Turner Syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. Comparing the healthy and individuals with Turner Syndrome may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner Syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). The co-expression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1 were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified 4 clusters in the PPI network constructed from the top 15 K ME enriched in significant functions. Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human health care system.

Defining dyssynchrony: The ongoing search for cardiac resynchronization therapy “response”Chinmaya Mareddy, MD and Pamela K. Mason, MDUniversity of Virginia Health System, Charlottesville, VACorresponding Author:Pamela K. Mason, MDProfessor of MedicineUniversity of Virginia Health SystemBox 800158Charlottesville, VA 22908434-924-2465Pkm5f@virginia.eduThere are no relevant disclosures.There are no sources of financial support.The first trial to demonstrate the benefits of cardiac resynchronization therapy (CRT) was published in 2001. The single-blind crossover study demonstrated significant improvement in quality of life, NYHA class, and 6 minute walk test for patients with a left ventricular ejection fraction less than 35%, NYHA class III, an enlarged left ventricle, and a QRS duration greater than 150 ms.1 CRT represented an exciting advancement in cardiac implantable electronic device (CIED) therapy. While implantable cardioverter defibrillators (ICDs) had been in use for decades and represented a reliable, life-saving measure to treat fatal ventricular arrhythmias, for the first time, there was a device therapy that could improve quality of life for heart failure patients. The CARE-HF trial went on to demonstrate reduction in hospitalization and mortality in a similar population, and subsequent studies, such as MADIT-CRT suggested that the benefits extended to patients with NYHA class I or II.2,3While there was quick adoption of CRT and over the years and many patients have benefitted, it quickly became clear that there were unresolved issues and questions.4 First, there were patients who could not receive a coronary sinus pacing lead. This was predominantly due to variation in the coronary sinus anatomy and phrenic nerve stimulation. Developments such as quadripolar left ventricular pacing leads and improved sheath design have certainly reduced the number of failed implants, however, they will never be completely eliminated. Second, despite successful implants in “good” locations, some patients simply did not have clinical improvement. Further work identified subgroups that were more likely to respond, particularly those with a wide left bundle branch block (LBBB); however, even now, only about 70% of patients who meet generally accepted criteria for CRT experience improvement after a successful implant. Finally, while symptom improvement was the standard measure for most studies, there were patients who were “super responders” who actually developed improvement in their left ventricular ejection fraction after CRT, and it is difficult to predict which patients might receive this advantage.5As the data increasingly have shown that patients with LBBB are more likely to benefit from CRT compared to right bundle branch block or non-specific intraventricular conduction delays, most society guidelines require a true LBBB to meet a class I indication for CRT.6,7 The difficulty with using LBBB as a metric for CRT candidacy is that defining it has been controversial. Multiple criteria have been proposed. In their 2021 guidelines statement for pacing and CRT, the European Society of Cardiology (ESC) altered their definition of LBBB.8 Specifically, they added the requirement of notching or slurring in 2 adjacent leads to define a true LBBB, thus making the definition of LBBB more restrictive. In addition, the 2021 guidelines also moved patients with narrower LBBB (120-149 ms) to a Class IIa recommendation. This obviously has important implications as to guidelines recommendations and benefits of CRT.In this edition of the Journal of Cardiovascular Electrophysiology, Rijik, et al present a retrospective analysis of 1202 consecutive patients from a registry who received a CRT device between 2000 and 2015. They applied the 2013 European Society of Cardiology (ESC) definition of left bundle branch block (LBBB) to the population and then the 2021 ESC definition of LBBB and assessed how patients would have qualified for CRT based upon those criteria. In addition, the authors reviewed the actual patient response to CRT in comparison to the guidelines recommendation for CRT implantation by 2013 and 2021 guidelines. Applying the more stringent 2021 criteria dramatically reduced the number of patients with a true LBBB from 80.9% of the population to 31.6%. This moved many patients out of a class I indication for CRT. In addition, they found that the 2013 criteria better discriminated the patients who actually did respond to CRT therapy. When evaluating a combined end point of transplantation, left ventricular assist device implantation, and mortality, the patients with a LBBB by the 2013 criteria and a QRS duration > 150 ms had significant benefit and those without did not. The same was true for echocardiographic response. When applying the 2021 criteria, differences were not seen between the two groups, implying that many patients who no longer had LBBB by 2021 guidelines still benefitted from CRT.The authors should be congratulated for adding important understanding to how we think about CRT and patient selection. These data show that employing a more strict definition of LBBB does not discriminate those who are most likely to benefit from CRT and might discourage implantation in patients who may benefit. The ESC is not the only society that has supported a more restrictive definition of LBBB.9 It is difficult to know how these definitions and guidelines directly influence practice, but we don’t want to risk denying patients an important therapy that could improve their quality and quantity of life. It is also difficult not to reflect that this paper shows both how far we have come with device therapy for our heart failure patients and how much further we have to go. We have been implanting CRT devices for over 20 years. Many patients have benefitted from this novel therapy, and yet there is so much that we don’t know.We must consider what the role for CRT will be in the future. Novel methods of leadless left ventricular pacing are being developed.10 There are observational and retrospective data suggesting that left bundle branch area pacing may be as good or better than CRT in improving clinical outcomes and heart function.11,12 Further, with experience, it is potentially faster to implant a left bundle area lead compared to a coronary sinus lead, and there has been wide early adoption of the technique compared to His bundle pacing. A multi-center, randomized controlled trial evaluating conduction system pacing compared to CRT should start enrolling soon and we should have more information in the coming years.13 It is possible to envision a future where coronary sinus pacing leads are no longer the norm in this patient population. It is also unlikely that the need for successful coronary sinus lead placement will be completely eliminated. Regardless of what the future holds, the insights from CRT studies, the effects on hemodynamics, electrical function, and outcomes will inform new directions.ReferencesCazeau S, Leclercq C, Lavergne T, et al. Affects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med2001;344:873-80.Cleland JGF, Daubert JC, Erdmann E, Freemantle N, et al. The effective cardiac resynchronization on morbidity and mortality and heart failure. N Engl J Med 2005;352:1539-1549.Moss AJ, Hall WJ, Cannom DS, et al. Cardiac resynchronization therapy for prevention of heart failure events. N Engl J Med2009;361:1329-1338.Sieniewicz BJ, Gould J, Porter B, et al. Understanding nonresponse to cardiac resynchronisation therapy: common problems and potential solutions. Heart Fail Rev 2019;24:41-54.Liang Y, Wang Q, Zhang M, et al. Cessation of pacing in super-responders of cardiac resynchronization therapy: a randomized controlled trial. J Cardiovasc Electrophysiol 2018; 29:1548-1555.Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: The task force on cardiac pacing and resynchronization therapy of the European society of Cardiology (ESC). Developed in collaboration with European heart rhythm Association (EHRA). Eur Heart J 2013;34:2281-329.Tracy CM, Epstein AE, Barbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device based therapy of cardiac rhythm abnormalities. Circulation 2012;126:1784-1800.Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: developed by the task for sudden cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) with a special contribution of the European Heart Rhythm Association (EHRA).Eur Heart J 2021;42:3427-3520.Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: Part 3: intraventricular conduction disturbances: A scientific statement from the American Heart Association Electrophysiology and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart rhythm Society: Endorsed by the International Society for Computerized Electrocardiography. Circulation 2009; 119:e235-40.Okabe O, Hummel JD, Bank AJ, et al. Leadless left ventricular stimulation with a WISE-CRT system: Initial experience results from the phase 1 of the SOLVE-CRT study (non randomized, role in phase).Heart Rhythm 2020; S1547-5271(21)01808-7.Vijayaraman P, Zalavadia D, Haseeb A, et al. Clinical outcomes of conduction system pacing compared to biventricular pacing in patients requiring cardiac resynchronization therapy. Heart Rhythm. 2022;19(8):1263-1271.Ezzeddine FM, Pistiolis SM, Pujol-Lopez M, et al. Outcomes of Conduction System Pacing for Cardiac Resynchronization Therapy in Patients with Heart Failure: A Multicenter Experience. Heart Rhythm. Published online February 24, 2023. doi:10.1016/j.hrthm.2023.02.018.Wang Y, Zhu H, Hou X, et al. Randomized trial of left bundle branch vs biventricular pacing for cardiac resynchronization therapy. J Am Coll Cardiol 2022;80:1205-1216.

