bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper limb neuropathy in computer operators? A clinical case study of 21 patients
Authors: Jepsen Jørgen Riis
Published: August 2004

Background

The character of upper limb disorder in computer operators remains obscure and their treatment and prevention have had limited success. Symptoms tend to be mostly perceived as relating to pathology in muscles, tendons or insertions. However, the conception of a neuropathic disorder would be supported by objective findings reflecting the common complaints of pain, subjective weakness, and numbness/tingling. By examining characteristics in terms of symptoms, signs, and course, this study aimed at forming a hypothesis concerning the nature and consequences of the disorder.

Methods

I have studied a consecutive series of 21 heavily exposed and severely handicapped computer-aided designers. Their history was recorded and questionnaire information was collected, encompassing their status 1/2 – 1 1/2 years after the initial clinical contact. The physical examination included an assessment of the following items: Isometric strength in ten upper limb muscles; sensibility in five homonymously innervated territories; and the presence of abnormal tenderness along nerve trunks at 14 locations.

Results

Rather uniform physical findings in all patients suggested a brachial plexus neuropathy combined with median and posterior interosseous neuropathy at elbow level. In spite of reduced symptoms at follow-up, the prognosis was serious in terms of work-status and persisting pain.

Conclusions

This small-scale study of a clinical case series suggests the association of symptoms to focal neuropathy with specific locations. The inclusion of a detailed neurological examination would appear to be advantageous with upper limb symptoms in computer operators.
Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae
Authors: Yao Xiao-Jian , Rougeau Nicole , Duisit Ghislaine , Lemay Julie , Cohen Éric A
Published: August 2004

Background

The HIV-1 genome encodes a well-conserved accessory gene product, Vpr, that serves multiple functions in the retroviral life cycle, including the enhancement of viral replication in nondividing macrophages, the induction of G2 cell-cycle arrest, and the modulation of HIV-1-induced apoptosis. We previously reported the genetic selection of a panel of di-tryptophan (W)-containing peptides capable of interacting with HIV-1 Vpr and inhibiting its cytostatic activity in Saccharomyces cerevisiae (Yao, X.-J., J. Lemay, N. Rougeau, M. Clément, S. Kurtz, P. Belhumeur, and E. A. Cohen, J. Biol. Chem. v. 277, p. 48816–48826, 2002). In this study, we performed a mutagenic analysis of Vpr to identify sequence and/or structural determinants implicated in the interaction with di-W-containing peptides and assessed the effect of mutations on Vpr-induced cytostatic activity in S. cerevisiae.

Results

Our data clearly shows that integrity of N-terminal α-helix I (17–33) and α-helix III (53–83) is crucial for Vpr interaction with di-W-containing peptides as well as for the protein-induced cytostatic effect in budding yeast. Interestingly, several Vpr mutants, mainly in the N- and C-terminal domains, which were previously reported to be defective for cell-cycle arrest or apoptosis in human cells, still displayed a cytostatic activity in S. cerevisiae and remained sensitive to the inhibitory effect of di-W-containing peptides.

Conclusions

Vpr-induced growth arrest in budding yeast can be effectively inhibited by GST-fused di-W peptide through a specific interaction of di-W peptide with Vpr functional domain, which includes α-helix I (17–33) and α-helix III (53–83). Furthermore, the mechanism(s) underlying Vpr-induced cytostatic effect in budding yeast are likely to be distinct from those implicated in cell-cycle alteration and apoptosis in human cells.
High versus low intensity exercise training in pulmonary rehabilitation: is more better?
Authors: Dattal D , ZuWallack R
Published: August 2004

Background:Exercise training is considered a necessary component of comprehensive pulmonary rehabilitation. However, to date, there is no consensus on an exercise training strategy for pulmonary rehabilitation, and this has resulted in varied approaches to this intervention in its literature. As in healthy individuals, the effect of exercise training on patients with chronic lung disease is dose dependent, with higher intensities resulting in greater physiological adaptations than lower intensities. Results:It is not clear from our review of the literature that these enhanced physiological effects from higher levels of exercise training translate into a reduced burden of symptoms, hence a better quality of life. Indeed, there is some evidence that pulmonary rehabilitation approaches incorporating lower intensities of exercise training are at least as good in improving questionnaire rated symptoms of health status. This provides food for thought, since the prominent goal of pulmonary rehabilitation should be to reduce bothersome symptoms or enhance health status, not simply increase endurance time on a cycle ergometer.
Randomized controlled trial of alendronate in airways disease and low bone mineral density
Authors: Smith B J , Laslett L L , Pile K D , Phillips P J , Phillipov G , Evans S M , Esterman A J , Berry J G
Published: August 2004

Background:Patients with airways disease have been demonstrated to be at risk of osteoporosis, and this is likely to be multifactorial. Our aim was to identify patients with low bone mineral density (BMD) using a screening program, and then evaluate the benefit of daily alendronate. Method:Subjects with hip or lumbar spine baseline T-scores <-2.5, or Z-score <-1.0 commenced on alendronate/calcium (10 mg/600 mg day) or placebo/calcium, in a double blind randomized controlled trial. BMD by dual emission X-ray absorptiometry (lumbar vertebrae 2-4, neck of femur, total femur) was repeated after 12 months, with adverse events recorded. Results: 145 subjects (74 male, 71 female, mean age 67, median FEV, 1.0 litres = 43% of predicted) were enrolled; 66 alendronate/calcium, 79 placebo/calcium with 24 and 26 withdrawals, respectively. Per protocol but not intention to treat analysis of covariance demonstrated statistically significant improvements in T and Z scores for lumbar spine bone mineral density (P = 0.035, P = 0.040), with no improvement demonstrated at the hip. Conclusions:Improvement in bone mineral density has been demonstrated at the lumbar spine, but not hip, by per protocol analysis, with daily alendronate, at 12 months.
Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques (incorporating postural drainage and vibration) versus test of incremental respiratory endurance
Authors: Patterson J E , Bradley J M , Elbom J S
Published: August 2004

Objectives:The purpose of this study was to compare the efficacy of the test of incremental respiratory endurance (TIRE) with active cycle of breathing techniques (ACBT) [incorporating postural drainage (PD) and vibration] as methods of airway clearance in adults with bronchiectasis. Design:A randomized crossover study in which a single session of ACBT (incorporating PD and vibration) was compared to a single session of TIRE was carried out in 20 patients (14 female) with stable, productive bronchiectasis. Measurements:Weight of sputum (treatment plus 30 min) was the primary outcome measure recorded. Pre and post-treatment measures of lung function and SpO2 were also recorded. Results:All 20 patients were stable during the study period. Sputum weight expectorated during and 30 min post-ACBT (incorporating PD and vibration) treatment was significantly greater than the sputum weight expectorated during and 30 min post-TIRE treatment [mean difference 2.44 g (95% CI 0.43-4.45)]. Conclusion:ACBT (incorporating PD and vibration) is a more effective method of airway clearance in bronchiectasis than TIRE during single treatment sessions.
Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40
Authors: Dupont Jakob , Tanwar Meena K. , Thaler Howard T. , Fleisher Martin , Kauff Noah , Hensley Martee L. , Sabbatini Paul , Anderson Sibyl , Aghajanian Carol , Holland Eric C. , Spriggs David R.
Published: August 2004

Purpose

YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer.

Materials and Methods

Serum YKL-40 levels were assayed by enzyme-linked immunosorbent assay for 46 healthy subjects, 61 high-risk individuals, 33 patients with benign gynecologic processes, and 50 preoperative patients subsequently diagnosed with predominantly early-stage ovarian cancer. Serum CA125 and CA15-3 values were obtained.

Results

Median YKL-40 level was 28 ng/mL (range, 15 to 166 ng/mL) for healthy subjects, 36 ng/mL (range, 9 to 69 ng/mL) for high-risk individuals without prior cancer, 44.5 ng/mL (range, 5 to 133 ng/mL) for high-risk patients with prior breast cancer, and 38 ng/mL (range, 5 to 67 ng/mL) for individuals with benign gynecologic processes (P = NS). Median preoperative YKL-40 level for ovarian cancer patients was 94 ng/mL (range, 17 to 517 ng/mL; P < .0001 compared with normal and high-risk). YKL-40 was elevated (≥ 62 ng/mL) in 36 (72%) of 50 patients compared with 23 (46%) of 50 and 13 (26%) of 50 patients for CA125 and CA15-3 (P < .008). Twenty (65%) of 31 early-stage patients had elevated serum YKL-40 levels compared with 11 (35%) of 31 and four (13%) of 31 patients for CA125 and CA15-3 (P = .039). YKL-40 levels increased with stage (P < .005), regardless of grade, histology, or patient age. Patients with early-stage tumors with YKL-40 values more than 80 ng/mL had a worse prognosis (71% recurrence v no recurrence [P = .034]).

Conclusion

YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer. YKL-40 levels in early-stage patients may also predict disease recurrence and survival. The utility of YKL-40 in detection of early-stage ovarian cancer deserves further investigation.
Cytoreductive Surgery Combined With Perioperative Intraperitoneal Chemotherapy for the Management of Peritoneal Carcinomatosis From Colorectal Cancer: A Multi-Institutional Study
Authors: Glehen O. , Kwiatkowski F. , Sugarbaker P.H. , Elias D. , Levine E.A. , De Simone M. , Barone R. , Yonemura Y. , Cavaliere F. , Quenet F. , Gutman M. , Tentes A.A.K. , Lorimier G. , Bernard J.L. , Bereder J.M. , Porcheron J. , Gomez-Portilla A. , Shen P. , Deraco M. , Rat P.
Published: August 2004

Purpose

The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival.

Patients and Methods

A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded.

Results

The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P < .001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators.

Conclusion

The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
Results of a Phase II Upfront Window of Pharmacokinetically Guided Topotecan in High-Risk Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor
Authors: Stewart Clinton F. , Iacono Lisa C. , Chintagumpala Murali , Kellie Stewart J. , Ashley David , Zamboni W.C. , Kirstein M.N. , Fouladi Maryam , Seele Louis G. , Wallace Dana , Houghton Peter J. , Gajjar Amar
Published: August 2004

Purpose

To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients.

Patients and Methods

After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL·h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization.

Results

Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range.

Conclusion

Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.
Positron Emission Tomography in Limited-Stage Small-Cell Lung Cancer: A Prospective Study
Authors: Bradley Jeffrey D. , Dehdashti Farrokh , Mintun Mark A. , Govindan Ramaswamy , Trinkaus Kim , Siegel Barry A.
Published: August 2004

Purpose

To determine how often positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC.

Patients and Methods

We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information.

Results

FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis.

Conclusion

FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.
Preoperative F-18 Fluorodeoxyglucose-Positron Emission Tomography Maximal Standardized Uptake Value Predicts Survival After Lung Cancer Resection
Authors: Downey Robert J. , Akhurst Timothy , Gonen Mithat , Vincent Alain , Bains Manjit S. , Larson Steven , Rusch Valerie
Published: August 2004

Purpose

A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose–positron emission tomography ([18F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival.

Patients and Methods

Non–small-cell lung cancer or carcinoid pT1–4, N0–2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier.

Results

One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUVMAX) was 9. The 2-year survival for patients with SUVMAX more than 9 was 68% and for those with SUVMAX less than 9, it was 96% (P < .01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUVMAX, only tumor size (T) more than 3 cm and SUVMAX more than 9 and their interaction were significant predictors of survival (P = .01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUVMAX less than 9 was 97%; for those with T less than 3 cm and SUVMAX more than 9, it was 94%; for those with T more than 3 cm and SUVMAX less than 9, it was 93%; and for those with T more than 3 cm and SUVMAX more than 9, it was 47% (P < .01).

Conclusion

In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUVMAX to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.
Phase II Study of Cisplatin and Vinorelbine in Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Morris Mitchell , Blessing John A. , Monk Bradley J. , McGehee Ramon , Moore David H.
Published: August 2004

Purpose

To evaluate the efficacy and toxicity of intravenous cisplatin and vinorelbine as combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix.

Patients and Methods

Between August 1997 and January 2001, 73 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Eligible patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. The initial doses administered were cisplatin 75 mg/m2 every 4 weeks and vinorelbine 30 mg/m2 weekly. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity and protocol guidelines. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria.

Results

Of 73 patients, 67 were eligible and assessable. The overall response rate was 30% (five complete and 15 partial responses). The overall median response duration was 5.5+ months. The major toxicity was neutropenia, with 16% grade 3 and 67% grade 4 reported. Gastrointestinal and neurotoxicity were infrequent and mild.

Conclusion

The combination of cisplatin and vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population.
Oil-based formulations for oral delivery of insulin
Authors: Li Chun-Lei , Deng Ying-Jie
Published: August 2004

Several oil-based solution formulations of insulin were prepared, in which insulin was solubilized in the form of anhydrous reverse micelles. The preparation process involved micellar dissolution of insulin followed by freeze drying, then reconstitution of lyophilized product with an oil phase. These formulations were stable at room temperature for up to 12 months. No significant changes in the appearance were observed and no degradation products of insulin were detected during the course of the stability study. The efficacy of these formulations was evaluated in-vivo using diabetic Wistar rat as an animal model and then a specific formulation was chosen for further study in non-diabetic New Zealand rabbits. It was found that the efficacy of insulin oil solution was dose dependent and insulin oil solution had the same efficacy as insulin emulsion with the same formulation composition. If ethylene-diaminetetraacetic acid (EDTA) was pre-delivered 40 min before the delivery of insulin oil solution, the hypoglycaemic effect of insulin oil solution was greatly enhanced, with an AUC (% glucose reduced) value increase from 28.5 ± 14.7 to 167.1 ± 72.3. The improvement of oral absorption induced by pre-delivery of EDTA might be attributed to enzyme inhibition, reduced gut mobility and the opening of paracellular routes.
Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity
Authors: Ruest Louis-Bruno , Xiang Xilin , Lim Kim-Chew , Levi Giovanni , Clouthier David E.
Published: August 2004

The lower jaw skeleton is derived from cephalic neural crest (CNC) cells that reside in the mandibular region of the first pharyngeal arch. Endothelin-A receptor (Ednra) signaling in crest cells is crucial for their development, as Ednra–/– mice are born with severe craniofacial defects resulting in neonatal lethality. In this study, we undertook a more detailed analysis of mandibular arch development in Ednra–/– embryos to better understand the cellular and molecular basis for these defects. We show that most lower jaw structures in Ednra–/– embryos undergo a homeotic transformation into maxillary-like structures similar to those observed in Dlx5/Dlx6–/– embryos, though lower incisors are still present in both mutant embryos. These structural changes are preceded by aberrant expansion of proximal first arch gene expression into the distal arch, in addition to the previously described loss of a Dlx6/Hand2 expression network. However, a small distal Hand2expression domain remains. Although this distal expression is not dependent on either Ednra or Dlx5/Dlx6 function, it may require one or more GATA factors. Using fate analysis, we show that these distal Hand2-positive cells probably contribute to lower incisor formation. Together, our results suggest that the establishment of a `mandibular identity' during lower jaw development requires both Ednra-dependent and -independent signaling pathways.
The CES-2-related transcription factor E4BP4 is an intrinsic regulator of motoneuron growth and survival
Authors: Junghans Dirk , Chauvet Sophie , Buhler Emmanuelle , Dudley Keith , Sykes Toby , Henderson Christopher E.
Published: August 2004

The regulation of neuronal growth and survival during development requires interplay between extrinsic and intrinsic factors. Among the latter,transcription factors play a key role. In the nematode, the transcription factor CES-2 predisposes neurosecretory motoneurons to death, whereas E4BP4(NFIL3), one of its vertebrate homologs, regulates survival of pro-B lymphocytes. We show that E4BP4 is expressed by embryonic rat and chicken motoneurons in vivo, with levels being highest in neurons that survive the period of naturally occurring cell death. Overexpression of E4BP4 by electroporation of purified motoneurons in culture protected them almost completely against cell death triggered by removal of neurotrophic factors or activation of death receptors. Moreover, E4BP4 strongly enhanced neuronal cell size and axonal growth. Axons of motoneurons transfected with E4BP4 were 3.5-fold longer than control neurons grown on laminin; this effect required the activity of PI3 kinase. In vivo, overexpression of E4BP4 in chicken embryos reduced the number of dying motoneurons by 45%. Our results define E4BP4 as a novel intrinsic regulator of motoneuron growth and survival. Pathways regulated by E4BP4 are of potential interest both for understanding neuromuscular development and for promoting neuronal survival and regeneration in pathological situations.
Maternal β-catenin and E-cadherin in mouse development
Authors: de Vries Wilhelmine N. , Evsikov Alexei V. , Haac Bryce E. , Fancher Karen S. , Holbrook Andrea E. , Kemler Rolf , Solter Davor , Knowles Barbara B.
Published: August 2004

The oocyte to embryo transition in metazoans depends on maternal proteins and transcripts to ensure the successful initiation of development, and the correct and timely activation of the embryonic genome. We conditionally eliminated the maternal gene encoding the cell adhesion molecule E-cadherin and partially eliminated the β-catenin gene from the mouse oocyte. Oocytes lacking E-cadherin, or expressing a truncated allele of β-catenin without the N-terminal part of the protein, give rise to embryos whose blastomeres do not adhere. Blastomere adhesion is restored after translation of protein from the wild-type paternal alleles: at the morula stage in embryos lacking maternal E-cadherin, and at the late four-cell stage in embryos expressing truncated β-catenin. This suggests that adhesion per se is not essential in the early cleavage stage embryos, that embryos develop normally if compaction does not occur until the morula stage, and that the zona pellucida suffices to maintain blastomere proximity. Although maternal E-cadherin is not essential for the completion of the oocyte-to-embryo transition, absence of wild-type β-catenin in oocytes does statistically compromise developmental success rates. This developmental deficit is alleviated by the simultaneous absence of maternal E-cadherin, suggesting that E-cadherin regulates nuclear β-catenin availability during embryonic genome activation.
Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes
Authors: Das Gishnu , Jenny Andreas , Klein Thomas J. , Eaton Suzanne , Mlodzik Marek
Published: August 2004

