Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

A validation of the Nottingham Clavicle Score: a clavicle, acromioclavicular joint and sternoclavicular joint–specific patient-reported outcome measure

Background Patients with acromioclavicular joint (ACJ) and sternoclavicular joint (SCJ) injuries and with clavicle fractures are typically younger and more active than those with other shoulder pathologies. We developed the Nottingham Clavicle Score (NCS) specifically for this group of patients to improve sensitivity for assessing the outcomes of treatment of these conditions compared with the more commonly used Constant Score (CS) and Oxford Shoulder Score (OSS). Materials and methods This was a cohort study in which the preoperative and 6-month postoperative NCS evaluations of outcome in 90 patients were compared with the CS, OSS, Imatani Score (IS), and the EQ-5D scores. Reliability was assessed using the Cronbach α. Reproducibility of the NCS was assessed using the test/retest method. Effect sizes were calculated for each score to assess sensitivity to change. Validity was examined by correlations between the NCS and the CS, OSS, IS, and EQ-5D scores obtained preoperatively and postoperatively. Results Significant correlations were demonstrated preoperatively with the OSS (P = .025) and all subcategories of the EQ-5D (P < .05) and postoperatively with the OSS (P < .001), CS (P = .008), IS (P < .001), and all subcategories of EQ-5D (P < .02). The NCS had the largest effect size (1.92) of the compared scores. Internal consistency was excellent (Cronbach α = 0.87). Conclusion The NCS has been proven to be a valid, reliable and sensitive outcome measure that accurately measures the level of function and disability in the ACJ, SCJ and clavicle after traumatic injury and in degenerative disease

Agricultural Land Use Planning and Groundwater Quality

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75123/1/j.1468-2257.1983.tb00394.x.pd

Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma

Multi-wavelength Analysis of the Merging Galaxy Cluster A115

A115 is a merging galaxy cluster at $z\sim0.2$ with a number of remarkable features including a giant ($\sim2.5$ Mpc) radio relic, two asymmetric X-ray peaks with trailing tails, and a peculiar line-of-sight velocity structure. We present a multi-wavelength study of A115 using optical imaging data from Subaru, X-ray data from $Chandra$, and spectroscopic data from the Keck/DEIMOS and MMT/Hectospec instruments. Our weak-lensing analysis shows that the cluster is comprised of two subclusters whose mass centroids are in excellent agreement with the two BCG positions ($\lesssim10$"). By modeling A115 with a superposition of two Navarro-Frenk-White halos, we determine the masses of the northern and southern subclusters to be $M_{200}=1.58_{-0.49}^{+0.56}\times 10^{14} \text{M}_{\odot}$ and $3.15_{-0.71}^{+0.79}\times 10^{14} \text{M}_{\odot}$, respectively. Combining the two halos, we estimate the total cluster mass to be $M_{200}=6.41_{-1.04}^{+1.08}\times10^{14} \text{M}_{\odot}$ at $R_{200}=1.67_{-0.09}^{+0.10}$ Mpc. These weak-lensing masses are significantly (a factor of 3-10) lower than what is implied by the X-ray and optical spectroscopic data. We attribute the difference to the gravitational and hydrodynamic disruption caused by the collision between the two subclusters.Comment: 20 pages, 17 figures, Accepted for publication in Ap

Safe and just operating spaces for regional social-ecological systems

Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockström et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development

The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey

We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and accepted by AJ. Provides background for the instrument responsible for SDSS and BOSS spectra. 4th in a series of survey technical papers released in Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral Classification), and arXiv:1208.0022 (BOSS Overview

W, Z and Higgs Scattering at SSC Energies

We examine the scattering of longitudinal $W$, $Z$ and Higgs bosons in the Standard Model using the equivalent Goldstone-boson Lagrangian. Our calculations include the full one-loop scattering matrix between the states $W^+_LW^-_L$, $Z_LZ_L$ and $HH$ with no restrictions on the relative sizes of $M_H$ and $\sqrt{s}$. In addition to deriving the perturbative eigen-amplitudes, we also obtain quite striking results by unitarizing the amplitudes with the use of the K-matrix and Pad\'e techniques. (Complete postscript file can be obtained by anonymous ftp from hal.physics.wayne.edu as dpf92g.ps in directory pub/physics )Comment: Talk presented at DPF92, November 10-14, 1992. 3 pages with 6 PostScript figures included. LaTeX fil

Modified‐Release Subantimicrobial Dose Doxycycline Enhances Scaling and Root Planing in Subjects With Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142084/1/jper0440.pd

Formation of Super-Earths

Super-Earths are the most abundant planets known to date and are characterized by having sizes between that of Earth and Neptune, typical orbital periods of less than 100 days and gaseous envelopes that are often massive enough to significantly contribute to the planet's overall radius. Furthermore, super-Earths regularly appear in tightly-packed multiple-planet systems, but resonant configurations in such systems are rare. This chapters summarizes current super-Earth formation theories. It starts from the formation of rocky cores and subsequent accretion of gaseous envelopes. We follow the thermal evolution of newly formed super-Earths and discuss their atmospheric mass loss due to disk dispersal, photoevaporation, core-cooling and collisions. We conclude with a comparison of observations and theoretical predictions, highlighting that even super-Earths that appear as barren rocky cores today likely formed with primordial hydrogen and helium envelopes and discuss some paths forward for the future.Comment: Invited review accepted for publication in the 'Handbook of Exoplanets,' Planet Formation section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Ed