Suurikokoisen kompleksisen sosiaalisen verkoston rakenne ja dynamiikka

Suurten verkostomuotoisten tietoaineistojen tutkimus on lisääntynyt valtavasti viimeisen vuosikymmenen aikana. Tämä johtuu sekä tietotekniikan kehittymisestä, joka mahdollistaa suurten aineistojen käsittelyn, myös sähköisen viestinnän lisääntymisestä, josta on huomattavan helppoa kerätä tarkkaa tietoa. Tässä työssä tutkitaan yhden eurooppalaisen matkapuhelinoperaattorin laskutukseen perustuvaa aineistoa. Alustavan analyysin perusteella voidaan sanoa, että aineisto on hyvin heterogeenistä: esimerkiksi yksilöiden käyttäytyminen vaihtelee paljon, samoin kuin kommunikointi eri vuorokaudenaikoina ja viikonpäivinä. Tarkemmin paneudutaan kahteen uuteen aiheeseen. Ensimmäisenä tutkitaan matkapuhelinviestinnän vastavuoroisuutta. Tasapuolisuus osoittautuu suhteellisen harvinaiseksi; toinen osapuoli soittaa usein huomattavasti enemmän kuin toinen. Tämä ei kuitenkaan johdu vain siitä, että toiset ihmiset ovat ylipäätään aktiivisempia, vaan tasapuolisuuden puute vaikuttaa olevan suhteen ominaisuus. Lisäksi voimme todeta, että aktiivisempi osapuoli on usein se, jolla on enemmän tuttavia. Toisena aiheena tutkitaan kausaalisuutta. Onko mahdollista erottaa, kuinka suuri osa soitetuista puheluista johtuu aiemmista vastatuista puheluista? Tähän kysymykseen on mahdotonta vastata minkään yksittäisen puhelun osalta, koska emme tunne puheluiden sisältöä, mutta voimme silti sanoa jotain keskiarvoista. Osoittautuu esimerkiksi, että jos vastattu puhelu saa aikaan uuden puhelun, se soitetaan keskimäärin 25 sekunnin kuluttua edellisen puhelun loppumisesta. Ongelmaksi muodostuu kuitenkin se, kuinka erottaa kausaalisuus korrelaatiosta.Research on large-scale complex social networks has increased considerably during the last decade. This has two basic reasons: the growth of computational power allows the study of ever larger data, and secondly the prevalence of electric communication makes it easier to collect data on a large number of people. This thesis studies a data set based on the billing information of one European mobile phone operator. Preliminary analysis reveals that the data is very heterogeneous: there are large variations between people, as well between different times of day and different weekdays. The thesis concentrates on two novel features. First we'll study the reciprocity of mobile phone communication. It turns out that evenness is quite rare; it's relatively common that one party is responsible for a large fraction of the calls. This is not only a result of the heterogeneity in human activity, but the unevenness seems to be a property of the relationship itself. Furthermore, the more active party appears to be the one with more acquaintances. The second feature concerns causality. Is it possible to tell how large a fraction of calls are caused by earlier calls It is impossible to give an answer in respect to any single call, since we do not know the contents of the calls, but we can still say something about averages. It turns out that if for example an incoming call induces a new call, that call takes place on average 25 seconds after the previous call ends. A large problem in this study is distinguishing causality from correlation

Communities and beyond: mesoscopic analysis of a large social network with complementary methods

Community detection methods have so far been tested mostly on small empirical networks and on synthetic benchmarks. Much less is known about their performance on large real-world networks, which nonetheless are a significant target for application. We analyze the performance of three state-of-the-art community detection methods by using them to identify communities in a large social network constructed from mobile phone call records. We find that all methods detect communities that are meaningful in some respects but fall short in others, and that there often is a hierarchical relationship between communities detected by different methods. Our results suggest that community detection methods could be useful in studying the general mesoscale structure of networks, as opposed to only trying to identify dense structures.Comment: 11 pages, 10 figures. V2: typos corrected, one sentence added. V3: revised version, Appendix added. V4: final published versio

Circadian pattern and burstiness in mobile phone communication

The temporal communication patterns of human individuals are known to be inhomogeneous or bursty, which is reflected as the heavy tail behavior in the inter-event time distribution. As the cause of such bursty behavior two main mechanisms have been suggested: a) Inhomogeneities due to the circadian and weekly activity patterns and b) inhomogeneities rooted in human task execution behavior. Here we investigate the roles of these mechanisms by developing and then applying systematic de-seasoning methods to remove the circadian and weekly patterns from the time-series of mobile phone communication events of individuals. We find that the heavy tails in the inter-event time distributions remain robustly with respect to this procedure, which clearly indicates that the human task execution based mechanism is a possible cause for the remaining burstiness in temporal mobile phone communication patterns.Comment: 17 pages, 12 figure

Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids The BLOOD FLOW Randomized Intervention Study

OBJECTIVE: Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. APPROACH AND RESULTS: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm,P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index CONCLUSIONS: Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964. GRAPHIC ABSTRACT: A graphic abstract is available for this article.Peer reviewe

Glutamine synthetase in human carotid plaque macrophages associates with features of plaque vulnerability : An immunohistological study

Publisher Copyright: © 2022 The AuthorsBackground and aims: Glutamine synthetase (GLUL), the sole generator of glutamine, is a metabolic nexus molecule also involved in atherosclerosis. We recently demonstrated a 2.2-fold upregulation of GLUL mRNA in stroke-causing carotid plaques when compared with plaques from asymptomatic patients. Here we compared in the same cohort GLUL mRNA expression with plaque gross morphology, and the colocalization of immunodetectable GLUL protein with histopathological changes and molecular and mechanical mediators linked to plaque development. Methods: Endarterectomy specimens from 19 asymptomatic and 24 stroke patients were sectioned longitudinally and immunostained for GLUL, CD68, α-smooth muscle actin, iron, heme oxygenase-1 and CD163, and graded semiquantitatively in every 1 mm2. The amounts of cholesterol clefts and erythrocytes were graded. The fibrous cap thickness within each 1 mm2 area was measured. The association between the local pathological findings was analyzed by a hierarchical mixed modelling approach. Results: The previously found correlation between GLUL mRNA and clinical symptomatology was supported by the increased GLUL mRNA in diseased tissue and increased local GLUL immunoreactivity in areas with multiple different atherosclerotic changes. A longer symptom-to-operation time correlated with lower GLUL mRNA (Rs = −0.423, p=0.050) but few outliers had a significantly higher GLUL mRNA levels, which persisted throughout the post-symptomatic period. Plaque ulceration associated with 1.8-fold higher GLUL mRNA (p=0.006). Macrophages were the main GLUL immunoreactive cells. GLUL immunostaining colocalized with erythrocytes, iron, CD163, and heme oxygenase-1. The correlations between local variables were consistent in both asymptomatic and stroke-causing plaques. An inverse correlation was found between the fibrous cap thickness and local GLUL immunoreactivity (p=0.012). Considerable variability in interplaque expression pattern of GLUL was present. Conclusions: Our results link connect macrophage GLUL expression with carotid plaque features characterizing plaque vulnerability.Peer reviewe

Morphology and histology of silent and symptom-causing atherosclerotic carotid plaques - Rationale and design of the Helsinki Carotid Endarterectomy Study 2 (the HeCES2)

Introduction: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.Materials and Methods: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses.Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing hot spot area 53%.Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis.Key MessagesThis article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment.In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.Peer reviewe

Circulating levels of adipokines and IGF-1 are associated with skeletal muscle strength of young and old healthy subjects

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Gene expression differences between stroke-associated and asymptomatic carotid plaques

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n = 43), where the most significant expression differences were found in CD36 (2.1-fold change, p = 0.005), CD163 (1.7-fold change, p = 0.007) and FABP4 (2.2-fold change, p = 0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p = 0.016), FUCA1 (2.2-fold change, p = 0.025), IL1RN (1.6-fold change, p = 0.034), and S100A8 (2.5-fold change, p = 0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization