Varna University of Management

Massive brane fluctuations, called branons, behave as weakly interacting massive particles, which is one of the most favored class of candidates to fulfill the role of the dark matter (DM), an elusive kind of matter beyond the Standard Model. We present a multi-target search in dwarf spheroidal galaxies for branon DM annihilation signatures with a total exposure of 354 hours with the ground-based gamma-ray telescope system MAGIC. This search led to the most constraining limits on branon DM in the sub-TeV and multi-TeV DM mass range. Our most stringent limit on the thermally-averaged annihilation cross-section (at 95% confidence level) corresponds to ⟨σv⟩ ≃ 1.9 × 10⁻²⁴ cm³s⁻¹ at a branon mass of ∼ 1.5 TeV.

Potentiostatic current transients of silver nucleation and growth were obtained on carbon screen printed electrodes (SPE) consisting of single walled carbon nanotubes, carbon nanofibers, and mesoporous carbon. Data for the number of deposited silver particles were obtained by field-emission scanning electron microscopy. All three types of SPE show the presence of large (μm-sized) crystals with surface density of about 10⁵ cm⁻² together with much smaller silver particles with sizes typically below 80 nm and surface density in the 10⁸ cm⁻² range. The different carbon structures do not affect the shape and size of the large crystals but influence the size and extent of aggregation of the nanometer-sized ones. The current transients are interpreted by the Scharifker-Mostany model for multiple nucleation and diffusion limited growth and data for the nucleation rate per active site (A) and number of active sites for nucleation (N0) were obtained. It was found that the numbers of micron-sized crystals correspond to the calculated data for N0. The physical meaning of the quantities A and N0, obtained by fitting current transients with maxima, was critically assessed. The long-time behavior of the current transients was analyzed and evidence for diffusion at nonzero surface concentration of the silver ions was obtained.

A composite gas-diffusion electrode containing carbon and zeolite, for rechargeable metal-air batteries was developed. To ensure the uniform distribution of the clinoptiolite particles in the carbon matrix, as well as mechanical stability of the gas-diffusion layer high-energy milling (5000 rpm for 1 min) and subsequent pressing of the mixture (300 kg.cm⁻² at 280 °C) were applied. By partially replacing the teflonized carbon black in the gas-diffusion layer with clinoptiolite the necessary hydrophobicity could be attained while maintaining the high gas permeability of the zeolite material. The teflonized carbon black: zeolite mass ratio was optimized in terms of the mechanical stability of the electrode and its electrochemical performance. The catalytic layer comprised a bimetallic catalyst consisting of Ag and γ-MnO2 in a 1:1 mass ratio. The morphology of the catalytic layer, as well as the pore size in the gas-diffusion layer, were studied using scanning electron microscopy and the Brunnauer-Emmett-Teller method. The determined pore size below 10 nm implies mainly the Knudsen diffusion through the gas-diffusion layer. In the preliminary durability tests high mechanical, chemical, and electrochemical stability (more than 750 cycles) was obtained for the newly developed composite gas-diffusion electrode.

In this paper, we propose a novel cross-attention-based generative adversarial network (GAN) for the challenging person image generation task. Cross-attention is a novel and intuitive multi-modal fusion method in which an attention/correlation matrix is calculated between two feature maps of different modalities. Specifically, we propose the novel XingGAN (or CrossingGAN), which consists of two generation branches that capture the person's appearance and shape, respectively. Moreover, we propose two novel cross-attention blocks to effectively transfer and update the person's shape and appearance embeddings for mutual improvement. This has not been considered by any other existing GAN-based image generation work. To further learn the long-range correlations between different person poses at different scales and sub-regions, we propose two novel multi-scale cross-attention blocks. To tackle the issue of independent correlation computations within the cross-attention mechanism leading to noisy and ambiguous attention weights, which hinder performance improvements, we propose a module called enhanced attention (EA). Lastly, we introduce a novel densely connected co-attention module to fuse appearance and shape features at different stages effectively. Extensive experiments on two public datasets demonstrate that the proposed method outperforms current GAN-based methods and performs on par with diffusion-based methods. However, our method is significantly faster than diffusion-based methods in both training and inference.

This study elaborates on the economics of the Metaverse in tourism and hospitality. It identifies the Metaverse stakeholders from a tourism perspective, namely: IT companies (infrastructure), IT companies (Metaverse presence), tourism and hospitality companies, other (non-tourism) companies, destination management organisations, tourists, and public authorities. The paper elaborates on the activities each stakeholder would be able to perform in the Metaverse and the associated revenue and costs. Based on this, the paper discusses the economic relationships between the stakeholders, their impacts on the financial performance of tourism and hospitality companies, and the potential economic externalities of the Metaverse. Theoretical, managerial and policy implications, limitations and future research directions are outlined as well.

The large amount of sludge that is generated in wastewater treatment plants /WWTP/ and the lack of drying fields to stabilize them necessitates the conduct of this study. The use of sludge in practice can be a source of biological contamination of soil, water and plants, including pathogenic microorganisms. Regardless of the developed normative documents, there are a number of problems in practice that limit the realization of sewage sludge. One of these problems is related to the disturbed microbiological parameters in most treatment plants. Sludge storage is used as the only way to eliminate pathogenic microorganisms. This method is not effective enough since it requires large areas for sludge storage. The purpose of the study was to determine the possibility of decontamination of sewage sludge using an ADAPT stabilizer for waste treatment produced by ‚Devnya Cement‘ AD. For the preparation of the cement clinker, mainly natural rock materials are used, which, after crushing and grinding, form a "raw material mixture" consisting of natural survins and industrial products containing the major minor oxides - CaO, Si02 , Al2 O3 and Fe2 O3. Fresh sludge from WWTP Varna was used, treated with 20, 25 and 35% of the stabilizer. The sludge was analyzed before and after treatment by agrochemicals and microbiological parameters. It was found that the most effective treatment was with 20% sludge dry stabilizer treatment for a period of 20 days. Treatment of the sludge with the stabilizer does not have a negative effect on their chemical and agrochemical characteristics.

Adaptation of semantic segmentation networks to different visual conditions is vital for robust perception in autonomous cars and robots. However, previous work has shown that most feature-level adaptation methods, which employ adversarial training and are validated on synthetic-to-real adaptation, provide marginal gains in condition-level adaptation, being outperformed by simple pixel-level adaptation via stylization. Motivated by these findings, we propose to leverage stylization in performing feature-level adaptation by aligning the internal network features extracted by the encoder of the network from the original and the stylized view of each input image with a novel feature invariance loss. In this way, we encourage the encoder to extract features that are already invariant to the style of the input, allowing the decoder to focus on parsing these features and not on further abstracting from the specific style of the input. We implement our method, named Condition-Invariant Semantic Segmentation (CISS), on the current state-of-the-art domain adaptation architecture and achieve outstanding results on condition-level adaptation. In particular, CISS sets the new state of the art in the popular daytime-to-nighttime Cityscapes $\rightarrow$ Dark Zurich benchmark. Furthermore, our method achieves the second-best performance on the normal-to-adverse Cityscapes $\rightarrow$ ACDC benchmark. CISS is shown to generalize well to domains unseen during training, such as BDD100K-night and ACDC-night. Code is publicly available at https://github.com/SysCV/CISS .

Objectives: The contemporary concept of carcinogenesis summarizes the role of hypoxia, neoangiogenesis, and hemostasis, including in the stage of progression and metastasis of the tumor process. Metastatic disease is a serious therapeutic challenge for any oncological condition. The purpose of this study was to evaluate the dynamics of specific indicators of neoangiogenesis and hypoxia as potential biomarkers for therapeutic efficacy or risk of disease progression in patients with brain metastases (BM) undergoing robotic stereotactic radiosurgery. Methods: Two groups of patients (lung cancer and other types of cancers) with oligometastatic disease and brain metastases were included. The patients (n=66) were treated with CyberKnife system. Human Angiopoietin-2, Hypoxia inducible factor 1 α (HIF-1α) and human Vascular Endothelial Growth Factor-А (VEGF-А) were measured in this prospective longitudinal study. Results: Analysis of human Angiopoietin-2, HIF-1α, human VEGF-A in the post-treatment period showed a statistically significant decrease between the baseline and the 6 months post-treatment time point in both patient groups. The baseline value of serum VEGF-А in the group with lung cancer decreased by 40%, Аngiopoietin-2-by 48%, HIF-1α -by 43%. In the group with other types of cancers, VEGF-А decreased by 54.75%, Аngiopoietin-2-by 52%, HIF-1α -by 39.5%. Despite the significant reduction, the levels remained significantly higher in both groups than in healthy controls. Conclusion: This study underscores the potential of integrating molecular markers like VEGF-A, Angiopoietin-2, and HIF-1α into clinical decision-making to enhance outcomes for patients with brain metastases undergoing RSRS.

IntroductionIn ESCAPE-TRD (NCT04338321), a randomized, open-label, rater-blinded, long-term, phase 3b trial, augmentation with esketamine nasal spray (ESK) demonstrated increased probability of achieving meaningful clinical benefit versus quetiapine extended release (QUE XR) in patients (pts) with treatment-resistant depression (TRD). This subgroup analysis of ESCAPE-TRD evaluated the incidence, duration, and impact of treatment-emergent adverse events (TEAEs) on treatment discontinuation in adults with TRD treated with ESK or QUE XR according to US prescribing information. Methods Pts aged 18-64 years were randomly assigned to receive flexibly dosed ESK (56 or 84 mg) or QUE XR (150-300 mg), both consistent with US label dosing and in combination with an ongoing oral antidepressant. The incidence and duration of the most commonly occurring TEAEs, as well as the most common TEAEs leading to treatment discontinuation, were summarized descriptively. All randomly assigned participants receiving ≥1 dose of study drug were included in the safety analyses. ResultsAmong the 636 pts included in the subgroup analysis, 316 and 320 were randomly assigned to ESK and QUE XR, respectively; 314 and 316 were included in the safety population. In the combined acute and maintenance phases, TEAEs occurred in 92.0% of pts in the ESK group and 78.5% of pts in the QUE XR group. The most commonly reported TEAEs with ESK or QUE XR in the combined acute and maintenance phases were dizziness (47.1% and 7.9%, respectively), headache (25.5% and 13.0%, respectively), somnolence (15.0% and 23.4%, respectively), and nausea (29.9% and 3.2%, respectively). Across all TEAE events reported in >5% of pts in either arm, 91.8% (5831 of 6351) resolved within 1 day in the ESK arm compared to 11.6% (90 of 776) with QUE XR. For specific TEAE events of clinical interest for ESK, same-day resolution rates for increased blood pressure, sedation, and dissociation in the ESK group were 93.5% (116 of 124), 96.2% (127 of 132), and 99.6% (740 of 743), respectively. The majority of TEAEs of clinical interest in the ESK group that occurred on the same day of dosing resolved within the first 2 hours after dosing. For the most frequently reported TEAEs with QUE XR, same-day resolution rates for somnolence, headache, and fatigue were 7.8% (8 of 103), 49.2% (29 of 59), and 9.5% (4 of 42), respectively. Fewer pts treated with ESK discontinued treatment due to TEAEs compared to QUE XR (4.4% versus 10.6%). Conclusions Safety data from this subgroup analysis were consistent with the overall study population as well as the known tolerability profile of each treatment. TEAEs were reported at higher incidence with ESK than with QUE XR; however, the majority of TEAEs occurring with ESK were transient in nature and did not result in a higher rate of treatment discontinuation compared to QUE XR. FundingJanssen Scientific Affairs, LLC

The paper elaborates on the positive effects of support activities for entrepreneurial ecosystems (EEs) on regional development in lagging regions beyond the obvious outcome of new enterprises. The emphasis on entrepreneurship support organisations to develop lively EE in lagging regions has been criticised for its limited success, high costs and low benefits for local citizens. We agree with this criticism in principle but argue that a meaningful evaluation of entrepreneurship support’s effects on regional development must also consider the wider impact of such promotion. Based on a literature review and empirical findings from our engagement in three EEs, we discuss such regional-level ‘outward causation’ and identify five broader effects how entrepreneurship support organisations strengthen development. They (1) promote innovative regional organisations, institutions and actors; (2) qualify and engage aspiring founders who later become qualified and motivated employees for incumbent companies and the public sector; (3) contribute to a positive regional image and identity; (4) enhance inter-sector and inter-municipality cooperation and (5) position start-ups as a positive impulse for developing declining cities. In conclusion, we propose an extended understanding of start-up support for developing lagging regions that considers entrepreneurship support organisations as catalysts of the positive effects associated with vibrant ecosystems.

When farmers leave their land, what version of nature takes over?

Here we describe the first detected VIM-2-producing representative of Pseudomonas putida group – Pseudomonas kurunegalensis from the largest Bulgarian hospital – St George University Hospital in Plovdiv. A 59-year-old female patient with right-sided lung abscess was hospitalized in the Second Clinic of Thoracoabdominal Surgery. She was repeatedly treated for pulmonary infections. Punctate from the abscess cavity was taken for microbiological investigation. Identification process and antimicrobial susceptibility were performed by Vitek 2. The species group P. putida was confirmed with MALDI-TOF system and whole genome sequencing defined it as P. kurunegalensis. Antibiotic susceptibility testing revealed susceptibility only to tobramycin and colistin. All phenotypic tests for carbapenemase and metallo-beta-lactamase (MBL) production were positive. Multiplex PCR was performed to search for nine common carbapenemase encoding genes whereas the variable region of the integron was determined by DNA sequencing. Molecular assays confirmed the presence of blaVIM-2 located within a typical Class I integron including also an aacA29b aminoglycoside N(6’)-acetyltransferase casette. Despite P. putida not being a common pathogen, it still could survive in hospital conditions causing difficult-to-treat infections and becoming a source of resistant genes, including MBL-encoding genes.

The private international law regime of cross-border insurance disputes in the European Union comprises a regime including rules in Regulations Brussels Ibis, Rome I and Rome II as well as a number of directives, which interact with each other, with overlaps and gaps at different places. Navigating within this maze may be difficult and one may reach different and not always very consistent results. The regime’s cornerstone is the treatment of the ‘weaker’ party to the insurance dispute. However, due to their nature, insurance disputes may entangle contract and tort law issues, and various points of law may end up being governed by different substantive laws. Against this complex background, to map the regime, the current work provides a high-level review of both the jurisdictional and applicable law rules including key features of the relevant pieces of legislation from EU law delineating their applicability and fundamental concepts. We also put these against the wider background of the nature of insurance matters and the specific characteristics of cross-border disputes in that area. The study is focused on the interaction between the Regulations, how these are treated and interpreted by courts, and to what extent concepts from one Regulation may be read into another for insurance disputes. It is argued that the regime on international jurisdiction under EU law confers a wide array of jurisdictional options to potential claimants under insurance disputes—be it insureds, policyholders, injured third parties or third parties subrogated in the rights of the latter. This is based on the understanding that these weaker parties should be offered to avail themselves of a court, which is more convenient and, most likely, better connected with them and/or the circumstances of the case. In contrast, Regulations Rome I and Rome II on substantive matters do not purport to offer a myriad of potentially applicable laws, which, it is demonstrated, may be seen to favour legal certainty. The EU regime on insurance disputes seems to be not that flexible on applicable substantive law; however, corrective mechanisms allow for altering the applicable rules in line with the specific features of the case. The case law of the CJEU is studied, too, and it indicates that EU regulations should be read independently when interpreting the connecting factors contained therein. The analysed CJEU cases clearly demonstrate that the court did pull on a number of occasions the rein on the attempts to read substantive law concepts into jurisdictional regulations, which may well be for the greater good of the EU system of cross-border litigation. Following this, it appears that Regulation Brussels Ibis should be read on its own without guidance stemming from conflict rules on applicable law. The study outlines that the jurisdictional or applicable law rules may be read in a flexible way to ensure the policy end of protection of the weaker party, but not that flexible as to acquire meaning beyond what is literally put in the Regulations.

This concluding chapter presents the rich tapestry of energy citizenship in Europe. It offers a summary and reflection on the various contexts and conditions for an emerging energy transition identified throughout the previous chapters. Across eight national settings, Belgium, Bulgaria, France, Germany, Hungary, Ireland, Latvia, and the Netherlands, many forms of energy citizenship were identified. These include individual and collective, and reformative and transformative forms. This chapter also reflects on the reality that the term “energy citizenship” is not (yet) widely known despite the many forms of it that flourish. The authors, themselves based in eight European countries, have highlighted case studies demonstrating exciting opportunities as well as considering the barriers different forms of energy citizenship encounter in various countries. In concluding this chapter, the authors ask So, what next for Energy Citizenship? and outline a summary of the ways in which energy citizenship initiatives can be supported and further developed. In addition, they highlight the significance of the overall research in providing opportunities to learn from the variety of energy citizenship that is prevalent across Europe. This collection concludes with a final reflection by the authors on the contribution of the overall collection and affirms the importance of sharing national and local experiences and showing case studies of energy citizenship.

This chapter examines the energy citizenship landscape in Bulgaria. Based on the review of 22 energy citizenship initiatives in the EnergyPROSPECTS project, the chapter establishes that a typical Bulgarian energy citizenship case can be described in the following way: it is supported by public funds (often the EU), operates on a local or municipal level, does not participate in larger networks, and is managed by or significantly benefits from the involvement of an NGO. The chapter then turns its attention to the external conditions, which support or hinder the emergence and development of energy citizenship in the country. It argues that Bulgaria’s current political situation is, in principle, conducive to cultivating energy citizenship but too unstable to offer concrete support. Technological developments are creating a range of opportunities, while concerns about climate change are a strong source of motivation. The analysis shows that the economic, legal, and social contexts strongly deter the development of energy citizenship in Bulgaria.

Nowadays, numerous devices are utilizing the IoT world, connecting and providing access to data and sensor measurements in vast networks of interconnected objects and devices. Considering the great communication distances that need to be covered occasionally, the LoRaWAN network was proposed as it employs Low Power (LP) and Long Range (LoRa) protocols that reduce device energy consumption while maximizing communication range. A gateway to the cloud authenticates LoRaWAN IoT devices before data transmission. This procedure begins with an unencrypted Join Request. A Join Request includes, among others, a Message Integrity Code (MIC), which is the result of encrypting the unencrypted contents of the message using an AppKey that is securely stored both in the cloud and the IoT device. However, malicious actors acting as Man-In-the-Middle (MITM) can interfere in the communication channel, reverse engineer the MIC value, and derive the AppKey. They can then initiate a Join Request that is misinterpreted as coming from a legitimate device and gain access to the communication channel. This paper introduces a novel approach that focuses on the continuous regeneration of the AppKey, necessitating frequent re-joining and re-authentication of IoT devices within the network. The suggested method, which can be added as an extra layer of security in LoRaWAN networks, uses a key rolling technique similar to the one used in automobile central locking systems, and is developed as an optimised and scalable microservice for various LoRaWAN installations and versions. Through the evaluation process, significant findings emerged, demonstrating the effectiveness of the proposed security solution in mitigating replay attacks. The system successfully prevented the server from getting flooded by malicious packets, distinguishing it from a system lacking the proposed mechanism. Remarkably, this accomplishment was made without causing any noticeable delay to the communication process. In addition, the timeframe required by the proposed mechanism to generate the new AppKey is assumed to be too short for attackers to execute a replay attack, considering the computational resources currently accessible.

Fitusiran is an investigational small interfering RNA therapeutic that targets antithrombin (AT) to rebalance hemostasis in people with hemophilia. Here we present the results of the completed Phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran in participants with moderate or severe hemophilia A or B, with or without inhibitors. Male participants who had completed the Phase 1 study (NCT02035605) were enrolled. Participants received monthly subcutaneous fitusiran (50 mg or 80 mg) under the original dose regimen until a voluntary dosing pause in 2020, following which the AT-based dose regimen was introduced, targeting the recommended AT activity levels of 15-35%. Thirty-four participants (hemophilia A [n=27]; hemophilia B [n=7]) were enrolled in the Phase 2 study and treated with fitusiran for a median exposure of 4.1 years. Adverse events reported on the original and the AT-based dose regimen were consistent with the identified risks of fitusiran. Following implementation of the AT-based dose regimen, no thrombotic events, and a reduction in the incidence of elevated transaminases and biliary events were reported. The observed median annualized bleeding rate (ABR) on the AT-based dose regimen (0.87) was comparable to the ABR under the original dose regimen (0.70). Furthermore, fitusiran prophylaxis was associated with improved health-related quality of life compared to baseline and provided successful hemostatic control during surgical procedures and invasive interventions. Overall, fitusiran was well tolerated and effective bleeding control was maintained on an AT-based dose regimen. This trial was registered at www.clinicaltrials.gov as #NCT02554773.

Background In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release. Aims To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release. Method ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had TRD (i.e. non-response to two or more antidepressive treatments within a major depressive episode). Patients were randomised 1:1 to flexibly dosed esketamine nasal spray or quetiapine extended release, while continuing an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. The primary end-point was achieving a Montgomery–Åsberg Depression Rating Scale score of ≤10 at Week 8, while the key secondary end-point was remaining relapse free through Week 32 after achieving remission at Week 8. Sensitivity analyses were performed on these end-points by varying the definition of remission based on timepoint, threshold and scale. Results Of 676 patients, 336 were randomised to esketamine nasal spray and 340 to quetiapine extended release. All sensitivity analyses on the primary and key secondary end-point favoured esketamine nasal spray over quetiapine extended release, with relative risks ranging from 1.462 to 1.737 and from 1.417 to 1.838, respectively (all p < 0.05). Treatment with esketamine nasal spray shortened time to first and confirmed remission (hazard ratio: 1.711 [95% confidence interval 1.402, 2.087], p < 0.001; 1.658 [1.337, 2.055], p < 0.001). Conclusion Esketamine nasal spray consistently demonstrated significant superiority over quetiapine extended release using all pre-specified definitions for remission and relapse. Sensitivity analyses supported the conclusions of the primary ESCAPE-TRD analysis and demonstrated robustness of the results.