A Novel Concept for a Positron Emission Tomography Scanner

Positron Emission Tomography (PET) allows physicians and researchers to visualize metabolic data in the human body and is widely used in cancer and neurological imaging. Traditional PET scanners consist of a thin ring of scintillators coupled to photo detectors but these scanners often take long periods of time to acquire an image, are very costly, and are too complex to fit inside other machinery such as MRI. In response to this, we are building a novel PET detector that utilizes non-traditional scintillators and photo detectors in an attempt to significantly decrease cost, allow combined PET/MRI modalities and reduce scan time

Antemortem diagnosis of asbestosis by screening chest radiograph correlated with postmortem histologic features of asbestosis: a study of 273 cases

BACKGROUND: Accuracy in the clinical diagnosis of asbestosis has significant implications for the future health of affected patients as well as serious medicolegal implications for both patients and asbestos-associated industries. The radiographic gold-standard for diagnosis of asbestosis has been the plain chest radiograph, and in many asbestosis-screening clinics, chest radiograph abnormalities in conjunction with a history of asbestos exposure have been the mainstay of diagnosis. No studies have yet compared the antemortem chest radiographic diagnosis of asbestosis with the subsequent presence of pulmonary fibrosis and lung tissue ferruginous bodies at autopsy. METHODS: Records were reviewed from 273 autopsies performed to investigate asbestosis over an 11-year period. Accrued data included age and gender as well as the presence or absence of the following: occupational exposure to asbestos, antemortem clinical diagnosis of asbestosis by chest radiograph, fibrous pleural plaques, peribronchiolar or interstitial pulmonary fibrosis, ferruginous bodies in histologic sections of lung tissue, and ferruginous bodies in digested lung tissue. RESULTS: 242 cases with the antemortem radiographic diagnosis of asbestosis (study group) were identified. 31 additional autopsies had been requested based on history of asbestos exposure without radiographic documentation of asbestosis (control group). Comparison of the two groups showed a statistically significant increase in the association of chest radiograph-diagnosed asbestosis and the presence at autopsy of pleural plaques (p = 0.0109), peribronchiolar or interstitial pulmonary fibrosis (p = 0.0472), and histologically-diagnostic asbestosis (p = 0.0021). At autopsy, histologically-diagnostic asbestosis was confirmed in only 90 of the 243 study group cases. Comparison of individual parameters within the 242 study group cases showed a statistically significant correlation between the presence of fibrous pleural plaques and histologically-proven pulmonary fibrosis (p = 0.0025) as well as the subsequent histologic diagnosis of asbestosis (p < 0.0001). CONCLUSION: Clinical diagnosis of asbestosis by screening chest radiograph is more predictive of the postmortem presence of fibrous pleural plaques, pulmonary fibrosis, and histologically-proven asbestosis than is occupational exposure history alone. However, chest radiograph-based diagnosis of asbestosis significantly overpredicts the subsequent histologic diagnosis of asbestosis

Activation of Transfer RNA-Guanine Ribosyltransferase by Protein Kinase C

Transfer RNA-guanine ribosyltransferase (TGRase) irreversibly incorporates queuine into the first position in the anticodon of four tRNA isoacceptors. Rat brain protein kinase C (PKC) was shown to stimulate rat liver TG Rase activity, TGRase preparations derived from rat liver have been observed to decrease in activity over time in storage at -20 or -70°C, Contamination of the samples by phosphatases was indicated by a p-nitrophenylphosphate conversion test, The addition of micromolar concentrations of the phosphatase inhibitors sodium pyrophosphate and sodium fluoride into TGRase isolation buffers resulted in a greater return of TGRase activity than without these inhibitors, Inactive TGRase preparations were reactivated to their original activity with the addition of PKC, In assays combining both TGRase and PKC enzymes, inhibitors of protein kinase C (sphingosine, staurosporine, H-7 and calphostin C) all blocked the reactivation of TGRase, whereas activators of protein kinase C (calcium, diacylglycerol and phosphatidyl serine) increased the activity of TGRase, None of the PKC modulators affected TGRase activity directly, Alkaline phosphatase, when added to assays, decreased the activity of TGRase and also blocked the reactivation of TGRase with PKC, Denaturing PAGE and autoradiography was performed on TGRase isolates that had been labelled with 32P by PKC, The resulting strong 60 kDa band (containing the major site for phosphorylation) and weak 34.5 kDa band (containing the TGRase activity) are suggested to associate to make up a 104 kDa heterodimer that comprises the TGRase enzyme, This was corroberated by native and denaturing size-exclusion chromatography These results suggest that PKC-dependent phosphorylation of TGRase is tied to efficient enzymatic function and therefore control of the queuine modification of tRNA

An integrated strain improvement and process development program for the production of UK-2A, the precursor of the fungicide InatreqTM active

Secondary metabolites produced by Actinobacteria serve a variety of functions including molecules having agricultural applications. Streptomyces sp. 517-02 produces a novel fungicidal compound called UK-2A, which through a single step chemical reaction is converted to Inatreq™ active. Inatreq utilizes a unique target site of action, ubiquinone reductase Qi site (inner side of membrane), and is intended for use in cereals and banana markets with strong residual protectant and curative activity in wheat against Zymoseptoria tritici, with additional activity on rust and other diseases. To achieve a commercially viable process an integrated multidiscipline approach was applied in parallel including mutagenesis, high-throughput (HTP) screening, fermentation process optimization, and targeted genetic engineering. The presentation will review how the integrated approach contributed to a rapid acceleration in productivity gains resulting in a 75% improvement in titer over a one-year period, more than a 2 fold improvement in 4 years and successful scale-up to the final commercial production plant. Examples of topics to be discussed: Development, deployment, and optimization of the mutagenesis and high-throughput screening process for the selection of improved strains. Deployment of targeted genetic engineering to alleviate biosynthesis bottlenecks identified using approaches such as biosynthetic gene overexpression and precursor feeding. Use of “omics” tools to identify native promoters which permit temporal gene expression suitable for enhanced precursor production and increased UK-2A production. Vetting of new strains and fermentation process improvements both in bioreactors at multiple scales and in the downstream process for product recovery. Use of experimental results from across the integrated program to guide prioritization of strain and process improvement targets. Incorporation of final product design and performance requirements into the program with a line of sight to manufacturing process constraints. ™ Trademark of The Dow Chemical Company ( Dow ) or an affiliated company of Do

A Novel Concept for a Positron Emission Tomography Scanner

Positron Emission Tomography (PET) allows physicians and researchers to visualize metabolic data in the human body and is widely used in cancer and neurological imaging. Traditional PET scanners consist of a thin ring of scintillators coupled to photo detectors but these scanners often take long periods of time to acquire an image, are very costly, and are too complex to fit inside other machinery such as MRI. In response to this, we are building a novel PET detector that utilizes non-traditional scintillators and photo detectors in an attempt to significantly decrease cost, allow combined PET/MRI modalities and reduce scan time

Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and Sjogren\u27s syndrome enrolled in a large observational US registry

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjogren\u27s syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (+/- 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for \u3e /= 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA

Prevalence of Sjogren\u27s syndrome associated with rheumatoid arthritis in the USA: an observational study from the Corrona registry

The objectives of this analysis were to assess the prevalence of Sjogren\u27s syndrome (SS) associated with rheumatoid arthritis (RA) and to compare baseline characteristics of patients with RA with and without SS. Adult patients with RA from a large observational US registry (Corrona RA), with \u3e /= 1 visit for assessment of SS status between 22 April 2010 and 28 February 2018, were considered. Patients with RA with versus without SS were compared. SS status was determined from a yes/no variable and reported at enrollment into the Corrona RA registry and follow-up visits. Outcomes were unadjusted prevalence of SS in patients with RA, prevalence of SS by RA disease duration, and baseline characteristics in patients with RA by SS status. Of 24,528 eligible patients, 7870 (32.1%) had a diagnosis of RA and SS. The unadjusted overall rate for SS prevalence in patients with RA was 0.30 (95% confidence interval 0.29, 0.31). SS prevalence increased with increasing RA duration. Patients with RA with versus without SS were more likely to be older, female, and seropositive; had a longer RA duration; higher disease activity; and a higher incidence of comorbidities (hypertension, cardiovascular disease, malignancies, and serious infections), erosive disease, and subcutaneous nodules at index date. Patients with RA and SS had a higher disease burden than those with RA only. The prevalence of SS increased as duration of RA increased. RA with SS was associated with seropositivity, more severe RA, extra-articular manifestations, and comorbidities.Key Points* The overall prevalence of SS among patients with RA was 30%.* The prevalence of SS increased with increasing RA disease duration.* Identifying specific clinical characteristics of patients with RA with SS, such as a greater incidence of extra-articular manifestations and comorbidities, may help clinicians to better characterize this patient population

Extraneous color affects female macaques’ gaze preference for photographs of male conspecifics

Humans find members of the opposite sex more attractive when their image is spatially associated with the color red. This effect even occurs when the red color is not on the skin or clothing (i.e. is extraneous). We hypothesize that this extraneous color effect could be at least partially explained by a low-level and biologically innate generalization process, and so similar extraneous color effects should be observed in non-humans. To test this possibility, we examined the influence of extraneous color in rhesus macaques (Macaca mulatta). Across two experiments, we determined the influence of extraneous red on viewing preferences (assessed by looking time) in free-ranging rhesus monkeys. We presented male and female monkeys with black and white photographs of the hindquarters of same and opposite sex conspecifics on either a red (experimental condition) or blue (control condition) background. As a secondary control, we also presented neutral stimuli (photographs of seashells) on red and blue backgrounds. We found that female monkeys looked longer at a picture of a male scrotum, but not a seashell, on a red background (Experiment 1), while males showed no bias. Neither male nor female monkeys showed an effect of color on looking time for female hindquarters or seashells (Experiment 2). The finding for females viewing males suggests that extraneous color affects preferences among rhesus macaques. Further, it raises the possibility that evolutionary processes gave rise to extraneous color effects during human evolution