276 research outputs found
The Cultural Entry Process in Japan and Mexico – Cultural Factors to be Considered
This paper is intended to present a triangular cultural comparison of American, Japanese, and Mexican societies. It is written primarily for Americans who plan to live for extended periods of time in either Japan or Mexico, and is written from an American cultural point of view. Included are descriptions of my cross-cultural experiences in the three countries. The main body of the paper deals with the cross-cultural factors which I consider to be the most important to consider when attempting to successfully adapt oneself to living in either Japanese or Mexican society. It is hoped that in some way my own experiences will provide a heightened awareness for future ESL teachers of the cultural challenges presented by Japan and Mexico. The final section of the paper lays down several areas of personal skills which I deem most crucial to successful acculturation in a foreign culture
In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas
Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic qRT-PCR and whole-mount immunostaining, and 4) dissociation of primary colonies into single-cell suspensions and re-plating into secondary colony assays to assess self-renewal or differentiation
Adaptive optics performance of a simulated coronagraph instrument on a large, segmented space telescope in steady state
Directly imaging Earth-like exoplanets (``exoEarths'') with a coronagraph
instrument on a space telescope requires a stable wavefront with optical path
differences limited to tens of picometers RMS during exposure times of a few
hours. While the structural dynamics of a segmented mirror can be directly
stabilized with telescope metrology, another possibility is to use a
closed-loop wavefront sensing and control system in the coronagraph instrument
that operates during the science exposures to actively correct the wavefront
and relax the constraints on the stability of the telescope. In this paper, we
present simulations of the temporal filtering provided using the example of
LUVOIR-A, a 15~m segmented telescope concept. Assuming steady-state aberrations
based on a finite element model of the telescope structure, we (1)~optimize the
system to minimize the wavefront residuals, (2)~ use an end-to-end numerical
propagation model to estimate the residual starlight intensity at the science
detector, and (3)~predict the number of exoEarth candidates detected during the
mission. We show that telescope dynamic errors of 100~pm~RMS can be reduced
down to 30~pm~RMS with a magnitude 0 star, improving the contrast performance
by a factor of 15. In scenarios where vibration frequencies are too fast for a
system that uses natural guide stars, laser sources can increase the flux at
the wavefront sensor to increase the servo-loop frequency and mitigate the high
temporal frequency wavefront errors. For example, an external laser with an
effective magnitude of -4 allows the wavefront from a telescope with 100~pm~RMS
dynamic errors and strong vibrations as fast as 16~Hz to be stabilized with
residual errors of 10~pm~RMS thereby increasing the number of detected planets
by at least a factor of 4.Comment: Published in JATIS. arXiv admin note: substantial text overlap with
arXiv:2108.0640
Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder
Bipolar disorder is an often-severe mental health condition characterized by alternation between extreme mood states of mania and depression. Despite strong heritability and the recent identification of 64 common variant risk loci of small effect, pathophysiological mechanisms remain unknown. Here, we analyzed genome sequences from 41 multiply-affected pedigrees and identified variants in 741 genes with nominally significant linkage or association with bipolar disorder. These 741 genes overlapped known risk genes for neurodevelopmental disorders and clustered within gene networks enriched for synaptic and nuclear functions. The top variant in this analysis - prioritized by statistical association, predicted deleteriousness, and network centrality - was a missense variant in the gene encoding D-amino acid oxidase (DAOG131V). Heterologous expression of DAOG131V in human cells resulted in decreased DAO protein abundance and enzymatic activity. In a knock-in mouse model of DAOG131, DaoG130V/+, we similarly found decreased DAO protein abundance in hindbrain regions, as well as enhanced stress susceptibility and blunted behavioral responses to pharmacological inhibition of N-methyl-D-aspartate receptors (NMDARs). RNA sequencing of cerebellar tissue revealed that DaoG130V resulted in decreased expression of two gene networks that are enriched for synaptic functions and for genes expressed, respectively, in Purkinje neurons or granule neurons. These gene networks were also down-regulated in the cerebellum of patients with bipolar disorder compared to healthy controls and were enriched for additional rare variants associated with bipolar disorder risk. These findings implicate dysregulation of NMDAR signaling and of gene expression in cerebellar neurons in bipolar disorder pathophysiology and provide insight into its genetic architecture
Cells with surface expression of CD133^(high)CD71^(low) are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas
Progenitor cells in the adult pancreas are potential sources of endocrine beta cells for treating type 1 diabetes. Previously, we identified tri-potent progenitor cells in the adult (2–4 month-old) murine pancreas that were capable of self-renewal and differentiation into duct, acinar, and endocrine cells in vitro. These progenitor cells were named pancreatic colony-forming units (PCFUs). However, because PCFUs are a minor population in the pancreas (~ 1%) they are difficult to study. To enrich PCFUs, strategies using cell-surface marker analyses and fluorescence-activated cell sorting were developed. We found that CD133^(high)CD71^(low) cells, but not other cell populations, enriched PCFUs by up to 30 fold compared to the unsorted cells. CD133^(high)CD71^(low) cells generated primary, secondary, and subsequent colonies when serially re-plated in Matrigel-containing cultures, suggesting self-renewal abilities. In the presence of a laminin hydrogel, CD133^(high)CD71^(low) cells gave rise to colonies that contained duct, acinar, and Insulin+ Glucagon+ double-hormonal endocrine cells. Colonies from the laminin hydrogel culture were implanted into diabetic mice, and five weeks later duct, acinar, and Insulin+ Glucagon− cells were detected in the grafts, demonstrating tri-lineage differentiation potential of CD133^(high)CD71^(low) cells. These CD133^(high)CD71^(low) cells will enable future studies of putative adult pancreas stem cells in vivo
Nutritional predictors of complications following radical cystectomy
To determine the impact of preoperative nutritional status on the development of surgical complications following cystectomy using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)
INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of percutaneous vertebroplasty
Background: The treatment of painful osteoporotic vertebral compression fractures has historically been limited to several weeks of bed rest, anti-inflammatory and analgesic medications, calcitonin injections, or external bracing. Percutaneous vertebroplasty (the injection of bone cement into the fractured vertebral body) is a relatively new procedure used to treat these
fractures. There is increasing interest to examine the efficacy and safety of percutaneous vertebroplasty and to study the possibility of a placebo effect or whether the pain relief is from local anesthetics placed directly on the bone during the vertebroplasty procedure.
Methods/Designs: Our goal is to test the hypothesis that patients with painful osteoporotic vertebral compression fractures who undergo vertebroplasty have less disability and pain at 1 month than patients who undergo a control intervention. The control intervention is placement of local anesthesia near the fracture, without placement of cement. One hundred sixty-six patients with painful osteoporotic vertebral compression fractures will be recruited over 5 years from US and foreign sites
performing the vertebroplasty procedure. We will exclude patients with malignant tumor deposit (multiple myeloma), tumor
mass or tumor extension into the epidural space at the level of the fracture.
We will randomly assign participants to receive either vertebroplasty or the control intervention. Subjects will complete a battery of validated, standardized measures of pain, functional disability, and health related quality of life
at baseline and at post-randomization time points (days 1, 2, 3, and 14, and months 1, 3, 6, and 12). Both subjects and research interviewers performing the follow-up assessments will be blinded to the randomization assignment. Subjects will have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end of the study (month 12) to determine subsequent fracture rates. Our co-primary outcomes are the modified Roland score and pain numerical rating scale at 1 month.
Discussion: Although extensively utilized throughout North America for palliation of pain, vertebroplasty still has not
undergone rigorous study. The study outlined above represents the first randomized, controlled study that can account for a placebo effect in the setting of vertebroplasty.
Trial Registration: Current Controlled Trials ISRCTN81871888.The source of funding for the study and all authors for this publication was National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria
The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes
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