Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes ...overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.
The PTOLEMY project aims to develop a scalable design for a Cosmic Neutrino Background (CNB) detector, the first of its kind and the only one conceived that can look directly at the image of the ...Universe encoded in neutrino background produced in the first second after the Big Bang. The scope of the work for the next three years is to complete the conceptual design of this detector and to validate with direct measurements that the non-neutrino backgrounds are below the expected cosmological signal. In this paper we discuss in details the theoretical aspects of the experiment and its physics goals. In particular, we mainly address three issues. First we discuss the sensitivity of PTOLEMY to the standard neutrino mass scale. We then study the perspectives of the experiment to detect the CNB via neutrino capture on tritium as a function of the neutrino mass scale and the energy resolution of the apparatus. Finally, we consider an extra sterile neutrino with mass in the eV range, coupled to the active states via oscillations, which has been advocated in view of neutrino oscillation anomalies. This extra state would contribute to the tritium decay spectrum, and its properties, mass and mixing angle, could be studied by analyzing the features in the beta decay electron spectrum.
Aims.
The goal of this study is to present the development of a machine learning based approach that utilizes phase space alone to separate the
Gaia
DR2 stars into two categories: those accreted onto ...the Milky Way from those that are in situ. Traditional selection methods that have been used to identify accreted stars typically rely on full 3D velocity, metallicity information, or both, which significantly reduces the number of classifiable stars. The approach advocated here is applicable to a much larger portion of
Gaia
DR2.
Methods.
A method known as “transfer learning” is shown to be effective through extensive testing on a set of mock
Gaia
catalogs that are based on the F
IRE
cosmological zoom-in hydrodynamic simulations of Milky Way-mass galaxies. The machine is first trained on simulated data using only 5D kinematics as inputs and is then further trained on a cross-matched
Gaia
/RAVE data set, which improves sensitivity to properties of the real Milky Way.
Results.
The result is a catalog that identifies ∼767 000 accreted stars within
Gaia
DR2. This catalog can yield empirical insights into the merger history of the Milky Way and could be used to infer properties of the dark matter distribution.
The caveolin-3 protein is expressed exclusively in muscle cells. Caveolin-3 expression is sufficient to form caveolae-sarcolemmal invaginations that are 50 to 100 nm in diameter. Monomers of ...caveolin-3 oligomerize to form high molecular mass scaffolding on the cytoplasmic surface of the sarcolemmal membrane. A mutation in one caveolin-3 allele produces an aberrant protein product capable of sequestering the normal caveolin-3 protein in the Golgi apparatus of skeletal muscle cells. Improper caveolin-3 oligomerization and membrane localization result in skeletal muscle T-tubule system derangement, sarcolemmal membrane alterations, and large subsarcolemmal vesicle formation. To date, there have been eight autosomal dominant caveolin-3 mutations identified in the human population. Caveolin-3 mutations can result in four distinct, sometimes overlapping, muscle disease phenotypes: limb girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. Thus, the caveolin-3 mutant genotype-to-phenotype relation represents a clear example of how genetic background can influence phenotypic outcome. This review examines in detail the reported cases of patients with caveolin-3 mutations and their corresponding muscle disease phenotypes.
Three Southern Italy red wines Aglianico, Casavecchia and Pallagrello with high content of total tannins but different initial anthocyanins composition were aged in bottle for 15 months with closures ...allowing different degrees of wine oxygen exposure. In all wines oxygen exposure resulted in a progressive decrease in monomeric anthocyanins, vanillin reactive flavans and content of tannins reactive toward salivary proteins. In contrast, no significant decrease in color intensity was detected due to the formation of polymeric pigments. For all wines, the closure with the highest oxygen ingress determined a higher intensity of red fruit notes.
The Ninth Annual Conference of “Anticancer Innovative Therapy”, organized by Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (Fondazione IRCCS INT) and hosted by Hotel Michelangelo, was held ...in Milan on 25 January 2019. Cutting-edge science was presented in two main scientific sessions: i) pre-clinical evidences and new targets, and ii) clinical translation. The Keynote lecture entitled “Cancer stem cells (CSCs): metabolic strategies for their identification and eradication” presented by M. Lisanti, was one of the highlights of the conference.
One key concept of the meeting was how the continuous advances in our knowledge about molecular mechanisms in various fields of research (cancer metabolism reprogramming, epigenetic regulation, transformation/invasiveness, and immunology, among others) are driving cancer research towards more effective personalized antineoplastic strategies. Specifically, recent preclinical data on the following topics were discussed: 1. Polycomb group proteins in cancer; 2. A d16HER2 splice variant is a flag of HER2 addiction across HER2-positive cancers; 3. Studying chromatin as a nexus between translational and basic research; 4. Metabolomic analysis in cancer patients; 5. CDK4-6 cyclin inhibitors: clinical activity and future perspectives as immunotherapy adjuvant; and 6. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. In terms of clinical translation, several novel approaches were presented: 1. Developing CAR-T cell therapies: an update of preclinical and clinical development at University of North Carolina; 2. Vγ9Vδ2 T-cell activation and immune suppression in multiple myeloma; 3. Predictive biomarkers for real-world immunotherapy: the cancer immunogram model in the clinical arena; and 4. Mechanisms of resistance to immune checkpoint blockade in solid tumors.
Overall, the pre-clinical and clinical findings presented could pave the way to identify novel actionable therapeutic targets to significantly enhance the care of persons with cancer.
The central regulatory role of the adipocyte in whole body energy homeostasis is well established. However, recent findings suggest that preadipocytes and adipocytes may play an important ...physiological role in the regulation of both the innate and adaptive immune response. To systematically characterize the molecular machinery of the adipocyte that mediates the recognition of pathogens, we have focused our analysis on the recently identified Toll-like receptors (TLRs). These receptors have been implicated as mediators of the cellular response to bacterial lipopolysacharides (LPSs). Here, we report the cloning and functional characterization of mouse TLR-2 from 3T3-L1 adipocytes. TLR-2 synthesis is strongly induced in the adipocyte by LPS, TNFα, and the yeast cell wall extract zymosan. TLR-2 undergoes a lengthy intracellular maturation process with a half-life of exit from the ER of approximately 3 h. Furthermore, LPS treatment of adipocytes results in dramatic changes at the level of gene expression, including the synthesis of a distinct set of secretory proteins such as interleukin-6. Our studies demonstrate the presence of a fully intact pathway of innate immunity in the adipocyte that can be activated by LPS binding to the cell surface and results in the secretion of immunomodulatory molecules.
Abstract
The PTOLEMY transverse drift filter is a new concept to
enable precision analysis of the energy spectrum of electrons near
the tritium
β
-decay endpoint. This paper details the
...implementation and optimization methods for successful operation of
the filter for electrons with a known pitch angle. We present the
first demonstrator that produces the required magnetic field
properties with an iron return-flux magnet. Two methods for the
setting of filter electrode voltages are detailed. The challenges of
low-energy electron transport in cases of low field are discussed,
such as the growth of the cyclotron radius with decreasing magnetic
field, which puts a ceiling on filter performance relative to fixed
filter dimensions. Additionally, low pitch angle trajectories are
dominated by motion parallel to the magnetic field lines and
introduce non-adiabatic conditions and curvature drift. To minimize
these effects and maximize electron acceptance into the filter, we
present a three-potential-well design to simultaneously drain the
parallel and transverse kinetic energies throughout the length of
the filter. These optimizations are shown, in simulation, to achieve
low-energy electron transport from a 1 T iron core (or 3 T
superconducting) starting field with initial kinetic energy of
18.6 keV drained to < 10 eV (< 1 eV) in about 80 cm. This
result for low field operation paves the way for the first
demonstrator of the PTOLEMY spectrometer for measurement of
electrons near the tritium endpoint to be constructed at the Gran
Sasso National Laboratory (LNGS) in Italy.
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