Seasonal variation in photosynthetic rates and satellite-based GPP estimation over mangrove forest.

In view of increasing anthropogenic influences and global changes, quantification of carbon assimilation through photosynthesis has gained tremendous significance. Precise estimation of Gross Primary Productivity (GPP) is essential for several ecosystem models and is typically done using coarser scale satellite data. The mangrove ecosystem, which offers significant protection to the coastal environment, is one of the critical habitats from a global change point of view. Light use efficiency (LUE) was measured using diurnal in situ photosynthetic rate observations for 13 dominant mangrove species for 3 seasons at each of the three mangrove dominant test-sites situated along the east and west coast of India. Variations in photosynthetic rates among these species were studied for 3 seasons that indicated varying responses of mangrove ecosystem at each site. Among all species, Rhizophora mucronata and Sonneratia apetala indicated higher values at two of the test-sites. IRS Resourcesat-2 LISS-IV datasets were used for the estimation of GPP. Mean GPP for all the sites varied from 1.2 to 7.7 g C m-2 day-1 with maximum value of 14.4 g C m-2 day-1. Mean values of GPP varied across the sites, based on its maximum LUE values and available photosynthetically active radiation (PAR). The results provide GPP values at much better spatial resolution for a threatened habitat like mangroves that typically survive in a narrow habitat along the coasts.

Sports in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy and desmosomal mutations.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare cardiomyopathy associated with life-threatening arrhythmias and an increased risk of sudden cardiac death. In addition to mutations in desmosomal genes, environmental factors such as exercise and sport have been implicated in the pathogenesis of the disease. Recent studies have shown that exercise may be associated with adverse outcomes in patients with ARVD/C. On the basis of current evidence, patients with ARVD/C are recommended to limit exercise irrespective of their mutation status. Some studies have suggested the presence of an entirely acquired form of the disease caused by exercise, which has been dubbed "exercise-induced ARVD/C."

Synthesis of some novel quinone diimine derivatives of benzo-15-crown-5 for application in Hg(2+) recognition.

A series of novel fluoroionophore bearing derivatives of benzo-15-crown-5 were synthesized by the amination of benzo-15-crown-5 followed by condensation with different quinones in the presence of titanium tetrachloride (TiCl4 ) and 1,4-diazabicyclo-[2.2.2]octane. The compounds were characterized by infrared, (1) H and (13) C nuclear magnetic resonance, mass spectroscopy and elemental analysis. Absorption and fluorescence spectral characteristics of these compounds were studied. It was observed that the anthraquinone derivative was acting as an Hg(2+) ion sensor.

CLASP2 facilitates dynamic actin filament organization along the microtubule lattice.

Coordination between the microtubule and actin networks is essential for cell motility, neuronal growth cone guidance, and wound healing. Members of the CLASP (cytoplasmic linker-associated protein) family of proteins have been implicated in the cytoskeletal cross-talk between microtubules and actin networks; however, the molecular mechanisms underlying the role of CLASP in cytoskeletal coordination are unclear. Here, we investigate CLASP2α's cross-linking function with microtubules and F-actin. Our results demonstrate that CLASP2α cross-links F-actin to the microtubule lattice in vitro. We find that the cross-linking ability is retained by L-TOG2-S, a minimal construct containing the TOG2 domain and serine-arginine-rich region of CLASP2α. Furthermore, CLASP2α promotes the accumulation of multiple actin filaments along the microtubule, supporting up to 11 F-actin landing events on a single microtubule lattice region. CLASP2α also facilitates the dynamic organization of polymerizing actin filaments templated by the microtubule network, with F-actin forming bridges between individual microtubules. Finally, we find that depletion of CLASPs in vascular smooth muscle cells results in disorganized actin fibers and reduced coalignment of actin fibers with microtubules, suggesting that CLASP and microtubules contribute to higher-order actin structures. Taken together, our results indicate that CLASP2α can directly cross-link F-actin to microtubules and that this microtubule-CLASP-actin interaction may influence overall cytoskeletal organization in cells.

A PCR assay and PCR-restriction fragment length polymorphism combination identifying the 3 primary Mycoplasma species causing mastitis.

