Faster and Simpler Distributed Algorithms for Testing and Correcting Graph Properties in the CONGEST-Model

In this paper we present distributed testing algorithms of graph properties in the CONGEST-model [Censor-Hillel et al. 2016]. We present one-sided error testing algorithms in the general graph model. We first describe a general procedure for converting $\epsilon$-testers with a number of rounds $f(D)$, where $D$ denotes the diameter of the graph, to $O((\log n)/\epsilon)+f((\log n)/\epsilon)$ rounds, where $n$ is the number of processors of the network. We then apply this procedure to obtain an optimal tester, in terms of $n$, for testing bipartiteness, whose round complexity is $O(\epsilon^{-1}\log n)$, which improves over the $poly(\epsilon^{-1} \log n)$-round algorithm by Censor-Hillel et al. (DISC 2016). Moreover, for cycle-freeness, we obtain a \emph{corrector} of the graph that locally corrects the graph so that the corrected graph is acyclic. Note that, unlike a tester, a corrector needs to mend the graph in many places in the case that the graph is far from having the property. In the second part of the paper we design algorithms for testing whether the network is $H$-free for any connected $H$ of size up to four with round complexity of $O(\epsilon^{-1})$. This improves over the $O(\epsilon^{-2})$-round algorithms for testing triangle freeness by Censor-Hillel et al. (DISC 2016) and for testing excluded graphs of size $4$ by Fraigniaud et al. (DISC 2016). In the last part we generalize the global tester by Iwama and Yoshida (ITCS 2014) of testing $k$-path freeness to testing the exclusion of any tree of order $k$. We then show how to simulate this algorithm in the CONGEST-model in $O(k^{k^2+1}\cdot\epsilon^{-k})$ rounds

Three Notes on Distributed Property Testing

In this paper we present distributed property-testing algorithms for graph properties in the CONGEST model, with emphasis on testing subgraph-freeness. Testing a graph property P means distinguishing graphs G = (V,E) having property P from graphs that are epsilon-far from having it, meaning that epsilon|E| edges must be added or removed from G to obtain a graph satisfying P. We present a series of results, including: - Testing H-freeness in O(1/epsilon) rounds, for any constant-sized graph H containing an edge (u,v) such that any cycle in H contain either u or v (or both). This includes all connected graphs over five vertices except K_5. For triangles, we can do even better when epsilon is not too small. - A deterministic CONGEST protocol determining whether a graph contains a given tree as a subgraph in constant time. - For cliques K_s with s >= 5, we show that K_s-freeness can be tested in O(m^(1/2-1/(s-2)) epsilon^(-1/2-1/(s-2))) rounds, where m is the number of edges in the network graph. - We describe a general procedure for converting epsilon-testers with f(D) rounds, where D denotes the diameter of the graph, to work in O((log n)/epsilon)+f((log n)/epsilon) rounds, where n is the number of processors of the network. We then apply this procedure to obtain an epsilon-tester for testing whether a graph is bipartite and testing whether a graph is cycle-free. Moreover, for cycle-freeness, we obtain a corrector of the graph that locally corrects the graph so that the corrected graph is acyclic. Note that, unlike a tester, a corrector needs to mend the graph in many places in the case that the graph is far from having the property. These protocols extend and improve previous results of [Censor-Hillel et al. 2016] and [Fraigniaud et al. 2016]

Human Muscle Progenitor Cells Overexpressing Neurotrophic Factors Improve Neuronal Regeneration in a Sciatic Nerve Injury Mouse Model

The peripheral nervous system has an intrinsic ability to regenerate after injury. However, this process is slow, incomplete, and often accompanied by disturbing motor and sensory consequences. Sciatic nerve injury (SNI), which is the most common model for studying peripheral nerve injury, is characterized by damage to both motor and sensory fibers. The main goal of this study is to examine the feasibility of administration of human muscle progenitor cells (hMPCs) overexpressing neurotrophic factor (NTF) genes, known to protect peripheral neurons and enhance axon regeneration and functional recovery, to ameliorate motoric and sensory deficits in SNI mouse model. To this end, hMPCs were isolated from a human muscle biopsy, and manipulated to ectopically express brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1). These hMPC-NTF were transplanted into the gastrocnemius muscle of mice after SNI, and motor and sensory functions of the mice were assessed using the CatWalk XT system and the hot plate test. ELISA analysis showed that genetically manipulated hMPC-NTF express significant amounts of BDNF, GDNF, VEGF, or IGF-1. Transplantation of 3 × 106 hMPC-NTF was shown to improve motor function and gait pattern in mice following SNI surgery, as indicated by the CatWalk XT system 7 days post-surgery. Moreover, using the hot-plate test, performed 6 days after surgery, the treated mice showed less sensory deficits, indicating a palliative effect of the treatment. ELISA analysis following transplantation demonstrated increased NTF expression levels in the gastrocnemius muscle of the treated mice, reinforcing the hypothesis that the observed positive effect was due to the transplantation of the genetically manipulated hMPC-NTF. These results show that genetically modified hMPC can alleviate both motoric and sensory deficits of SNI. The use of hMPC-NTF demonstrates the feasibility of a treatment paradigm, which may lead to rapid, high-quality healing of damaged peripheral nerves due to administration of hMPC. Our approach suggests a possible clinical application for the treatment of peripheral nerve injury

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been employed in the past decade as therapeutic agents in various diseases, including central nervous system (CNS) disorders. We currently aimed to use MSC-EVs as potential treatment for cerebral small vessel disease (CSVD), a complex disorder with a variety of manifestations. MSC-EVs were intranasally administrated to salt-sensitive hypertension prone SBH/y rats that were DOCA-salt loaded (SBH/y-DS), which we have previously shown is a model of CSVD. MSC-EVs accumulated within brain lesion sites of SBH/y-DS. An in vitro model of an inflammatory environment in the brain demonstrated anti-inflammatory properties of MSC-EVs. Following in vivo MSC-EV treatment, gene set enrichment analysis (GSEA) of SBH/y-DS cortices revealed downregulation of immune system response-related gene sets. In addition, MSC-EVs downregulated gene sets related to apoptosis, wound healing and coagulation, and upregulated gene sets associated with synaptic signaling and cognition. While no specific gene was markedly altered upon treatment, the synergistic effect of all gene alternations was sufficient to increase animal survival and improve the neurological state of affected SBH/y-DS rats. Our data suggest MSC-EVs act as microenvironment modulators, through various molecular pathways. We conclude that MSC-EVs may serve as beneficial therapeutic measure for multifactorial disorders, such as CSVD

A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress

Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive ‘Sabra’ hypertension-prone rats (SBH/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics