A document by Claudia Schmied. Click on the document to view its contents.

Afforestation is the primary ecosystem measure to address the issue of ecosystem degradation in in the Horqin sandy region of northern China. However , It is yet unclear how afforestation may affect the recovery of sandy grassland. This study took the ecological stoichiometry as indicators, and conducted a field investigation and indoor analysis to assess the afforestation strategies of three indigenous tree species for the restoration of sandy grassland , three restoration strategies were: (1) grasslands were enclosed via a Populus × beijingensis shelterbelt (FG); (2) Pinussylvestris var. mongolica was used for the afforestation of small, well-distributed grassland patches (MG); (3) Ulmus pumila was used for the afforestation of small, well-distributed patches (UG). Our result showed that the C, N, and P contents as well as the C: N: P ratio in plants, litters, and soils varied significantly between FG, MG, and UG. All three treatments were found to significantly impact the soil ratios of C:N, N:P, and C:P relative to CK treatment after more than 20 years of recovery. The results of N : P in different tissues showed that FG , MG and UG vegetation restorations were N-limited. N and P homeostasis was present in trees, especially Ulmus pumila, while the degree of homeostasis was significantly impacted by afforestation species and plant tissues. The N:P results suggested that lower N deficiency stress may have been experienced by three experimental plants. We concluded that UG was better suited to the dry climate in Horqin Sandy Land.

HIV is a serious disease that threatens and affects capital stock, population composition and economic growth. This research paper aims to study the mathematical modeling and disease dynamics of HIV/AIDS with memory effect. We propose two fractional models in the Caputo sense for HIV/AIDS with and without migration. First, we prove the existence and positivity of both models and calculate the basic reproduction number R 0 using the next generation method. Then, we study the local and global stability of the obtained equilibria. In addition, numerical simulations are provided for different values of the fractional order ρ using the Adams-Bashforth-Moulton fractional scheme, to verify the theoretical results. Moreover, a sensitivity analysis of the parameters for the model with migration is carried out.

The analysis of spontaneous EEG is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Alterations in specific frequency bands have been reported, including a predominance of delta power in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients in contrast with a predominance of alpha activity in minimally conscious state patients (MCS). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that consciousness can be present despite either large delta or reduced alpha activity in spontaneous EEG. Quantifying the complexity of EEG responses to direct cortical perturbations (Perturbational Complexity Index; PCI) may complement the observational approach and provide a reliable assessment of consciousness even when spontaneous EEG features are inconclusive. To systematically test this hypothesis, we compared PCI to EEG spectral measures in the same population of MCS patients (n=40) hospitalized in rehabilitation facilities. We found a remarkable EEG background variability across MCS patients as compared to healthy controls and a non-negligible number of patients with predominant delta and highly reduced alpha power in spontaneous EEG. Conversely, PCI values invariably suggested a capacity for consciousness in all MCS patients, consistent with the presence of clearly discernible, albeit fleeting, behavioral signs of awareness. These results confirm that spontaneous EEG rhythms may dissociate from the actual capacity for consciousness and suggest that a perturbational approach can effectively compensate for this pitfall with practical implications for the individual patient’s stratification and tailored rehabilitation.

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

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.

Coagulation factors used in prophylactic treatment of patients with clotting disorders are associated with significant costs to health care systems. These products have complex pharmacokinetic profiles subject to large inter-individual variation making their efficient use challenging. Prior to this project, pharmacists were not involved as part of the Hemophilia care teams across Canada. The purpose of this pilot project was to determine whether employment of a pharmacist with expertise and a focus on plasma protein and related products including hemophilia treatments, would be an effective strategy to reduce costs associated with clotting factor prophylaxis regimens and identify the pharmacist’s activities associated with this new role. A cost-minimization analysis was conducted to compare the addition of a pharmacist to the care team of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving 500,000 children and youth. The analysis was performed from the perspective of the formulary manager, Canadian Blood Services, over a 1-year period including 9 months of interventions. The pharmacist performed 18 therapeutic optimizations on 14 patients with moderate to severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18 years old. As a result of the pharmacist’s intervention, clotting factor treatment costs extrapolated over one year were reduced by 20.5% for these patients. This represents a net savings of $225K CAD/year, or $12.5K CAD/optimization/year. The addition of a pharmacist to the HTC to manage recombinant and plasma-derived coagulation factors can optimise the treatment plan and significantly reduce the costs of managing patients with hemophilia.

Systemic-Onset Juvenile Idiopathic Arthritis with unusual Cutaneous Manifestation and peripheral eosinophilia: Case Report Author details:Albraa Babiker , MBBS, Omdurman Islamic University, Faculty of Medicine. (Author) Anas Babiker and Mohammedalmujtaba Gamar, MBBS, University of Khartoum, Faculty of Medicine. (Co-Author)AbstractIntroduction: Systemic-onset juvenile idiopathic arthritis (SoJIA) is unique subtype of juvenile idiopathic arthritis (JIA) with very special clinical manifestations, complications and management options. The simultaneous presentation of tinea capitis has not been reported in the context of Systemic-Onset Juvenile Idiopathic Arthritis before.The case: in march 2021 a 5-years old Sudanese male presented to Ahmed Gasim Hospital with fever and bilateral ankle arthritis in a background of extensive scalp lesions which were scaly, itchy and associated with hair loss. On examination: his weight was 15 kg (on the 5thcentile). There was cervical lymphadenopathy, hepatomegaly and swelling and tenderness in both ankle joints with restriction of movements. Complete blood counts revealed leucocytosis, thrombocytosis, mild eosinophilia and microcytic hypochromic anaemia. Anti-dsDNA antibody was 45 IU/ml (positive), ANA profile was 0,8 Ratio (Equivocal), CRP was 34.4 mg/l, LDH was very high, these results support the diagnosis of SoJIA in a background of a kerion. Patient received: antibiotic, systemic antifungal, Corticosteroids, Hydroxychloroquine, Calcium and Vitamin D to which he achieved good results.Consent:Witten informed consent was obtained from patient’s parent to publish this report in accordance with the journal’s patient consent policy.Keywords: Systemic-onset juvenile idiopathic arthritis; Systemic juvenile idiopathic arthritis; Tinea capitis; eosinophilia; case report.1.Introduction and literature reviewJuvenile idiopathic arthritis is a group of arthritis that occur before 16 years and last more than 6 weeks after exclusion of other aetiologies which is classified according to the International league of Associations for Rheumatology (ILAR) into 3 subtypes according to the clinical manifestations, complications and therapeutic options.(1–3) Systemic-onset juvenile idiopathic arthritis (SoJIA) is a very special subtype of juvenile idiopathic arthritis (JIA) that is characterized by fever which has a characteristic one or two spikes (>39°C) per day.(4) Also more than 80% of patients of this disease has a transient salmon-coloured macular or maculopapular rash that that accompanies the fever. They may have also myalgias and tenosynovitis and arthritis which may be oligoarticular to polyarticular.(3) The widely affected joints include wrists, knee, and ankles; but any joint can be affected, even the temporomandibular joints(5), cervical spine(6), hips(7), and the small joints of the hand and feet. SoJIA may present as painless lymphadenopathy (25%) hepatomegaly, splenomegaly or pericarditis which may be complicated by cardiac tamponade (3,4) There is no specific laboratory features that distinguishes SoJIA from other conditions, but the pattern of laboratory abnormalities may support the diagnosis, for examples; microcytic hypochromic anaemia, neutrophilic leucocytosis, thrombocytosis, high ESR, high CRP, high serum ferritin, low serum albumin, mildly elevated AST, high D-dimer and negative autoantibodies.(3) The treatment of JIA as whole focuses on suppressing inflammation, preserving functions, and preventing deformity and blindness.(8) the currently available drugs include nonsteroidal anti-inflammatory drugs (NSAID), Systemic corticosteroids and Disease-modifying anti-rheumatic drugs (DMARDs).(3,9,10) Eosinophil cells were associated with allergic bronchopulmonary aspergillosis and asthma exacerbation due to fungal antigens.(11) Moreover, a case report of kerion associated eosinophilia was described in which a dermatophytid reaction was thought to be the cause which responded to corticosteroid and antifungal.(12) 2 Case reports of 2 patients with systemic lupus erythromatosis in which tinea capitis was disseminated, one of them was using steroid the other was not.(13,14) and this is the first report related to juvenile idiopathic arthritis.Case reportHistory : In March 2021; a 5-years old Sudanese male from Algazira, center of Sudan presented with bilateral ankle swelling, bilateral knee and hip pain and fever which started 1 month prior to presentation. His mother was also concerned about scales and hair loss all over the scalp which started 2 months prior to presentation. His symptoms started insidiously with the fever mainly at night and relieved by antipyretics. He had anorexia and weight loss but neither abdominal pain, vomiting, diarrhea, cough, upper respiratory tract symptoms, headache nor history of trauma. He had a past history of right knee swelling which was resolved spontaneously. He had no family history of autoimmune disease or malignancy and not exposed to any medications.Examination: On examination the patient was ill but not pale, jaundiced or cyanosed. His weight was 15 Kg (along the 5th centile) (fig. 1). The scalp had white-yellow scales with some swelling, hair loss and dried pus over some areas of the scalp (Fig. 2). There were Bilateral cervical lymphadenopathy which were non-tender, discrete and maximum diameter was 1×1 cm. Both ankle joints were Swollen (fig. 3),and tender to palpation and there was restriction of movements. Other joint examinations were normal. Abdominal examination revealed palpable liver which was 4 cm below the costal margin and palpable paraaortic lymph nodes.Investigations: Complete blood count and peripheral blood picture revealed leucocytosis (WBCS=13.4*\(10^{3}\) which is high), neutrophil% = 49%, lymphocyte% = 38%, monocyte% = 5% and eosinophil% = 8% (mild eosinophilia) Thrombocytosis (614*\(10^{3}\)) and mild hypochromia (Hb=10.3 g/dl, MCV=71.8 fl, MCH=22.3 pg, MCHC=31.1 g/dl) were also present. Anti-dsDNA antibody was 45 IU/ml (positive). ANA profile was 0.8 Ratio (Equivocal). CRP was 34.4 mg/l (high) and ESR = 49 mm/hr. LDH was very high. Patient was treated with: Methylprednisolone 30mg/kg/day for 3 days. Followed by oral prednisone 1mg/kg/day. Hydroxychloroquine tabs 5mg/kg/day. Griseofulvin syrup 7.3mg/kg/day. Antibiotic Calcium and vitamin D. After 1 month of treatment follow-up the patient was improved and we refer him to the ophthalmologist for slit lamp examination.Discussion: In this case the full detailed history and proper clinical examination in addition to laboratory findings are in favour of the diagnosis of systemic-onset juvenile idiopathic arthritis. This case may show that, musculoskeletal manifestations may be present earlier than any other symptoms. Also, we noticed that in the lipid profile the HDL was very high but serum ferritin and ESR was normal, a complicating macrophage activation syndrome was putted in mind and then excluded.(15,16) Does tinea capitis occur more extensively in this patient due to the disease itself we don’t know fully but in a previous case report to a patient with systemic lupus erythromatosis in which disseminated infection occurred simultaneously at the time of the diagnosis before even the use of corticosteroid.(13) in that case the causative agent was Microsporum gypseum but unfortunately in our case the diagnosis was made clinically only and microbiological consultation was not ordered due to financial problems but what make our case unique is its association with systemic-onset juvenile idiopathic arthritis and not Systemic lupus erythromatosis even before the start of immunosuppressive therapy.(13,14) Mild peripheral eosinophilia explanation in our case was challenging; whether it is related to a dermatophytid reaction with no obvious morbilliform or lichenoid lesions or due to other causes that are not typical with the present history such as drug tubulointerstitial nephritis or any other occult helminthic infection. But according to the other laboratory and history points the later causes were excluded and we left with the occult dermatophytid reaction which was consistent with the same observation from another case report of kerion due to T. tonsurans with 21% eosinophil in the complete which was reduced to 6% one month later after oral griseofulvin and corticosteroid were used.(12) but unlike that case in which the patient was 45 year old female with a clear medical background unlike our case. But this may point to the fact that complete blood count is not routinely ordered in tinea capitis and eosinophilia may be underreported if we associate this to the fact that eosinophil recognizes ß-glucan of the fungal cell wall and react to it by releasing its granules and this area is an area of investigation in the future.(11)Conclusion: Physicians should be alert to the presentation of systemic-onset JIA in our country in order to make prompt diagnosis and treatment decisions as early as possible. Careful follow-up of prolonged febrile patients with arthritis of unknown origin is important to reaching the diagnosis early and initiating treatment.Conflict of interest:NO conflict of interest.Recommendations:Further studies about the eosinophil count and its role in tinea capitis and systemic-onset juvenile idiopathic arthritis.Further studies about the immune response against fungi in the setting of juvenile idiopathic arthritis.Multidisciplinary team consultation (rheumatologist, ophthalmologist, orthopaedics and paediatrician) in case of SoJIA.Educate the patients about the disease and its complications, which are important to monitor the disease and long-term morbidity and mortality.References:1. Ravelli A MA. Juvenile idiopathic arthritis. Lancet. 2007;369:767–78.2. Petty RE, Southwood TR MP. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis second revision, Edmonton, 2001. J Rheumatol. 2004;31((2)):390–2.3. Lee, Jennifer JY and RS. “Systemic juvenile idiopathic arthritis.” Pediatr Clin. 2018;(65.4):691–709.4. Calabro JJ, Holgerson WB SG. Juvenile rheumatoid arthritis: a general review and report of 100 patients observed for 15 years. Semin Arthritis Rheum. 1976;5(3):257–98.5. Ringold S CR. The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic. Pediatr Rheumatol Online J. 2009;7(1):11.6. Ornilla E, Ansell BM SA. Cervical spine involvement in patients with chronic arthritis undergoing orthopaedic surgery. Ann Rheum Dis. 1972;31:364–8.7. Modesto C, Woo P, García-Consuegra J, Merino R, García-Granero M, Arnal C, et al. Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. Clin Exp Rheumatol. 2001;19(2):211–7.8. Nelson essentials of pediatrics, 7th edition.9. Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015 Oct;74(10):1854–60.10. Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017 Nov;19(1):256.11. Manuscript A. NIH Public Access. 2009;181(4):2907–15.12. Martin ES, Elewski BE. bacterial pyoderma. 2003;177–9.13. Sanusi T, Gong J, Wang X, Zhao M, Zhao Y, An X, et al. Disseminated Favus Caused by Microsporum gypseum in a Patient with Systemic Lupus Erythematosus. 2016;(c):270–1.14. Feng J, Liu F, Wu F, Deng Q De. Tinea Infection with Scutula-like Lesions Caused by Microsporum Gypseum in a SLE Patient : Case Report and Literature Review. 2013;255–8.15. Cortis E, Insalaco A. Macrophage activation syndrome in juvenile idiopathic arthritis. Acta Paediatr Suppl. 2006 Jul;95(452):38–41.16. Ravelli, A., Magni-Manzoni, S., Pistorio, A. et al. Preliminary diagnostic guidelines for macrophage acti- vation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2004;12.016(146):598–604.17. Colella, M. , Buttaro, G. , Masi, L. , Palma, E. , Amelio, R. and Vallone A. The difficult management of systemic-onset juvenile rheumatoid arthritis. Level of serum ferritin as aspecific diagnostic finding. Open J Pediatr. 2012;2:53–5.18. Jandus, P., Wang, W., Seitz, M. et al. High serum ferritin in adult-onset still’s disease. International Journal of Clinical Medicine. 2010;1:81–3.19. Meijvis, H., Endeman, A.B.M., Geers, E.J. and Borg EJ. Extremely high serum ferritin levels as diagnostic tool in adult-onset still’s disease. Netherl J Med. 2007;65:212–4.

