bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Impact of Further Treatments on Distant Metastasis in Patients With Minimally Invasive Follicular Thyroid Carcinoma: Verification Using Inverse Probability of Treatment Weighting
Authors: Lee Yu‐Mi , Lee Yi Ho , Song Dong Eun , Kim Won Bae , Sung Tae‐Yon , Yoon Jong Ho , Chung Ki‐Wook , Hong Suck Joon
Published: June 2016

Background

The aim of this study was to evaluate the prognostic impact of further treatments in minimally invasive follicular thyroid carcinoma (MIFTC) patients.

Methods

The risk factors for distant metastases were analyzed, and the impact of surgical extent on distant metastasis was verified by using weighted logistic regression models with inverse‐probability of treatment weighting (IPTW).

Results

166 patients including 31 males (18.7 %) and 135 females (81.3 %), with the mean age of 41.5 ± 13.5 years, were enrolled for this study. The median follow‐up period was 103.5 months (range, 13–244 months). Seven patients (4.2 %) had distant metastases during follow‐up period. The presence of vascular invasion (Hazard ratio [HR] = 29.06; 95 % Confidence Interval [CI] = 3.06–209.08; p = 0.015) and extensive vascular invasion ≥4 foci (HR = 40.57; 95 % CI = 2.09–789.13; p = 0.014) were the independent risk factors for distant metastasis by multivariate analysis. Surgical extent did not influence distant metastasis. Logistic regression with IPTW also demonstrated that there were no statistically significant differences in the development of distant metastasis based on surgical extent (HR = 1.28; 95 % CI = 0.15–10.87; p = 0.823).

Conclusions

The presence of extensive vascular invasion is the most powerful predictor of distant metastasis. However, it is noteworthy that further treatments do not demonstrate an advantageous effect on preventing distant metastasis during the follow‐up period.
A New Type of Sulfobetaine Surfactant with Double Alkyl Polyoxyethylene Ether Chains for Enhanced Oil Recovery
Authors: Li Peiqian , Yang Cheng , Cui Zhenggang , Song Binglei , Jiang Jianzhong , Wang Zhijun
Published: June 2016

A new type of sulfobetaine with double alkyl polyoxyethylene (n) ether chains, dicoconut oil alcohol polyoxethylene (n) ether methylhydroxylpropyl sulfobetaine (diC12–14EnHSB) was synthesized using a commercial nonionic surfactant, coconut oil alcohol polyoxethylene (n) ether, as raw material and its properties as a surfactant for enhanced oil recovery (EOR) in the absence of alkali was studied. The purified product is a mixture of homologues with mainly C12/C12, C12/C14 and C14/C14 alkyl chains and widely distributed EO chains (n = 2.2 on average) with an average molar mass of 742.6 g/mol. The diC12–14E2.2HSB has an improved aqueous solubility at 25 °C compared with didodecylmethylhydroxylpropyl sulfobetaine (diC12HSB), a homologue without an EO chain, and is highly surface active as reflected by its low CMC (4.6 × 10−6 mol/L), high saturated adsorption (6.8 × 10−10 mol/cm2) and small cross sectional area (0.24 nm2/molec.) at the air/water interface. With a hydrophile–lipophile balance well matched with Daqing crude oil/connate water system, the sulfobetaine can reduce Daqing crude oil/connate water interfacial tension to ultra‐low values at 45 °C in the absence of alkali, and displays a low saturated adsorption at the sandstone/water interface (0.0024 mmol/g), reduced by 69 and 92 % respectively in comparison with that of the corresponding carboxyl betaine, diC12–14E2.2B and its homologue without an EO chain, didodecylmethylcarboxyl betaine (diC12B). With these excellent properties diC12–14E2.2HSB gives a high tertiary recovery, 18.4 % original oil in place, when mixed with other hydrophobic and hydrophilic sulfobetaines in surfactant‐polymer (SP) flooding free of alkali. The insertion of EO chains in combination with the replacement of carboxyl betaine by sulfobetaine is therefore very efficient for improving the properties of the double chain hydrophobic carboxyl betaines as surfactants for SP flooding free of alkali.
Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP‐1c in L‐02 Cells
Authors: Qin Shumin , Yin Jinjin , Huang Keer
Published: June 2016

Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L‐02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L‐02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L‐02 cells, which could only be reversed with 50 μΜ WY14643 (the PPARα agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator‐activated receptor alpha (PPARα), which contributed to the increased activation of sterol regulatory element binding protein‐1c (SREBP‐1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L‐02 cells by upregulating SREBP‐1c expression through the suppression of PPARα.
Pediatric forearm fractures with in situ intramedullary implants
Authors: Kelly Brian A. , Shore Benjamin J. , Bae Donald S. , Hedequist Daniel J. , Glotzbecker Michael P.
Published: June 2016

Purpose

The purpose of this investigation is to present our institutional experience with fractures of the pediatric forearm with in situ intramedullary nails.

Methods

Six patients treated at our institution for forearm fracture with in situ intramedullary implants between 2004 and 2013 were reviewed. Patient demographics, injury and radiographic characteristics, method of treatment, time to union, and complications were collected from the medical record.

Results

485 patients with forearm fractures were treated with intramedullary implants and six patients presented with a fracture with in situ implants (1.2 %). Fractures in all six patients resulted from a second traumatic event after radiographic healing but before implant removal at a mean of 13.0 months from the initial procedure. One patient had an adequately aligned fracture and was treated with casting without reduction. The remaining five patients (83 %) returned to the operating room for treatment. Two patients underwent rod removal and placement of new intramedullary implants, and two patients were treated with rod removal and plating without attempt at closed reduction. One patient underwent closed reduction in the operating room with successful re-bending of the radial implant and replacement of the ulna implant. All patients went on to uncomplicated radiographic union at a mean 3.6 months.

Conclusions

The incidence of fracture of pediatric forearm with in situ intramedullary implants is low. This rare complication can be treated by several different methods, including revision TENS placement, revision to plate fixation, or in situ bending of rods, with the expectation for successful uncomplicated union.
Fairer Citation Based Metrics
Authors: Arandjelović Ognjen
Published: June 2016

I describe a simple modification which can be applied to any citation count based index (e.g. Hirsch’s h-index) quantifying a researcher’s publication output. The key idea behind the proposed approach is that the merit for the citations of a paper should be distributed amongst its authors according to their relative contributions. In addition to producing inherently fairer metrics I show that the proposed modification has the potential to normalize partially for the unfair effects of honorary authorship and thus discourage this practice.
Genetics of Lipid and Lipoprotein Disorders and Traits
Authors: Dron Jacqueline S. , Hegele Robert A.
Published: June 2016

Purpose of Review

Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components.

Recent Findings

Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1, APOC3, LDLR, APOA5, and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4.

Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a “one stop shop” for the interested reader.
A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice
Authors: Abreu‐Villaça Yael , Correa‐Santos Monique , Dutra‐Tavares Ana C. , Paes‐Branco Danielle , Nunes‐Freitas Andre , Manhães Alex C. , Filgueiras Cláudio C. , Ribeiro‐Carvalho Anderson
Published: June 2016

The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8 h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74 mg nicotine/cigarette) or 4A1 (LowNic group: 0.14 mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short‐ (PN50) and long‐term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short‐term deprivation. The high‐affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short‐term deprivation; of LowNic mice at long‐term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.
Prevention of Clostridium difficile Infection: A Systematic Survey of Clinical Practice Guidelines
Authors: Lytvyn Lyubov , Mertz Dominik , Sadeghirad Behnam , Alaklobi Faisal , Selva Anna , Alonso-Coello Pablo , Johnston Bradley C.
Published: June 2016

BACKGROUND

Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infectious diarrhea.

OBJECTIVE

To analyze the methodological quality, content, and supporting evidence among clinical practice guidelines (CPGs) on CDI prevention.

DESIGN AND SETTING

We searched medical databases and gray literature for CPGs on CDI prevention published January 2004-January 2015. Three reviewers independently screened articles and rated CPG quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, composed of 23 items, rated 1–7, within 6 domains. We reported each domain score as a percentage of its maximum possible score and standardized range. We summarized recommendations, extracted their supporting articles, and rated individually the level of evidence using the Oxford Centre for Evidence-Based Medicine Levels of Evidence.

RESULTS

Of 2,578 articles screened, 5 guidelines met inclusion criteria. Median AGREE II scores and interquartile ranges were: clarity of presentation, 75.9% (75.9%–79.6%); scope and purpose, 74.1% (68.5%–85.2%); editorial independence, 63.9% (47.2%–66.7%); applicability, 43.1% (19.4%–55.6%); stakeholder involvement, 40.7% (38.9%–44.4%); and rigor of development, 18.1% (17.4%–35.4%). CPGs addressed several common strategies for CDI prevention, including antibiotic stewardship, hypochlorite solutions, probiotic prophylaxis, and bundle strategies. Recommendations were often not consistent with evidence, and most were based on low-level studies.

CONCLUSION

CPGs did not adhere well to AGREE II reporting standards. Furthermore, there was limited transparency in moving from evidence to recommendations. CDI prevention CPGs need to better adhere to AGREE-II and be transparent in moving from evidence to recommendations, and recommendations need to be consistent with available evidence.

Infect Control Hosp Epidemiol 2016;37:901–908
On the topology of the eigenframe of the subgrid-scale stress tensor
Authors: Yang Zixuan , Wang Bing-Chen
Published: June 2016

In this paper, the geometrical properties of the subgrid-scale (SGS) stress tensor are investigated through its eigenvalues and eigenvectors. The concepts of Euler rotation angle and axis are utilized to investigate the relative rotation of the eigenframe of the SGS stress tensor with respect to that of the resolved strain rate tensor. Both Euler rotation angle and axis are natural invariants of the rotation matrix, which uniquely describe the topological relation between the eigenframes of these two tensors. Different from the reference frame fixed to a rigid body, the eigenframe of a tensor consists of three orthonormal eigenvectors, which by their nature are subjected to directional aliasing. In order to describe the geometric relationship between the SGS stress and resolved strain rate tensors, an effective method is proposed to uniquely determine the topology of the eigenframes. The proposed method has been used for testing three SGS stress models in the context of homogeneous isotropic turbulence at three Reynolds numbers, using both a priori and a posteriori approaches.
Modeling the thickness of perennial ice covers on stratified lakes of the Taylor Valley, Antarctica
Authors: OBRYK M. K. , DORAN P. T. , HICKS J. A. , McKAY C. P. , PRISCU J. C.
Published: June 2016

A 1-D ice cover model was developed to predict and constrain drivers of long-term ice thickness trends in chemically stratified lakes of Taylor Valley, Antarctica. The model is driven by surface radiative heat fluxes and heat fluxes from the underlying water column. The model successfully reproduced 16 a (between 1996 and 2012) of ice thickness changes for the west lobe of Lake Bonney (average ice thickness = 3.53 m) and Lake Fryxell (average ice thickness = 4.22 m). Long-term ice thickness trends require coupling with the thermal structure of the water column. The heat stored within the temperature maximum of lakes exceeding a liquid water column depth of 20 m can either impede or facilitate ice thickness change depending on the predominant climatic trend (cooling or warming). As such, shallow (<20 m deep water columns) perennially ice-covered lakes without deep temperature maxima are more sensitive indicators of climate change. The long-term ice thickness trends are a result of surface energy flux and heat flux from the deep temperature maximum in the water column, the latter of which results from absorbed solar radiation.
ON THE MODIFIED FUTAKI INVARIANT OF COMPLETE INTERSECTIONS IN PROJECTIVE SPACES
Authors: TAKAHASHI RYOSUKE
Published: June 2016

Let $M$ be a Fano manifold. We call a Kähler metric ${\it\omega}\in c_{1}(M)$ a Kähler–Ricci soliton if it satisfies the equation $\text{Ric}({\it\omega})-{\it\omega}=L_{V}{\it\omega}$ for some holomorphic vector field $V$ on $M$. It is known that a necessary condition for the existence of Kähler–Ricci solitons is the vanishing of the modified Futaki invariant introduced by Tian and Zhu. In a recent work of Berman and Nyström, it was generalized for (possibly singular) Fano varieties, and the notion of algebrogeometric stability of the pair $(M,V)$ was introduced. In this paper, we propose a method of computing the modified Futaki invariant for Fano complete intersections in projective spaces.
How reliable are randomised controlled trials for studying the relationship between diet and disease? A narrative review
Authors: Temple Norman J.
Published: June 2016

Large numbers of randomised controlled trials (RCT) have been carried out in order to investigate diet–disease relationships. This article examines eight sets of studies and compares the findings with those from epidemiological studies (cohort studies in seven of the cases). The studies cover the role of dietary factors in blood pressure, body weight, cancer and heart disease. In some cases, the findings from the two types of study are consistent, whereas in other cases the findings appear to be in conflict. A critical evaluation of this evidence suggests factors that may account for conflicting findings. Very often RCT recruit subjects with a history of the disease under study (or at high risk of it) and have a follow-up of only a few weeks or months. Cohort studies, in contrast, typically recruit healthy subjects and have a follow-up of 5–15 years. Owing to these differences, findings from RCT are not necessarily more reliable than those from well-designed prospective cohort studies. We cannot assume that the results of RCT can be freely applied beyond the specific features of the studies.
Neutral change
Authors: KAUHANEN HENRI
Published: June 2016

Language change is neutral if the probability of a language learner adopting any given linguistic variant only depends on the frequency of that variant in the learner’s environment. Ruling out non-neutral motivations of change, be they sociolinguistic, computational, articulatory or functional, a theory of neutral change insists that at least some instances of language change are essentially due to random drift, demographic noise and the social dynamics of finite populations; consequently, it has remained little investigated in the historical and sociolinguistics literature, which has generally been on the lookout for more substantial causes of change. Indeed, recent computational studies have argued that a neutral mechanism cannot give rise to ‘well-behaved’ time series of change which would align with historical data, for instance to generate S-curves. In this paper, I point out a methodological shortcoming of those studies and introduce a mathematical model of neutral change which represents the language community as a dynamic, evolving network of speakers. With computer simulations and a quantitative operationalization of what it means for change to be well-behaved, I show that this model exhibits well-behaved neutral change provided that the language community is suitably clusterized. Thus, neutral change is not only possible but is in fact a characteristic emergent property of a class of social networks. From a theoretical point of view, this finding implies that neutral theories of change deserve more (serious) consideration than they have traditionally received in diachronic and variationist linguistics. Methodologically, it urges that if change is to be successfully modelled, some of the traditional idealizing assumptions employed in much mathematical modelling must be done away with.
Politicizing the Pastoral: Taiwan's Homeland Performances
Authors: DIAMOND CATHERINE
Published: June 2016

Since the Sunflower Movement of 2014, when thousands of Taiwanese students protested against a trade deal the Nationalist government had made with China, the issue of Taiwan's sovereignty has again been brought to the political fore. Home to twenty-three million people, not only is Taiwan beset by threats from China and isolated by international organizations, but in its rapid push to industrialize it also has incurred severe environmental degradation. Two contemporary theatre troupes incorporated the Sunflower demonstration's ‘pro-Taiwanese homeland’ agenda into their works about the environment. Addressing both the pollution of the countryside and the demise of rural communities, they idealized pastoral life and emphasized Taiwan's roots in agrarian culture. Sun Son's Mulian Rescues Mother Earth imagined a perfectly organized small agricultural community trying to sustain its success, and San Que Yi's Earth Project portrayed two examples of rural communities engaged in David-and-Goliath struggles against industrial pollution.
THE MODAL PARTICLE IN GREEK
Authors: Colvin Stephen
Published: June 2016

Five forms of the modal particle are attested in ancient Greek (ἄν, κε, κεν, κᾱ, and κ’). This article argues that ἄν is an inherited particle, and that thek-forms were the result of reanalysis of prevocalic οὐκ and εἰκ (i.e. εἰκ was reanalysed as εἰ κ’), supported by the vestiges of an old topicalising/conditional force of the IE particle *kwe(which appears elsewhere in Greek as connective τε). The attested forms in Greek grew out of *kwein contexts where an adjacentucaused the labiovelar *kw>k(West Greek κᾱ was influenced by indefinite *kwā). The form κεν is a creation of epic diction.
Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales
Authors: Zaneveld Jesse R. , Burkepile Deron E. , Shantz Andrew A. , Pritchard Catharine E. , McMinds Ryan , Payet Jérôme P. , Welsh Rory , Correa Adrienne M. S. , Lemoine Nathan P. , Rosales Stephanie , Fuchs Corinne , Maynard Jeffrey A. , Thurber Rebecca Vega
Published: June 2016

Losses of corals worldwide emphasize the need to understand what drives reef decline. Stressors such as overfishing and nutrient pollution may reduce resilience of coral reefs by increasing coral–algal competition and reducing coral recruitment, growth and survivorship. Such effects may themselves develop via several mechanisms, including disruption of coral microbiomes. Here we report the results of a 3-year field experiment simulating overfishing and nutrient pollution. These stressors increase turf and macroalgal cover, destabilizing microbiomes, elevating putative pathogen loads, increasing disease more than twofold and increasing mortality up to eightfold. Above-average temperatures exacerbate these effects, further disrupting microbiomes of unhealthy corals and concentrating 80% of mortality in the warmest seasons. Surprisingly, nutrients also increase bacterial opportunism and mortality in corals bitten by parrotfish, turning normal trophic interactions deadly for corals. Thus, overfishing and nutrient pollution impact reefs down to microbial scales, killing corals by sensitizing them to predation, above-average temperatures and bacterial opportunism.
Spatializing 6,000 years of global urbanization from 3700 BC to AD 2000
Authors: Reba Meredith , Reitsma Femke , Seto Karen C.
Published: June 2016

How were cities distributed globally in the past? How many people lived in these cities? How did cities influence their local and regional environments? In order to understand the current era of urbanization, we must understand long-term historical urbanization trends and patterns. However, to date there is no comprehensive record of spatially explicit, historic, city-level population data at the global scale. Here, we developed the first spatially explicit dataset of urban settlements from 3700 BC to AD 2000, by digitizing, transcribing, and geocoding historical, archaeological, and census-based urban population data previously published in tabular form by Chandler and Modelski. The dataset creation process also required data cleaning and harmonization procedures to make the data internally consistent. Additionally, we created a reliability ranking for each geocoded location to assess the geographic uncertainty of each data point. The dataset provides the first spatially explicit archive of the location and size of urban populations over the last 6,000 years and can contribute to an improved understanding of contemporary and historical urbanization trends.
Broken selection rule in the quantum Rabi model
Authors: Forn-Díaz P. , Romero G. , Harmans C. J. P. M. , Solano E. , Mooij J. E.
Published: June 2016

Understanding the interaction between light and matter is very relevant for fundamental studies of quantum electrodynamics and for the development of quantum technologies. The quantum Rabi model captures the physics of a single atom interacting with a single photon at all regimes of coupling strength. We report the spectroscopic observation of a resonant transition that breaks a selection rule in the quantum Rabi model, implemented using an LC resonator and an artificial atom, a superconducting qubit. The eigenstates of the system consist of a superposition of bare qubit-resonator states with a relative sign. When the qubit-resonator coupling strength is negligible compared to their own frequencies, the matrix element between excited eigenstates of different sign is very small in presence of a resonator drive, establishing a sign-preserving selection rule. Here, our qubit-resonator system operates in the ultrastrong coupling regime, where the coupling strength is 10% of the resonator frequency, allowing sign-changing transitions to be activated and, therefore, detected. This work shows that sign-changing transitions are an unambiguous, distinctive signature of systems operating in the ultrastrong coupling regime of the quantum Rabi model. These results pave the way to further studies of sign-preserving selection rules in multiqubit and multiphoton models.
HDAC inhibition promotes both initial consolidation and reconsolidation of spatial memory in mice
Authors: Villain Hélène , Florian Cédrick , Roullet Pascal
Published: June 2016

Accumulating evidence suggests a critical role for epigenetic regulations in long term memory (LTM) formation. Among them, post-translational modifications of proteins, as histone acetylation, are an important regulator of chromatin remodelling and gene transcription. While the implication of histone acetylation in memory consolidation is widely accepted, less is known about its role in memory reconsolidation i.e. during memory restabilization after its reactivation. In the present study, we investigated the role of histone acetylation during the initial consolidation and the reconsolidation of spatial memory, using a weak massed learning procedure in the Morris water maze paradigm in mice. Usually a weak learning is sufficient for short term memory (STM) formation, but insufficient to upgrade STM to LTM. We found that promoting histone acetylation through intra-hippocampal infusion of a class I selective histone deacetylase (HDAC) inhibitor immediately after a subthreshold spatial learning improved LTM but not STM retention. More importantly, inhibiting HDAC activity after the reactivation of a weak memory promoted specifically LTM reconsolidation without affecting post-reactivation STM. These findings argue in favour of an important role for histone acetylation in memory consolidation, and more particularly during the reconsolidation of spatial memory in mice.
Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
Authors: Choi IL-Whan , Ahn Do Whan , Choi Jang-Kyu , Cha Hee-Jae , Ock Mee Sun , You EunAe , Rhee SangMyung , Kim Kwang Chul , Choi Yung Hyun , Song Kyoung Seob
Published: June 2016

Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, which depend on activator of G-protein signaling (AGS) 3 and to identify specific molecules that suppress CXCL12-induced airway inflammation by acting on G-protein-coupled receptors. Herein, AGS3 suppresses CXCL12-mediated upregulation of MUC1 and TNFα by regulating Gαi. We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to Gαi and downregulates MUC1 expression; in contrast, this motif upregulates TNFα expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGFβ but decreased the expression of TNFα and IL-6. Moreover, CXCR4-induced dendritic extensions in 2D and 3D matrix cultures were inhibited by the GPR Q34A peptide compared with a wild-type GPR peptide. The GPR Q34A peptide also inhibited CXCL12-induced morphological changes and inflammatory cell infiltration in the mouse lung, and production of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid and the lungs. Our data indicate that the GPR motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment.
A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing
Authors: Rout Bhimsen
Published: June 2016

The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore “temoporfin”, which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection.
Stenosis triggers spread of helical Pseudomonas biofilms in cylindrical flow systems
Authors: Espeso David R. , Carpio Ana , Martínez-García Esteban , de Lorenzo Victor
Published: June 2016

Biofilms are multicellular bacterial structures that adhere to surfaces and often endow the bacterial population with tolerance to antibiotics and other environmental insults. Biofilms frequently colonize the tubing of medical devices through mechanisms that are poorly understood. Here we studied the helicoidal spread of Pseudomonas putida biofilms through cylindrical conduits of varied diameters in slow laminar flow regimes. Numerical simulations of such flows reveal vortical motion at stenoses and junctions, which enhances bacterial adhesion and fosters formation of filamentous structures. Formation of long, downstream-flowing bacterial threads that stem from narrowings and connections was detected experimentally, as predicted by our model. Accumulation of bacterial biomass makes the resulting filaments undergo a helical instability. These incipient helices then coarsened until constrained by the tubing walls and spread along the whole tube length without obstructing the flow. A three-dimensional discrete filament model supports this coarsening mechanism and yields simulations of helix dynamics in accordance with our experimental observations. These findings describe an unanticipated mechanism for bacterial spreading in tubing networks which might be involved in some hospital-acquired infections and bacterial contamination of catheters.
Polymer Morphological Change Induced by Terahertz Irradiation
Authors: Hoshina Hiromichi , Suzuki Hal , Otani Chiko , Nagai Masaya , Kawase Keigo , Irizawa Akinori , Isoyama Goro
Published: June 2016

As terahertz (THz) frequencies correspond to those of the intermolecular vibrational modes in a polymer, intense THz wave irradiation affects the macromolecular polymorph, which determines the polymer properties and functions. THz photon energy is quite low compared to the covalent bond energy; therefore, conformational changes can be induced “softly,” without damaging the chemical structures. Here, we irradiate a poly(3-hydroxybutylate) (PHB) / chloroform solution during solvent casting crystallization using a THz wave generated by a free electron laser (FEL). Morphological observation shows the formation of micrometer-sized crystals in response to the THz wave irradiation. Further, a 10−20% increase in crystallinity is observed through analysis of the infrared (IR) absorption spectra. The peak power density of the irradiating THz wave is 40 MW/cm2, which is significantly lower than the typical laser intensities used for material manipulation. We demonstrate for the first time that the THz wave effectively induces the intermolecular rearrangement of polymer macromolecules.
Low molecular weight glutenin subunit gene Glu-B3h confers superior dough strength and breadmaking quality in wheat (Triticum aestivum L.)
Authors: Wang Yaping , Zhen Shoumin , Luo Nana , Han Caixia , Lu Xiaobing , Li Xiaohui , Xia Xianchun , He Zhonghu , Yan Yueming
Published: June 2016

Low molecular weight glutenin subunit is one of the important quality elements in wheat (Triticum aestivum L.). Although considerable allelic variation has been identified, the functional properties of individual alleles at Glu-3 loci are less studied. In this work, we performed the first comprehensive study on the molecular characteristics and functional properties of the Glu-B3h gene using the wheat cultivar CB037B and its Glu-B3 deletion line CB037C. The results showed that the Glu-B3h deletion had no significant effects on plant morphological or yield traits, but resulted in a clear reduction in protein body number and size and main quality parameters, including inferior mixing property, dough strength, loaf volume and score. Molecular characterization showed that the Glu-B3h gene consists of 1179 bp and its encoded B-subunit has a longer repetitive domain and an increased number of α-helices, as well as higher expression, which could contribute to superior flour quality. The SNP-based allele-specific PCR markers designed for the Glu-B3h gene were developed and validated with bread wheat holding various alleles at Glu-B3 locus, which could effectively distinguish the Glu-B3h gene from others at the Glu-B3 locus and have potential applications for wheat quality improvement through marker-assisted selection.
Experiments with Seasonal Forecasts of ocean conditions for the Northern region of the California Current upwelling system
Authors: Siedlecki Samantha A. , Kaplan Isaac C. , Hermann Albert J. , Nguyen Thanh Tam , Bond Nicholas A. , Newton Jan A. , Williams Gregory D. , Peterson William T. , Alin Simone R. , Feely Richard A.
Published: June 2016

Resource managers at the state, federal, and tribal levels make decisions on a weekly to quarterly basis, and fishers operate on a similar timeframe. To determine the potential of a support tool for these efforts, a seasonal forecast system is experimented with here. JISAO’s Seasonal Coastal Ocean Prediction of the Ecosystem (J-SCOPE) features dynamical downscaling of regional ocean conditions in Washington and Oregon waters using a combination of a high-resolution regional model with biogeochemistry and forecasts from NOAA’s Climate Forecast System (CFS). Model performance and predictability were examined for sea surface temperature (SST), bottom temperature, bottom oxygen, pH, and aragonite saturation state through model hindcasts, reforecast, and forecast comparisons with observations. Results indicate J-SCOPE forecasts have measurable skill on seasonal timescales. Experiments suggest that seasonal forecasting of ocean conditions important for fisheries is possible with the right combination of components. Those components include regional predictability on seasonal timescales of the physical environment from a large-scale model, a high-resolution regional model with biogeochemistry that simulates seasonal conditions in hindcasts, a relationship with local stakeholders, and a real-time observational network. Multiple efforts and approaches in different regions would advance knowledge to provide additional tools to fishers and other stakeholders.
The topology of large Open Connectome networks for the human brain
Authors: Gastner Michael T. , Ódor Géza
Published: June 2016

The structural human connectome (i.e. the network of fiber connections in the brain) can be analyzed at ever finer spatial resolution thanks to advances in neuroimaging. Here we analyze several large data sets for the human brain network made available by the Open Connectome Project. We apply statistical model selection to characterize the degree distributions of graphs containing up to "Equation missing"nodes and "Equation missing"edges. A three-parameter generalized Weibull (also known as a stretched exponential) distribution is a good fit to most of the observed degree distributions. For almost all networks, simple power laws cannot fit the data, but in some cases there is statistical support for power laws with an exponential cutoff. We also calculate the topological (graph) dimensionDand the small-world coefficient σ of these networks. While σ suggests a small-world topology, we found thatD < 4 showing that long-distance connections provide only a small correction to the topology of the embedding three-dimensional space.
Discrimination of Breast Cancer with Microcalcifications on Mammography by Deep Learning
Authors: Wang Jinhua , Yang Xi , Cai Hongmin , Tan Wanchang , Jin Cangzheng , Li Li
Published: June 2016

Microcalcification is an effective indicator of early breast cancer. To improve the diagnostic accuracy of microcalcifications, this study evaluates the performance of deep learning-based models on large datasets for its discrimination. A semi-automated segmentation method was used to characterize all microcalcifications. A discrimination classifier model was constructed to assess the accuracies of microcalcifications and breast masses, either in isolation or combination, for classifying breast lesions. Performances were compared to benchmark models. Our deep learning model achieved a discriminative accuracy of 87.3% if microcalcifications were characterized alone, compared to 85.8% with a support vector machine. The accuracies were 61.3% for both methods with masses alone and improved to 89.7% and 85.8% after the combined analysis with microcalcifications. Image segmentation with our deep learning model yielded 15, 26 and 41 features for the three scenarios, respectively. Overall, deep learning based on large datasets was superior to standard methods for the discrimination of microcalcifications. Accuracy was increased by adopting a combinatorial approach to detect microcalcifications and masses simultaneously. This may have clinical value for early detection and treatment of breast cancer.
Efficacy and Safety of Panobinostat in Relapsed or/and Refractory Multiple Myeloma: Meta Analyses of Clinical Trials and Systematic Review
Authors: Liu Jing-di , Sun Chun-yan , Tang Liang , Wu Ying-ying , Wang Qing-yun , Hu Bei , Hu Yu
Published: June 2016

During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31–0.59, I2 = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.
Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects
Authors: Liu Chen , Fu Xuekun , Pan Haobo , Wan Peng , Wang Lei , Tan Lili , Wang Kehong , Zhao Ying , Yang Ke , Chu Paul K.
Published: June 2016

A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications.
Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway
Authors: Jeong Ae Lee , Han Sora , Lee Sunyi , Su Park Jeong , Lu Yiling , Yu Shuangxing , Li Jane , Chun Kyung-Hee , Mills Gordon B. , Yang Young
Published: June 2016

Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo.
Summer diapause induced by high temperatures in the oriental tobacco budworm: ecological adaptation to hot summers
Authors: Liu Zhudong , Xin Yucui , Zhang Yanan , Fan Jianting , Sun Jianghua
Published: June 2016

Summer diapause in Helicoverpa assulta (Hübner), which prolongs the pupal stage, particularly in males, is induced by high temperatures. In the laboratory, 3rd-, 4th-, 6th-instar and prepupal larvae were exposed to high temperatures – 33 and 35 °C with a photoperiod of LD16:8 – until pupation to induce summer diapause. The results showed that the incidence of summer diapause was influenced by temperature, stage exposed and sex. The higher the temperature, the more often summer diapause was attained. Sixth-instar and prepupal larvae were the sensitive stages for summer diapause induction. H. assulta summer-diapausing pupae needed diapause development to resume development when temperatures became favorable. Furthermore, both body mass and energy storage capacity (lipid and glycogen) were significantly affected by diapause rather than sex and were significantly higher in summer-diapausing pupae than in non-diapausing pupae. In addition, the body mass loss and respiration rate showed that the rate of metabolism in the summer-diapausing pupae was consistently lower than in non-diapausing pupae, which were significantly affected by diapause and pupal age. We conclude that summer diapause in H. assulta is a true diapause and H. assulta has evolved mechanisms to accumulate energy storage and to lower its metabolism to adapt to hot summers.
Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes
Authors: Jacob Yael , Winetraub Yonatan , Raz Gal , Ben-Simon Eti , Okon-Singer Hadas , Rosenberg-Katz Keren , Hendler Talma , Ben-Jacob Eshel
Published: June 2016

Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network’s hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions.
Real-time device-scale imaging of conducting filament dynamics in resistive switching materials
Authors: Lee Keundong , Tchoe Youngbin , Yoon Hosang , Baek Hyeonjun , Chung Kunook , Lee Sangik , Yoon Chansoo , Park Bae Ho , Yi Gyu-Chul
Published: June 2016

ReRAM is a compelling candidate for next-generation non-volatile memory owing to its various advantages. However, fluctuation of operation parameters are critical weakness occurring failures in ‘reading’ and ‘writing’ operations. To enhance the stability, it is important to understand the mechanism of the devices. Although numerous studies have been conducted using AFM or TEM, the understanding of the device operation is still limited due to the destructive nature and/or limited imaging range of the previous methods. Here, we propose a new hybrid device composed of ReRAM and LED enabling us to monitor the conducting filament (CF) configuration on the device scale during resistive switching. We directly observe the change in CF configuration across the whole device area through light emission from our hybrid device. In contrast to former studies, we found that minor CFs were formed earlier than major CF contributing to the resistive switching. Moreover, we investigated the substitution of a stressed major CF with a fresh minor CF when large fluctuation of operation voltage appeared after more than 50 times of resistive switching in atmospheric condition. Our results present an advancement in the understanding of ReRAM operation mechanism, and a step toward stabilizing the fluctuations in ReRAM switching parameters.