Testing Cluster Structure of Graphs

We study the problem of recognizing the cluster structure of a graph in the framework of property testing in the bounded degree model. Given a parameter $\varepsilon$, a $d$-bounded degree graph is defined to be $(k, \phi)$-clusterable, if it can be partitioned into no more than $k$ parts, such that the (inner) conductance of the induced subgraph on each part is at least $\phi$ and the (outer) conductance of each part is at most $c_{d,k}\varepsilon^4\phi^2$, where $c_{d,k}$ depends only on $d,k$. Our main result is a sublinear algorithm with the running time $\widetilde{O}(\sqrt{n}\cdot\mathrm{poly}(\phi,k,1/\varepsilon))$ that takes as input a graph with maximum degree bounded by $d$, parameters $k$, $\phi$, $\varepsilon$, and with probability at least $\frac23$, accepts the graph if it is $(k,\phi)$-clusterable and rejects the graph if it is $\varepsilon$-far from $(k, \phi^*)$-clusterable for $\phi^* = c'_{d,k}\frac{\phi^2 \varepsilon^4}{\log n}$, where $c'_{d,k}$ depends only on $d,k$. By the lower bound of $\Omega(\sqrt{n})$ on the number of queries needed for testing graph expansion, which corresponds to $k=1$ in our problem, our algorithm is asymptotically optimal up to polylogarithmic factors.Comment: Full version of STOC 201

THE DIABETIC FOOT: RELEVANCE OF ENDOTHELIAL PROGENITOR CELLS AS A PROGNOSTIC MARKER OF MORTALITY AND DISEASE PROGRESSION.

The World Health Organization estimated that the incidence of the diabetes is projected to rise from 120 million in 1996 to 366 million in 2030. Diabetes mellitus refers to a metabolic disorder of multiple etiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The effects of diabetes mellitus include long\u2013term damage, dysfunction and failure of various organs. Nowadays, the main issues for diabetic patients are no longer those associated with survival but those associated with the chronic complications of the diabetes. In this context, diabetic foot ulcers represent a serious medical and socio-economic issue worldwide. To date, the best predictors of clinical outcomes are the presence or the absence of ischemia, infection, footwear, pressure relief, and overall glycaemic control. None of them, however, reflects the activity of endogenous repair mechanisms. Endothelial progenitor cell (EPCs) availability and functionality are relevant to vascular repair. It was demonstrated in patients with diabetes, the availability of EPCs is reduced. Different mechanisms may potentially be involved, including impaired mobilization, proliferation, and apoptosis.. Based on this consideration, the goal of my thesis is to determine the additive value of circulating EPCs in predicting major end-points such as mortality, amputation and post-angioplasty restenosis in a cohort of 120 type 2 diabetic patients with Critical Limb Ischemia (CLI). Moreover, we aimed to obtain mechanistic insights into diabetic progenitor cells impairment and to provide the first characterization of the EPC-associated miRNA with special respect to those potentially involved in the control of angiogenesis. To perform functional and molecular analysis normal criteria were not available so we decided to include in the study two different control groups: a groups of not diabetic CLI subjects and a group of healthy volunteer. To assess the first objective of this project we have to wait the end of 12 months follow-up (FU) so we reported an ad interim analysis of the data. To date, about 60% of patients have reached one year FU visit and we have registered 37 restenosis, 10 major amputations and 7 death events. We did not observe any statistical difference in the number of antigenically defined EPCs between complicated (with at least one event) and not complicated (no event) diabetic patients. Also the migration capacity analysis did not show difference between the two groups. Interestingly, our preliminary data showed a significant increase in the basal migration of EPC in patients with event compared with patients with no event, so we propose that the unspecific motility associated with altered directed migration may be indicative of the incapacity of the cells to find their way to injured tissues thereby compromising the healing process. This preliminary finding need to be confirmed after the end of the study. Second, to assess the other objective of the study we analyzed the diabetic EPC characteristics and functionality. We first measured by flow cytometry the percentage of antigenically-selected MNCs subpopulations with pro-angiogenic potential in all of the three groups of enrolled subject. We observed a decrease in CD34pos and EPCs (CD45dim,CD34pos,CXCR4pos,KDRpos) in ischemic patients as compared to healthy volunteer. Unexpectedly however, diabetic patients showed a higher percentage of progenitor cells compared with non diabetic controls. Functionally, migration assay showed an impairment of cell motility in chronic limb ischemic patients with or without diabetes compared to healthy subjects. Migration assay results showed an enrichment of EPCs in the controls only; these data are in line with those previously published on an altered migratory function of EPCs from diabetic patients. Mechanisms underlying the reduction of EPCs in diabetes are largely unknown. Weak bone marrow mobilization, impaired peripheral differentiation, and short survival in peripheral blood are all candidates and we therefore attempted to investigate the mechanisms involved in this impairment. Recently, miRNAs have been shown to regulate EC functions, including proliferation, migration and assembling in branched networks. To this aim, we performed a preliminary screening on EPCs from the patients enrolled and demonstrated that diabetes induces specific microRNAs de-regulation. Next, we selected two miRNAs, mir-15a and mir-16 based on their already known role in controlling migratory and apoptotic mechanisms in cancer. To investigate the role of mir-15a and mir-16, we transfected these miRNAs into healthy EPCs. We then analyzed cell functionality in migration and angiogenic assays and we observed that only co-expression of mir-15a/16 blocks EPCs migration and induce apoptosis. Next, we investigated if down-regulation of mir-15a/16 could restore diabetic EPC migratory ability. We observed that inhibition of mir-15a/16 recover FBS and SDF-1 induced migration in diabetic EPCs but no effect was observed in apoptotic assay. Bionformatic analyses predict BCL2, VEGFA and AKT3 to be target genes of miRNA-15a and -16, which support an anti-angiogenic and pro-apoptotic role of these miRNAs. In diabetic EPCs and mir over-expressing EPCs, we found a down-regulation of AKT3, a protein involved in many EPCs functions like cell cycle progression, migration and survival. This study demonstrates, for the first time, that the spontaneous migration ability of a well antigenically characterized MNCs subpopulation of cells with EPC phenotype is significantly increased in diabetic patients that manifest at least one major adverse event (restenosis, amputation, death). This is the first evidence generated in a clinical trial that EPC migration could be used as prognostic marker for diabetic vascular complications. At the end of the study, the analysis of the follow up data generated on the entire patient cohort will enable us to generate crucial data on the a new EPC-associated risk for diabetic CLI patients to develop life-threatening vascular complications. Second, in this work we show for the first time that mir-15a and mir-16 are key regulator of diabetic EPCs pro-angiogenic function. In the future we want to deepen the role of microRNA in diabetic dysfunction because we know that miRNAs have tremendous therapeutic potential for the treatment of vascular diseases associated with aberrant pathological angiogenesis. In conclusion, EPCs have recently generated considerable attention as potential novel prognostic biomarkers for vascular integrity, and therapeutic clinical approaches using these cells are ongoing. Although the role of EPCs in these processes is well established, the challenge for the next decade is to identify and evaluate methods that increase EPC homing and incorporation, thereby enabling targeted delivery of EPCs to a site of interest. This goal might be achieved through the continued characterization of EPCs in animals and humans, coupled with investigations of the long-term potential of EPCs in vivo

PlGFMMP9-engineered iPS cells supported on a PEGfibrinogen hydrogel scaffold possess an enhanced capacity to repair damaged myocardium

Cell-based regenerative therapies are significantly improved by engineering allografts to express factors that increase vascularization and engraftment, such as placental growth factor (PlGF) and matrix metalloproteinase 9 (MMP9). Moreover, the seeding of therapeutic cells onto a suitable scaffold is of utmost importance for tissue regeneration. On these premises, we sought to assess the reparative potential of induced pluripotent stem (iPS) cells bioengineered to secrete PlGF or MMP9 and delivered to infarcted myocardium upon a poly(ethylene glycol)-fibrinogen scaffold. When assessing optimal stiffness of the PEG-fibrinogen (PF) scaffold, we found that the appearance of contracting cells after cardiogenic induction was accelerated on the support designed with an intermediate stiffness. Revascularization and hemodynamic parameters of infarcted mouse heart were significantly improved by injection into the infarct of this optimized PF scaffold seeded with both MiPS (iPS cells engineered to secrete MMP9) and PiPS (iPS cells engineered to secrete PlGF) cells as compared with nonengineered cells or PF alone. Importantly, allograft-derived cells and host myocardium were functionally integrated. Therefore, survival and integration of allografts in the ischemic heart can be significantly improved with the use of therapeutic cells bioengineered to secrete MMP9 and PlGF and encapsulated within an injectable PF hydrogel having an optimized stiffness

Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes

This study was funded by the Sars Centre core budget to M. Adamska. Sequencing was performed at the Norwegian High Throughput Sequencing Centre funded by the Norwegian Research Council. O.M.R. and D.E.K.F. acknowledge support from the BBSRC and the School of Biology, University of St Andrews.Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors1,2,3,4, including homeobox genes belonging to the Antennapedia (ANTP) class5,6, which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queenslandica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians5. It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians5,7. On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis)8. Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis8, and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.PostprintPeer reviewe

Optimization of a stand - alone renewable energy system for a small load requirement

Optimization of a stand-alone Renewable Energy (RE) system involves selecting the best RE resources and components, and sizing the system accordingly to get the most efficient and cost-effective solution. Design and optimization of an RE power system to serve the lighting in a University of the South Pacific car park was carried out using HOMER software and compared to manual calculations. Resource analysis showed that on average the site received 3.8 kWh m−2 day−1 of solar energy, with 1,387 full sun hours annually. Monthly average wind speed of 3.88 m s−1 at 10 m above ground level extrapolated to 15 m (the hub height of the wind turbine) resulted in an average wind speed of 4 m s−1, with power density of 70 Wm−2. With this wind resource, a Whisper 100 wind turbine would be in operation for approximately 50 % of the time in the year. The complementary nature of solar and wind resources showed good potential for a solar-wind hybrid system. In this study three possible systems—a PV system, a wind power system, and a hybrid power system (PV-wind)—were analyzed. It was found that a hybrid system is the best and most cost-effective option, as it is able to provide reliable power whilst minimizing the need for battery storage compared to a single RE power system. The optimum system comprised 0.270 kWp PV combined with a 900 W Whisper wind turbine with total battery storage capacity of 440 Ah at 12 V. Manual calculations yielded results similar to the HOMER simulations

Allelic Variation of Wheat Flour Allergens in a Collection of Wheat Genotypes

Wheat is the most widely grown crop in the world and provides 20% of the daily protein and food calories for 4.5 billion people. Together with rice, it is the most important food crop in the developing world. In the last decades, various symptoms have been recorded across the population due to the consumption of wheat products, also summarized as "wheat allergy." Wheat allergy is usually reported as a food allergy but can also be a contact allergy as a result of exposure to wheat. Several important wheat allergens have been characterized in the last years through biochemical, immunological, and molecular biological techniques. In the present work, the identification of allelic variation of genes involved in wheat allergy was reported. A collection of wheat genotypes was screened in order to identify new alleles. A total of 14 new alleles were identified forprofilin, triosephosphate-isomerase, dehydrin, glyceraldehyde-3-phosphate-dehydrogenase,α/βgliadin, GluB3-23,andGlutathione transferaseallergen genes (located on chromosomes 1B, 3B, 6A, and homoelogous groups 5 and 7), potentially related to a minor allergenicity and useful in breeding programs

Laser-induced graphene from paper for non-enzymatic uric acid electrochemical sensing in urine

This work was developed within the scope of project i3N (LA/P/0037/2020. I.P. N. F. Santos thanks i3N for the BPD Grant BPD/UI96/5177/2020. S. O. Pereira thanks i3N for the BPD Grant BPD/UI96/5808/2017. The authors also thank Jonas Deuermeier for the XPS measurements. Publisher Copyright: © 2022 Elsevier LtdLaser-induced graphene from paper (paper-LIG) was applied in non-enzymatic electrochemical sensing of uric acid (UA) in human urine. Paper-LIG was formed by CO2 laser modification of paper into a 3D graphene arrangement. Kinetic analysis of paper-LIG electrodes returned effective heterogeneous electron transfer standard rate constants of 1.4 × 10−3 cm s−1 and 7.8 × 10−4 cm s−1 for [Ru(NH3)6]2+/3+ and [Fe(CN)6]4−/3− redox probes, respectively. These electrodes were able to detect and quantify uric acid in PBS within the 10–300 μM range at pH between 5.6 and 7.4. At pH 7.4, a linear response (R2 = 0.999) from 10 to 250 μM was achieved, with a limit of detection of 3.97 μM and a sensitivity of 0.363 μA cm−2 μM−1. Paper-LIG electrodes denoted adequate selectivity in synthetic urine as well as in ascorbic acid (AA) and dopamine (DA)-containing electrolytes. Determination of urinary UA content in human samples returned a concentration of c.a. 1.8–1.9 mM, within the range for healthy individuals. Recoveries of samples spiked with 50 and 100 μM UA were 100.6% and 95.4%, respectively, with satisfactory reproducibility and stability. These cheap, lightweight, flexible, and eco-friendly paper-LIG biosensors for non-enzymatic quantification of UA in human urine pave the way to widespread application in the detection of other important biomarkers.publishersversionpublishe

Analytically solvable potentials for γ\gamma-unstable nuclei

An analytical solution of the collective Bohr equation with a Coulomb-like and a Kratzer-like $\gamma-$unstable potential in quadrupole deformation space is presented. Eigenvalues and eigenfunctions are given in closed form and transition rates are calculated for the two cases. The corresponding SO(2,1)$\times$SO(5) algebraic structure is discussed.Comment: 9 pages, 4 figures in one .ps fil

Fear of covid-19 for individuals and family members: Indications from the national cross-sectional study of the epicovid19 web-based survey

The study analyzed the association of the fear of contagion for oneself and for family members (FMs) during the first wave of the COVID-19 pandemic, with demographic and socioeconomic status (SES) and health factors. The study was performed within the EPICOVID19 web-based Italian survey, involving adults from April–June 2020. Out of 207,341 respondents, 95.9% completed the questionnaire (60% women with an average age of 47.3 vs. 48.9 years among men). The association between fear and demographic and SES characteristics, contacts with COVID-19 cases, nasopharyngeal swab, self-perceived health, flu vaccination, chronic diseases and specific symptoms was analyzed by logistic regression model; odds ratios adjusted for sex, age, education and occupation were calculated (aORs). Fear for FMs prevailed over fear for oneself and was higher among women than men. Fear for oneself decreased with higher levels of education and in those who perceived good health. Among those vaccinated for the flu, 40.8% responded they had feelings of fear for themselves vs. 34.2% of the not vaccinated. Fear increased when diseases were declared and it was higher when associated with symptoms such as chest pain, olfactory/taste disorders, heart palpitations (aORs > 1.5), lung or kidney diseases, hypertension, depression and/or anxiety. Trends in fear by region showed the highest percentage of positive responses in the southern regions. The knowledge gained from these results should be used to produce tailored messages and shared public health decisions