Thermal decoupling and the smallest subhalo mass in dark matter models with Sommerfeld-enhanced annihilation rates

We consider dark matter consisting of weakly interacting massive particles (WIMPs) and revisit in detail its thermal evolution in the early universe, with a particular focus on models where the annihilation rate is enhanced by the Sommerfeld effect. After chemical decoupling, or freeze-out, dark matter no longer annihilates but is still kept in local thermal equilibrium due to scattering events with the much more abundant standard model particles. During kinetic decoupling, even these processes stop to be effective, which eventually sets the scale for a small-scale cutoff in the matter density fluctuations. Afterwards, the WIMP temperature decreases more quickly than the heat bath temperature, which causes dark matter to reenter an era of annihilation if the cross-section is enhanced by the Sommerfeld effect. Here, we give a detailed and self-consistent description of these effects. As an application, we consider the phenomenology of simple leptophilic models that have been discussed in the literature and find that the relic abundance can be affected by as much two orders of magnitude or more. We also compute the mass of the smallest dark matter subhalos in these models and find it to be in the range of about 10^{-10} to 10 solar masses; even much larger cutoff values are possible if the WIMPs couple to force carriers lighter than about 100 MeV. We point out that a precise determination of the cutoff mass allows to infer new limits on the model parameters, in particular from gamma-ray observations of galaxy clusters, that are highly complementary to existing constraints from g-2 or beam dump experiments.Comment: minor changes to match published versio

Effects of S-wave thresholds

The opening of a new S-wave threshold is frequently accompanied by an abrupt dip in the magnitude of an amplitude for an already-open channel. One familiar example is the behavior of the I=0 S-wave $\pi \pi$ scattering amplitude at $K \bar K$ threshold. Numerous other examples of this phenomenon in recent data are noted, and a unified description of the underlying dynamics is sought.Comment: 17 pages, 2 figures. Two additional references; typographic correction. To be published in Phys. Rev.

A measles virus-based vaccine induces robust chikungunya virus-specific CD4⁺ T-cell responses in a phase II clinical trial

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date, no vaccine has been licensed, but multiple vaccine candidates are under evaluation in clinical trials. One of these vaccines is based on a measles virus vector encoding for the CHIKV structural genes C, E3, E2, 6K, and E1 (MV-CHIK), which proved safe in phase I and II clinical trials and elicited CHIKV-specific antibody responses in adult measles seropositive vaccine recipients. Here, we predicted T-cell epitopes in the CHIKV structural genes and investigated whether MV-CHIK vaccination induced CHIKV-specific CD4+ and/or CD8+ T-cell responses. Immune-dominant regions containing multiple epitopes in silico predicted to bind to HLA class II molecules were found for four of the five structural proteins, while no such regions were predicted for HLA class I. Experimentally, CHIKV-specific CD4+ T-cells were detected in six out of twelve participants after a single MV-CHIK vaccination and more robust responses were found 4 weeks after two vaccinations (ten out of twelve participants). T-cells were mainly directed against the three large structural proteins C, E2 and E1. Next, we sorted and expanded CHIKV-specific T cell clones (TCC) and identified human CHIKV T-cell epitopes by deconvolution. Interestingly, eight out of nine CD4+ TCC recognized an epitope in accordance with the in silico prediction. CHIKV-specific CD8+ T-cells induced by MV-CHIK vaccination were inconsistently detected. Our data show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4+ T cell response which, together with the evidence of neutralizing antibodies as correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate in the prevention of chikungunya.</p

Oscillator Strengths and Damping Constants for Atomic Lines in the J and H Bands

We have built a line list in the near-infrared J and H bands (1.00-1.34, 1.49-1.80 um) by gathering a series of laboratory and computed line lists. Oscillator strengths and damping constants were computed or obtained by fitting the solar spectrum. The line list presented in this paper is, to our knowledge, the most complete one now available, and supersedes previous lists.Comment: Accepted, Astrophysical Journal Supplement, tentatively scheduled for the Sep. 1999 Vol. 124 #1 issue. Text and tables also available at http://www.iagusp.usp.br/~jorge

