A Concise Total Synthesis of (--)-Maoecrystal Z

The first total synthesis of (--)-maoecrystal Z is described. The key steps of the synthesis include a diastereoselective Ti^(III)-mediated reductive epoxide coupling reaction and a diastereoselective Sm^(II)-mediated reductive cascade cyclization reaction. These transformations enabled the preparation of (--)-maoecrystal Z in only 12 steps from (--)-γ-cyclogeraniol

Perturbations in Lineage Specification of Granulosa and Theca Cells May Alter Corpus Luteum Formation and Function

Anovulation is a major cause of infertility, and it is the major leading reproductive disorder in mammalian females. Without ovulation, an oocyte is not released from the ovarian follicle to be fertilized and a corpus luteum is not formed. The corpus luteum formed from the luteinized somatic follicular cells following ovulation, vasculature cells, and immune cells is critical for progesterone production and maintenance of pregnancy. Follicular theca cells differentiate into small luteal cells (SLCs) that produce progesterone in response to luteinizing hormone (LH), and granulosa cells luteinize to become large luteal cells (LLCs) that have a high rate of basal production of progesterone. The formation and function of the corpus luteum rely on the appropriate proliferation and differentiation of both granulosa and theca cells. If any aspect of granulosa or theca cell luteinization is perturbed, then the resulting luteal cell populations (SLC, LLC, vascular, and immune cells) may be reduced and compromise progesterone production. Thus, many factors that affect the differentiation/lineage of the somatic cells and their gene expression profiles can alter the ability of a corpus luteum to produce the progesterone critical for pregnancy. Our laboratory has identified genes that are enriched in somatic follicular cells and luteal cells through gene expression microarray. This work was the first to compare the gene expression profiles of the four somatic cell types involved in the follicle-to-luteal transition and to support previous immunofluorescence data indicating theca cells differentiate into SLCs while granulosa cells become LLCs. Using these data and incorporating knowledge about the ways in which luteinization can go awry, we can extrapolate the impact that alterations in the theca and granulosa cell gene expression profiles and lineages could have on the formation and function of the corpus luteum. While interactions with other cell types such as vascular and immune cells are critical for appropriate corpus luteum function, we are restricting this review to focus on granulosa, theca, and luteal cells and how perturbations such as androgen excess and inflammation may affect their function and fertility

Molecular manipulation of keratin 8/18 intermediate filaments: modulators of FAS-mediated death signaling in human ovarian granulosa tumor cells

Background: Granulosa cell tumors (GCT) are a rare ovarian neoplasm but prognosis is poor following recurrence. Keratin intermediate filaments expressed in these tumors are a diagnostic marker, yet paradoxically, may also constitute a target for therapeutic intervention. In the current study, we evaluated keratin 8/18 (K8/18) filament expression as a mechanism of resistance to apoptosis in GCT, specifically focusing on regulation of the cell surface death receptor, Fas (FAS). Methods: The GCT cell line, KGN, was transiently transfected with siRNA to KRT8 and KRT18 to reduce K8/18 filament expression. Expression of K8/18, FAS, and apoptotic proteins (PARP, cleaved PARP) were evaluated by fluorescence microscopy, flow cytometric analysis, and immunoblotting, respectively. The incidence of FAS-mediated apoptosis in KGN cells was measured by caspase 3/7 activity. All experiments were performed independently three to six times, using a fresh aliquot of KGN cells for each experiment. Quantitative data were analyzed by one- or two-way analysis of variance (ANOVA), followed by a Tukey’s post-test for multiple comparisons; differences among means were considered statistically significant at P \u3c 0.05. Results: Control cultures of KGN cells exhibited abundant K8/18 filament expression (~90 % of cells), and minimal expression of FAS (\u3c25 % of cells). These cells were resistant to FAS-activating antibody (FasAb)-induced apoptosis, as determined by detection of cleaved PARP and measurement of caspase 3/7 activity. Conversely, siRNA-mediated knock-down of K8/18 filament expression enhanced FAS expression (\u3e 70 % of cells) and facilitated FasAb-induced apoptosis, evident by increased caspase 3/7 activity (P \u3c 0.05). Additional experiments revealed that inhibition of protein synthesis, but not MEK1/2 or PI3K signaling, also prompted FasAb-induced apoptosis. Conclusions: The results demonstrated that K8/18 filaments provide resistance to apoptosis in GCT by impairing FAS expression. The abundance of keratin filaments in these cells and their role in apoptotic resistance provides a greater mechanistic understanding of ovarian tumorgenicity, specifically GCT, as well as a clinically-relevant target for potential therapeutic intervention

Moment tensor inversions of icequakes on Gornergletscher, Switzerland

We have determined seismic source mechanisms for shallow and intermediate-depth icequake clusters recorded on the glacier Gornergletscher, Switzerland, during the summers of 2004 and 2006. The selected seismic events are part of a large data set of over 80,000 seismic events acquired with a dense seismic network deployed in order to study the yearly rapid drainage of Gornersee lake, a nearby ice-marginal lake. Using simple frequency and distance scaling and Green’s functions for a homogeneous half-space, we calculated moment tensor solutions for icequakes with M_w-1.5 using a full-waveform inversion method usually applied to moderate seismic events (M_w>4) recorded at local to regional distances (≈50–700 km). Inversions from typical shallow events are shown to represent tensile crack openings. This explains well the dominating Rayleigh waves and compressive first motions observed at all recording seismograms. As these characteristics can be observed in most icequake signals, we believe that the vast majority of icequakes recorded in the 2 yr is due to tensile faulting, most likely caused by surface crevasse openings. We also identified a shallow cluster with somewhat atypical waveforms in that they show less dominant Rayleigh waves and quadrantal radiation patterns of first motions. Their moment tensors are dominated by a large double-couple component, which is strong evidence for shear faulting. Although less than a dozen such icequakes have been identified, this is a substantial result as it shows that shear faulting in glacier ice is generally possible even in the absence of extreme flow changes such as during glacier surges. A third source of icequakes was located at 100 m depth. These sources can be represented by tensile crack openings. Because of the high-hydrostatic pressure within the ice at these depths, these events are most likely related to the presence of water lenses that reduce the effective stress to allow for tensile faulting

Returning to Learning: Adults' Success in College Is Key to America's Future

Provides an overview of research on adult learners' characteristics, risk factors, and needs at four-year institutions and in for-credit and non-credit courses, and what changes institutions and governments can implement to help adult students succeed

Effect of Brief Biofeedback via a Smartphone App on Stress Recovery: Randomized Experimental Study.

BACKGROUND:Smartphones are often vilified for negatively influencing well-being and contributing to stress. However, these devices may, in fact, be useful in times of stress and, in particular, aid in stress recovery. Mobile apps that deliver evidence-based techniques for stress reduction, such as heart rate variability biofeedback (HRVB) training, hold promise as convenient, accessible, and effective stress-reducing tools. Numerous mobile health apps that may potentially aid in stress recovery are available, but very few have demonstrated that they can influence health-related physiological stress parameters (eg, salivary biomarkers of stress). The ability to recover swiftly from stress and reduce physiological arousal is particularly important for long-term health, and thus, it is imperative that evidence is provided to demonstrate the effectiveness of stress-reducing mobile health apps in this context. OBJECTIVE:The purpose of this research was to investigate the physiological and psychological effects of using a smartphone app for HRVB training following a stressful experience. The efficacy of the gamified Breather component of the Happify mobile health app was examined in an experimental setting. METHODS:In this study, participants (N=140) underwent a laboratory stressor and were randomly assigned to recover in one of three ways: with no phone present, with a phone present, with the HRBV game. Those in the no phone condition had no access to their phone. Those in the phone present condition had their phone but did not use it. Those in the HRVB game condition used the serious game Breather on the Happify app. Stress recovery was assessed via repeated measures of salivary alpha amylase, cortisol, and self-reported acute stress (on a 1-100 scale). RESULTS:Participants in the HRVB game condition had significantly lower levels of salivary alpha amylase during recovery than participants in the other conditions (F2,133=3.78, P=.03). There were no significant differences among the conditions during recovery for salivary cortisol levels or self-reported stress. CONCLUSIONS:These results show that engaging in a brief HRVB training session on a smartphone reduces levels of salivary alpha amylase following a stressful experience, providing preliminary evidence for the effectiveness of Breather in improving physiological stress recovery. Given the known ties between stress recovery and future well-being, this study provides a possible mechanism by which gamified biofeedback apps may lead to better health

Government-Industry Cooperative Fisheries Research in the North Pacific under the MSFCMA

The National Marine Fisheries Service’s Alaska Fisheries Science Center (AFSC) has a long and successful history of conducting research in cooperation with the fishing industry. Many of the AFSC’s annual resource assessment surveys are carried out aboard chartered commercial vessels and the skill and experience of captains and crew are integral to the success of this work. Fishing companies have been contracted to provide vessels and expertise for many different types of research, including testing and evaluation of survey and commercial fishing gear and development of improved methods for estimating commercial catch quantity and composition. AFSC scientists have also participated in a number of industry-initiated research projects including development of selective fishing gears for bycatch reduction and evaluating and improving observer catch composition sampling. In this paper, we describe the legal and regulatory provisions for these types of cooperative work and present examples to illustrate the process and identify the requirements for successful cooperative research

Vibration Isolation Design for the Micro-X Rocket Payload

Micro-X is a NASA-funded, sounding rocket-borne X-ray imaging spectrometer that will allow high precision measurements of velocity structure, ionization state and elemental composition of extended astrophysical systems. One of the biggest challenges in payload design is to maintain the temperature of the detectors during launch. There are several vibration damping stages to prevent energy transmission from the rocket skin to the detector stage, which causes heating during launch. Each stage should be more rigid than the outer stages to achieve vibrational isolation. We describe a major design effort to tune the resonance frequencies of these vibration isolation stages to reduce heating problems prior to the projected launch in the summer of 2014.Comment: 6 pages, 7 figures, LTD15 Conference Proceeding