bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESTIMA, a tool for EST management in a multi-project environment
Authors: Kumar Charu G , LeDuc Richard , Gong George , Roinishivili Levan , Lewin Harris A , Liu Lei 
Published: November 2004

Abstract
Background
Single-pass, partial sequencing of complementary DNA (cDNA) libraries generates thousands of chromatograms that are processed into high quality expressed sequence tags (ESTs), and then assembled into contigs representative of putative genes. Usually, to be of value, ESTs and contigs must be associated with meaningful annotations, and made available to end-users.

Results
A web application, Expressed Sequence Tag Information Management and Annotation (ESTIMA), has been created to meet the EST annotation and data management requirements of multiple high-throughput EST sequencing projects. It is anchored on individual ESTs and organized around different properties of ESTs including chromatograms, base-calling quality scores, structure of assembled transcripts, and multiple sources of comparison to infer functional annotation, Gene Ontology associations, and cDNA library information. ESTIMA consists of a relational database schema and a set of interactive query interfaces. These are integrated with a suite of web-based tools that allow a user to query and retrieve information. Further, query results are interconnected among the various EST properties. ESTIMA has several unique features. Users may run their own EST processing pipeline, search against preferred reference genomes, and use any clustering and assembly algorithm. The ESTIMA database schema is very flexible and accepts output from any EST processing and assembly pipeline.
ESTIMA has been used for the management of EST projects of many species, including honeybee (Apis mellifera), cattle (Bos taurus), songbird (Taeniopygia guttata), corn rootworm (Diabrotica vergifera), catfish (Ictalurus punctatus, Ictalurus furcatus), and apple (Malus x domestica). The entire resource may be downloaded and used as is, or readily adapted to fit the unique needs of other cDNA sequencing projects.

Conclusions
The scripts used to create the ESTIMA interface are freely available to academic users in an archived format from http://titan.biotec.uiuc.edu/ESTIMA/. The entity-relationship (E-R) diagrams and the programs used to generate the Oracle database tables are also available. We have also provided detailed installation instructions and a tutorial at the same website. Presently the chromatograms, EST databases and their annotations have been made available for cattle and honeybee brain EST projects. Non-academic users need to contact the W.M. Keck Center for Functional and Comparative Genomics, University of Illinois at Urbana-Champaign, Urbana, IL, for licensing information.
Efficacy of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients with spinal symptoms
Authors: Hellwig Kerstin , Stein Franz Josef , Przuntek Horst , Müller Thomas 
Published: November 2004

Abstract
Background
There are controversial results on the efficacy of the abandoned, intrathecal predominant methylprednisolone application in multiple sclerosis (MS) in contrast to the proven effectiveness in intractable postherpetic neuralgia.

Methods
We performed an analysis of the efficacy of the application of 40 mg of the sustained release steroid triamcinolone acetonide (TCA). We intrathecally injected in sterile saline dissolved TCA six times within three weeks on a regular basis every third day in 161 hospitalized primary and predominant secondary progressive MS patients with spinal symptoms. The MS patients did not experience an acute onset of exacerbation or recent distinct increased progression of symptoms. We simultaneously scored the MS patients with the EDSS and the Barthel index, estimated the walking distance and measured somatosensory evoked potentials. Additionally the MS patients received a standardized rehabilitation treatment.

Results
EDSS score and Barthel index improved, walking distance increased, latencies of somatosensory evoked potentials of the median and tibial nerves shortened in all MS patients with serial evaluation (p < 0.0001 for all variables). Side effects were rare, five patients stopped TCA application due to onset of a post lumbar puncture syndrome.

Conclusions
Repeated intrathecal TCA application improves spinal symptoms, walking distance and SSEP latencies in progressive MS patients in this uncontrolled study. Future trials should evaluate the long-term benefit of this invasive treatment.
Biology and Clinical Development of Vascular Endothelial Growth Factor–Targeted Therapy in Renal Cell Carcinoma
Authors: Rini Brian I. , Small Eric J. 
Published: November 2004

PurposeTo review the biology of renal cell carcinoma (RCC) leading to vascular endothelial growth factor (VEGF) overexpression and the clinical results of VEGF blockade in metastatic RCC.MethodsA review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken.ResultsVEGF is the major proangiogenic protein that exerts a biologic effect through interaction with cellular receptors. The majority of sporadic clear-cell RCC tumors are characterized by VHL tumor suppressor gene inactivation. The resulting VHL gene silencing leads to VEGF overexpression. An antibody to VEGF (bevacizumab) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Small molecules with inhibitory effects against the VEGF receptor have undergone initial clinical testing in metastatic RCC with substantial objective response rates.ConclusionTherapeutic targeting of VEGF in RCC has strong biologic rationale and preliminary clinical efficacy. Further investigation will determine the optimal timing, sequence, and utility of these agents in RCC.
Phase I Trial of Iodine-131 Tositumomab With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Relapsed Non-Hodgkin's Lymphoma
Authors: Vose Julie M. , Bierman Philip J. , Enke Charles , Hankins Jordan , Bociek Gregory , Lynch James C. , Armitage James O. 
Published: November 2004

Purpose To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Patients and Methods Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT. Results The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%. Conclusion There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.
An investigation into plate deformation in flexographic printing
Authors: Bould D C , Claypole T C , Bohan M F J 
Published: November 2004

Deformation of the flexographic printing plate is an important factor in determining the quality of the printed image. A numerical model of the individual dots has been developed and used to examine the deformation of the plate under a range of printing conditions and image characteristics. Two mechanisms have been identified for the deformation of the image on the plate: expansion of the dot surface and dot barrelling. These results have been combined with those from an experimental study to apportion the dot gain due to ink spreading and physical deformation of the dot. The results have shown the low-coverage dots at high line rulings to be particularly affected by the effect of variation in the impression pressure. This has significant implications for the ability of the process to reproduce high-resolution images that combine both highlight and shadow regions successfully and consistently. Ink spreading has been identified as the major cause of dot gain, except at low coverages, where the deformation of the dots makes a significant contribution.
Heat management in solid free-form fabrication based on deposition by welding
Authors: Jandric Z , Kovacevic R 
Published: November 2004

Solid free-form fabrication (SFF) based on gas-tungsten arc welding (GTAW) is one of the few rapid prototyping techniques that has the capability to build three-dimensional metallic parts. For this application, a mild steel (AISI 1018) was used. The most important problem in this process was to find the optimal process parameters. The goal is to build complex three-dimensional parts by depositing metal by welding in a form of layers. The building of a three-dimensional part by welding is especially sensitive to inadequate heat input. The traditional way of manually adjusting the heat input cannot be used because of the dynamic changes in the underlying substrate geometry. To investigate this problem a finite element model (FEM) has been developed that correlates the influence of the different underlying substrate geometry to the quality of the welding-based deposition process. The results from the FEM suggested that influence of the geometry is significant and cannot be neglected. Extensive experiments were designed and performed in order to verify the conclusions derived from the results of the FEM. A real-time adaptive controller of the welding parameters is proposed. This controller performs heat management in real time according to the volume changes of the material of the underlying layers in the vicinity of the heat source. In addition, the overall system performance was monitored and recorded by through-the-arc sensing in order to demonstrate the versatility and robustness of the controller.
Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor‐1 relationship in breast cancer
Authors: Toi Masakazu , Bando Hiroko , Ogawa Taeko , Muta Mariko , Hornig Carsten , Weich Herbert A. 
Published: November 2004

AbstractAngiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor‐1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety‐four of 110 tumors showed ≥0.1 ng/mg protein of sVEGFR1 (range:0. 1–6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme‐linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico‐pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intratumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10‐fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co‐expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer. © 2001 Wiley‐Liss, Inc.
Use of the human MDR1 promoter for heat‐inducible expression of therapeutic genes
Authors: Walther Wolfgang , Stein Ulrike , Schlag Peter M. 
Published: November 2004

AbstractThe promoter of the human multidrug resistance gene (mdr1) harbors stress‐responsive elements, which can be induced e.g., by heat or cytostatic drugs. In previous studies the drug‐responsiveness of the mdr1 promoter was successfully used for the drug‐inducible expression of the human TNF‐α gene in vitro and in vivo. Beside the drug‐responsive elements of the mdr1 promoter, heat‐shock responsive elements have also been identified, which could be exploited for construction of heat‐inducible expression vectors. To analyze the hyperthermia‐inducibility of the mdr1 promoter we used the pmdr‐p‐CAT and pM3mdr‐p‐hTNF vector constructs. Both constructs carry the mdr1 promoter fragment spanning from −207 to +153 to drive expression of the CAT‐reporter or TNF‐α gene. We tested the heat‐induced CAT‐reporter and TNF‐α expression in vitro in transduced HCT15 and HCT116 human colon carcinoma cells. For the studies the transduced tumor cells were treated with hyperthermia at 41.5°C or 43°C for 2 hr to induce CAT or TNF‐α expression. Cells and supernatants were harvested before hyperthermia and at certain time points (0–120 hr) after heat shock. The heat‐induced CAT‐reporter expression or TNF‐α secretion was determined by specific ELISA. The experiments indicate that hyperthermia activates the mdr1 promoter in a temperature and time dependent manner. This induction leads to an 2‐ to 4‐fold increase in CAT‐reporter or 2‐ to 7‐fold increase in TNFα expression in the tumor cell lines. These experiments reveal that the mdr1 promoter driven expression of therapeutic genes can be employed for combined cancer gene therapy approaches. © 2001 Wiley‐Liss, Inc.
Hepatocyte growth factor enhances protein phosphatase Cdc25A inhibitor compound 5‐induced hepatoma cell growth inhibition via Akt‐mediated MAPK pathway
Authors: Wang Ziqiu , Wang Meifang , Carr Brian I. 
Published: November 2004

AbstractWe have previously shown that Compound 5 (Cpd 5), an inhibitor of protein phosphatase Cdc25A, inhibits Hep3B human hepatoma cell growth. We now show that hepatocyte growth factor (HGF), a hepatocyte growth stimulant, can strongly enhance Cpd 5‐induced growth inhibition in Hep3B cells, and this enhancement in cell growth inhibition is correlated with a much stronger ERK phosphorylation when compared to cells treated with Cpd 5 or HGF separately. We found that HGF/Cpd 5‐induced ERK phosphorylation and cell growth inhibition were mediated by Akt (protein kinase B) pathway, since combination HGF/Cpd 5 treatment of Hep3B cells inhibited Akt phosphorylation at Ser‐473 and its kinase activity, which led to the suppression of Raf‐1 phosphorylation at Ser‐259. The suppression of Raf‐1 Ser‐259 phosphorylation caused the induction of Raf‐1 kinase activity, as well as hyper‐ERK phosphorylation. Transient transfection of Hep3B cells with dominant negative Akt c‐DNA further enhanced both Cpd 5‐ and HGF/Cpd 5‐induced ERK phosphorylation, while over‐expression of wild‐type Akt c‐DNA diminished their effects. In contrast, HGF antagonized the growth inhibitory actions of Cpd 5 on normal rat hepatocytes, thus showing a selective effect on tumor cells compared to normal cells. Our data suggest that Akt kinase negatively regulates MAPK activity at the Akt‐Raf level. Suppression of Akt activity by either combination HGF/Cpd 5 treatment or by dominant negative Akt c‐DNA transfection antagonizes the Akt inhibitory effect on Raf‐1, resulting in an enhancement of Cpd 5‐induced MAPK activation and cell growth inhibition. © 2004 Wiley‐Liss, Inc.
Heart inflow tract of the African lungfish Protopterus dolloi
Authors: Icardo José M. , Ojeda José L. , Colvee Elvira , Tota Bruno , Wong Wai P. , Ip Yuen K. 
Published: November 2004

AbstractWe report a morphologic study of the heart inflow tract of the African lungfish Protopterus dolloi. Attention was paid to the atrium, the sinus venosus, the pulmonary vein, and the atrioventricular (AV) plug, and to the relationships between all these structures. The atrium is divided caudally into two lobes, has a common part above the sinus venosus, and appears attached to the dorsal wall of the ventricle and outflow tract through connective tissue covered by the visceral pericardium. The pulmonary vein enters the sinus venosus and runs longitudinally toward the AV plug. Then it fuses with the pulmonalis fold and disappears as an anatomic entity. However, the oxygenated blood is directly conveyed into the left atrium by the formation of a pulmonary channel. This channel is formed cranially by the pulmonalis fold, ventrally by the AV plug, and caudally and dorsally by the atrial wall. The pulmonalis fold appears as a wide membranous fold which arises from the left side of the AV plug and extends dorsally to form the roof of the pulmonary channel. The pulmonalis fold also forms the right side of the pulmonary channel and sequesters the upper left corner of the sinus venosus from the main circulatory return. The AV plug is a large structure, firmly attached to the ventricular septum, which contains a hyaline cartilaginous core surrounded by connective tissue. The atrium is partially divided into two chambers by the presence of numerous pectinate muscles extended between the dorsal wall of the atrium and the roof of the pulmonary channel. Thus, partial atrial division is both internal and external, precluding the more complete division seen in amphibians. The present report, our own unpublished observations on other Protopterus, and a survey of the literature indicate that not only the Protopterus, but also other lungfish share many morphologic traits. J. Morphol. 263:30–38, 2005. © 2004 Wiley‐Liss, Inc.
Ultrastructure of testicular macrophages in aging mice
Authors: Giannessi Francesco , Giambelluca Maria A. , Scavuzzo Maria C. , Ruffoli Riccardo 
Published: November 2004

AbstractTesticular macrophages of aging mice were studied by TEM. Testicular macrophages retained with Leydig cells the close morphological relationships observed in the adult young animals, but digitations were not found. Lipofuscin granules like those of the Leydig cells from aging mice were observed in the cytoplasm. These organelles were generally absent in the testicular macrophages of young adult mice. Testicular macrophages did not display phagocytosis of the lipofuscin granules. In addition, the latter were not found in the intercellular spaces. These observations indicated that lipofuscin granules were formed, at least in a great part, within testicular macrophages as a consequence of metabolic changes occurring with age. Fine lamellar organization was seen in the lipofuscin granules of both Leydig cells and testicular macrophages. Frequently, lipofuscin granules originated from secondary lysosomes containing lipidic vacuoles only. Together with accumulation of the lipofuscin granules, changes of testicular macrophage fine morphology were observed. Endoplasmic reticulum and Golgi apparatus became poorly developed, and coated vesicles were rarely found. Fewer mitochondria were encountered, but their ultrastructure was not altered. These results suggest that in testicular macrophages lipofuscin accumulation is associated with a functional involution. J. Morphol. 263:39–46, 2005.© 2004 Wiley‐Liss, Inc.
Ultrastructure of mesoderm in embryos of Opisthopatus roseus (Onychophora, Peripatopsidae): Revision of the “long germ band” hypothesis for Opisthopatus
Authors: Mayer Georg , Bartolomaeus Thomas , Ruhberg Hilke 
Published: November 2004

AbstractIn previous studies, an unusual pattern of development which resembles the “long germ band” development of some insects has been described in the onychophoran Opisthopatus cinctipes. This pattern has been proposed to be a characteristic of the genus Opisthopatus. To test this assumption, the ultrastructure of embryos of O. roseus, the sister species of O. cinctipes, was examined. Two kinds of paired, segmentally arranged coelomic cavities were found in the embryos studied: 1) dorsolateral coelomic cavities lined by extremely thin epithelia, and 2) ventral coelomic cavities situated within the anlagen of ventrolateral body appendages. Only the dorsolateral coelomic cavities can be considered “somites,” since they occur earlier during embryogenesis. This is in contrast with the previous view that suggested a ventral position of “somites” in O. cinctipes. In addition, an anterior‐to‐posterior gradient occurs in the development of O. roseus. Based on our findings, we reevaluated the previous data on O. cinctipes. From this survey, no evidence in support of a “long germ band” hypothesis in Opisthopatus was found. Instead, the embryogenesis in representatives of Opisthopatus is more similar to that in other onychophorans than expected. J. Morphol. 263:60–70, 2005. © 2004 Wiley‐Liss, Inc.
Diel vertical distribution of fish larvae during the winter-mixing period in the Northwestern Mediterranean
Authors: Sabatés A. 
Published: November 2004

Abstract
The vertical distributions of the larvae of shelf and oceanic fish species that spawn during the winter-mixing period in the Mediterranean are described from 22 vertically stratified plankton tows. Diel differences in the vertical distribution patterns in relation to physical data and potential prey abundance throughout the water column were examined. Even in absence of stratification, the larvae of the various fish species showed different patterns of vertical distribution and diel changes. The larvae of shelf-dwelling species were found in the surface layers, mainly above 50-m depth, and with some exceptions, with very little diel variation in depth distribution. Therefore, the vertical distribution of the larvae of these species coincided with the maximum concentrations of their potential food, nauplii and copepodite stages of copepods. The larvae of mesopelagic fishes showed deeper distributions in the water column and most of these species were located closer to the surface during the day than at night. Given the homogeneity of the physical characteristics throughout the water column, except for light, this behaviour may be determined not only by the higher concentration of prey in the surface layers but also by adequate light levels for feeding.