Origins of Hidden Sector Dark Matter I: Cosmology

We present a systematic cosmological study of a universe in which the visible sector is coupled, albeit very weakly, to a hidden sector comprised of its own set of particles and interactions. Assuming that dark matter (DM) resides in the hidden sector and is charged under a stabilizing symmetry shared by both sectors, we determine all possible origins of weak-scale DM allowed within this broad framework. We show that DM can arise only through a handful of mechanisms, lending particular focus to Freeze-Out and Decay and Freeze-In, as well as their variations involving late time re-annihilations of DM and DM particle anti-particle asymmetries. Much like standard Freeze-Out, where the abundance of DM depends only on the annihilation cross-section of the DM particle, these mechanisms depend only on a very small subset of physical parameters, many of which may be measured directly at the LHC. In particular, we show that each DM production mechanism is associated with a distinctive window in lifetimes and cross-sections for particles which may be produced in the near future. We evaluate prospects for employing the LHC to definitively reconstruct the origin of DM in a companion paper.Comment: 32 pages, 19 figures; v2: references added, published versio

A novel role for the TIR domain in association with pathogen-derived elicitors

Plant innate immunity is mediated by Resistance (R) proteins, which bear a striking resemblance to animal molecules of similar function. Tobacco N is a TIR-NB-LRR R gene that confers resistance to Tobacco mosaic virus, specifically the p50 helicase domain. An intriguing question is how plant R proteins recognize the presence of pathogen-derived Avirulence (Avr) elicitor proteins. We have used biochemical cell fraction and immunoprecipitation in addition to confocal fluorescence microscopy of living tissue to examine the association between N and p50. Surprisingly, both N and p50 are cytoplasmic and nuclear proteins, and N's nuclear localization is required for its function. We also demonstrate an in planta association between N and p50. Further, we show that N's TIR domain is critical for this association, and indeed, it alone can associate with p50. Our results differ from current models for plant innate immunity that propose detection is mediated solely through the LRR domains of these molecules. The data we present support an intricate process of pathogen elicitor recognition by R proteins involving multiple subcellular compartments and the formation of multiple protein complexes. © 2007 Burch-Smith et al

Generalised risk-sensitive control with full and partial state observation

This paper generalises the risk-sensitive cost functional by introducing noise dependent penalties on the state and control variables. The optimal control problems for the full and partial state observation are considered. Using a change of probability measure approach, explicit closed-form solutions are found in both cases. This has resulted in a new risk-sensitive regulator and filter, which are generalisations of the well-known classical results

Detection of coupling misalignment by extended orbits

In this paper a ‘SpectraQuest’ demonstrator is used to introduce misalignment into a rotating machinery set-up. Depending on the coupling used in the set-up, angular and/or parallel misalignment can be brought in the rotating system. Traditionally, the data captured by accelerometers is transferred into the frequency domain in order to interpret the vibrations measured by the accelerometers. The frequency domain has proven its usefulness but even the time domain can come in handy to draw the right conclusions regarding to misalignment in a rotating set-up. Orbit plots display the integrated data captured by accelerometers, in order to display the movement of the rotating shaft. The influence of the misalignment and imbalance on these orbits will be discussed

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Six years survival on imatinib with no disease progression after diagnosis of metastatic duodenal gastrointestinal stromal tumour: a case report

Introduction: A duodenal Gastrointestinal Stromal Tumour (GIST) is a rare finding and until recently advanced disease had a poor prognosis. A PubMed search revealed no reports of more than five years survival of inoperable GIST on chemotherapy with WHO performance status zero. Case Presentation: A 68 year old female was diagnosed with unresectable GIST in the duodenum with metastasis to liver, pancreas and omentum in November 2001. She was commenced on imatinib mesylate (Glivec) chemotherapy. This case report was prepared from the medical records and radiology reports. She had good tolerance with stable disease. After six years her CT scan showed no disease progression and her WHO performance status was zero. Conclusion: This report supports the view that imatinib is a safe and effective drug in controlling disease progression in advanced metastatic GIST and plays an important role in improving the patient's quality of life

Surgery corrects asynchrony of ribcage secondary to extra-thoracic tumor but leads to expiratory dysfunction during exercise

BACKGROUND: The effect of chest wall tumours on chest wall mechanics is uncertain even less is known about the effects of resection and reconstruction. Our aim is to study how chest wall mechanics are altered in chest wall sarcoma and to determine the effect of chest wall reconstruction on chest wall kinetics. CASE PRESENTATION: Using Optoelectronic Plethysmography (OEP), total and regional chest wall volumes were measured in a patient with unilateral extra-thoracic chest wall sarcoma, before and 5 months after resection and reconstruction, during quiet breathing and exercise using cycle ergometry. During quiet breathing the unilateral tumour was associated with reduced in motion of the lower rib cage and abdominal compartments on both sides of the chest as well as asynchronous motion of the contralateral lower rib cage. Surgery corrected these abnormalities in quiet breathing. But during exercise there was a reduction in the upper rib cage motion compared to pre-operative measures from 0.43+/−0.06 to 0.36 +/− 0.02 L postoperatively (p <0.05). This impairment was characterised by a significant increase in the end expiratory volume on the operated side of the chest 5 months after surgery by 6.5 +/− 0.6 and 5.7 +/− 0.7 % during 50 and 100 % exercise respectively (p <0.0001) a finding that was not replicated in the non-operated side. CONCLUSION: This physiological study demonstrates the negative effect of chest wall tumours on global chest wall mechanics during quiet breathing and exercise and shows that surgery reverses this abnormality, but only at rest

An automated multiwell plate reading film microscope for live cell autofluorescence lifetime assays

Fluorescence lifetime imaging (FLIM) is increasingly used to read out cellular autofluorescence originating from the coenzyme NADH in the context of investigating cell metabolic state. We present here an automated multiwell plate reading FLIM microscope optimized for UV illumination with the goal of extending high content fluorescence lifetime assays to readouts of metabolism. We demonstrate its application to automated cellular autofluorescence lifetime imaging and discuss the key practical issues associated with its implementation. In particular, we illustrate its capability to read out the NADH-lifetime response of cells to metabolic modulators, thereby illustrating the potential of the instrument for cytotoxicity studies, assays for drug discovery and stratified medicine

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.We acknowledge the Wellcome Trust for supporting this work. H.B was supported by a Wellcome Trust clinical PhD fellowship. We acknowledge the Research Foundation Flanders (FWO) (FWO-G.A093.11 and FWO-G.0924.15 to T.V.; the travel grant V.4.140.10.N.00 to T.V.; N.V.d.A., E.F.G. and K.T. are Ph.D. students supported by FWO 1.1.H.28.12, FWO G.0924.15 and FWO 1126016N, respectively) and KU Leuven SymBioSys (PFV/10/016 to T.V.; P.K. is a PhD. student supported with PFV/10/016).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1116

Accuracy of elastic fusion biopsy in daily practice: results of a multicenter study of 2115 patients

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate