bluuebunny/crossref_metadata_2025 huggingface dataset:
THE WAR ON POVERTY: MEASUREMENT, TRENDS, AND POLICY
Authors: Haveman Robert , Blank Rebecca , Moffitt Robert , Smeeding Timothy , Wallace Geoffrey
Published: May 2015

We present a 50‐year historical perspective of the nation's antipoverty efforts, describing the evolution of policy during four key periods since 1965. Over this half‐century, the initial heavy reliance on cash income support to poor families has eroded; increases in public support came largely in the form of in‐kind (e.g., Food Stamps) and tax‐related (e.g., the Earned Income Tax Credit) benefits. Work support and the supplementation of earnings substituted for direct support. These shifts eroded the safety net for the most disadvantaged in American society. Three poverty‐related analytical developments are also described. The rise of the Supplemental Poverty Measure (SPM)—taking account of noncash and tax‐related benefits—has corrected some of the serious weaknesses of the official poverty measure (OPM). The SPM measure indicates that the poverty rate has declined over time, rather than being essentially flat as the OPM implies. We also present snapshots of the composition of the poor population in the United States using both the OPM and the SPM, showing progress in reducing poverty overall and among specific socioeconomic subgroups since the beginning of the War on Poverty. Finally, we document the expenditure levels of numerous antipoverty programs that have accompanied the several phases of poverty policy and describe the effect of these efforts on the level of poverty. Although the effectiveness of government antipoverty transfers is debated, our findings indicate that the growth of antipoverty policies has reduced the overall level of poverty, with substantial reductions among the elderly, disabled, and blacks. However, the poverty rates for children, especially those living in single‐parent families, and families headed by a low‐skill, low‐education person, have increased. Rates of deep poverty (families living with less than one‐half of the poverty line) for the nonelderly population have not decreased, reflecting both the increasing labor market difficulties faced by the low‐skill population and the tilt of means‐tested benefits away from the poorest of the poor.
End of induction minimal residual disease alone is not a useful determinant for risk stratified therapy in pediatric T‐cell acute lymphoblastic leukemia
Authors: Parekh Chintan , Gaynon Paul S. , Abdel‐Azim Hisham
Published: May 2015

The role of end of induction minimal residual disease (MRD) as determined by flow cytometry for treatment assignment in pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) is not well defined. We studied 33 children with newly diagnosed T‐ALL. Thirty‐two of 33 patients remain in continuous complete remission at a median of 4 years. Nineteen patients were MRD positive at the end of induction and all remain in remission with augmented Berlin Frankfurt Münster‐based therapy. One patient underwent hematopoietic stem cell transplant for rising MRD. Persistent end of induction MRD alone is not an indication to alter therapy in pediatric T‐ALL. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
Effect of thermal aging on microstructures of aramid composites
Authors: Li Chang‐Sheng , Huang Xian‐Cong , Yan Li , Zhou Hong , Shen Zhihao , Fan Xing‐He
Published: May 2015

The effect of thermal aging on aramid composites was assessed in this study. Poly(vinyl butyral)/phenol formaldehyde (PVB/PF) resin was used to prepare the aramid composites, which were programmed at 70, 90, 120, and 150°C for various periods of time up to 2,688 h. The microstructures and aging mechanisms were investigated by dynamical mechanical thermal analysis, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Ballistic limited velocity of composites was determined by 1.1g Fragment projectiles. The results suggest that three microphases exist in the PVB/PF system. Each phase exhibits different aging mechanisms at different aging temperatures. Reduction of ballistic limited velocity was strongly affected by aging conditions. POLYM. COMPOS., 38:252–259, 2017. © 2015 Society of Plastics Engineers
Under the snow: a new camera trap opens the white box of subnivean ecology
Authors: Soininen Eeva M. , Jensvoll Ingrid , Killengreen Siw T. , Ims Rolf A.
Published: May 2015

Snow covers the ground over large parts of the world for a substantial portion of the year. Yet very few methods are available to quantify biotic variables below the snow, with most studies of subnivean ecological processes relying on comparisons of data before and after the snow cover season. We developed a camera trap prototype to quantify subnivean small mammal activity. The trap consists of a camera that is attached facing downward from the ceiling of a box, which is designed to function as a snow‐free tunnel. We tested it by placing nine traps with passive infrared sensors in a subarctic habitat where snow cover lasted for about 6 months. The traps were functional for the whole winter, permitting continuous data collection of site‐specific presence and temporal activity patterns of all three small mammal species present (the insectivorous common shrew, Sorex araneus, the herbivorous tundra vole, Microtus oeconomus, and the carnivorous stoat, Mustela erminea) as well as abiotic conditions (presence/absence of snow cover and subnivean temperature). Based on their successful functioning (only 6% of the photographs appeared empty or were of poor quality, whereas ca 80% were of small mammals and the remaining of birds and invertebrates), we discuss how the new camera trap can enable subnivean studies of small mammal communities. This greatly increases the temporal resolution and extent of data collection and thereby provides unpreceded opportunities to understand population and food web dynamics in ecosystems with snow cover.
A comparative study of adaptive dose‐finding designs for phase I oncology trials of combination therapies
Authors: Hirakawa Akihiro , Wages Nolan A. , Sato Hiroyuki , Matsui Shigeyuki
Published: May 2015

Little is known about the relative performance of competing model‐based dose‐finding methods for combination phase I trials. In this study, we focused on five model‐based dose‐finding methods that have been recently developed. We compared the recommendation rates for true maximum‐tolerated dose combinations (MTDCs) and over‐dose combinations among these methods under 16 scenarios for 3 × 3, 4 × 4, 2 × 4, and 3 × 5 dose combination matrices. We found that performance of the model‐based dose‐finding methods varied depending on (1) whether the dose combination matrix is square or not; (2) whether the true MTDCs exist within the same group along the diagonals of the dose combination matrix; and (3) the number of true MTDCs. We discuss the details of the operating characteristics and the advantages and disadvantages of the five methods compared. Copyright © 2015 John Wiley & Sons, Ltd.
Wax Ester Analysis of Bats Suffering from White Nose Syndrome in Europe
Authors: Řezanka Tomáš , Viden Ivan , Nováková Alena , Bandouchová Hana , Sigler Karel
Published: May 2015

The composition of wax esters (WE) in the fur of adult greater mouse–eared bats (Myotis myotis), either healthy or suffering from white nose syndrome (WNS) caused by the psychrophilic fungus Pseudogymnoascus destructans, was investigated by high‐resolution mass spectrometry analysis in the positive ion mode. Profiling of lipid classes showed that WE are the most abundant lipid class, followed by cholesterol esters, and other lipid classes, e.g., triacylglycerols and phospholipids. WE abundance in non‐polar lipids was gender‐related, being higher in males than in females; in individuals suffering from WNS, both male and female, it was higher than in healthy counterparts. WE were dominated by species containing 18:1 fatty acids. Fatty alcohols were fully saturated, dominated by species containing 24, 25, or 26 carbon atoms. Two WE species, 18:1/18:0 and 18:1/20:0, were more abundant in healthy bats than in infected ones.
The Mobilization of Supplier Resources for Complex Projects: A Case Study of Routines in the Offshore Wind Turbine Industry
Authors: Lutz Salla , Ellegaard Chris
Published: May 2015

Companies depend on supplier resources and boundary spanning managers need to find suppliers, and combine and coordinate resource bundles in exchange. But adequate and fitting resource flows are not automatic, as suppliers allocate and activate their resources for more customers in their portfolio. Therefore, buying companies also need to influence supplier actors to prioritize and optimize resource flows into their specific exchange. Based on a theoretical basis comprising the literature on buyer-seller relationship, including resource based research of the Industrial Marketing and Purchasing (IMP) group, as well as Dynamic Capabilities theory and the project management literature, this paper presents the results from a study of applied buying company resource mobilization routines. We report on a qualitative investigation of routines applied in complex construction projects in the North European offshore wind turbine industry. Complex construction/production projects are widespread global business phenomena, but knowledge of resource mobilization routines in this context is scarce in the literature. We find that the complex project owner (buying company) applies a series of 11 particular routines to mobilize resources for the wind turbine constructions and that several of these routines differ from the routines applied in conventional production exchanges.
Function of human WIPI proteins in autophagosomal rejuvenation of endomembranes?
Authors: Müller Amelie Johanna , Proikas-Cezanne Tassula
Published: May 2015

Despite the availability of a large pool of experimental approaches and hypothetical considerations, the hunt for the enigmatic membrane origin of autophagosomes is still on. In mammalian cells proposed scenarios for the formation of the autophagosomal membrane include both de novo assembly, and rearrangements plus maturation of pre‐existing membrane sections from the endoplasmic reticulum (ER), plasma membrane, Golgi or mitochondria. Earlier, we identified the human WD‐repeat protein interacting with phosphoinositides (WIPI) family and showed that WIPI proteins function as essential phosphatidylinositol 3‐phosphate (PtdIns3P) effectors at the nascent autophagosome. Interestingly, WIPI proteins localize to both pre‐existing endomembranes and nascent autophagosomes. In this context, and on the basis of historical records on the formation of autophagosomes, we discuss with appropriate modesty an alternative perspective on the membrane origin of autophagosomes.
Restraint‐based three‐dimensional modeling of genomes and genomic domains
Authors: Serra François , Di Stefano Marco , Spill Yannick G. , Cuartero Yasmina , Goodstadt Michael , Baù Davide , Marti-Renom Marc A.
Published: May 2015

