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1.
Cogn Affect Behav Neurosci ; 24(3): 402-420, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38291309

ABSTRACT

We investigated the simultaneous influence of expectation and experience on metacontrol, which we define as the instantiation of context-specific control states. These states could entail heightened control states in preparation for frequent task switching or lowered control states for task repetition. Specifically, we examined whether "expectations" regarding future control demands prompt proactive metacontrol, while "experiences" with items associated with specific control demands facilitate reactive metacontrol. In Experiment 1, we utilized EEG with a high temporal resolution to differentiate between brain activities associated with proactive and reactive metacontrol. We successfully observed cue-locked and image-locked ERP patterns associated with proactive and reactive metacontrol, respectively, supporting concurrent instantiation of two metacontrol modes. In Experiment 2, we focused on individual differences to investigate the modulatory role of working memory capacity (WMC) in the concurrent instantiation of two metacontrol modes. Our findings revealed that individuals with higher WMC exhibited enhanced proactive metacontrol, indicated by smaller response time variability (RTV). Additionally, individuals with higher WMC showed a lower tendency to rely on reactive metacontrol, indicated by a smaller item-specific switch probability (ISSP) effect. In conclusion, our results suggest that proactive and reactive metacontrol can coexist, but their interplay is influenced by individuals' WMC. Higher WMC promotes the use of proactive metacontrol while attenuating reliance on reactive metacontrol. This study provides insights into the interplay between proactive and reactive metacontrol and highlights the impact of WMC on their concurrent instantiation.


Subject(s)
Electroencephalography , Evoked Potentials , Memory, Short-Term , Humans , Memory, Short-Term/physiology , Male , Female , Young Adult , Electroencephalography/methods , Adult , Evoked Potentials/physiology , Brain/physiology , Reaction Time/physiology , Executive Function/physiology , Adolescent , Individuality , Anticipation, Psychological/physiology
2.
Br J Haematol ; 191(5): 806-815, 2020 12.
Article in English | MEDLINE | ID: mdl-33065767

ABSTRACT

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Gene Rearrangement , Hematopoietic Stem Cell Transplantation , Lymphoma, B-Cell, Marginal Zone , Lymphoma, Follicular , Neoplasm Proteins/genetics , Positron-Emission Tomography , Adult , Aged , Autografts , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, Follicular/diagnostic imaging , Lymphoma, Follicular/genetics , Lymphoma, Follicular/mortality , Lymphoma, Follicular/therapy , Male , Middle Aged , Prednisone/administration & dosage , Rituximab/administration & dosage , Survival Rate , Vincristine/administration & dosage
3.
J Appl Microbiol ; 129(3): 474-485, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31800143

ABSTRACT

Consumers' demand is increasing for safe foods without impairing the phytochemical and sensory quality. In turn, it has increased research interest in the exploration of innovative food processing technologies. Cold plasma technology is getting popularity now days owing to its high efficacy in decontamination of microbes in fruit and fruit-based products. As a on-thermal approach, plasma processing maintains the quality of fruits and minimizes the thermal effects on nutritional properties. Cold plasma is also exploited for inactivating enzymes and degrading pesticides as both are directly related with quality loss and presently are most important concerns in fresh produce industry. The present review covers the influence of cold plasma technology on reducing microbial risks and enhancing the quality attributes in fruits.


Subject(s)
Food Contamination/prevention & control , Food Quality , Fruit/chemistry , Fruit/microbiology , Plasma Gases/chemistry , Food Handling , Food Safety , Pesticides/chemistry
4.
Support Care Cancer ; 28(8): 3801-3812, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31832822

ABSTRACT

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.


Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/complications , Docetaxel/adverse effects , Febrile Neutropenia/etiology , Granulocyte Colony-Stimulating Factor/therapeutic use , Breast Neoplasms/drug therapy , Female , Hospitalization , Humans , Middle Aged , Retrospective Studies
5.
Nephrology (Carlton) ; 25(8): 644-651, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31900988

ABSTRACT

AIM: Many patients, especially the elderly, who require renal replacement therapies (RRT) have delayed or rejected dialysis for various reasons. Current dialysis guidelines may not be relevant for the elderly or frail patients. We aim to determine survival advantage of initiating dialysis in patients deemed to require RRT. METHODS: This was an observational cohort on incident end-stage kidney disease (ESKD) patients from January 1, 2007 to December 31, 2008. The primary outcome was all-cause mortality. Patients contributed person-time from the date of ESKD diagnosis until death, transplant or end of study on December 31, 2014, whichever occurred first. An extended Cox regression model with time-varying exposure to dialysis was used to account for immortal time bias. RESULTS: Of 3990 incident ESKD patients included, 70.2% patients initiated dialysis; 78.8% with haemodialysis (HD) while the remaining 21.2% with peritoneal dialysis (PD). Dialysis reduced hazard of death in both elderly and non-elderly patients even after controlling for comorbidities (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.50, 0.68 and HR 0.76, 95% CI 0.69, 0.85, respectively). HD was protective in both the elderly and non-elderly (HR 0.53, 95% CI 0.45, 0.63 and HR 0.71, 95% CI 0.64, 0.80, respectively). PD significantly reduced risk of death compared to no dialysis in the elderly but not in the non-elderly. CONCLUSION: Dialysis improved survival in all incident ESKD patients. The findings suggested a larger protection offered by HD. Although improvement in survival from initiating dialysis was large, its true benefit should take overall quality of life into account. SUMMARY AT A GLANCE This observational study showed that initiation of dialysis improves the survival of end-stage kidney disease (ESKD) patients of all age groups, but the quality of life is an important aspect that has not been explored.


Subject(s)
Kidney Failure, Chronic , Quality of Life , Renal Replacement Therapy , Time-to-Treatment , Age Factors , Aged , Female , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/psychology , Kidney Failure, Chronic/therapy , Malaysia/epidemiology , Male , Middle Aged , Mortality , Outcome and Process Assessment, Health Care , Renal Replacement Therapy/methods , Renal Replacement Therapy/statistics & numerical data , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical data
6.
Med J Malaysia ; 75(2): 103-109, 2020 03.
Article in English | MEDLINE | ID: mdl-32281589

ABSTRACT

INTRODUCTION: Chlamydia trachomatis is one of the most common sexually transmitted diseases (STDs) globally. However, data on its prevalence and risk factors in Malaysia is still scarce. OBJECTIVE: We aimed to identify the prevalence and risk factors of genitourinary C.trachomatis infection among patients attending STD clinics in northern Peninsular Malaysia. METHODS: A hospital-based cross-sectional study was conducted in STD clinics of Hospital Pulau Pinang and Hospital Sultanah Bahiyah, Kedah from January to November 2014. Participants were individually interviewed using a structured data collection form followed by a physical examination and laboratory tests. Nucleic Acid Amplification Test (NAAT) was used to detect C.trachomatis infection. Analysis was carried out using SPSS Version 15. RESULTS: Eighty-three sexually active patients were enrolled, consisting of 51 males and 32 females. The median age was 28.0 years. In general, 32.5% patients were asymptomatic, the remaining presented with genital discharge (41.0%), genital warty lesion (25.3%), genital ulcer (13.3%), dysuria (13.3%), dyspareunia (2.4%), urine hesistancy (1.2%) and genital swelling (1.2%). The prevalence of genitourinary C.trachomatis infection was 21.7% in the study population; 17.6% in males and 28.1% in females. Among the infected females, 44.4% were pregnant. Of those infected 56.6% did not show any symptoms of genital infection, and 77.8% were aged between 18 and 30 years, of which most were females. Among newly diagnosed HIV patients, the prevalence was 14.3%. From multivariable logistic regression analysis, age under 28 years, being married and engagement in oral sex had significantly increased odds of C.trachomatis infection. CONCLUSIONS: C.trachomatis infection was common among patients attending STD clinics in northern Penisular Malaysia especially in the younger age groups. Majority of the infected patients were asymptomatic.


Subject(s)
Chlamydia Infections/epidemiology , Chlamydia Infections/etiology , Chlamydia trachomatis/isolation & purification , Adolescent , Adult , Ambulatory Care Facilities , Chlamydia Infections/diagnosis , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Malaysia/epidemiology , Male , Middle Aged , Prevalence , Qualitative Research , Risk Factors , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/etiology , Young Adult
7.
Opt Lett ; 44(2): 327-330, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30644892

ABSTRACT

The design criterion of thermal conductivity for the GaAs/AlAs distributed Bragg reflector (DBR) superlattice structure was thoroughly investigated to precisely analyze the thermal behaviors of the optically pumped vertically external cavity surface-emitting laser (VECSEL). A finite element model with detailed configuration of a VECSEL gain chip was constructed to fulfill the analysis. A 1060 nm VECSEL with different pump conditions was further demonstrated to verify the finite element analysis. At the VECSEL thermal rollover point, the analysis results show that the model with the superlattice property predicts more precise temperature values than that using a bulk composite property. It reveals that the accurate determination of the thermal conductivity of the DBR superlattice is significantly important for the VECSEL thermal analysis.

8.
Colorectal Dis ; 21(4): 432-440, 2019 04.
Article in English | MEDLINE | ID: mdl-30578740

ABSTRACT

AIM: Whether some diseases are related to the occurrence of synchronous colorectal carcinoma (sCRC) is unknown. Investigating the risk factors and presentation of sCRC could aid in the treatment of patients with colorectal cancer (CRC). The prognosis of sCRC compared with that of solitary CRC remains unclear. METHODS: A total of 17 093 CRC patients were recruited between 1st January 1995 and 31th December 2016. The risk factors of sCRC development were assessed using univariate and multivariate logistic regression. The effect of sCRC on survival was analysed using the multivariate Cox regression model. RESULTS: The prevalence of sCRC was 5.6% in this study. The independent risk factors of sCRC development were advanced age (P < 0.001), male sex (P < 0.001), hereditary cancer (P < 0.001), hypertension (P < 0.001) and liver cirrhosis (P = 0.024). Compared with solitary CRC, a higher number of patients with sCRC presented with an abnormal carcinoembryonic antigen (CEA) level (P = 0.011), anaemia (P < 0.001) and hypoalbuminemia (P < 0.001). Multivariate analysis revealed that sCRC was a significant factor for poor survival in patients at TNM Stage I [hazard ratio (HR) = 1.86; P < 0.001], Stage II (HR = 1.65; P < 0.001) and Stage III (HR = 1.40; P < 0.001). CONCLUSIONS: In addition to hypertension and liver cirrhosis, other risk factors for sCRC were identified in this study. The prognosis of patients with sCRC was significantly worse than that of those with solitary CRC through TNM Stages I to III. Anaemia, abnormal CEA and hypoalbuminemia were more commonly seen in patients with sCRC.


Subject(s)
Carcinoma/mortality , Colorectal Neoplasms/mortality , Neoplasms, Multiple Primary/mortality , Aged , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Carcinoma/pathology , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Female , Humans , Logistic Models , Male , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/blood , Neoplasms, Multiple Primary/pathology , Prognosis , Proportional Hazards Models , Prospective Studies , Retrospective Studies , Risk Factors , Survival Rate
9.
J Biol Chem ; 290(2): 1066-74, 2015 Jan 09.
Article in English | MEDLINE | ID: mdl-25371207

ABSTRACT

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme involved in photosynthetic carbon fixation, converting atmospheric CO2 to organic compounds. Form I Rubisco is a cylindrical complex composed of eight large (RbcL) subunits that are capped by four small subunits (RbcS) at the top and four at the bottom. Form I Rubiscos are phylogenetically divided into green- and red-type. Some red-type enzymes have catalytically superior properties. Thus, understanding their folding and assembly is of considerable biotechnological interest. Folding of the green-type RbcL subunits in cyanobacteria is mediated by the GroEL/ES chaperonin system, and assembly to holoenzyme requires specialized chaperones such as RbcX and RAF1. Here, we show that the red-type RbcL subunits in the proteobacterium Rhodobacter sphaeroides also fold with GroEL/ES. However, assembly proceeds in a chaperone-independent manner. We find that the C-terminal ß-hairpin extension of red-type RbcS, which is absent in green-type RbcS, is critical for efficient assembly. The ß-hairpins of four RbcS subunits form an eight-stranded ß-barrel that protrudes into the central solvent channel of the RbcL core complex. The two ß-barrels stabilize the complex through multiple interactions with the RbcL subunits. A chimeric green-type RbcS carrying the C-terminal ß-hairpin renders the assembly of a cyanobacterial Rubisco independent of RbcX. Our results may facilitate the engineering of crop plants with improved growth properties expressing red-type Rubisco.


Subject(s)
Chaperonin 60/metabolism , Photosynthesis/genetics , Ribulose-Bisphosphate Carboxylase/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Chaperonin 60/chemistry , Molecular Chaperones/chemistry , Molecular Chaperones/metabolism , Protein Folding , Proto-Oncogene Proteins c-raf/metabolism , Rhodobacter sphaeroides/metabolism , Ribulose-Bisphosphate Carboxylase/genetics , Ribulose-Bisphosphate Carboxylase/metabolism , Ribulosephosphates/chemistry , Ribulosephosphates/metabolism
10.
Am J Transplant ; 16(8): 2352-9, 2016 08.
Article in English | MEDLINE | ID: mdl-26841727

ABSTRACT

Pediatric centers are implanting durable adult continuous-flow ventricular assist devices (CFVADs) in children who are smaller than the industry-recommended size. Waitlist and posttransplant outcomes data in pediatric patients supported with CFVADs as a bridge to transplant are limited. We analyzed the United Network of Organ Sharing and Organ Procurement and Transplantation Network registry to identify patients aged ≤18 years with a CFVAD at the time of listing or transplantation. Patients were stratified by body surface area (BSA; >1.5 vs. ≤1.5 m(2) ) at time of listing. We identified 138 patients with a durable CFVAD during the listing period (100 with BSA >1.5 m(2) , 38 with BSA ≤1.5 m(2) ). Patients with BSA ≤1.5 m(2) were more likely to have a noncardiomyopathy diagnosis (18% vs. 4%, p = 0.007) and to be implanted with a centrifugal-flow rather than an axial-flow device (74% vs. 30%, p = 0.001). There was no difference in failure-free waitlist survival between BSA groups (p = 0.99) among patients with a CFVAD at listing. Posttransplantation survival was 100% and 88% at 1 and 5 years, respectively, for the entire cohort and did not differ by BSA group (p = 0.99). Consequently, waitlist and posttransplant outcomes are favorable for pediatric CFVAD recipients. Small patients (≤1.5 m(2) ) had pre- and posttransplant outcomes similar to those of larger patients that met the industry-recommended size for implantation.


Subject(s)
Graft Survival , Heart Failure/surgery , Heart Transplantation , Heart-Assist Devices , Waiting Lists , Adolescent , Child , Female , Follow-Up Studies , Humans , Male , Prognosis , Registries , Retrospective Studies , Time Factors , Treatment Outcome
11.
J Nucl Cardiol ; 23(3): 366-78, 2016 06.
Article in English | MEDLINE | ID: mdl-26358085

ABSTRACT

OBJECTIVE: The objective of this study is to compare the incremental prognostic and net risk reclassification value of exercise testing alone vs exercise myocardial perfusion imaging (MPI) for estimating the risk of death in patients with suspected and known coronary artery disease (CAD). METHODS: 6702 patients with suspected CAD and 2008 with known CAD had treadmill exercise MPI and were followed for 2.5 ± 0.9 years for the occurrence of all-cause death. The estimation of risk of death and net reclassification improvement (NRI) were examined in three models. Model 1: clinical variables; Model 2: model 1+Duke Treadmill Score; and Model 3: model 2+ MPI variables. Risk estimates were categorized as <1%, 1-3%, and >3% risk of death per year. RESULTS: In patients with suspected CAD, the global Chi-square for predicting risk of death increased significantly for Model 2 compared to Model 1 (74.78 vs 63.86 to (P = .001). However, adding MPI variables in Model 3 did not further improve predictive value (Chi-square 79.38, P = .10). In patients with suspected CAD risk, reclassification improved significantly in Model 2 over Model 1 (NRI = 0.12, 95% CI 0.02 to 0.22, P = .019), but not in Model 3 (NRI = 0.0009, 95% CI -0.072 to 0.070; P = .98). In contrast, in patients with known CAD Model 2 did not yield significant improvements for predicting risk and risk reclassification compared to Model 1. However, global Chi-square of Model 3 was significantly higher than that of Model 2 (30.03 vs 6.56, P < .0001) with associated significant reclassification improvement (NRI = 0.26 95% CI 0.067 to 0.46. P = .0084). CONCLUSION: Risk reclassification by diagnostic testing is importantly influenced by baseline characteristics of patient cohorts. In patients with suspected CAD, NRI is predominately achieved by exercise variables, whereas in patients with known CAD, greatest NRI is obtained by MPI variables.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Death, Sudden, Cardiac/epidemiology , Exercise Test/statistics & numerical data , Myocardial Perfusion Imaging/statistics & numerical data , Proportional Hazards Models , Tomography, Emission-Computed, Single-Photon/statistics & numerical data , Female , Humans , Male , Middle Aged , Myocardial Perfusion Imaging/methods , Prevalence , Prognosis , Reproducibility of Results , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity , Singapore/epidemiology , Survival Analysis
12.
Pediatr Transplant ; 19(7): E165-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26374667

ABSTRACT

Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28-month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/drug therapy , Heart Transplantation , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Postoperative Complications/drug therapy , Recombinant Fusion Proteins/therapeutic use , Autoimmune Diseases/etiology , Basiliximab , Child, Preschool , Female , Humans , Inflammatory Bowel Diseases/etiology
13.
Plant J ; 76(4): 580-91, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23964816

ABSTRACT

Molecular-genetic control of the flowering time of temperate-climate plants is best understood in Arabidopsis and the cereals wheat and barley. However, key regulators such as FLC and cereal VRN2 are not found in legumes. Therefore, we used forward genetics to identify flowering time genes in the model legume Medicago truncatula (Medicago) which is induced to flower by vernalisation and long-day photoperiods. A screen of a Tnt1 retroelement tagging population yielded two mutants, spring2 and spring3, with a dominant early flowering phenotype. These mutants overexpress the floral activator FTa1 and two candidate downstream flowering genes SOC1a and FULb, similar to the spring1 somaclonal variant that we identified previously. We demonstrate here that an increase in the expression of FTa1, SOC1a and FULb and early flowering does not occur in all conditions in the spring mutants. It depends on long-day photoperiods but not on vernalisation. Isolation of flanking sequence tags and linkage analysis identified retroelement insertions at FTa1 that co-segregated with the early flowering phenotype in all three spring mutants. These were Tnt1 insertions in the FTa1 third intron (spring3) or the 3' intergenic region (spring2) and an endogenous MERE1-4 retroelement in the 3' intergenic region in spring1. Thus the spring mutants form an allelic series of gain-of-function mutations in FTa1 which confer a spring growth habit. The spring retroelement insertions at FTa1 separate long-day input from vernalisation input into FTa1 regulation, but this is not due to large-scale changes in FTa1 DNA methylation or transcript processing in the mutants.


Subject(s)
Flowers/physiology , Medicago truncatula/genetics , Photoperiod , Plant Proteins/genetics , Retroelements , Seasons , 3' Flanking Region , DNA Methylation , Mutagenesis, Insertional , Mutation , Phenotype
15.
Opt Express ; 22(21): 26358-64, 2014 Oct 20.
Article in English | MEDLINE | ID: mdl-25401668

ABSTRACT

We demonstrate broadband (20 THz), high electric field, terahertz generation using large area interdigitated antennas fabricated on semi-insulating GaAs. The bandwidth is characterized as a function of incident pulse duration (15-35 fs) and pump energy (2-30 nJ). Broadband spectroscopy of PTFE is shown. Numerical Drude-Lorentz simulations of the generated THz pulses are performed as a function of the excitation pulse duration, showing good agreement with the experimental data.


Subject(s)
Computer-Aided Design , Lasers , Lighting/instrumentation , Terahertz Radiation , Transducers , Electric Conductivity , Equipment Design , Photons
16.
J Imaging Inform Med ; 37(2): 601-610, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38343226

ABSTRACT

Patella alta (PA) and patella baja (PB) affect 1-2% of the world population, but are often underreported, leading to potential complications like osteoarthritis. The Insall-Salvati ratio (ISR) is commonly used to diagnose patellar height abnormalities. Artificial intelligence (AI) keypoint models show promising accuracy in measuring and detecting these abnormalities.An AI keypoint model is developed and validated to study the Insall-Salvati ratio on a random population sample of lateral knee radiographs. A keypoint model was trained and internally validated with 689 lateral knee radiographs from five sites in a multi-hospital urban healthcare system after IRB approval. A total of 116 lateral knee radiographs from a sixth site were used for external validation. Distance error (mm), Pearson correlation, and Bland-Altman plots were used to evaluate model performance. On a random sample of 2647 different lateral knee radiographs, mean and standard deviation were used to calculate the normal distribution of ISR. A keypoint detection model had mean distance error of 2.57 ± 2.44 mm on internal validation data and 2.73 ± 2.86 mm on external validation data. Pearson correlation between labeled and predicted Insall-Salvati ratios was 0.82 [95% CI 0.76-0.86] on internal validation and 0.75 [0.66-0.82] on external validation. For the population sample of 2647 patients, there was mean ISR of 1.11 ± 0.21. Patellar height abnormalities were underreported in radiology reports from the population sample. AI keypoint models consistently measure ISR on knee radiographs. Future models can enable radiologists to study musculoskeletal measurements on larger population samples and enhance our understanding of normal and abnormal ranges.

17.
J Biol Chem ; 287(24): 20471-81, 2012 Jun 08.
Article in English | MEDLINE | ID: mdl-22518837

ABSTRACT

The chloroplast chaperonin system of plants and green algae is a curiosity as both the chaperonin cage and its lid are encoded by multiple genes, in contrast to the single genes encoding the two components of the bacterial and mitochondrial systems. In the green alga Chlamydomonas reinhardtii (Cr), three genes encode chaperonin cofactors, with cpn10 encoding a single ∼10-kDa domain and cpn20 and cpn23 encoding tandem cpn10 domains. Here, we characterized the functional interaction of these proteins with the Escherichia coli chaperonin, GroEL, which normally cooperates with GroES, a heptamer of ∼10-kDa subunits. The C. reinhardtii cofactor proteins alone were all unable to assist GroEL-mediated refolding of bacterial ribulose-bisphosphate carboxylase/oxygenase but gained this ability when CrCpn20 and/or CrCpn23 was combined with CrCpn10. Native mass spectrometry indicated the formation of hetero-oligomeric species, consisting of seven ∼10-kDa domains. The cofactor "heptamers" interacted with GroEL and encapsulated substrate protein in a nucleotide-dependent manner. Different hetero-oligomer arrangements, generated by constructing cofactor concatamers, indicated a preferential heptamer configuration for the functional CrCpn10-CrCpn23 complex. Formation of heptamer Cpn10/Cpn20 hetero-oligomers was also observed with the Arabidopsis thaliana (At) cofactors, which functioned with the chloroplast chaperonin, AtCpn60α(7)ß(7). It appears that hetero-oligomer formation occurs more generally for chloroplast chaperonin cofactors, perhaps adapting the chaperonin system for the folding of specific client proteins.


Subject(s)
Algal Proteins/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Chaperonin 10/metabolism , Chlamydomonas reinhardtii/metabolism , Chloroplast Proteins/metabolism , Group I Chaperonins/metabolism , Multiprotein Complexes/metabolism , Algal Proteins/genetics , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Chaperonin 10/genetics , Chaperonin 60/genetics , Chaperonin 60/metabolism , Chlamydomonas reinhardtii/genetics , Chloroplast Proteins/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Group I Chaperonins/genetics , Multiprotein Complexes/genetics , Protein Folding/drug effects
18.
J Laryngol Otol ; 137(12): 1389-1394, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37114322

ABSTRACT

OBJECTIVE: To assess the effect of the coronavirus disease 2019 pandemic on paediatric bilateral myringotomy and tube insertion rates in New Brunswick, Canada. METHODS: All paediatric bilateral myringotomy and tube insertion cases from 1 July 2015 through 30 June 2021 were provided by New Brunswick Medicare. The numbers of otolaryngologists, cataract surgical procedures, total hip arthroplasties and thyroidectomies were collected to assess the availability of operating theatres and otolaryngologists. Negative binomial logarithmic regressions were used for analyses. RESULTS: Of the 5175 paediatric bilateral myringotomy and tube insertion cases that were included, the bilateral myringotomy and tube insertion rate significantly decreased by 2.9 times (p < 0.001) during the pandemic. Thyroidectomies, cataract surgical procedures and total hip arthroplasties did not significantly decrease. The number of otolaryngologists increased (20 vs 16-17). CONCLUSION: Paediatric bilateral myringotomy and tube insertion rates significantly decreased during the pandemic. This cannot be accounted for by reduced otolaryngologists or operating theatre availability. The paediatric bilateral myringotomy and tube insertion rate decrease is likely due to public health measures reducing the transmission of upper respiratory tract infections, resulting in fewer indications for paediatric bilateral myringotomy and tube insertion.


Subject(s)
COVID-19 , Cataract , Otitis Media with Effusion , Aged , Child , Humans , New Brunswick , Pandemics , Otitis Media with Effusion/epidemiology , Otitis Media with Effusion/surgery , COVID-19/epidemiology , National Health Programs , Middle Ear Ventilation/methods , Canada/epidemiology
19.
Materials (Basel) ; 16(6)2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36984372

ABSTRACT

This study proposed wavelet-based approaches to characterise random vibration road excitations for durability prediction of coil springs. Conventional strain-life approaches require long computational time, while the accuracy of the vibration fatigue methods is unsatisfactory. It is therefore a necessity to establish an accurate fatigue life prediction model based on vibrational features. Wavelet-based methods were applied to determine the low-frequency energy and multifractality of road excitations. Strain-life models were applied for fatigue life evaluation from strain histories. ANFIS modelling was subsequently adopted to associate the vibration features with the fatigue life of coil springs. Results showed that the proposed wavelet-based methods were effective to determine the signal energy and multifractality of vibration signals. The established vibration-based models showed good fatigue life conservativity with a data survivability of more than 90%. The highest Pearson coefficient of 0.955 associated with the lowest RMSE of 0.660 was obtained by the Morrow-based model. It is suggested that the low-frequency energy and multifractality of the vibration signals can be used as fatigue-related features in life predictions of coil springs under random loading. Finally, the proposed model is an acceptable fatigue life prediction method based on vibration features, and it can reduce the dependency on strain data measurement.

20.
Diabetologia ; 55(6): 1721-32, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22382519

ABSTRACT

AIMS/HYPOTHESIS: A leading cause of type 2 diabetes is a reduction in functional beta cell mass partly due to increased beta cell death, triggered by stressors such as glucolipotoxicity (GLT). This study evaluates the hypothesis that lactogens can protect beta cells against GLT and examines the mechanism behind the pro-survival effect. METHODS: The effect of exogenous treatment or endogenous expression of lactogens on GLT-induced beta cell death was examined in INS-1 cells, and in rodent and human islets. The mechanism behind the pro-survival effect of lactogens was determined using an inhibitor, siRNAs, a dominant negative (DN) mutant, and Cre-lox-mediated gene deletion analysis. RESULTS: Lactogens significantly protect INS-1 and primary rodent beta cells against GLT-induced cell death. The pro-survival effect of lactogens in rodent beta cells is mediated through activation of the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-5 (STAT5) signalling pathway. Lactogen-induced increase in the anti-apoptotic B cell lymphoma-extra large (BCLXL) protein is required to mediate its pro-survival effects in both INS-1 cells and primary rodent beta cells. Most importantly, lactogens significantly protect human beta cells against GLT-induced cell death, and their pro-survival effect is also mediated through the JAK2/STAT5 pathway. CONCLUSIONS/INTERPRETATION: These studies, together with previous work, clearly demonstrate the pro-survival nature of lactogens and identify the JAK2/STAT5 pathway as an important mediator of this effect in both rodent and human beta cells. Future studies will determine the effectiveness of this peptide in vivo in the pathophysiology of type 2 diabetes.


Subject(s)
Islets of Langerhans/cytology , Islets of Langerhans/drug effects , Janus Kinase 2/metabolism , Placental Lactogen/pharmacology , STAT5 Transcription Factor/metabolism , Signal Transduction/drug effects , Animals , Cell Line, Tumor , Cells, Cultured , Female , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Islets of Langerhans/metabolism , Janus Kinase 2/genetics , Male , Mice , Mice, Transgenic , RNA, Small Interfering , Rats , STAT5 Transcription Factor/genetics , Signal Transduction/genetics
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