Carbon capture, storage and utilization have become familiar terms when discussing climate change mitigation actions. Such endeavors demand the availability of smart and inexpensive devices for CO2 monitoring. To date, CO2 detection relies on optical properties and there is a lack of devices based on solid-state devices, which can be miniaturized and easily made compatible with IoT platforms. With this purpose, we present an innovative semiconductor as functional material for CO2 detection. Nanostructured In2O3 films, functionalized by Na, proves to enhance the surface reactivity of pristine oxide so much that even rather stable a molecule as CO2 is reduced. An advanced operando equipment based on surface-sensitive diffuse infrared Fourier transform is used to investigate its improved surface reactivity. The role of sodium is to increase the concentration of active sites such as oxygen vacancies and, in turn, to strengthen CO2 adsorption and reaction at the surface. It results in a change in film conductivity, i.e., in transduction of a concentration of CO2. The films exhibit excellent sensitivity and selectivity to CO2 over an extra-wide range of concentration (250-5000 ppm), which covers most indoor and outdoor applications with marginal influence by environmental humidity.

A document by ting zhou. Click on the document to view its contents.

A document by Lin Li. Click on the document to view its contents.

Recently, in-plane graphene/h-BN (G/h-BN) heterostructure was reported to be the catalytic activity for H2O2 synthesis by 2 e- oxygen reduction reaction (ORR). However, there is rare report for the vertically-stacked G/h-BN heterostructure, which refers to the stacking of graphene domains on the surface of h-BN. Herein, a simulated chemical vapor deposition method was proposed for fabricating abundant vertically-stacked G/h-BN heterostructure by in-situ growing graphene quantum dots (GQDs) on porous h-BN sheets. The catalytic performance of our vertically-stacked heterostructure catalyst is superior to the reported carbon-based electrocatalysts in an alkaline environment, with the H2O2 selectivity of 90%-99% in a wide potential range (0.35 V-0.7 V vs. RHE), over 90% faradaic efficiency and high mass activity of 1167 mmolgcatalyst-1 h-1. The experimental results and density functional theory simulation verifies that the vertically-stacked heterostructure possesses greatly catalytic performance for 2 e- ORR and the edge B atoms in the B-centered AB stacking model are the most active catalytic sites. This research well demonstrates the promising catalytic activity for the vertically-stacked G/h-BN heterostructure and provide a facile route for fabricating other vertically-stacked heterostructures.

Introduction: We describe one rare case of successful ablation of a right epicardial accessory pathway (AP) via the right ventricular diverticulum in a patient with Wolff-Parkinson-White syndrome. Methods: A 42-year-old woman being referred to the hospital for a catheter ablation of a Wolf-Parkinson White syndrome. Earliest activation was shown to be present in the region of the tricuspid annulus. However, ablation had no effect on the AP. Results: We decided to do a selected angiography, in which a big diverticulum near to the right tricuspid annulus was shown to be present. Ablation in this region successfully repressed the AP without any recurrences within a follow-up period of 12 months. Conclustion: The ventricular diverticulum mediated AP is a novel variant of pre-excitation. It can serve as an anatomical substrate of supraventricular tachycardia, and can be ablated endocardially using an irrigation tip catheter within the diverticulum.

Background To study the effects of combination TACE and anti-PD-L1 liposome drug in treating HCC in mice models. Methods We constructed the liposome drug with lecithin and cholesterol and mannitol, etc. Besides, the HCC mice model was established through abdominal subcutaneous injection HepG2 cancer cells in SD mice, then the PE-10 polyethylene catheter was used for TACE therapy. The SD mice were separately received TACE treatment, avelumab liposome drug therapy, and TACE combined with avelumab liposome drug therapy. Results The liposomes drug was successfully constructed with a diameter of 125.5 nm. After the mice received TACE and (or) immunotherapy, the combined liposome drug therapy significantly reduced the volume of hepatic carcinoma tissues, besides, the apoptotic rates of hepatic carcinoma cells in the combined liposome drug treatment group was increased obiviously compared with other groups. Moreover, the protein TGFβR2 located in the cellular membrane was obiviously down-regulated in the combined liposome drug therapy, whilst, the expression of SMAD7 and PTPN14 was up-regulated in the treatment groups compared with the mice without treatment, besides, the protein PTPN14 was mainly located in the nucleus. Additionally, the mRNA expression of genes SNAI1 and Vimentin was significantly down-regulated in the combined liposome drug therapy. Conclusion Combination of transcatheter arterial chemoembolization and anti-PD-L1 liposome drug therapy significantly suppressed hepatocellular carcinoma proliferation and metastasis in mice models.

ChatGPT is a generative pretrained transformer language model created using artificial intelligence implemented as chatbot which can provide very detailed responses to a wide variety of questions. As a very contemporary phenomenon, this tool has a wide variety of potential use cases that have yet to be explored. With the significant extent of information on a broad assortment of potential topics, ChatGPT could add value to many information security uses cases both from an efficiency perspective as well as to offer another source of security information that could be used to assist with securing Internet accessible assets of organizations. One information security practice that could benefit from ChatGPT is the reconnaissance phase of penetration testing. This research uses a case study methodology to explore and investigate the uses of ChatGPT in obtaining valuable reconnaissance data. ChatGPT is able to provide many types of intel regarding targeted properties which includes Internet Protocol (IP) address ranges, domain names, network topology, vendor technologies, SSL/TLS ciphers, ports & services, and operating systems used by the target. The reconnaissance information can then be used during the planning phase of a penetration test to determine the tactics, tools, and techniques to guide the later phases of the penetration test in order to discover potential risks such as unpatched software components and security misconfiguration related issues. The study provides insights into how artificial intelligence language models can be used in cybersecurity and contributes to the advancement of penetration testing techniques.

Software architecture determines success or failure in the domain of software development and design. As a system evolves, software architecture erodes. This phenomenon is called architectural erosion. Several studies that focused on various approaches to the problem of architectural erosion have been conducted. As a direct consequence of this, the metrics strategy has emerged as the most widely used solution for architectural erosion. However, providing a comprehensive perception of the elements required to evaluate the phenomenon of architectural erosion with an acceptable level of quality is a challenge. The primary goals of this research, which drew from the prior literature about identifying architectural erosion, were to (1) determine whether various adopted measures approaches determine architectural erosion in order to develop a formal model, and (2) evaluate the construct reliability and construct validity of the model. This research presents a model based on the chosen measures approaches for identifying architectural degradation. This model can be used as the cornerstone for a formal definition of general approaches and adopted metrics. Data was collected from 130 software engineering professionals with experience in architecture erosion and software metrics via a questionnaire-based survey. Structural equation Modelling (SEM) was used to analyse construct reliability, construct validity, and research hypotheses. The results demonstrate a substantial association between all metrics approach classes and architectural erosion, except for architectural complexity and architectural technical debt. Both researchers and practitioners can significantly benefit from this model’s empirical assessment and evaluation, which includes a valuable information in this context.

The purpose of this work is to achieve the analytic solution of non-linear Liouville-Caputo fractional initial value problem including time fractional Rosenau–Hyman equation by means of ARA transform and iterative method. First of all, ARA transform is employed to reduce the problem into a simpler one. Then the series solution of the non-linear fractional initial value problem is acquired by applying iterative method which leads to the analytic solution of the Rosenau–Hyman equation (RHE) with initial condition. The obtained results verify that the combination of ARA transform with iterative method produces an effective method to tackle with non-linear fractional problems.

Dijkstra’s Dutch Flag algorithm (DFA) can be used as a member of a quicksort hybrid to deal with, among others, a ‘difficult’ segment. We first show that the DFA can be wrapped so that this combination (with insertion sort and heapsort) is a ‘decent’ sorter. Subsequently we describe a different implementation of the DFA with a similar wrapper and compare their performance. Thirdly we show how these ‘mini’ sorters can be included in a five member hybrid quicksort sorter and we explain their contributions. The combination has NlogN worst case complexity and for constant input it has linear complexity. We compare several of these versions favorably against quicksort versions we found in libraries.

Abstract Information on the skin microbiota of amphibians can provide a solid basis for exploring the interactions between symbiotic microorganisms and hosts, thereby deepening our understanding of adaptation to the changing environment. Studies on the skin microbiota of amphibians in different disturbed habitats can clarify the relationships between skin microbiota composition and environmental factors and have practical implications for the conservation of endangered species. In this study, 16S rRNA high-throughput sequencing was used to profile the skin microbiota of the Maoershan hynobiid (Hynobius maoershanensis). Our results illustrated that the alpha diversity of the skin microbiota significantly differed between individuals in disturbed and undisturbed habitats. The diversity of the skin microbiota in forelimb bud stage tadpoles from disturbed habitats was higher than that in their counterparts from undisturbed habitats (Shannon index: 2.244 ± 0.601 vs. 1.731 ± 0.688; Simpson index: 0.230 ± 0.129 vs. 0.407 ± 0.205). The richness of the skin microbiota in hindlimb bud stage tadpoles was greater in disturbed habitats than in undisturbed habitats (ACE: 366.303 ± 186.993 vs. 148.357 ± 66.579; Chao: 355.946 ± 177.974 vs. 146.026 ± 65.794). Furthermore, stepwise regression analysis indicated that the skin microbiota diversity and relative abundance of dominant bacteria decreased with both increasing temperature and pH; conversely, skin microbiota richness increased with increasing humidity. In addition, the diversity and richness of the skin microbiota increased with increasing anthropogenic disturbance, and the relative abundance of dominant bacteria was influenced by anthropogenic disturbance. We conclude that the skin microbiota of Maoershan hynobiids is affected by ecological factors and anthropogenic disturbance, highlighting the importance of the skin microbiota in response to habitat alteration and the need to develop more efficient measures to protect Maoershan hynobiids.

A case of renal cell carcinoma in the contralateral kidney withTFE3 gene translocation following successful treatment of nephroblastomaShunsuke Fujisawa1), Junya Furukawa1), Takuto Hara1), Keiske Okada1), Kouji Chiba1),Yuzo Nakano1), Toshiki Hyodo2), Yoji Nagashima3), Masato Fujisawa1)1)Department of Urology, Kobe University Graduate School of Medicine2) Department of Diagnostic Pathology, Kobe University Graduate School of Medicine3) Division of Surgical Pathology, Tokyo Women’s Medical University Hospital

MULTICENTRIC RETICULOHISTIOCYTOSIS- A RARE AND DISABLING DISEASEOmowunmi Ashaolu1, Selwyn Ng2, Shaun Smale3, Jenny Hughes11Clinical fellow, Department of Dermatology, Princess of Wales Hospital, Bridgend, UK, wunmi.ashaolu@wales.nhs.uk2Consultant, Department of Histopathology, Morriston Hospital, Swansea, UK, selwyn.ng@wales.nhs.uk3Consultant, Department of Rheumatology, Princess of Wales Hospital, Bridgend UK, shaun.smale@wales.nhs.uk1Consultant, Department of Dermatology, Princess of Wales Hospital, Bridgend, UK,jenny.hughes@wales.nhs.uk.A 39-year-old man presented with 5-week history of multiple discrete and skin-coloured lesions on his hands, forearms, and face. He also had severely painful, stiff, and swollen fingers. He was otherwise well with no relevant personal or family history. Skin examination showed multiple discrete and coalescing firm, reddish brown, tender papules of varying sizes distributed mainly over the dorsum of the hands and nail folds (Fig 1) with no mucosal involvement. There was bilateral swelling and stiffness of the joints, especially the distal interphalangeal joints.Baseline investigations, autoantibody, viral screen, and staging CT to rule out underlying malignancy were normal. Radiographs of both hands showed soft tissue swelling and subtle perierosions in the small joints of the hands. Histopathology of the skin biopsy showed infiltration of the dermis and subcutaneous fat by mononuclear and multinucleated histiocytes with granular eosinophilic cytoplasm that showed positivity for CD45, CD68 and factor 13a and negativity for S100- and CD1a (Fig 2). Based on these findings a diagnosis of multicentric reticulohistiocytosis was made.He was initially treated with non-steroidal anti-inflammatory, Morphine, Alendronate and Oral corticosteroids. With worsening disease activity, Denosumab, oral methotrexate, hydroxychloroquine, infliximab, tocilizumab and leflunomide were added sequentially, however there was no symptom improvement. He was then considered for Tofacitinib 5mg twice daily with improvement after 4 weeks of initiating this therapy evidenced by improved sleep, skin symptoms and joint pains.Multicentric reticulohistiocytosis is a rare, multisystem inflammatory disease with unknown aetiology. It was first reported by Weber and Freudenthal in 1937, however Goltz and Laymon coined the term multicentric reticulohistiocytosis in 1954. Approximately 300 cases have been reported in the literature with most from Europe and United States. It is slightly predominant in women1 and symptoms manifest from the fourth decade of life2. Associated involvement of the joints impacts significantly on patients’ quality of life due to limitations on activities of daily living which inadvertently increases the risk of increased anxiety and depression.The cause of MRH is not known but activated macrophages and increased levels of TNF-alpha, IL-12, IL-1, and IL-63 have been documented.Cutaneous manifestation of MRH includes firm, discrete clustered reddish brown to flesh-coloured papules or nodules that gradually enlarge in size. It typically occurs over the joints of fingers and wrists giving a characteristic coral bead appearance1 as seen in our patient. Other commonly affected include the face giving leonine facies. However any part of the body can be affected including nail4 , mucosal surfaces1, lungs and heart. Fever, weight loss and malaise have also been reported. In addition, symmetrical polyarthritis mainly affecting the hands can potentially progress to arthritis mutilans. Differential diagnosis includes rheumatoid arthritis and psoriatic arthritis.Although MRH is not a paraneoplastic disease, solid organ especially breast and stomach carcinomas and haematological malignancies have been reported in 31% of cases5 therefore underlying malignancy should always be ruled out in a patient with MRH.There is no laboratory test specific for MRH. Histological studies show multinucleated giant cells with pale, fine, granular eosinophilic cytoplasm in the dermis. Stains are negative for S100, CD34, factor XIIIa and alpha-1-antitrypsin but positive for PAS and histiocytes (vimentin, CD68, CD45 and MAC387)2. Langerhans granules are absent on electron microscopy.There are no established treatment guidelines owing to the rarity and lack of controlled studies of the disease. The disease can be self-limiting, however this may have caused severe joint destruction. Prednisolone, immunomodulatory and disease modifying antirheumatic drugs, TNF inhibitors either as monotherapies or combination therapies have shown varying response. Tofacitinib, a selective JAK inhibitor, licenced for the treatment of rheumatoid arthritis has also been reported to be of benefit in the treatment of MRH6.MRH is a rare disease that cause disfiguring skin lesions and disabling arthritis therefore early recognition, and treatment is important to prevent long term deformities. In conclusion, we present a patient with a very rare non-Langerhans cell histiocytosis with typical clinical, histopathological and immunohistochemical findings.aFig 1: Showing coral bead appearance of multicentric reticulohistiocytosis

Journal: Allergy

Chagas disease is a chronic infection caused by Trypanosoma cruzi. The first-line drugs approved for treatment have several limitations and are associated with toxicity. The recombinant TSA-1-C4 and Tc24-C4 proteins have been profiled as promising candidates for the formulation of therapeutic vaccines, leading us to propose them in combination as a bivalent recombinant protein strategy. In this study, we evaluated the immunomodulatory effect of TSA-1-C4 plus Tc24-C4 recombinant protein combination by in-vitro assays. Macrophages from naïve BALB/c mice were isolated and stimulated with TSA-1-C4+Tc24-C4 proteins, supernatants were recovered to measure NO, H 2O 2, and, TNF-α, IL-1β, IL-6 and IL-10 cytokines. Stimulated macrophages were co-cultured with CD8 + T cells from naïve mice, and inflammatory cytokine-profile was measured from supernatants. Additionally, by experimental T. cruzi acute infection model, cytotoxicity was evaluated in mice after the treatment with TSA-1-C4+Tc24-C4 proteins in presence of a TLR-4 agonist adjuvant, E6020-SE. We observed that the bivalent recombinant protein strategy activates macrophages by NO and H 2O 2 production, also induced a significant Th1 immune-response compared to either TSA-1-C4 or Tc24-C4 stimulated macrophages. Moreover, naïve CD8 + T cells in presence of TSA-1-C4+Tc24-C4 stimulated-macrophages similarly boosted Th1 profile by significant production of IFN-γ and TNF-α cytokines. These results support the synergistic effect of the bivalent recombinant protein strategy, which leads activation of peritoneal macrophages and CD8 + T cells eliciting the Th1 immune response. Although the administration of TSA-1-C4+Tc24-C4+E6020-SE showed cytotoxic activity in T. cruzi-infected mice, there was not a benefit compared to stimulate with TSA-1-C4 or Tc24-C4 antigens formulated with E6020-SE adjuvant.

Most of the first eight pilot regions in China have entered the long-period continuous operation stage, and the second batch of six power spot pilots have started their simulation trial runs; however, the construction of power markets in the hydropower-rich regions of China (i.e., Sichuan and Yunnan) still faces multiple problems, including poor reliability of medium- and long-term power supplies, inefficient hydropower resource utilization and consumption scales, and unstable market prices. In this study, we establish a multi-scale joint clearing model for different market models (considering both long- and short-term operation strategies) and perform simulations of different market models at different time scales, to compare and analyze their optimization results and electricity price fluctuations. The model can stabilize the market price and reasonably reflect the true value of hydropower; it can also promote the consumption of clean energy and ensure the reliability of power supplies in the medium and long term. Finally, suggestions are made regarding the selection of electricity market models, the security of energy supplies, and the design of sustainable development mechanisms for hydropower in hydropower-rich regions, with a view to providing useful references for the development of China’s electricity market.

This paper proposes three-phase steady-state models for distributed generators (DGs) with different control strategies and an augmented rectangular load flow method is used for three-phase distribution systems. For two kinds of DGs with power electronic devices: photovoltaic power generators and doubly-fed induction generators, the nodal voltage equations and the output power equations are derived. Moreover, under the unbalanced conditions, the control strategies are applied and formulated as the function of the nodal voltage and the injected current to reduce the effects caused by the negative-sequence components. Furthermore, the models are incorporated into an augmented rectangular load flow method with nodal voltage and injected current as state variables in three-phase systems. Case studies are conducted to verify the correctness and accuracy of the proposed models by comparing the results obtained from MATLAB and PASCAD.

Code smells are usually ignored as they are neither a bug, nor a vulnerability. Quality engineers and, specially, security architects ignore them. As some of the code smells may lead towards vulnerability which may further be exploited by the hackers, therefore, such vulnerable code smells must be considered and further mitigated by threat modelers. In order to provide a repository of such code smells to security designers, a process had been devised and experimented. During the execution, various web applications had been passed through SAST and resulting code smells had been extracted and then inserted into a new dataset via Python. Later on, the code smells deposited in the dataset had been classified into various categories. Finally, machine learning algorithms had been assessed through WEKA and the fastest as well the most accurate algorithm had been selected. Current security standards do not ensure mitigation of threats caused by leading-to-vulnerability code smells, till to date. Typically, threat modelers assess security of a system through modeling threats via CIA, STRIDE and LINDDUN standards on its DFD and various architectural / infrastructural diagrams. Unless, they do not know that exploitable vulnerability still exists even after performing all secure design principles, the system would still be open to attacks. Our hypothesis was that vulnerable code smells still exist even after complying with all threat modeling standards. In the end, descriptive and inferential statistics had been used to analyse the results as well as test our hypothesis.

Our previous study has shown that ferromagnetic gadolinium silicide (Gd5Si4) nanoparticles (NP) could be potentially efficient T2 CA for MRI with significantly reduced echo time (TE) compared to Superparamagnetic Iron Oxide Nanoparticles (SPION) [1]. T2 CA are defined by their relaxivity, r2, which is dependent on both the saturation magnetization (Ms) and size of the NPs [1,2,4]. In this study, effect of Gd5Si4 NPs of varying sizes and concentrations are investigated on T1, T2 and T2* (effective/observed T2) relaxations times. Gd5Si4 NPs categorized into three fractions (named S1, S2 and S3) based on average sizes of 586 nm, 287 nm and 135 nm respectively as analyzed from SEM images (Fig. 1). XRD analysis on the combined samples shows that Gd5Si4 is the major phase while GdSi and Gd5Si3 are present as the minor phases in all fractions (Fig. 1). Magnetic properties measured in VSM reveal that the Curie temperature (Tc) decreases for Gd5Si4 phase from 312 K for S1 to 304 K for S2 and is undetectable in S3. The M-H curves at 300 K exhibits ferromagnetic behavior descending to paramagnetic as we move from S1 to S3 fraction (Fig. 1). MR data were acquired on the 21.1 T (900 MHz) magnet. The results shown in Table 1 indicate that higher concentrations of NPs shorten the T2 and T2* relaxation times and the contrast disappears rapidly at higher dilutions. The S2 fraction at 1/20 dilution shows notably shortened T1 and T2 relaxation times compared to the other two fractions. Although S1 has higher Gd5Si4 phase volume fraction and larger average particle size compared to S2, further investigation is needed inorder to establish the reason for shortened relaxation times compared to the S1 fraction. Acknowledgements

The way in which biological motion is processed, globally or locally, may depend upon the observer’s perceptual skill or experience with the stimulus. Skilled athletes with extensive perceptual experience observing sport-specific movements use globally distributed motion information across an opponent’s body to anticipate actions, while less skilled athletes focus on single-reliable kinematic cues. Published reports have demonstrated that attention can be primed globally or locally before perceptual tasks, and such an intervention could highlight motion processing mechanisms used by skilled and less skilled observers. In this study, we investigate skill-differences in biological motion processing using attentional priming. Skilled (N = 16) and less skilled (N = 16) players anticipated temporally occluded videos of beach volleyball attacks while being primed using a Navon matching task. EEG at parietal regions was measured to index global or local attention. Skilled players were more accurate than less skilled players across occlusion intervals and priming conditions. Global priming resulted in better performance for both skill groups. Skilled players showed significantly reduced alpha and beta power in the right compared to left parietal region, but brain activity was not affected by priming interventions. Our findings highlight the importance of right parietal dominance for skilled performers, which may be functional for inhibiting left hemispheric local processing or enhancing visual spatial attention for dynamic visual scenes. Further work is needed to systematically determine the function of this pattern of brain activity during skilled anticipation in other contexts.

Abstract Aim: We aim to compare nephrotoxic spectrum of IOCM and that of LOCM in a more intensive and comprehensive perspective using the real-world database. Methos: This is an observational, retrospective, pharmacovigilance study based on Vigibase. 7 products (iodixanol, iohexol, iopamidol, iopromide, iobitridol, ioversol and iomeprol) of ICM were included. Variable matching method was used for deduplication procedure. Two data mining method, reporting odds ratio (ROR) and bayesian confidence propagation neural networks of information components (IC) were used to detect signals for the full database, gender stratums (male and female), age stratum (0 to 64 years, 65 to 74 years and 75 or more years) and pooled analysis of total renal adverse events (AEs). Package ‘base’, ‘utils’ and ‘pheatmap’ of R language (version 4.1.2) were used to perform analysis and plot figures. Results: We got 2703 ICSRs and 3155 renal AE reports. The five most frequently reported were acute kidney injury, renal failure, renal impairment azotaemia and anuria. All ICM had highest signal value detected in age ≥75 years. Iodaxinal and iohexol had most signals detected. In pooled analysis of renal AEs, no signals detected for iopamidol, iomeprol and iopromide in the full database stratum. Conclusion: No evidence approved IOCM has safer nephrotoxicity than LOCM. CIN spectrum varies a lot within LOCM. Regarding to the whole population, not all products of ICM, such as iopamidol, iomeprol and iopromide, is likely to cause CIN.

Potato peel waste (PPW), a zero-value byproduct generated from potato processing, is a promising fermentation substrate due to its large quantity of starch, non-starch polysaccharide, lignin, protein, and lipid. Rhizopus oryzae is a filamentous fungus that is mainly known as a lactic acid producer and can ferment various agro-wastes. This study aimed to use R. oryzae for the fermentation of PPW. A series of batch fermentations were conducted to investigate the effects of different PPW loading rates (2 – 8%) and particle sizes (0 – 4mm). Under an initial PPW loading rate of 8% and particle size of 1 – 2mm, the maximum ethanol (23.9 mL/L) and lactic acid (2.60 mL/L) concentrations, the highest ethanol (11.93 mL/L•day) and lactic acid (1.56 mL/L•day) maximum production rates were obtained. Under these conditions, the yield of ethanol and lactic acid were 298 mL/mgPPW and 33 mL/mgPPW, respectively. R. oryzae was shown to utilize PPW as a substrate to produce value-added bioproducts such as ethanol (major product) and lactic acid.