bluuebunny/crossref_metadata_2025 huggingface dataset:
Infarction of tumor vessels by NGR-peptide–directed targeting of tissue factor: experimental results and first-in-man experience
Authors: Bieker Ralf , Kessler Torsten , Schwöppe Christian , Padró Teresa , Persigehl Thorsten , Bremer Christoph , Dreischalück Johannes , Kolkmeyer Astrid , Heindel Walter , Mesters Rolf M. , Berdel Wolfgang E.
Published: January 2009

We induced thrombosis of blood vessels in solid tumors in mice by a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the integrin αvβ3 (CD51/CD61) on tumor vascular endothelium. The designed fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by coagulation assays. In vivo studies in mice bearing established human adenocarcinoma (A549), melanoma (M21), and fibrosarcoma (HT1080) revealed that systemic administration of tTF-NGR induced partial or complete thrombotic occlusion of tumor vessels as shown by histologic analysis. tTF-NGR, but not untargeted tTF, induced significant tumor growth retardation or regression in all 3 types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was also shown by contrast enhanced magnetic resonance imaging (MRI). In the human fibrosarcoma xenograft model, MRI revealed a significant reduction of tumor perfusion by administration of tTF-NGR. Clinical first-in-man application of low dosages of this targeted coagulation factor revealed good tolerability and decreased tumor perfusion as measured by MRI. Targeted thrombosis in the tumor vasculature induced by tTF-NGR may be a promising strategy for the treatment of cancer.
Runx2 induces acute myeloid leukemia in cooperation with Cbfβ-SMMHC in mice
Authors: Kuo Ya-Huei , Zaidi Sayyed K. , Gornostaeva Svetlana , Komori Toshihisa , Stein Gary S. , Castilla Lucio H.
Published: January 2009

The core-binding factor (CBF) is a master regulator of developmental and differentiation programs, and CBF alterations are frequently associated with acute leukemia. The role of the CBF member RUNX2 in hematopoiesis is poorly understood. Genetic evidence suggests that deregulation of Runx2 may cause myeloid leukemia in mice expressing the fusion oncogene Cbfb-MYH11. In this study, we show that sustained expression of Runx2 modulates Cbfβ-smooth muscle myosin heavy chain (SMMHC)–mediated myeloid leukemia development. Expression of Runx2 is high in the hematopoietic stem cell compartment and decreases during myeloid differentiation. Sustained Runx2 expression hinders myeloid progenitor differentiation capacity and represses expression of CBF targets Csf1R, Mpo, Cebpd, the cell cycle inhibitor Cdkn1a, and myeloid markers Cebpa and Gfi1. In addition, full-length Runx2 cooperates with Cbfβ-SMMHC in leukemia development in transplantation assays. Furthermore, we show that the nuclear matrix–targeting signal and DNA-binding runt-homology domain of Runx2 are essential for its leukemogenic activity. Conversely, Runx2 haplo-insufficiency delays the onset and reduces the incidence of acute myeloid leukemia. Together, these results indicate that Runx2 is expressed in the stem cell compartment, interferes with differentiation and represses CBF targets in the myeloid compartment, and modulates the leukemogenic function of Cbfβ-SMMHC in mouse leukemia.
IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease
Authors: Einarsdottir Elisabet , Koskinen Lotta LE , Dukes Emma , Kainu Kati , Suomela Sari , Lappalainen Maarit , Ziberna Fabiana , Korponay-Szabo Ilma R , Kurppa Kalle , Kaukinen Katri , Ádány Róza , Pocsai Zsuzsa , Széles György , Färkkilä Martti , Turunen Ulla , Halme Leena , Paavola-Sakki Paulina , Not Tarcisio , Vatta Serena , Ventura Alessandro , Löfberg Robert , Torkvist Leif , Bresso Francesca , Halfvarson Jonas , Mäki Markku , Kontula Kimmo , Saarialho-Kere Ulpu , Kere Juha , D'Amato Mauro , Saavalainen Päivi
Published: January 2009

Background

Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases.

Methods

We studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease.

Results

Association of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples.

Conclusion

Our study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated.
Altering the ribosomal subunit ratio in yeast maximizes recombinant protein yield
Authors: Bonander Nicklas , Darby Richard AJ , Grgic Ljuban , Bora Nagamani , Wen Jikai , Brogna Saverio , Poyner David R , O'Neill Michael AA , Bill Roslyn M
Published: January 2009

Background

The production of high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences that has yet to be addressed in a truly rational manner. Typically eukaryotic protein production experiments have relied on varying expression construct cassettes such as promoters and tags, or culture process parameters such as pH, temperature and aeration to enhance yields. These approaches require repeated rounds of trial-and-error optimization and cannot provide a mechanistic insight into the biology of recombinant protein production. We published an early transcriptome analysis that identified genes implicated in successful membrane protein production experiments in yeast. While there has been a subsequent explosion in such analyses in a range of production organisms, no one has yet exploited the genes identified. The aim of this study was to use the results of our previous comparative transcriptome analysis to engineer improved yeast strains and thereby gain an understanding of the mechanisms involved in high-yielding protein production hosts.

Results

We show that tuning BMS1 transcript levels in a doxycycline-dependent manner resulted in optimized yields of functional membrane and soluble protein targets. Online flow microcalorimetry demonstrated that there had been a substantial metabolic change to cells cultured under high-yielding conditions, and in particular that high yielding cells were more metabolically efficient. Polysome profiling showed that the key molecular event contributing to this metabolically efficient, high-yielding phenotype is a perturbation of the ratio of 60S to 40S ribosomal subunits from approximately 1:1 to 2:1, and correspondingly of 25S:18S ratios from 2:1 to 3:1. This result is consistent with the role of the gene product of BMS1 in ribosome biogenesis.

Conclusion

This work demonstrates the power of a rational approach to recombinant protein production by using the results of transcriptome analysis to engineer improved strains, thereby revealing the underlying biological events involved.
A case of Meigs syndrome mimicking metastatic breast carcinoma
Authors: Lanitis Sophocles , Sivakumar Sivahamy , Behranwala Kasim , Zacharakis Emmanouil , Al Mufti Ragheed , Hadjiminas Dimitri J
Published: January 2009

Background

Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity.

Case presentation

A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma.

Conclusion

Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.
Impact of GnRH ovarian stimulation protocols on intracytoplasmic sperm injection outcomes
Authors: Pinto Fátima , Oliveira Cristiano , Cardoso Margarida F , Teixeira-da-Silva José , Silva Joaquina , Sousa Mário , Barros Alberto
Published: January 2009

Background

Although a large number of studies have been conducted in relation to ovarian response and pregnancy after GnRH agonist and GnRH antagonist controlled ovarian hyperstimulation protocols, most of them used single or combinations of a few predictive factors, and none included the stimulation protocol in the multivariable analysis. The present study was thus primarily designed to investigate the predictive value of the stimulation protocol and to analyze the possible relationships between stimulation protocols and treatment outcomes after adjusting for a large set of variables that potentially affect reproductive outcomes. Factors related to pregnancy achievement and predictive of the number of oocytes retrieved and high quality of the embryos obtained were also analyzed.

Methods

To analyze the impact of GnRH ovarian stimulation protocols on the independent predictors of ovarian response, high quality embryos and clinical pregnancy, two groups out of 278 ICSI treatment cycles were compared prospectively, 123 with a GnRH agonist and 155 with a GnRH antagonist, with multivariable analysis assessing outcomes after adjusting for a large set of variables.

Results

Antagonists were significantly associated with lower length and total dose of GnRH, lower length of rFSH, and higher numbers of oocytes and high quality embryos, whereas the agonist presented a higher fertilization rate and probability of pregnancy. Significant predictors of retrieved oocytes and high quality embryos were the antagonist protocol, lower female age, lower serum levels of basal FSH and higher total number of antral follicles. Significant predictors of clinical pregnancy were the agonist protocol, reduced number of attempts, increased endometrial thickness and lower female age. The probability of pregnancy increased until 30 years-old, with a decline after that age and with a sharp decline after 40 years-old.

Conclusion

The models found suggest that not only the protocol but also factors as female age, basal FSH, antral follicles, number of attempts and endometrial thickness should be analyzed for counselling patients undergoing an ICSI treatment.
Sensorineural hearing loss in Lassa fever: two case reports
Authors: Okokhere Peter O. , Ibekwe Titus S. , Akpede George O.
Published: January 2009

Introduction

Lassa fever is an acute arena viral haemorrhagic fever with varied neurological sequelae. Sensorineural hearing loss is one of the rare complications which occur usually during the convalescent stage of the infection.

Case presentation

The cases of two female patients aged 19 and 43 years old, respectively, with clinical features suggestive of Lassa fever and confirmed by immunoserological/Lassa-virus-specific reverse transcriptase polymerase chain reaction are presented. Both patients developed severe sensorineural hearing loss at acute phases of the infections.

Conclusion

Sensorineural hearing loss from Lassa fever infections can occur in both acute and convalescent stages and is probably induced by an immune response.
The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells
Authors: Zhuang Hong-Qing , Wang Jun-Jie , Liao An-Yan , Wang Ji-Dong , Zhao Yong
Published: January 2009

Background

To investigate the effectiveness and mechanism of125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro.

Methods

The CL187 cell line was exposed to radiation of60Coγ ray at high dose rate of 2 Gy/min and125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI) staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR) and Raf under continuous low dose rate irradiation (CLDR) and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence.

Results

The relative biological effect (RBE) for125I seeds compared with60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%.P< 0.05 vs. control groups by Student's t-test were found in every treated group both in apoptosis and in G2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change.

Conclusion

125I seeds resulted in more effective inhibition than60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could influence the proliferation of cells via MAPK signal transduction.
Regulation of the Rac GTPase pathway by the multifunctional Rho GEF Pebble is essential for mesoderm migration in theDrosophilagastrula
Authors: van Impel Andreas , Schumacher Sabine , Draga Margarethe , Herz Hans-Martin , Großhans Jörg , Müller H. Arno J.
Published: January 2009

The Drosophila guanine nucleotide exchange factor Pebble (Pbl) is essential for cytokinesis and cell migration during gastrulation. In dividing cells, Pbl promotes Rho1 activation at the cell cortex, leading to formation of the contractile actin-myosin ring. The role of Pbl in fibroblast growth factor-triggered mesoderm spreading during gastrulation is less well understood and its targets and subcellular localization are unknown. To address these issues we performed a domain-function study in the embryo. We show that Pbl is localized to the nucleus and the cell cortex in migrating mesoderm cells and found that, in addition to the PH domain, the conserved C-terminal tail of the protein is crucial for cortical localization. Moreover,we show that the Rac pathway plays an essential role during mesoderm migration. Genetic and biochemical interactions indicate that during mesoderm migration, Pbl functions by activating a Rac-dependent pathway. Furthermore,gain-of-function and rescue experiments suggest an important regulatory role of the C-terminal tail of Pbl for the selective activation of Rho1-versus Rac-dependent pathways.
The NAC-domain transcription factor GOBLET specifies leaflet boundaries in compound tomato leaves
Authors: Berger Yael , Harpaz-Saad Smadar , Brand Arnon , Melnik Hadas , Sirding Neti , Alvarez John Paul , Zinder Michael , Samach Alon , Eshed Yuval , Ori Naomi
Published: January 2009

Leaves are formed at the flanks of the shoot apical meristem (SAM) and develop into a variety of forms. In tomato, prolonged leaf patterning enables the elaboration of compound leaves by reiterative initiation of leaflets with lobed margins. In goblet (gob) loss-of-function mutants,primary leaflets are often fused, secondary leaflets and marginal serrations are absent, and SAMs often terminate precociously. We show that GOBencodes a NAC-domain transcription factor expressed in narrow stripes at the leaf margins, flanking the distal side of future leaflet primordia, and at the boundaries between the SAM and leaf primordia. Leaf-specific overexpression of the microRNA miR164, a negative regulator of GOB-like genes,also leads to loss of secondary-leaflet initiation and to smooth leaflet margins. Plants carrying a dominant gob allele with an intact ORF but disrupted miR164 binding site produce more cotyledons and floral organs, have split SAMs and, surprisingly, simpler leaves. Overexpression of a form of GOB with an altered miR164 binding site in leaf primordia leads to delayed leaflet maturation, frequent, improperly timed and spaced initiation events, and a simple mature leaflet form owing to secondary-leaflet fusion. miR164 also affects leaflet separation in Cardamine hirsuta, a Brassicaceae species with complex leaves. Genetic and molecular analyses suggest that GOB expression is intact in the simplified leaves of entire tomato mutants, which have a defect in a putative repressor of auxin responses. Our results show that GOB marks leaflet boundaries and that its accurate spatial, temporal and quantitative activity affects leaf elaboration in a context-dependent manner.
Steroids initiate a signaling cascade that triggers rapid sporulation inDictyostelium
Authors: Anjard Christophe , Su Yongxuan , Loomis William F.
Published: January 2009

Encapsulation of prespore cells of Dictyostelium discoideum is controlled by several intercellular signals to ensure appropriate timing during fruiting body formation. Acyl-CoA-binding protein, AcbA, is secreted by prespore cells and processed by the prestalk protease TagC to form the 34 amino acid peptide SDF-2 that triggers rapid encapsulation. AcbA is secreted when γ-aminobutyric acid (GABA) is released from prespore cells and binds to GrlE, a G protein-coupled receptor (GPCR). Analysis of SDF-2 production in mutant strains lacking Gα subunits and GPCRs, either as pure populations or when mixed with other mutant strains, uncovered the non-cell-autonomous roles of GrlA, Gα4 and Gα7. We found that Gα7 is essential for the response to GABA and is likely to be coupled to GrlE. GrlA-null and Gα4-null cells respond normally to GABA but fail to secrete it. We found that they are necessary for the response to a small hydrophobic molecule, SDF-3, which is released late in culmination. Pharmacological inhibition of steroidogenesis during development blocked the production of SDF-3. Moreover, the response to SDF-3 could be blocked by the steroid antagonist mifepristone, whereas hydrocortisone and other steroids mimicked the effects of SDF-3 when added in the nanomolar range. It appears that SDF-3 is a steroid that elicits rapid release of GABA by acting through the GPCR GrlA, coupled to G protein containing the Gα4 subunit. SDF-3 is at the head of the cascade that amplifies the signal for encapsulation to ensure the rapid, synchronous formation of spores.
SoxFis part of a novel negative-feedback loop in thewinglesspathway that controls proliferation in theDrosophilawing disc
Authors: Dichtel-Danjoy Marie-Laure , Caldeira Joana , Casares Fernando
Published: January 2009

Wnt molecules act as mitogenic signals during the development of multiple organs, and the aberrant activity of their pathway is often associated with cancer. Therefore, the production of Wnts and the activity of their signaling pathway must be tightly regulated. We have investigated the mechanisms of this regulation in the Drosophila hinge, a domain within the wing imaginal disc that depends on the fly Wnt1 ortholog wingless (wg) for its proliferation. Our results uncover a new feedback loop in the wgpathway in which the spatially restricted activation of the Sox gene SoxF (Sox15) by wg represses its own transcription,thus ensuring tight regulation of growth control. rotund, a wing proximodistal patterning gene, excludes SoxF from a thin rim of cells. These cells are thus allowed to express wg and act as the source of mitogenic signal. This novel mode of action of a Sox gene on the Wnt pathway - through transcriptional repression of a Wnt gene - might be relevant to human disease, as loss of human SoxF genes has been implicated in colon carcinoma.
Priority Shifting and the Dynamics of Managing Eradicable Infectious Diseases
Authors: Tebbens Radboud J. Duintjer , Thompson Kimberly M.
Published: January 2009

Public health budget constraints force policy makers to prioritize resources toward those interventions that yield the highest perceived benefits. Intuitively, it appears optimal to focus resources on affordable interventions against prevalent diseases. However, due to the dynamics of infectious disease eradication, policies focusing on a static perception of priorities may lead to economically suboptimal outcomes. Using a hypothetical two-disease dynamic transmission model, we explore several different decision rules with respect to vaccination policy for eradicable diseases. The simulations show that cost-effectiveness decreases as the extent of priority shifting increases. This model suggests the need for a longer-term dynamic perspective to appropriately recognize costs and benefits of different policies for eradicable diseases.
Education, education, education: postgraduate assessments and the consultant contract
Authors: Mukhtar S , Compson J
Published: January 2009

Recent changes in medical training have involved the introduction of a number of different tools for the assessment of trainees at all levels. These are completed by all doctors ranging from the level of foundation year 1 (FY1) trainees (previously pre-registration house officers) to final year specialty trainees (STs). While consultants are required to be an integral part of this assessment process, no formal time has been set aside and protected for these sessions. We propose the correct number of sessions for this activity be part of a new consultant contract, especially given the significant increase in the quantity of assessment and appraisals in the current training system. But how many hours are required?
From nature, through chemical synthesis, toward use in agriculture: Oryzoxymycin case study
Authors: Bwire Regina N. , Majinda Runner R. , Masesane Ishmael B. , Steel Patrick G.
Published: January 2009

The Diels-Alder adducts of ethyl (E)-3-nitroacrylate and furan provided a common and versatile template for the stereocontrolled synthesis of an isomer of the natural product oryzoxymycin and polyhydroxylated cyclohexyl β-amino acid derivatives. The strategy for the synthesis of the polyhydroxylated cyclic β-amino acid derivatives involved base-induced fragmentation of the oxanorbornene skeleton and face selective oxidation reactions. A Pd-catalyzed transfer hydrogenation reaction in the presence of organic acids is also described. This reaction is amenable to being enantioselective through use of optical pure chiral organic acids.
Prospects for processing wastes into products used in agriculture
Authors: Pawełczyk Adam , Szczygieł Bogdan
Published: January 2009

The authors have proposed their own newly developed universal procedure for assessing waste and selecting methods of processing the waste for agricultural purposes. Increasingly more rigorous environmental legal regulations, especially pertaining to sustainability in agricultural and chemical production, were the most convincing motivation for such approach. The procedure is based on technological and environmental safety criteria. Special attention is devoted to the chemical processing of hazardous wastes into fertilizer products and the underlying reasons for such methodology. As opposed to physical and biochemical processes, in chemical processes the agents used completely change the chemical structure of the waste materials or at least that of some of their components. As a result, new phases are formed and the harmful properties of the initial material are eliminated. Prospects for the chemical processing of hazardous wastes are demonstrated using as an example the utilization of asbestos wastes. There are vast amounts of asbestos materials installed in industrial, communal, and service facilities. Landfill asbestos waste disposal is the common practice, but this does not solve properly the problem of environmental hazard. The proposed utilization concept consists in destroying asbestos with a phosphoric acid solution in a two-stage process. The obtained suspension is then filtered, and the solution of phosphates containing an excess of phosphoric acid is subsequently neutralized with lime and processed into phosphate fertilizers of TSP (triple superphosphate) or DCP (dicalcium phosphate) type. Experiments showed that the process yielded asbestos-free products which did not contain any respirable fibers. Comparative immunological tests showed that the products did not cause any degeneration of human lung cells exposed to them, as opposed to the original asbestos, which had a highly damaging effect on the cells.
Self-assembled ordered mesoporous metals
Authors: Warren Scott C. , Wiesner Ulrich
Published: January 2009

Control over the structure of metals at the mesoscale (2-50 nm) is crucial for emerging applications such as energy conversion, sensing, and information processing. The self-assembly of nanoparticles with block copolymers provides a natural entry point to materials of this length scale. The field's historical development, relevant physical models, and recent results are presented.
Immunological effects of mercury (IUPAC Technical Report)
Authors: Schwenk Michael , Klein Reinhild , Templeton Douglas M.
Published: January 2009

Various chemical species of mercury differ considerably with regard to their route of absorption and their distribution in the body, yet many of them and their metabolites exhibit high-affinity binding to sulfanyl groups of proteins. Among all metals, mercury appears to have the most diverse effects on the immune system. Depending on the animal species and experimental conditions, mercury compounds may cause immunosuppression or immunostimulation, autoimmune reactions, or hypersensitivity. Mercury-sensitive strains of rats and mice are often used as model organisms to study the time course and events in autoimmunity. Within about 14 days after onset of oral mercury(II) exposure, levels of immunoglobulins E and G (IgE and IgG) increase, including autoantibodies to biomolecules such as laminin and fibrillarin. Antigen-antibody complexes are formed and are the cause of subsequent autoimmune diseases of blood vessels and organs. Mercury may induce local mercury hypersensitivity in humans, but the evidence for a role of mercury in autoimmune disease of humans is at best weak. Models for the immune effects of mercury are presented on the basis of current knowledge.
Pathologic Analysis of the Brain from Streptococcus suis Type 2 Experimentally Infected Pigs
Authors: Zheng P. , Zhao Y. X. , Zhang A. D. , Kang C. , Chen H. C. , Jin M. L.
Published: January 2009

Streptococcus suis type 2 ( S. suis 2) is known as a major porcine pathogen worldwide and causes meningitis, septicemia, endocarditis, arthritis, and septic shock in pigs. Suilysin, a secreted protein of S. suis 2, is considered to be an important S. suis 2 virulence-associated factor. In this paper, the cerebellar lesions following experimental infection of pigs with S. suis 2 were studied. An immunohistochemical technique was applied to compare the distribution of bacteria and secreted suilysin protein in brain. The infected pigs developed histologic lesions of meningoencephalitis. Immunohistochemistry identified bacteria within the cytoplasm of neutrophils and macrophages localized in meningeal lesions. The secreted suilysin protein showed a similar localization within the cytoplasm of inflammatory cells, indicating that suilysin had high expression in vivo and may contribute to the pathogenesis of streptococcal meningoencephalitis.
Pleomorphic Corneal Sarcoma Resembling Malignant Peripheral Nerve Sheath Tumor in a Horse
Authors: Kappe E. C. , KÖHLER K. , Felbert I. v. , Teifke J. P. , TÓTH J. , Reinacher M.
Published: January 2009

A 14-year-old Haflinger gelding presented with a protruding mass involving the cornea of the right eye. The mass was resected and submitted for histopathologic and immunohistochemical examination. The preliminary diagnosis was corneal sarcoma, most likely fibrosarcoma. The immunohistochemical results confirmed the mesenchymal origin of the neoplastic cells, which were most consistent with a malignant peripheral nerve sheath tumor. Corneal mesenchymal neoplasms are extremely uncommon tumors in human beings and domestic animals. The cause for this tumor was not determined; infection with bovine papillomavirus was not detected.
Expression of Androgen Receptor in Mammary Glands in Ovariectomized Cynomolgus Monkeys
Authors: Kawaguchi H. , Umekita Y. , Fukuzaki K. , Maeda H. , Miyajima H. , Nagata R. , Yoshida H.
Published: January 2009

This study investigated structural alterations and the immunohistochemical expression of androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) in the mammary glands from surgically postmenopausal cynomolgus monkeys ( Macaca fascicularis). Fourteen animals were divided into 2 groups. Seven animals underwent an ovariectomy (OVX), and the other 7 animals underwent a sham operation (sham). The in-life phase of study was 78 weeks. Atrophy in the mammary glands of OVX monkeys was similar to early postmenopausal atrophy of the human breast. The proportion of AR-positive cells in the OVX group was significantly higher than in the sham group, but the proportion of ER and PgR-positive cells was significantly lower. These results suggest that use of a primate model for hormone receptor expression has potential applications in basic human endocrinology, particularly in research in hormone receptor expression in mammary glands (both normal and neoplastic).
Molecular Characterization of Feline COX-2 and Expression in Feline Mammary Carcinomas
Authors: Sayasith K. , Sirois J. , DorÉ M.
Published: January 2009

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the biosynthesis of prostaglandins, plays an important role in inflammation and tumorigenesis. COX-2 primary structure has been characterized in many species and its expression demonstrated in a variety of cancers in humans and dogs, including mammary cancer. In contrast, there is currently little information on the structure of feline COX-2. Also, information on COX-2 expression in feline mammary cancer is limited and conflicting. The objectives of this study were therefore to characterize the molecular structure of feline COX-2 and to evaluate by immunohistochemistry its expression in mammary carcinomas. Our results show that the predicted coding region of feline COX-2 encodes a 604-amino acid protein, which is identical in length to several COX-2 homologs. Feline COX-2 amino acid sequence is highly similar to other mammalian COX-2 homologs. Immunohistochemical analysis of 40 mammary carcinomas showed that the majority of tumors studied (35/40; 87%) expressed COX-2 at a level varying from low (20/40; 50%) to intermediate (13/40; 32%) and high (2/40; 5%). These results provide the first molecular characterization of feline COX-2 and demonstrate that COX-2 is expressed in the majority of feline mammary carcinomas.
Review Paper: The Role of Inflammation in Mouse Pulmonary Neoplasia
Authors: Bauer A. K. , Rondini E. A.
Published: January 2009

Inflammation is a risk factor for the development of many types of neoplasia, including skin, colon, gastric, and mammary cancers, among others. Chronic pulmonary diseases, such as chronic bronchitis and asthma, predispose to lung neoplasia. We will review the mouse literature examining the role of inflammation in lung neoplasia, focusing specifically on genetic susceptibility, pharmacologic modulation of inflammatory pathways, and both transgenic and knockout mouse models used to assess pro- and anti-inflammatory pathways involved in lung neoplasia. Identification of molecular mechanisms that govern the association between inflammation and pulmonary neoplasia could provide novel preventive, diagnostic, and therapeutic strategies for a disease in which few biomarkers currently exist.
An Overview of Technology and Equipment for Hardening of Large Steel Parts
Authors: Deyneko L. N. , Kobasko N. I. , Dobryvechir V. V. , Litvinenko E. I.
Published: January 2009

In the paper, multi-step accelerated-interrupted (AI) quenching is illustrated by its application to fittings for oil and gas pipelines with a diameter up to 1420 mm (1.42 m) and wall thickness from 16 to 80 mm. The multi-step AI quenching is used to improve the mechanical properties of steel parts on the basis of regularities of full film boiling. The developed technology is ecofriendly since it uses water instead of oil as a quenchant. The industrial conditions are described for an automated quench system where the quenchant was water at 60–90°C, which was circulated at different velocities. Favorable temperature differences along the thickness of the wall of parts to be quenched can be achieved by applying multi-step quenching. Software and hardware have been developed to govern the process.
Mitochondria and human preimplantation embryo development
Authors: Wilding Martin , Coppola Gianfranco , Dale Brian , Di Matteo Loredana
Published: January 2009

Human reproduction, like all biological systems, is characterised by a large level of variability. In this field, the variability is observed as a large difference in implantation potential of human embryos developingin vitro, despite similarities in observable parameters such as rate of development and morphology of these embryos. One of the underlying factors that determines developmental potential in these embryos is the availability of energy in the form of ATP for development. Here, we suggest that, despite the evidence suggesting that mitochondrial metabolism is relatively inactive during preimplantation embryo development, aerobic (mitochondrial) metabolism contributes a major role in the supply of ATP. A second pathway, anaerobic respiration, is also active and the two pathways work in synchrony to supply all the ATP necessary. We discuss the differences in the two forms of energy production and suggest that, although anaerobic respiration can supplement deficiencies in the energy supply in the short term, this is not sufficient to substitute for aerobic respiration over long periods. Therefore, we suggest that deficiencies in the levels of aerobic respiration can explain variability in the implantation potential of apparently equivalent embryos.
Meeting AYP in a High‐Need School: A Formative Experiment
Authors: Fisher Douglas , Frey Nancy , Lapp Diane
Published: January 2009

This formative experiment was designed to ensure that a group of high school students developed their literacy habits. The intervention consisted of a schoolwide approach to literacy using four instructional routines: think‐alouds, note‐taking writing to learn, and dedicated reading time. As part of the formative experiment, we document the two‐and‐a‐half‐year process required for the school to implement the initiative as well as the outcomes of the effort.

تم تصميم هذه التجربة التكوينية ليؤكد أن مجموعة من طلاب الثانوية العامة طوروا عاداتهم في معرفة القراءة والكتابة. وكان التدخل مؤلفاً من منهاج معرفة القراءة والكتابة على نطاق المدرسة مستخدماً ثلاثة مكونات: التفكير الجهري وكتابة ملاحظات للتعلم وتخصيص وقت للقراءة. لقد سجلنا العملية التي بلغت مدتها سنتين ونصف كجزء من التجربة التكوينية وهي ضرورة للمدرسة كي تنفذ المبادرة بالإضافة إلى نتائج الجهود.

本研究是一项形成性实验研究，其设计是要确保一组高中学生在读写文化实践上得到发展。这干预采用全校性的读写能力教学方法，并利用四个教学常序：出声思维、笔记记录、通过写作来学习，和特定的阅读时间。作为该项形成性实验研究的一部分，我们记录了两年半以来该学校实施这个计划的过程，以及该学校在这方面努力而得出的成果。

Cette expérience de formation a été planifiée afin qu'un groupe d'élèves de lycée développent leurs pratiques de littératie. L'intervention a consisté en une approche de la littératie à l'échelle de l'établissement recourant à quatre routines pédagogiques: penser à haute voix, prendre des notes, écrire pour apprendre, et dédier du temps à la lecture. Dans le cadre de cette expérience de formation, nous apportons des informations sur le processus de deux ans et demi qui a été nécessaire à l'établissement pour mettre en place ce projet, ainsi que sur les conséquences de cet effort.

Разработчики данного формативного эксперимента стремились обеспечить развитие навыков грамотности среди старшеклассников. Вмешательство заключалось в становлении грамотности на всех без исключения уроках на основе таких методических приемов, как размышление вслух, конспектирование, обучающее письмо и отведение отдельного времени на чтение. В рамках эксперимента фиксировались все этапы и детали этого проекта, длившегося два с половиной года, и его результаты.

Este experimento formativo fue diseñado para asegurar que un grupo de alumnos de secundaria desarrollarían sus hábitos de aprendizaje. La intervención consistió en un acercamiento al aprendizaje en toda la escuela usando cuatro rutinas de instrucción: pensar en voz alta, tomar notas, escribir para aprender, y tiempo dedicado a la lectura. Como parte de la experiencia formativa, documentamos este proceso de dos años y medio que fue el tiempo necesario para no sólo lograr la implementación en la escuela de las iniciativas sino también para documentar los resultados del esfuerzo.
Online Book Clubs: Bridges Between Old and New Literacies Practices
Authors: Scharber Cassandra
Published: January 2009

In this Digital Literacies column, online book clubs are offered as one example of how to effectively bridge old and new literacy practices. These Internet‐based book clubs capitalize on children's interest in new literacy practices while complementing, and hopefully encouraging, traditional reading practices. Examples from online book clubs offered through a public library system are used to illustrate the possibilities these clubs.

في عمود معرفة القراءة والكتابة الرقمي هذا تم تقديم نوادي الكتاب على الشبكة العالمية مثالاً لبناء جسر بين معارف القراءة والكتابة القديمة والحديثة بشكل فعال. وتستغل نوادي الكتاب هذه اهتمام الأطفال بمعارف القراءة والكتابة الجديدة حين تتكمل ومتأملاً تشجع ممارسات القراءة التقليدية. إذ الأمثلة من نوادي الكتاب على الشبكة العالمية المقدمة من نظام المكاتب العامة مستخدمة لتبيين الاحتمالات التي توفر هذه النوادي للصفوف من الروضة للصف الثاني عشر.

本期的《数位素质》专栏提出网上书会是一个有效连接新的与传统的读写文化实践的例子。这些驻扎于互联网的书会，利用儿童对于新的读写文化的兴趣，同时与传统的阅读文化实践产生互补作用，甚至有可能因而促进传统的读写文化实践。本文以公立图书馆系统提供给读者的一些网上书会为例子，说明这些书会把幼儿园到十二年级课堂及学校教育加以延展的各种可能性。

Dans cette rubrique des Littératies numériques, on présente des clubs du livre en ligne comme exemple de la façon dont on peut bâtir avec efficacité un pont entre les anciennes et les nouvelles littératies. Ces clubs du livre sur Internet reposent sur l'intérêt des enfants pour les nouvelles pratiques de littératie tout en rendant hommage et, nous l'espérons, en encourageant les pratiques de lecture traditionnelles. On présente des exemples de clubs du livre en ligne au moyen d'un système de bibliothèque publique pour montrer quelles possibilités offrent ces clubs pour les classes et les établissements du jardin d'enfants à la fin des études secondaires.

В этой колонке, посвященной цифровой грамотности, речь идет о книжных онлайн‐клубах как о способе эффективно сочетать старые и новые методы грамотности. Пользуясь интересом детей к новейшим информационным технологиям, эти книжные клубы объединяют их в Интернете и одновременно приобщают их к традиционному чтению. На примере деятельности книжных онлайн‐клубов, в которых можно общаться и дома и в общедоступной библиотеке, видно, каким подспорьем они могут служить для любых возрастных групп школьников.

En esta columna de Competencias Digitales, se ofrecen clubes de lectura en el internet como un ejemplo de cómo efectivamente tender un puente entre las prácticas de aprendizaje antiguas y nuevas. Estos clubes en el internet toman ventaja del interés de los niños en prácticas de aprendizaje nuevas al mismo tiempo que complementan y, se espera, incentivan prácticas de lectura tradicionales. Se usaron ejemplos de clubes de lectura en el internet ofrecidos por un sistema de bibliotecas públicas para ilustrar las posibilidades que estos clubes les ofrecen a todos los grados (K‐12) y las escuelas.
Parents and Teachers: Talking With or Past One Another—or Not Talking at All?
Authors: Risko Victoria J. , Walker‐Dalhouse Doris
Published: January 2009

Parent and family involvement in schools can have a positive influence on students' school achievement. When parents feel good about their school involvement and the school's instructional efforts, they tend to hold high expectations for their children, which in turn can have a positive impact on their children's interests, aspirations, and learning — and on teachers' morale and self‐confidence. These positive outcomes are associated with parents and teachers forming partnerships that are respectful of one another's perspectives.

قد يؤثر انشغال الوالدين والعائلة في المدارس تأثيراً إيجابياً في إنجاز الطلاب الدراسي. وحين يشعر الوالدان جيداً تجاه انشغالهما في المدرسة وجهود المدرسة التعليمية يميلان إلى أن يتمسكا بتوقعات عالية لأطفالهما الأمر الذي قد يؤثر بدوره في اهتمام أطفالهما وطموحاتهم وتعلمهم تأثيراً إيجابياً وكذلك في معنوية المعلمين وثقتهم بالنفس. إذ تتعلق هذه النتائج الإيجابية بالوالدين والمعلمين الذين يشاركون مشاركة ذات الاحترام لوجهات نظر الآخر.

家长与家人的学校参与，能够正面影响到学生在学校的成绩。当家长对学校的参与和对学校为教学所作出的努力感到有意义时，他们会倾向于对他们子女持有高度的期望，从而正面地影响到他们子女的兴趣、志向及学习更正面地影响到教师的士气与自信心。这些正面的成效，是与家长和教师之间建立起互相尊重对方观点的伙伴关系有关的。

L'implication des parents et de la famille dans l'école peut avoir un effet positif sur la réussite scolaire des élèves. Quand les parents vivent bien leur implication dans l'école et les efforts pédagogiques de celle‐ci, ils ont tendance à avoir de hauts niveaux d'attente pour leurs enfants, ce qui à son tour a un impact positif sur les intérêts, les aspirations et l'apprentissage de leur enfant — ainsi que sur le moral et la confiance en soi des enseignants. Ces conséquences positives apparaissent quand les parents et les enseignants forment des partenaires respectueux les uns des autres.

Вовлеченность родителей и других членов семей учащихся в жизнь школы может оказать положительное влияние на академические успехи детей. Когда родителям приятно бывать в школе, когда они довольны тем, что делает школа для их детей, они склонны поднимать планку своих ожиданий в отношении детей, что в свою очередь положительно отражается на интересе детей к учебе, на их стремлениях и на самом учебном процессе – а в конечном итоге и на моральном состоянии учителей и их уверенности в себе. Эти положительные результаты связаны тем, что между родителями и учителями формируются товарищеские отношения, они испытывают взаимное уважение и ценят мнения друг друга.

La participación de los padres y las familias en las escuelas puede tener una influencia positiva en los logros escolares de los alumnos. Cuando los padres se sienten satisfechos con su participación en las escuelas y en los esfuerzos educativos de la escuela, tienden a tener expectativas altas para sus niños, y esto, a su vez, puede tener un impacto positivo en el interés, las aspiraciones y el aprendizaje de los niños—y en la confianza y la moral de los maestros. Estos resultados positivos provienen de una asociación entre padres y maestros en la que se respetan las perspectivas de cada uno.
Keg impact damage to fibre-reinforced paving flags
Authors: Sinnott D. , West R. P.
Published: January 2009

The incidence of cracked and unserviceable paving slabs (or flags) in pedestrian walkways is high, often due to the fact that plain concrete flags cannot withstand impact loading arising from unloading of materials during delivery. Subsequently, lack of maintenance eventually leads to sufficient damage such that a trip hazard develops, creating a public safety issue. For example, in the delivery of beer kegs to hotels, restaurants, bars and nightclubs, the use of a buffer bag to absorb the impact energy of a falling cask is often ineffective, resulting in clearly recognisable cracking patterns in the flags. This paper will describe the crack patterns that arise from cask impact loading on pavements. It will outline how the addition of macro polypropylene or steel fibres into the concrete mix used for paving flags affects the impact response. The extent to which the fibres provide residual post-cracking strength to resist the subsequent vehicle or other loading will also be discussed. Further, a yield-line analysis will reveal the reduced dependency on the contribution of the subgrade to the response when the ductile behaviour provided by the fibres is taken into account.
Improving the impact resistance of masonry parapet walls
Authors: Hobbs B. , Gilbert M. , Molyneaux T. , Newton P. , Beattie G. , Burnett S.
Published: January 2009

In the UK and other countries roadside masonry parapet walls are commonplace. Such walls were, however, generally not designed from the outset to resist out-of-plane impact loadings from highway vehicles. The consequences of an impact can obviously be severe, particularly in the case of railway overbridges. Following a programme of experimental impact tests performed in the 1990s on unreinforced masonry walls, this paper describes an investigation of the performance of reinforced masonry walls, tested under carefully controlled conditions in the laboratory. A total of 17 tests were performed on unreinforced and reinforced walls. The reinforced walls incorporated either bed joint reinforcement or one of two different types of drilled-in reinforcement. Whereas the bed-joint reinforcement was found to be largely ineffectual, the drilled-in reinforcing systems were found to be capable of enhancing the ability of plain masonry walls to resist impacts, ensuring a ductile response to the applied transient loading. The effect of drilled-in reinforcement on the resistance of walls with low-strength mortar was found to be particularly dramatic, changing the response from that of penetration and disintegration of the masonry to ductile behaviour, with the integrity of the wall maintained and only minimal wall displacement.