Design Studies for a High Current Bunching System for CLIC Test Facility (CTF3) Drive Beam

A bunching system is proposed for the initial stage of CTF3 which consists of one (two) 3 GHz prebunchers and one 3 GHz travelling wave (TW) buncher with variable phase velocities. The electron beam is emitted from a 140 KV DC gun. Since the macropulse beam current (3.5 A) at the exit of the TW buncher is rather high, inside the TW buncher one has to take the beam loading effect into consideration. By using PARMELA, it is shown numerically that the bunching system can provide the bunches whose properties satisfy the design requirement of CTF3. The 0.8 m long TW buncher working at 2pi/3 mode has two phase velocities, 0.75 and 1. The dimensions of the caities in the two phase velocity regions are proposed considering the beam loading effect. The transient beam loading effect and the multibunch transverse instabilities are studied numerically, and it is concluded that higher order mode couplers should be installed in the TW buncher with the loaded quality factor of the dipole mode lower than 80.Comment: 5 figures, presented at the Linear Accelerator Conference 2000, August 2000, US

Evaluating and improving the Community Land Model's sensitivity to land cover

Modeling studies have shown the importance of biogeophysical effects of deforestation on local climate conditions but have also highlighted the lack of agreement across different models. Recently, remote-sensing observations have been used to assess the contrast in albedo, evapotranspiration (ET), and land surface temperature (LST) between forest and nearby open land on a global scale. These observations provide an unprecedented opportunity to evaluate the ability of land surface models to simulate the biogeophysical effects of forests. Here, we evaluate the representation of the difference of forest minus open land (i.e., grassland and cropland) in albedo, ET, and LST in the Community Land Model version 4.5 (CLM4.5) using various remote-sensing and in situ data sources. To extract the local sensitivity to land cover, we analyze plant functional type level output from global CLM4.5 simulations, using a model configuration that attributes a separate soil column to each plant functional type. Using the separated soil column configuration, CLM4.5 is able to realistically reproduce the biogeophysical contrast between forest and open land in terms of albedo, daily mean LST, and daily maximum LST, while the effect on daily minimum LST is not well captured by the model. Furthermore, we identify that the ET contrast between forests and open land is underestimated in CLM4.5 compared to observation-based products and even reversed in sign for some regions, even when considering uncertainties in these products. We then show that these biases can be partly alleviated by modifying several model parameters, such as the root distribution, the formulation of plant water uptake, the light limitation of photosynthesis, and the maximum rate of carboxylation. Furthermore, the ET contrast between forest and open land needs to be better constrained by observations to foster convergence amongst different land surface models on the biogeophysical effects of forests. Overall, this study demonstrates the potential of comparing subgrid model output to local observations to improve current land surface models' ability to simulate land cover change effects, which is a promising approach to reduce uncertainties in future assessments of land use impacts on climate

Associations between anxiety, body mass index, and sex hormones in women

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group

A laser triggered electron source for pulsed radiolysis

We present the design of a photo-injector based accelerator for pulsed radiolysis applications. This machine is destined to meet the needs of the physical chemistry community at the Universite de Paris XI. A 4 MeV Energy electron pulse of a few picoseconds duration and with a charge in the range of 1 to 10 nC is produced from a Cs/sub 2 /Te photocathode. The photocathode is placed in the half energy spread cell of a 1-1/2 cell, 3 GHz RF gun, whose design is based on the gun used for the drive beam of the CERN CLIC Test facility. A 4 cell "booster" cavity is then used to accelerate the beam to an energy of 9 MeV. The transport system consists of a quadrupole triplet downsteam of the booster, two rectangular, 30 degree bend, dipoles with a pair of quadrupoles between them and a second triplet downstream of the second dipole. Energy dependent path length effects in the two dipoles allow the possibility of magnetic bunch compression depending on the phase-energy correlation of the bunch exiting the booster cavity. The beam envelope and the bunch length have been calculated through the transport line using TRACE-3d and PARMELA. These codes allow us to verify the required beam parameters at the experimental areas. We discuss the adjustment of the optics, aimed at producing the minimum electron bunch length at the experimental targets. (4 refs)

Astellas' Drug Discovery Strategy: Focus on Oncology

Based on the goal of delivering innovative and reliable pharmaceutical products to cancer patients for whom no effective treatments exist, Astellas is focusing its efforts on a strategy of precision medicine in its drug discovery which is carried out at three research sites with diversity in their research platforms and research styles

SPHK1 regulates proliferation and survival responses in triplenegative breast cancer

Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer

Keep it SMPL: Automatic Estimation of 3D Human Pose and Shape from a Single Image

We describe the first method to automatically estimate the 3D pose of the human body as well as its 3D shape from a single unconstrained image. We estimate a full 3D mesh and show that 2D joints alone carry a surprising amount of information about body shape. The problem is challenging because of the complexity of the human body, articulation, occlusion, clothing, lighting, and the inherent ambiguity in inferring 3D from 2D. To solve this, we first use a recently published CNN-based method, DeepCut, to predict (bottom-up) the 2D body joint locations. We then fit (top-down) a recently published statistical body shape model, called SMPL, to the 2D joints. We do so by minimizing an objective function that penalizes the error between the projected 3D model joints and detected 2D joints. Because SMPL captures correlations in human shape across the population, we are able to robustly fit it to very little data. We further leverage the 3D model to prevent solutions that cause interpenetration. We evaluate our method, SMPLify, on the Leeds Sports, HumanEva, and Human3.6M datasets, showing superior pose accuracy with respect to the state of the art.Comment: To appear in ECCV 201