bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability, Predictability, and Race Factors Affecting Performance in Elite Biathlon
Authors: Skattebo Øyvind , Losnegard Thomas
Published: June 2017

Purpose: To investigate variability, predictability, and smallest worthwhile performance enhancement in elite biathlon sprint events. In addition, the effects of race factors on performance were assessed. Methods: Data from 2005 to 2015 including >10,000 and >1000 observations for each sex for all athletes and annual top-10 athletes, respectively, were included. Generalized linear mixed models were constructed based on total race time, skiing time, shooting time, and proportions of targets hit. Within-athlete race-to-race variability was expressed as coefficient of variation of performance times and standard deviation (SD) in proportion units (%) of targets hit. The models were adjusted for random and fixed effects of subject identity, season, event identity, and race factors. Results: The within-athlete variability was independent of sex and performance standard of athletes: 2.5–3.2% for total race time, 1.5–1.8% for skiing time, and 11–15% for shooting times. The SD of the proportion of hits was ∼10% in both shootings combined (meaning ±1 hit in 10 shots). The predictability in total race time was very high to extremely high for all athletes (ICC .78–.84) but trivial for top-10 athletes (ICC .05). Race times during World Championships and Olympics were ∼2–3% faster than in World Cups. Moreover, race time increased by ∼2% per 1000 m of altitude, by ∼5% per 1% of gradient, by 1–2% per 1 m/s of wind speed, and by ∼2–4% on soft vs hard tracks. Conclusions: Researchers and practitioners should focus on strategies that improve biathletes’ performance by at least 0.8–0.9%, corresponding to the smallest worthwhile enhancement (0.3 × within-athlete variability).
Mysterious unchanging DNA finds a purpose in life
Authors: Pennisi Elizabeth
Published: June 2017

Ultraconserved elements have developmental roles.
Circular DNA throws biologists for a loop
Authors: Pennisi Elizabeth
Published: June 2017

Studies hint at health and disease roles of unusual DNAs.
Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474
Authors: van Esbroeck Annelot C. M. , Janssen Antonius P. A. , Cognetta Armand B. , Ogasawara Daisuke , Shpak Guy , van der Kroeg Mark , Kantae Vasudev , Baggelaar Marc P. , de Vrij Femke M. S. , Deng Hui , Allarà Marco , Fezza Filomena , Lin Zhanmin , van der Wel Tom , Soethoudt Marjolein , Mock Elliot D. , den Dulk Hans , Baak Ilse L. , Florea Bogdan I. , Hendriks Giel , De Petrocellis Luciano , Overkleeft Herman S. , Hankemeier Thomas , De Zeeuw Chris I. , Di Marzo Vincenzo , Maccarrone Mauro , Cravatt Benjamin F. , Kushner Steven A. , van der Stelt Mario
Published: June 2017

A clue to a drug's neurotoxicity?

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered brain damage. As an initial step in investigating whether inhibition of off-target proteins by BIA 10-2474 might contribute to its clinical neurotoxicity, van Esbroeck
et al.
used activity-based proteomic assays to identify proteins targeted by the drug. Studying human cells and brain samples from subjects not associated with the trial, they found that BIA 10-2474 targeted several different lipases in addition to FAAH. It also substantially altered lipid metabolism in cultured neurons.

Science
, this issue p.
1084
Neutron scattering in the proximate quantum spin liquid α-RuCl
3
Authors: Banerjee Arnab , Yan Jiaqiang , Knolle Johannes , Bridges Craig A. , Stone Matthew B. , Lumsden Mark D. , Mandrus David G. , Tennant David A. , Moessner Roderich , Nagler Stephen E.
Published: June 2017

Sighting of magnetic Majorana fermions?

Quantum spin liquids—materials whose magnetic spins do not settle into order even at absolute zero temperature—have long captured the interest of physicists. A particularly lofty goal is finding a material that can be described by the so-called Kitaev spin model, a network of spins on a honeycomb lattice that harbors Majorana fermions as its excitations. Banerjee
et al.
present a comprehensive inelastic neutron scattering study of single crystals of the material α-RuCl
3
, which has been predicted to a host a Kitaev spin liquid. The unusual dependence of the data on energy, momentum, and temperature is consistent with the Kitaev model.

Science
, this issue p.
1055
Bloch oscillations in the absence of a lattice
Authors: Meinert Florian , Knap Michael , Kirilov Emil , Jag-Lauber Katharina , Zvonarev Mikhail B. , Demler Eugene , Nägerl Hanns-Christoph
Published: June 2017

Detecting unusual oscillations

Under the influence of a constant force, an electron in the periodic potential of a
crystal lattice undergoes so-called Bloch oscillations. The same phenomenon has been
seen with ultracold atoms in optical lattices, but it is not expected to occur in a
uniform system. Meinert
et al
. observed Bloch oscillations of an
impurity atom in one-dimensional tubes of strongly interacting cesium atoms—a system
without built-in periodicity. Owing to the strong interactions, the bosonic atoms stayed
away from one another, forming an effective lattice. The researchers observed
reflections of the impurity atoms of this effective lattice in momentum space, with the
lattice constant corresponding to the interatomic distance of the host gas.

