Search results for: functional magnetic resonance imaging (fMRI)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5486

Search results for: functional magnetic resonance imaging (fMRI)

3956 Effect of Non-Invasive Electrical Stimulation on Partial Hearing Loss: Pilot Study

Authors: Geetanjali Saggar

Abstract:

Background: Partial hearing loss is the inability to hear effectively as a normal hearing individual whose hearing threshold is 20 dB or better in both ears. Individuals with partial hearing loss may benefit from non-invasive electrical stimulation as a method of therapy and possible intervention. Objective: The project aims to assess and relate the efficacy of electrical stimulation on individuals with partial hearing loss. The study's goal was to evaluate the different sorts of non-invasive electrical stimulation in tinnitus and hearing loss in order to build the framework for future research. Method: In this pilot study, a total of five patients of age group above 50 years were selected with partial hearing loss. The electrical modality of Repetitive Transcranial Magnetic Stimulation (RTMS) was used among the patients and was evaluated using gold questionnaires- HHIA and APHAB for hearing at intervals of 0-7-14 days. The statistical data was analyzed by SPSS software-16. Results: There were not much significant changes in the hearing of the patients when non-invasive electrical modality was applied as an intervention in the partial hearing loss condition. However, there was minimal change in the daily functioning of the patient with the application of intervention. Conclusion: This study concluded that non-invasive electrical stimulation had minimal to no effect on the partial hearing of the patients.

Keywords: non-invasive, hearing loss, transcranial magnetic stimulation, partial deafness, transcranial direct current stimulation, tinnitus

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3955 Adomian’s Decomposition Method to Functionally Graded Thermoelastic Materials with Power Law

Authors: Hamdy M. Youssef, Eman A. Al-Lehaibi

Abstract:

This paper presents an iteration method for the numerical solutions of a one-dimensional problem of generalized thermoelasticity with one relaxation time under given initial and boundary conditions. The thermoelastic material with variable properties as a power functional graded has been considered. Adomian’s decomposition techniques have been applied to the governing equations. The numerical results have been calculated by using the iterations method with a certain algorithm. The numerical results have been represented in figures, and the figures affirm that Adomian’s decomposition method is a successful method for modeling thermoelastic problems. Moreover, the empirical parameter of the functional graded, and the lattice design parameter have significant effects on the temperature increment, the strain, the stress, the displacement.

Keywords: Adomian, decomposition method, generalized thermoelasticity, algorithm

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3954 Correction of Skeletal Deformity by Surgical Approach – A Case Report

Authors: Davender Kumar, Virender Singh, Rekha Sharma

Abstract:

Correction of skeletal deformities in adult patients with orthodontics is limited. In adult severe cases, the combined approach, orthodontic and orthognathic surgery, is always the treatment of choice, and the results obtained usually ensure a better esthetic, functional, and stable results Orthognathic surgery is the best option for cases when camouflage treatment is questionable and growth modulation is not possible. This case report illustrates the benefit of the team approach in correcting mandible retrusion along with class II skeletal deformity with 100% deep bite. Correction was achieved by anterior repositioning of mandible osteotomy along with orthodontic treatment. The patient's facial appearance was markedly improved along with functional and stable occlusion.

Keywords: camouflage, skeletal, orthognathic, dental

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3953 Conflicts and Complexities: a Study of Hong Kong's Bilingual Street Signs from Functional Perspective on Translation

Authors: Ge Song

Abstract:

Hong Kong’s bilingual street signs declare a kind of correspondence, equivalence and thus translation between the English and Chinese languages. This study finds four translation phenomena among the street signs: domestication with positive connotation, foreignization with negative connotation, bilingual incompatibilities, and cross-street complexities. The interplay of, and the tension between, the four features open up a space where the local and the foreign, the vulgar and the elegant, alternate and experiment with each other, creating a kaleidoscope of methods for expressing and domesticating foreign otherness by virtue of translation. An analysis of the phenomena from the functional perspective reveals how translation has been emancipated to inform a variety of dimensions. This study also renews our understanding of translation as both a concept and a practice.

Keywords: street signs, linguistic landscape, cultural hybridity, Hong Kong

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3952 Fundamental Natural Frequency of Chromite Composite Floor System

Authors: Farhad Abbas Gandomkar, Mona Danesh

Abstract:

This paper aims to determine Fundamental Natural Frequency (FNF) of a structural composite floor system known as Chromite. To achieve this purpose, FNFs of studied panels are determined by development of Finite Element Models (FEMs) in ABAQUS program. American Institute of Steel Construction (AISC) code in Steel Design Guide Series 11, presents a fundamental formula to calculate FNF of a steel framed floor system. This formula has been used to verify results of the FEMs. The variability in the FNF of the studied system under various parameters such as dimensions of floor, boundary conditions, rigidity of main and secondary beams around the floor, thickness of concrete slab, height of composite joists, distance between composite joists, thickness of top and bottom flanges of the open web steel joists, and adding tie beam perpendicular on the composite joists, is determined. The results show that changing in dimensions of the system, its boundary conditions, rigidity of main beam, and also adding tie beam, significant changes the FNF of the system up to 452.9%, 50.8%, -52.2%, %52.6%, respectively. In addition, increasing thickness of concrete slab increases the FNF of the system up to 10.8%. Furthermore, the results demonstrate that variation in rigidity of secondary beam, height of composite joist, and distance between composite joists, and thickness of top and bottom flanges of open web steel joists insignificant changes the FNF of the studied system up to -0.02%, -3%, -6.1%, and 0.96%, respectively. Finally, the results of this study help designer predict occurrence of resonance, comfortableness, and design criteria of the studied system.

Keywords: Fundamental Natural Frequency, Chromite Composite Floor System, Finite Element Method, low and high frequency floors, Comfortableness, resonance.

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3951 Optimization of Ultrasound Assisted Extraction and Characterization of Functional Properties of Dietary Fiber from Oat Cultivar S2000

Authors: Muhammad Suhail Ibrahim, Muhammad Nadeem, Waseem Khalid, Ammara Ainee, Taleeha Roheen, Sadaf Javaria, Aftab Ahmed, Hira Fatima, Mian Nadeem Riaz, Muhammad Zubair Khalid, Isam A. Mohamed Ahmed J, Moneera O. Aljobair

Abstract:

This study was executed to explore the efficacy of ultrasound-assisted extraction of dietary fiber from oat cultivar S2000. Extraction (variables time, temperature and amplitude) was optimized by using response surface methodology (RSM) conducted by Box Behnken Design (BBD). The effect of time, temperature and amplitude were studied at three levels. It was observed that time and temperature exerted more impact on extraction efficiency as compared to amplitude. The highest yield of total dietary fiber (TDF), soluble dietary fiber (SDF) and In-soluble dietary fiber (IDF) fractions were observed under ultrasound processing for 20 min at 40 ◦C with 80% amplitude. Characterization of extracted dietary fiber showed that it had better crystallinity, thermal properties and good fibrous structure. It also showed better functional properties as compared to traditionally extracted dietary fiber. Furthermore, dietary fibers from oats may offer high-value utilization and the expansion of comprehensive utilization in functional food and nutraceutical development.

Keywords: extraction, ultrasonication, response surface methodology, box behnken design

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3950 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

Abstract:

Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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3949 Recent Development on Application of Microwave Energy on Process Metallurgy

Authors: Mamdouh Omran, Timo Fabritius

Abstract:

A growing interest in microwave heating has emerged recently. Many researchers have begun to pay attention to microwave energy as an alternative technique for processing various primary and secondary raw materials. Compared to conventional methods, microwave processing offers several advantages, such as selective heating, rapid heating, and volumetric heating. The present study gives a summary on our recent works related to the use of microwave energy for the recovery of valuable metals from primary and secondary raw materials. The research is mainly focusing on: Application of microwave for the recovery and recycling of metals from different metallurgical industries wastes (i.e. electric arc furnace (EAF) dust, blast furnace (BF), basic oxygen furnace (BOF) sludge). Application of microwave for upgrading and recovery of valuable metals from primary raw materials (i.e. iron ore). The results indicated that microwave heating is a promising and effective technique for processing primary and secondary steelmaking wastes. After microwave treatment of iron ore for 60 s and 900 W, about a 28.30% increase in grindability.Wet high intensity magnetic separation (WHIMS) indicated that the magnetic separation increased from 34% to 98% after microwave treatment for 90 s and 900 W. In the case of EAF dust, after microwave processing at 1100 W for 20 min, Zinc removal from 64 % to ~ 97 %, depending on mixture ratio and treatment time.

Keywords: dielectric properties, microwave heating, raw materials, secondary raw materials

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3948 Parametric Evaluation for the Optimization of Gastric Emptying Protocols Used in Health Care Institutions

Authors: Yakubu Adamu

Abstract:

The aim of this research was to assess the factors contributing to the need for optimisation of the gastric emptying protocols in nuclear medicine and molecular imaging (SNMMI) procedures. The objective is to suggest whether optimisation is possible and provide supporting evidence for the current imaging protocols of gastric emptying examination used in nuclear medicine. The research involved the use of some selected patients with 30 dynamic series for the image processing using ImageJ, and by so doing, the calculated half-time, retention fraction to the 60 x1 minute, 5 minute and 10-minute protocol, and other sampling intervals were obtained. Results from the study IDs for the gastric emptying clearance half-time were classified into normal, abnormal fast, and abnormal slow categories. In the normal category, which represents 50% of the total gastric emptying image IDs processed, their clearance half-time was within the range of 49.5 to 86.6 minutes of the mean counts. Also, under the abnormal fast category, their clearance half-time fell between 21 to 43.3 minutes of the mean counts, representing 30% of the total gastric emptying image IDs processed, and the abnormal slow category had clearance half-time within the range of 138.6 to 138.6 minutes of the mean counts, representing 20%. The results indicated that the calculated retention fraction values from the 1, 5, and 10-minute sampling curves and the measured values of gastric emptying retention fraction from sampling curves of the study IDs had a normal retention fraction of <60% and decreased exponentially with an increase in time and it was evident with low percentages of retention fraction ratios of < 10% after the 4 hours. Thus, this study does not change categories suggesting that these values could feasibly be used instead of having to acquire actual images. Findings from the study suggest that the current gastric emptying protocol can be optimized by acquiring fewer images. The study recommended that the gastric emptying studies should be performed with imaging at a minimum of 0, 1, 2, and 4 hours after meal ingestion.

