Introducing the new paradigm of Social Dispersed Computing: Applications, Technologies and Challenges

[EN] If last decade viewed computational services as a utility then surely this decade has transformed computation into a commodity. Computation is now progressively integrated into the physical networks in a seamless way that enables cyber-physical systems (CPS) and the Internet of Things (IoT) meet their latency requirements. Similar to the concept of ¿platform as a service¿ or ¿software as a service¿, both cloudlets and fog computing have found their own use cases. Edge devices (that we call end or user devices for disambiguation) play the role of personal computers, dedicated to a user and to a set of correlated applications. In this new scenario, the boundaries between the network node, the sensor, and the actuator are blurring, driven primarily by the computation power of IoT nodes like single board computers and the smartphones. The bigger data generated in this type of networks needs clever, scalable, and possibly decentralized computing solutions that can scale independently as required. Any node can be seen as part of a graph, with the capacity to serve as a computing or network router node, or both. Complex applications can possibly be distributed over this graph or network of nodes to improve the overall performance like the amount of data processed over time. In this paper, we identify this new computing paradigm that we call Social Dispersed Computing, analyzing key themes in it that includes a new outlook on its relation to agent based applications. We architect this new paradigm by providing supportive application examples that include next generation electrical energy distribution networks, next generation mobility services for transportation, and applications for distributed analysis and identification of non-recurring traffic congestion in cities. The paper analyzes the existing computing paradigms (e.g., cloud, fog, edge, mobile edge, social, etc.), solving the ambiguity of their definitions; and analyzes and discusses the relevant foundational software technologies, the remaining challenges, and research opportunities.Garcia Valls, MS.; Dubey, A.; Botti, V. (2018). Introducing the new paradigm of Social Dispersed Computing: Applications, Technologies and Challenges. Journal of Systems Architecture. 91:83-102. https://doi.org/10.1016/j.sysarc.2018.05.007S831029

Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes

Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90β1 is a potential target for the treatment of nephropathy and renal failure in diabetes

Cuff inflation time significantly affects blood flow recorded with venous occlusion plethysmography

© 2019, The Author(s). Purpose: We tested whether the values of limb blood flow calculated with strain-gauge venous occlusion plethysmography (VOP) differ when venous occlusion is achieved by automated, or manual inflation, so providing rapid and slower inflation, respectively. Method: In 9 subjects (20–30 years), we calculated forearm blood flows (FBF) values at rest and following isometric handgrip at 70% maximum voluntary contraction (MVC) when rapid, or slower inflation was used. Result: Rapid and slower cuff inflation took 0.23 ± 0.01 (mean ± SEM) and 0.92 ± 0.02 s, respectively, reflecting the range reported in published studies. At rest, FBF calculated from the 1st cardiac cycle after rapid and slower inflation gave similar values: 10.5 ± 1.4 vs. 9.6 ± 1.3 ml dl − 1  min − 1 , respectively (P > 0.05). However, immediately post-contraction, FBF was ~ 40% lower with slower inflation: 54.6 ± 5.1 vs. 33.8 ± 4.2 ml dl − 1  min − 1 (P < 0.01). The latter value was similar to that calculated over the 3rd cardiac cycle following rapid inflation: 2nd cardiac cycle: 40.5 ± 4.5; 3rd cycle: 32.6 ± 4.5 ml dl − 1  min − 1 . Regression analyses of FBFs recorded at intervals post-contraction showed those calculated over the 1st, 2nd, or 3rd cardiac cycles with rapid inflation correlated well with those from the 1st cardiac cycle with manual inflation (r = 0.79, 0.82, 0.79; P < 0.01). However, only the slope for the 3rd cycle with rapid inflation vs. slower inflation was close to unity (2.07, 1.34, and 0.94, respectively). Conclusion: These findings confirm that the 1st cardiac cycle following venous occlusion should be used when calculating FBF using VOP and, but importantly, indicate that cuff inflation should be almost instantaneous; just ≥ 0.9 s leads to substantial underestimation, especially at high flows

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

ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4

The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation. ARF has also been linked to the DNA-damage-induced response of p53 because of its ability to inhibit murine double minute 2 (MDM2). Here, however, we provide genetic evidence for a role of ARF in nucleotide excision repair (NER) that is independent of p53. Cells lacking ARF are deficient in NER. Expression of ARF restores the repair activity, which coincides with increased expression of the damaged-DNA recognition protein xeroderma pigmentosum, complementation group C (XPC). We provide evidence that, by disrupting the interaction between E2F transcription factor 4 (E2F4) and DRTF polypeptide 1 (DP1), ARF reduces the interaction of the E2F4–p130 repressor complex with the promoter of XPC to ensure high-level expression of XPC. Together, our results point to an important ‘care-taker'-type tumour-suppression function for ARF in NER through the increased expression of XPC