The focus of the current research was to develop real-time PCR assays with improved sensitivity and the capacity to simultaneously speciate the 3 most common mycoplasma mastitis agents: Mycoplasma bovis, Mycoplasma californicum, and Mycoplasma bovigenitalium. Real-time PCR was chosen because it provides rapid results. Partial 16S rRNA gene sequencing was used as the gold standard for evaluating candidate real-time PCR assays. To ascertain the real-time PCR assay specificity, reference strains of Mycoplasma species, Acholeplasma axanthum, and common gram-positive and gram-negative mastitis pathogens were tested. No cross-reactions were observed. Mycoplasma spp. isolated from bovine milk samples (n=228) and other organ sites (n=40) were tested by the real-time PCR assays and the partial 16S rRNA gene sequencing assay. Overall accuracy of this novel real-time PCR was 98.51%; 4 of 228 isolates identified as M. bovis by the partial 16S rRNA gene sequencing assay were identified as both M. bovis and M. californicum by real-time PCR. Subsequent amplicon sequencing suggested the presence of both M. bovis and M. californicum in these 4 samples. Using a cycle threshold of 37, the detection limits for real-time PCR were 10 copies of DNA template for both M. bovis and M. bovigenitalium, and 1 copy for M. californicum. This real-time PCR assay is a diagnostic technique that may be used as a screening tool or as a confirmation test for mycoplasma mastitis.

Virtual bronchoscopy-guided lung SAbR: dosimetric implications of using AAA versus Acuros XB to calculate dose in airways.

In previous works, we showed that incorporating individual airways as organs-at-risk (OARs) in the treatment of lung stereotactic ablative radiotherapy (SAbR) patients potentially mitigates post-SAbR radiation injury. However, the performance of common clinical dose calculation algorithms in airways has not been thoroughly studied. Airways are of particular concern because their small size and the density differences they create have the potential to hinder dose calculation accuracy. To address this gap in knowledge, here we investigate dosimetric accuracy in airways of two commonly used dose calculation algorithms, the anisotropic analytical algorithm (AAA) and Acuros-XB (AXB), recreating clinical treatment plans on a cohort of four SAbR patients. A virtual bronchoscopy software was used to delineate 856 airways on a high-resolution breath-hold CT (BHCT) image acquired for each patient. The planning target volumes (PTVs) and standard thoracic OARs were contoured on an average CT (AVG) image over the breathing cycle. Conformal and intensity-modulated radiation therapy plans were recreated on the BHCT image and on the AVG image, for a total of four plan types per patient. Dose calculations were performed using AAA and AXB, and the differences in maximum and mean dose in each structure were calculated. The median differences in maximum dose among all airways were ≤0.3Gy in magnitude for all four plan types. With airways grouped by dose-to-structure or diameter, median dose differences were still ≤0.5Gy in magnitude, with no clear dependence on airway size. These results, along with our previous airway radiosensitivity works, suggest that dose differences between AAA and AXB correspond to an airway collapse variation ≤0.7% in magnitude. This variation in airway injury risk can be considered as not clinically relevant, and the use of either AAA or AXB is therefore appropriate when including patient airways as individual OARs so as to reduce risk of radiation-induced lung toxicity.

Validation of a CT-based motion model with in-situ fluoroscopy for lung surface deformation estimation.

Many surrogate-based motion models (SMMs), proposed to guide motion management in radiotherapy, are constructed by correlating motion of an external surrogate and internal anatomy during CT-simulation. Changes in this correlation define model break down. We validate a methodology that incorporates fluoroscopic (FL) images acquired during treatment for SMM construction and update. Under a prospective IRB, 4DCT scans, VisionRT (VRT) surfaces, and orthogonal FLs were collected from five lung cancer patients. VRT surfaces and two FL time-series were acquired pre- and post-treatment. A simulated annealing optimization scheme was used to estimate optimal lung deformations by maximizing the mutual information (MI) between digitally reconstructed radiographs (DRRs) of the SMM-estimated 3D images and FLs. Our SMM used partial-least-regression and was trained using the optimal deformations and VRT surfaces from the first breathing-cycle. SMM performance was evaluated using the MI score between reference FLs and the corresponding SMM or phase-assigned 4DCT DRRs. The Hausdorff distance for contoured landmarks was used to evaluate target position estimation error. For four out of five patients, two principal components approximated lung surface deformations with submillimeter accuracy. Analysis of the MI score between more than 4000 pairs of FL and DRR demonstrated that our model led to more similarity between the FL and DRR images compared to 4DCT and DRR images from a model based on an a priori correlation model. Our SMM consistently displayed lower mean and 95th percentile Hausdorff distances. For one patient, 95th percentile Hausdorff distance was reduced by 11 mm. Patient-averaged reductions in mean and 95th percentile Hausdorff distances were 3.6 mm and 7 mm for right-lung, and 3.1 mm and 4 mm for left-lung targets. FL data were used to evaluate model performance and investigate the feasibility of model update. Despite variability in breathing, use of post-treatment FL preserved model fidelity and consistently outperformed 4DCT for position estimation.