Keywords: gastric emptying, retention fraction, clearance halftime, optimisation, protocol

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3947 Functional Outcome of Femoral Neck System (FNS) In the Management of Neck of Femur Fractures

Authors: Ronak Mishra, Sachin Kale

Abstract:

Background: The clinical outcome of a new fixation device (femoral neck system, FNS) for femoral neck fractures is not described properly. The main purpose of this study was to evaluate the functional outcome of the patients of femoral neck fractures treated with FNS. Methods: A retrospective study was done among patients aged 60 years or less. On the basis of inclusion and exclusion criteria a final sample size of 30 was considered. Blood loss, type of fracture internal fixation, and length of clinical follow-up were all acquired from patient records. The volume of blood loss was calculated. The mean and standard deviation of continuous variables were reported (with range). Harris Hip score (HHS) And Post op xrays at intervals(6 weeks, 6 months ,12 months ) we used to clinically asses the patient. Results: Out of all 60% were females and 40% were males. The mean age of the patients was. 44.12(+-) years The comparison of functional outcomes of the patients treated with FNS using Harris Hip Score. It showed a highly significant comparison between the patients at post operatively , 6 weeks and 3 months and 12 months . There were no postoperative complications seen among the patients. Conclusion: FNS offers superior biomechanical qualities and greatly improved overall build stability. It allows for a significant reduction in operation time, potentially lowering risks and consequences associated with surgery.

Keywords: FNS, trauma, hip, neck femur fracture, minimally invasive surgery

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3946 Development of Novel Amphiphilic Block Copolymer of Renewable ε-Decalactone for Drug Delivery Application

Authors: Deepak Kakde, Steve Howdle, Derek Irvine, Cameron Alexander

Abstract:

The poor aqueous solubility is one of the major obstacles in the formulation development of many drugs. Around 70% of drugs are poorly soluble in aqueous media. In the last few decades, micelles have emerged as one of the major tools for solubilization of hydrophobic drugs. Micelles are nanosized structures (10-100nm) obtained by self-assembly of amphiphilic molecules into the water. The hydrophobic part of the micelle forms core which is surrounded by a hydrophilic outer shell called corona. These core-shell structures have been used as a drug delivery vehicle for many years. Although, the utility of micelles have been reduced due to the lack of sustainable materials. In the present study, a novel methoxy poly(ethylene glycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer was synthesized by ring opening polymerization (ROP) of renewable ε-decalactone (ε-DL) monomers on methoxy poly(ethylene glycol) (mPEG) initiator using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a organocatalyst. All the reactions were conducted in bulk to avoid the use of toxic organic solvents. The copolymer was characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC).The mPEG-b-PεDL block copolymeric micelles containing indomethacin (IND) were prepared by nanoprecipitation method and evaluated as drug delivery vehicle. The size of the micelles was less than 40nm with narrow polydispersity pattern. TEM image showed uniform distribution of spherical micelles defined by clear surface boundary. The indomethacin loading was 7.4% for copolymer with molecular weight of 13000 and drug/polymer weight ratio of 4/50. The higher drug/polymer ratio decreased the drug loading. The drug release study in PBS (pH7.4) showed a sustained release of drug over a period of 24hr. In conclusion, we have developed a new sustainable polymeric material for IND delivery by combining the green synthetic approach with the use of renewable monomer for sustainable development of polymeric nanomedicine.

Keywords: dopolymer, ε-decalactone, indomethacin, micelles

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3945 Adaptation of the Scenario Test for Greek-speaking People with Aphasia: Reliability and Validity Study

Authors: Marina Charalambous, Phivos Phylactou, Thekla Elriz, Loukia Psychogios, Jean-Marie Annoni

Abstract:

Background: Evidence-based practices for the evaluation and treatment of people with aphasia (PWA) in Greek are mainly impairment-based. Functional and multimodal communication is usually under assessed and neglected by clinicians. This study explores the adaptation and psychometric testing of the Greek (GR) version of The Scenario Test. The Scenario Test assesses the everyday functional communication of PWA in an interactive multimodal communication setting with the support of an active communication facilitator. Aims: To define the reliability and validity of The Scenario Test GR and discuss its clinical value. Methods & Procedures: The Scenario Test-GR was administered to 54 people with chronic stroke (6+ months post-stroke): 32 PWA and 22 people with stroke without aphasia. Participants were recruited from Greece and Cyprus. All measures were performed in an interview format. Standard psychometric criteria were applied to evaluate reliability (internal consistency, test-retest, and interrater reliability) and validity (construct and known – groups validity) of the Scenario Test GR. Video analysis was performed for the qualitative examination of the communication modes used. Outcomes & Results: The Scenario Test-GR shows high levels of reliability and validity. High scores of internal consistency (Cronbach’s α = .95), test-retest reliability (ICC = .99), and interrater reliability (ICC = .99) were found. Interrater agreement in scores on individual items fell between good and excellent levels of agreement. Correlations with a tool measuring language function in aphasia (the Aphasia Severity Rating Scale of the Boston Diagnostic Aphasia Examination), a measure of functional communication (the Communicative Effectiveness Index), and two instruments examining the psychosocial impact of aphasia (the Stroke and Aphasia Quality of Life questionnaire and the Aphasia Impact Questionnaire) revealed good convergent validity (all ps< .05). Results showed good known – groups validity (Mann-Whitney U = 96.5, p < .001), with significantly higher scores for participants without aphasia compared to those with aphasia. Conclusions: The psychometric qualities of The Scenario Test-GR support the reliability and validity of the tool for the assessment of functional communication for Greek-speaking PWA. The Scenario Test-GR can be used to assess multimodal functional communication, orient aphasia rehabilitation goal setting towards the activity and participation level, and be used as an outcome measure of everyday communication. Future studies will focus on the measurement of sensitivity to change in PWA with severe non-fluent aphasia.

Keywords: the scenario test GR, functional communication assessment, people with aphasia (PWA), tool validation

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3944 Oligoalkylamine Modified Poly(Amidoamine) Generation 4.5 Dendrimer for the Delivery of Small Interfering RNA

Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

Abstract:

In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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3943 Exchange Bias in Ceramics: From Polyol Made CoFe₂O₄-core@CoO-Shell NPs to Nanostructured Ceramics

Authors: N. Flores-Martinez, G. Franceschin, T. Gaudisson, J.-M. Greneche, R. Valenzuela-Monjaras, S. Ammar

Abstract:

Tailoring bulk materials keeping their nanoscale properties is the daydream of material scientists. But especially in magnetism, this single desire can revolutionize our everyday life. Now, thanks to the methods of synthesis, based on the combination of colloidal chemistry (CC) to flash sintering (FS), customizing magnets becomes each time more 'easy', 'cheap' and 'clean'. Although by CC we can obtain straightway nanopowders with good magnetic featuring, like exchange bias (EB) phenomenon, it does not result so attractive for applications. Since a solid material is simple to manipulate and integrate in a device, many consolidation methods have been tested aiming to keep the nanopowders characteristics after consolidation. Unfortunately, the lack of structural crystalline arrangement and the grain growth worsen the magnetic properties. In this work, we exhibit, for the first-time author’s best knowledge, the EB in sintered ceramics, starting from CoFe₂O₄-core@CoO-shell NPs obtained by CC. Despite the fact that EB field is about 28 mT in ceramics and it is not yet considered for applications, this work opens an alternative in the permanent magnets fabrication through a FS method, the spark plasma sintering, starting from CC synthesized nanopowders.

Keywords: core-shell nanoparticles, exchange bias, nanostructured ceramics, spark plasma sintering

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3942 Dependence of the Structural, Electrical and Magnetic Properties of YBa2Cu3O7−δ Bulk Superconductor on the Sm Doping

Authors: Raheleh Hajilou

Abstract:

In this study, we report the synthesis and characterization of YBa2Cu3O7-δ (YBCO) high-temperature superconductor prepared by solid-state method and doped with Sm in different weight percentages, 0, 0.01, 0.02 and 0.05 wt. The result of X-ray diffraction (XRD) analysis conforms to the formation of an orthorhombic phase of superconductivity in our samples. This is an important finding and indicates that the samples may exhibit superconductivity properties at certain conditions. Our results unequivocally point to a different structural order or disorder in SM/Y samples as compared to Sm based samples. We suggest that different site preferences of oxygen vacancies, predominantly created in CuO2 planes (CuO chains) of Y and Sm-based samples, might be responsible for the observed difference in the behavior. This contention is supported by a host of other considerations and experimental observations. The study investigated the effects of Sm doping on the YBCO system on various properties such as structural, critical temperature (Tc), scanning electron microscope (SEM), irresistibility line(IL), critical current density, jc, and flux line pinning force. It Seems the sample x=0.05 undergoes an insulator transition, which suppresses its superconducting transition temperature (Tc). Additionally, magnetization was measured as a function of temperature (M-T) and magnetic loops (M-H) at constant temperatures of 10. 20, 30, 40, 50 and 60K up to 10KG.

Keywords: high-Tc superconductors, Scanning electron microscopy, X-ray scattering, Irreversibility line

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3941 Structural Evolution of Na6Mn(SO4)4 from High-Pressure Synchrotron Powder X-ray Diffraction

Authors: Monalisa Pradhan, Ajana Dutta, Irshad Kariyattuparamb Abbas, Boby Joseph, T. N. Guru Row, Diptikanta Swain, Gopal K. Pradhan

Abstract:

Compounds with the Vanthoffite crystal structure having general formula Na6M(SO₄)₄ (M= Mg, Mn, Ni , Co, Fe, Cu and Zn) display a variety of intriguing physical properties intimately related to their structural arrangements. The compound Na6Mn(SO4)4 shows antiferromagnetic ordering at low temperature where the in-plane Mn-O•••O-Mn interactions facilitates antiferromagnetic ordering via a super-exchange interaction between the Mn atoms through the oxygen atoms . The inter-atomic bond distances and angles can easily be tuned by applying external pressure and can be probed using high resolution X-ray diffraction. Moreover, because the magnetic interaction among the Mn atoms are super-exchange type via Mn-O•••O-Mn path, the variation of the Mn-O•••O-Mn dihedral angle and Mn-O bond distances under high pressure inevitably affects the magnetic properties. Therefore, it is evident that high pressure studies on the magnetically ordered materials would shed light on the interplay between their structural properties and magnetic ordering. This will indeed confirm the role of buckling of the Mn-O polyhedral in understanding the origin of anti-ferromagnetism. In this context, we carried out the pressure dependent X-ray diffraction measurement in a diamond anvil cell (DAC) up to a maximum pressure of 17 GPa to study the phase transition and determine equation of state from the volume compression data. Upon increasing the pressure, we didn’t observe any new diffraction peaks or sudden discontinuity in the pressure dependences of the d values up to the maximum achieved pressure of ~17 GPa. However, it is noticed that beyond 12 GPa the a and b lattice parameters become identical while there is a discontinuity in the β value around the same pressure. This indicates a subtle transition to a pseudo-monoclinic phase. Using the third order Birch-Murnaghan equation of state (EOS) to fit the volume compression data for the entire range, we found the bulk modulus (B0) to be 44 GPa. If we consider the subtle transition at 12 GPa, we tried to fit another equation state for the volume beyond 12 GPa using the second order Birch-Murnaghan EOS. This gives a bulk modulus of ~ 34 GPa for this phase.

Keywords: mineral, structural phase transition, high pressure XRD, spectroscopy

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3940 Study on Construction of 3D Topography by UAV-Based Images

Authors: Yun-Yao Chi, Chieh-Kai Tsai, Dai-Ling Li

Abstract:

In this paper, a method of fast 3D topography modeling using the high-resolution camera images is studied based on the characteristics of Unmanned Aerial Vehicle (UAV) system for low altitude aerial photogrammetry and the need of three dimensional (3D) urban landscape modeling. Firstly, the existing high-resolution digital camera with special design of overlap images is designed by reconstructing and analyzing the auto-flying paths of UAVs, which improves the self-calibration function to achieve the high precision imaging by software, and further increased the resolution of the imaging system. Secondly, several-angle images including vertical images and oblique images gotten by the UAV system are used for the detail measure of urban land surfaces and the texture extraction. Finally, the aerial photography and 3D topography construction are both developed in campus of Chang-Jung University and in Guerin district area in Tainan, Taiwan, provide authentication model for construction of 3D topography based on combined UAV-based camera images from system. The results demonstrated that the UAV system for low altitude aerial photogrammetry can be used in the construction of 3D topography production, and the technology solution in this paper offers a new, fast, and technical plan for the 3D expression of the city landscape, fine modeling and visualization.

Keywords: 3D, topography, UAV, images

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3939 3D Vision Transformer for Cervical Spine Fracture Detection and Classification

Authors: Obulesh Avuku, Satwik Sunnam, Sri Charan Mohan Janthuka, Keerthi Yalamaddi

Abstract:

In the United States alone, there are over 1.5 million spine fractures per year, resulting in about 17,730 spinal cord injuries. The cervical spine is where fractures in the spine most frequently occur. The prevalence of spinal fractures in the elderly has increased, and in this population, fractures may be harder to see on imaging because of coexisting degenerative illness and osteoporosis. Nowadays, computed tomography (CT) is almost completely used instead of radiography for the imaging diagnosis of adult spine fractures (x-rays). To stop neurologic degeneration and paralysis following trauma, it is vital to trace any vertebral fractures at the earliest. Many approaches have been proposed for the classification of the cervical spine [2d models]. We are here in this paper trying to break the bounds and use the vision transformers, a State-Of-The-Art- Model in image classification, by making minimal changes possible to the architecture of ViT and making it 3D-enabled architecture and this is evaluated using a weighted multi-label logarithmic loss. We have taken this problem statement from a previously held Kaggle competition, i.e., RSNA 2022 Cervical Spine Fracture Detection.

Keywords: cervical spine, spinal fractures, osteoporosis, computed tomography, 2d-models, ViT, multi-label logarithmic loss, Kaggle, public score, private score

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3938 Structural Investigation and Hyperfine Interactions of BaBiₓLaₓFe₁₂₋₂ₓO₁₉ (0.0 ≤ X ≤ 0.5) Hexaferrites

Authors: Hakan Gungunes, Ismail A. Auwal, Abdulhadi Baykal, Sagar E. Shirsath

Abstract:

Barium hexaferrite, BaFe₁₂O₁₉, substituted by Bi³⁺ and La³⁺ (BaBiₓLaₓFe₁₂₋₂ₓO₁₉ where 0.0 ≤ x ≤ 0.5) were prepared by solid state synthesis route. The effect of substituted Bi³⁺ and La³⁺ ions on the structure, morphology, magnetic and cation distributions of barium hexaferrite were investigated by X-ray powder diffractometry (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR) and Mössbauer spectroscopy. XRD powder patterns were refined by the Rietveld analysis method which confirmed the formation of single phase magneto-plumbite structure and the substitution of La³⁺ and Bi³⁺ ions into the lattice of barium ferrite. These results show that both La³⁺ and Bi³⁺ ions completely enter into barium hexaferrite lattice without disturbing the hexagonal ferrite structure. The EDX spectra confirmed the presence of all the constituents in expected elemental percentage. From 57Fe Mössbauer spectroscopy data, the variation in line width, isomer shift, quadrupole splitting and hyperfine magnetic field values on Bi and La substitutions have been determined. Cation distribution in the presently investigated hexaferrite system was estimated using the relative area of Mössbauer spectroscopy.

Keywords: hexaferrite, mössbauer, cation distribution, solid state synthesis

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3937 Heat-Induced Uncertainty of Industrial Computed Tomography Measuring a Stainless Steel Cylinder

Authors: Verena M. Moock, Darien E. Arce Chávez, Mariana M. Espejel González, Leopoldo Ruíz-Huerta, Crescencio García-Segundo

Abstract:

Uncertainty analysis in industrial computed tomography is commonly related to metrological trace tools, which offer precision measurements of external part features. Unfortunately, there is no such reference tool for internal measurements to profit from the unique imaging potential of X-rays. Uncertainty approximations for computed tomography are still based on general aspects of the industrial machine and do not adapt to acquisition parameters or part characteristics. The present study investigates the impact of the acquisition time on the dimensional uncertainty measuring a stainless steel cylinder with a circular tomography scan. The authors develop the figure difference method for X-ray radiography to evaluate the volumetric differences introduced within the projected absorption maps of the metal workpiece. The dimensional uncertainty is dominantly influenced by photon energy dissipated as heat causing the thermal expansion of the metal, as monitored by an infrared camera within the industrial tomograph. With the proposed methodology, we are able to show evolving temperature differences throughout the tomography acquisition. This is an early study showing that the number of projections in computer tomography induces dimensional error due to energy absorption. The error magnitude would depend on the thermal properties of the sample and the acquisition parameters by placing apparent non-uniform unwanted volumetric expansion. We introduce infrared imaging for the experimental display of metrological uncertainty in a particular metal part of symmetric geometry. We assess that the current results are of fundamental value to reach the balance between the number of projections and uncertainty tolerance when performing analysis with X-ray dimensional exploration in precision measurements with industrial tomography.

Keywords: computed tomography, digital metrology, infrared imaging, thermal expansion

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3936 Structural, Electronic and Optical Properties of LiₓNa1-ₓH for Hydrogen Storage

Authors: B. Bahloul

Abstract:

This study investigates the structural, electronic, and optical properties of LiH and NaH compounds, as well as their ternary mixed crystals LiₓNa1-ₓH, adopting a face-centered cubic structure with space group Fm-3m (number 225). The structural and electronic characteristics are examined using density functional theory (DFT), while empirical methods, specifically the modified Moss relation, are employed for analyzing optical properties. The exchange-correlation potential is determined through the generalized gradient approximation (PBEsol-GGA) within the density functional theory (DFT) framework, utilizing the projected augmented wave pseudopotentials (PAW) approach. The Quantum Espresso code is employed for conducting these calculations. The calculated lattice parameters at equilibrium volume and the bulk modulus for x=0 and x=1 exhibit good agreement with existing literature data. Additionally, the LiₓNa1-ₓH alloys are identified as having a direct band gap.

Keywords: DFT, structural, electronic, optical properties

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3935 Design, Simulation and Fabrication of Electro-Magnetic Pulse Welding Coil and Initial Experimentation

Authors: Bharatkumar Doshi

Abstract:

Electro-Magnetic Pulse Welding (EMPW) is a solid state welding process carried out at almost room temperature, in which joining is enabled by high impact velocity deformation. In this process, high voltage capacitor’s stored energy is discharged in an EM coil resulting in a damped, sinusoidal current with an amplitude of several hundred kiloamperes. Due to these transient magnetic fields of few tens of Tesla near the coil is generated. As the conductive (tube) part is positioned in this area, an opposing eddy current is induced in this part. Consequently, high Lorentz forces act on the part, leading to acceleration away from the coil. In case of a tube, it gets compressed under forming velocities of more than 300 meters per second. After passing the joining gap it collides with the second metallic joining rod, leading to the formation of a jet under appropriate collision conditions. Due to the prevailing high pressure, metallurgical bonding takes place. A characteristic feature is the wavy interface resulting from the heavy plastic deformations. In the process, the formation of intermetallic compounds which might deteriorate the weld strength can be avoided, even for metals with dissimilar thermal properties. In order to optimize the process parameters like current, voltage, inductance, coil dimensions, workpiece dimensions, air gap, impact velocity, effective plastic strain, shear stress acting in the welding zone/impact zone etc. are very critical and important to establish. These process parameters could be determined by simulation using Finite Element Methods (FEM) in which electromagnetic –structural couple field analysis is performed. The feasibility of welding could thus be investigated by varying the parameters in the simulation using COMSOL. Simulation results shall be applied in performing the preliminary experiments of welding the different alloy steel tubes and/or alloy steel to other materials. The single turn coil (S.S.304) with field shaper (copper) has been designed and manufactured. The preliminary experiments are performed using existing EMPW facility available Institute for Plasma Research, Gandhinagar, India. The experiments are performed at 22kV charged into 64µF capacitor bank and the energy is discharged into single turn EM coil. Welding of axi-symetric components such as aluminum tube and rod has been proven experimentally using EMPW techniques. In this paper EM coil design, manufacturing, Electromagnetic-structural FEM simulation of Magnetic Pulse Welding and preliminary experiment results is reported.

Keywords: COMSOL, EMPW, FEM, Lorentz force

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3934 Reliability of Diffusion Tensor Imaging in Differentiation of Salivary Gland Tumors

Authors: Sally Salah El Menshawy, Ghada M. Ahmed GabAllah, Doaa Khedr M. Khedr

Abstract:

Background: Our study aims to detect the diagnostic role of DTI in the differentiation of salivary glands benign and malignant lesions. Results: Our study included 50 patients (25males and 25 females) divided into 4 groups (benign lesions n=20, malignant tumors n=13, post-operative changes n=10 and normal n=7). 28 patients were with parotid gland lesions, 4 patients were with submandibular gland lesions and only 1 case with sublingual gland affection. The mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of malignant salivary gland tumors (n = 13) (0.380±0.082 and 0.877±0.234× 10⁻³ mm² s⁻¹) were significantly different (P<0.001) than that of benign tumors (n = 20) (0.147±0.03 and 1.47±0.605 × 10⁻³ mm² s⁻¹), respectively. The mean FA and ADC of post-operative changes (n = 10) were (0.211±0.069 and 1.63±0.20× 10⁻³ mm² s⁻¹) while that of normal glands (n =7) was (0.251±0.034and 1.54±0.29× 10⁻³ mm² s⁻¹), respectively. Using ADC to differentiate malignant lesions from benign lesions has an (AUC) of 0.810, with an accuracy of 69.7%. ADC used to differentiate malignant lesions from post-operative changes has (AUC) of 1.0, and an accuracy of 95.7%. FA used to discriminate malignant from benign lesions has (AUC) of 1.0, and an accuracy of 93.9%. FA used to differentiate malignant from post-operative changes has (AUC) of 0.923, and an accuracy of 95.7%. Combined FA and ADC used to differentiate malignant from benign lesions has (AUC) of 1.0, and an accuracy of 100%. Combined FA and ADC used to differentiate malignant from post-operative changes has (AUC) of 1.0, and an accuracy of 100%. Conclusion: Combined FA and ADC can differentiate malignant tumors from benign salivary gland lesions.

Keywords: diffusion tensor imaging, MRI, salivary gland, tumors

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3933 Design and Optimization of an Electromagnetic Vibration Energy Converter

Authors: Slim Naifar, Sonia Bradai, Christian Viehweger, Olfa Kanoun

Abstract:

Vibration provides an interesting source of energy since it is available in many indoor and outdoor applications. Nevertheless, in order to have an efficient design of the harvesting system, vibration converters have to satisfy some criterion in terms of robustness, compactness and energy outcome. In this work, an electromagnetic converter based on mechanical spring principle is proposed. The designed harvester is formed by a coil oscillating around ten ring magnets using a mechanical spring. The proposed design overcomes one of the main limitation of the moving coil by avoiding the contact between the coil wires with the mechanical spring which leads to a better robustness for the converter. In addition, the whole system can be implemented in a cavity of a screw. Different parameters in the harvester were investigated by finite element method including the magnet size, the coil winding number and diameter and the excitation frequency and amplitude. A prototype was realized and tested. Experiments were performed for 0.5 g to 1 g acceleration. The used experimental setup consists of an electrodynamic shaker as an external artificial vibration source controlled by a laser sensor to measure the applied displacement and frequency excitation. Together with the laser sensor, a controller unit, and an amplifier, the shaker is operated in a closed loop which allows controlling the vibration amplitude. The resonance frequency of the proposed designs is in the range of 24 Hz. Results indicate that the harvester can generate 612 mV and 1150 mV maximum open circuit peak to peak voltage at resonance for 0.5 g and 1 g acceleration respectively which correspond to 4.75 mW and 1.34 mW output power. Tuning the frequency to other values is also possible due to the possibility to add mass to the moving part of the or by changing the mechanical spring stiffness.

Keywords: energy harvesting, electromagnetic principle, vibration converter, moving coil

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3932 Fluorescence Resonance Energy Transfer in a Supramolecular Assembly of Luminescent Silver Nanoclusters and Cucurbit[8]uril Based Host-Guest System

Authors: Srikrishna Pramanik, Sree Chithra, Saurabh Rai, Sameeksha Agrawal, Debanggana Shil, Saptarshi Mukherjee

Abstract:

The understanding of interactions between organic chromophores and biologically useful luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host-guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host-guest chemistry between a cationic guest, Ethidium Bromide and the anionic host Cucurbit[8]uril using spectroscopic and calorimetric techniques to decipher their interaction mechanism in modulating photophysical properties of the chromophore. Next, we synthesized a series of blue-emitting AgNCs using different templates such as protein, peptides, and cyclodextrin. The as-prepared AgNCs were characterized by various spectroscopic techniques. We have established that these AgNCs can be employed as donors in the FRET process with the above acceptor for FRET-based emission color tuning. Our in-depth studies revealed that surface ligands play a key role in modulating FRET efficiency. Overall, by employing a non-covalent strategy, we have tried to develop FRET pairs using blue-emitting NCs and a host-guest complex, which could find potential applications in constructing advanced white light-emitting, anti-counterfeiting materials, and developing biosensors.

Keywords: absorption spectroscopy, cavities, energy transfer, fluorescence, fluorescence resonance energy transfer

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3931 First-Principles Density Functional Study of Nitrogen-Doped P-Type ZnO

Authors: Abdusalam Gsiea, Ramadan Al-habashi, Mohamed Atumi, Khaled Atmimi

Abstract:

We present a theoretical investigation on the structural, electronic properties and vibrational mode of nitrogen impurities in ZnO. The atomic structures, formation and transition energies and vibrational modes of (NO3)i interstitial or NO4 substituting on an oxygen site ZnO were computed using ab initio total energy methods. Based on Local density functional theory, our calculations are in agreement with one interpretation of bound-excition photoluminescence for N-doped ZnO. First-principles calculations show that (NO3)i defects interstitial or NO4 substituting on an Oxygen site in ZnO are important suitable impurity for p-type doping in ZnO. However, many experimental efforts have not resulted in reproducible p-type material with N2 and N2O doping. by means of first-principle pseudo-potential calculation we find that the use of NO or NO2 with O gas might help the experimental research to resolve the challenge of achieving p-type ZnO.