Planar cell polarity (PCP) in the Drosophila eye is established by the distinct fate specifications of photoreceptors R3 and R4, and is regulated by the Frizzled (Fz)/PCP signaling pathway. Before the PCP proteins become asymmetrically localized to opposite poles of the cell in response to Fz/PCP signaling, they are uniformly apically colocalized. Little is known about how the apical localization is maintained. We provide evidence that the PCP protein Diego (Dgo) promotes the maintenance of apical localization of Flamingo (Fmi), an atypical Cadherin-family member, which itself is required for the apical localization of the other PCP factors. This function of Dgo is redundant with Prickle (Pk) and Strabismus (Stbm), and only appreciable in double mutant tissue. We show that the initial membrane association of Dgo depends on Fz, and that Dgo physically interacts with Stbm and Pk through its Ankyrin repeats, providing evidence for a PCP multiprotein complex. These interactions suggest a positive feedback loop initiated by Fz that results in the apical maintenance of other PCP factors through Fmi.
LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest
Authors: Perez-Alcala Siro , Nieto M. Angela , Barbas Julio A.
Published: August 2004

Members of the Sox family of transcription factors are involved in a number of crucial developmental processes, including sex determination, neurogenesis and skeletal development. LSox5 is a member of the group D Sox factors that,in conjunction with Sox6 and Sox9, promotes chondrogenesis by activating the expression of cartilage-specific extracellular matrix molecules. We have cloned the chicken homologue of LSox5 and found that it is initially expressed in the premigratory and migratory neural crest after Slugand FoxD3. Subsequently, the expression of LSox5 is maintained in cephalic crest derivatives, and it appears to be required for the development of the glial lineage, the Schwann cells and satellite glia in cranial ganglia.

Misexpression of LSox5 in the cephalic neural tube activated RhoB expression throughout the dorsoventral axis. Furthermore, the prolonged forced expression of LSox5 enlarged the dorsal territory in which the neural crest is generated, extended the `temporal window' of neural crest segregation, and led to an overproduction of neural crest cells in cephalic regions. In addition to HNK-1, the additional neural crest cells expressed putative upstream markers (Slug, FoxD3) indicating that a regulatory feedback mechanism may operate during neural crest generation. Thus, our data show that in addition to the SoxE genes(Sox9 and Sox10) a SoxD gene (Sox5) also participates in neural crest development and that a cooperative interaction may operate during neural crest generation, as seen during the formation of cartilage.
Elastic Buckling of Inter-Braced Parallel Beam Systems
Authors: Zhang Lei , Tong Gengshu
Published: August 2004

This paper investigates elastic buckling of inter-braced parallel beams when beams are not equally loaded. For beams under uniform bending, analytical solutions and approximate solutions using the Rayleigh-Ritz method are obtained respectively, and it is found that they agree with the exact solutions excellently. The Rayleigh-Ritz method is further used to study inter-braced parallel beams subjected to uniformly distributed loads and concentrated loads at mid-spans, and approximate interactive relations of the two buckling moments for mono-symmetric section beams are obtained, which can include the effects of load height, positions of bracing, shapes of bending moment diagrams, and mono-symmetry of the cross-section. The approximate formulae are in good agreement with those of the Rayleigh-Ritz method and also with those obtained from ANSYS using shell elements.
Performance Based Fire Safety Design of Structures — A Multi-Dimensional Integration
Authors: Liew J. Y. Richard
Published: August 2004

Design codes for fire safety in buildings can be either a prescriptive type or performance-based type. It is now widely recognized that performance-based codes provide greater advantages over the prescriptive codes in that it allows designers to use the fire engineering methods to assess the fire safety of the structure. However, as the assessment of the whole structure performance is not easy, most codes currently used are still prescriptive codes or a combination of prescriptive codes and performance-based codes. The key feature for implementing the performance-based fire design codes is the assessment of the fire resistance of the structure. This paper provides an overall view on performance-based code and the approaches for designing steel structure in fire considering a multi-dimensional integration of fire engineering simulation, emergency evacuation and structural resistance. Various fire models and heat transfer analysis methods are reviewed and discussed. The basis to modelling of large deflection and plasticity using appropriate stress-strain relationship at elevated temperature is explained. Finally, structural response calculations from simplified hand calculation method to advanced numerical procedures are presented. Future trends for research are identified.
Nonlinear Analysis of R/C Low-Rise Shear Walls
Authors: Mansour M. Y. , Dicleli M. , Lee J.Y.
Published: August 2004

An analysis method for predicting the response of low-rise shear walls under both monotonic and cyclic loading is presented in this paper. The proposed analysis method is based on the softened truss model theory but utilizes newly proposed cyclic constitutive relationships for concrete and steel bars obtained from cyclic shear testing. The successfulness of the analysis method, when combined with new materials constitutive relationships, is checked against the test results of 33 low-rise shear walls reported in the technical literature. The theoretical predictions are compared with the reported test results and are found to be applicable throughout the loading history. The effects of loading types (monotonic versus cyclic) as well as the effects of the boundary elements on the predicted results are also addressed.
Tension Capacity of Very High Strength (VHS) Circular Steel Tubes after Welding
Authors: Jiao Hui , Zhao Xiao-Ling
Published: August 2004

The details and results of an investigation into the tension capacity of very high strength (VHS) circular steel tubes after welding are presented. Two types of welded connections are used in the study: (1) complete penetration butt-welded VHS tubes, and (2) VHS tubes fillet welded to a steel plate along the whole perimeter of the tube. Both butt welded connections and transverse fillet welded connections failed in the heat-affected-zone (HAZ). The failure modes are compared with those of welded cold-formed square hollow sections. Significant strength reduction was observed in the HAZ compared with the strength of the VHS tubes. A strength reduction factor is proposed in this paper to modify the existing design rules. The FOSM (First Order Second Moment) reliability analysis method is used to calibrate the reduction factor. It seems that the tension member rules in the existing standards can be used along with the proposed reduction factors. The issue of matching between the parent metal and weld metal is also discussed.
Applications of FRP Composites in Concrete Columns
Authors: Xiao Y.
Published: August 2004

One of the most promising applications of fiber reinforced polymer (FRP) composites is in reinforced concrete columns. This paper provides a review of recent research in this area. Based on the literature available, it is found that most applications and research are focused on the FRP retrofit or repair of existing reinforced concrete columns primarily for improved ductility. Some recent research efforts have been directed to the new design of columns using FRP tubes or FRP bars. The use of FRP tubes is reviewed in comparison to previous research on concrete filled steel tubular (CFT) structures and the tubed structures. It is more likely favorable for the FRP tube or rebar to be used as transverse reinforcement of concrete columns for better ductility needed for seismic design. A new concept by the author on confined concrete filled tubular (CCFT) columns is also introduced along with promising test results.
On the Jump of Buckling Capacity of Beams via Piezoelectric Layers
Authors: Wang Q.
Published: August 2004

The paper presents research on the effect of a follower tensile force on the buckling capacity of beam structures subjected to non-follower compression. The potential of the research is for the application of smart materials on the buckling enhancement of beams, since the follower force is always and properly modelled at the interaction between the smart materials and the substrate. The buckling capacities of beams with different boundary conditions are obtained analytically. The phenomenon of a jump in buckling capacity for beams with one end fixed and the other end restrained by a translational spring is found. This observation indicates that by properly applying a follower force through the use of smart materials, the buckling capacities of a beam can be enhanced dramatically. The voltage, needed for the jump in the buckling capacity, applied to a pair of piezoelectric layers is hence studied and properly made.

It is hoped that this work will enable designers to capitalise on the effectiveness of piezoelectric actuators or Shape Memory Alloy (SMA) in enhancing the buckling capacities of beams.
Shear Strengthening of a PC Bridge Girder with NSM CFRP Rectangular Bars
Authors: Nanni Antonio , Ludovico Marco Di , Parretti Renato
Published: August 2004

Bridges worldwide are falling into a state of disrepair caused by deterioration, traffic overloading, and poor maintenance. It is estimated that over 100,000 of the half million existing bridges in the US are in need of repair or replacement. Although the full replacement option could be viable, it is an expensive solution with significant disruption of service. This paper focuses on the use of carbon fiber reinforced polymer (CFRP) rectangular bars installed as near surface mounted (NSM) reinforcement for shear strengthening in conjunction with an externally bonded pre-cured CFRP laminate to increase the flexural capacity of a prestressed concrete (PC) bridge girder. The specimen, which was removed from an overloaded bridge in Kansas was strengthened and tested in the laboratory. Test results showed that the proposed NSM reinforcement technique represents an effective solution to increase shear capacity.
A stop codon-dependent internal secondary translation initiation region in Escherichia coli rpoS
Authors: SUBBARAYAN POCHI RAMALINGAM , SARKAR MALANCHA
Published: August 2004

Sigma S (σs) encoded by rpoS is a stationary phase-specific σ subunit of the Escherichia coli RNA polymerase holoenzyme. In many E. coli strains, rpoS has an amber stop as codon 33 (rpoSAm), resulting in a 32-amino-acid-long peptide. Nevertheless, suppressor-free rpoSAm strains have functional σS. This led us to hypothesize the presence of an intracistronic secondary translational initiation region (STIR) in the E. coli rpoS gene. Here, we demonstrate that the STIR is functional and is controlled by the upstream amber stop codon 33. Removal of the primary translational initiation region did not abolish translation from STIR, ruling out translational coupling. Importantly, the functional STIR conferred survival advantage. Taken together, our results reveal a hitherto unknown physiologically significant post-transcriptional process in E. coli rpoSAm strains.
Sensitivity and Specificity of Single-Nucleotide Polymorphism Scanning by High-Resolution Melting Analysis
Authors: Reed Gudrun H , Wittwer Carl T
Published: August 2004

Background: Screening for heterozygous sequence changes in PCR products, also known as “mutation scanning”, is an important tool for genetic research and clinical applications. Conventional methods require a separation step.

Methods: We evaluated the sensitivity and specificity of homogeneous scanning, using a saturating DNA dye and high-resolution melting. Heterozygous single-nucleotide polymorphism (SNP) detection was studied in three different sequence backgrounds of 40%, 50%, and 60% GC content. PCR products of 50–1000 bp were generated in the presence of LCGreen™ I. After fluorescence normalization and temperature overlay, melting curve shape was used to judge the presence or absence of heterozygotes among 1632 cases.

Results: For PCR products of 300 bp or less, all 280 heterozygous and 296 wild-type cases were correctly called without error. In 672 cases between 400 and 1000 bp with the mutation centered, the sensitivity and specificity were 96.1% and 99.4%, respectively. When the sequence background and product size with the greatest error rate were used, the sensitivity of off-center SNPs (384 cases) was 95.6% with a specificity of 99.4%. Most false negatives occurred with SNPs that were compared with an A or T wild type sequence.

Conclusions: High-resolution melting analysis with the dye LCGreen I identifies heterozygous single-base changes in PCR products with a sensitivity and specificity comparable or superior to nonhomogeneous techniques. The error rate of scanning depends on the PCR product size and the type of base change, but not on the position of the SNP. The technique requires only PCR reagents, the dye LCGreen I, and 1–2 min of closed-tube, post-PCR analysis.
Rapid and Simultaneous Determination of Coproporphyrin and Protoporphyrin in Feces by Derivative Matrix Isopotential Synchronous Fluorescence Spectrometry
Authors: Lin Dan-Li , He Li-Fang , Li Yao-Qun
Published: August 2004

Background: Measurement of fecal porphyrins is important in the diagnosis of porphyria, but conventional methods to measure them have drawbacks. We explored the use of derivative matrix isopotential synchronous fluorescence (MISF) spectrometry for the measurement of coproporphyrin and protoporphyrin.

Methods: The MISF scanning route was selected based on information from the three-dimensional fluorescence spectrum, which was a combination of the contour line of protoporphyrin via a detection point of coproporphyrin and that of coproporphyrin via a detection point of protoporphyrin. Derivative technique eliminated the constant interfering signals. MISF was used to measure porphyrins in stools from 2 pregnant women and 20 healthy volunteers.

Results: The coproporphyrin and protoporphyrin spectra were resolved with almost no mutual interference. The amplitudes of the derivative peaks were linearly related to the concentrations of coproporphyrin up to 310 nmol/L and protoporphyrin up to 590 nmol/L. The detection limits for coproporphyrin and protoporphyrin were 1.2 and 1.7 nmol/L, respectively. The within-run imprecision (CV; n = 6) was 2.2% at 175 nmol/L for coproporphyrin and 2.3% at 500 nmol/L for protoporphyrin. Bland–Altman analysis indicated no significant differences between the proposed MISF method and conventional spectrophotometry or fluorimetry. Mean (SD) recoveries of porphyrins added to fecal samples were of 98 (7)% for coproporphyrin and 102 (4)% for protoporphyrin.

Conclusions: This technique provides spectral resolution of coproporphyrin and protoporphyrin, obviating the need for chromatographic separation, and measurements can be made in a single scanning. The method also appears suitable for routine testing of large numbers of samples.
NMDA Receptor GluRϵ/NR2 Subunits Are Essential for Postsynaptic Localization and Protein Stability of GluRζ1/NR1 Subunit
Authors: Abe Manabu , Fukaya Masahiro , Yagi Takeshi , Mishina Masayoshi , Watanabe Masahiko , Sakimura Kenji
Published: August 2004

In NMDA receptors, GluRϵ/NR2 subunits strictly require the GluRζ1/NR1 subunit to exit from endoplasmic reticulum (ER) to the cell surfacein vitroand to the postsynapsein vivo, whereas C terminus-dependent self-surface delivery has been demonstrated for the GluRζ1 subunitin vitro. To test whether this leads to C terminus-dependent self-postsynaptic expression in neuronsin vivo, we investigated the GluRζ1 subunit in cerebellar granule cells lacking two major GluRϵ subunits, GluRϵ1/NR2A and GluRϵ3/NR2C. In the mutant cerebellum, synaptic labeling for the GluRζ1 subunit containing the C2 (GluRζ1-C2) or C2′ (GluRζ1-C2′) cassette was reduced at mossy fiber-granule cell synapses to the extrasynaptic level. The loss was not accompanied by decreased transcription and translation levels, increased extrasynaptic labeling, or ER accumulation. Quantitative immunoblot revealed substantial reductions in the mutant cerebellum of GluRζ1-C2 and GluRζ1-C2′. The most severe deficit was observed in the postsynaptic density (PSD) fraction: mutant levels relative to the wild-type level were 12.3 ± 3.3% for GluRζ1-C2 and 17.0 ± 4.6% for GluRζ1-C2′. The GluRζ1 subunit carrying the C1 cassette (GluRζ1-C1) was, although low in cerebellar content, also reduced to 12.7 ± 3.5% in the mutant PSD fraction. Considering a trace amount of other GluRϵ subunits in the mutant cerebellum, the severe reductions thus represent that the GluRζ1 subunit, by itself, is virtually unable to accumulate at postsynaptic sites, regardless of C-terminal forms. By protein turnover analysis, the degradation of the GluRζ1 subunit was accelerated in the mutant cerebellum, being particularly rapid for that carrying the C2 cassette. Therefore, accompanying expression of GluRϵ subunits is essential for postsynaptic localization and protein stability of the GluRζ1 subunit.
A New Method for the Experimental Assessment of Finger Haemodynamic Effects Induced by a Hydraulic Breaker in Operative Conditions
Authors: Valentino Matteo , Rapisarda Venerando , Scalise Lorenzo , Paone Nicola , Santarelli Lory , Fenga Concettina , Rossi Gian Luca
Published: August 2004

A New Method for the Experimental Assessment of Finger Haemodynamic Effects Induced by a Hydraulic Breaker in Operative Conditions: Matteo Valentino, et al. Clinic of Occupational Medicine, University of Ancona, Italy—The haemodynamic effects, in terms of grip force and hand‐transmitted accelerations, produced on the fingers of 10 healthy subjects by operation of a hydraulic breaker held with a low or a high grip were investigated with a new experimental set‐up. A novel apparatus consisting of a capacitive sensor matrix and a laser Doppler vibrometer was used to measure the two parameters during breaker operation. Finger blood flow in basal conditions and after each test was evaluated in the four long fingers of both hands with a photoplethysmograph and superficial skin thermometry. The amplitude of the accelerations transmitted to the hand surface was greater during the test with the low grip. Photoplethysmographic and thermometric values were significantly lower than basal values after either test. The amplitude of photoplethysmographic values during the tests was significantly lower with the low than with the high grip in 6 subjects, in both index fingers, and in the right middle finger. The authors show that the level of grip force used for holding the breaker causes transmission of vibrations of wider amplitude, resulting in greater reduction in finger blood flow. In line with the literature, stimulus magnitude, frequency and duration affected finger blood flow, especially in the index finger.
Determination of Urinary Metabolites of Alkyl Cellosolves by Solid Phase Extraction and GC/FID
Authors: Choi Hong Soon , Park Jun Ho , Song Jae Seok , Cho Yong Bong
Published: August 2004

Determination of Urinary Metabolites of Alkyl Cellosolves by Solid Phase Extraction and GC/FID: Hong Soon Choi, et al. Department of Environment Engineering, Yonsei University, South Korea—Alkyl cellosolves include ethylene glycol monomethylether, ethylene glycol monoethylether, ethylene glycol monobuthylether. And their urine metabolites are methoxyacetic acid, ethoxyacetic acid and butoxyacetic acid. The current analytical method for urinary alkoxyacetic acid is liquid‐liquid phase extraction. But the liquid‐liquid phase extraction method needs a more complex pre‐treatment process and has a low recovery rate. We determined the appropriate extraction solvent and its flow rate. We also evaluated the non‐absorptive rate and recovery rate according to particle size. Finally we developed a convenient solid phase extraction method for the analysis of urine cellosolve metabolites. As a result, the recovery rates for methoxyacetic acid, ethoxyacetic acid and butoxyacetic acid were 100.4 ± 1.6%, 100.2 ± 1.8% and 100.7 ± 10.0% respectively, when acetone was used as the extraction solution. The most appropriate flow rate was 0.1 ml/min. At a particle size of 140–200 mesh, non‐absorption percentages for methoxyacetic acid, ethoxyacetic acid, butoxyacetic acid were 3.2 ± 0.3%, 1.0 ± 0.1% and 1.1 ± 0.1%, and the recovery rates according to particle size were similar. Further evaluation of the recovery rate and non‐absorptive rate according to the mini column shape, stationary phase and recovery rate with various extracting solutions is required.