bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass Casualty Incidents in the Underground Mining Industry: Applying the Haddon Matrix on an Integrative Literature Review
Authors: Engström Karl Gunnar , Angrén John , Björnstig Ulf , Saveman Britt-Inger
Published: June 2017

Objective

Underground mining is associated with obvious risks that can lead to mass casualty incidents. Information about such incidents was analyzed in an integrated literature review.

Methods

A literature search (1980-2015) identified 564 modern-era underground mining reports from countries sharing similar occupational health legislation. These reports were condensed to 31 reports after consideration of quality grading and appropriateness to the aim. The Haddon matrix was used for structure, separating human factors from technical and environmental details, and timing.

Results

Most of the reports were descriptive regarding injury-creating technical and environmental factors. The influence of rock characteristics was an important pre-event environmental factor. The organic nature of coal adds risks not shared in hard-rock mines. A sequence of mechanisms is commonly described, often initiated by a human factor in interaction with technology and step-wise escalation to involve environmental circumstances. Socioeconomic factors introduce heterogeneity. In the Haddon matrix, emergency medical services are mainly a post-event environmental issue, which were not well described in the available literature. The US Quecreek Coal Mine incident of 2002 stands out as a well-planned rescue mission.

Conclusion

Evaluation of the preparedness to handle underground mining incidents deserves further scientific attention. Preparedness must include the medical aspects of rescue operations. (Disaster Med Public Health Preparedness. 2018;12:138–146)
DistinguishingClostridium difficileRecurrence From Reinfection: Independent Validation of Current Recommendations
Authors: Durovic Ana , Widmer Andreas F. , Frei Reno , Tschudin-Sutter Sarah
Published: June 2017

OBJECTIVE

Distinguishing recurrentClostridium difficileinfection (CDI), defined as CDI caused by the same genotype, from reinfection with a different genotype, has important implications for surveillance and clinical trials investigating treatment effectiveness. We validated the proposed 8-week period for distinguishing “same genotype CDI” from “different genotype CDI,” and we aimed to identify clinical variables with distinctiveness to propose an improved definition.

METHODS

From January 2004 to December 2013, a cohort of all inpatients with CDI at the University Hospital Basel, Switzerland, was established, and respective strains were collected. In patients with a second episode of CDI, both strains were compared using polymerase chain reaction (PCR) ribotyping. The standard definition of recurrence (within 8 weeks after initial diagnosis) was evaluated for its performance to predict CDI caused by the same genotype.

RESULTS

Among 750 patients with CDI, 130 (17.3%) were diagnosed with recurrence or reinfection. Strains from both episodes were available from 106 patients. Identical strains were identified in 36 patients with recurrence (36 of 47) and 27 patients with reinfection (27 of 59). Sensitivity, specificity, and negative and positive predictive values of the standard definition were 56%, 74%, 53%, and 76%, respectively. An extended period of 20 weeks resulted in the best match for both sensitivity and specificity (83% and 58%, respectively), while none of the clinical characteristics revealed independent distinctive power.

CONCLUSIONS

Our results challenge the utility of the 8-week cutoff for distinguishing recurrent CDI from reinfection. An extended period of 20 weeks may result in improved overall performance characteristics, but this finding requires external validation.

Infect Control Hosp Epidemiol2017;38:891–896
ITÔ’S THEOREM AND MONOMIAL BRAUER CHARACTERS
Authors: CHEN XIAOYOU , LEWIS MARK L.
Published: June 2017

Let $G$ be a finite solvable group and let $p$ be a prime. In this note, we prove that $p$ does not divide $\unicode[STIX]{x1D711}(1)$ for every irreducible monomial $p$-Brauer character $\unicode[STIX]{x1D711}$ of $G$ if and only if $G$ has a normal Sylow $p$-subgroup.
ON GROUPS WITH FINITE CONJUGACY CLASSES IN A VERBAL SUBGROUP
Authors: DELIZIA COSTANTINO , SHUMYATSKY PAVEL , TORTORA ANTONIO
Published: June 2017

Let $w$ be a group-word. For a group $G$, let $G_{w}$ denote the set of all $w$-values in $G$ and let $w(G)$ denote the verbal subgroup of $G$ corresponding to $w$. The group $G$ is an $FC(w)$-group if the set of conjugates $x^{G_{w}}$ is finite for all $x\in G$. It is known that if $w$ is a concise word, then $G$ is an $FC(w)$-group if and only if $w(G)$ is $FC$-embedded in $G$, that is, the conjugacy class $x^{w(G)}$ is finite for all $x\in G$. There are examples showing that this is no longer true if $w$ is not concise. In the present paper, for an arbitrary word $w$, we show that if $G$ is an $FC(w)$-group, then the commutator subgroup $w(G)^{\prime }$ is $FC$-embedded in $G$. We also establish the analogous result for $BFC(w)$-groups, that is, groups in which the sets $x^{G_{w}}$ are boundedly finite.
The Escape from Institution-Building in a Globalized World: Lessons from Russia
Authors: Sharafutdinova Gulnaz , Dawisha Karen
Published: June 2017

Strong institutions and accountable governments are imperative for any country’s long-term prosperity. Yet the development of such institutions has presented a continuous challenge for many countries around the world. Using Russia as a case, this study brings attention to the unexpected negative impact of global interdependence and shows that institutional arbitrage opportunities have enabled economic actors to solve for institutional weaknesses and constraints in the domestic realm by using foreign institutions, thereby limiting the emergence of a domestic rule of law regime. We argue that such opportunities lower the propensity of asset-holders, normally interested in strong institutions at home, to organize collective action to lobby for better institutions. We demonstrate the main ways through which Russia’s capital-owners make use of foreign legal and financial infrastructures such as capital flight, the use of foreign corporate structures, offshore financial centers, real estate markets, the round-tripping of foreign direct investment, and reliance on foreign law in contract-writing and foreign courts in dispute-resolution.
The Immanent Potential of Economic and Monetary Integration: A Critical Reading of the Eurozone Crisis
Authors: Verovšek Peter J.
Published: June 2017

The Eurozone crisis revealed fundamental flaws in the institutional architecture of the Economic and Monetary Union. Its lack of political steering capacity has demonstrated the need for a broad but seemingly unachievable political union with shared economic governance and a common treasury. Agreement on further measures has been difficult to achieve, as different actors have imposed divergent external criteria for the success of the Eurozone. As part of their heritage in Western Marxism, the critical theorists of the Frankfurt School sought to overcome such problems by identifying internal standards for social criticism. Building on their understanding of immanent critique, I argue that the Eurozone already contains the normative principles necessary to support greater political integration. While the citizens of Europe must provide the democratic legitimation necessary to realize this latent potential, the flaws revealed by the crisis are already pushing Europe towards greater transnational solidarity.
A Discussion of Aviezer Tucker's The Legacies of Totalitarianism: A Theoretical Framework
Authors: Bozóki András
Published: June 2017

The concept of totalitarianism emerged between the two world wars in twentieth-century Europe to become a central concept of Cold War social science designed to highlight similarities between the Nazi and Soviet regimes and implicitly to contrast these forms of dictatorship with liberal democracy. While in the 1960s and 1970s many critics challenged the concept’s Cold War uses as an ideology of “the West,” the idea of totalitarianism and later “post-totalitarianism” played important roles in East Central Europe, where they helped dissident intellectuals, academics, and activists both to understand and to challenge Soviet-style communism. The concept of “totalitarianism” remains heavily contested. But whatever one thinks about the concept’s social scientific validity, there can be no doubt that it played a crucial role in both the scholarship of communism and the public intellectual debates about the possibilities of post-communism. Aviezer Tucker’s The Legacies of Totalitarianism: A Theoretical Framework (Cambridge 2015) addresses many of these issues, and so we have invited a range of political scientists to comment on the book and the broader theme denoted by its title.
When fascism met empire in Japanese-occupied Manchuria
Authors: Young Louise
Published: June 2017

Focusing on the case of Japanese-occupied Manchuria, this article asks what set Japan, Germany, and Italy apart from other empires during the ‘fascist moment’ from the aftermath of the First World War to the defeat of the Axis powers in 1945. While scholars have examined the politics and culture of fascism in metropolitan Japan, there is virtually no literature on fascist imperialism. Indeed, the consensus term is ‘wartime empire’ and the dominant framework is of an empire mobilized for total war. One of the goals is to think through what the concept ‘fascist imperialism’ might mean and what the Japanese case might contribute to its definition. Detailed comparison with Germany and Italy is beyond the scope of this article, which builds a definition of fascism around four core elements drawn from the Japanese case: the ideology of Asianism and its vision for Japanese leadership over a regional movement of anti-colonial nationalisms; hyper-militarism that went well beyond military imperialism pursued since the late nineteenth century and that constituted a new celebration of military action and the aesthetics of violence; red peril thinking that propelled the creation of a police state targeting communist intellectuals, politicians, and labour activists within the archipelago as well as communist nationalists in the empire; and radical statism, which signified the turn to the state as the spear tip and staging ground of action to address the crisis. All four dimensions of fascism in Japan intensified in the process of territorial expansion from 1931 to 1945, and linked transformations across the nation-state-empire.
A pilot case series of a brief acceptance and commitment therapy (ACT)-based guided self-help intervention for improving quality of life and mood in muscle disorders
Authors: Graham Christopher D. , Chalder Trudie , Rose Michael R. , Gavriloff Dimitri , McCracken Lance M. , Weinman John
Published: June 2017

This study aimed to demonstrate proof of concept and acceptability of a brief acceptance and commitment therapy (ACT)-based guided self-help intervention for improving quality of life (QoL) and mood for people with muscle disorders (MD). A case-series with an AB design was used to assess changes in primary (QoL) and secondary (depression and anxiety) outcome variables across the period of study. Change in the psychological process targeted by ACT – psychological flexibility – was also investigated, to allow insight into possible treatment mechanisms. Post-intervention, participants also completed a brief free-text evaluation. Relative to pre-intervention scores, four (of seven) participants showed varying degrees of improvement in all primary and secondary outcome variables and were thus considered responders. However, consistent concomitant improvements in psychological flexibility were not apparent. Participants reported a mostly positive experience of the intervention; all appeared to complete the intervention, and no adverse events were reported. Nonetheless, there was evidence that those with compromised concentration or who report good initial QoL and low levels of distress may derive less benefit. Although several methodological weaknesses limit the strength of our conclusions, this ACT-based guided self-help intervention shows encouraging utility for improving QoL and mood in MD.
Relative Safety of Preemergence Corn Herbicides Applied to Coarse-Textured Soil
Authors: Vollmer Kurt M. , VanGessel Mark J. , Johnson Quintin R. , Scott Barbara A.
Published: June 2017

Crop safety is an important consideration in determining PRE herbicide application, especially when multiple herbicide sites-of-action are used. This research examined relative corn injury as the result of PRE applications containing ALS- and/or HPPD-inhibiting herbicides to a sandy loam soil. Herbicide premixes containing clopyralid, flumetsulam, isoxaflutole, mesotrione, rimsulfuron, tembotrione, thifensulfuron, and thiencarbazone were applied at twice the labeled rate. In general, isoxaflutole alone was the safest herbicide evaluated, while PRE applications of rimsulfuron-containing herbicides caused the most corn stunting, had a lower recovery rate, and lower yields. However, POST applications of mesotrione plus rimsulfuron stunted corn less than 2%. Although there was little correlation between corn injury and yield, growers should be aware of the other factors, such as soil texture and environment that may impact crop production.
Wissensstrukturen – eine wichtige Basis für Lehrende und Lernende
Authors: Schneider Kordula , Roth Christian
Published: June 2017

Zusammenfassung. Wissensstrukturen stellen Inhalte mit ihren logischen Zusammenhängen grafisch dar. Sie helfen dabei, verschiedene Wissensarten aufzunehmen und mentale Repräsentationen sowohl beim Lehrenden als auch beim Lernenden aufzubauen.
EGR-1/ASPP1 inter-regulatory loop promotes apoptosis by inhibiting cyto-protective autophagy
Authors: Zhao Kunming , Yu Miao , Zhu Yifu , Liu Dong , Wu Qiong , Hu Ying
Published: June 2017

The decrease of ASPP1 (Apoptosis-Stimulating Protein of p53 1), a known p53 activator, has been linked to carcinogenesis and the cytotoxic resistance in various cancers, yet the underlying mechanisms of ASPP1 expression and its complex functions are not yet clear. Here, we report that ASPP1 forms an inter-regulatory loop with Early Growth Response 1 (EGR-1), and promotes apoptosis via inhibiting cyto-protective autophagy, independent of the well-documented p53-dependent mechanisms. We show that ASPP1 mRNA and protein were remarkably elevated by ectopic EGR-1 expression or endogenous EGR-1 activation, in cells with different tissue origins and p53 status. Conversely, RNAi-mediated EGR-1 knockdown suppressed ASPP1. The further mechanism studies revealed that ASPP1 promoter, mapped to −283/+88, which contained three conserved EGR-1 binding sites, was required for both binding and transactivity of EGR-1. In addition, we demonstrate that ASPP1 promoted EGR-1 in a positive feedback loop by preventing proteasome-mediated EGR-1 degradation or promoting EGR-1 nuclear import in response to anticancer natural compound Quercetin. Furthermore, albeit activating p53 in the nucleus is the well-studied function of ASPP1, we found that ASPP1 was predominately localized in the cytoplasm. Interestingly, the cytoplasmic ASPP1 retained its pro-apoptosis capability. Mechanistically, ASPP1 suppressed Atg5–Atg12 and also bound with Atg5–Atg12 to prevent its further complex formation with Atg16, resulting in the inhibition of cyto-protective autophagy. In conclusion, our results provide new insights into EGR-1/ASPP1 regulatory loop in sensitizing Quercetin-induced apoptosis. EGR-1/ASPP1, therefore, may be potentially used as therapeutic targets to improve cancer’s response to pro-apoptosis treatments.
The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation
Authors: Lee Chih-Yuan , Lai Ting-Yu , Tsai Meng-Kun , Chang Yung-Chi , Ho Yu-Hsin , Yu I-Shing , Yeh Tzu-Wen , Chou Chih-Chang , Lin You-Sheng , Lawrence Toby , Hsu Li-Chung
Published: June 2017

Caveolin-1 (CAV1), the major constituent of caveolae, plays a pivotal role in various cellular biological functions, including cancer and inflammation. The ubiquitin/proteasomal pathway is known to contribute to the regulation of CAV1 expression, but the ubiquitin ligase responsible for CAV1 protein stability remains unidentified. Here we reveal that E3 ubiquitin ligase ZNRF1 modulates CAV1 protein stability to regulate Toll-like receptor (TLR) 4-triggered immune responses. We demonstrate that ZNRF1 physically interacts with CAV1 in response to lipopolysaccharide and mediates ubiquitination and degradation of CAV1. The ZNRF1–CAV1 axis regulates Akt–GSK3β activity upon TLR4 activation, resulting in enhanced production of pro-inflammatory cytokines and inhibition of anti-inflammatory cytokine IL-10. Mice with deletion of ZNRF1 in their hematopoietic cells display increased resistance to endotoxic and polymicrobial septic shock due to attenuated inflammation. Our study defines ZNRF1 as a regulator of TLR4-induced inflammatory responses and reveals another mechanism for the regulation of TLR4 signalling through CAV1.
Spaser as a biological probe
Authors: Galanzha Ekaterina I. , Weingold Robert , Nedosekin Dmitry A. , Sarimollaoglu Mustafa , Nolan Jacqueline , Harrington Walter , Kuchyanov Alexander S. , Parkhomenko Roman G. , Watanabe Fumiya , Nima Zeid , Biris Alexandru S. , Plekhanov Alexander I. , Stockman Mark I. , Zharov Vladimir P.
Published: June 2017

Understanding cell biology greatly benefits from the development of advanced diagnostic probes. Here we introduce a 22-nm spaser (plasmonic nanolaser) with the ability to serve as a super-bright, water-soluble, biocompatible probe capable of generating stimulated emission directly inside living cells and animal tissues. We have demonstrated a lasing regime associated with the formation of a dynamic vapour nanobubble around the spaser that leads to giant spasing with emission intensity and spectral width >100 times brighter and 30-fold narrower, respectively, than for quantum dots. The absorption losses in the spaser enhance its multifunctionality, allowing for nanobubble-amplified photothermal and photoacoustic imaging and therapy. Furthermore, the silica spaser surface has been covalently functionalized with folic acid for molecular targeting of cancer cells. All these properties make a nanobubble spaser a promising multimodal, super-contrast, ultrafast cellular probe with a single-pulse nanosecond excitation for a variety of in vitro and in vivo biomedical applications.
Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro
Authors: Yoshida Mari , Reyes Sabrina Galiñanes , Tsuda Soichiro , Horinouchi Takaaki , Furusawa Chikara , Cronin Leroy
Published: June 2017

Multi-drug strategies have been attempted to prolong the efficacy of existing antibiotics, but with limited success. Here we show that the evolution of multi-drug-resistant Escherichia coli can be manipulated in vitro by administering pairs of antibiotics and switching between them in ON/OFF manner. Using a multiplexed cell culture system, we find that switching between certain combinations of antibiotics completely suppresses the development of resistance to one of the antibiotics. Using this data, we develop a simple deterministic model, which allows us to predict the fate of multi-drug evolution in this system. Furthermore, we are able to reverse established drug resistance based on the model prediction by modulating antibiotic selection stresses. Our results support the idea that the development of antibiotic resistance may be potentially controlled via continuous switching of drugs.
Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance
Authors: Ali Moiez , Kaltenbrun Erin , Anderson Gray R. , Stephens Sarah Jo , Arena Sabrina , Bardelli Alberto , Counter Christopher M. , Wood Kris C.
Published: June 2017

KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRASQ61 mutations that function even when protein expression is low. Finally, cancer cells upregulate translation to facilitate KRASG12-driven acquired resistance, resulting in hypersensitivity to translational inhibitors. These findings demonstrate that codon bias plays a critical role in KRAS-driven resistance and provide a rationale for targeting translation to overcome resistance.
Cross-orientation suppression in visual area V2
Authors: Rowekamp Ryan J. , Sharpee Tatyana O.
Published: June 2017

Object recognition relies on a series of transformations among which only the first cortical stage is relatively well understood. Already at the second stage, the visual area V2, the complexity of the transformation precludes a clear understanding of what specifically this area computes. Previous work has found multiple types of V2 neurons, with neurons of each type selective for multi-edge features. Here we analyse responses of V2 neurons to natural stimuli and find three organizing principles. First, the relevant edges for V2 neurons can be grouped into quadrature pairs, indicating invariance to local translation. Second, the excitatory edges have nearby suppressive edges with orthogonal orientations. Third, the resulting multi-edge patterns are repeated in space to form textures or texture boundaries. The cross-orientation suppression increases the sparseness of responses to natural images based on these complex forms of feature selectivity while allowing for multiple scales of position invariance.
Vector assembly of colloids on monolayer substrates
Authors: Jiang Lingxiang , Yang Shenyu , Tsang Boyce , Tu Mei , Granick Steve
Published: June 2017

The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize ‘vector assembly’ by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers.
Formation and electronic properties of palladium hydrides and palladium-rhodium dihydride alloys under pressure
Authors: Yang Xiao , Li Huijian , Ahuja Rajeev , Kang Taewon , Luo Wei
Published: June 2017

We present the formation possibility for Pd-hydrides and Pd-Rh hydrides system by density functional theory (DFT) in high pressure upto 50 GPa. Calculation confirmed that PdH2in face-centered cubic (fcc) structure is not stable under compression that will decomposition to fcc-PdH and H2. But it can be formed under high pressure while the palladium is involved in the reaction. We also indicate a probably reason why PdH2can not be synthesised in experiment due to PdH is most favourite to be formed in Pd and H2environment from ambient to higher pressure. With Rh doped, the Pd-Rh dihydrides are stabilized in fcc structure for 25% and 75% doping and in tetragonal structure for 50% doping, and can be formed from Pd, Rh and H2at high pressure. The electronic structural study on fcc type PdxRh1−xH2indicates the electronic and structural transition from metallic to semi-metallic as Pd increased from x = 0 to 1.
The early metabolomic response of adipose tissue during acute cold exposure in mice
Authors: Lu Xiyuan , Solmonson Ashley , Lodi Alessia , Nowinski Sara M. , Sentandreu Enrique , Riley Christopher L. , Mills Edward M. , Tiziani Stefano
Published: June 2017

To maintain core body temperature in cold conditions, mammals activate a complex multi-organ metabolic response for heat production. White adipose tissue (WAT) primarily functions as an energy reservoir, while brown adipose tissue (BAT) is activated during cold exposure to generate heat from nutrients. Both BAT and WAT undergo specific metabolic changes during acute cold exposure. Here, we use an untargeted metabolomics approach to characterize the initial metabolic response to cold exposure in multiple adipose tissue depots in mice. Results demonstrate dramatically distinct metabolic responses during cold exposure in BAT and WAT. Amino acids, nucleotide pathways, and metabolites involved in redox regulation were greatly affected 4 hours post-exposure in BAT, while no polar metabolites were observed to significantly change in WAT depots up to 6 hours post exposure. Lipid metabolism was activated early (2 hours) in both BAT and the subcutaneous WAT depots, with the most striking change being observed in the modulation of diglyceride and monoglyceride levels in BAT. Overall, these data provide a timeline of global thermogenic metabolism in adipose depots during acute cold exposure. We have highlighted differences in visceral and subcutaneous WAT thermogenic metabolism and demonstrate the distinct metabolism of BAT during cold exposure.
Thermal and structural studies of carbon coated Mo2C synthesized via in-situ single step reduction-carburization
Authors: Mir Rameez Ahmad , Sharma Piyush , Pandey Om Prakash
Published: June 2017

Carbon coated nano molybdenum carbide (Mo2C) has been synthesized at 800 °C through single step reduction route using molybdenum trioxide (MoO3) as a precursor, polypropylene (P.P) as a carbon source and magnesium (Mg) as a catalyst in an autoclave. The synthesized samples were characterized by X-ray diffraction (XRD), thermal analysis techniques (TG/DTA/DTG), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Williamson- Hall (W-H) analysis has been done to estimate various parameters like strain, stress and strain energy density. Multi-stage kinetic analysis of the product phase has been studied to establish the nature of the thermal decomposition. Coats-Redfern method applied to determine the mechanism involved in the decomposition of the product phase shows that initial and final stage follow F1 mechanism whereas middle stage follow F3 mechanism. The activation energy (Ea) and pre-exponential factor (A) has also been determined. The morphological studies shows that the particles have partially spherical/faceted shape, with carbon coated having wide particle size distribution. The surface chemistry and surface area analysis were studied by X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmet-Teller (BET), respectively. The formation mechanism of carbon coated Mo2C nano particles has been predicted based on the XRD, TG/DTA & DTG and microstructural results.
Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer
Authors: Kim Ji Young , Lee Hyebin , Woo Jongmin , Yue Wang , Kim Kwangsoo , Choi Seongmin , Jang Ja-June , Kim Youngsoo , Park In Ae , Han Dohyun , Ryu Han Suk
Published: June 2017

Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair. We further elaborated the global interaction networks of molecular events via nicotinamide-inducible expression changes at the mRNA and functional protein levels. This approach indicated that nicotinamide treatment rewires interaction networks toward dysfunction in DNA damage repair and away from a pro-growth state in TNBC. To our knowledge, the high-resolution network interactions identified in the present study provide the first evidence to comprehensively support the hypothesis of nicotinamide as a novel therapeutic agent in TNBC.
Bacteriocin Gene-Trait matching across the complete Lactobacillus Pan-genome
Authors: Collins Fergus W. J. , O’Connor Paula M. , O’Sullivan Orla , Gómez-Sala Beatriz , Rea Mary C. , Hill Colin , Ross R. Paul
Published: June 2017

Lactobacilli constitute a large genus of Gram-positive lactic acid bacteria which have widespread roles ranging from gut commensals to starters in fermented foods. A combination of in silico and laboratory-based screening allowed us to determine the overall bacteriocin producing potential of representative strains of each species of the genus. The genomes of 175 lactobacilli and 38 associated species were screened for the presence of antimicrobial producing genes and combined with screening for antimicrobial activity against a range of indicators. There also appears to be a link between the strains’ environment and bacteriocin production, with those from the animal and human microbiota encoding over twice as many bacteriocins as those from other sources. Five novel bacteriocins were identified belonging to differing bacteriocin classes, including two-peptide bacteriocins (muricidin and acidocin X) and circular bacteriocins (paracyclicin). In addition, there was a clear clustering of helveticin type bacteriolysins in the Lactobacillus acidophilus group of species. This combined in silico and in vitro approach to screening has demonstrated the true diversity and complexity of bacteriocins across the genus. It also highlights their biological importance in terms of communication and competition between closely related strains in diverse complex microbial environments.
Programmable Deployment of Tensegrity Structures by Stimulus-Responsive Polymers
Authors: Liu Ke , Wu Jiangtao , Paulino Glaucio H. , Qi H. Jerry
Published: June 2017

Tensegrity structures with detached struts are naturally suitable for deployable applications, both in terrestrial and outer-space structures, as well as morphing devices. Composed of discontinuous struts and continuous cables, such systems are only structurally stable when self-stress is induced; otherwise, they lose the original geometrical configuration (while keeping the topology) and thus can be tightly packed. We exploit this feature by using stimulus responsive polymers to introduce a paradigm for creating actively deployable 3D structures with complex shapes. The shape-change of 3D printed smart materials adds an active dimension to the configurational space of some structural components. Then we achieve dramatic global volume expansion by amplifying component-wise deformations to global configurational change via the inherent deployability of tensegrity. Through modular design, we can generate active tensegrities that are relatively stiff yet resilient with various complexities. Such unique properties enable structural systems that can achieve gigantic shape change, making them ideal as a platform for super light-weight structures, shape-changing soft robots, morphing antenna and RF devices, and biomedical devices.
Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
Authors: Kulkarni Mangesh , Leszczynska Aleksandra , Wei Gabbie , Winkler Michael A. , Tang Jie , Funari Vincent A. , Deng Nan , Liu Zhenqiu , Punj Vasu , Deng Sophie X. , Ljubimov Alexander V. , Saghizadeh Mehrnoosh
Published: June 2017

Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.
Understanding ‘saturation’ of radar signals over forests
Authors: Joshi Neha , Mitchard Edward T. A. , Brolly Matthew , Schumacher Johannes , Fernández-Landa Alfredo , Johannsen Vivian Kvist , Marchamalo Miguel , Fensholt Rasmus
Published: June 2017