Science
, this issue p.
945
Polymeric peptide pigments with sequence-encoded properties
Authors: Lampel Ayala , McPhee Scott A. , Park Hang-Ah , Scott Gary G. , Humagain Sunita , Hekstra Doeke R. , Yoo Barney , Frederix Pim W. J. M. , Li Tai-De , Abzalimov Rinat R. , Greenbaum Steven G. , Tuttle Tell , Hu Chunhua , Bettinger Christopher J. , Ulijn Rein V.
Published: June 2017

Designing molecular disorder

Melanins are a group of natural pigments that are the primary factor affecting skin color. Lampel
et al.
examined a family of melanin-inspired materials based on tripeptides containing tyrosine as precursors for polymeric pigments. They found that the supramolecular organization of the tripeptide assembly is the most important factor for the enzymatic oxidation, with the position of the tyrosine residue playing a dominant role. Thus, simply juggling the order of the peptides allowed tuning of the optical and electrical properties of the resulting polymers.

Science
, this issue p.
1064
Palladium-catalyzed carbon-sulfur or carbon-phosphorus bond metathesis by reversible arylation
Authors: Lian Zhong , Bhawal Benjamin N. , Yu Peng , Morandi Bill
Published: June 2017

Teaching sulfur and phosphorus to share

Wouldn't it be nice if real chemistry worked like a modeling kit, and you could just pull a group off one molecule and tack it onto another? Lian
et al.
report that palladium catalysis can swap aryl rings between pairs of organosulfur or organophosphorus fragments in just this way. They showcase the sulfur swap by breaking down the commercial thermoplastic polyphenylene sulfide into simple monomers.

Science
, this issue p.
1059
Is ice sheet collapse in West Antarctica unstoppable?
Authors: Hulbe Christina
Published: June 2017

Most climate scenarios paint a bleak future for the West Antarctic Ice Sheet
Applying plasmonics to a sustainable future
Authors: Naldoni Alberto , Shalaev Vladimir M. , Brongersma Mark L.
Published: June 2017

Plasmonic technologies may form components of a future clean and sustainable society
The dishonest HONEST Act
Authors: Michaels David , Burke Thomas
Published: June 2017

The Trump administration aims to eliminate many regulations and make it more difficult to adopt new ones. More subtle and dangerous are attempts in Congress to undermine public health and environmental protections by limiting the use of scientific evidence under the guise of increased transparency. This effort, which as envisioned by U.S. Environmental Protection Agency (EPA) leadership would greatly reduce the amount of science used in decision-making, undermines the credibility and application of scientific evidence, weakens the scientific enterprise, and imperils public and environmental health.
Association of Atypical Enteropathogenic Escherichia coli with Diarrhea and Related Mortality in Kittens
Authors: Watson Victoria E. , Jacob Megan E. , Flowers James R. , Strong Sandra J. , DebRoy Chitrita , Gookin Jody L.
Published: June 2017

Diarrhea is responsible for the death of approximately 900,000 children per year worldwide. In children, typical enteropathogenic
Escherichia coli
(EPEC) is a common cause of diarrhea and is associated with a higher hazard of death. Typical EPEC infection is rare in animals and poorly reproduced in experimental animal models. In contrast, atypical EPEC (aEPEC) infection is common in both children and animals, but its role in diarrhea is uncertain. Mortality in kittens is often attributed to diarrhea, and we previously identified enteroadherent EPEC in the intestines of deceased kittens. The purpose of this study was to determine the prevalence and type of EPEC in kittens and whether infection was associated with diarrhea, diarrhea-related mortality, gastrointestinal pathology, or other risk factors. Kittens with and without diarrhea were obtained from two shelter facilities and determined to shed atypical EPEC at a culture-based prevalence of 18%. In contrast, quantitative PCR detected the presence of the gene for intimin (
eae
) in feces from 42% of kittens. aEPEC was isolated from kittens with and without diarrhea. However, kittens with diarrhea harbored significantly larger quantities of aEPEC than kittens without diarrhea. Kittens with aEPEC had a significantly greater severity of small intestinal and colonic lesions and were significantly more likely to have required subcutaneous fluid administration. These findings identify aEPEC to be prevalent in kittens and a significant primary or contributing cause of intestinal inflammation, diarrhea, dehydration, and associated mortality in kittens.
Enfuvirtide (T20)-Based Lipopeptide Is a Potent HIV-1 Cell Fusion Inhibitor: Implications for Viral Entry and Inhibition
Authors: Ding Xiaohui , Zhang Xiujuan , Chong Huihui , Zhu Yuanmei , Wei Huamian , Wu Xiyuan , He Jinsheng , Wang Xinquan , He Yuxian
Published: June 2017

The peptide drug enfuvirtide (T20) is the only viral fusion inhibitor used in combination therapy for HIV-1 infection, but it has relatively low antiviral activity and easily induces drug resistance. Emerging studies demonstrate that lipopeptide-based fusion inhibitors, such as LP-11 and LP-19, which mainly target the gp41 pocket site, have greatly improved antiviral potency and
in vivo
stability. In this study, we focused on developing a T20-based lipopeptide inhibitor that lacks pocket-binding sequence and targets a different site. First, the C-terminal tryptophan-rich motif (TRM) of T20 was verified to be essential for its target binding and inhibition; then, a novel lipopeptide, termed LP-40, was created by replacing the TRM with a fatty acid group. LP-40 showed markedly enhanced binding affinity for the target site and dramatically increased inhibitory activity on HIV-1 membrane fusion, entry, and infection. Unlike LP-11 and LP-19, which required a flexible linker between the peptide sequence and the lipid moiety, addition of a linker to LP-40 sharply reduced its potency, implying different binding modes with the extended N-terminal helices of gp41. Also, interestingly, LP-40 showed more potent activity than LP-11 in inhibiting HIV-1 Env-mediated cell-cell fusion while it was less active than LP-11 in inhibiting pseudovirus entry, and the two inhibitors displayed synergistic antiviral effects. The crystal structure of LP-40 in complex with a target peptide revealed their key binding residues and motifs. Combined, our studies have not only provided a potent HIV-1 fusion inhibitor, but also revealed new insights into the mechanisms of viral inhibition.

IMPORTANCE
T20 is the only membrane fusion inhibitor available for treatment of viral infection; however, T20 requires high doses and has a low genetic barrier for resistance, and its inhibitory mechanism and structural basis remain unclear. Here, we report the design of LP-40, a T20-based lipopeptide inhibitor that has greatly improved anti-HIV activity and is a more potent inhibitor of cell-cell fusion than of cell-free virus infection. The binding modes of two classes of membrane-anchoring lipopeptides (LP-40 and LP-11) verify the current fusion model in which an extended prehairpin structure bridges the viral and cellular membranes, and their complementary effects suggest a vital strategy for combination therapy of HIV-1 infection. Moreover, our understanding of the mechanism of action of T20 and its derivatives benefits from the crystal structure of LP-40.
Case-Control Comparison of Enteric Viromes in Captive Rhesus Macaques with Acute or Idiopathic Chronic Diarrhea
Authors: Kapusinszky Beatrix , Ardeshir Amir , Mulvaney Usha , Deng Xutao , Delwart Eric
Published: June 2017

Diarrhea is the major cause of non-research-associated morbidity and mortality affecting the supply of rhesus macaques and, potentially, their responses to experimental treatments. Idiopathic chronic diarrhea (ICD) in rhesus macaques also resembles ulcerative colitis, one form of human inflammatory bowel disease. To test for viral etiologies, we characterized and compared the fecal viromes from 32 healthy animals, 31 animals with acute diarrhea, and 29 animals with ICD. The overall fractions of eukaryotic viral reads were 0.063% for the healthy group, 0.131% for the acute-diarrhea group, and 0.297% for the chronic-diarrhea group. Eukaryotic viruses belonging to 6 viral families, as well as numerous circular Rep-encoding single-stranded DNA (CRESS DNA) viral genomes, were identified. The most commonly detected sequences were from picornaviruses, making up 59 to 88% of all viral reads, followed by 9 to 17% for CRESS DNA virus sequences. The remaining 5 virus families,
Adenoviridae
,
Astroviridae
,
Anelloviridae
,
Picobirnaviridae
, and
Parvoviridae
, collectively made up 1 to 3% of the viral reads, except for parvoviruses, which made up 23% of the viral reads in the healthy group. Detected members of the families
Picornaviridae
and
Parvoviridae
were highly diverse, consisting of multiple genera, species, and genotypes. Coinfections with members of up to six viral families were detected. Complete and partial viral genomes were assembled and used to measure the number of matching short sequence reads in feces from the 92 animals in the two clinical and the healthy control groups. Several enterovirus genotypes and CRESS DNA genomes were associated with ICD relative to healthy animals. Conversely, higher read numbers from different parvoviruses were associated with healthy animals. Our study reveals a high level of enteric coinfections with diverse viruses in a captive rhesus macaque colony and identifies several viruses positively or negatively associated with ICD.
Can an FDA-Approved Alzheimer’s Drug Be Repurposed for Alleviating Neuronal Symptoms of Zika Virus?
Authors: Sirohi Devika , Kuhn Richard J.
Published: June 2017

Zika virus caught the world by surprise by its rapid spread and frightening disease outcomes. This major epidemic motivated many scientists to focus their attention on controlling this emerging pathogen. As many as 45 vaccine candidates are being developed, but progress in the antiviral arena has been slower. In a recent article (mBio 8:e00350-17, 2017,
https://doi.org/10.1128/mBio.00350-17
), Costa and colleagues showed that an FDA-approved drug used to treat Alzheimer’s disease may moderate Zika virus-induced neuronal damage. This work is based on the premise that overstimulation of
N
-methyl-
d
-aspartate receptors (NMDARs) may drive neurodegeneration and that this may be responsible for neuronal cell death associated with Zika virus infection of the central nervous system (CNS). Thus, blockage of the NMDAR channel activity with FDA-approved memantine or other antagonists may reduce neurological complications associated with Zika virus infection. Repurposing a preapproved drug and targeting the host represent intriguing strategies and yet require more analysis prior to moving into clinical trials.
Physiological and Molecular Understanding of Bacterial Polysaccharide Monooxygenases
Authors: Agostoni Marco , Hangasky John A. , Marletta Michael A.
Published: June 2017

Bacteria have long been known to secrete enzymes that degrade cellulose and chitin. The degradation of these two polymers predominantly involves two enzyme families that work synergistically with one another: glycoside hydrolases (GHs) and polysaccharide monooxygenases (PMOs). Although bacterial PMOs are a relatively recent addition to the known biopolymer degradation machinery, there is an extensive amount of literature implicating PMO in numerous physiological roles. This review focuses on these diverse and physiological aspects of bacterial PMOs, including facilitating endosymbiosis, conferring a nutritional advantage, and enhancing virulence in pathogenic organisms. We also discuss the correlation between the presence of PMOs and bacterial lifestyle and speculate on the advantages conferred by PMOs under these conditions. In addition, the molecular aspects of bacterial PMOs, as well as the mechanisms regulating PMO expression and the function of additional domains associated with PMOs, are described. We anticipate that increasing research efforts in this field will continue to expand our understanding of the molecular and physiological roles of bacterial PMOs.
Topological Insulators: Electronic Structure, Material Systems and Applications
Authors: Sengupta Parijat
Published: June 2017

Topological insulators are a new class of materials characterized by fully spin-polarized surface states, a linear dispersion, imperviousness to external non-magnetic perturbations, and a helical character arising out of the perpendicular spin-momentum locking. This article answers in a pedagogical way the distinction between a topological and normal insulator, the role of topology in band theory of solids, and the origin of these surface states. Numerical techniques including diagonalization of the TI Hamiltonians are described to quantitatively evaluate the behaviour of topological insulator states. The Hamiltonians based on continuum and tight binding approaches are contrasted. The application of TIs as components of a fast switching environment or channel material for transistors is examined through I-V curves. The potential pitfall of such devices is presented along with techniques that could potentially circumvent the problem. Additionally, it is demonstrated that a strong internal electric field can also induce topological insulator behaviour with wurtzite nitride quantum wells as representative materials.
A Bicriteria Approach for Single Machine Scheduling with Resource Allocation, Learning Effect and a Deteriorating Maintenance Activity
Authors: Liu Zhusong , Wang Zhenyou , Lu Yuan-Yuan
Published: June 2017

This paper considers the single machine scheduling with learning effect, resource allocation and deteriorating maintenance activity simultaneously. For the convex resource allocation consumption function, we provide a bicriteria analysis where the first (schedule) criterion is to minimize the total weighted sum of makespan, total completion time and total absolute differences in completion times, and the second (resource) criterion is to minimize the total weighted resource consumption. Our aim is to find the optimal resource allocations and job sequence that minimize the three different models of considering the two criterion. We show that these three models are polynomially solvable respectively.
Iterative-decreasing calibration method based on regional circle
Authors: Zhao Hongyang
Published: June 2017

In the field of computer vision, camera calibration is a hot issue. For the existing coupled problem of calculating distortion center and the distortion factor in the process of camera calibration, this paper presents an iterative-decreasing calibration method based on regional circle, uses the local area of the circle plate to calculate the distortion center coordinates by iterative declining, and then uses the distortion center to calculate the local area calibration factors. Finally, makes distortion center and the distortion factor for the global optimization. The calibration results show that the proposed method has high calibration accuracy.
Classification of different kinds of pesticide residues on lettuce based on fluorescence spectra and WT–BCC–SVM algorithm
Authors: Zhou Xin , Jun Sun , Zhang Bing , Jun Wu
Published: June 2017

In order to improve the reliability of the spectrum feature extracted by wavelet transform, a method combining wavelet transform (WT) with bacterial colony chemotaxis algorithm and support vector machine (BCC–SVM) algorithm (WT–BCC–SVM) was proposed in this paper. Besides, we aimed to identify different kinds of pesticide residues on lettuce leaves in a novel and rapid non-destructive way by using fluorescence spectra technology. The fluorescence spectral data of 150 lettuce leaf samples of five different kinds of pesticide residues on the surface of lettuce were obtained using Cary Eclipse fluorescence spectrometer. Standard normalized variable detrending (SNV detrending), Savitzky–Golay coupled with Standard normalized variable detrending (SG–SNV detrending) were used to preprocess the raw spectra, respectively. Bacterial colony chemotaxis combined with support vector machine (BCC–SVM) and support vector machine (SVM) classification models were established based on full spectra (FS) and wavelet transform characteristics (WTC), respectively. Moreover, WTC were selected by WT. The results showed that the accuracy of training set, calibration set and the prediction set of the best optimal classification model (SG–SNV detrending-WT–BCC–SVM) were 100%, 98% and 93.33%, respectively. In addition, the results indicated that it was feasible to use WT–BCC–SVM to establish diagnostic model of different kinds of pesticide residues on lettuce leaves.
Unconventional or Preset αβ T Cells: Evolutionarily Conserved Tissue-Resident T Cells Recognizing Nonpeptidic Ligands
Authors: Legoux Francois , Salou Marion , Lantz Olivier
Published: June 2017

A majority of T cells bearing the αβ T cell receptor (TCR) are specific for peptides bound to polymorphic classical major histocompatibility complex (MHC) molecules. Smaller subsets of T cells are reactive toward various nonpeptidic ligands associated with nonpolymorphic MHC class-Ib (MHC-Ib) molecules. These cells have been termed unconventional for decades, even though only the composite antigen is different from the one seen by classical T cells. Herein, we discuss the identity of these particular T cells in light of the coevolution of their TCR and MHC-Ib restricting elements. We examine their original thymic development: selection on hematopoietic cells leading to the acquisition of an original differentiation program. Most of these cells acquire memory cell features during thymic maturation and exhibit unique patterns of migration into peripheral nonlymphoid tissues to become tissue resident. Thus, these cells are termed preset T cells, as they also display a variety of effector functions. They may act as microbial or danger sentinels, fight microbes, or regulate tissue homeostasis.
Reduced SCD1 activity alters markers of fatty acid reesterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes
Authors: Dragos Steven M. , Bergeron Karl F. , Desmarais Frédérik , Suitor Katherine , Wright David C. , Mounier Catherine , Mutch David M.
Published: June 2017

White adipose tissue (WAT) has a critical role in lipid handling. Previous work demonstrated that SCD1 is an important regulator of WAT fatty acid (FA) composition; however, its influence on the various interconnected pathways influencing WAT lipid handling remains unclear. Our objective was to investigate the role of SCD1 on WAT lipid handling using Scd1 knockout (KO) mice and SCD1-inhibited 3T3-L1 adipocytes by measuring gene, protein, and metabolite markers related to FA reesterification, glyceroneogenesis, and lipolysis. Triacylglycerol (TAG) content was higher in inguinal WAT (iWAT) from KO mice compared with wild-type, but significantly lower in epididymal WAT (eWAT). The SCD1 desaturation index was decreased in both WAT depots in KO mice. FA reesterification, as measured with a NEFA:glycerol ratio, was reduced in both WAT depots in KO mice, as well as SCD1-inhibited 3T3-L1 adipocytes. Pck1, Atgl, and Hsl gene expression was reduced in both WAT depots of KO mice, while Pck2 and Pdk4 gene expression showed depot-specific regulation. Pck1, Atgl, and Hsl gene expression was reduced, and phosphoenolpyruvate carboxykinase protein content was ablated, in SCD1-inhibited adipocytes. Our data provide evidence that SCD1 has a broad impact on WAT lipid handling by altering TAG composition in a depot-specific manner, reducing FA reesterification, and regulating markers of lipolysis and glyceroneogenesis.
Mitochondrial quality control in alveolar epithelial cells damaged by S. aureus pneumonia in mice
Authors: Suliman Hagir B. , Kraft Bryan , Bartz Raquel , Chen Lingye , Welty-Wolf Karen E. , Piantadosi Claude A.
Published: June 2017

Mitochondrial damage is often overlooked in acute lung injury (ALI), yet most of the lung’s physiological processes, such as airway tone, mucociliary clearance, ventilation-perfusion (Va/Q) matching, and immune surveillance require aerobic energy provision. Because the cell’s mitochondrial quality control (QC) process regulates the elimination and replacement of damaged mitochondria to maintain cell survival, we serially evaluated mitochondrial biogenesis and mitophagy in the alveolar regions of mice in a validated Staphylococcus aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho- mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1. Cell death in alveolar type I (AT1) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation end points (RAGE) levels was high, yet AT2 cell death was limited while both mitochondrial biogenesis and mitophagy were induced. These mitochondrial QC mechanisms were evaluated mainly in AT2 cells by localizing increases in citrate synthase content, increases in nuclear mitochondrial biogenesis regulators nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and increases in light chain 3B protein (LC3-I)/LC3II ratios. Concomitant changes in p62, Pink 1, and Parkin protein levels indicated activation of mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy were often observed on day 1 within the same AT2 cells. These findings imply that mitochondrial QC activation in pneumonia-damaged AT2 cells promotes cell survival in support of alveolar function.
NMR Pore Structure and Dynamic Characteristics of Sandstone Caused by Ambient Freeze-Thaw Action
Authors: Ke Bo , Zhou Keping , Deng Hongwei , Bin Feng
Published: June 2017

For a deeper understanding of the freeze-thaw weathering effects on the microstructure evolution and deterioration of dynamic mechanical properties of rock, the present paper conducted the nuclear magnetic resonance (NMR) tests and impact loading experiments on sandstone under different freeze-thaw cycles. The results of NMR test show that, with the increase of freeze-thaw cycles, the pores expand and pores size tends to be uniform. The experimental results show that the stress-strain curves all go through four stages, namely, densification, elasticity, yielding, and failure. The densification curve is shorter, and the slope of elasticity curve decreases as the freeze-thaw cycles increase. With increasing freeze-thaw cycles, the dynamic peak stress decreases and energy absorption of sandstone increases. The dynamic failure form is an axial splitting failure, and the fragments increase and the size diminishes with increasing freeze-thaw cycles. The higher the porosity is, the more severe the degradation of dynamic characteristics is. An increase model for the relationships between the porosity or energy absorption and freeze-thaw cycles number was built to reveal the increasing trend with the freeze-thaw cycles increase; meanwhile, a decay model was built to predict the dynamic compressive strength degradation of rock after repeated freeze-thaw cycles.
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer
Authors: Bang Yung-Jue , Cho Jae Yong , Kim Yeul Hong , Kim Jin Won , Di Bartolomeo Maria , Ajani Jaffer A. , Yamaguchi Kensei , Balogh Agnes , Sanchez Teresa , Moehler Markus
Published: June 2017

Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.

Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS).

Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61–5.16 vs. 4.90 months, 95% CI, 3.45–6.54, HR = 1.44; 80% CI, 1.09–1.91; P = 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5–18.9) and 12.1 months (95% CI, 9.3–not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients.

Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer. Clin Cancer Res; 23(19); 5671–8. ©2017 AACR.
Antimelanogenic Efficacy of Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) in Melanocytes and Three-Dimensional Human Skin Equivalent
Authors: Lee John Hwan , Lee Eun-Soo , Bae Il-Hong , Hwang Jeong-Ah , Kim Se-Hwa , Kim Dae-Yong , Park Nok-Hyun , Rho Ho Sik , Kim Yong Jin , Oh Seong-Geun , Lee Chang Seok
Published: June 2017

Background/Aims: Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. Methods: The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Results: Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Conclusion: Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy.
TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells
Authors: Zhou Guangyao , Yang Zuqin , Wang Xiaodong , Tao Ran , Zhou Yuanping
Published: June 2017

Background/Aims: Cholangiocarcinoma (CCA), arising from varying locations within the biliary tree, is the second most common primary liver malignancy worldwide. Shikonin, an active compound extracted from the Chinese herb Zicao, holds anti-bacterial, anti-inflammatory, and anti-tumor activities. However, the effect of shikonin on human cholangiocarcinoma and detailed mechanisms of TRAIL enhancement remains to be elucidated. The purpose of the study was to investigate the protective functions of TRAIL enhancement for shikonin induced apoptosis in cholangiocarcinoma cells. Methods: We use MTT assay, apoptosis assay, caspase activity assay, flow cytometry assay, real time PCR and Western blot to observe the effects of TRAIL on shikonin induced cholangiocarcinoma cells apoptosis and its mechanism. Results: Shikonin inhibited cell viability and induced apoptosis of CCA cells, effects enhanced by TRAIL treatment via activation of caspase-3, -8, -9. Furhermore, TRAIL enhanced anti-proliferation of shikonin and shikonin induced apoptosis through induction of ROS mediated JNK activation, while AKT activation had an effect on shikonin anti-proliferation activity, but not in the TRAIL enhanced counterparts. Finally, shikonin upregulated DR5 expression, an effect essential for TRAIL-enhanced activities of shikonin in RBE cells. Conclusions: Our results revealed that shikonin could inhibit cells viability and induce apoptosis of CCA cells, effects enhanced by TRAIL treatment via ROS mediated JNK signalling pathways, involving up-regulation of DR5 expression. Our results provide further insight into the mechanism underlying the anti-tumor effects of shikonin by TRAIL enhanced in CCA and a new therapeutic strategy to CCA treatment.
Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats
Authors: Gomes Rodrigo Mello , de Paulo Luis Fernando , Bonato Panizzon Cynthia Priscilla do Nascimento , Neves Camila Quaglio , Cordeiro Bruna Colombo , Zanoni Jacqueline Nelisis , Francisco Flávio Andrade , Piovan Silvano , de Freitas Mathias Paulo Cezar , Longhini Renata , de Mello João Carlos Palazzo , de Oliveira Júlio Cezar , Pedrino Gustavo Rodrigues , da Silva Reis Angela Adamski , Cecchini Alessandra Lourenço , Marçal Natali Maria Raquel
Published: June 2017

Background/Aims: Trichilia catigua A. Juss., known as “catuaba” in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF) of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. Methods: Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group). The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ) injection (35 mg/kg). Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. Results: EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the number of pancreatic β-cells and the size of the islets had increased by β-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. Conclusion: The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats.
Introdução
Authors: Leviathan Editores
Published: June 2017

Introdução Leviathan
Intervenção estatal: o eterno retorno
Authors: Ferraz Alexandre
Published: June 2017

O debate moderno sobre o retorno do liberalismo devotou pouca atenção às discuções anteriores sobre o período de formação das empresas estatais, particularmente ao fim do liberalismo e inicio do Estado intervencionista no principio do seculo 20, e sobre o período de crescimento do Estado intervencionista. Neste trabalho procuro recuperar um pouco desses dois momentos no intuito de fornecer algum subsídio para uma discussão mais apurada sobre a crise do intervencionismo estatal e o retorno do liberalismo enquanto pensamento hegemônico.
Voto e avaliação do Plano Real em 1998
Authors: Silva Paulo Sérgio da
Published: June 2017

O objetivo, neste trabalho, é explicar o voto dos eleitores, na eleição presidencial de 1998, por meio da avaliação de custo e benefício do Plano Real. A literatura está centrada nas teorias econômicas que focalizam o voto como resultado da escolha racional dos indivíduos. A fonte de dados é uma pesquisa realizada pelo Núcleo de Relações Internacionais (NUPRI), da Universidade de São Paulo. As técnicas estatísticas empregadas baseiam-se na construção de tabelas e cálculo dos coeficientes de associação, Phi e V de Cramér
Estrutura tributária, receita "rentista" e regressividade em América Latina. Um análise da situação atual
Authors: Patrucchi Leticia , Grottola Leonardo Patricio
Published: June 2017

Durante la última década, la mayoría de los países latinoamericanos experimentaron procesos de reconstrucción de sus capacidades de intervención estatal. A fin de indagar en las fuentes de recursos fiscales que sostuvieron dicho proceso, este trabajo analiza la estructura de ingresos corrientes en Sudamérica y México considerando: a) la relevancia de los ingresos “rentísticos” en la recaudación total y b) las características de la estructura tributaria. Los resultados arrojan una importante incidencia de los primeros en relación a la presión tributaria y al carácter regresivo de la misma
What is R2 all about?
Authors: Figueiredo Filho Dalson Britto , Silva Júnior José Alexandre , Rocha Enivaldo Carvalho
Published: June 2017

Which substantive meaning we can draw from the R2 statistic? The coefficient of determination is defined as the sum of squares due to the regression divided by the sum of total squares. Usually, R2 is interpreted as representing the percentage of variation in the dependent variable explained by variation in the independent variables. This definition is found by both econometrics and statistics handbooks and is widely accepted among quantitative scholars. However, this view is challenged by one of the most distinguished political science methodologists. Gary King argues that the R2 is highly misused as a measure of the influence of X on Y. This paper analyzes the R2 statistic using a non-technical approach. Our purpose is to provide an intuitive understanding of the coefficient of determination and its major shortcomings.
Antídoto y utopía Una lectura de la dimensión comunitaria en el liberalismo clásico
Authors: Grondona Ana Lucia
Published: June 2017

El presente trabajo aborda una lectura en clave comunitarista de dos autores centrales del liberalismo clásico: Alexis de Tocqueville y John Locke. Ello a fin de poner en cuestión el diagnóstico según el cual la articulación entre “comunitarismo” y “liberalismo” corresponde a una singularidad del gobierno neoliberal de las poblaciones. El artículo está organizado en cuatro secciones, en la primera se introducen los términos generales del problema; en la segunda, se analiza el diagnóstico de Alexis de Tocqueville a porpósito de la “cuestión social”, para analizar, en la tercera, los antídotos “comunitarista” propuestos para administrarla. En la cuarta sección, se aborda la dimensión utópica que sostiene este planteo y el de John Locke. Por último, en unas breves reflexiones finales, se retoman las preguntas formuladas al comienzo del recorrido
Desenvolvimento imobiliário em São Paulo: em defesa de uma análise política
Authors: Hoyler Telma
Published: June 2017

Com destaque para o cenário paulistano, o artigo recupera historicamente o desenvolvimento do setor imobiliário, faz um balanço da produção já realizada sobre o tema e traça perspectivas futuras de análise deste agente setorial da política urbana. A partir da revisão das principais pesquisas que versam sobre a incorporação imobiliária e seus temas correlatos, organizouse tais estudos em cinco períodos que encerram um conjunto coeso de instituições impactantes na atividade da incorporação imobiliária e na formação de seu mercado econômico em São Paulo. O artigo aponta para a necessidade de uma canalização de esforços para a compreensão da produção urbana por meio da análise estruturada da prática política dos agentes sociais envolvidos na construção das cidades e das relações que estabelecem com o poder público na consecução de políticas
An Unbiased High-Throughput Screen to Identify Novel Effectors That Impact on Cardiomyocyte Aggregate Levels
Authors: McLendon Patrick M. , Davis Gregory , Gulick James , Singh Sonia R. , Xu Na , Salomonis Nathan , Molkentin Jeffery D. , Robbins Jeffrey
Published: June 2017

