Miracle-dz/UniFAR-FTUs huggingface dataset:
Label Switched Path Stitching with Generalized Multiprotocol Label Switching Traffic Engineering (GMPLS TE)

In certain scenarios, there may be a need to combine several Generalized Multiprotocol Label Switching (GMPLS) Label Switched Paths (LSPs) such that a single end-to-end (e2e) LSP is realized and all traffic from one constituent LSP is switched onto the next LSP. We will refer to this as "LSP stitching", the key requirement being that a constituent LSP not be allocated to more than one e2e LSP. The constituent LSPs will be referred to as "LSP segments" (S-LSPs). This document describes extensions to the existing GMPLS signaling protocol (Resource Reservation Protocol-Traffic Engineering (RSVP-TE)) to establish e2e LSPs created from S-LSPs, and describes how the LSPs can be managed using the GMPLS signaling and routing protocols. It may be possible to configure a GMPLS node to switch the traffic from an LSP for which it is the egress, to another LSP for which it is the ingress, without requiring any signaling or routing extensions whatsoever and such that the operation is completely transparent to other nodes. This will also result in LSP stitching in the data plane. However, this document does not cover this scenario of LSP stitching. [STANDARDS-TRACK]
Manufacture of Networks from Large Diameter Single-Walled Carbon Nanotubes of Particular Electrical Character

We have demonstrated that the aqueous two-phase extraction (ATPE) can differentiate between large diameter single-walled carbon nanotubes (CNTs) by electrical character. Introduction of “hydration modulators” to the ATPE machinery has enabled us to isolate metallic and semiconducting CNTs with ease. We have also shown that often there is a trade-off between the purity of the obtained fractions and the ability to separate both metallic and semiconducting CNTs at the same time. To isolate the separated CNTs from the matrices, we have proposed a method based on precipitation and hydrolysis, which can eliminate the need to use lengthy dialysis routines. In the final step, we prepared thin free-standing films from the sorted material and probed how electrical charge is transported through such macroscopic ensembles.
An Investigation on Glucuronidation Metabolite Identification, Isozyme Contribution, and Species Differences of GL-V9 In Vitro and In Vivo

GL-V9 is a prominent derivative of wogonin with a wide therapeutic spectrum and potent anti-tumor activity. The metabolism characteristics of GL-V9 remain unclear. This study aimed to clarify the metabolic pathway of GL-V9 and investigate the generation of its glucuronidation metabolites in vitro and in vivo. HPLC-UV-TripleTOF was used to identify metabolites. The main metabolite that we found was chemically synthesized and the synthetic metabolite was utilized as standard substance for the subsequent metabolism studies of GL-V9, including enzyme kinetics in liver microsomes of five different species and reaction phenotyping metabolism using 12 recombinant human UDP-glucuronosyltransferase (UGT) isoforms. Results indicated that the glucuronidation reaction occurred at C5-OH group, and 5-O-glucuronide GL-V9 is the only glucuronide metabolite and major phase II metabolite of GL-V9. Among 12 recombinant human UGTs, rUGT1A9 showed the strongest catalytic capacity for the glucuronidation reaction of GL-V9. rUGT1A7 and rUGT1A8 were also involved in the glucuronidation metabolism. Km of rUGT1A7-1A9 was 3.25 ± 0.29, 13.92 ± 1.05, and 4.72 ± 0.28 μM, respectively. In conclusion, 5-O-glucuronide GL-V9 is the dominant phase II metabolite of GL-V9 in vivo and in vitro, whose formation rate and efficiency are closely related to isoform-specific metabolism profiles and the distribution of UGTs in different tissues of different species.
Telomerase-Targeted Cancer Immunotherapy

Telomerase, an enzyme responsible for the synthesis of telomeres, is activated in many cancer cells and is involved in the maintenance of telomeres. The activity of telomerase allows cancer cells to replicate and proliferate in an uncontrolled manner, to infiltrate tissue, and to metastasize to distant organs. Studies to date have examined the mechanisms involved in the survival of cancer cells as targets for cancer therapeutics. These efforts led to the development of telomerase inhibitors as anticancer drugs, drugs targeting telomere DNA, viral vectors carrying a promoter for human telomerase reverse transcriptase (hTERT) genome, and immunotherapy targeting hTERT. Among these novel therapeutics, this review focuses on immunotherapy targeting hTERT and discusses the current evidence and future perspectives.
The holistic structure of causal quantum theory, its implementation in the Einstein-Jordan conundrum and its violation in more recent particle theories

Recent insights into the conceptual structure of localization in QFT (”modular localization”) led to clarifications of old unsolved problems. The oldest one is the Einstein-Jordan conundrum which led Jordan in 1925 to the discovery of quantum field theory. This comparison of fluctuations in subsystems of heat bath systems (Einstein) with those resulting from the restriction of the QFT vacuum state to an open subvolume (Jordan) leads to a perfect analogy; the globally pure vacuum state becomes upon local restriction a strongly impure KMS state. This phenomenon of localization-caused thermal behavior as well as the vacuum-polarization clouds at the causal boundary of the localization region places localization in QFT into a sharp contrast with quantum mechanics and justifies the attribute ”holstic”. In fact it positions the E-J Gedankenexperiment into the same conceptual class as the cosmological constant problem and the Unruh Gedankenexperiment and the problem of the cosmological constant. The holistic structure of QFT resulting from ”modular localization” also leads to a revision of the conceptual origin of the crucial crossing property which entered particle theory at the time of the bootstrap S-matrix approach but suffered from incorrect use in the S-matrix settings of the dual model
StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis[S]

How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD)5 leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. ER stress increases StarD5 expression in mouse hepatocytes, which results in an increase in accessible PM cholesterol in WT but not in StarD5−/− hepatocytes. StarD5−/− mice store higher levels of cholesterol and triglycerides, which leads to altered expression of cholesterol-regulated genes. In vitro, a recombinant GST-StarD5 protein transfers cholesterol between synthetic liposomes. StarD5 overexpression leads to a marked increase in PM cholesterol. Phasor analysis of 6-dodecanoyl-2-dimethylaminonaphthalene fluorescence lifetime imaging microscopy data revealed an increase in PM fluidity in StarD5−/− macrophages. Taken together, these studies show that StarD5 is a stress-responsive protein that regulates PM cholesterol and intracellular cholesterol homeostasis.
Rheumatic complications in cancer patients treated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.
Auditory system dysfunction in Brazilian gasoline station workers

Abstract Objective: To examine the auditory system of Brazilian gasoline station workers using an extensive audiological test battery. Design: This was a cross-sectional study. The audiological evaluation included a questionnaire, pure-tone audiometry, acoustic immittance tests, transient-evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), auditory brainstem response (ABR) and P300 auditory-evoked potentials. Study sample: A total of 77 Brazilian gasoline station workers were evaluated, and their results were compared with those of 36 participants who were not exposed to chemicals or noise at work. The gasoline station employees worked in 18 different gas stations, and the noise area measurements from all gas stations revealed time-weighted averages below 85 dBA. Results: Of the 77 gasoline station workers evaluated, 67.5% had audiometric results within the normal range, but 59.7% reported difficulties in communication in noisy places. Gasoline station workers showed significantly poorer results than non-exposed control participants in one or more conditions of each of the audiological tests used, except P300. Conclusions: The results suggest that the gasoline station workers have both peripheral and central auditory dysfunctions that could be partly explained by their exposure to gasoline.
Visual Exploration of Malicious Network Objects Using Semantic Zoom, Interactive Encoding and Dynamic Queries 2 System Design 2.1 Design Overview 2.4 System Architecture and Implementation

This paper explores the application of visualization techniques to aid in the analysis of malicious and non-malicious binary objects. These objects may include any logically distinct chunks of binary data such as image files, word processing documents and network packets. To facilitate this analysis, we present a novel visualization technique for comparing and navigating among 600-1000+ such objects at one time. While the visualization technique alone has powerful application for both directed and undirected exploration of many classes of binary objects, we chose to study network packets. To increase effectiveness, we strengthened the visualization technique with novel, domain-specific semantic zooming, interactive encoding and dynamic querying capabilities. We present results and lessons learned from implementing these techniques and from studying both malicious and non-malicious network packets. Our results indicate that the information visualization system we present is an efficient and effective way to compare large numbers of network packets, visually examine their payloads and navigate to areas of interest within large network datasets. 1 INTRODUCTION Visualization of security data has recently emerged as a powerful technique to provide insight and support analysis that is difficult with traditional text and charting techniques as well as signature and anomaly based machine processing. Current best practices in the network visualization domain employ scatterplots [1,2,3], parallel coordinate plots and line segments [4,5,6], glyphs [7], geographic layout [8,9,10], text representation [11], graphs [12,13] and similar high-level techniques to support security analysts. While current techniques have been proven useful through anecdotal evidence and evaluations [14,15,16,17], we believe that they should be combined with low-level representations of network packets, including payloads, to create domain-specific highly interactive systems. To this end, we present both a novel low-level visualization technique which we call a binary rainfall and a visualization system which allows users to semantically zoom [18] through eight representations of network traffic. We also explore the use of dynamic queries [19] and interactive encoding to enhance the performance of the system. Some of the most promising network security visualization systems to date make excellent use of packet header data, particularly at the network and transport layers. While very useful in certain instances, these systems do not adequately visualize data at the application level and subsequently miss payload based malicious activity. To address this issue, our binary rainfall technique allows users to compare payloads of 600-1000+ packets at one time. The system, shown in Figure 1, plots pixels in direct …
Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled,

Objective Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments

The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.
Overall Dietary Quality Relates to Gut Microbiota Diversity and Abundance

Disturbances in gut microbiota homeostasis may have metabolic consequences with potentially serious clinical manifestations. Diet influences the host’s metabolic health in several ways, either directly or indirectly by modulating the composition and function of gut microbiota. This study investigated the extent to which dietary quality is reflected in gut microbiota diversity in overweight and obese pregnant women at risk for metabolic complications. Dietary quality was measured by a validated index of diet quality (IDQ) and microbiota composition was analyzed using 16SrRNA gene sequencing from 84 women pregnant less than 18 weeks. The alpha diversity, measured as Chao1, observed operational taxonomic units (OTUs), phylogenetic diversity, and the Shannon index were calculated. The IDQ score correlated positively with the Shannon index (rho = 0.319, p = 0.003), but not with the other indexes. The women who had the highest dietary quality (highest IDQ quartile) had higher gut microbiota diversity in all the investigated indexes, when compared to the women with the lowest dietary quality (lowest IDQ quartile; p < 0.032). Consequently, a higher dietary quality was reflected in a higher gut microbiota diversity. The presented approach may aid in devising new tools for dietary counseling aiming at holistic health, as well as in microbiome studies, to control for dietary variance.
Cognitive and Sensory Dimensions of Older People’s Preferences of Outdoor Spaces for Walking: A Survey Study in Ireland

Background: Physical exercise, particularly walking, benefits healthy ageing. Understanding the environmental circumstances in which exercise occurs is crucial to the promotion of physical activity in older age. Most studies have focused on the structural dimensions of environments that may foster walking; however, individual differences in how older people perceive and interact with outdoor spaces need further attention. This study explored the cognitive and sensory dimensions of preferences of outdoor spaces for walking. Methods: We invited 112 healthy community-dwelling people aged ≥60 years to complete a survey to test associations between walking preferences and cognitive/sensory vulnerability. A subsample also completed focus groups/walk along interviews to explore qualitatively the cognitive/sensory reasons for outdoor walking preferences. Results: While most participants indicated a preference for outdoor spaces that offer variety and greenery, we observed a complex association between individual cognitive/sensory needs (stimulation seeking vs. avoidance), preferences for social interactions, and the place of residence urbanity level. Furthermore, walking preferences varied based on the purpose of the walk (recreation vs. transportation). Conclusions: Our findings support an ecological approach to understanding determinants of physical activity in older age, which consider the interaction between individual cognitive processing and the environment.
Characteristics and Challenges for the Development of Nature-Based Adult Day Services in Urban Areas for People with Dementia and Their Family Caregivers

Nature-based adult day services (ADSs) for people with dementia (PwD) are well-known in rural areas. In recent years, a number of providers have started offering these services in urban contexts, e.g., in city farms and community gardens, where people with dementia participate in outdoor activities, such as gardening and caring for animals. At the moment, little is known about these services within an urban context, and the aim of this study is to characterize different types of nature-based ADSs in urban areas for PwD living at home, as well as to identify general and specific challenges with regard to the development of different types of ADSs. An inventory was carried out and 17 ADS providers in urban areas were interviewed about their initiatives, settings, client groups, motivations for starting their nature-based ADS, and their experiences with, competences for, and funding of urban nature-based ADS. The interviews were recorded, transcribed verbatim and thematically analyzed. Five types of nature-based ADSs were identified: (1) services offered by social entrepreneurs, (2) nursing homes opening their garden to people with dementia, (3) social care organization setting up nature-based, (4) community garden set up by citizens, and (5) hybrid initiatives. Common activities were gardening, preparing meals, and taking care of farm animals. The main activities organized by nursing homes included sitting and walking in the garden and attending presentations and excursions. General challenges included the availability of green urban spaces and acquiring funding for the nature-based services. Initiatives of social entrepreneurs depended strongly on their commitment. Challenges for nursing homes included a lack of commitment among nursing staff, involvement of PwD living at home and a lack of interaction with the neighborhood. Volunteers played a key role in the initiatives organized by social care organizations and in community gardens. However, it was a major challenge to find volunteers who know enough about care and gardening. Specific challenges for the hybrid types were related to differences in work culture between social entrepreneurs and care organizations. Different types of care-oriented and community-oriented nature-based adult day services in urban areas for people with dementia have been developed, facing different types of challenges. Care oriented initiatives like nursing homes opening their garden focus on risk prevention and their nature-based services tended to be less diverse and stimulating for people with dementia living at home. Collaboration between such care-oriented initiatives with initiatives of other types of organizations or social entrepreneurs can lead to more appealing community-oriented nature-based services.
C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression

Cancer is a leading cause of death and disease worldwide, with a tremendous financial impact. Thus, the development of cost-effective novel approaches for suppressing tumor growth and progression is essential. In an attempt to identify the mechanisms responsible for tumor suppression, we screened for molecules downregulated in a cancer progression model and found that the chemokine CXCL14, also called BRAK, was the most significantly downregulated. Increasing the production of CXCL14 protein by transfecting tumor cells with a CXCL14 expression vector and transplanting the cells into the back skin of immunodeficient mice suppressed tumor cell growth compared with that of parental tumor cells, suggesting that CXCL14 suppressed tumor growth in vivo. However, some studies have reported that over-expression of CXCL14, especially in stromal cells, stimulated the progression of tumor formation. Transgenic mice expressing 10-fold more CXCL14 protein than wild-type C57BL/6 mice showed reduced rates of chemical carcinogenesis, transplanted tumor growth, and metastasis without apparent side effects. CXCL14 also acts as an antimicrobial molecule. In this review, we highlight recent studies involving the identification and characterization of CXCL14 in cancer progression and discuss the reasons for the context-dependent effects of CXCL14 on tumor formation.