Arhivske vijesti o pučkoj drami u srednjoj Dalmaciji

© 2017 Association for Computing Machinery. Context: The research literature on software development projects usually assumes that effort is a good proxy for cost. Practice, however, suggests that there are circumstances in which costs and effort should be distinguished. Objectives: We determine similarities and differences between size, effort, cost, duration, and number of defects of software projects. Method: We compare two established repositories (ISBSG and EBSPM) comprising almost 700 projects from industry. Results: We demonstrate a (log)-linear relation between cost on the one hand, and size, duration and number of defects on the other. This justifies conducting linear regression for cost. We establish that ISBSG is substantially different from EBSPM, in terms of cost (cheaper) and duration (faster), and the relation between cost and effort. We show that while in ISBSG effort is the most important cost factor, this is not the case in other repositories, such as EBSPM in which size is the dominant factor. Conclusion: Practitioners and researchers alike should be cautious when drawing conclusions from a single repository

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Senescent cells evade immune clearance via HLA-E-mediated NK and CD8(+) T cell inhibition

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with the inhibitory receptor NKG2A expressed by NK and highly differentiated CD8 + T cells to inhibit immune responses against senescent cells. HLA-E expression is induced by senescence-associated secretary phenotype-related pro-inflammatory cytokines, and is regulated by p38 MAP kinase signalling in vitro. Consistently, HLA-E expression is increased on senescent cells in human skin sections from old individuals, when compared with those from young, and in human melanocytic nevi relative to normal skin. Lastly, blocking the interaction between HLA-E and NKG2A boosts immune responses against senescent cells in vitro. We thus propose that increased HLA-E expression contributes to persistence of senescent cells in tissues, thereby suggesting a new strategy for eliminating senescent cells during ageing

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

The effects of upper limb loading on spinal shrinkage during treadmill walking

Everyday activities such as walking either loaded or unloaded may elicit spinal shrinkage in an order of magnitude that has been related to lower back pain. The present study aims to compare the effects of unloaded treadmill walking with walking carrying loads representing everyday shopping tasks. Walking tasks were performed on 7 healthy males, consisting of unloaded walking and walking carrying 7.5% and 15% of body weight. Motion analysis was used to track four reflective markers at 100Hz, dividing the spine into three segments and static data was collected in 5 minute intervals over a 30 minute period. Total spine and segment length changes were compared to original length in the sagittal plane and the effects of load, time and their interaction were analysed using ANOVA. Total spinal length and lumbar segment decreased with respect to time (p < 0.001). Load affected the percentage length change at each spinal segment (p < 0.005), with the lumbar segment showing greatest height loss at the highest load. Inter-segmental variations in length resulted in the non-significant effect of load on the percentage length change of the total spine (P = 0.263). The upper and lower thoracic segments showed greater anterior lean with the heavier loads (p = 0.000) and the lumbar segment showed the opposite trend (p = 0.000). Results suggest that the body adopts less anterior lean with an immediate load bearing demand, to decrease the flexion moment arm of the load about the lumbar spine and thus decrease the necessary extension moment generated by the spinal extensors for spinal stability. Further postural alteration in the same direction is observed with prolonged loading. In combination with lumbar spinal shrinkage, such postural changes are likely to increase the loading on the facet joints with potential deleterious consequences for low back pai