ABSTRACT
Major polyamines include putrescine, spermidine, spermine and thermospermine, which play vital roles in growth and adaptation against environmental changes in plants. Thermospermine (T-Spm) is synthetised by ACL5. The function of ACL5 in rice is still unknown. In this study, we used a reverse genetic strategy to investigate the biological function of OsACL5. We generated several knockout mutants by pYLCRISPR/Cas9 system and overexpressing (OE) lines of OsACL5. Interestingly, the OE plants exhibited environmentally-dependent leaf rolling, smaller grains, lighter 1000-grain weight and reduction in yield per plot. The area of metaxylem vessels of roots and leaves of OE plants were significantly smaller than those of WT, which possibly caused reduction in leaf water potential, resulting in leaf rolling with rise in the environmental temperature and light intensity and decrease in humidity. Additionally, the T-Spm contents were markedly increased by over ninefold whereas the ethylene evolution was reduced in OE plants, suggesting that T-Spm signalling pathway interacts with ethylene pathway to regulate multiple agronomic characters. Moreover, the osacl5 exhibited an increase in grain length, 1000-grain weight, and yield per plot. OsACL5 may affect grain size via mediating the expression of OsDEP1, OsGS3 and OsGW2. Furthermore, haplotypes analysis indicated that OsACL5 plays a conserved function on regulating T-Spm levels during the domestication of rice. Our data demonstrated that identification of OsACL5 provides a theoretical basis for understanding the physiological mechanism of T-Spm which may play roles in triggering environmentally dependent leaf rolling; OsACL5 will be an important gene resource for molecular breeding for higher yield.
Subject(s)
Oryza , Spermine/analogs & derivatives , Oryza/metabolism , Spermine/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Ethylenes/metabolism , Edible Grain/genetics , Edible Grain/metabolism , Gene Expression Regulation, Plant/geneticsABSTRACT
We introduce a new scanning probe microscopy (SPM) concept called reverse tip sample scanning probe microscopy (RTS SPM), where the tip and sample positions are reversed as compared to traditional SPM. The main benefit of RTS SPM over the standard SPM configuration is that it allows for simple and fast tip changes. This overcomes two major limitations of SPM which are slow data acquisition and a strong dependency of the data on the tip condition. A probe chip with thousands of sharp integrated tips is the basis of our concept. We have developed a nanofabrication protocol for Si based probe chips and their functionalization with metal and diamond coatings, evaluated our probe chips for various RTS SPM applications (multi-tip imaging, SPM tomography, and correlative SPM), and showed the high potential of the RTS SPM concept.
ABSTRACT
Effective project planning and management in the global software development landscape relies on addressing major issues like cost estimation and effort allocation. Timely estimation of software development is a critical focus in software engineering research. With the industry increasingly relying on diverse teams worldwide, accurate estimation becomes vital. Software size serves as a common measure for costs and schedules, but advanced estimation methods consider various variables, such as project purpose, personnel expertise, time and efficiency constraints, and technology requirements. Estimating software costs involve significant financial and strategic commitments, making it crucial to address complexity and versatility related to cost drivers. To achieve enhanced accuracy and convergence, we employ the cuckoo algorithm in our proposed NFDLNN (Neuro Fuzzy Logic and Deep Learning Neural Networks) model. Through extensive validation with industrial project data, using Function Point Analysis as the algorithmic models, our NFA model demonstrates high accuracy in software cost approximation, outperforming existing methods insights of MRE of 3.33, BRE of 0.13, and PI of 74.48. Our research contributes to improved project planning and decision-making processes in global software development endeavours.
ABSTRACT
BACKGROUND: Alpine skiing involves the conversion of potential energy into kinetic energy, with the "velocity barrier" (VB) at each moment corresponding to the maximal velocity at which the athlete can ski while staying within the boundaries of the gates and maintaining control. Nevertheless, this concept has never been proven by evidence. The aim of this study was to experimentally test the existence of the VB and clarify its relationship with skier's force production/application capacities. METHODS: Fourteen skiers were equipped with ski-mounted force plates and a positional device and ran a 2-turn Giant Slalom section starting from eight different heights on the slope. Three conditions were selected for further analysis: minimal entrance velocity (vmin ); entrance velocity allowing the better section time (VB); maximal entrance velocity (vmax ). Entrance velocity, section time, mean force output, ratio of force application effectiveness, velocity normalized energy dissipation, and path length were compared between the three conditions. Moreover, skier's mechanical energy and velocity curves were compared all along the section between the three conditions using SPM analysis. RESULTS: The section time was reduced in VB compared to vmin (p < 0.001) and vmax (p = 0.002). Skiers presented an incapacity to increase force output beyond the VB (p = 0.441) associated with a lower force application effectiveness (p = 0.005). Maximal entrance velocity was associated to higher energy dissipation (p < 0.001) and path length (p = 0.005). CONCLUSION: The present study experimentally supports the existence of the VB. The force production/application capacities seem to limit the skiing effectiveness beyond the VB, associated to increased energy dissipations and path length.
Subject(s)
Skiing , Humans , Biomechanical Phenomena , AthletesABSTRACT
Human phagocytes have key functions in the resolution of inflammation. Here, we assessed the role of the proposed 4S,5S-epoxy-resolvin intermediate in the biosynthesis of both resolvin D3 and resolvin D4. We found that human neutrophils converted this synthetic intermediate to resolvin D3 and resolvin D4. M2 macrophages transformed this labile epoxide intermediate to resolvin D4 and a previously unknown cysteinyl-resolvin isomer without appreciable amounts of resolvin D3. M2 macrophages play critical roles in the resolution of inflammation and in wound healing. Human M2 macrophages also converted leukotriene A4 to lipoxins. The cysteinyl-resolvin isomer significantly accelerated tissue regeneration of surgically injured planaria. In a model of human granuloma formation, the cysteinyl-resolvin isomer significantly inhibited granuloma development by human peripheral blood leukocytes. Together, these results provide evidence for a human cell type-specific role of 4S,5S-epoxy-resolvin in the biosynthesis of resolvin D3 by neutrophils, resolvin D4 by both M2 macrophages and neutrophils, and a unique cysteinyl-resolvin isomer produced by M2 macrophages that carries potent biological activities in granuloma formation and tissue regeneration.
Subject(s)
Fatty Acids, Unsaturated/metabolism , Leukocytes/metabolism , Macrophages/metabolism , Cells, Cultured , Granuloma , HumansABSTRACT
INTRODUCTION: Previous research indicates that children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) experience sensory reactivity differences that impact occupational performance. The purpose of this study was to determine whether there are differences in sensory reactivity in these children across two different time points; during exacerbation and during remission, using the Sensory Processing Measure (SPM) Home-Form. The study also sought to investigate whether children with PANS experience sensory differences during remission periods, when compared with SPM Home-Form norms. METHODS: A two-period bidirectional case-crossover design was used, and an online assessment was conducted to measure sensory reactivity. Parents of children aged 4.6 to 13.1 years with a diagnosis of PANS were recruited from various sites across Australia, USA, England, Ireland, Scotland, Canada, and New Zealand. The SPM Home-Form was used to measure sensory reactivity at two time points, when PANS was in remission (T-R) and in exacerbation (T-E). Study entry was permitted at either T-E or T-R. Participant exacerbation status was monitored over a maximum 12-month period, and a follow-up SPM Home-Form was sent when a change in exacerbation status was indicated. A linear mixed model was used to assess the difference between SPM Home-Form norm-referenced scores during exacerbation and remission. RESULTS: The study included 82 participants, with 80 providing data at study entry, and 27 providing data at follow-up. Results showed a statistically significant decline in performance across the SPM Home-Form domains of Hearing, Social Participation, Planning and Ideas, and Total Sensory Systems T-scores during exacerbation when compared with remission data. Results also demonstrated atypical sensory reactivity across Vision, Hearing, Touch, Balance and Motion, and Total Sensory Systems domains during periods of remission compared with SPM Home-Form norms. CONCLUSION: This study found that children with PANS experience significant sensory reactivity differences during exacerbation and remission across multiple sensory domains, with a decline in performance during exacerbation. Where there are occupational performance challenges, occupational therapists should consider administering sensory assessments so that effective intervention plans addressing the unique sensory reactivity needs of children with PANS can be developed.
Subject(s)
Occupational Therapy , Humans , Child , Male , Female , Occupational Therapy/methods , Child, Preschool , Adolescent , Cross-Over Studies , Sensation/physiology , Australia , Autoimmune Diseases , Obsessive-Compulsive DisorderABSTRACT
Thermally-induced dehydrogenative coupling of polyphenylenes on metal surfaces is an important technique to synthesize ð-conjugated carbon nanostructures with atomic precision. However, this protocol has rarely been utilized to fabricate structurally defined carbon nanosheets composed of sp- and sp2-hybridized carbon atoms. Here, we present the synthesis of butadiyne-linked hexabenzocoronenes (HBCs) on Au(111) surfaces as core-expanded graphdiynes. The reaction started from hexa(4-ethylphenyl)benzene, which undergoes dehydrogenation toward hexa(4-vinylphenyl)benzene, followed by planarization to hexabenzocoronene, coupling between the vinyl groups, and further dehydrogenation. In addition to butadiyne linkages, benzene groups were also found as another type of linker. The reaction sequences were monitored by scanning tunneling microscopy and bond-resolved non-contact atomic force microscopy, which disclose the structures of intermediates and final products. In combination with density functional theory simulations, the key steps from ethyl substituents to butadiyne and benzene linkers were elucidated. This is a new on-surface synthesis of core-expanded graphdiynes with unprecedented electronic properties.
ABSTRACT
A surge in the prevalence of obesity and metabolic syndrome, which promote systemic inflammation, underlies an increase in cardiometabolic disease. Free fatty acid receptor 4 is a nutrient sensor for long-chain fatty acids, like ω3-polyunsaturated fatty acids (ω3-PUFAs), that attenuates metabolic disease and resolves inflammation. Clinical trials indicate ω3-PUFAs are cardioprotective, and this review discusses the mechanistic links between ω3-PUFAs, free fatty acid receptor 4, and attenuation of cardiometabolic disease.
Subject(s)
Cardiovascular Diseases , Fatty Acids, Omega-3 , Fatty Acids, Nonesterified , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/therapeutic use , Humans , Inflammation , Signal TransductionABSTRACT
The aim of this study was to explore the influences of age-matched control and/or age-specific template on voxel-wise analysis of brain 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) data in pediatric epilepsy patients. We, retrospectively, included 538 pediatric (196 females; age range of 12 months to 18 years) and 35 adult subjects (18 females; age range of 20-50 years) without any cerebral pathology as pediatric and adult control group, respectively, as well as 109 pediatric patients with drug-resistant epilepsy (38 females; age range of 13 months to 18 years) as epilepsy group. Statistical parametric mapping (SPM) analysis for 18 F-FDG PET data of each epilepsy patients was performed in four types of procedures, by using age-matched controls with age-specific template, age-matched controls with adult template, adult controls with age-specific template or adult controls with adult template. The numbers of brain regions affected by artifacts among these four types of SPM analysis procedures were further compared. Any template being adopted, the artifacts were significantly less in SPM analysis procedures using age-matched controls than those using adult controls in each age range (p < .001 in each comparison), except in the age range of 15-18 (p > .05 in each comparison). No significant difference was found in artifacts, when compared procedures using the identical control group with different templates (p = 1.000 in each comparison). In conclusion, the age stratification for age-matched control should be divided as many layers as possible for the SPM analysis of brain 18 F-FDG PET images, especially in pediatric patients ≤14-year-old, while age-specific template is not mandatory.
Subject(s)
Epilepsy , Fluorodeoxyglucose F18 , Adult , Female , Humans , Child , Infant , Young Adult , Middle Aged , Adolescent , Fluorodeoxyglucose F18/metabolism , Retrospective Studies , Epilepsy/diagnostic imaging , Epilepsy/metabolism , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Brain Mapping , Age Factors , RadiopharmaceuticalsABSTRACT
Specialized pro-resolving lipid mediators (SPMs) such as lipoxins or resolvins are formed by the consecutive action of 5-lipoxygenase (5-LO, ALOX5) and different types of arachidonic acid 12- or 15-lipoxygenases using arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid as substrate. Lipoxins are trihydroxylated oxylipins which are formed from arachidonic and eicosapentaenoic acid. The latter can also be converted to di- and trihydroxylated resolvins of the E series, whereas docosahexaenoic acid is the substrate for the formation of di- and trihydroxylated resolvins of the D series. Here, we summarize the formation of lipoxins and resolvins in leukocytes. From the data published so far, it becomes evident that FLAP is required for the biosynthesis of most of the lipoxins and resolvins. Even in the presence of FLAP, formation of the trihydroxylated SPMs (lipoxins, RvD1-RvD4, RvE1) in leukocytes is very low or undetectable which is obviously due to the extremely low epoxide formation by 5-LO from oxylipins such as 15-H(p)ETE, 18-H(p)EPE or 17-H(p)DHA. As a result, only the dihydroxylated oxylipins (5 S,15S-diHETE, 5 S,15S-diHEPE) and resolvins (RvD5, RvE2, RvE4) can be consistently detected using leukocytes as SPM source. However, the reported levels of these dihydroxylated lipid mediators are still much lower than those of the typical pro-inflammatory mediators including the monohydroxylated fatty acid derivatives (e.g. 5-HETE), leukotrienes or cyclooxygenase-derived prostaglandins. Since 5-LO expression is mainly restricted to leukocytes these cells are considered as the main source of SPMs. The low formation of trihydroxylated SPMs in leukocytes, the fact that they are hardly detected in biological samples as well as the lack of functional signaling by their receptors make it highly questionable that trihydroxylated SPMs play a role as endogenous mediators in the resolution of inflammation.
Subject(s)
Lipoxins , Humans , Lipoxins/metabolism , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid , Arachidonic Acid , Oxylipins , Eicosanoids/metabolism , Inflammation/metabolism , LeukocytesABSTRACT
In patients with coronary artery disease (CAD), plasma levels of pro-inflammatory lipid mediators such as PGE2 and TxA2 are increased. They could increase vascular contraction while EPA and DHA could reduce it. Studies have been mostly conducted on animal vessels. Therefore, the aim of the study was to investigate if EPA, DHA, and DHA-derived metabolites: RvD1, RvD5 and MaR1 can modulate contraction of human coronary arteries (HCA) induced by PGE2 or TxA2 stable analogue (U46619). DHA and EPA relaxed HCA pre-contracted with PGE2. 18 h-incubation with DHA but not EPA reduced the PGE2-induced contractions. Pre-incubation with RvD1, RvD5 and MaR1 reduced the PGE2-induced contractions. Indomethacin did not significantly modify the PGE2 responses. L-NOARG (inhibitor of nitric oxide synthase), reduced only the PGE2-induced contractions in RvD1-treated rings. Finally, FPR2/ALX, GPR32 and LGR6 receptors are detected in HCA by immunofluorescence. Our results indicate that DHA and its metabolites could be beneficial for HCA blood flow and could be a therapeutic perspective for patients with CAD.
Subject(s)
Coronary Vessels , Dinoprostone , Animals , Humans , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid , Dinoprostone/pharmacology , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/pharmacology , Thromboxane A2 , Eicosapentaenoic AcidABSTRACT
Pseudomonas aeruginosa is considered as one of the human health care problems, P. aeruginosa's carbapenem resistance emerges by several different mechanisms, some of which include carbapenems genes. P. aeruginosa's carbapenem resistance is a significant health concern, So this study aims to evaluate MBL gene expressions. The study was conducted at the Department of Microbiology, AL-Mahmoodia Hospital, over one year from January to December 2022. The samples were collected from patients with different clinical sources (Burn, Urine, Wound, Sputum, Ear, and Blood), from different ages while. Samples were collected from three hospitals in Baghdad including Al-Yarmouk Teaching Hospital, AL-Mahmmodiya Hospital, and Child's Central Teaching Hospital. A study analyzed 55 P. aeruginosa strains from various clinical sources, the study utilizes the chemical characterization, VITEK 2 system, 16s rRNA, antibiogram sensitivity tests, antibiotic susceptibility using eight antibiotics, including Amikacin, Ciprofloxacin, Levofloxacin, Imipenem Meropenem, Piperacillin, Cefepim and Aztreonam. The test of bacterial susceptibility revealed that each isolate was highly resistant to piperacillin, which are 96.36%, and lower resistance to Ciprofloxacin, which are 32%. Phenotypic screening carbapenem resistance methods combined the disk synergy test and conventional PCR that were used to detect isolates by using 16 S rRNA. This proves that the bacteria is P. aeruginosa and computed by measuring gene expression of the target genes (GIM, VIM, SPM) by using the real-time PCR, which is employed for twenty-five isolates. The result indicates that the expression level of the VIM gene is highly regulated in carbapenem-resistance isolates compared to control isolates that is 1.00. While the expression level of gene GIM and SPM is downregulated in carbapenem-resistance isolates compared to control isolates that is 6. The carbapenem VIM and GIM, SPM (class B) genes are essential for resistance in P. aeruginosa induced by chromosomal changes that modify membrane permeability efflux pump overexpression for genes. As a result, many studies require for discovering new strategies to reduce the threat to public health through preventing the spread of these isolates via tight infections, control measures, and the reduction of the danger to public health.
Subject(s)
Pseudomonas Infections , beta-Lactamases , Child , Humans , beta-Lactamases/genetics , beta-Lactamases/metabolism , Pseudomonas aeruginosa/genetics , RNA, Ribosomal, 16S , Pseudomonas Infections/genetics , Pseudomonas Infections/microbiology , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Real-Time Polymerase Chain Reaction , Piperacillin , Ciprofloxacin , Gene Expression , Microbial Sensitivity TestsABSTRACT
Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.
Subject(s)
Inflammatory Bowel Diseases , Receptors, Formyl Peptide , Animals , Mice , Humans , Receptors, Formyl Peptide/metabolism , Inflammation/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/metabolism , Neutrophils/metabolism , Inflammatory Bowel Diseases/drug therapyABSTRACT
The purpose was to investigate full-body kinematics and vertical ground reaction forces in the lower extremities of the delivery and to determine delivery changes over time after many deliveries in ten-pin bowling. Six male elite ten-pin bowlers completed six bouts of twelve bowling deliveries, all strike attempts, while measuring full-body kinematics and vertical ground reaction forces. Full-body joint angles, peak vertical ground reaction forces in the feet, vertical breaking impulse, centre of mass velocity, bowling score, and ball release velocity (BRvel) were measured. Results revealed that the BRvel was significantly decreased over bouts (p < 0.001). Additionally, increased flexion of the dominant wrist (p < 0.001) and elbow (p = 0.004) prior to ball release (BR) and increased pronation of the dominant wrist during BR (p = 0.034) were observed at later bouts. It was concluded that these kinematic changes in the dominant wrist and elbow prior to and during BR were performed to compensate for the change in traction between ball and lane during a bowling match. This, in turn, caused a decrease in BRvel. A conservation of energy perspective was discussed to highlight training applications and possibilities to enhance elite athletes' bowling performance.
Subject(s)
Sports , Humans , Male , Biomechanical Phenomena , Upper Extremity , Lower Extremity , FootABSTRACT
Water quality is one of the essential parameters of environmental monitoring; even a slight variation in its characteristics may significantly influence the ecosystem. The water quality of Vembanad Lake is affected by anthropogenic effects such as industrial effluents and tourism. The optical parameters representing water quality, such as diffuse attenuation (Kd), turbidity, suspended particulate matter (SPM), and chlorophyll-a (Chl-a), are considered in this study to evaluate the water quality of Vembanad Lake, Kerala, India. As this lake is regarded as of ecological importance by the Ramsar Convention and has faced severe concerns over recent years, there was a substantial change in the water quality during the lockdowns of the COVID-19 pandemic. This research is aimed at examining the change in water quality using optical data from Sentinel-2 satellites in the ACOLITE processing software from 2016 to 2021. The analyses showed a 2.5% decrease in the values of Kd, whereas SPM and turbidity show a reduction of about 4.3% from the year 2016 to 2021. The flood and the COVID lockdown had an impact on the improvement in the quality of water from 2018 to 2021. The findings indicated that the reduction in industrial activities and tourism had a more significant effect on the improvement in the water quality of the lake. There was no substantial change in the Chl-a until 2020, whereas an average decrease of 12% in Chl-a values was observed throughout 2021. This decrease can be attributed to the reduction in the lake's hydrological residence time (HRT). Thus, these findings will be a valuable reference to help the government and non-government organizations (NGO) during strategic planning.
Subject(s)
COVID-19 , Lepidoptera , Humans , Animals , Water Quality , Environmental Monitoring , Ecosystem , Lakes , Pandemics , Remote Sensing Technology , COVID-19/epidemiology , Communicable Disease Control , India , Particulate MatterABSTRACT
This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the "autocorrelation", metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P < 0.05). AI in contralateral cerebellum exterior cortex was significantly positively correlated with that in ipsilateral caudate, putamen, pallidum, thalamus proper, ventral diencephalon, red nucleus and pons among CCD+ group (all P < 0.01), but only with that in ipsilateral caudate and putamen among CCD- group (both P < 0.001). These results provide additional insight into the involvement of both cortico-ponto-cerebellar and cortico-rubral pathways in the presence of CCD, underlining the need for further investigation about the role of their aberrant metabolic connectivities in the associated symptoms of CCD.
Subject(s)
Diaschisis , Cerebellum/pathology , Cerebrovascular Circulation , Fluorodeoxyglucose F18/metabolism , Humans , Pons , Positron-Emission TomographyABSTRACT
Task-fMRI researchers have great flexibility as to how they analyze their data, with multiple methodological options to choose from at each stage of the analysis workflow. While the development of tools and techniques has broadened our horizons for comprehending the complexities of the human brain, a growing body of research has highlighted the pitfalls of such methodological plurality. In a recent study, we found that the choice of software package used to run the analysis pipeline can have a considerable impact on the final group-level results of a task-fMRI investigation (Bowring et al., 2019, BMN). Here we revisit our work, seeking to identify the stages of the pipeline where the greatest variation between analysis software is induced. We carry out further analyses on the three datasets evaluated in BMN, employing a common processing strategy across parts of the analysis workflow and then utilizing procedures from three software packages (AFNI, FSL, and SPM) across the remaining steps of the pipeline. We use quantitative methods to compare the statistical maps and isolate the main stages of the workflow where the three packages diverge. Across all datasets, we find that variation between the packages' results is largely attributable to a handful of individual analysis stages, and that these sources of variability were heterogeneous across the datasets (e.g., choice of first-level signal model had the most impact for the balloon analog risk task dataset, while first-level noise model and group-level model were more influential for the false belief and antisaccade task datasets, respectively). We also observe areas of the analysis workflow where changing the software package causes minimal differences in the final results, finding that the group-level results were largely unaffected by which software package was used to model the low-frequency fMRI drifts.
Subject(s)
Brain Mapping , Brain/diagnostic imaging , Brain/physiology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Brain/anatomy & histology , Brain Mapping/methods , Brain Mapping/standards , Humans , Image Processing, Computer-Assisted/methods , Image Processing, Computer-Assisted/standards , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standardsABSTRACT
Insights into the differential binding characteristics of anti-Lea and anti-LeaLex monoclonal antibodies (mAbs) provide information to develop LeaLex-based cancer immunotherapeutics while avoiding anti-Lea autoimmune reactions. We characterized the epitope recognized by anti-Lea mAb SPM 522. We synthesized the Lea 6-aminohexyl glycoside and report experimental evidence of a minor conformation in solution. The Lea and three other 6-aminohexyl glycosides were conjugated to BSA and titration experiments with SPM 522 show that: 1. SPM 522 binds to LeaLex better than to Lea; 2. the non-reducing Lea galactosyl residue is essential to binding. Competitive ELISA experiments using a panel of tri- to pentasaccharide fragments of LeaLex as well as Lea analogues indicate that: 1. the Lea ß-d-galactosyl α hydrophobic patch is crucial to binding; 2. the Lea fucosyl residue contributes to binding; 3. the Lexd-galactosyl residue also contributes to binding. These results indicate that anti-Lea mAb SPM 522 recognizes the Lea[1,3]-ß-d-Gal tetrasaccharide. We propose that a major recognition element is the extended hydrophobic surface defined by the Lea-ß-d-Gal residue extending to the α faces of the ß-d-GlcNAc and ß-d-Gal residues.
Subject(s)
Antibodies, Monoclonal/immunology , Epitopes/immunology , Glycoconjugates/immunology , Antibodies, Monoclonal/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Glycoconjugates/chemical synthesis , Glycoconjugates/chemistry , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
PURPOSE: Radiotherapy is being used increasingly in the treatment of prostate cancer. However, ionising radiation may confer a small risk of a radiation-induced secondary malignancy. We aim to assess the risk of rectal cancer following pelvic radiotherapy for prostate cancer. METHODS: A search was conducted of the PubMed/MEDLINE, EMBASE and Web of Science databases identifying studies reporting on the risk of rectal cancer following prostatic radiotherapy. Studies must have included an appropriate control group of non-irradiated prostate cancer patients. A meta-analysis was performed to assess the risk of prostatic radiotherapy on subsequent rectal cancer diagnosis. RESULTS: In total, 4757 articles were screened with eight studies meeting the predetermined criteria. A total of 796,386 patients were included in this meta-analysis which showed an increased odds ratio (OR) for subsequent rectal cancer in prostate cancer patients treated with radiotherapy compared to those treated by non-radiotherapy means (OR 1.45, 1.07-1.97, p = 0.02). CONCLUSION: These findings confirm that prostate radiotherapy significantly increases the risk of subsequent rectal cancer. This risk has implications for treatment selection, surveillance and patient counselling. However, it is crucial that this information is presented in a rational and comprehensible manner that does not disproportionately frighten or deter patients from what might be their most suitable treatment modality.
Subject(s)
Neoplasms, Radiation-Induced , Prostatic Neoplasms , Rectal Neoplasms , Humans , Incidence , Male , Prostate , Prostatic Neoplasms/etiology , Prostatic Neoplasms/radiotherapy , Radiotherapy/adverse effects , Rectal Neoplasms/etiology , Rectal Neoplasms/radiotherapyABSTRACT
PURPOSE: To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. METHODS: In total, 106 children aged 4.7-18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. RESULTS: Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87-0.98; r = 0.78-0.96; relative volume difference other than CSFV = 6.8-18.5% [SyMRI vs. SPM T1] and 11.3-22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78-0.91. The Bland-Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject's age (p < 0.05). CONCLUSION: SyMRI and SPM segmentation results were consistent except for CSFV, which supports routine clinical use of SyMRI-based volumetry in pediatric neuroimaging. However, caution should be taken in the interpretation of the CSF segmentation results.