PSR J1024–0719: A Millisecond Pulsar in an Unusual Long-period Orbit

PSR J1024–0719 is a millisecond pulsar that was long thought to be isolated. However, puzzling results concerning its velocity, distance, and low rotational period derivative have led to a reexamination of its properties. We present updated radio timing observations along with new and archival optical data which show that PSR J1024–0719 is most likely in a long-period (2–20 kyr) binary system with a low-mass (≈0.4 M⊙), low-metallicity (z ≈ -0.9 dex) main-sequence star. Such a system can explain most of the anomalous properties of this pulsar. We suggest that this system formed through a dynamical exchange in a globular cluster that ejected it into a halo orbit, which is consistent with the low observed metallicity for the stellar companion. Further astrometric and radio timing observations such as measurement of the third period derivative could strongly constrain the range of orbital parameters

Defined Interactions of Protein Kinases with Hsp90 and Cdc37

Protein kinases function to transduce the countless number of signals that allow a cell to grow and adapt to its environment. A significant number of protein kinases require assistance in being folded and converted into functional signal transducers from nascent polypeptides or in maintaining their functional conformation once folded. This assistance is provided by the molecular chaperone Hsp90 and its cohort Cdc37 which together function to fold protein kinases through a series of direct interactions: a dynamic process which remains poorly understood. Deletion and site specific mutagenesis was used to generate newly synthesized epitope tagged protein kinase constructs in a reticulocyte lysate coupled transcription and translation system. This was followed by immunoabsorption of the constructs and subsequent analysis of the co-absorbing endogenous Hsp90 and Cdc37.Findings and Conclusions: In this work the interactions of three unique protein kinases with Hsp90 and Cdc37 were studied. Lck, a Src-family tyrosine kinase, which is widely known to interact with Hsp90 and Cdc37. Cdk2, a cyclin-dependent protein kinase, which has been found to genetically, although not physically, interact with Hsp90 and Cdc37. And JNK1-alpha-1, a stress activated protein kinase, which has been shown not to interact with either Hsp90 or Cdc37. The results of this work indicate that: (i) Hsp90 interacts with structural motifs found in both the N-terminal and C-terminal lobes protein kinases; (ii) Cdc37 interacts exclusively with the N-terminal lobe of protein kinases; (iii) depending on the kinase the presence of different structural motifs within the N-terminal lobe are required for Cdc37 interaction; and (iv) the minimum protein kinase structure required for high affinity salt stable Hsp90 and Cdc37 interaction is the N-terminal lobe through the stabilized alpha-E-helix in the C-terminal lobe. In turn, these findings provide insight into how Hsp90 and Cdc37 recognize, bind and fold client protein kinases. In addition, these findings provide clues to the evolutionary relationship between the Hsp90 chaperone machine and protein kinases.Department of Biochemistry and Molecular Biolog

Photometric variability of candidate white dwarf binary systems from Palomar Transient Factory archival data

We present a sample of 59 periodic variables from the Palomar Transient Factory, selected from published catalogues of white dwarf (WD) candidates. The variability can likely be attributed to ellipsoidal variation of the tidally distorted companion induced by the gravity of the primary (WD or hot subdwarf) or to the reflection of hot emission by a cooler companion. We searched 11311 spectroscopically or photometrically selected WD candidates from three hot star/WD catalogues, using the Lomb-Scargle periodogram to single out promising sources. We present period estimates for the candidates, 45 of which were not previously identified as periodic variables, and find that most have a period shorter than a few days. Additionally, we discuss the eclipsing systems in our sample and present spectroscopic data on selected sources

Characterization of the interaction of Aha1 with components of the Hsp90 chaperone machine and client proteins

AbstractThe activator of Hsp90 ATPase, Aha1, is an Hsp90 co-chaperone that has been suggested to act as a general stimulator of Hsp90 function. In this report, we have characterized the interaction of Aha1 with Hsp90 and its co-chaperones in rabbit reticulocyte lysate (RRL) and in HeLa cell extracts. Complexes formed by Aha1 with Hsp90 in RRL were stabilized by molybdate and contained the co-chaperones FKBP52 and p23/Sba1, but lacked HOP/Sti1 and Cdc37. Aha1 complexes isolated from HeLa cell extracts also contained Hsp70 and DNAJA1. Over-expression of Aha1 has been reported to stimulate the activity of v-Src and steroid hormone receptors ectopically expressed in yeast, however, no interaction between Aha1 and nascent v-Src or the progesterone receptor could be detected in RRL. Contrary to expectations, over-expression of Aha1 also inhibited the rate of Hsp90-dependent refolding of denatured luciferase. A number of potential client proteins that specifically associated with Aha1 were identified by liquid chromatography/ tandem mass spectrometry (LC–MS/MS) and verified by Western blotting. The proteins identified suggest that Aha1 may play roles in modulating RNA splicing and DNA repair, in addition to other cellular processes

Electronic, mobile and telehealth tools for vulnerable patients with chronic disease: A systematic review and realist synthesis

Objectives The objective of this review was to assess the benefit of using electronic, mobile and telehealth tools for vulnerable patients with chronic disease and explore the mechanisms by which these impact patient self-efficacy and self-management. Design We searched MEDLINE, all evidence-based medicine, CINAHL, Embase and PsychINFO covering the period 2009 to 2018 for electronic, mobile or telehealth interventions. Quality was assessed according to rigour and relevance. Those studies providing a richer description ('thick') were synthesised using a realist matrix. Setting and participants Studies of any design conducted in community-based primary care involving adults with one or more diagnosed chronic health condition and vulnerability due to demographic, geographic, economic and/or cultural characteristics. Results Eighteen trials were identified targeting a range of chronic conditions and vulnerabilities. The data provided limited insight into the mechanisms underpinning these interventions, most of which sought to persuade vulnerable patients into believing they could self-manage their conditions through improved symptom monitoring, education and support and goal setting. Patients were relatively passive in the interaction, and the level of patient response attributed to their intrinsic level of motivation. Health literacy, which may be confounded with motivation, was only measured in one study, and eHealth literacy was not assessed. Conclusions Research incorporating these tools with vulnerable groups is not comprehensive. Apart from intrinsic motivation, health literacy may also influence the reaction of vulnerable groups to technology. Social persuasion was the main way interventions sought to achieve better self-management. Efforts to engage patients by healthcare providers were lower than expected. Use of social networks or other eHealth mechanisms to link patients and provide opportunities for vicarious experience could be further explored in relation to vulnerable groups. Future research could also assess health and eHealth literacy and differentiate the specific needs for vulnerable groups when implementing health technologies

PSR J1024–0719: A Millisecond Pulsar in an Unusual Long-period Orbit

PSR J1024–0719 is a millisecond pulsar that was long thought to be isolated. However, puzzling results concerning its velocity, distance, and low rotational period derivative have led to a reexamination of its properties. We present updated radio timing observations along with new and archival optical data which show that PSR J1024–0719 is most likely in a long-period (2–20 kyr) binary system with a low-mass (≈0.4 M⊙), low-metallicity (z ≈ -0.9 dex) main-sequence star. Such a system can explain most of the anomalous properties of this pulsar. We suggest that this system formed through a dynamical exchange in a globular cluster that ejected it into a halo orbit, which is consistent with the low observed metallicity for the stellar companion. Further astrometric and radio timing observations such as measurement of the third period derivative could strongly constrain the range of orbital parameters

“Bull's-eye” sign on gadolinium-enhanced magnetic resonance venography determines thrombus presence and age: A preliminary study

AbstractPurpose: Venous thrombosis is associated with a significant inflammatory response, which can be visualized by gadolinium magnetic resonance venography (MRV). Gadolinium extravasates into tissue during inflammation, producing perithrombus enhancement on magnetic resonance scanning. This study determines (1) whether gadolinium enhancement occurs during deep venous thrombosis (DVT); and (2) whether this enhancement changes with time and can therefore establish the age of thrombus.Methods: Patients with a diagnosis of iliofemoral DVT by duplex ultrasound who were referred for MRV to document central thrombus extent were studied. T1 weighted images were obtained before and after gadolinium injection (0.1 mmol/kg); repeat scans were obtained up to 3 months thereafter. At the level of maximum thrombus, measurements of signal intensity were made at the periphery (rim), and the center of the thrombosed vein, as well as the contralateral normal vein, on images after gadolinium enhancement. Rim-center vein signal intensity ratios were then calculated and followed.Results: A total of 39 scans were obtained in 14 patients (eight men, six women). The thrombosed veins were enlarged, with a peripheral rim of enhancement (“bull's-eye” sign). The rim-center ratio for thrombosed veins (2.16 ± 0.18) was different from that of normal veins (0.66 ± 0.10; n = 39; p < 0.001). For all acute studies (≤14 days) the rim-center ratio was 2.38 ± 0.17 (n = 31), whereas for all chronic studies (>14 days) the rim-center ratio was 1.29 ± 0.44 (n = 8; p = 0.001). Among patients who underwent both early and late studies, the rim-center ratio dropped significantly, from 2.33 ± 0.20 acutely to 1.29 ± 0.44 in chronic studies (n = 8; p = 0.03). One patient with active malignancy had a paradoxic increase in rim-center ratio over time and a clinical recurrence of symptoms, suggesting active thrombosis.Conclusions: We conclude that (1) a pattern of peripheral gadolinium enhancement (bull's-eye sign) is seen around acutely thrombosed veins on gadolinium-enhanced MRV, facilitating DVT diagnosis; and (2) the ratio of signal intensity at the rim versus the center of the thrombosed vein may be a good discriminator of acute compared with chronic DVT, which may help direct therapy. (J Vasc Surg 1997;26:809-16.

Heat shock proteins are essential components in transformation and tumor progression: Cancer cell intrinsic pathways and beyond

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.Fil: Lang, Benjamin J.. Harvard Medical School; Estados UnidosFil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Prince, Thomas L.. Geisinger Medical Center; Estados UnidosFil: Ackerman, Andrew. Geisinger Medical Center; Estados UnidosFil: Bonorino, Cristina. Universidade Federal de Ciências da Saúde de Porto Alegre; Brasil. University of California; Estados UnidosFil: Calderwood, Stuart K.. Harvard Medical School; Estados Unido

Contrast-enhanced MR angiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42396/1/261-23-5-469_23n5p469.pd