bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Nutrition Risk and Status in Critically Ill Patients: What Are Our Considerations?
Authors: Lee Zheng‐Yii , Heyland Daren K.
Published: November 2018

The stress catabolism state predisposes critically ill patients to a high risk of malnutrition. This, coupled with inadequate or delayed nutrition provision, will lead to further deterioration of nutrition status. Preexisting malnutrition and iatrogenic underfeeding are associated with increased risk of adverse complications. Therefore, accurate detection of patients who are malnourished and/or with high nutrition risk is important for timely and optimal nutrition intervention. Various tools have been developed for nutrition screening and assessment for hospitalized patients, but not all are studied or validated in critically ill populations. In this review article, we consider the pathophysiology of malnutrition in critical illness and the currently available literature to develop recommendations for nutrition screening and assessment. We suggest the use of the (modified) Nutrition Risk in the Critically Ill (mNUTRIC) for nutrition risk screening and the subjective global assessment (SGA) together with other criteria relevant to the critically ill patients, such as gastrointestinal function, risk of aspiration, determination of sarcopenia and frailty, and risk of refeeding syndrome for nutrition assessment. Further research is needed to identify suitable nutrition monitoring indicators to determine the response to the provision of nutrition.
On the development of uniaxially‐oriented PET tapes for weaving, woven tape fabrics, and their applications
Authors: Bashir Zahir , Bandyopadhyay Sumanda , Kummetha Reddy , Lohmeijer Jan
Published: November 2018

This article reports the development of weavable, uniaxially‐oriented PET tape, and woven‐tape fabric. Fabric from uniaxially‐oriented polypropylene (PP) tape has been commercially produced since the 1960s, and it is the dominant material for flexible industrial packaging, carpet backing, geotextiles and self‐reinforced composites. Attempts had been made over the same period to produce similar poly(ethylene terephthalate) (PET) tape fabric, knowing that it would offer superior performance over PP due to PET's higher stiffness and strength, lower creep, abrasion resistance, and higher temperature capability. However, these attempts could not be translated into industrial production because the PET tapes had a tendency to splinter when subjected to sudden pulls and twists in the weaving loom. This was solved here by blending polymeric additives such as 2% polycarbonate (PC) and 2% linear low‐density polyethylene (LLDPE). Transmission electron microscopy of the oriented tapes showed the 2% PC formed a profusion of nano ellipsoids that adhered well to the PET matrix, and these prevented axial cracks from running through in a brittle manner. The LLDPE formed larger domains with poorer adhesion, but it imparted resistance to splitting from twists and axial folding. The combination of PC and polyolefin imparted a synergistic toughening of the tape. POLYM. ENG. SCI., 59:E120–E132, 2019. © 2018 Society of Plastics Engineers
Tumor‐Derived Extracellular Vesicles as a Novel Source of Protein Biomarkers for Cancer Diagnosis and Monitoring
Authors: Ruhen Olivia , Meehan Katie
Published: November 2018

“Liquid biopsies” have received attention as a complementary tool for traditional tissue biopsies that may enhance the spectrum of analysis for tumor‐derived factors. One such factor gaining prominence in the liquid biopsy field is extracellular vesicles (EVs), membrane‐bound nanovesicles which are secreted by cells into biofluids such as blood, urine, and saliva. EVs are released in both physiological and pathological conditions and can transport a variety of molecules, including proteins, metabolites, RNA, microRNAs, and DNA, to distant sites throughout the body. As such, they are emerging as a promising source of tumor biomarkers for the noninvasive diagnosis, prognosis, and monitoring of cancer patients. In particular, the wealth of tumor‐related information that can be gleaned from the EV proteomic cargo has become apparent through mass spectrometric analysis, which has provided new benchmarks for clinically focused biomarker research. In this review, the current achievements in the use of MS for identifying potential EV‐derived protein biomarkers of cancer are explored, and the techniques and challenges involved in this pursuit are summarized.
Proteomic Signature of Mesenchymal Stromal Cell‐Derived Small Extracellular Vesicles
Authors: van Balkom Bas W. M. , Gremmels Hendrik , Giebel Bernd , Lim Sai Kiang
Published: November 2018

Small extracellular vesicles (EVs) are 50–200 nm vesicles secreted by most cells. They are considered as mediators of intercellular communication, and EVs from specific cell types, in particular mesenchymal stem/stromal cells (MSCs), offer powerful therapeutic potential, and can provide a novel therapeutic strategy. They appear promising and safe (as EVs are non‐self‐replicating), and eventually MSC‐derived EVs (MSC‐EVs) may be developed to standardized, off‐the‐shelf allogeneic regenerative and immunomodulatory therapeutics. Promising pre‐clinical data have been achieved using MSCs from different sources as EV‐producing cells. Similarly, a variety EV isolation and characterization methods have been applied. Interestingly, MSC‐EVs obtained from different sources and prepared with different methods show in vitro and in vivo therapeutic effects, indicating that isolated EVs share a common potential. Here, well‐characterized and controlled, publicly available proteome profiles of MSC‐EVs are compared to identify a common MSC‐EV protein signature that might be coupled to the MSC‐EVs’ common therapeutic potential. This protein signature may be helpful in developing MSC‐EV quality control platforms required to confirm the identity and test for the purity of potential therapeutic MSC‐EVs.
Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives
Authors: Barrachina Maria N. , Calderón‐Cruz Beatriz , Fernandez‐Rocca Lucía , García Ángel
Published: November 2018

Extracellular vesicles (EVs) are a heterogeneous population of vesicles composed of a lipid bilayer that carry a large repertoire of molecules including proteins, lipids, and nucleic acids. In this review, some guidelines for plasma‐derived EVs isolation, characterization, and proteomic analysis, and the application of the above to cardiovascular disease (CVD) studies are provided. For EVs analysis, blood samples should be collected using a 21‐gauge needle, preferably in citrate tubes, and plasma stored for up to 1 year at −80°, using a single freeze–thaw cycle. For proteomic applications, differential centrifugation (including ultracentrifugation steps) is a good option for EVs isolation. EVs characterization is done by transmission electron microscopy, particle enumeration techniques (nanoparticle‐tracking analysis, dynamic light scattering), and flow cytometry. Regarding the proteomics strategy, a label‐free and gel‐free quantitative method is a good choice due to its accuracy and because it minimizes the amount of sample required for clinical applications. Besides the above, main EVs proteomic findings in cardiovascular‐related diseases are presented and analyzed in this review, paying especial attention to overlapping results between studies. The latter might offer new insights into the clinical relevance and potential of novel EVs biomarkers identified to date in the context of CVD.
Fine mapping of hydrophobic contacts reassesses the organization of the first three dystrophin coiled‐coil repeats
Authors: Mias‐Lucquin Dominique , Chéron Angélique , Le Rumeur Elisabeth , Hubert Jean‐François , Delalande Olivier
Published: November 2018

Coiled‐coil domain is a structural motif found in proteins crucial for achievement of central biological processes, such as cellular cohesion or neuro‐transmission. The coiled‐coil fold consists of alpha‐helices bundle that can be repeated to form larger filament. Hydrophobic residues, distributed following a regular seven‐residues’ pattern, named heptad pattern, are commonly admitted to be essential for the formation and the stability of canonical coiled‐coil repeats. Here we investigated the first three coiled‐coil repeats (R1–R3) of the central domain of dystrophin, a scaffolding protein in muscle cells whose deficiency leads to Duchenne and Becker Muscular Dystrophies. By an atomic description of the hydrophobic interactions, we highlighted (i) that coiled‐coil filament conformational changes are associated to specific patterns of inter‐helices hydrophobic contacts, (ii) that inter‐repeat hydrophobic interactions determine the behavior of linker regions including filament kinks, and (iii) that a non‐strict conservation of the heptad patterns is leading to a relative plasticity of the dystrophin coiled‐coil repeats. These structural features and modulations of the coiled‐coil fold could better explain the mechanical properties of the central domain of dystrophin. This contribution to the understanding of the structure–function relationship of dystrophin, and especially of the R1–R3 fragment frequently used in the design of protein for gene therapies, should help in the improvement of the strategies for the cure of muscular dystrophies.
Synthesis, in vitro stability, and antiproliferative effect of d‐cysteine modified GnRH‐doxorubicin conjugates
Authors: Li Songtao , Zhao Hongling , Chang Xiaomin , Wang Jianping , Zhao Enhong , Yin Zhifeng , Mao Xiaoxia , Deng Shuhua , Hao Ting , Wang Huina , Yang Yaqi
Published: November 2018

Overexpression of gonadotropin‐releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [d‐Cys6, desGly10, Pro9‐NH2]‐GnRH, [d‐Cys6, desGly10, Pro9‐NHEt]‐GnRH, and [d‐Cys6, α‐aza‐Gly10‐NH2]‐GnRH were conjugated with doxorubicin (Dox), respectively, through N‐succinimidyl‐3‐maleimidopropionate as a linker to afford three new GnRH‐Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP‐HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor‐positive MCF‐7 human breast cancer cell line by MTT assay. The three GnRH‐Dox conjugates showed improved metabolic stability in human serum in comparison with AN‐152. The antiproliferative effect of conjugate II ([d‐Cys6, desGly10, Pro9‐NHEt]‐GnRH‐Dox) on MCF‐7 cells was higher than that of conjugate I ([d‐Cys6, desGly10, Pro9‐NH2]‐GnRH‐Dox) and conjugate III ([d‐Cys6, α‐aza‐Gly10‐NH2]‐GnRH‐Dox), and the cytotoxicity of conjugate II against GnRH receptor‐negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [d‐Cys6‐des‐Gly10‐Pro9‐NHEt]‐GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [d‐Cys6‐des‐Gly10‐Pro9‐NHEt]‐GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors.
Characterization of Graphite/ZnO Schottky Barriers Formed on Polar and Nonpolar ZnO Surfaces
Authors: Yatskiv Roman , Tiagulskyi Stanislav , Grym Jan
Published: November 2018

The authors demonstrate that the electrical properties of Schottky junctions fabricated by the deposition of colloidal graphite strongly depend on the crystallographic orientation of the ZnO substrate. The current‐voltage, capacitance‐voltage, and impedance measurements indicate that near‐ideal Schottky junctions form on c‐plane, while on a‐ and m‐plane the junctions are laterally inhomogeneous. This behavior is assigned to higher concentration of native point defects in the near‐surface region of nonpolar ZnO substrates. The authors further present an extended equivalent circuit model, which corresponds to actual structure of the junctions, and sheds light on their electrical transport properties.
Bulk and Surface‐Related Degradation in Lifetime Samples Made of Czochralski Silicon Passivated by Plasma‐Enhanced Chemical Vapor Deposited Layer Stacks
Authors: Sperber David , Schwarz Anton , Herguth Axel , Hahn Giso
Published: November 2018

Significant bulk‐related degradation (BRD) is followed by surface‐related degradation (SRD) of effective excess charge carrier lifetime in lifetime samples made of Czochralski silicon during illuminated treatment at 80–150 °C. Samples are passivated with either AlOx:H/SiOxNy:H/SiNx:H or SiOxNy:H/SiNx:H stacks stemming entirely from plasma‐enhanced chemical vapor deposition. Samples show strong variations in BRD depending on passivation stacks and treatment conditions, and a potential link to light and elevated temperature‐induced degradation (LeTID) is discussed. All samples are fired in a belt furnace, and variations of firing temperature and belt speed are shown to influence SRD slightly. SRD is furthermore accelerated with increasing treatment temperature and an apparent activation energy Eapp = 1.07 ± 0.02 eV is determined in SiOxNy:H/SiNx:H passivated samples. Interpretation of Eapp is, however, difficult as both changes in interfacial defect and fixed charge density occur in parallel during SRD.
The role of time‐varying rare disaster risks in predicting bond returns and volatility
Authors: Gupta Rangan , Suleman Tahir , Wohar Mark E.
Published: November 2018

This paper aims to provide empirical evidence to the theoretical claim that rare disaster risks affect government bond market movements. Using a nonparametric quantiles‐based methodology, we show that rare disaster‐risks affect only volatility, but not returns, of 10‐year government bond of the United States over the monthly period of 1918:01 to 2013:12. In addition, the predictability of volatility holds for the majority of the conditional distribution of the volatility, with the exception of the extreme ends. Moreover, in general, similar results are also obtained for long‐term government bonds of an alternative developed country (UK) and an emerging market (South Africa).
Fluorine Substituted Bithiophene Imide‐Based n‐Type Polymer Semiconductor for High‐Performance Organic Thin‐Film Transistors and All‐Polymer Solar Cells
Authors: Sun Huiliang , Tang Yumin , Guo Han , Uddin Mohammad Afsar , Ling Shaohua , Wang Ruizhi , Wang Yingfeng , Zhou Xin , Woo Han Young , Guo Xugang
Published: November 2018

Bithiophene imide (BTI) is a promising building block for constructing n‐type organic semiconductors. The β‐positions of thiophene in BTI offer an exceptional opportunity for further structural expansion and optimization. Herein, a novel fluorinated BTI, s‐FBTI2, is designed and successfully synthesized, and its incorporation into a polymer backbone led to the resulting semiconductor s‐FBTI2‐FT with improved polymer backbone planarity enabled by the intramolecular non‐covalent S···F interactions and optimized electronic structure attributed to the high electronegativity of F atoms. When applied in organic thin‐film transistors (OTFTs), s‐FBTI2‐FT shows a unipolar n‐type transport with a remarkable electron mobility approaching 3.0 cm2 V−1 s−1, which is >3‐fold higher than that of the polymer analogue without F. Moreover, all‐polymer solar cells (all‐PSCs) with s‐FBTI2‐FT as the electron acceptor polymer achieve a power conversion efficiency of 6.50% with a remarkably high open‐circuit voltage of 1.04 V, which is substantially greater than that of solar cells based on the nonfluorinated analogue acceptor showing negligible photovoltaic performance. The results demonstrate that s‐FBTI‐FT is one of best‐performing n‐type polymer semiconductors reported till today in terms of both OTFT and all‐PSC performances, and fluorination offers an effective approach for optimizing optoelectronic properties of BTI‐based polymers for device performance improvement.
Postcracking tensile behavior of blended steel fiber‐reinforced concrete
Authors: Hu Hang , Wang Zhao , Figueiredo Fabio P. , Papastergiou Panos , Guadagnini Maurizio , Pilakoutas Kypros
Published: November 2018

Fiber blends have the potential to improve the mechanical and sustainability credentials of steel fiber‐reinforced concrete (SFRC), but at which ratios these can work is not known a priori. This paper investigates the uniaxial tensile stress–strain (
σ − ε) relationship of blended SFRC using manufactured steel fibers on their own, or blended with sorted steel fibers recycled from end‐of‐life tires (recycled tire steel fiber [RTSF]), at total fiber dosages of 30, 35, and 45 kg/m3. The accuracy of two
σ − ε relations proposed by RILEM TC 162‐TDF and Model Code 2010 is assessed using the experimental results from concrete prisms. By using nonlinear finite element (FE) analysis, it is found that the RILEM approach can lead to significant overestimation (up to 72%) of peak flexural load and energy absorption capacity (up to 39%), while the Model Code 2010 can provide a rather accurate prediction of the energy absorption capacity and some overestimation (less than 34%) of the peak flexural load. Inverse FE analysis is used to determine indirectly the uniaxial tensile
σ − ε relations of the examined SFRC mixes, and a simplified trilinear relation for SFRC is proposed. It is concluded that the tensile strength of SFRC with RTSF at a low total fiber dosage is only marginally improved by fiber addition, and the postcracking tensile strengths at different strains can be determined directly from residual flexural tensile strengths (f
Ri) of prisms.
Spinorial flux tubes in SO(N) gauge theories in 2+1 dimensions
Authors: Teper Michael
Published: November 2018

Abstract

We investigate whether one can observe in SO(3) and SO(4) (lattice) gauge theories the presence of spinorial flux tubes, i.e. ones that correspond to the fundamental representation of SU(2); and similarly for SO(6) and SU(4). We do so by calculating the finite volume dependence of the J

p
= 2+ glueball in 2 + 1 dimensions, using lattice simulations. We show how this provides strong evidence that these SO(N) gauge theories contain states that are composed of (conjugate) pairs of winding spinorial flux tubes, i.e. ones that are in the (anti)fundamental of the corresponding SU(N
′) gauge theories. Moreover, these two flux tubes can be arbitrarily far apart. This is so despite the fact that the fields that are available in the SO(N) lattice field theories do not appear to allow us to construct operators that project onto single spinorial flux tubes.
New 3d $$ \mathcal{N} $$ = 2 dualities from quadratic monopoles
Authors: Amariti Antonio , Garozzo Ivan , Mekareeya Noppadol
Published: November 2018

Abstract

Aspects of three dimensional

$$ \mathcal{N} $$

N

= 2 gauge theories with monopole super-potentials and their dualities are investigated. The moduli spaces of a number of such theories are studied using Hilbert series. Moreover, we propose new dualities involving quadratic powers for the monopole superpotentials, for unitary, symplectic and orthogonal gauge groups. These dualities are then tested using the three sphere partition function and matching of the Hilbert series. We also provide an argument for the obstruction to the duality for theories with quartic monopole superpotentials.
On three-loop RGE for the Higgs sector of 2HDM
Authors: Bednyakov A. V.
Published: November 2018

Abstract

We discuss renormalization group equations (RGE) for the parameters of the Higgs sector in general Two-Higgs-Doublet Model (2HDM). We present the three-loop results but consider only contributions due to self-couplings of the Higgs doublets. We study the structure of RGE and express beta-functions in terms of reparametrization invariants with respect to higgs-basis rotations. The Cayley-Hamilton theorem is utilized to reduce both the number of independent tensor structures in matrix RGE and the number of invariants to a minimal set. As a by-product of our calculation we discovered that two-loop RGE of the scalar sector in general QFT with multiple higgses were not properly implemented in a number of public packages. The latter give rise to a wrong result when mixing in the scalar sector is allowed.
AncestryPainter: A Graphic Program for Displaying Ancestry Composition of Populations and Individuals
Authors: Feng Qidi , Lu Dongsheng , Xu Shuhua
Published: November 2018

Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program, AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry. AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.
Border closures and the externalization of immigration controls in the Mediterranean: A comparative analysis of Morocco and Turkey – RETRACTED
Authors: Üstübici Ayşen , İçduygu Ahmet
Published: November 2018

This article traces the recent history of border closures in Turkey and Morocco and their impact on human mobility at the two ends of the Mediterranean. Border closures in the Mediterranean have produced new spaces where borders are often fenced, immigration securitized, and border crossings and those facilitating border crossings criminalized. Here, bordering practices are conceptualized as physical bordering practices, border controls, and legal measures. Turkey and Morocco constitute comparable cases for an analysis of border closures insofar as they utilize similar mechanisms of closure, despite having quite different outcomes in terms of numbers. The article’s findings are based on fieldwork conducted at both locations between 2012 and 2014, as well as on analysis of Frontex Risk Assessment Reports from 2010 to 2016. The first part of the article reflects on the concepts of border closure and securitization, together with their implications, and draws for its argument on critical security studies and critical border studies. The second part of the article is an overview of controls over mobility exercised in the Mediterranean from the 1990s onward. Then, in the third and fourth parts, we turn to the particular cases—respectively, Turkey and Morocco—in order to discuss their processes of border closure and the various implications thereof. Through analysis of the two country cases, we show that border closures are neither linear nor irreversible.
Release site selection: reintroductions and the habitat concept
Authors: Stadtmann Sven , Seddon Philip J.
Published: November 2018

Identifying release sites with good habitat quality is one of the most important steps in any reintroduction project. However, despite their wide application in legislation and research, the habitat concept and habitat-related terms remain poorly defined and subject to confusion. Reviewing a variety of definitions, we advocate for understanding habitat as an area with a species-specific set of resources and environmental conditions that enable a population to persist and reproduce. Using this understanding we investigated release site selection as well as the usage of the term habitat and other habitat-related terms in 324 reintroduction case studies and reintroduction policy documents published during January 1990–May 2016. Although the use of the habitat concept in these publications remained mostly unclear because of the lack of definitions provided, we found an overall improvement in the quality of reintroduction site assessment, and a shift towards more systematic approaches, such as habitat modelling and experimental translocation. To further improve reporting on release site selection, we recommend updating IUCN reintroduction publications and encouraging practitioners to consider the spatial and temporal heterogeneity of habitat, as well as the multiple scales at which a species selects its habitat, in the design of a release site assessment.
THE IMPACT OF LEARNING ON BUSINESS CYCLE FLUCTUATIONS IN THE CONSUMER UNSECURED CREDIT MARKET
Authors: Luzzetti Matthew N. , Neumuller Seth
Published: November 2018

We document that the credit spread on consumer unsecured debt exhibits a persistent, hump-shaped response to an increase in the charge-off rate. This stylized fact poses a significant challenge for a standard model of consumer default in which lenders have rational expectations and, therefore, the credit spread continuously adjusts to reflect the true default incentives of each borrower. In an effort to explain this feature of the data, we construct a model of consumer default with countercyclical income risk in which lenders learn about default risk over time by observing the history of repayment decisions, as is the case in practice. In addition to matching credit spread dynamics, allowing lenders to learn about default risk substantially improves the model’s ability to generate realistic business cycle fluctuations in the consumer unsecured credit market and match the cross-sectional distribution of unsecured debt and dispersion of interest rates observed in the data.
Top food sources of percentage of energy, nutrients to limit and total gram amount consumed among US adolescents: National Health and Nutrition Examination Survey 2011–2014
Authors: Leme Ana Carolina , Baranowski Tom , Thompson Debbe , Philippi Sonia , O’Neil Carol , Fulgoni Victor , Nicklas Theresa
Published: November 2018

Objective

To identify most commonly consumed foods by adolescents contributing to percentage of total energy, added sugars, SFA, Na and total gram intake per day.

Design

Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014.

Setting

NHANES is a cross-sectional study nationally representative of the US population.

Participants

One 24 h dietary recall was used to assess dietary intake of 3156 adolescents aged 10–19 years. What We Eat in America food category classification system was used for all foods consumed. Food sources of energy, added sugars, SFA, Na and total gram amount consumed were sample-weighted and ranked based on percentage contribution to intake of total amount.

Results

Three-highest ranked food subgroup sources of total energy consumed were: sugar-sweetened beverages (SSB; 7·8 %); sweet bakery products (6·9 %); mixed dishes – pizza (6·6 %). Highest ranked food sources of total gram amount consumed were: plain water (33·1 %); SSB (15·8 %); milk (7·2 %). Three highest ranked food sources of total Na were: mixed dishes – pizza (8·7 %); mixed dishes – Mexican (6·7 %); cured meats/poultry (6·6 %). Three highest ranked food sources of SFA were: mixed dishes – pizza (9·1 %); sweet bakery products (8·3 %); mixed dishes – Mexican (7·9 %). Three highest ranked food sources of added sugars were: SSB (42·1 %); sweet bakery products (12·1 %); coffee and tea (7·6 %).

Conclusions

Identifying current food sources of percentage energy, nutrients to limit and total gram amount consumed among US adolescents is critical for designing strategies to help them meet nutrient recommendations within energy needs.
Memory of Medical Scenarios for End-of-Life Support Preferences
Authors: García-Bajos Elvira , Migueles Malen
Published: November 2018

We studied memory of health scenarios for end-of-life support decisions and stability of life support preferences. Psychology students (n= 36, ageM= 27.25,SD= 6.21, 64% females) were administered the Life Support Preferences Questionnaire to assess their memory of six medical scenarios with different prognoses, care treatment, and end-of-life support choices. Recall, recognition, confidence and decision stability were assessed immediately and one month later. Correct recall decreased and incorrect recall increased from immediate to long-term recall,F(2, 68) = 74.38,p< .001, η2p= .69. In recall, participants spontaneously gave false information consistent with prior knowledge of illnesses and medical scenarios. Participants who had suffered a disease or serious accident did worse on correct recall,F(1, 34) = 6.59,p= .015, η2p= .16, and had more errors,F(1, 34) = 4.68,p= .038, η2p= .12, than participants who had not. In the recognition test there were no differences between hits and false alarms, showing the difficulty in discriminating between true and false contents. Confidence was greater for hits than for false alarms,F(1, 34) = 10.86,p= .002, η2p= .24, but this subjective measure did not seem to be a good predictor of accuracy because confidence was greater than the mean value for hits (p =.001,d= 1.74) and for false alarms (p =.001,d= 0.96). Long-term memory was quite poor and biased, but life support preferences did not change much.
Morbus Fabry – das Porträt einer seltenen Erkrankung
Authors: Tamò Raphaël , Zweifel Sandrine A. , Beuschlein Felix , Nowak Albina
Published: November 2018

Zusammenfassung. Morbus Fabry ist eine lysosomale Speicherkrankheit (LSK), welche durch eine gestörte lysosomale Funktion charakterisiert ist. Pathophysiologisch steht der Ausfall des Enzyms α-Galaktosidase A als Folge von Mutationen im GLA-Gen im Vordergrund. Konsekutiv kommt es hauptsächlich zur Überladung der des Organismus mit dem Enzymsubstrat Globotriaosylzeramid (Gb3). Der Morbus Fabry ist eine X-chromosomal vererbte Krankheit. Frauen mit einem Krankheitsallel zeigen deshalb zumeist eine mildere Symptomatik. Regelmässige, unspezifische Erstsymptome im Kindesalter sind Akroparästhesien, Hypo- oder Anhidrose und Angiokeratome. Im späteren Erwachsenenalter treten die lebenslimitierenden Komplikationen wie progressive Niereninsuffizienz, Kardiomyopathie und zerebrale Insulte auf. Zur Diagnose ist die Messung der α-Galaktosidase A – Aktivität im Plasma oder in peripheren Leukozyten erforderlich. Zur spezifischen Therapie ist beim Morbus Fabry die rekombinante Enzymersatztherapie zugelassen, pharmakologische Chaperone können, je nach Genotyp, ebenfalls zum Einsatz kommen.
Hämochromatose assoziierte Arthropathie
Authors: Nowak Peter
Published: November 2018

Zusammenfassung. Die Hämochromatose ist eine meist durch eine HFE-Genmutation (High Iron Fe) verursachte autosomal rezessive Erkrankung. Pathophysiologisch liegt als Auswirkung der Mutation eine erhöhte Eisenresorption im Darm vor. Es handelt sich um eine Systemerkrankung, welche neben dem Befall des muskuloskelettalen Systems (MSK) zu einer diabetischen Stoffwechsellage, Leberzirrhose und Hautverfärbungen sowie zu anderen Organmanifestationen wie Kardiopathie oder Hypogonadismus im Spätstadium führen kann. Zu den MSK-Komplikationen zählen die Arthropathie in Form von Arthrose typischerweise der MCP-2- und -3-Gelenke und der Calciumpyrophosphat-assoziierten Arthritis (CPPD). Die Osteoporose als weitere Komplikation ist multifaktoriell bedingt. Die Therapie der Hämochromatose besteht in Aderlässen, die orale Gabe von Eisenchelatoren ist ebenfalls möglich. Diese Massnahmen wirken zwar günstig auf die Entstehung von Organkomplikationen wie Leberzirrhose, zeigen jedoch wenig Einfluss auf die MSK-Manifestationen, welche in Analogie zur idiopathischen Arthrose oder Pseudogicht behandelt werden. Gleiches gilt für die Osteoporose.
Flux of Particulate Elements in the North Atlantic Ocean Constrained by Multiple Radionuclides
Authors: Hayes Christopher T. , Black Erin E. , Anderson Robert F. , Baskaran Mark , Buesseler Ken O. , Charette Matthew A. , Cheng Hai , Cochran J. Kirk , Edwards R. Lawrence , Fitzgerald Patrick , Lam Phoebe J. , Lu Yanbin , Morris Stephanie O. , Ohnemus Daniel C. , Pavia Frank J. , Stewart Gillian , Tang Yi
Published: November 2018

Sinking particles strongly regulate the distribution of reactive chemical substances in the ocean, including particulate organic carbon and other elements (e.g., P, Cd, Mn, Cu, Co, Fe, Al, and 232Th). Yet, the sinking fluxes of trace elements have not been well described in the global ocean. The U.S. GEOTRACES campaign in the North Atlantic (GA03) offers the first data set in which the sinking flux of carbon and trace elements can be derived using four different radionuclide pairs (238U:234Th ;210Pb:210Po; 228Ra:228Th; and 234U:230Th) at stations co‐located with sediment trap fluxes for comparison. Particulate organic carbon, particulate P, and particulate Cd fluxes all decrease sharply with depth below the euphotic zone. Particulate Mn, Cu, and Co flux profiles display mixed behavior, some cases reflecting biotic remineralization, and other cases showing increased flux with depth. The latter may be related to either lateral input of lithogenic material or increased scavenging onto particles. Lastly, particulate Fe fluxes resemble fluxes of Al and 232Th, which all have increasing flux with depth, indicating a dominance of lithogenic flux at depth by resuspended sediment transported laterally to the study site. In comparing flux estimates derived using different isotope pairs, differences result from different timescales of integration and particle size fractionation effects. The range in flux estimates produced by different methods provides a robust constraint on the true removal fluxes, taking into consideration the independent uncertainties associated with each method. These estimates will be valuable targets for biogeochemical modeling and may also offer insight into particle sinking processes.
Effects of Version 2 of the International Sunspot Number on Naïve Predictions of Solar Cycle 25
Authors: Pesnell W. Dean
Published: November 2018

The recalibration of the International Sunspot Number brings new challenges to predictions of Solar Cycle 25. One is that the list of extrema for the original series is no longer usable because the values of all maxima and minima are different for the new version of the sunspot number. Timings of extrema are less sensitive to the recalibration but are a natural result of the calculation. Predictions of Solar Cycle 25 published before 2016 must be converted to the new version of the sunspot number. Any prediction method that looks across the entire time span will have to be reconsidered because values in the nineteenth century were corrected by a larger factor than those in the twentieth century. We report a list of solar maxima and minima values and timings based on the recalibrated sunspot number. Naïve forecasts that depend only on the current values of the time series are common in economic studies. Several naïve predictions of Solar Cycle 25, the climatological average (180 ± 60), two versions of the inertial forecast, and two versions of the even‐odd forecast, are derived from that table. The climatological average forecast is the baseline for more accurate predictions and the initial forecast in assimilative models of the Sun. It also provides the error estimate for Monte Carlo techniques that anticipate the long‐term effects on the terrestrial environment. The other four predictions are shown to be statistically insignificant.
Watt-scale super-octave mid-infrared intrapulse difference frequency generation
Authors: Gaida Christian , Gebhardt Martin , Heuermann Tobias , Stutzki Fabian , Jauregui Cesar , Antonio-Lopez Jose , Schülzgen Axel , Amezcua-Correa Rodrigo , Tünnermann Andreas , Pupeza Ioachim , Limpert Jens
Published: November 2018

The development of high-power, broadband sources of coherent mid-infrared radiation is currently the subject of intense research that is driven by a substantial number of existing and continuously emerging applications in medical diagnostics, spectroscopy, microscopy, and fundamental science. One of the major, long-standing challenges in improving the performance of these applications has been the construction of compact, broadband mid-infrared radiation sources, which unify the properties of high brightness and spatial and temporal coherence. Due to the lack of such radiation sources, several emerging applications can be addressed only with infrared (IR)-beamlines in large-scale synchrotron facilities, which are limited regarding user access and only partially fulfill these properties. Here, we present a table-top, broadband, coherent mid-infrared light source that provides brightness at an unprecedented level that supersedes that of synchrotrons in the wavelength range between 3.7 and 18 µm by several orders of magnitude. This result is enabled by a high-power, few-cycle Tm-doped fiber laser system, which is employed as a pump at 1.9 µm wavelength for intrapulse difference frequency generation (IPDFG). IPDFG intrinsically ensures the formation of carrier-envelope-phase stable pulses, which provide ideal prerequisites for state-of-the-art spectroscopy and microscopy.
Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia
Authors: Hackinger Sophie , Prins Bram , Mamakou Vasiliki , Zengini Eleni , Marouli Eirini , Brčić Luka , Serafetinidis Ioannis , Lamnissou Klea , Kontaxakis Vassilis , Dedoussis George , Gonidakis Fragiskos , Thanopoulou Anastasia , Tentolouris Nikolaos , Tsezou Aspasia , Zeggini Eleftheria
Published: November 2018

The epidemiologic link between schizophrenia (SCZ) and type 2 diabetes (T2D) remains poorly understood. Here, we investigate the presence and extent of a shared genetic background between SCZ and T2D using genome-wide approaches. We performed a genome-wide association study (GWAS) and polygenic risk score analysis in a Greek sample collection (GOMAP) comprising three patient groups: SCZ only (n = 924), T2D only (n = 822), comorbid SCZ and T2D (n = 505); samples from two separate Greek cohorts were used as population-based controls (n = 1,125). We used genome-wide summary statistics from two large-scale GWAS of SCZ and T2D from the PGC and DIAGRAM consortia, respectively, to perform genetic overlap analyses, including a regional colocalisation test. We show for the first time that patients with comorbid SCZ and T2D have a higher genetic predisposition to both disorders compared to controls. We identify five genomic regions with evidence of colocalising SCZ and T2D signals, three of which contain known loci for both diseases. We also observe a significant excess of shared association signals between SCZ and T2D at nine out of ten investigatedpvalue thresholds. Finally, we identify 29 genes associated with both T2D and SCZ, several of which have been implicated in biological processes relevant to these disorders. Together our results demonstrate that the observed comorbidity between SCZ and T2D is at least in part due to shared genetic mechanisms.
Honey bee Royalactin unlocks conserved pluripotency pathway in mammals
Authors: Wan Derrick C. , Morgan Stefanie L. , Spencley Andrew L. , Mariano Natasha , Chang Erin Y. , Shankar Gautam , Luo Yunhai , Li Ted H. , Huh Dana , Huynh Star K. , Garcia Jasmine M. , Dovey Cole M. , Lumb Jennifer , Liu Ling , Brown Katharine V. , Bermudez Abel , Luong Richard , Zeng Hong , Mascetti Victoria L. , Pitteri Sharon J. , Wang Jordon , Tu Hua , Quarta Marco , Sebastiano Vittorio , Nusse Roel , Rando Thomas A. , Carette Jan E. , Bazan J. Fernando , Wang Kevin C.
Published: November 2018

Royal jelly is the queen-maker for the honey bee Apis mellifera, and has cross-species effects on longevity, fertility, and regeneration in mammals. Despite this knowledge, how royal jelly or its components exert their myriad effects has remained poorly understood. Using mouse embryonic stem cells as a platform, here we report that through its major protein component Royalactin, royal jelly can maintain pluripotency by activating a ground-state pluripotency-like gene network. We further identify Regina, a mammalian structural analog of Royalactin that also induces a naive-like state in mouse embryonic stem cells. This reveals an important innate program for stem cell self-renewal with broad implications in understanding the molecular regulation of stem cell fate across species.
Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels
Authors: Novo David , Heath Nikki , Mitchell Louise , Caligiuri Giuseppina , MacFarlane Amanda , Reijmer Dide , Charlton Laura , Knight John , Calka Monika , McGhee Ewan , Dornier Emmanuel , Sumpton David , Mason Susan , Echard Arnaud , Klinkert Kerstin , Secklehner Judith , Kruiswijk Flore , Vousden Karen , Macpherson Iain R. , Blyth Karen , Bailey Peter , Yin Huabing , Carlin Leo M. , Morton Jennifer , Zanivan Sara , Norman Jim C.
Published: November 2018

Mutant p53s (mutp53) increase cancer invasiveness by upregulating Rab-coupling protein (RCP) and diacylglycerol kinase-α (DGKα)-dependent endosomal recycling. Here we report that mutp53-expressing tumour cells produce exosomes that mediate intercellular transfer of mutp53’s invasive/migratory gain-of-function by increasing RCP-dependent integrin recycling in other tumour cells. This process depends on mutp53’s ability to control production of the sialomucin, podocalyxin, and activity of the Rab35 GTPase which interacts with podocalyxin to influence its sorting to exosomes. Exosomes from mutp53-expressing tumour cells also influence integrin trafficking in normal fibroblasts to promote deposition of a highly pro-invasive extracellular matrix (ECM), and quantitative second harmonic generation microscopy indicates that this ECM displays a characteristic orthogonal morphology. The lung ECM of mice possessing mutp53-driven pancreatic adenocarcinomas also displays increased orthogonal characteristics which precedes metastasis, indicating that mutp53 can influence the microenvironment in distant organs in a way that can support invasive growth.
High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer
Authors: Echeverria Gloria V. , Powell Emily , Seth Sahil , Ge Zhongqi , Carugo Alessandro , Bristow Christopher , Peoples Michael , Robinson Frederick , Qiu Huan , Shao Jiansu , Jeter-Jones Sabrina L. , Zhang Xiaomei , Ramamoorthy Vandhana , Cai Shirong , Wu Wenhui , Draetta Giulio , Moulder Stacy L. , Symmans William F. , Chang Jeffrey T. , Heffernan Timothy P. , Piwnica-Worms Helen
Published: November 2018

Most triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during metastasis were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary breast tumors of TNBC patients diagnosed with synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated clonal tracking reveal robust alterations in clonal architecture between primary tumors and corresponding metastases. Polyclonal seeding and maintenance of heterogeneous populations of low-abundance subclones is observed in each metastasis. However, lung, liver, and brain metastases are enriched for an identical population of high-abundance subclones, demonstrating that primary tumor clones harbor properties enabling them to seed and thrive in multiple organ sites. Further, clones that dominate multi-organ metastases share a genomic lineage. Thus, intrinsic properties of rare primary tumor subclones enable the seeding and colonization of metastases in secondary organs in these models.
Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome
Authors: Goswami Panchali , Abid Ali Ferdos , Douglas Max E. , Locke Julia , Purkiss Andrew , Janska Agnieszka , Eickhoff Patrik , Early Anne , Nans Andrea , Cheung Alan M. C. , Diffley John F. X. , Costa Alessandro
Published: November 2018

Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.
A synthetic microbial biosensor for high-throughput screening of lactam biocatalysts
Authors: Yeom Soo-Jin , Kim Moonjeong , Kwon Kil Koang , Fu Yaoyao , Rha Eugene , Park Sung-Hyun , Lee Hyewon , Kim Haseong , Lee Dae-Hee , Kim Dong-Myung , Lee Seung-Goo
Published: November 2018

Biocatalytic cyclization is highly desirable for efficient synthesis of biologically derived chemical substances, such as the commodity chemicals ε-caprolactam and δ-valerolactam. To identify biocatalysts in lactam biosynthesis, we develop a caprolactam-detecting genetic enzyme screening system (CL-GESS). TheAlcaligenes faecalisregulatory protein NitR is adopted for the highly specific detection of lactam compounds against lactam biosynthetic intermediates. We further systematically optimize the genetic components of the CL-GESS to enhance sensitivity, achieving 10-fold improvement. Using this highly sensitive GESS, we screen marine metagenomes and find an enzyme that cyclizes ω-amino fatty acids to lactam. Moreover, we determine the X-ray crystal structure and catalytic residues based on mutational analysis of the cyclase. The cyclase is also used as a helper enzyme to sense intracellular ω-amino fatty acids. We expect this simple and accurate biosensor to have wide-ranging applications in rapid screening of new lactam-synthesizing enzymes and metabolic engineering for lactam bio-production.
The disease resistance protein SNC1 represses the biogenesis of microRNAs and phased siRNAs
Authors: Cai Qiang , Liang Chao , Wang Suikang , Hou Yingnan , Gao Lei , Liu Li , He Wenrong , Ma Wenbo , Mo Beixin , Chen Xuemei
Published: November 2018

Plants evolved an array of disease resistance genes (R genes) to fight pathogens. In the absence of pathogen infection, NBS-LRR genes, which comprise a major subfamily of R genes, are suppressed by a small RNA cascade involving microRNAs (miRNAs) that trigger the biogenesis of phased siRNAs (phasiRNAs) from R gene transcripts. However, whether or how R genes influence small RNA biogenesis is unknown. In this study, we isolate a mutant with global defects in the biogenesis of miRNAs and phasiRNAs in Arabidopsis thaliana and trace the defects to the over accumulation and nuclear localization of an R protein SNC1. We show that nuclear SNC1 represses the transcription of miRNA and phasiRNA loci, probably through the transcriptional corepressor TPR1. Intriguingly, nuclear SNC1 reduces the accumulation of phasiRNAs from three source R genes and concomitantly, the expression of a majority of the ~170R genes is up-regulated. Taken together, this study suggests an R gene-miRNA-phasiRNA regulatory module that amplifies plant immune responses.