Chromosomes are large polymer molecules composed of nucleotides. In some species, such as humans, this polymer can sum up to meters long and still be properly folded within the nuclear space of few microns in size. The exact mechanisms of how the meters long DNA is folded into the nucleus, as well as how the regulatory machinery can access it, is to a large extend still a mystery. However, and thanks to newly developed molecular, genomic and computational approaches based on the Chromosome Conformation Capture (3C) technology, we are now obtaining insight on how genomes are spatially organized. Here we review a new family of computational approaches that aim at using 3C‐based data to obtain spatial restraints for modeling genomes and genomic domains.
Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
Authors: Tian Weili , Li Wen , Chen Yinqin , Yan Zeming , Huang Xia , Zhuang Haixia , Zhong Wangtao , Chen Yusen , Wu Wenxian , Lin Chunxia , Chen Hao , Hou Xiaoyan , Zhang Liangqing , Sui Senfang , Zhao Bin , Hu Zhe , Li Longxuan , Feng Du
Published: May 2015

UNC‐51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found that hypoxia induces phosphorylation of ULK1 at Serine‐555 by Adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK). Unlike wild‐type ULK1, an ULK1 (S555A) mutant cannot translocate to mitochondria in response to hypoxia. Inhibition or knockdown of AMPK prevents ULK1 translocation and inhibits mitophagy. Finally, the phospho‐mimic ULK1 (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK‐knockdown cells. Thus, we conclude that AMPK‐dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress.
A case‐control study of correlates of severe acute maternal morbidity in Kabul, Afghanistan
Authors: Todd Catherine S. , Mansoor Ghulam Farooq , Haider Sadia , Hashimy Pashtoon , Mustafavi Nazifa , Nasir Abdul , Miller Suellen
Published: May 2015

Objective

To identify correlates of severe acute maternal morbidity (SAMM) in Kabul, Afghanistan.

Methods

The present case‐control study enrolled postpartum couples at four public maternity hospitals between September 2007 and December 2009. Eligibility was determined by: spousal consent; SAMM criteria from chart review for cases; and matching by age, parity, and time since previous delivery for controls (uncomplicated deliveries). Staff administered questionnaires to women and their husbands separately. SAMM correlates were analyzed with conditional logistic regression in models including (proximate) and excluding (distal) care factors.

Results

Among 285 case and 285 control couples, the most frequent SAMM diagnoses were obstructed labor (104 [36.5%]) and hemorrhage requiring transfusion (102 [35.8%]). In both models, SAMM was associated with the husband having more than one wife (distal: adjusted odds ratio [aOR] 48.6, 95% CI 5.4–436.5; proximate: 141.8, 3.5–5819.0), prior stillbirth(s) (distal: 16.2, 6.1–42.9; proximate: 8.0, 2.9–22.4), and complications in a prior pregnancy (distal: 5.4, 95% CI 2.5–12.1; proximate: 7.1, 2.5–20.4). In the proximate model, SAMM was associated with visiting another facility before hospitalization (aOR 7.5, 95% CI 3.1–17.9), male‐reported planned home delivery (5.5, 1.5–20.0), and provider‐determined care‐seeking (4.8, 1.6–14.9).

Conclusion

Planned home delivery and referral to multiple facilities or by providers are factors associated with SAMM that are potentially amenable to intervention in Afghanistan.
The Integrated Gateway Model: A catalytic approach to behavior change
Authors: Schwandt Hilary M. , Skinner Joanna , Takruri Adel , Storey Douglas
Published: May 2015

Objectives

To develop and test an Integrated Gateway Model of behaviors and factors leading to subsequent positive reproductive, maternal, and child health behaviors.

Methods

A secondary analysis was conducted using previously published household survey data collected from men (n = 5551; 2011) and women (n = 16 144; 2011) in Nigeria and women in Egypt (n = 2240; 2004–2007). The number of health behaviors each potential gateway behavior predicted was assessed by multivariate regression, adjusting for potential confounders. The influence of gateway factors on gateway behaviors was tested via interaction terms. Gateway behaviors and factors were ranked by the number of health outcomes predicted, both separately and synergistically.

Results

The key gateway behavior identified in both datasets was spousal communication about family planning, whereas the key gateway factor was exposure to family planning messages.

Conclusions

The model could facilitate innovative research and programming that in turn might promote cascades of positive behaviors in reproductive, maternal, and child health.
Usefulness of the wearable cardioverter defibrillator in patients in the early post‐myocardial infarction phase with high risk of sudden cardiac death: A single‐center European experience
Authors: Kondo Yusuke , Linhart Markus , Andrié René P. , Schwab Joerg O.
Published: May 2015

Background

The effectiveness of the wearable cardioverter defibrillator (WCD) therapy in early post‐myocardial infarction (MI) patients remains uncertain.

Methods

We analyzed the characteristics and outcomes of patients who received a WCD in the early post‐MI phase.

Results

Twenty‐four patients were followed‐up for 8 months (range, 4–16 months). Two patients (8.3%) received appropriate shocks. Left ventricular ejection fraction improved after the WCD therapy (P<0.01). Fourteen patients (58%) received an implantable cardioverter defibrillator at the end of the follow‐up period.

Conclusion

Early post‐MI patients at high risk of sudden cardiac death may benefit from WCD therapy.
On the derivation of the HOMFLYPT polynomial invariant for fluid knots
Authors: Liu Xin , Ricca Renzo L.
Published: May 2015

By using and extending earlier results (Liu & Ricca,J. Phys. A, vol. 45, 2012, 205501), we derive the skein relations of the HOMFLYPT polynomial for ideal fluid knots from helicity, thus providing a rigorous proof that the HOMFLYPT polynomial is a new, powerful invariant of topological fluid mechanics. Since this invariant is a two-variable polynomial, the skein relations are derived from two independent equations expressed in terms of writhe and twist contributions. Writhe is given by addition/subtraction of imaginary local paths, and twist by Dehn’s surgery. HOMFLYPT then becomes a function of knot topology and field strength. For illustration we derive explicit expressions for some elementary cases and apply these results to homogeneous vortex tangles. By examining some particular examples we show how numerical implementation of the HOMFLYPT polynomial can provide new insight into fluid-mechanical behaviour of real fluid flows.
Capillary bridges between a plane and a cylindrical wall
Authors: Reyssat Etienne
Published: May 2015

We report experimental, theoretical and numerical results on the shapes of liquid menisci connecting a planar boundary and the surface of a horizontal cylinder placed above. The gradient of confinement traps the wetting drops in the most confined regions, which promotes their elongation along the line of smallest gap between the walls. The experimental shapes of these stretched capillary bridges are shown to be in good quantitative agreement with the numerical solution of the equation describing their contour. In particular, we show that the measured shapes are better described when taking into account the correction resulting from the coupling of in-plane and transverse interfacial curvatures calculated by Park & Homsy (J. Fluid Mech., vol. 139, 1984, pp. 291–308) over thirty years ago.
Modelling turbulence generation in solitary waves on shear shallow water flows
Authors: Richard G. L. , Gavrilyuk S. L.
Published: May 2015

We derive a dispersive model of shear shallow water flows which takes into account a non-uniform horizontal velocity. This model generalizes the Green–Naghdi model to the case of shear flows. Besides the classical dispersion term in the Green–Naghdi model related to the acceleration of the free surface, it also contains a new dispersion parameter related to the flow structure. This parameter is related to the second moment of the velocity fluctuation with respect to the vertical coordinate. The distinction between shearing and turbulence based on the scale of variation of the velocity fluctuation is proposed. In particular, an equation for the turbulence generation is derived. Solitary waves for this model are obtained in explicit form. Comparison of solitary wave profiles with experimental ones is also performed. The agreement is very good apart from the small region near the top of the wave.
WHO AM I? WHO ARE YOU? WHO ARE WE? LAW, RELIGION, AND APPROACHES TO AN ETHIC OF MIGRATION
Authors: Allard Silas W.
Published: May 2015

In her essay “The Decline of the Nation-State and the End of the Rights of Man,” Hannah Arendt famously wrote, “Nobody had been aware that mankind, for so long a time considered under the image of a family of nations, had reached the state where whoever was thrown out of one of these tightly organized closed communities found himself thrown out of the family of nations altogether.” Surveying the aftermath of the world wars, the same aftermath that eventually led to the Universal Declaration of Human Rights, Arendt found that a person had to be emplaced—the subject of a political space—in the state-oriented order of geopolitics to be cognizable as a subject of human rights. The stateless, being displaced, were excluded from such a regime of rights and from the global political community. Bare humanity, Arendt argued, was an insufficiently binding political identity. As she wrote in her arresting language, “The world found nothing sacred in the abstract nakedness of being human.”
Phrenology, heredity and progress in George Combe'sConstitution of Man
Authors: JENKINS BILL
Published: May 2015

TheConstitution of Manby George Combe (1828) was probably the most influential phrenological work of the nineteenth century. It not only offered an exposition of the phrenological theory of the mind, but also presented Combe's vision of universal human progress through the inheritance of acquired mental attributes. In the decades before the publication of Darwin'sOrigin of Species, theConstitutionwas probably the single most important vehicle for the dissemination of naturalistic progressivism in the English-speaking world. Although there is a significant literature on the social and cultural context of phrenology, the role of heredity in Combe's thought has been less thoroughly explored, although both John van Wyhe and Victor L. Hilts have linked Combe's views on heredity with the transformist theories of Jean-Baptiste Lamarck. In this paper I examine the origin, nature and significance of his ideas and argue that Combe's hereditarianism was not directly related to Lamarckian transformism but formed part of a wider discourse on heredity in the early nineteenth century.
The Indian Machiavelli: Pragmatism versus morality, and the reception of theArthasastrain India, 1905–2014
Authors: MISRA MARIA
Published: May 2015

This article explores the ways in which theArthasastra(The Science of WealthorThe Science of Power), an ancient text rediscovered in 1905, was interpreted by Indian politicians and commentators. It seeks to explain why the text's popularity changed so drastically over time, and why, despite the excitement about it in the first 20 years following its reappearance, it was largely ignored in the Gandhian and Nehruvian eras, until a striking revival of interest from the late 1980s onwards. It argues that these changes in the text's fortunes can be explained partly as a result of significant shifts in elite Indian political culture. It also suggests that we need to reassess our analysis of the fundamental fault-lines in Indian politics, questioning Chatterjee's and Nandy's argument on the centrality of tensions between Gandhian ‘indigenous’ thought and Nehruvian ‘Western’ modernity, and arguing for the importance of the conflict between a moral politics, endorsed by both Gandhi and Nehru, and a ‘pragmatic’ politics justified by theArthasastra.
A Reappraisal of Iberian Copper Age Goldwork: Craftmanship, Symbolism and Art in a Non-funerary Gold Sheet from Valencina de la Concepción
Authors: Murillo-Barroso Mercedes , Eleazar Costa Caramé Manuel , Díaz-Guardamino Uribe Marta , García Sanjuán Leonardo , Mora Molina Coronada
Published: May 2015

Taking as a point of departure the in-depth analysis and description of an exceptional discovery, consisting of a large hammered gold sheet decorated with embossed motifs from the well-known Chalcolithic settlement of Valencina de la Concepción (Seville, Spain), this article presents a general appraisal of the social and ideological role of gold in Copper Age Iberia. The information available for this find, including both its context and its inherent characteristics, opens up new perspectives for research into the technology, use, sociology and symbolism of gold during this time period. We describe and analyse this unique item in detail, including the characterization of the raw material used and the manufacturing process (via SEM-BSE and LA-ICP-MS), as well as an extensive reconstruction of the graphic motifs that are represented, by using digital imaging processing techniques (RTI). We compare this find with the data currently available for the (approximately) 100 Chalcolithic golden artefacts (or fragments of artefacts) found in Iberia to date. Finally, we present an appraisal of the social and ideological framework in which gold was used in Copper Age Iberia, discussing its relevance in aspects such as the dynamics of social complexity, worldviews or artistic creations.
Rethinking the Structural Analysis of Palaeolithic Art: New Perspectives on Leroi-Gourhan's Structuralism
Authors: Moro Abadía Oscar , Palacio-Pérez Eduardo
Published: May 2015

André Leroi-Gourhan's work is usually considered a paradigmatic example of the application of structuralist ideas to the study of Palaeolithic art. The association between Leroi-Gourhan and structuralism is, however, problematic. Leroi-Gourhan explicitly distinguished his approach from that of Lévi-Strauss. Furthermore, he developed an explanatory model for the analysis of cave and portable art based on a number of postulates that were not necessarily connected to structuralism. We examine Leroi-Gourhan's understanding of Palaeolithic art in order to determine the influence of structuralism upon his work. This examination will help us to consider some alternative perspectives on the so-called structural analysis of Palaeolithic art. Moreover, Leroi-Gourhan's case will allow us to reflect on how archaeologists appropriate theory from other disciplines and how intellectual production in archaeology works.
Fibromuscular dysplasia of the coronary arteries: a rare cause of death in infants and young children
Authors: Mogler Carolin , Springer Wolfgang , Gorenflo Matthias
Published: May 2015

Fibromuscular dysplasia is a common vascular disease, which mainly affects the renal arteries. In this study, we report the case of a 1-day-old infant who presented with severe left ventricular dysfunction immediately after birth, and subsequently died 3 days postnatally. At autopsy, an extensive myocardial infarction of the left ventricle and the septum was found, caused by an isolated fibromuscular dysplasia of left coronary artery.
Knowing our ‘ABCs’: self-reflection using cognitive-behavioural formulation of client–therapist interaction in work with a survivor of torture
Authors: Martin Faith , Khan Sobia
Published: May 2015

Self-reflection can aid therapist development, particularly interpersonal skills. It can be achieved through using cognitive-behavioural therapy techniques, for example, formulations of the therapist's cognitions and behaviours have been used to aid self-reflection. As interpersonal skills may be an area that benefits from self-reflection, an approach to formulating the interaction between client and therapist may be beneficial. This study reports the use of simple ‘antecedent-belief-consequence’ (ABC) formulations for the client and therapist to conceptualize their interaction. This description of a treatment failure focuses on cross-cultural work with a survivor of torture, where self-reflection may be particularly indicated to promote cultural competence and address the impact of the content on the therapist. ABC formulations for the client and therapist were completed and through this structured self-reflection, the therapist was able to identify the impact of her own beliefs on the process of therapy. This method identified areas for further development and generated hypotheses for how to continue therapy with this client. Using ABC formulations then may provide a useful and structured way to conduct self-reflection with explicit focus on the interaction between client and therapist.
Protecting Earth from Solar Storms
Authors: Wendel JoAnna
Published: May 2015

A task force on space weather recently released a national strategy to reduce damage resulting from solar storms. The plan is now open for public comment.
RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells
Authors: Yang Y , Xu H , Shen J , Yang Y , Wu S , Xiao J , Xu Y , Liu X-Y , Chu L
Published: May 2015

Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (OncoAd.RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. OncoAd.RGD-hTERT-EGFP had enhanced infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but little cytoxicity on normal urothelial SV-HUC-1 cells compared with the unmodified virus OncoAd.hTERT-EGFP. Notably, OncoAd.RGD-hTERT-TRAIL induced apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited xenograft initiation established by the oncolytic adenovirus-pretreated T24 sphere cells, and significantly suppressed tumor growth by intratumoral injection. These results provided a promising therapeutic strategy for CAR-negative bladder cancer through targeting CICs.
Exploring the quantum critical behaviour in a driven Tavis–Cummings circuit
Authors: Feng M. , Zhong Y.P. , Liu T. , Yan L.L. , Yang W.L. , Twamley J. , Wang H.
Published: May 2015

Quantum phase transitions play an important role in many-body systems and have been a research focus in conventional condensed-matter physics over the past few decades. Artificial atoms, such as superconducting qubits that can be individually manipulated, provide a new paradigm of realising and exploring quantum phase transitions by engineering an on-chip quantum simulator. Here we demonstrate experimentally the quantum critical behaviour in a highly controllable superconducting circuit, consisting of four qubits coupled to a common resonator mode. By off-resonantly driving the system to renormalize the critical spin-field coupling strength, we have observed a four-qubit nonequilibrium quantum phase transition in a dynamical manner; that is, we sweep the critical coupling strength over time and monitor the four-qubit scaled moments for a signature of a structural change of the system’s eigenstates. Our observation of the nonequilibrium quantum phase transition, which is in good agreement with the driven Tavis–Cummings theory under decoherence, offers new experimental approaches towards exploring quantum phase transition-related science, such as scaling behaviours, parity breaking and long-range quantum correlations.
Exotic topological density waves in cold atomic Rydberg-dressed fermions
Authors: Li Xiaopeng , Sarma S Das
Published: May 2015

Versatile controllability of interactions in ultracold atomic and molecular gases has now reached an era where quantum correlations and unconventional many-body phases can be studied with no corresponding analogues in solid-state systems. Recent experiments in Rydberg atomic gases have achieved exquisite control over non-local interactions, allowing novel quantum phases unreachable with the usual local interactions in atomic systems. Here we study Rydberg-dressed atomic fermions in a three-dimensional optical lattice predicting the existence of hitherto unheard-of exotic mixed topological density wave phases. By varying the spatial range of the non-local interaction, we find various chiral density waves with spontaneous time-reversal symmetry breaking, whose quasiparticles form three-dimensional quantum Hall and Weyl semimetal states. Remarkably, certain density waves even exhibit mixed topologies beyond the existing topological classification. Our results suggest gapless fermionic states could exhibit far richer topology than previously expected.
Microbe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes
Authors: Hampton Henry R. , Bailey Jacqueline , Tomura Michio , Brink Robert , Chtanova Tatyana
Published: May 2015

Neutrophil recruitment to the site of injury is an essential first step of an anti-bacterial response. However, little is known about the basis for and relevance of neutrophil migration from inflamed tissue into lymphoid organs. We established a photoconversion-based system to monitor the fate of neutrophils recruited to inflamed skin. While neutrophils are efficiently recruited to sites of both microbial and sterile lesions, subsequent re-localization to draining lymph nodes happens only when bacteria are present in the primary lesion. Skin egress of neutrophils occurs via lymphatic vessels and is dependent on CD11b and CXCR4 but not CCR7. Neutrophils are the predominant immune cell to migrate from inflamed skin into lymph nodes where they augment lymphocyte proliferation. Furthermore, inhibition of neutrophil migration from skin reduces T-cell proliferation in draining lymph nodes. Thus neutrophils mediate rapid cellular communication between the initial injury site and secondary lymphoid organs and modulate immune responsiveness.
Long-term decline in grassland productivity driven by increasing dryness
Authors: Brookshire E. N. J. , Weaver T.
Published: May 2015

Increasing aridity and drought severity forecast for many land areas could reduce the land carbon (C) sink. However, with limited long-term direct measures, it is difficult to distinguish direct drying effects from counter effects of CO2 enrichment and nitrogen (N) deposition. Here, we document a >50% decline in production of a native C3 grassland over four decades and assign the forcing and timing to increasing aridity and specifically to declining late-summer rainfall. Analysis of C and N stable isotopes in biomass suggests that enhanced water use efficiency via CO2 enrichment may have slightly ameliorated the productivity decline but that changes in N had no effects. Identical declines in a long-term snow-addition experiment definitively identified increasing late-summer dryness as the cause. Our results demonstrate lasting consequences of recent climate change on grassland production and underscore the importance of understanding past climate–ecosystem coupling to predicting future responses to changing climate.
Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier
Authors: Gouyer Valérie , Dubuquoy Laurent , Robbe-Masselot Catherine , Neut Christel , Singer Elisabeth , Plet Ségolène , Geboes Karel , Desreumaux Pierre , Gottrand Frédéric , Desseyn Jean-Luc
Published: May 2015

A weakening of the gut mucous barrier permits an increase in the access of intestinal luminal contents to the epithelial cells, which will trigger the inflammatory response. In inflammatory bowel diseases, there is an inappropriate and ongoing activation of the immune system, possibly because the intestinal mucus is less protective against the endogenous microflora. General strategies aimed at improving the protection of the intestinal epithelium are still missing. We generated a transgenic mouse that secreted a molecule consisting of 12 consecutive copies of a mucin domain into its intestinal mucus, which is believed to modify the mucus layer by establishing reversible interactions. We showed that the mucus gel was more robust and that mucin O-glycosylation was altered. Notably, the gut epithelium of transgenic mice housed a greater abundance of beneficial Lactobacillus spp. These modifications were associated with a reduced susceptibility of transgenic mice to chemically induced colitis. Furthermore, transgenic mice cleared faster Citrobacter rodentium bacteria which were orally given and mice were more protected against bacterial translocation induced by gavage with adherent–invasive Escherichia coli. Our data show that delivering the mucin CYS domain into the gut lumen strengthens the intestinal mucus blanket which is impaired in inflammatory bowel diseases.
Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS
Authors: Momen-Heravi Fatemeh , Bala Shashi , Kodys Karen , Szabo Gyongyi
Published: May 2015

Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes derived from ethanol-treated Huh7.5 cells were taken up by the recipients THP1 monocytes and horizontally transferred a mature form of liver-specific miRNA-122. In vivo, liver mononuclear cells and Kupffer cells from alcohol-fed mice had increased miRNA-122 levels. In monocytes, miRNA-122 transferred via exosomes inhibited the HO-1 pathway and sensitized to LPS stimulation and increased levels of pro-inflammatory cytokines. Finally, inflammatory effects of exosomes from ethanol-treated hepatocytes were prevented by using RNA interference via exosome-mediated delivery of a miRNA-122 inhibitor. These results demonstrate that first, exosomes mediate communication between hepatocytes and monocytes/macrophages and second, hepatocyte-derived miRNA-122 can reprogram monocytes inducing sensitization to LPS.
Rational design of metallic nanocavities for resonantly enhanced four-wave mixing
Authors: Almeida Euclides , Prior Yehiam
Published: May 2015

Optimizing the shape of nanostructures and nano-antennas for specific optical properties has evolved to be a very fruitful activity. With modern fabrication tools a large variety of possibilities is available for shaping both nanoparticles and nanocavities; in particular nanocavities in thin metal films have emerged as attractive candidates for new metamaterials and strong linear and nonlinear optical systems. Here we rationally design metallic nanocavities to boost their Four-Wave Mixing response by resonating the optical plasmonic resonances with the incoming and generated beams. The linear and nonlinear optical responses as well as the propagation of the electric fields inside the cavities are derived from the solution of Maxwell’s equations by using the 3D finite-differences time domain method. The observed conversion-efficiency of near-infrared to visible light equals or surpasses that of BBO of equivalent thickness. Implications to further optimization for efficient and broadband ultrathin nonlinear optical materials are discussed.
Multiscale Modeling of Drug-induced Effects of ReDuNing Injection on Human Disease: From Drug Molecules to Clinical Symptoms of Disease
Authors: Luo Fang , Gu Jiangyong , Zhang Xinzhuang , Chen Lirong , Cao Liang , Li Na , Wang Zhenzhong , Xiao Wei , Xu Xiaojie
Published: May 2015

ReDuNing injection (RDN) is a patented traditional Chinese medicine and the components of it were proven to have antiviral and important anti-inflammatory activities. Several reports showed that RDN had potential effects in the treatment of influenza and pneumonia. Though there were several experimental reports about RDN, the experimental results were not enough and complete due to that it was difficult to predict and verify the effect of RDN for a large number of human diseases. Here we employed multiscale model by integrating molecular docking, network pharmacology and the clinical symptoms information of diseases and explored the interaction mechanism of RDN on human diseases. Meanwhile, we analyzed the relation among the drug molecules, target proteins, biological pathways, human diseases and the clinical symptoms about it. Then we predicted potential active ingredients of RDN, the potential target proteins, the key pathways and related diseases. These attempts may offer several new insights to understand the pharmacological properties of RDN and provide benefit for its new clinical applications and research.
An Integrated Metagenomics/Metaproteomics Investigation of the Microbial Communities and Enzymes in Solid-state Fermentation of Pu-erh tea
Authors: Zhao Ming , Zhang Dong-lian , Su Xiao-qin , Duan Shuang-mei , Wan Jin-qiong , Yuan Wen-xia , Liu Ben-ying , Ma Yan , Pan Ying-hong
Published: May 2015

Microbial enzymes during solid-state fermentation (SSF), which play important roles in the food, chemical, pharmaceutical and environmental fields, remain relatively unknown. In this work, the microbial communities and enzymes in SSF of Pu-erh tea, a well-known traditional Chinese tea, were investigated by integrated metagenomics/metaproteomics approach. The dominant bacteria and fungi were identified as Proteobacteria (48.42%) and Aspergillus (94.98%), through pyrosequencing-based analyses of the bacterial 16S and fungal 18S rRNA genes, respectively. In total, 335 proteins with at least two unique peptides were identified and classified into 28 Biological Processes and 35 Molecular Function categories using a metaproteomics analysis. The integration of metagenomics and metaproteomics data demonstrated that Aspergillus was dominant fungus and major host of identified proteins (50.45%). Enzymes involved in the degradation of the plant cell wall were identified and associated with the soft-rotting of tea leaves. Peroxiredoxins, catalase and peroxidases were associated with the oxidation of catechins. In conclusion, this work greatly advances our understanding of the SSF of Pu-erh tea and provides a powerful tool for studying SSF mechanisms, especially in relation to the microbial communities present.
A new gender-specific model for skin autofluorescence risk stratification
Authors: Ahmad Muhammad S. , Damanhouri Zoheir A. , Kimhofer Torben , Mosli Hala H. , Holmes Elaine
Published: May 2015

Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79–4.84 AU) and 2.20 AU (0.75–4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis.
Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice
Authors: Zhao Lei , Zhong Shan , Qu Haiyang , Xie Yunxia , Cao Zhennan , Li Qing , Yang Ping , Varghese Zac , Moorhead John F. , Chen Yaxi , Ruan Xiong Z.
Published: May 2015

The prevalence of nonalcoholic fatty liver disease (NAFLD) increases with increasing body mass index (BMI). However, approximately 40–50% of obese adults do not develop hepatic steatosis. The level of inflammatory biomarkers is higher in obese subjects with NAFLD compared to BMI-matched subjects without hepatic steatosis. We used a casein injection in high-fat diet (HFD)-fed C57BL/6J mice to induce inflammatory stress. Although mice on a HFD exhibited apparent phenotypes of obesity and hyperlipidemia regardless of exposure to casein injection, only the HFD+Casein mice showed increased hepatic vacuolar degeneration accompanied with elevated inflammatory cytokines in the liver and serum, compared to mice on a normal chow diet. The expression of genes related to hepatic fatty acid synthesis and oxidation were upregulated in the HFD-only mice. The casein injection further increased baseline levels of lipogenic genes and decreased the levels of oxidative genes in HFD-only mice. Inflammatory stress induced both oxidative stress and endoplasmic reticulum stress in HFD-fed mice livers. We conclude that chronic inflammation precedes hepatic steatosis by disrupting the balance between fatty acid synthesis and oxidation in the livers of HFD-fed obese mice. This mechanism may operate in obese individuals with chronic inflammation, thus making them more prone to NAFLD.
Lung microbiota across age and disease stage in cystic fibrosis
Authors: Coburn Bryan , Wang Pauline W. , Diaz Caballero Julio , Clark Shawn T. , Brahma Vijaya , Donaldson Sylva , Zhang Yu , Surendra Anu , Gong Yunchen , Elizabeth Tullis D. , Yau Yvonne C. W. , Waters Valerie J. , Hwang David M. , Guttman David S.
Published: May 2015

Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4–17 and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function.