Improved Color-Temperature Relations and Bolometric Corrections for Cool Stars

We present new grids of colors and bolometric corrections for F-K stars having 4000 K < Teff < 6500 K, 0.0 < log g < 4.5 and -3.0 < [Fe/H] < 0.0. A companion paper extends these calculations into the M giant regime. Colors are tabulated for Johnson U-V and B-V; Cousins V-R and V-I; Johnson-Glass V-K, J-K and H-K; and CIT/CTIO V-K, J-K, H-K and CO. We have developed these color-temperature (CT) relations by convolving synthetic spectra with photometric filter-transmission-profiles. The synthetic spectra have been computed with the SSG spectral synthesis code using MARCS stellar atmosphere models as input. Both of these codes have been improved substantially, especially at low temperatures, through the incorporation of new opacity data. The resulting synthetic colors have been put onto the observational systems by applying color calibrations derived from models and photometry of field stars which have Teffs determined by the infrared-flux method. The color calibrations have zero points and slopes which change most of the original synthetic colors by less than 0.02 mag and 5%, respectively. The adopted Teff scale (Bell & Gustafsson 1989) is confirmed by the extraordinary agreement between the predicted and observed angular diameters of the field stars. We have also derived empirical CT relations from the field-star photometry. Except for the coolest dwarfs (Teff < 5000 K), our calibrated, solar-metallicity model colors are found to match these and other empirical relations quite well. Our calibrated, 4 Gyr, solar-metallicity isochrone also provides a good match to color-magnitude diagrams of M67. We regard this as evidence that our calibrated colors can be applied to many astrophysical problems, including modelling the integrated light of galaxies. (abridged)Comment: To appear in the March 2000 issue of the Astronomical Journal. 72 pages including 16 embedded postscript figures (one page each) and 6 embedded postscript tables (18 pages total

Measurement of neutron capture on 48^{48}Ca at thermal and thermonuclear energies

At the Karlsruhe pulsed 3.75\,MV Van de Graaff accelerator the thermonuclear $^{48}$Ca(n,$\gamma$)$^{49}$Ca(8.72\,min) cross section was measured by the fast cyclic activation technique via the 3084.5\,keV $\gamma$-ray line of the $^{49}$Ca-decay. Samples of CaCO$_3$ enriched in $^{48}$Ca by 77.87\,\% were irradiated between two gold foils which served as capture standards. The capture cross-section was measured at the neutron energies 25, 151, 176, and 218\,keV, respectively. Additionally, the thermal capture cross-section was measured at the reactor BR1 in Mol, Belgium, via the prompt and decay $\gamma$-ray lines using the same target material. The $^{48}$Ca(n,$\gamma$)$^{49}$Ca cross-section in the thermonuclear and thermal energy range has been calculated using the direct-capture model combined with folding potentials. The potential strengths are adjusted to the scattering length and the binding energies of the final states in $^{49}$Ca. The small coherent elastic cross section of $^{48}$Ca+n is explained through the nuclear Ramsauer effect. Spectroscopic factors of $^{49}$Ca have been extracted from the thermal capture cross-section with better accuracy than from a recent (d,p) experiment. Within the uncertainties both results are in agreement. The non-resonant thermal and thermonuclear experimental data for this reaction can be reproduced using the direct-capture model. A possible interference with a resonant contribution is discussed. The neutron spectroscopic factors of $^{49}$Ca determined from shell-model calculations are compared with the values extracted from the experimental cross sections for $^{48}$Ca(d,p)$^{49}$Ca and $^{48}$Ca(n,$\gamma$)$^{49}$Ca.Comment: 15 pages (uses Revtex), 7 postscript figures (uses psfig), accepted for publication in PRC, uuencoded tex-files and postscript-files also available at ftp://is1.kph.tuwien.ac.at/pub/ohu/Ca.u

Epidermal growth factor mediates detachment from and invasion through collagen I and Matrigel in Capan-1 pancreatic cancer cells

BACKGROUND: Pancreatic adenocarcinoma is a highly invasive neoplasm. Epidermal growth factor (EGF) and its receptor are over expressed in pancreatic cancer, and expression correlates with invasion and metastasis. We hypothesized that EGF receptor and integrin signalling pathways interact in mediating cellular adhesion and invasion in pancreatic cancer, and that invasiveness correlates temporally with detachment from extracellular matrix. METHODS: We tested this hypothesis by investigating the role of EGF in mediating adhesion to and invasion through collagen I and Matrigel in the metastatic pancreatic adenocarcinoma cell line Capan-1. Adhesion and invasion were measured using in vitro assays of fluorescently-labeled cells. Adhesion and invasion assays were also performed in the primary pancreatic adenocarcinoma cell line MIA PaCa-2. RESULTS: EGF inhibited adhesion to collagen I and Matrigel in Capan-1 cells. The loss of adhesion was reversed by AG825, an inhibitor of erbB2 receptor signalling and by wortmannin, a PI3K inhibitor, but not by the protein synthesis inhibitor cycloheximide. EGF stimulated invasion through collagen I and Matrigel at concentrations and time courses similar to those mediating detachment from these extracellular matrix components. Adhesion to collagen I was different in MIA PaCa-2 cells, with no significant change elicited following EGF treatment, whereas treatment with the EGF family member heregulin-alpha elicited a marked increase in adhesion. Invasion through Matrigel in response to EGF, however, was similar to that observed in Capan-1 cells. CONCLUSION: An inverse relationship exists between adhesion and invasion capabilities in Capan-1 cells but not in MIA PaCa-2 cells. EGF receptor signalling involving the erbB2 and PI3K pathways plays a role in mediating these events in Capan-1 cells

UK vaccines network:Mapping priority pathogens of epidemic potential and vaccine pipeline developments

During the 2013–2016 Ebola outbreak in West Africa an expert panel was established on the instructions of the UK Prime Minister to identify priority pathogens for outbreak diseases that had the potential to cause future epidemics. A total of 13 priority pathogens were identified, which led to the prioritisation of spending in emerging diseases vaccine research and development from the UK. This meeting report summarises the process used to develop the UK pathogen priority list, compares it to lists generated by other organisations (World Health Organisation, National Institutes of Allergy and Infectious Diseases) and summarises clinical progress towards the development of vaccines against priority diseases. There is clear technical progress towards the development of vaccines. However, the availability of these vaccines will be dependent on sustained funding for clinical trials and the preparation of clinically acceptable manufactured material during inter-epidemic periods

Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer

Background:Breast cancer anti-oestrogen resistance 4 (BCAR4) was identified in a search for genes involved in anti-oestrogen resistance in breast cancer. We explored whether BCAR4 is predictive for tamoxifen resistance and prognostic for tumour aggressiveness, and studied its function.Methods:BCAR4 mRNA levels were measured in primary breast tumours, and evaluated for association with progression-free survival (PFS) and clinical benefit in patients with oestrogen receptor (ERα)-positive tumours receiving tamoxifen as first-line monotherapy for advanced disease. In a separate cohort of patients with lymph node-negative, ERα-positive cancer, and not receiving systemic adjuvant therapy, BCAR4 levels were evaluated for association with distant metastasis-free survival (MFS). The function of BCAR4 was studied with immunoblotting and RNA interference in a cell model.Results:Multivariate analyses established high BCAR4 mRNA levels as an independent predictive factor for poor PFS after start of tamoxifen therapy for recurrent disease. High BCAR4 mRNA levels were associated with poor MFS and overall survival, reflecting tumour aggressiveness. In BCAR4-expressing cells, phosphorylation of v-erb-b2 erythroblastic leukaemia viral oncogene homolog (ERBB)2, ERBB3, and their downstream mediators extracellular signal-regulated kinase 1/2 and v-akt murine thymoma viral oncogene homolog (AKT) 1/2, was increased. Selective knockdown of ERBB2 or ERBB3 inhibited proliferation, confirming their role in BCAR4-induced tamoxifen resistance.Conclusion:BCAR4 may have clinical relevance for tumour aggressiveness and tamoxifen resistance. Our cell model suggests that BCAR4-positive breast tumours are driven by ERBB2/ERBB3 signalling. Patients with such tumours may benefit from ERBB-targeted therapy

Differential Effects of Pravastatin and Simvastatin on the Growth of Tumor Cells from Different Organ Sites

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established risk-benefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influences cholesterol biosynthesis and prenylation of signaling proteins. Pravastatin is a hydrophilic statin that is selectively taken up by a sodium-independent organic anion transporter protein-1B1 (OATP1B1) exclusively expressed in liver. Simvastatin is a hydrophobic statin that enters cells by other mechanisms. Poorly-differentiated and well-differentiated cancer cell lines were selected from various tissues and examined for their response to these two statins. Simvastatin inhibited the growth of most tumor cell lines more effectively than pravastatin in a dose dependent manner. Poorly-differentiated cancer cells were generally more responsive to simvastatin than well-differentiated cancer cells, and the levels of HMGCR expression did not consistently correlate with response to statin treatment. Pravastatin had a significant effect on normal hepatocytes due to facilitated uptake and a lesser effect on prostate PC3 and colon Caco-2 cancer cells since the OATP1B1 mRNA and protein were only found in the normal liver and hepatocytes. The inhibition of cell growth was accompanied by distinct alterations in mitochondrial networks and dramatic changes in cellular morphology related to cofilin regulation and loss of p-caveolin. Both statins, hydrophilic pravastatin and hypdrophobic simvastatin caused redistribution of OATP1B1 and HMGCR to perinuclear sites. In conclusion, the specific chemical properties of different classes of statins dictate mechanistic properties which may be relevant when evaluating biological responses to statins