Keywords: DFF, nitrogen, p-type, ZnO

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3930 Evaluation of the Impact of Functional Communication Training on Behaviors of Concern for Students at a Non-Maintained Special School

Authors: Kate Duggan

Abstract:

Introduction: Functional Communication Training (FCT) is an approach which aims to reduce behaviours of concern by teaching more effective ways to communicate. It requires identification of the function of the behaviour of concern, through gathering information from key stakeholders and completing observations of the individual’s behaviour including antecedents to, and consequences of the behaviour. Appropriate communicative alternatives are then identified and taught to the individual using systematic instruction techniques. Behaviours of concern demonstrated by individuals with autism spectrum conditions (ASC) frequently have a communication function. When contributing to positive behavior support plans, speech and language therapists and other professionals working with individuals with ASC need to identify alternative communicative behaviours which are equally reinforcing as the existing behaviours of concern. Successful implementation of FCT is dependent on an effective ‘response match’. The new way of communicating must be equally as effective as the behaviour previously used and require the same amount or less effort from the individual. It must also be understood by the communication partners the individual encounters and be appropriate to their communicative contexts. Method: Four case studies within a non-maintained special school environment were described and analysed. A response match framework was used to identify the effectiveness of functional communication training delivered by the student’s speech and language therapist, teacher and learning support assistants. The success of systematic instruction techniques used to develop new communicative behaviours was evaluated using the CODES framework. Findings: Functional communication training can be used as part of a positive behaviour support approach for students within this setting. All case studies reviewed demonstrated ‘response success’, in that the desired response was gained from the new communicative behaviour. Barriers to the successful embedding of new communicative behaviours were encountered. In some instances, the new communicative behaviour could not be consistently understood across all communication partners which reduced ‘response recognisability’. There was also evidence of increased physical or cognitive difficulty in employing the new communicative behaviour which reduced the ‘response effectivity’. Successful use of ‘thinning schedules of reinforcement’, taught students to tolerate a delay to reinforcement once the new communication behaviour was learned.

Keywords: augmentative and alternative communication, autism spectrum conditions, behaviours of concern, functional communication training

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3929 Functional Vision of Older People in Galician Nursing Homes

Authors: C. Vázquez, L. M. Gigirey, C. P. del Oro, S. Seoane

Abstract:

Early detection of visual problems plays a key role in the aging process. However, although vision problems are common among older people, the percentage of aging people who perform regular optometric exams is low. In fact, uncorrected refractive errors are one of the main causes of visual impairment in this group of the population. Purpose: To evaluate functional vision of older residents in order to show the urgent need of visual screening programs in Galician nursing homes. Methodology: We examined 364 older adults aged 65 years and over. To measure vision of the daily living, we tested distance and near presenting visual acuity (binocular visual acuity with habitual correction if warn, directional E-Snellen) Presenting near vision was tested at the usual working distance. We defined visual impairment (distance and near) as a presenting visual acuity less than 0.3. Exclusion criteria included immobilized residents unable to reach the USC Dual Sensory Loss Unit for visual screening. Association between categorical variables was performed using chi-square tests. We used Pearson and Spearman correlation tests and the variance analysis to determine differences between groups of interest. Results: 23,1% of participants have visual impairment for distance vision and 16,4% for near vision. The percentage of residents with far and near visual impairment reaches 8,2%. As expected, prevalence of visual impairment increases with age. No differences exist with regard to the level of functional vision between gender. Differences exist between age group respect to distance vision, but not in case of near vision. Conclusion: prevalence of visual impairment is high among the older people tested in this pilot study. This means a high percentage of older people with limitations in their daily life activities. It is necessary to develop an effective vision screening program for early detection of vision problems in Galician nursing homes.

Keywords: functional vision, elders, aging, nursing homes

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3928 Experimental Investigation of Beams Having Spring Mass Resonators

Authors: Somya R. Patro, Arnab Banerjee, G. V. Ramana

Abstract:

A flexural beam carrying elastically mounted concentrated masses, such as engines, motors, oscillators, or vibration absorbers, is often encountered in mechanical, civil, and aeronautical engineering domains. To prevent resonance conditions, the designers must predict the natural frequencies of such a constrained beam system. This paper investigates experimental and analytical studies on vibration suppression in a cantilever beam with a tip mass with the help of spring-mass to achieve local resonance conditions. The system consists of a 3D printed polylactic acid (PLA) beam screwed at the base plate of the shaker system. The top of the free end is connected by an accelerometer which also acts as a tip mass. A spring and a mass are attached at the bottom to replicate the mechanism of the spring-mass resonator. The Fast Fourier Transform (FFT) algorithm converts time acceleration plots into frequency amplitude plots from which transmittance is calculated as a function of the excitation frequency. The mathematical formulation is based on the transfer matrix method, and the governing differential equations are based on Euler Bernoulli's beam theory. The experimental results are successfully validated with the analytical results, providing us essential confidence in our proposed methodology. The beam spring-mass system is then converted to an equivalent two-degree of freedom system, from which frequency response function is obtained. The H2 optimization technique is also used to obtain the closed-form expression of optimum spring stiffness, which shows the influence of spring stiffness on the system's natural frequency and vibration response.

Keywords: euler bernoulli beam theory, fast fourier transform, natural frequencies, polylactic acid, transmittance, vibration absorbers

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3927 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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