There is an urgent need to quantify anthropogenic influence on forest carbon stocks. Using satellite-based radar imagery for such purposes has been challenged by the apparent loss of signal sensitivity to changes in forest aboveground volume (AGV) above a certain ‘saturation’ point. The causes of saturation are debated and often inadequately addressed, posing a major limitation to mapping AGV with the latest radar satellites. Using ground- and lidar-measurements across La Rioja province (Spain) and Denmark, we investigate how various properties of forest structure (average stem height, size and number density; proportion of canopy and understory cover) simultaneously influence radar backscatter. It is found that increases in backscatter due to changes in some properties (e.g. increasing stem sizes) are often compensated by equal magnitude decreases caused by other properties (e.g. decreasing stem numbers and increasing heights), contributing to the apparent saturation of the AGV-backscatter trend. Thus, knowledge of the impact of management practices and disturbances on forest structure may allow the use of radar imagery for forest biomass estimates beyond commonly reported saturation points.
Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis
Authors: Kim Jinwook , Lindsey Brooks D. , Chang Wei-Yi , Dai Xuming , Stavas Joseph M. , Dayton Paul A. , Jiang Xiaoning
Published: June 2017

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.
Autotransporter domain-dependent enzymatic analysis of a novel extremely thermostable carboxylesterase with high biodegradability towards pyrethroid pesticides
Authors: Cai Xianghai , Wang Wei , Lin Lin , He Dannong , Huang Gang , Shen Yaling , Wei Wei , Wei Dongzhi
Published: June 2017

The EstPS1 gene, which encodes a novel carboxylesterase of Pseudomonas synxantha PS1 isolated from oil well-produced water, was cloned and sequenced. EstPS1 has an open reading frame of 1923 bp and encodes the 640-amino acid carboxylesterase (EstPS1), which contains an autotransporter (AT) domain (357–640 amino acids). Homology analysis revealed that EstPS1 shared the highest identity (88%) with EstA from Pseudomonas fluorescens A506 (NCBI database) and belonged to the carboxylesterase family (EC 3.1.1.1). The optimum pH and temperature of recombinant EstPS1 were found to be 8.0 and 60 °C, respectively. EstPS1 showed high thermostability, and the half-lives (T1/2 thermal inactivation) at 60, 70, 80, 90, and 100 °C were 14 h, 2 h, 31 min, 10 min, and 1 min, respectively. To understand the role of the AT domain in carboxylesterase, AT domain-truncated carboxylesterase (EstPS1ΔAT) was generated. EstPS1ΔAT showed a clearly decreased secretion rate, owing to the AT domain strongly improved secretory expression in the heterogeneous system. EstPS1 degraded various pyrethroid pesticides, and hydrolysis efficiencies were dependent on the pyrethroid molecular structure. EstPS1 degraded all the tested pyrethroid pesticides and hydrolysed the p-nitrophenyl esters of medium-short-chain fatty acids, indicating that EstPS1 is an esterase with broad specificity.
Nomogram model to predict postoperative infection after mandibular osteoradionecrosis surgery
Authors: Liu Zhonglong , Dai Tianguo , Wang Zhonghe , Zhang Zhiyuan , Qiu Weiliu , He Yue
Published: June 2017

Osteoradionecrosis of the mandible (ORNM) is one of the most dreaded complications of radiotherapy. The poor healing capacity of soft tissue after radiation may lead to surgical failure. The current study was designed to identify prognostic factors for postoperative infection (PPI) and propose corresponding prophylaxis and intervention protocols. A retrospective study was conducted concerning ORNM patients from 2000 to 2015. A risk-stratification score and nomogram model were established to predict the risk of PPI. A total of 257 patients were analyzed, and the total incidence of PPI was 23.3% (60/257). In multiple logistic regression analysis, radiation dose$$\geqslant $$⩾80 Gy (versus <80 Gy, OR = 2.044, P = 0.035, 95% CI: 1.05–3.979), bilateral ORNM (versus unilateral, OR = 4.120, P = 0.006, 95% CI: 1.501–11.307), skin fistula (versus none, OR = 3.078, P = 0.040, 95% CI: 1.05–9.023), and implant utilization (versus none, OR = 2.115, P = 0.020, 95% CI: 1.125–3.976) were significantly associated with PPI. The susceptibility to PPI in patients with risk-stratification scores of 14–22 was 2.833 times that of patients with scores of 7–13, and 7.585 times that of cases defined as scores of 0–6. The discrimination capability of the nomogram model was estimated using a ROC curve with an AUC of 0.708, revealing potentially useful predictive abilities. In conclusion, current risk-stratification scores and nomogram models effectively predicted the risk of PPI in ORNM patients.
Identification and characterization of a rich population of CD34+ mesenchymal stem/stromal cells in human parotid, sublingual and submandibular glands
Authors: Togarrati Padma Priya , Sasaki Robson T. , Abdel-Mohsen Mohamed , Dinglasan Nuntana , Deng Xutao , Desai Shivani , Emmerson Elaine , Yee Elizabeth , Ryan William R. , da Silva Marcelo C. P. , Knox Sarah M. , Pillai Satish K. , Muench Marcus O.
Published: June 2017

Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34+ cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34+ SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34+ cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34+ derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs.
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development
Authors: Tsiantoulas Dimitrios , Kiss Mate , Bartolini-Gritti Barbara , Bergthaler Andreas , Mallat Ziad , Jumaa Hassan , Binder Christoph J.
Published: June 2017

Mice lacking secreted IgM (sIgM−/−) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells insIgM−/−mice display increased B cell receptor (BCR) signaling as judged by increased levels of phosphorylated Bruton’s tyrosine kinase (pBtk), phosphorylated Spleen tyrosine kinase (pSyk), and nuclear receptor Nur77. Low dosage treatment with the pBtk inhibitor Ibrutinib reversed the altered B cell development in the spleen ofsIgM−/−mice, suggesting that sIgM regulate splenic B cell differentiation by decreasing BCR signaling. Mechanistically, we show that B cells, which express BCRs specific to hen egg lysozyme (HEL) display diminished responsiveness to HEL stimulation in presence of soluble anti-HEL IgM antibodies. Our data identify sIgM as negative regulators of BCR signaling and suggest that they can act as decoy receptors for self-antigens that are recognized by membrane bound BCRs.
miRNA profiling during antigen-dependent T cell activation: A role for miR-132-3p
Authors: Gutiérrez-Vázquez Cristina , Rodríguez-Galán Ana , Fernández-Alfara Marcos , Mittelbrunn María , Sánchez-Cabo Fátima , Martínez-Herrera Dannys Jorge , Ramírez-Huesca Marta , Pascual-Montano Alberto , Sánchez-Madrid Francisco
Published: June 2017

microRNAs (miRNAs) are tightly regulated during T lymphocyte activation to enable the establishment of precise immune responses. Here, we analyzed the changes of the miRNA profiles of T cells in response to activation by cognate interaction with dendritic cells. We also studied mRNA targets common to miRNAs regulated in T cell activation. pik3r1 gene, which encodes the regulatory subunits of PI3K p50, p55 and p85, was identified as target of miRNAs upregulated after T cell activation. Using 3′UTR luciferase reporter-based and biochemical assays, we showed the inhibitory relationship between miR-132-3p upregulation and expression of the pik3r1 gene. Our results indicate that specific miRNAs whose expression is modulated during T cell activation might regulate PI3K signaling in T cells.
Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice
Authors: Laumonier Thomas , Bermont Flavien , Hoffmeyer Pierre , Kindler Vincent , Menetrey Jacques
Published: June 2017

Satellite cells, localized within muscles in vivo, are Pax7+ muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2.9% of the nuclei were localized in myotubes and 38 ± 2.9% in the mononucleated non-fusing MRC. Eighty percent of freshly isolated human MRC expressed a phenotype similar to human quiescent satellite cells (CD56+/Pax7+/MyoD−/Ki67− cells). Fourteen days and 21 days after cell transplantation in immunodeficient mice, live human cells were significantly more numerous and the percentage of Pax7+/human lamin A/C+ cells was 2 fold higher in muscles of animals injected with MRC compared to those injected with human myoblasts, despite that percentage of spectrin+ and lamin A/C+ human fibers in both groups MRC were similar. Taken together, these data provide evidence that MRC generated in vitro represent a promising source of cells for improving regeneration of injured skeletal muscles.
The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
Authors: Rodríguez-Gil Alfonso , Ritter Olesja , Saul Vera V. , Wilhelm Jochen , Yang Chen-Yuan , Grosschedl Rudolf , Imai Yumiko , Kuba Keiji , Kracht Michael , Schmitz M. Lienhard
Published: June 2017

The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6. Increased expression of MHC II genes after knock-down or knock-out of either CNOT subunit was seen in a variety of cell systems and also in naïve macrophages from CNOT3 conditional knock-out mice. CNOT2-mediated repression of MHC II genes occurred also in the absence of the master regulator class II transactivator (CIITA) and did not cause detectable changes of the chromatin structure at the chromosomal MHC II locus. CNOT2 downregulation resulted in an increasedde novotranscription of mRNAs whereas tethering of CNOT2 to a regulatory region governing MHC II expression resulted in diminished transcription. These results expand the known repertoire of CCR4-NOT members for immune regulation and identify CNOT proteins as a novel group of corepressors restricting class II expression.