Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

The development of common data elements for a multi-institute prostate cancer tissue bank: The Cooperative Prostate Cancer Tissue Resource (CPCTR) experience

BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers. To facilitate this effort, it was critical to arrive at agreed upon common data elements (CDEs) that could be used to collect demographic, pathologic, treatment and clinical outcome data. METHODS: The CPCTR investigators convened a CDE curation subcommittee to develop and implement CDEs for the annotation of collected prostate tissues. The draft CDEs were refined and progressively annotated to make them ISO 11179 compliant. The CDEs were implemented in the CPCTR database and tested using software query tools developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE subcommittee developed 145 data elements to annotate the tissue samples collected. These included for each case: 1) demographic data, 2) clinical history, 3) pathology specimen level elements to describe the staging, grading and other characteristics of individual surgical pathology cases, 4) tissue block level annotation critical to managing a virtual inventory of cases and facilitating case selection, and 5) clinical outcome data including treatment, recurrence and vital status. These elements have been used successfully to respond to over 60 requests by end-users for tissue, including paraffin blocks from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as frozen tissue collected prospectively for genomic profiling and genetic studies. The CPCTR CDEs have been fully implemented in two major tissue banks and have been shared with dozens of other tissue banking efforts. CONCLUSION: The freely available CDEs developed by the CPCTR are robust, based on "best practices" for tissue resources, and are ISO 11179 compliant. The process for CDE development described in this manuscript provides a framework model for other organ sites and has been used as a model for breast and melanoma tissue banking efforts

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

BACKGROUND: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. METHODS: Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. RESULTS: Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence. CONCLUSION: Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems

Non-invasive Approaches for the Diagnosis of Autoimmune/Autoinflammatory Skin Diseases—A Focus on Psoriasis and Lupus erythematosus

The traditional diagnostic gold standard for inflammatory skin lesions of unclear etiology is dermato-histopathology. As this approach requires an invasive skin biopsy, biopsy processing and analysis by specialized histologists, it is a resource intensive approach requiring trained healthcare professionals. In many health care settings access to this diagnostic approach can be difficult and outside emergency cases will usually take several weeks. This scenario leads to delayed or inappropriate treatment given to patients. With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation—they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin diseases.With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation – they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin disease

Pectopexy vs sacrocolpopexy: an analysis of 50 cases in a North American hospitalAJOG Global Reports at a Glance

BACKGROUND: Laparoscopic pectopexy is an alternative to sacrocolpopexy that was first reported in 2010. This procedure has been performed at our hospital since 2019 in patients with contraindications to sacrocolpopexy. OBJECTIVE: This study aimed to compare the outcomes of 50 cases of pectopexy with historical outcomes data for sacrocolpopexy. STUDY DESIGN: This was a retrospective review of 50 laparoscopic pectopexies performed from July 2020 to July 2022 at an academic tertiary referral center; this was the second reported use of this technique in North America. The outcomes from laparoscopic pectopexy were compared with laparoscopic sacrocolpopexy performed at the same institution by the same surgeons (n=207). The primary outcomes were complication rate, rate of recurrent prolapse (stage II or greater), and reoperation. RESULTS: Overall complication rates were 6.0% for pectopexy and 16.5% for sacrocolpopexy (relative risk, 0.79; P=.65). Recurrent prolapse was seen among 2.0% of patients who underwent pectopexy and 6.3% of patients who underwent sacrocolpopexy at most recent follow-up (relative risk, 1.27; P=.66). The rates of reoperation were 2.0% for pectopexy and 3.9% for sacrocolpopexy (relative risk, 1.04; P=.96). The average operative times were 138 minutes for pectopexy and 158 minutes for sacrocolpopexy. The average lengths of follow-up were 88.1 days for pectopexy and 325.5 for sacrocolpopexy. CONCLUSION: Although pectopexy was typically employed in patients with extensive pelvic adhesions or other conditions that placed them at higher risk of complications, both the success rate and the adverse event rate were similar to those in the historical cohort who underwent sacrocolpopexy. Although sacrocolpopexy remains the gold standard operation for apical prolapse, our data suggest that pectopexy can be employed to offer similar outcomes in many patients with contraindications to sacral fixation. These data give us increasing confidence that we can counsel our patients that this operation is likely to produce an outcome similar to a sacrocolpopexy