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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Boström, Ola, 1963, et al.
(författare)
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Prediction of neck injuries in rear impacts based on accident data and simulations
- 1997
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Ingår i: PROCEEDINGS OF THE 1997 INTERNATIONAL IRCOBI CONFERENCE ON THE BIOMECHANICS OF IMPACT. ; , s. 251-264
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Konferensbidrag (refereegranskat)abstract
- Whiplash associated disorders, occurring in car accidents, are an increasing problem worldwide. According to real-life data from police records, the struck car's velocity change (delta V) and occupant gender are two of the most important factors related to Abbreviated Injury Scale (AIS) 1 neck injuries. In this study, a new rear-impact ranking of cars based on 4432 police reported accidents is presented. The ranking concerns the relative neck injury risk and compensates for the influences of car weight and gender. Moreover, some important factors influencing the risk of AIS 1 neck injury are proposed. These include: the stiffness, damping and yielding characteristics of the seat back, the muscle response of the occupant, and the delta V of the struck car and acceleration pulse. Using a mathematical model it is shown that the influence from these factors can be explained by a recently proposed neck injury criterion (NIC). This criterion is based on the neck motion at the passage of full neck retraction. The NIC, based on a number of volunteer tests, is analysed and validated. The consequence of injury outcome of an observed overall seat back stiffening is also discussed. In conclusion, for delta V below 20 km/h, real-life data show that the geometry of the head restraint is of minor importance. A seat back with low yielding limit or soft performance may be preferable. Moreover, the new NIC seems to be a good predictor of real-life neck injuries.
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| 4. |
- Eichberger, Arno, et al.
(författare)
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EVALUATION OF THE APPLICABILITY OF THE NECK INJURY CRITERION (NIC) IN REAR END IMPACTS ON THE BASIS OF HUMAN SUBJECT TESTS
- 1998
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Ingår i: PROCEEDINGS OF THE 1998 INTERNATIONAL IRCOBI CONFERENCE ON THE BIOMECHANICS OF IMPACT. ; , s. 321-233
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Konferensbidrag (refereegranskat)abstract
- The purpose of this investigation is to apply the neck injury criterion (NIC) Criterion to data measured in human subject tests. 70 volunteer tests and 28 cadaver tests were analyzed in order to investigate the movement of the human spine. The NIC was calculated for all these tests and compared to other data that could be of interest for neck injuries (for instance angular acceleration of the head). It is concluded that the NIC in conjunction with other parameters is a useful indicator for the prediction of neck injuries following rear end impacts.
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| 5. |
- Eichberger, Arno, et al.
(författare)
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Pressure measurements in the spinal canal of post-mortem human subjects during rear-end impact and correlation of results to the neck injury criterion.
- 2000
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Ingår i: Accident Analysis and Prevention. ; 32:2, s. 251-60
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to validate the pressure effect theory on human beings during a realistic rear-end impact and to correlate the neck injury criterion to pressure in the spinal canal. Sled experiments were performed using a test setup similar to real rear-end collisions. Test conditions were chosen based on accident statistics and recordings of real accidents. In particular, velocity change and acceleration level were reproduced similar to actual collisions. The head restraint as well as the seat back were adjusted to different positions. Two small pressure transducer were implemented to the spinal canal of postmortem human subjects and pressure measurement similar to the pig experiments (using exactly the same equipment) were performed. A total set of 21 experiments with four different subjects were performed. The subjects were additionally instrumented with triaxial accelerometers that allowed for calculation of the NIC criterion. Results showed that NIC and pressure amplitudes of the CSF correlate well and therefore NIC seems to be able to predict these amplitudes also for human beings. Conclusions whether these pressure effects induce soft tissue neck injuries or not could not be drawn and should be investigated in further research.
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| 6. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 7. |
- Törnvall, Fredrik, 1975, et al.
(författare)
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EVALUATION OF DUMMY SHOULDER KINEMATICS IN OBLIQUE FRONTAL COLLISIONS
- 2008
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Ingår i: IRCOBI. - 9783033015807 ; , s. 195-210
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Konferensbidrag (refereegranskat)abstract
- The present study evaluates shoulder kinematics of the Hybrid III and THOR NT, with the firstversion of a new shoulder design (SD-1), in 45° far-side, full frontal and 30° near-side collisions. Intotal eleven dummy tests were conducted in the three collision angles, while film and instrument datawere generated and compared with those of PMHS data from Törnvall (2008). For the 45° far-sideimpact, the THOR SD-1NT dummy retained the shoulder belt on the shoulder during on-loading, as didthe PMHSs, whereas the THOR NT did not. In the 30° near-side impact,
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