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Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer

Journal of Cancer Therapy 2014年第14期5卷 1354-1361页

作者： Annika Gustafsson Asting Kristina K.Lagerstedt Erik Kristiansson Christina Lonnroth marianne andersson Elham Rekabdar Elisabeth Hansson Ulf Kressner Fredrik Enlund Kent Lundholm Department of Surgery Surgical Metabolic Research LaboratorySahlgrenska University HospitalUniversity of GothenburgGothenburgSweden Department of Mathematical Sciences Mathematical StatisticsChalmers University of TechnologyGothenburgSweden Genomics Core Facility Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden Department of Surgery Uddevalla HospitalUddevallaSweden Department of Surgery Danderyds HospitalStockholmSweden Department of Surgery South HospitalStockholmSweden Department of Clinical Chemistry Sahlgrenska University HospitalUniversity of GothenburgGothenburgSweden

Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer;These DNA alterations may have? been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.

关键词： Copy Number Variation DNA Array CGH Colorectal Cancer

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Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer

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Journal of Cancer Therapy（癌症治疗） 2014年第14期

作者： Annika Gustafsson Asting Kristina K. Lagerstedt Eri kKristiansson Christina Lönnroth marianne andersson Elham Rekabdar Elisabeth Hansson Ulf Kressner Fredrik Enlund Kent Lundholm

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Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention

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World Journal of Gastroenterology 2010年第17期16卷 2094-2099页

作者： Roland andersson Department of Surgery Clinical Sciences LundLund University Lund University Hospital SE-221 85 LundSweden

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem,with a mortality rate in the range of 30%-40%.The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical *** mediators and pathophysiological pathways are involved during the different phases of ALI and *** initial exudative phase is characterized by diffuse alveolar damage,microvascular injury and influx of inflammatory *** phase is followed by a fibro-proliferative phase with lung repair,type Ⅱ pneumocyte hypoplasia and proliferation of *** derived from polymorphonuclear neutrophils,various pro-inflammatory mediators,and phospholipases are all involved,among *** factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric *** is a lack of complete understanding of the underlying mechanisms,and by improving our knowledge,novel tools for prevention and intervention may be developed,thus contributing to improved outcome.

关键词： Acute lung injury Acute respiratory distress syndrome Acute pancreatitis Etiology Pathophysiology

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Pancreatic function,quality of life and costs at long-term follow-up after acute pancreatitis

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World Journal of Gastroenterology 2010年第39期16卷 4944-4951页

作者： Bodil andersson Marie-Louise Pendse Roland andersson Department of Surgery Clinical Siences LundLund University Lund University Hospital

AIM:To evaluate long-term endocrine and exocrine pancreatic function,quality of life and health care costs after mild acute pancreatitis and severe acute pancreatitis(SAP).METHODS:Patients prospectively included in 2001-2005 were followed-up after 42(36-53)*** function was evaluated with laboratory tests,the oral glucose tolerance test(OGTT),fecal elastase-1 and a *** Form(SF)-36,was ***:Fourteen patients with a history of SAP and 26 with mild acute pancreatitis were *** glucose after OGTT was higher after SAP(9.2 mmol/L vs 7.0 mmol/L,P=0.044).Diabetes mellitus or impaired glucose tolerance in fasting plasma glucose and/or 120 min plasma glucose were more common in SAP patients(11/14 vs 11/25,P=0.037).Sick leave,time until the patients could take up recreational activities and time until they had recovered were all longer after SAP(P <0.001).No significant differences in SF-36 were seen between the groups,or when comparing with age and gender matched reference *** hospital costs,including primary care,follow-up and treatment of complications,were higher after SAP(median€16572 vs €5000,P<0.001).CONCLUSION:Endocrine pancreatic function was affected,especially after severe *** requires greater resource use with long recovery,but most patients regained a good quality of life.

关键词： Acute pancreatitis Endocrine function Exocrine function Quality of life Cost

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Tissue factor in predicted severe acute pancreatitis

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World Journal of Gastroenterology 2010年第48期16卷 6128-6134页

作者： Ellen andersson Jakob Axelsson Gunilla Eckerwall Daniel Ansari Roland andersson Department of Surgery Clinical Sciences LundLund University Lund University Hospital

AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation Ⅱ score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6.

关键词： Acute pancreatitis Coagulation Prediction of severity Tissue factor

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Deformation,fragmentation and acceleration of a controlled fragmentation charge casing

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Defence Technology（防务技术） 2019年第5期15卷 786-795页

作者： Andreas Helte Olof andersson Patrik Lundberg FOI Defence and SecuritySystems and Technology

Two different finite element software,LS-DYNA and Impetus,have been evaluated to test their ability to predict the deformation,fragmentation and acceleration of a controlled fragmentation charge *** general-purpose program LS-DYNA was used with a multi-material ALE formulation and a masspreserving erosion criterion coupled to a Johnson-Cook fracture *** the Impetus simulations,a third order Lagrangian element formulation was used for the casing and a node-splitting element erosion treatment coupled to a Cockcroft-Latham failure criterion was used to describe casing *** high-explosive gases were described by a discrete particle *** order to acquire data to validate our computational tools and constitutive models,a series of experiments have been performed using a laboratory charge with an internal grooved *** the test series,the charge geometry was fixed except that the groove depth were varied from very shallow to very deep resulting in different deformation patterns,fracture modes and terminal *** diagnostic tools captured the different stages of the expansion and fragmentation of the casing.A high-speed framing camera depicted the deformation pattern before fragmentation and was used to determine the moment when the casing *** different complementary techniques were used to follow the acceleration of the fragments;a Photon Doppler velocimetry to determine the initial acceleration of the casing,double exposed radiographs to estimate the fragment velocity after break-up and a high-speed video to determine the terminal velocity of the fragment after leaving the *** addition,the fragments were soft recovered in a set of sawdust pit tests and their final shape and weight were measured.A SEM was used to characterise the fracture surfaces and to determine the modus of fracture(tensile or shear failure).Comparisons to experiments show that both software can predict the change in deformation behaviour

关键词： Controlled fragmentation Fracture mechanics LS-DYNA Impetus

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Micromechanical modeling of polycrystalline high manganese austenitic steel subjected to abrasive contact

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Friction 2020年第3期8卷 626-642页

作者： Matti LINDROOS Anssi LA UKK ANEN Tom andersson VTT Lifecycle Solutions Tampere 33720Finland

This study focuses on microstructural and micromechanical modeling of abrasive sliding contacts of wear-resistant Hadfield steel.3 D finite element representation of the microstructure was employed with a crystal plasticity model including dislocation slip,deformation twinning,and their *** results showed that deformation twinning interacting with dislocations had a key role in the surface hardening of the material,and it was also important for the early hardening process of the sub-surface grains beyond the heavily distorted surface *** effects of grain orientation and microstructural features were discussed and analyzed according to the micromechanical model to give a perspective to the anisotropy of the material and the feasibility of using micromechanics in virtual material design.

关键词： crystal plasticity micromechanical modeling of abrasion austenitic manganese steel deformation twinning

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Effective and Sustainable Flood and Landslide Risk Reduction Measures:An Investigation of Two Assessment Frameworks

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International Journal of Disaster Risk Science 2016年第4期7卷 374-392页

作者： Yvonne andersson-Skld Lars Nyberg Swedish National Road and Transport Research Institute(VTI) Centre for Climate and Safety Karlstad University

Natural events such as floods and landslides can have severe *** risks are expected to increase,both as a consequence of climate change and due to increased vulnerabilities,especially in urban *** preventive measures are often cost-effective,some measures are beneficial to certain values,while some may have negative impacts on other *** aim of the study presented here was to investigate two frameworks used for assessing the effectiveness and sustainability of physical and nonphysical flood and landslide risk reduction *** study is based on literature,available information from authorities and municipalities,expert knowledge and experience,and stakeholder views and *** results indicate that the risks for suboptimization or maladaptation are reduced if many aspects are included and a broad spectrum of stakeholders are *** sustamability assessment tools applied here can contribute to a more transparent and sustainable risk management process by assessing strategies and interventions with respect to both short- and long-term perspectives,including local impacts and wider environmental impacts caused by climate change,for *** tools can also cover social and economic *** assessment tools provide checklists that can support decision processes,thus allowing for more transparent decisions.

关键词： Flood risk Landslide risk Risk reduction measures Sustainability assessment tools Sweden

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Intervention on toll-like receptors in pancreatic cancer

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World Journal of Gastroenterology 2014年第19期20卷 5808-5817页

作者： Juan Vaz Roland andersson Department of Surgery Clinical Sciences LundSkne University Hospital LundLund UniversitySE-221 85 LundSweden

Pancreatic ductal adenocarcinoma(PDA)is a devastating disease with pronounced morbidity and a high mortality *** available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success *** stimulation of the immune system in murine PDA models has revealed some promising *** receptors(TLRs)are pillars of the immune system that have been linked to several forms of malignancy,including lung,breast and colon *** humans,TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines,whereas they are not expressed in the normal *** the present review,we explore the current knowledge concerning the role of different TLRs associated to *** if almost all known TLRs are expressed in the pancreatic cancer microenvironment,there are only five TLRs suggested as possible therapeutic *** data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as *** adjuvant *** elucidation of the role of TLR3 in PDA is only in its initial *** inhibition/blockage of TLR4-related pathways has shown some promising effects,but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic ***,TLR7 antagonists seem to be potential candidates for *** of their potential in immunotherapies,all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.

关键词： Pancreatic cancer Pathophysiological mechanism Toll-like receptor Intervention Adjuvant therapy

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Influence of confining prestress on the transition from interface defeat topenetration in ceramic targets

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Defence Technology（防务技术） 2016年第3期12卷 263-271页

作者： Patrik LUNDBERG RenéRENSTROM Olof andersson FOI Swedish Defence Research AgencySE-164 90 StockholmSweden

Replica scaled impact experiments with unconfined ceramic targets have shown that the transition velocity,i.e.,the impact velocity at which interface defeat ceases and ceramic penetration occurs,decreased as the length scale increased.A possible explanation of how this scale effect is related to the formation of a cone crack in the ceramic has been presented by the authors in an earlier ***,the influence of confinement and prestress on cone cracking and transition velocity is *** hypothesis is that prestress will suppress the formation and growth of the cone crack by lowering the driving stress.A set of impact experiments has been performed in which the transition velocity for four different levels of prestress has been *** transition velocities as a function of the level of confining prestress is compared to an analytical model for the influence of prestress on the formation and extension of the cone crack in the ceramic *** experiments and model indicate that prestress has a strong influence on the transition from interface defeat to penetration,although the model underestimates the influence of prestress.

关键词： Impact Ceramic Armour Interface defeat Dwell Confinement Prestress

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