CKS1 expression in melanocytic nevi and melanoma

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway. © Brozyna et al

On the Inadequacy of Species Distribution Models for Modelling the Spread of SARS-CoV-2: Response to Araújo and Naimi

The ongoing pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing significant damage to public health and economic livelihoods, and is putting significant strains on healthcare services globally. This unfolding emergency has prompted the preparation and dissemination of the article “Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate” by Araújo and Naimi (2020). The authors present the results of an ensemble forecast made from a suite of species distribution models (SDMs), where they attempt to predict the suitability of the climate for the spread of SARS-CoV-2 over the coming months. They argue that climate is likely to be a primary regulator for the spread of the infection and that people in warm-temperate and cold climates are more vulnerable than those in tropical and arid climates. A central finding of their study is that the possibility of a synchronous global pandemic of SARS-CoV-2 is unlikely. Whilst we understand that the motivations behind producing such work are grounded in trying to be helpful, we demonstrate here that there are clear conceptual and methodological deficiencies with their study that render their results and conclusions invalid. What follows is a response to the Araújo and Naimi article centered around three main criticisms: 1) Given the fact that SARS-CoV-2 has a primary infection pathway of direct contact, it is in an active spreading phase, and remains largely underreported in the Global South, it represents an inappropriate system for analysis using the SDM framework. 2) Even if we were to accept that an SDM framework would be applicable here, the methodology presented in the article strays far from best-practice guidelines for the application of SDMs. 3) The dissemination strategy of the authors failed to respect the frameworks of risks adhered to in other academic disciplines pertaining to public health, resulting in erroneous but well-publicised claims with broad policy implications before any scientific oversight could be applied

Pre- and post- prandial appetite hormone levels in normal weight and severely obese women

<p>Abstract</p> <p>Background</p> <p>Appetite is affected by many factors including the hormones leptin, ghrelin and adiponectin. Ghrelin stimulates hunger, leptin promotes satiety, and adiponectin affects insulin response. This study was designed to test whether the pre- and postprandial response of key appetite hormones differs in normal weight (NW) and severely obese (SO) women.</p> <p>Methods</p> <p>Twenty three women ages 25–50 were recruited for this study including 10 NW (BMI = 23.1 ± 1.3 kg/m²) and 13 SO (BMI = 44.5 ± 7.1 kg/m²). The study was conducted in a hospital-based clinical research centre. Following a 12-hour fast, participants had a baseline blood draw, consumed a moderately high carbohydrate meal (60% carbohydrate, 20% protein, 20% fat) based on body weight. Postprandially, participants had six blood samples drawn at 0, 15, 30, 60, 90, and 120 minutes. Primary measures included pre- and post-prandial total ghrelin, leptin, adiponectin and insulin. A repeated measures general linear model was used to evaluate the hormone changes by group and time (significance p ≤ 0.05).</p> <p>Results</p> <p>There were significant differences between the NW and the SO for all hormones in the preprandial fasting state. The postprandial responses between the SO versus NW revealed: higher leptin (p < 0.0001), lower adiponectin (p = 0.04), trend for lower ghrelin (p = 0.06) and insulin was not different (p = 0.26). Postprandial responses over time between the SO versus NW: higher leptin (p < 0.001), lower ghrelin and adiponectin (p = 0.004, p = 0.015, respectively), and trend for higher insulin (p = 0.06).</p> <p>Conclusion</p> <p>This study indicates that significant differences in both pre- and selected post- prandial levels of leptin, ghrelin, adiponectin and insulin exist between NW and SO women. Improving our understanding of the biochemical mechanisms accounting for these differences in appetite hormones among individuals with varying body size and adiposity should aid in the development of future therapies to prevent and treat obesity.</p

NEC FUTURE Tier I Scoping Process: Public Comment

Utilizing its special expertise, the Regional Transportation Planning and High Speed Rail Research Group at the Massachusetts Institute of Technology (MIT) sought to provide input via public comment to the NEC FUTURE Tier I scoping process. Earlier in 2012, we completed a comprehensive look at the complexities and challenges associated with mobility in the NEC. This submittal is based on a report prepared for and funded by the Institute for Transportation Policy Studies (ITPS) in Tokyo, Japan, entitled Transportation in the Northeast Corridor of the U.S.: A Multimodal and Intermodal Conceptual Framework. We applied novel combinations of system analysis methods to seek new insights for planning in this corridor. With the lessons learned from this account, we seek to provide input to the NEC FUTURE scoping process, and enrich the NEC FUTURE Tier I EIS study. We recognize that the Purpose and Need and a comprehensive and carefully articulated range of alternatives are of utmost importance for the EIS process, and we are focusing our comments in these two areas. With our lessons learned, we hope to offer insights useful in formulating and refining the project’s Purpose and Need, and as well in defining the alternatives to be considered

NEC FUTURE Preliminary Alternatives Report: Public Comment

The United States Department of Transportation's Federal Railroad Administration (FRA) is currently in the early stages of a planning process to define a 30-year passenger rail investment plan for the Northeast Corridor (NEC), between Boston and Washington, D.C. In the Spring of 2013, NEC FUTURE (the name of the planning process), released a Preliminary Alternatives Report, containing 15 possible alternatives for passenger rail infrastructure investment. This working paper contains a memo from the Regional Transportation Planning and High Speed Rail Research Group at the Massachusetts Institute of Technology (MIT) responding to the Preliminary Alternatives Report, as well as following up on the group's previous public comments to NEC FUTURE (ESD-WP-2012-27 NEC FUTURE Tier I Scoping Process: Public Comment). The memo focuses on the group's reactions in three areas: “goals and objectives, and evaluation of the alternatives,” “planning under uncertainty and flexible alternatives,” and “institutional assumptions.” These comments also build on the knowledge gained from report prepared for and funded by the Institute for Transportation Policy Studies (ITPS) in Tokyo, Japan, entitled Transportation in the Northeast Corridor of the U.S.: A Multimodal and Intermodal Conceptual Framework

A Francisella tularensis Live Vaccine Strain That Improves Stimulation of Antigen-Presenting Cells Does Not Enhance Vaccine Efficacy

Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system

Models of the SL9 Impacts II. Radiative-hydrodynamic Modeling of the Plume Splashback

We model the plume "splashback" phase of the SL9 collisions with Jupiter using the ZEUS-3D hydrodynamic code. We modified the Zeus code to include gray radiative transport, and we present validation tests. We couple the infalling mass and momentum fluxes of SL9 plume material (from paper I) to a jovian atmospheric model. A strong and complex shock structure results. The modeled shock temperatures agree well with observations, and the structure and evolution of the modeled shocks account for the appearance of high excitation molecular line emission after the peak of the continuum light curve. The splashback region cools by radial expansion as well as by radiation. The morphology of our synthetic continuum light curves agree with observations over a broad wavelength range (0.9 to 12 microns). A feature of our ballistic plume is a shell of mass at the highest velocities, which we term the "vanguard". Portions of the vanguard ejected on shallow trajectories produce a lateral shock front, whose initial expansion accounts for the "third precursors" seen in the 2-micron light curves of the larger impacts, and for hot methane emission at early times. Continued propagation of this lateral shock approximately reproduces the radii, propagation speed, and centroid positions of the large rings observed at 3-4 microns by McGregor et al. The portion of the vanguard ejected closer to the vertical falls back with high z-component velocities just after maximum light, producing CO emission and the "flare" seen at 0.9 microns. The model also produces secondary maxima ("bounces") whose amplitudes and periods are in agreement with observations.Comment: 13 pages, 9 figures (figs 3 and 4 in color), accepted for Ap.J. latex, version including full figures at: http://oobleck.tn.cornell.edu/jh/ast/papers/slplume2-20.ps.g

Exclusive Production of Higgs Bosons in Hadron Colliders

We study the exclusive, double--diffractive production of the Standard Model Higgs particle in hadronic collisions at LHC and FNAL (upgraded) energies. Such a mechanism would provide an exceptionally clean signal for experimental detection in which the usual penalty for triggering on the rare decays of the Higgs could be avoided. In addition, because of the color singlet nature of the hard interaction, factorization is expected to be preserved, allowing the cross--section to be related to similar hard--diffractive events at HERA. Starting from a Fock state expansion in perturbative QCD, we obtain an estimate for the cross section in terms of the gluon structure functions squared of the colliding hadrons. Unfortunately, our estimates yield a production rate well below what is likely to be experimentally feasible.Comment: 17 pages, RevTeX file, four uufiled PostScript figures. UMPP #94-177. (Revised version. Some mistakenly missing Feynman diagrams are now added. Results do not change qualitatively. Paper reorganized.