Rationale:

Postmitotic cells, such as cardiomyocytes, seem to be particularly susceptible to proteotoxic stimuli, and large, proteinaceous deposits are characteristic of the desmin-related cardiomyopathies and crystallin cardiomyopathic diseases. Increased activity of protein clearance pathways in the cardiomyocyte, such as proteasomal degradation and autophagy, has proven to be beneficial in maintaining cellular and cardiac function in the face of multiple proteotoxic insults, holding open the possibility of targeting these processes for the development of effective therapeutics.

Objective:

Here, we undertake an unbiased, total genome screen for RNA transcripts and their protein products that affect aggregate accumulations in the cardiomyocytes.

Methods and Results:

Primary mouse cardiomyocytes that accumulate aggregates as a result of a mutant CryAB (αB-crystallin) causative for human desmin-related cardiomyopathy were used for a total genome-wide screen to identify gene products that affected aggregate formation. We infected cardiomyocytes using a short hairpin RNA lentivirus library in which the mouse genome was represented. The screen identified multiple candidates in many cell signaling pathways that were able to mediate significant decreases in aggregate levels.

Conclusions:

Subsequent validation of one of these candidates, Jak1 (Janus kinase 1), a tyrosine kinase of the nonreceptor type, confirmed the usefulness of this approach in identifying previously unsuspected players in proteotoxic processes.
Health Insurance Expansion and Incidence of Out‐of‐Hospital Cardiac Arrest: A Pilot Study in a US Metropolitan Community
Authors: Stecker Eric C. , Reinier Kyndaron , Rusinaru Carmen , Uy‐Evanado Audrey , Jui Jon , Chugh Sumeet S.
Published: June 2017

Background

Health insurance has many benefits including improved financial security, greater access to preventive care, and better self‐perceived health. However, the influence of health insurance on major health outcomes is unclear. Sudden cardiac arrest prevention represents one of the major potential benefits from health insurance, given the large impact of sudden cardiac arrest on premature death and its potential sensitivity to preventive care.

Methods and Results

We conducted a pre–post study with control group examining out‐of‐hospital cardiac arrest (
OHCA
) among adult residents of Multnomah County, Oregon (2015 adult population 636 000). Two time periods surrounding implementation of the Affordable Care Act were evaluated: 2011–2012 (“pre‐expansion”) and 2014–2015 (“postexpansion”). The change in
OHCA
incidence for the middle‐aged population (45–64 years old) exposed to insurance expansion was compared with the elderly population (age ≥65 years old) with constant near‐universal coverage. Rates of
OHCA
among middle‐aged individuals decreased from 102 per 100 000 (95%
CI
: 92–113 per 100 000) to 85 per 100 000 (95%
CI
: 76–94 per 100 000),
P
value 0.01. The elderly population experienced no change in
OHCA
incidence, with rates of 275 per 100 000 (95%
CI
: 250–300 per 100 000) and 269 per 100 000 (95%
CI
: 245–292 per 100 000),
P
value 0.70.

Conclusions

Health insurance expansion was associated with a significant reduction in
OHCA
incidence. Based on this pilot study, further investigation in larger populations is warranted and feasible.
Intersections between Iconographic and Gendered Approaches to Biblical Interpretation
Authors: DiPalma Brian Charles
Published: June 2017

This paper explores the intersections between two approaches to biblical interpretation: iconographic and gendered approaches. Focusing on the ways that visual images from the ancient Near East have been incorporated in studying gender in the Hebrew Bible, I identify four intersections. These examples demonstrate that participating in an iconographic turn is an important way that gender studies in the Hebrew Bible can develop. I also seek to show that the interactions can be mutually fruitful. In other words, including gender as an area of inquiry is a way that the iconographic turn itself can develop in biblical studies.
Confirmation Candidates in the Church of Sweden
Authors: Willander Erika
Published: June 2017

This article is about confirmation preparation in the Church of Sweden from the viewpoint of the confirmation candidates. It focuses on whether or not the confirmation candidates’ expectations, experiences and beliefs support the goals of confirmation that the Church of Sweden has formulated in its general guidelines for confirmation. The results showed points of agreement (e.g. expectations to come to one’s own decision about God, having fun and experiencing community in the confirmation group) and points of departure (e.g. expectations of gifts at the end of the confirmation period). The results also showed that experiences met the confirmation candidates’ expectations (e.g. experiences of learning while having fun). In addition, the confirmation candidates’ beliefs were changed by confirmation preparation. The article ends with a discussion on how general guidelines may function as guiding principles for confirmation.