The Sacred Geography of Dawei: Buddhism in peninsular Myanmar (Burma)

The paper opens by recounting the beginnings of Buddhism in Dawei as preserved in local chronicles and sustained in stupas marking the episodes of the chronicle narrative. The chronicles start with a visit of the Buddha whose arrival triggers a series of events bringing together pre-existing tutelary figures, weiza, a hermit and offspring born of a golden fish, culminating in the establishment of the first Buddhist kingdom circa the eighth to tenth century CE. The enshrinement of sacred hairs gifted by the Buddha also includes patronage by a king of the ‘Suvannbhumi’ lineage. Associated with the monks Sona and Uttara from Sri Lanka sent by King Asoka’s son Mahinda, ‘Suvannbhumi’ literally can refer to the archaeology of Thaton, a walled site in the present day Mon State, or, as is the case here, more widely to the missionary tradition associated with Asoka (Sao Saimong Mengrai 1976). The third story in the establishment of the Buddhist king at Thagara is the longest of the chronicle, the tale of a royal hunter who failed to capture a golden peacock for the queen. The hunter became a hermit living by a pond with a golden fish and as he urinated in the pond, two children were born from the fish. The boy becomes the first Buddhist king of Thagara, 11 km north of Dawei, where artefacts from survey and excavation confirm the chronology of the chronicle, with the closest archaeological parallels found not at the ancient sites of the Mon State but to the first millennium CE Buddhist ‘Pyu’ heritage of Upper Myanmar which is notably absent in the chronicle compilation

TB153: A Long-Term Study of an Oak Pine Forest Ecosystem: Techniques Manual for the Holt Research Forest

The manual is a compilation of the study techniques used for the long-term forest ecosystem research project at the Holt Research Forest in Arrowsic, Maine, plus brief evaluations of each method\u27s advantages and drawbacks. It is based on 12 years of work by a team of three university professors, an associate scientist who has lived on the forest since 1983, a research assistant, several graduate students, and numerous undergraduate field assistants. We hope this manual will be useful to other researchers planning, or already involved in, other forest ecosystem studies.https://digitalcommons.library.umaine.edu/aes_techbulletin/1053/thumbnail.jp

Porcine Bladder Urothelial, Myofibroblast, and Detrusor Muscle Cells: Characterization and ATP Release

ATP is released from the bladder mucosa in response to stretch, but the cell types responsible are unclear. Our aim was to isolate and characterize individual populations of urothelial, myofibroblast, and detrusor muscle cells in culture, and to examine agonist-stimulated ATP release. Using female pig bladders, urothelial cells were isolated from bladder mucosa following trypsin-digestion of the luminal surface. The underlying myofibroblast layer was dissected, minced, digested, and cultured until confluent (10–14 days). A similar protocol was used for muscle cells. Cultures were used for immunocytochemical staining and/or ATP release investigations. In urothelial cultures, immunoreactivity was present for the cytokeratin marker AE1/AE3 but not the contractile protein α-smooth muscle actin (α-SMA) or the cytoskeletal filament vimentin. Neither myofibroblast nor muscle cell cultures stained for AE1/AE3. Myofibroblast cultures partially stained for α-SMA, whereas muscle cultures were 100% stained. Both myofibroblast and muscle stained for vimentin, however, they were morphologically distinct. Ultrastructural studies verified that the suburothelial layer of pig bladder contained abundant myofibroblasts, characterized by high densities of rough endoplasmic reticulum. Baseline ATP release was higher in urothelial and myofibroblast cultures, compared with muscle. ATP release was significantly stimulated by stretch in all three cell populations. Only urothelial cells released ATP in response to acid, and only muscle cells were stimulated by capsaicin. Tachykinins had no effect on ATP release. In conclusion, we have established a method for culture of three cell populations from porcine bladder, a well-known human bladder model, and shown that these are distinct morphologically, immunologically, and pharmacologically

Characterization of Retinal Structure in ATF6-Associated Achromatopsia.

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM

Structural school characteristics and neighborhood risk factors: Associations with student-reported school climate in a large, urban public school district in the United States

IntroductionSchool climate consistently predicts youth academic success, social–emotional well-being, and substance use, and positive school climate can buffer the negative effects of community violence exposure on youth development. Various structural school and neighborhood factors have been associated with school climate, but prior research has not examined these relations comprehensively.MethodsWe examined the relation between 18 school building and school neighborhood factors with student-reported school climate among 15,833 students in 124 public schools in a large, urban district in the United States.ResultsIn this sample, attendance rate was most consistently associated with school climate (β = 0.015; p < 0.001). Teacher years of experience, mobility rate, number of students in special education, adult arrests in the school neighborhood, and service calls for shootings and dirty streets and alleys in the school neighborhood were also significantly associated with various domains of school climate.ConclusionsThese findings highlight the need for future longitudinal research on the influence of both school building and school neighborhood factors on school climate for public schools. Schools in our sample had a wide range of school climate scores despite consistently high crime rates and other structural risk factors such as low socioeconomic status throughout the city, so there are implications for researchers and education leaders to work together to identify opportunities for schools to foster positive school climate despite systemic school and/or neighborhood risk factors

Historic clinical trial external control arm provides actionable GEN-1 efficacy estimate before a randomized trial

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients\u27 end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy. METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA). RESULTS: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions. CONCLUSION: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development

Exploring early developmental changes in face scanning patterns during the perception of audiovisual mismatch of speech cues

Young infants are capable of integrating auditory and visual information and their speech perception can be influenced by visual cues, while 5-month-olds detect mismatch between mouth articulations and speech sounds. From 6 months of age, infants gradually shift their attention away from eyes and towards the mouth in articulating faces, potentially to benefit from intersensory redundancy of audiovisual (AV) cues. Using eye tracking, we investigated whether 6- to 9-month-olds showed a similar age-related increase of looking to the mouth, while observing congruent and/or redundant versus mismatched and non-redundant speech cues. Participants distinguished between congruent and incongruent AV cues as reflected by the amount of looking to the mouth. They showed an age-related increase in attention to the mouth, but only for non-redundant, mismatched AV speech cues. Our results highlight the role of intersensory redundancy and audiovisual mismatch mechanisms in facilitating the development of speech processing in infants under 12 months of age

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD