Multiprotocol Label Switching Virtual Private Networks

U ovom diplomskom radu opisana je arhitektura mreža pružatelja telekomunikacijskih usluga. Nadalje, definiran je način rada, ciljevi razvoja te prednosti primjene MPLS tehnologije. Također, definirani su osnovni elementi MPLS mreže, protokoli koji se primjenjuju za distribuciju oznaka i usmjeravanje paketa te neka od MPLS aplikacijskih proširenja. Budući da se MPLS VPN smatra najprihvaćenijim aplikacijskim proširenjem, opisane su njegove inačice po slojevima: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service i Virtual private LAN service. Osim toga, opisan je proces planiranja mreže koji se sastoji od telekomunikacijskog predviđanja dimenzioniranja te tehnika upravljanja mrežnim prometom, pri čemu su opisana dva najčešće korištena alata za planiranje MPLS mreže: IP/MPLSView i iVNT. U praktičnom djelu rada odrađena je OSPF, MPLS i VPLS konfiguracija MikroTik-ova prema zadanoj testnoj mrežnoj topologiji (Slika 8.1.) te je omogućen pristup Internetu putem MikroTik-a P1.This graduate thesis is based on trends according to Internet service provider's core networks – ISP, MPLS development, operation mode, some of it's development goals and advantages of it's application. Also, in this thesis are defined some of main elements of MPLS networks, main MPLS protocols which are used for distribution and routing, and some of MPLS application extensions. Since we consider MPLS VNP as most successful application extension, here are desribed his variants by layers: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service and Virtual private LAN service. Beside that, this thesis is describing network planning process which consists of telecommunication predictions, dimensioning and traffic engineering whereby are described two most used tools for MPLS network planning: IP/MPLSView and iVNT. Practical part of this thesis consist of OSPF, MPLS and VPLS configuration of MikroTik's according to default network topology (picture 8.1.) and Internet access is enabled via MicroTik P1

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Multiprotocol Label Switching Virtual Private Networks

U ovom diplomskom radu opisana je arhitektura mreža pružatelja telekomunikacijskih usluga. Nadalje, definiran je način rada, ciljevi razvoja te prednosti primjene MPLS tehnologije. Također, definirani su osnovni elementi MPLS mreže, protokoli koji se primjenjuju za distribuciju oznaka i usmjeravanje paketa te neka od MPLS aplikacijskih proširenja. Budući da se MPLS VPN smatra najprihvaćenijim aplikacijskim proširenjem, opisane su njegove inačice po slojevima: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service i Virtual private LAN service. Osim toga, opisan je proces planiranja mreže koji se sastoji od telekomunikacijskog predviđanja dimenzioniranja te tehnika upravljanja mrežnim prometom, pri čemu su opisana dva najčešće korištena alata za planiranje MPLS mreže: IP/MPLSView i iVNT. U praktičnom djelu rada odrađena je OSPF, MPLS i VPLS konfiguracija MikroTik-ova prema zadanoj testnoj mrežnoj topologiji (Slika 8.1.) te je omogućen pristup Internetu putem MikroTik-a P1.This graduate thesis is based on trends according to Internet service provider's core networks – ISP, MPLS development, operation mode, some of it's development goals and advantages of it's application. Also, in this thesis are defined some of main elements of MPLS networks, main MPLS protocols which are used for distribution and routing, and some of MPLS application extensions. Since we consider MPLS VNP as most successful application extension, here are desribed his variants by layers: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service and Virtual private LAN service. Beside that, this thesis is describing network planning process which consists of telecommunication predictions, dimensioning and traffic engineering whereby are described two most used tools for MPLS network planning: IP/MPLSView and iVNT. Practical part of this thesis consist of OSPF, MPLS and VPLS configuration of MikroTik's according to default network topology (picture 8.1.) and Internet access is enabled via MicroTik P1

Methods and tools for QoS verification and testing

U radu je glavni zadatak bio analizirati kvalitetu usluge za pojedine aplikacije. U prvom djelu rada opisan je razvoj i arhitektura višeuslužnih mreža te Interneta. Zatim su opisane tri vrste usluga; podatkovne, video i audio usluge. Nakon toga definiran je pojam kvalitete usluge te parametri koje svaka od usluga mora zadovoljiti. Osim parametara, opisani su i mehanizmi za osiguranje kvalitete usluge u različitim tehnologijama. Za određivanje kvalitete usluge potrebne su neke od subjektivnih ili objektivnih metoda koje su opisane u radu. Također, za određivanje zadovoljstva korisnika, vrlo je važna iskustvena kvaliteta. Parametri kvaliteta usluge za tipične mrežne aplikacije mjereni su pomoću dva programska alata, Wireshark i PRTG.The main task of this final paper was to analyze quality of service for certain applications. In the first part of this paper it is described development and architecture of multiservice networks and the Internet. Afterwards it is defined the notion of quality of service and parameters that each of the services must satisfy. In addition to parameters, it are described mechanisms for quality assurance services in different technologies. To determine the quality of service are required some of the subjective and objective methods described in the paper. Also, to determine customer satisfaction, it is very important experiential quality. The parameters of quality of service for the typical network application were measured using two software tools, Wireshark and PRTG

Multiprotocol Label Switching Virtual Private Networks

U ovom diplomskom radu opisana je arhitektura mreža pružatelja telekomunikacijskih usluga. Nadalje, definiran je način rada, ciljevi razvoja te prednosti primjene MPLS tehnologije. Također, definirani su osnovni elementi MPLS mreže, protokoli koji se primjenjuju za distribuciju oznaka i usmjeravanje paketa te neka od MPLS aplikacijskih proširenja. Budući da se MPLS VPN smatra najprihvaćenijim aplikacijskim proširenjem, opisane su njegove inačice po slojevima: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service i Virtual private LAN service. Osim toga, opisan je proces planiranja mreže koji se sastoji od telekomunikacijskog predviđanja dimenzioniranja te tehnika upravljanja mrežnim prometom, pri čemu su opisana dva najčešće korištena alata za planiranje MPLS mreže: IP/MPLSView i iVNT. U praktičnom djelu rada odrađena je OSPF, MPLS i VPLS konfiguracija MikroTik-ova prema zadanoj testnoj mrežnoj topologiji (Slika 8.1.) te je omogućen pristup Internetu putem MikroTik-a P1.This graduate thesis is based on trends according to Internet service provider's core networks – ISP, MPLS development, operation mode, some of it's development goals and advantages of it's application. Also, in this thesis are defined some of main elements of MPLS networks, main MPLS protocols which are used for distribution and routing, and some of MPLS application extensions. Since we consider MPLS VNP as most successful application extension, here are desribed his variants by layers: MPLS Layer 3 VPN, MPLS Layer 2 VPN, Virtual Private Wire Service and Virtual private LAN service. Beside that, this thesis is describing network planning process which consists of telecommunication predictions, dimensioning and traffic engineering whereby are described two most used tools for MPLS network planning: IP/MPLSView and iVNT. Practical part of this thesis consist of OSPF, MPLS and VPLS configuration of MikroTik's according to default network topology (picture 8.1.) and Internet access is enabled via MicroTik P1

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n\ua0=\ua0888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n\ua0=\ua02,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics

Combinatorial, additive and dose-dependent drug–microbiome associations

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker\ua0discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects,\ua0and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic\ua0agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease