Modulation of LISA free-fall orbits due to the Earth-Moon system

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies.Comment: 15 pages, 5 figure

Optical nanofibers and spectroscopy

We review our recent progress in the production and characterization of tapered optical fibers with a sub-wavelength diameter waist. Such fibers exhibit a pronounced evanescent field and are therefore a useful tool for highly sensitive evanescent wave spectroscopy of adsorbates on the fiber waist or of the medium surrounding. We use a carefully designed flame pulling process that allows us to realize preset fiber diameter profiles. In order to determine the waist diameter and to verify the fiber profile, we employ scanning electron microscope measurements and a novel accurate in situ optical method based on harmonic generation. We use our fibers for linear and non-linear absorption and fluorescence spectroscopy of surface-adsorbed organic molecules and investigate their agglomeration dynamics. Furthermore, we apply our spectroscopic method to quantum dots on the surface of the fiber waist and to caesium vapor surrounding the fiber. Finally, towards dispersive measurements, we present our first results on building and testing a single-fiber bi-modal interferometer.Comment: 13 pages, 18 figures. Accepted for publication in Applied Physics B. Changes according to referee suggestions: changed title, clarification of some points in the text, added references, replacement of Figure 13

Health problems and help-seeking in a nationwide sample of operational Norwegian ambulance personnel

Background To estimate the prevalence of anxiety and depression symptoms, and their association with professional help-seeking, among operational ambulance personnel and a general working population, and to study the symptoms of musculoskeletal pain and disturbed sleep among ambulance personnel. Methods The results of a comprehensive nationwide questionnaire survey of operational ambulance personnel (n = 1180) were compared with the findings of a population-based Norwegian health study of working people (n = 31,987). The questionnaire included measures of help-seeking, the Hospital Anxiety and Depression Scale, the Subjective Health Complaints Questionnaire, the Karolinska Sleep Questionnaire and the Need for Recovery after Work Scale. Results Compared with those in the reference population, the mean of level anxiety symptoms in the ambulance sample was lower for men (3.5 vs. 3.9, P < 0.001) and women (4.0 vs. 4.4, P < 0.05), and the mean level of depression symptoms in ambulance workers was lower for men (2.3 vs. 2.8, P < 0.05) but not for women (2.9 vs. 3.1, P = 0.22). A model adjusted for anxiety and depression symptoms indicated that ambulance personnel had lower levels of help-seeking except for seeing a chiropractor (12% vs. 5%, P < 0.01). In the ambulance sample, symptoms of musculoskeletal pain were most consistently associated with help-seeking. In the adjusted model, only symptoms of disturbed sleep were associated with help-seeking from a psychologist/psychiatrist (total sample = 2.3%). Help-seeking was more often reported by women but was largely unaffected by age. Conclusion The assumption that ambulance personnel have more anxiety and depression symptoms than the general working population was not supported. The level of musculoskeletal pain and, accordingly, the level of help-seeking from a chiropractor were higher for ambulance workers. More research should address the physical strains among ambulance personnel

The Role of Rumination and Reduced Concreteness in the Maintenance of Posttraumatic Stress Disorder and Depression Following Trauma

Rumination has been linked to posttraumatic stress disorder (PTSD) and depression following trauma. A cross-sectional (N = 101) and a prospective longitudinal study (N = 147) of road traffic accident survivors assessed rumination, PTSD and depression with self-report measures and structured interviews. We tested the hypotheses that (1) rumination predicts the maintenance of PTSD and depression and (2) reduced concreteness of ruminative thinking may be a maintaining factor. Rumination significantly predicted PTSD and depression at 6 months over and above what could be predicted from initial symptom levels. In contrast to the second hypothesis, reduced concreteness in an iterative rumination task was not significantly correlated with self-reported rumination frequency, and did not consistently correlate with symptom severity measures. However, multiple regression analyses showed that the combination of reduced concreteness and self-reported frequency of rumination predicted subsequent PTSD better than rumination frequency alone. The results support the view that rumination is an important maintaining factor of trauma-related emotional disorders

Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencingin aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

available in PMC 2011 February 3.MCL-1 has emerged as a major oncogenic and chemoresistance factor. A screen of stapled peptide helices identified the MCL-1 BH3 domain as selectively inhibiting MCL-1 among the related anti-apoptotic Bcl-2 family members, providing insights into the molecular determinants of binding specificity and a new approach for sensitizing cancer cells to apoptosis.National Institutes of Health (U.S.) (NIH award 5RO1GM084181)National Institutes of Health (U.S.) (NIH grant 5P01CA92625)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F31CA144566)Burroughs Wellcome Fund (Career Award

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma