the elevation or transverse (front/back) dimensions of virtual space, suggesting that position on the interaural (left/right) axis is the crucial factor to consider in auditory display design. The relative importance of interaural spacing effects was corroborated in a second, free-field (real space) experiment. Two additional experiments showed that (a) positioning signals to the side of the listener is superior to placing them in front even when two sounds are presented in the same location, and (b) the optimal distance on the interaural axis varies with the amplitude of the sounds. These results are well predicted by the behavior of an ideal observer under the different display conditions. This suggests that guidelines for auditory display design that allow for effective perception of speech information can be developed from an analysis of the physical sound patterns.
Ecological Interface Design for Pasteurizer II: A Process Description of Semantic Mapping
Authors: Vernon Dal , Reising C. , Sanderson Penelope M.
Published: July 2005

Ecological interface design (EID) is proving to be a promising approach to the design of interfaces for complex dynamic systems. Although the principles of EID and examples of its effective use are widely available, few readily available examples exist of how the individual displays that constitute an ecological interface are developed. This paper presents the semantic mapping process within EID in the context of prior theoretical work in this area. The semantic mapping process that was used in developing an ecological interface for the Pasteurizer II microworld is outlined, and the results of an evaluation of the ecological interface against a more conventional interface are briefly presented. Subjective reports indicate features of the ecological interface that made it particularly valuable for participants. Finally, we outline the steps of an analytic process for using EID. The findings presented here can be applied in the design of ecological interfaces or of configural displays for dynamic processes.
Endocannabinoid Signaling in Rat Somatosensory Cortex: Laminar Differences and Involvement of Specific Interneuron Types
Authors: Bodor Ágnes L. , Katona István , Nyíri Gábor , Mackie Ken , Ledent Catherine , Hájos Norbert , Freund Tamás F.
Published: July 2005

Endocannabinoid-mediated retrograde signaling exerts powerful control over synaptic transmission in many brain areas. However, in the neocortex, the precise laminar, cellular, and subcellular localization of the type 1 cannabinoid receptor (CB1) as well as its function has been elusive. Here we combined multiple immunolabeling with whole-cell recordings to investigate the morpho-functional characteristics of cannabinoid signaling in rat somatosensory cortex.

Immunostaining for CB1revealed axonal and somatic labeling with striking layer specificity: a high density of CB1-positive fibers was seen in layers II-III, in layer VI, and in upper layer V, whereas other layers had sparse (layer IV) or hardly any (layer I) staining. Membrane staining for CB1was only found in axon terminals, all of which contained GABA and formed symmetric synapses. Double immunostaining also revealed that CB1-positive cells formed two neurochemically distinct subpopulations: two-thirds were cholecystokinin positive and one-third expressed calbindin, each subserving specific inhibitory functions in cortical networks.

In addition, cannabinoid sensitivity of GABAergic input showed striking layer specificity, as revealed by both electrophysiological and anatomical experiments. We found a unique population of large pyramidal neurons in layer VB that received much less perisomatic innervation from CB1-expressing GABAergic axon terminals and, accordingly, showed no depolarization-induced suppression of inhibition, unlike pyramidal cells in layer II, and a population of small pyramidal cells in layer V. This suggests that inhibitory control of pyramidal cells involved in intracortical or corticostriatal processing is fine-tuned by activity-dependent endocannabinoid signaling, whereas inhibition of pyramidal cells relaying cortical information to lower subcortical effector centers often lacks this plasticity.