830 research outputs found
Взрывоопасность угольной пыли и метана в горном деле
Данная статья посвящена проблеме предотвращения аварий на предприятиях горнодобывающей промышленности за счёт влияния. Рассматриваются причины повышения содержания газа в горных выработках. Дана сравнительная характеристика угольной пыли и метана по их опасности. Выявлено, что угольная пыль опаснее метана. Приведены меры по профилактике аварийности на горнодобывающих предприятиях. This article is devoted to the prevention of accidents in the mining industry at the expense of influence. It discusses reasons for the increase in gas content in mine workings. The author describes comparative characteristics of coal dust and methane at their danger. It is revealed that the coal dust is more dangerous than methane. The author gives measures for the prevention of accidents at mining enterprises
A Robust Solution Procedure for Hyperelastic Solids with Large Boundary Deformation
Compressible Mooney-Rivlin theory has been used to model hyperelastic solids,
such as rubber and porous polymers, and more recently for the modeling of soft
tissues for biomedical tissues, undergoing large elastic deformations. We
propose a solution procedure for Lagrangian finite element discretization of a
static nonlinear compressible Mooney-Rivlin hyperelastic solid. We consider the
case in which the boundary condition is a large prescribed deformation, so that
mesh tangling becomes an obstacle for straightforward algorithms. Our solution
procedure involves a largely geometric procedure to untangle the mesh: solution
of a sequence of linear systems to obtain initial guesses for interior nodal
positions for which no element is inverted. After the mesh is untangled, we
take Newton iterations to converge to a mechanical equilibrium. The Newton
iterations are safeguarded by a line search similar to one used in
optimization. Our computational results indicate that the algorithm is up to 70
times faster than a straightforward Newton continuation procedure and is also
more robust (i.e., able to tolerate much larger deformations). For a few
extremely large deformations, the deformed mesh could only be computed through
the use of an expensive Newton continuation method while using a tight
convergence tolerance and taking very small steps.Comment: Revision of earlier version of paper. Submitted for publication in
Engineering with Computers on 9 September 2010. Accepted for publication on
20 May 2011. Published online 11 June 2011. The final publication is
available at http://www.springerlink.co
Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer
Background Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies
Effect of Forest Site Preparation and Livestock Grazing on Stormflow and Water Quality in the South East
The commercial forestlands of East Texas and Louisiana are the most water-efficient producing areas of the two states. Current and projected water shortages for Texas makes this water-rich area extremely important to future growth and development of Texas. However, little is known about the influence of intensive forest practices or livestock grazing on water quality, yield or site productivity in Texas. This is the only instrumented watershed study in Texas or Louisiana that is currently evaluating the influence of livestock grazing on water and the second study evaluating the impact of intensive forest practices on water.
This research is providing information that will enable forest managers, state and federal agencies to select livestock grazing and/or forest management practices that will maintain a productive forest environment and minimize off-site water quality impacts. It is imperative that if Texas in the next 30 years is: 1) to help meet the timber product demand that is projected to be placed on the Southeast, and 2) to meet the projected water shortages we need to understand the impact of intensive forest and livestock grazing practices on site productivity and water. This research is helping provide the basic information needed to manage Southeast forestlands for timber products, red meat and water.
The southern states are currently producing half of the nation's wood supply with large demands to increase timber production expected in the next 20 years. The challenge facing forestry in the South is in developing technology and management to meet this increased demand and maintain an acceptable forest environment in the face of increased taxes, rising labor, equipment and energy costs. The intensive forest management practices of harvesting and site preparation have been identified as causing potential declines in site production and as sources of nonpoint pollution. The Clean Water Act (PL 92-500 and PL 95-217) requires identification and control of silvicultural activities and livestock grazing which contribute to nonpoint source pollution. Implementation of "best management practices", either voluntary or mandatory, are the suggested means for maintaining water quality and site productivity.
Hydrologic impacts of livestock grazing result primarily from the interactions of climate, vegetation, soil, and intensity and duration of livestock use. Thus, grazing impacts will vary naturally from area to area due to the normal variability of these factors. Few studies have attempted to account for these natural variations. Documentation of the intensity and duration of livestock grazing has been poor or completely ignored in most studies.
In East Texas, the impact of livestock grazing on water quality has had no research effort. Most research regarding the impact of grazing upon water quality has been conducted outside the Southern Region and, more importantly, outside of the Gulf Coastal Plains. Because geology, soils , topography, climate, etc. are different, extensions of that research to the East Texas and Louisiana areas may be misleading
Establishment of a patient-derived orthotopic osteosarcoma mouse model
Background: Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Methods: Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. Results: A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. Conclusion: We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS
The FLASHForward Facility at DESY
The FLASHForward project at DESY is a pioneering plasma-wakefield
acceleration experiment that aims to produce, in a few centimetres of ionised
hydrogen, beams with energy of order GeV that are of quality sufficient to be
used in a free-electron laser. The plasma wave will be driven by high-current
density electron beams from the FLASH linear accelerator and will explore both
external and internal witness-beam injection techniques. The plasma is created
by ionising a gas in a gas cell with a multi-TW laser system, which can also be
used to provide optical diagnostics of the plasma and electron beams due to the
<30 fs synchronisation between the laser and the driving electron beam. The
operation parameters of the experiment are discussed, as well as the scientific
program.Comment: 19 pages, 9 figure
MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation.
Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of the early initiating steps of MYCN-driven tumor formation is still enigmatic. We performed a detailed transcriptome landscaping during murine TH-MYCN-driven neuroblastoma tumor formation at different time points. The neuroblastoma dependency factor MEIS2, together with ASCL1, was identified as a candidate tumor-initiating factor and shown to be a novel core regulatory circuit member in adrenergic neuroblastomas. Of further interest, we found a KEOPS complex member (gm6890), implicated in homologous double-strand break repair and telomere maintenance, to be strongly upregulated during tumor formation, as well as the checkpoint adaptor Claspin (CLSPN) and three chromosome 17q loci CBX2, GJC1 and LIMD2. Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma
Recommended from our members
Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored
Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer
Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies
Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas.
BACKGROUND
Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors.
METHODS
In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed.
RESULTS
Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors.
CONCLUSIONS
Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker
- …