In this paper, we study several problems of the fifth-order Camassa-Holm type (FOCHT) equation. The local well-posedness and blow-up scenario are established at first. Then we prove the global existence under some conditions and analyze the large-time behavior of the support of momentum density. Finally, we discuss the persistence property in Sobolev space.

A document by Yin-Hua Chen. Click on the document to view its contents.

Clostridium sordellii: A cause of toxic shock syndrome after a breach in the GI tractSydney Pence,1 Rajshri Joshi,2Kasturi Shrestha31. Ohio University Heritage College of Osteopathic Medicine, 4180 Warrensville Center Rd, Warrensville Heights, OH 44122. Email: [email protected]. Internal Medicine, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307. Email: [email protected]. Infectious Disease, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH 44307. Email: [email protected]

Background: Methamphetamine use disorders (MAUD) can substantially jeopardize public security due to their high-risk social psychology and behavior. Given that the dopamine reward system is intimately associated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of DRD4, COMT genes and paranoid, motor impulsive symptoms in MAUD patients. Methods: A total of 189 MAUD patients participated in our study. Samples of peripheral blood were used to detecte for 3 SNPs and levels of 35 CpG units of methylation in the DRD4 gene’s promoter region, 5 SNPs and 39 CpG units in the COMT gene. Results: MAUD patients with rs1800955 C allele have a lower percentage of paranoid symptom than those with rs1800955 TT. Individuals with paranoid symptom exhibited reduced methylation degree at particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree resulted in the lower occurrence of the paranoid symptom. Meanwhile, those with COMT rs4818 CC allele have lower motor impulsivity scores in MAUD patients, but greater COMT methylation levels in the promotor region and methylation degree at COMT CpG 51.52 unit. Therefore, based only on COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor impulsivity scores in the MAUD patients. Conclusions: Our results found that the combination of SNP genotyping and methylation status of the DRD4 and COMT genes may serve as biological indicators to evaluate the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

Title pageTitle: Rust-colored patches of the lower extremity in a COVID-19 patientAuthrors: Jacem Rouatbi1, Mouna Korbi1*, Nouha Ben Abdeljalil2, Hichem Belhadjali1*, Jameleddine Zili1*

Team formation in an environment where some relevant parameters are not known in advance is a challenging problem. Communicating automata and distributed algorithms have been used to describe protocols for team formation. A high-level specification provides a mathematical description of a protocol or a program. TLA + is a formal specification language designed to provide high-level specifications of concurrent and distributed systems. The associated model checker known as TLC is capable of model checking the TLA + specifications. Recently formal specification of a team formation protocol is given using TLA + when there is a single initiator (an agent or a robot), that initiates the team formation. Using TLA +, we examine the formal specification for the multiple initiator situation and demonstrate that a composition technique can yield a single monolithic specification for the multiple initiator situation from the single initiator situation specification. We have used models of varying sizes, and the TLC model checker has confirmed that the protocol’s specifications meet certain desired characteristics in each case.

Among the power inverters, modular multilevel converters (MMC) have gained popularity due to their advantages over conventional two-level inverters. Although the MMC utilizes more power switches than traditional inverters, the former exhibits notable benefits such as low total harmonic distortion, low switching losses with lower voltage stress, high power quality, reduced electromagnetic interface, and modularity with numerous degrees of freedom to synthesize output waveforms. Concerning the synthesized voltage quality, several low-frequency modulation techniques have been proposed to produce output voltage with low harmonic content. A particular case of study consisting of a three-phase even-level MMC inverter is taken as a benchmark to comparatively evaluate four methods for synthesizing high-quality output voltage. The employed techniques are ( i) selective harmonic elimination (SHE), ( ii) generalized SHE, ( iii) THD Voltage Minimization, and ( iv) Optimum Nearest Level Modulation, selected based on the phase and line-to-line output voltage THD. The model is formulated to compute the commutating angles to control the MMC submodules. Simulations show individual performance under the same operating conditions. A lab-scale prototype is built to corroborate the theoretical approach. The results allow the selection of the most convenient modulation technique based on the number of commutations and harmonic spectrum.

It is found that there are two piecewise functions to satisfy the conditions in the impulsive fractional partial differential system (IFrPDS), which deduce that the three different equivalent integral equations of the IFrPDS given in the cited papers are inappropriate. Next, by applying two limit properties of the IFrPDS and the properties of piecewise function, the new formula of equivalent integral equation of the IFrPDS is discovered that is the integral equation with an arbitrary continuously differentiable function of t on [0,c] to reveal the non-uniqueness of the IFrPDE's solution. Finally, an example is provided to expound the computation of the equivalent integral equation of the IFrPDS.

This study proposes a fault estimation and tolerant anti-disturbance switching control (ADSC) approach for the switched systems subject to the system fault and multiple disturbances. The fault dose not required to have a model.The disturbances contain the modeled unmeasurable part and the unmodeled measurable part. First, a composite switching estimator is constructed to simultaneously estimate the unavailable system state, fault and modeled disturbance. Then, by means of the estimator, a switching controller is developed to tolerant the fault and complement the modeled disturbance. Further, under the dwell time relevant switching signals, criteria are established to ensure the fault estimation performance and robustness property for the switched systems. Finally, via implementing the presented fault estimation and tolerant ADSC scheme on a switched circuit system to regulate the charge and flux, the reasonability of the established result is verified.

Radiative cooling materials continue to underperform compared to their theoretical potential due to parasitic heating from contact with ambient air. Solutions to this problem are expensive or complex to fabricate. Here, a potentially inexpensive, simply fabricated material that improves cooling performance by reducing parasitic heating was created using naturally abundant salts. NaCl and KCl are not typically considered for radiative cooling because of their high hygroscopicity and low mechanical strength; however, these compounds are highly infrared-transparent and can be fabricated into aerogel-like structures to provide thermally insulating properties. Salt aerogels, described herein, scattered (reflected) visible light, transmitted infrared radiation, and provided thermal insulation. They were packaged into mechanical supporting panels to avoid physical disruption and the nanostructure was stabilized to moisture by adding anti-caking agent. The panels were able to keep an underlying surface below ambient temperature for a full 24-hour cycle and reduced parasitic heating rate by more than half (compared to an uncovered surface). The panels were able to cool a variety of underlying surfaces, even highly absorbing surfaces that are normally well above ambient temperature during the day. This work demonstrates an affordable, easily produced, electricity-free cooling technology with potential to be manufactured for large-scale practical applications.