bluuebunny/crossref_metadata_2025_split huggingface dataset:
European and US publications in the 50 highest ranking pathology journals from 2000 to 2006
Authors: Fritzsche F R , Oelrich B , Dietel M , Jung K , Kristiansen G 
Published: August 2007

Aims:To analyse the contributions of the 15 primary member states of the European Union and selected non-European countries to pathological research between 2000 and 2006.Methods:Pathological journals were screened using ISI Web of Knowledge database. The number of publications and related impact factors were determined for each country. Relevant socioeconomic indicators were related to the scientific output. Subsequently, results were compared to publications in 10 of the leading biomedical journals.Results:The research output remained generally stable. In Europe, the UK, Germany, France, Italy and Spain ranked top concerning contributions to publications and impact factors in the pathological and leading general biomedical journals. With regard to socioeconomic data, smaller, mainly northern European countries showed a relatively higher efficiency. Of the lager countries, the UK is the most efficient in that respect. The rising economic powers of China and India were consistently in the rear.Conclusions:Results mirror the leading role of the USA in pathology research but also show the relevance of European scientists. The scientometric approach in this study provides a new fundamental and comparative overview of pathology research in the European Union and the USA which could help to benchmark scientific output among countries.
Foundation construction at the Bristol Royal Infirmary—Phase 1
Authors: Phillips Lionel , Knill John Lawrence 
Published: September 2007

Summary

The Bristol Royal Infirmary is located on the south-easterly face of Kingsdown Hill overlooking the centre of Bristol. A series of extensions to the Infirmary have been constructed since 1966 and are planned for the future. The hill is underlain by alternating hard sandstones and mudstones of the Quartzitic Sandstone Group which dip towards the south-east at a steeper angle than the ground slope. The Carboniferous rocks are overlain by the Triassic Dolomitic Conglomerate in the upper part of the site, and by Triassic marls and fill at lower elevations. The hillside has a past record of instability both in superficial materials and in bedrock. The stability of the site had to be judged both overall and in relation to the design and construction of individual structures. The design of the foundations for each of these structures was based upon drilling coupled with a programme of laboratory and
in situ
tests. The largest building is the Outpatients Department which required major basements involving deep excavation into the hillside undercutting the bedding. The foundations for this structure were primarily created by buttresses formed in trench and combined with cross walls so ensuring total stability at all stages of excavation. In contrast, the Radiotherapy Centre is mainly founded on isolated bases carried down to bedrock and appropriately stepped in level. The thick walls between the treatment rooms in the basement were keyed into the quartzitic sandstone or very firm mudstone. The Maternity Hospital, located at the top of the site on thick Triassic deposits, has been founded on large diameter bored piles drilled into the Dolomitic Conglomerate. Attention is drawn to the special problems which arose during construction including the need for controlled blasting for excavation and the control of water, partly in relation to a medieval tunnel system.
Toward Understanding Massive Star Formation
Authors: Zinnecker Hans , Yorke Harold W. 
Published: September 2007

Although fundamental for astrophysics, the processes that produce massive stars are not well understood. Large distances, high extinction, and short timescales of critical evolutionary phases make observations of these processes challenging. Lacking good observational guidance, theoretical models have remained controversial. This review offers a basic description of the collapse of a massive molecular core and a critical discussion of the three competing concepts of massive star formation:▪  monolithic collapse in isolated cores ▪  competitive accretion in a protocluster environment ▪  stellar collisions and mergers in very dense systemsWe also review the observed outflows, multiplicity, and clustering properties of massive stars, the upper initial mass function and the upper mass limit. We conclude that high-mass star formation is not merely a scaled-up version of low-mass star formation with higher accretion rates, but partly a mechanism of its own, primarily owing to the role of stellar mass and radiation pressure in controlling the dynamics.
Melanoma Cells Exhibit Variable Signal Transducer and Activator of Transcription 1 Phosphorylation and a Reduced Response to IFN-α Compared with Immune Effector Cells
Authors: Lesinski Gregory B. , Trefry John , Brasdovich Melanie , Kondadasula Sri Vidya , Sackey Korkor , Zimmerer Jason M. , Chaudhury Abhik Ray , Yu Lianbo , Zhang Xiaoli , Crespin Tim R. , Walker Michael J. , Carson William E. 
Published: September 2007

AbstractPurpose: IFN-α is administered to melanoma patients and its endogenous production is essential for immune-mediated tumor recognition. We hypothesized that a reduced capacity for signal transducer and activator of transcription (STAT) 1 activation allows melanoma cells to evade the direct actions of IFN-α.Experimental Design: Tyr701-phosphorylated STAT1 (P-STAT1) was measured by flow cytometry in IFN-α–stimulated human melanoma cell lines, melanoma cells derived from patient tumors, and peripheral blood mononuclear cells (PBMC). Expression of other Janus-activated kinase (Jak)-STAT intermediates (STAT1, STAT2, Jak1, tyrosine kinase 2, IFN-α receptor, STAT3, and STAT5) was evaluated by flow cytometry, immunoblot, or immunohistochemistry.Results: Significant variability in P-STAT1 was observed in human melanoma cell lines following IFN-α treatment (P &lt; 0.05) and IFN-α–induced P-STAT1 correlated with the antiproliferative effects of IFN-α (P = 0.042). Reduced formation of P-STAT1 was not explained by loss of Jak-STAT proteins or enhanced STAT5 signaling as reported previously. Basal levels of P-STAT3 were inversely correlated with IFN-α–induced P-STAT1 in cell lines (P = 0.013). IFN-α–induced formation of P-STAT1 was also variable in melanoma cells derived from patient tumors; however, no relationship between P-STAT3 and IFN-α–induced P-STAT1 was evident. Because IFN-α acts on both tumor and immune cells, we examined the ability of IFN-α to induce P-STAT1 in patient-derived melanoma cells and PBMCs. IFN-α induced significantly lower levels of P-STAT1 in melanoma cells compared with matched PBMCs (P = 0.046). Melanoma cells and human melanocytes required 10-fold higher IFN-α doses to exert P-STAT1 levels comparable with PBMCs.Conclusions: Melanoma cells are variable in their IFN-α responsiveness, and cells of the melanocytic lineage exhibit a lower capacity for IFN-α–induced Jak-STAT signaling compared with immune cells.
Inherited Variation in Hormone-Regulating Genes and Prostate Cancer Survival
Authors: Lindström Sara , Adami Hans-Olov , Bälter Katarina Augustsson , Xu Jianfeng , Zheng S. Lilly , Stattin Pär , Grönberg Henrik , Wiklund Fredrik 
Published: September 2007

Abstract
Purpose: Hormonal manipulation is the mainstay treatment of prostate cancer, notably in advanced stages. Despite initial favorably response, the cancer eventually develops hormone resistance resulting in disease progression and death. However, little is known about genetic determinants of disease progression and prostate cancer–specific death.
Experimental Design: We analyzed a population-based cohort comprising 2,761 men diagnosed with prostate cancer from March 2001 to October 2003 and with complete follow-up through July 2006. During a median follow-up time of 3.8 years, a total of 300 men had died from prostate cancer. We genotyped 23 haplotype tagging single nucleotide polymorphisms in the genes AR, CYP17, and SRD5A2 and used Cox proportional hazards analyses to quantify associations between genotype and risk of dying from prostate cancer.
Results: The variant ‘A’ allele of an AR promoter single nucleotide polymorphism, rs17302090, was borderline associated with a 50% increased risk of dying from prostate cancer (95% confidence interval, 1.0-2.3; P = 0.07). This finding was more pronounced in patients who received hormonal therapy as primary treatment at diagnosis (hazard ratio, 1.9; 95% confidence interval, 1.3-2.9; P = 0.007). We did not identify any associations between CYP17 or SRD5A2 variation and prostate cancer–specific death.
Conclusions: Our results suggest that inherited genetic variation in the androgen receptor gene affects hormonal treatment response and ultimately prostate cancer death.
Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers
Authors: Hassan Raffit , Bullock Susie , Premkumar Ahalya , Kreitman Robert J. , Kindler Hedy , Willingham Mark C. , Pastan Ira 
Published: September 2007

Abstract
Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers.
Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced mesothelioma (n = 20), ovarian (n = 12), and pancreatic (n = 2) cancer.
Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation, 17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD of 45 μg/kg, the mean Cmax of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other mesothelin-expressing malignancies.
Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation
Authors: Martin Robert C.G. , Liu Qiaohong , Wo John M. , Ray Mukunda B. , Li Yan 
Published: September 2007

Abstract
Purpose: Oxidative stress is related to the carcinogenic pathway of reflux esophagitis to Barrett's metaplasia to esophageal adenocarcinoma (EAC). Recent studies have shown that a decreased manganese superoxide dismutase (MnSOD) level is associated with the increased incidences of Barrett's esophagus (BE) and EAC. The aim of this study was to investigate MnSOD supplementation as a chemopreventive agent to prevent oxidative injury and subsequent BE and EAC formation.
Experimental Design: Our esophagoduodenal anastomotic (EDA) model was done on rats according to our established procedure and treated with Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP; 10 mg/kg, i.p. every 3 days). Histologic changes were determined after the EDA model at 1, 3, and 6 months. Lipid peroxidation and 8-hydroxy-deoxyguanosine for DNA oxidative damage were determined by thiobarbituric acid–reactive substance assay and immunohistochemical staining. Enzymatic activities of MnSOD and Cu/ZnSOD were evaluated, and the rate of proliferation was determined by proliferating cell nuclear antigen staining.
Results: Severe esophagitis was seen in 100% of the EDA rats, and morphologic transformation within the esophageal epithelium was observed with intestinal metaplasia (40% of animals) and cancer (40% of animals) identified after 3 months. Decreased oxidative damage, along with the decreased degree of esophagitis and incidence of BE (20%) and EAC (0%), was found in MnTBAP-treated EDA rats comparing with the saline-treated EDA control. Decreased proliferation (46%) and increased SOD enzymatic activities (25%) were also found in the EDA rats treated with MnTBAP.
Conclusion: MnTBAP protected rat esophageal epithelium from oxidative injury induced by EDA, and it could prevent the transformation of esophageal epithelial cell to BE to EAC by preservation of antioxidants.
Involvement of Rho Kinase in Endothelial Barrier Maintenance
Authors: van Nieuw Amerongen G.P. , Beckers C.M.L. , Achekar I.D. , Zeeman S. , Musters R.J.P. , van Hinsbergh V.W.M. 
Published: August 2007

Objective—Rho kinase mediates vascular leakage caused by many vasoactive agents including thrombin. Enhanced Rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of Myosin Phosphatase (MP). Here, we investigated the contribution of basal Rho kinase activity to the regulation of endothelial barrier integrity.Methods and Results—Using a phospho-specific antibody against the myosin phosphatase targeting subunit (Thr696−MYPT1) as a marker for Rho kinase activity, basal endothelial Rho kinase activity was observed at cell-cell contact sites, in vitro and in situ. Thrombin enhanced MYPT phosphorylation at F-actin stress fibers. Inhibition of basal Rho kinase activity for 24 hours or depletion of Rho kinase (ROCK-I and -II) by siRNA disrupted endothelial barrier integrity, opposite to the previously observed protection from the thrombin-enhanced endothelial permeability. This barrier dysfunction could not be explained by changes in RhoA, Rac1, eNOS, or apoptosis. Remarkably, basal Rho kinase activity was essential for proper expression of the adhesion molecule VE-cadherin.Conclusions—Rho kinase has opposing activities in regulation of endothelial barrier function: (1) an intrinsic barrier-protective activity at the cell margins, and (2) an induced barrier-disruptive activity at contractile F-actin stress fibers. These findings may have implications for long-term antivascular leak therapy.
Asymmetry of the Tripole Rainfall Pattern during the East Asian Summer
Authors: Hsu Huang-Hsiung , Lin Shih-Ming 
Published: August 2007

Abstract
This study investigates the tripole rainfall pattern in East Asia during the northern summer. The tripole pattern is characterized by a zonally elongated and meridionally banded structure with signs changing alternatively from 20° to 50°N along the East Asian coast. The positive (negative) phase of the pattern is characterized by more (less) rainfall in central-eastern China, Japan, and South Korea, and less (more) rainfall in northern and southern China. Asymmetry between the positive and negative phases is one of the key findings of this study. The tripole pattern is closely associated with two wavelike patterns: the Pacific–Japan pattern and the Silk Road pattern. The former, which emanates from the tropical western Pacific to extratropical East Asia, is more evident in the positive phase, while the latter, emanating across the Eurasian continent, is more evident in the negative phase. The positive phase appears to have a stronger tropical connection, while the negative phase has a stronger extratropical connection. The positive and negative phases are associated with the positive and negative SSTA in the equatorial eastern Pacific, respectively. It is suggested that in the positive phase the zonally oriented overturning circulation driven by the positive SSTA in the equatorial eastern Pacific induces heating anomalies in the tropical western Pacific, which in turn triggers a wavelike pattern emanating northward toward extratropical East Asia. This indirect SSTA effect is not evident in the negative phase, which is predominantly affected by the extratropical Eurasian wavelike perturbations. On the other hand, anomalous heating over the eastern Tibetan Plateau seems to induce the eastward-propagating wavelike structure in both phases. It is suggested that the tripole pattern is a result of the amplification of an intrinsic dynamic mode that can be triggered by various factors despite their different origins.
Global Warming and the Weakening of the Tropical Circulation
Authors: Vecchi Gabriel A. , Soden Brian J. 
Published: August 2007

Abstract
This study examines the response of the tropical atmospheric and oceanic circulation to increasing greenhouse gases using a coordinated set of twenty-first-century climate model experiments performed for the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). The strength of the atmospheric overturning circulation decreases as the climate warms in all IPCC AR4 models, in a manner consistent with the thermodynamic scaling arguments of Held and Soden. The weakening occurs preferentially in the zonally asymmetric (i.e., Walker) rather than zonal-mean (i.e., Hadley) component of the tropical circulation and is shown to induce substantial changes to the thermal structure and circulation of the tropical oceans. Evidence suggests that the overall circulation weakens by decreasing the frequency of strong updrafts and increasing the frequency of weak updrafts, although the robustness of this behavior across all models cannot be confirmed because of the lack of data. As the climate warms, changes in both the atmospheric and ocean circulation over the tropical Pacific Ocean resemble “El Niño–like” conditions; however, the mechanisms are shown to be distinct from those of El Niño and are reproduced in both mixed layer and full ocean dynamics coupled climate models. The character of the Indian Ocean response to global warming resembles that of Indian Ocean dipole mode events. The consensus of model results presented here is also consistent with recently detected changes in sea level pressure since the mid–nineteenth century.
The mitochondrial genome of Phallusia mammillata and Phallusia fumigata (Tunicata, Ascidiacea): high genome plasticity at intra-genus level
Authors: Iannelli Fabio , Griggio Francesca , Pesole Graziano , Gissi Carmela 
Published: August 2007

Abstract

Background
Within Chordata, the subphyla Vertebrata and Cephalochordata (lancelets) are characterized by a remarkable stability of the mitochondrial (mt) genome, with constancy of gene content and almost invariant gene order, whereas the limited mitochondrial data on the subphylum Tunicata suggest frequent and extensive gene rearrangements, observed also within ascidians of the same genus.

Results
To confirm this evolutionary trend and to better understand the evolutionary dynamics of the mitochondrial genome in Tunicata Ascidiacea, we have sequenced and characterized the complete mt genome of two congeneric ascidian species, Phallusia mammillata and Phallusia fumigata (Phlebobranchiata, Ascidiidae). The two mtDNAs are surprisingly rearranged, both with respect to one another and relative to those of other tunicates and chordates, with gene rearrangements affecting both protein-coding and tRNA genes. The new data highlight the extraordinary variability of ascidian mt genome in base composition, tRNA secondary structure, tRNA gene content, and non-coding regions (number, size, sequence and location). Indeed, both Phallusia genomes lack the trnD gene, show loss/acquisition of DHU-arm in two tRNAs, and have a G+C content two-fold higher than other ascidians. Moreover, the mt genome of P. fumigata presents two identical copies of trnI, an extra tRNA gene with uncertain amino acid specificity, and four almost identical sequence regions. In addition, a truncated cytochrome b, lacking a C-terminal tail that commonly protrudes into the mt matrix, has been identified as a new mt feature probably shared by all tunicates.

Conclusion
The frequent occurrence of major gene order rearrangements in ascidians both at high taxonomic level and within the same genus makes this taxon an excellent model to study the mechanisms of gene rearrangement, and renders the mt genome an invaluable phylogenetic marker to investigate molecular biodiversity and speciation events in this largely unexplored group of basal chordates.
Glycerate kinase of the hyperthermophilic archaeon Thermoproteus tenax: new insights into the phylogenetic distribution and physiological role of members of the three different glycerate kinase classes
Authors: Kehrer Daniel , Ahmed Hatim , Brinkmann Henner , Siebers Bettina 
Published: August 2007

Abstract

Background
The presence of the branched Entner-Doudoroff (ED) pathway in two hyperthermophilic Crenarchaea, the anaerobe Thermoproteus tenax and the aerobe Sulfolobus solfataricus, was suggested. However, so far no enzymatic information of the non-phosphorylative ED branch and especially its key enzyme – glycerate kinase – was available. In the T. tenax genome, a gene homolog with similarity to putative hydroxypyruvate reductase/glycerate dehydrogenase and glycerate kinase was identified.

Results
The encoding gene was expressed in E. coli in a recombinant form, the gene product purified and the glycerate kinase activity was confirmed by enzymatic studies. The enzyme was active as a monomer and catalyzed the ATP-dependent phosphorylation of D-glycerate forming exclusively 2-phosphoglycerate. The enzyme was specific for glycerate and highest activity was observed with ATP as phosphoryl donor and Mg2+ as divalent cation. ATP could be partially replaced by GTP, CTP, TTP and UTP. The enzyme showed high affinity for D-glycerate (Km 0.02 ± 0.01 mM, Vmax of 5.05 ± 0.52 U/mg protein) as well as ATP (Km of 0.03 ± 0.01 mM, Vmax of 4.41 ± 0.04 U/mg protein), although at higher glycerate concentrations, substrate inhibition was observed. Furthermore, the enzyme was inhibited by its product ADP via competitive inhibition. Data bank searches revealed that archaeal glycerate kinases are members of the MOFRL (multi-organism fragment with rich leucine) family, and homologs are found in all three domains of life.

Conclusion
A re-evaluation of available genome sequence information as well as biochemical and phylogenetic studies revealed the presence of the branched ED pathway as common route for sugar degradation in Archaea that utilize the ED pathway. Detailed analyses including phylogenetic studies demonstrate the presence of three distinct glycerate kinase classes in extant organisms that share no common origin. The affiliation of characterized glycerate kinases with the different enzyme classes as well as their physiological/cellular function reveals no association with particular pathways but a separate phylogenetic distribution. This work highlights the diversity and complexity of the central carbohydrate metabolism. The data also support a key function of the conversion of glycerate to 2- or 3-phosphoglycerate via glycerate kinase in funneling various substrates into the common EMP pathway for catabolic and anabolic purposes.