Metabolism, pharmacokinetics and excretion of the GABA(A) receptor partial agonist [(14)C]CP-409,092 in rats.

The metabolism and excretion of a GABA(A) partial agonist developed for the treatment of anxiety, CP-409,092; 4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (4-methylaminomethyl-phenyl)-amide, were studied in rats following intravenous and oral administration of a single doses of [(14)C]CP-409,092. The pharmacokinetics of CP-409,092 following single intravenous and oral doses of 4 and 15 mg kg(-1), respectively, were characterized by high clearance of 169 + or - 18 ml min(-1) kg(-1), a volume of distribution of 8.99 + or - 1.46 l kg(-1), and an oral bioavailability of 2.9% + or - 3%. Following oral administration of 100 mg kg(-1) [(14)C]CP-409,092, the total recovery was 89.1% + or - 3.2% for male rats and 89.3% + or - 0.58% for female rats. Approximately 87% of the radioactivity recovered in urine and faeces were excreted in the first 48 h. A substantial portion of the radioactivity was measured in the faeces as unchanged drug, suggesting poor absorption and/or biliary excretion. There were no significant gender-related quantitative/qualitative differences in the excretion of metabolites in urine or faeces. The major metabolic pathways of CP-409,092 were hydroxylation(s) at the oxo-tetrahydro-indole moiety and oxidative deamination to form an aldehyde intermediate and subsequent oxidation to form the benzoic acid. The minor metabolic pathways included N-demethylation and subsequent N-acetylation and oxidation. The present work demonstrates that oxidative deamination at the benzylic amine of CP-409,092 and subsequent oxidation to form the acid metabolite seem to play an important role in the metabolism of the drug, and they contribute to its oral clearance and low exposure.

Controls to Minimize Disruption of the Pharmaceutical Supply Chain During the COVID-19 Pandemic.

This article reviews currently available scientific literature related to the epidemiology, infectivity, survival, and susceptibility to disinfectants of Coronaviruses, in the context of the controls established to meet good manufacturing practice (GMP) regulations and guidance, and the public health guidance issued specifically to combat the COVID-19 pandemic. The possible impact of the COVID-19 pandemic on the pharmaceutical supply chain is assessed and recommendations are listed for risk mitigation steps to minimize supply disruption to pharmaceutical drug products. Areas addressed include a brief history of the COVID-19 viral pandemic, a description of the virus, the regulatory response to the pandemic, the screening of employees, the persistence of the virus on inanimate surfaces, cleaning and disinfection of manufacturing facilities, the use of GMP-mandated personal protective equipment to counter the spread of the disease, the role of air changes in viral clearance, and approaches to risk assessment and mitigation. Biological medicinal products have a great record of safety, yet the cell cultures used for production can be susceptible to viruses, and contamination events have occurred. Studies on SARS-CoV-2 for it ability to replicate in various mammalian cell lines used for biopharmaceutical manufacturing suggests that the virus poses a low risk and any contamination would be detected by currently used adventitious virus testing. The consequences of the potential virus exposure of manufacturing processes as well as the effectiveness of mitigation efforts are discussed. The pharmaceutical supply chain is complex, traversing many geographies and companies that range from large multinationals to mid- and small-size operations. This paper recommends practices that can be adopted by all companies, irrespective of their size, geographic location, or position in the supply chain.

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.