Analysis of the isolation valve system in water distribution networks using the segment graph

The mechanical reliability of Water Distribution Networks (WDNs) is a relevant technical and scientific issue. During planned maintenance or unplanned interruptions, the affected area must be isolated by valves shutdown. This operation involves the alteration of the network structure, i.e., the domain of the hydraulic system, and for this reason the isolation valve system plays a central role. Some studies started to consider the presence of the isolation valve system in WDNs reliability analysis. Accordingly, this work uses the Complex Network Theory to analyse the isolation valve system performance and to assess the importance of the segments generated by valves shutdown. Differently from the classic complex network theory approach, in this work the recently proposed WDN-relevance-based betweenness centrality is applied to the segment graph to introduce information about the relevance of the different elements into the network, considering geometric and hydraulic parameters, such as length, demand, risk of disconnection, etc. The proposed strategy also suggests an improvement in the representation of the segment graph with respect to the presence of parallel edges. The strategy is presented using a small network, while it is demonstrated and discussed using a real WDN. The results indicate that the WDN-relevance-based betweenness centrality allows to effectively assess the importance of the segments generated by valves shutdowns, also providing indications to improve the isolation valve system design

Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens

Potentialities of Complex Network Theory Tools for Urban Drainage Networks Analysis

Urban drainage networks (UDNs) represent important infrastructures to protect and maintain community health and safety. For these reasons, technicians and researcher are focusing more and more on topics related to vulnerability, resilience and monitoring for controlling illicit intrusions, contaminant and pathogenic spread. In the last years the complex network theory (CNT) is attracting attention as a new, useful and structured approach to analyze urban systems. The aim of this work is to evaluate potentialities of CNT approaches for UDNs vulnerability assessment and monitoring system planning. Limits and potentialities of applicability of CNT tools to UDNs are first provided evaluating the performances of standard centrality metrics. Then, it is proposed the use of tailored metrics embedding prior information, as intrinsic relevance of each node and pipe flow direction, which derive from the Horton's hierarchy and geometric data (pipe slope), respectively, without performing hydraulic simulations. The analysis is applied on two schematic literature networks of different complexity and to a real case-study. The results suggest that vulnerability/resilience, monitoring design, contaminant and pathogenic spreads can be effectively analyzed using tailored metrics. Therefore, the proposed approach represents a complementary tool respect the more complex and computationally expensive methodologies and it is particular useful for large complex networks

Diagnostic factors for recurrent pregnancy loss: an expanded workup

Purpose: There is limited information on the risk factors for recurrent pregnancy loss (RPL). Methods: In this study, a patient-based approach was used to investigate the possible involvement and relative relevance of a large number of diagnostic factors in 843 women with RPL who underwent an extensive diagnostic workup including 44 diagnostic factors divided into 7 major categories. Results: The rates of abnormalities found were: (1) genital infections: 11.74%; (2) uterine anatomic defects: 23.72%; (3) endocrine disorders: 29.42%; (4) thrombophilias: 62%; (5) autoimmune abnormalities: 39.2%; (6) parental karyotype abnormalities 2.25%; (7) clinical factors: 87.78%. Six hundred and fifty-nine out of eight hundred and forty-three women (78.17%) had more than one abnormality. The mean number of pregnancy losses increased by increasing the number of the abnormalities found (r = 0.86949, P < 0.02). The factors associated with the highest mean number of pregnancy losses were cervical isthmic incompetence, anti-beta-2-glycoprotein-1 antibodies, unicornuate uterus, anti-prothrombin A antibodies, protein C deficiency, and lupus anticoagulant. The majority of the considered abnormalities had similar, non-significant prevalence between women with 2 versus ≥ 3 pregnancy losses with the exception of age ≥ 35 years and MTHFR A1298C heterozygote mutation. No difference was found between women with primary and secondary RPL stratified according to the number of abnormalities detected (Chi-square: 8.55, P = 0.07). In these women, the only factors found to be present with statistically different rates were age ≥ 35 years, cigarette smoking, and genital infection by Ureaplasma. Conclusion: A patient-based diagnostic approach in women with RPL could be clinically useful and could represent a basis for future research

HLA-G and Recurrent Pregnancy Loss

Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, seems to be one of the main molecules involved in the modulation of both local and systemic maternal immune response. The prevalence of recurrent pregnancy loss (RPL), probably underestimated, is 5% of all women who achieve pregnancy, and about 40–60% percent of RPL cases are unexplained. There is an immunological analogy between allograft rejection and miscarriage, and the purpose of this review is to describe how the HLA-G pathway alterations are involved in disrupting the immunologic balance and in increasing the risk of recurrent pregnancy loss

Hardware prototyping and validation of a W-ΔDOR digital signal processor

Microwave tracking, usually performed by on ground processing of the signals coming from a spacecraft, represents a crucial aspect in every deep-space mission. Various noise sources, including receiver noise, affect these signals, limiting the accuracy of the radiometric measurements obtained from the radio link. There are several methods used for spacecraft tracking, including the Delta-Differential One-Way Ranging (ΔDOR) technique. In the past years, European Space Agency (ESA) missions relied on a narrowband ΔDOR system for navigation in the cruise phase. To limit the adverse effect of nonlinearities in the receiving chain, an innovative wideband approach to ΔDOR measurements has recently been proposed. This work presents the hardware implementation of a new version of the ESA X/Ka Deep Space Transponder based on the new tracking technique named Wideband ΔDOR (W-ΔDOR). The architecture of the new transponder guarantees backward compatibility with narrowband ΔDOR

Kaon physics with the KLOE detector

In this paper we discuss the recent finalized analyses by the KLOE experiment at DA$\Phi$NE: the CPT and Lorentz invariance test with entangled $K^0 \bar{K}^0$ pairs, and the precision measurement of the branching fraction of the decay ${ K^+} \rightarrow \pi^+\pi^-\pi^+(\gamma)$. We also present the status of an ongoing analysis aiming to precisely measure the $K^{\pm}$ mass

High Energy & High Luminosity γγ\gamma\gamma Colliders

With the best of modern standard lasers, high-energy $\gamma\gamma$ colliders from electron beams of E larger than 250 GeV are only possible at the expense of photon luminosity, i.e. 10 times lower than for photon colliders at c.m. energies below 0.5 TeV. For existing state-of-the art lasers, an optimistic upper energy limit for x=4.8 is an electron beam of less than 250 GeV. This Snowmass21 Contributed Paper shows how Free Electron Lasers (FEL) pave the way for High Energy & High Luminosity $\gamma\gamma$ colliders. We present and assess a conceptual design study of a FEL with wavelength of 2.4 $\mu$m and an x-factor in the range of 2 to 40, to maximize the luminosity of a $\gamma\gamma$ collider as second interaction region of 0.5 TeV to 10 TeV c.m. $e^+e^-$ colliders.Comment: Contribution to Snowmass 202

From genetics to histomolecular characterization: An insight into colorectal carcinogenesis in lynch syndrome

Lynch syndrome is a hereditary cancer‐predisposing syndrome caused by germline defects in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Carriers of pathogenic mutations in these genes have an increased lifetime risk of developing colorectal cancer (CRC) and other malignancies. Despite intensive surveillance, Lynch patients typically develop CRC after 10 years of follow‐up, regardless of the screening interval. Recently, three different molecular models of colorectal carcinogenesis were identified in Lynch patients based on when MMR deficiency is acquired. In the first pathway, adenoma formation occurs in an MMR‐proficient background, and carcinogenesis is characterized by APC and/or KRAS mutation and IGF2, NEU‐ ROG1, CDK2A, and/or CRABP1 hypermethylation. In the second pathway, deficiency in the MMR pathway is an early event arising in macroscopically normal gut surface before adenoma for-mation. In the third pathway, which is associated with mutations in CTNNB1 and/or TP53, the adenoma step is skipped, with fast and invasive tumor growth occurring in an MMR‐deficient context. Here, we describe the association between molecular and histological features in these three routes of colorectal carcinogenesis in Lynch patients. The findings summarized in this review may guide the use of individualized surveillance guidelines based on a patient’s carcinogenesis subtype