bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of remnant forest patches for habitat restoration in degraded areas of Palau
Authors: Dendy Julian , Cordell Susan , Giardina Christian P. , Hwang Bernice , Polloi Edwin , Rengulbai Kashgar
Published: September 2015

To be successful, prescriptions for tropical forest restoration should facilitate natural recovery while also being easy to implement and inexpensive. In the Lake Ngardok Nature Reserve, Palau, we monitored native forest patches (4–275 m2) over 3 years to assess the influence of several low‐cost restoration methods on patch expansion, growth of naturally established tree saplings, density of naturally establishing tree seedlings, growth of planted tree seedlings, flower and fruit production, and bird and flying fox visitations. Treatments included fertilization, trimming of surrounding herbaceous vegetation, mulching of patch perimeters, and planting native tree seedlings. Fertilized patches expanded faster and were associated with higher growth rates of perimeter saplings, higher fruit and flower production and growth of adjacent planted Acacia auriculiformis trees. Trimming perimeter vegetation led to higher tree seedling densities and species diversity, but both trimming and fertilizer effects on patch perimeter measures decreased over time. Pterocarpus indicus, a high value native legume, was the fastest growing planted tree species. The most common visitors were small, omnivorous, predominately endemic bird species. Visitations to fertilized patches were more frequent than to non‐fertilized patches. The strongest predictors of visitation frequency were patch area, mean number of total fruits, and mean height of nearest neighboring trees. We conclude that forest succession can be accelerated by applying small amounts of fertilizer (approximately 22.5 g/m2 per application) to enhance tree growth and increase visitation rates of native pollinators and dispersers.
Investigation of Residual Stress in 2D Plane Weave Aramid Fibre Composite Plates Using Moiré Interferometry and Hole‐Drilling Technique
Authors: Wu L. F. , Zhu J. G. , Xie H. M.
Published: September 2015

Residual stress (RS) is crucial to the fabrications of woven composite plates and difficult to measure experimentally because of the complex structures of these plates. This study aims to investigate the RS in 2D plane weave aramid fiber composite plates using hole‐drilling technique coupled with moiré interferometry. A two‐step drilling method is proposed to solve the problems caused by the ‘peel up’ phenomenon, which facilitates the analyses of the obtained moiré patterns. The holes are deliberately selected at the intersection points of the symmetry axes of warp and weft yarns to obtain symmetrically released displacement fields. Moreover, finite element method calibration is conducted to measure RS using a model created based on the real structure of the woven composite. Based on the error analysis in numerical simulations, the less sensitive points are proposed for the RS calculation. The results show that the RS components of each specimen are compressive along the aramid yarns and tensile perpendicular to them. In addition, investigating of the influence of drilling depths on RS shows that RS decreases along the hole‐depth direction. Findings of this study are helpful for the manufacture and quality evaluation of woven aramid fibre composites.
Human neutrophil antigen‐3a antibodies induce neutrophil stiffening and conformational activation of CD11b without shedding of L‐selectin
Authors: Berthold Tom , Glaubitz Michael , Muschter Stefan , Groß Stefan , Palankar Raghavendra , Reil Angelika , Helm Christiane A. , Bakchoul Tamam , Schwertz Hansjörg , Bux Jürgen , Greinacher Andreas , Delcea Mihaela
Published: September 2015

BACKGROUND

HNA‐3a antibodies induce severe transfusion‐related acute lung injury (TRALI) in which neutrophils play a major role. As neutrophil passage through the pulmonary microvasculature is a critical step in the pathogenesis of TRALI, we investigated the impact of HNA‐3a antibodies on two important factors that could impair granulocyte passage through lung capillaries: the elasticity of neutrophils and the expression and activation of adhesion molecules.

STUDY DESIGN AND METHODS

The impact of HNA‐3a antibodies on the elasticity of neutrophils was investigated using atomic force microscopy (AFM). Neutrophils were settled on poly‐2‐hydroxyethyl‐methacrylate–coated glass slides before treatment with anti‐HNA‐3a plasma samples, control plasma, or control plasma containing formyl‐methionyl‐leucyl‐phenylalanine (fMLP). Elasticity measurements were carried out in a temperature‐controlled perfusion chamber using an atomic force microscopy (AFM) device. The impact of HNA‐3a antibodies on the surface expression of total CD11b, activation of CD11b, and L‐selectin (CD62L) shedding was investigated by flow cytometry. The functional impact of HNA‐3a antibodies on neutrophil adhesion was assessed using fibrinogen‐coated plates.

RESULTS

HNA‐3a antibodies induced stiffening of neutrophils (+24%‐40%; p < 0.05) to a similar extent as fMLP. This effect was blocked by treatment of neutrophils with cytochalasin D. While total surface expression of CD11b and L‐selectin on neutrophils was largely unaffected, HNA‐3a antibodies induced alloantigen‐specific activation of CD11b (+72%‐107%; p < 0.05) and increased adhesion of neutrophils to fibrinogen.

CONCLUSION

Accumulation of neutrophils in the pulmonary microvasculature during severe TRALI is likely mediated by increased rigidity and CD11b‐mediated adhesion of neutrophils leading to retention of neutrophils.
Erythrocytapheresis versus phlebotomy in the maintenance treatment of HFE hemochromatosis patients: results from a randomized crossover trial
Authors: Rombout‐Sestrienkova Eva , Winkens Bjorn , Essers Brigitte A.B. , Nieman Fred H.M. , Noord Paulus A.H. , Janssen Mirian C.H. , van Deursen Cees Th.B.M. , Boonen Annelies , Reuser‐Kaasenbrood Ellen P.J.M. , Heeremans Judith , van Kraaij Marian , Masclee Ad , Koek Ger H.
Published: September 2015

BACKGROUND

Phlebotomy is standard maintenance treatment of patients with hereditary hemochromatosis (HH). Erythrocytapheresis, which selectively removes red blood cells, provides a new, potentially more effective treatment option. Our aim was to evaluate the effectiveness of erythrocytapheresis over phlebotomy for maintenance therapy in patients with HH.

STUDY DESIGN AND METHODS

We conducted a two‐treatment‐arms, randomized, crossover clinical trial, involving 46 patients, treated for 1 year with either erythrocytapheresis or phlebotomy to keep the ferritin level at not more than 50 µg/L. After 1 year, patients were switched to the other treatment modality. Primary endpoint was the number of treatment procedures per treatment year. Secondary endpoints were intertreatment intervals, several aspects of health‐related quality of life, costs, and patient discomfort as well as preference for one of both treatments.

RESULTS

The mean number of required treatment procedures per treatment year was significantly higher using phlebotomy versus erythrocytapheresis (3.3 vs. 1.9; mean difference, 1.4; 95% confidence interval, 1.1‐1.7). The median intertreatment time was 2.3 times longer for erythrocytapheresis. There was no significant difference in overall health assessed by SF‐36 and EQ‐5D, respectively, between both treatments arms. The number of self‐reported swollen joints was significantly higher during phlebotomy treatment. The mean treatment costs of one treatment year were 235€ for phlebotomy versus 511€ for erythrocytapheresis. Eighty percent of patients preferred erythrocytapheresis as treatment method.

CONCLUSION

Erythrocytapheresis significantly reduced the number of treatment procedures per treatment year, although the mean treatment costs per year are higher in our health care system. It is the preferred treatment for the majority of patients.
Tissue physical property of the harbor porpoise Phocoena phocoena for investigation of the sound emission process
Authors: Kuroda Mika , Sasaki Motoki , Yamada Kazutaka , Miki Nobuhiro , Matsuishi Takashi
Published: September 2015

The process by which sound is propagated in the head of a toothed whale is still a subject of discussion. Investigating the distribution of acoustic impedance calculated by density and Young's modulus is effective for quantitative comprehension because acoustic impedance determines the reflection coefficient of a sound wave. However, the sound propagation process of the toothed whale has been mainly examined by either anatomical techniques or the measurement of density or sound velocity. In the current study, the acoustic impedance of head tissue of harbor porpoise was measured. Results of this study should be a helpful information for further discussion about the relationship between the structure of sound-producing organ and clicks property.
Subwavelength acoustic metamaterial panels for underwater noise isolation
Authors: Hicks Ashley J. , Haberman Michael R. , Wilson Preston S.
Published: September 2015

Acoustically thin metamaterial underwater noise isolation panels have been developed that provide as much as 16 dB of noise isolation for a panel with a thickness just 160th of the wavelength in the host medium (fresh water) at 2.5 kHz. The panels are composed of thin layers of neoprene rubber and polyoxymethylene containing air-filled voids. The level of isolation provided by the panels is shown to correlate positively with the volume fraction of air voids within the panel.
Distinct effects of moisture and air contents on acoustic properties of sandy soil
Authors: Oshima Takuya , Hiraguri Yasuhiro , Okuzono Takeshi
Published: September 2015

Knowledge of distinct effects of moisture content and air volume on acoustic properties of soil is sought to predict the influence of human activities such as cultivation on acoustic propagation outdoors. This work used an impedance tube with the two-thickness method to investigate such effects. For a constant moisture weight percentage, the magnitude of the characteristic impedance became smaller and the absorption coefficient became higher with increase of the air space ratio. For a constant air space ratio, the absorption coefficient became larger and the magnitude of the propagation constant became smaller with increasing moisture weight percentage.
Improvement of Repeated-Sprint Ability and Horizontal-Jumping Performance in Elite Young Basketball Players With Low-Volume Repeated-Maximal-Power Training
Authors: Gonzalo-Skok Oliver , Tous-Fajardo Julio , Arjol-Serrano José Luis , Suarez-Arrones Luis , Casajús José Antonio , Mendez-Villanueva Alberto
Published: September 2015

Purpose:

To examine the effects of a low-volume repeated-power-ability (RPA) training program on repeated-sprint and changeof-direction (COD) ability and functional jumping performance.

Methods:

Twenty-two male elite young basketball players (age 16.2 ± 1.2 y, height 190.0 ± 10.0 cm, body mass 82.9 ± 10.1 kg) were randomly assigned either to an RPA-training group (n = 11) or a control group (n = 11). RPA training consisted of leg-press exercise, twice a week for 6 wk, of 1 or 2 blocks of 5 sets × 5 repetitions with 20 s of passive recovery between sets and 3 min between blocks with the load that maximized power output. Before and after training, performance was assessed by a repeated-sprint-ability (RSA) test, a repeated-COD-ability test, a hop for distance, and a drop jump followed by tests of a double unilateral hop with the right and left legs.

Results:

Within-group and between-groups differences showed substantial improvements in slowest (RSAs) and mean time (RSAm) on RSA; best, slowest and mean time on repeated-COD ability; and unilateral right and left hop in the RPA group in comparison with control. While best time on RSA showed no improvement in any group, there was a large relationship (r = .68, 90% CI .43;.84) between the relative decrement in RSAm and RSAs, suggesting better sprint maintenance with RPA training. The relative improvements in best and mean repeated-COD ability were very largely correlated (r = .89, 90% CI .77;.94).

Conclusions:

Six weeks of low-volume (4–14 min/wk) RPA training improved several physical-fitness tests in basketball players.
Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch
Authors: Dehorter Nathalie , Ciceri Gabriele , Bartolini Giorgia , Lim Lynette , del Pino Isabel , Marín Oscar
Published: September 2015

Changing properties of interneurons

Neuronal identity is determined early during development. It is assumed that once a neuron has adopted its identity, this remains stable throughout life. However, Dehorter
et al.
investigated the mechanisms controlling the specification of fast-spiking interneurons. They found that the transcription factor Er81 is crucial for the normal specification of these cells by regulating the expression of a potassium channel subunit.

Science
, this issue p.
1216
Rethinking heritability of the microbiome
Authors: Opstal Edward J. van , Bordenstein Seth R.
Published: September 2015

How should microbiome heritability be measured and interpreted?
Draft Genome Sequence of Veillonella tobetsuensis ATCC BAA-2400
T
Isolated from Human Tongue Biofilm
Authors: Mashima Izumi , Nakazawa Futoshi
Published: September 2015

Here, we report the draft genome sequence of
Veillonella tobetsuensis
ATCC-BAA 2400
T
. This bacterium has the remarkable ability to form oral biofilms. The genome is predicted to encode the necessary enzymes involved in the pathway that facilitates the conversion of lactate to propionate.
Draft Genome Sequence of Brevibacillus brevis DZQ7, a Plant Growth-Promoting Rhizobacterium with Broad-Spectrum Antimicrobial Activity
Authors: Hou Qihui , Wang Chengqiang , Hou Xiaoyang , Xia Zhilin , Ye Jiangping , Liu Kai , Liu Hu , Wang Jun , Guo Haimeng , Yu Xiaoning , Yang Yanan , Du Binghai , Ding Yanqin
Published: September 2015

Brevibacillus brevis
DZQ7 is a plant growth-promoting rhizobacterium (PGPR) isolated from tobacco rhizosphere. Here, we report the draft genome sequence of
B. brevis
DZQ7. Several functional genes related to antimicrobial activity were identified in the genome.
Complete Genome Sequence of Acinetobacter baumannii Strain B8342, a Motility-Positive Clinical Isolate
Authors: Vijaykumar Saranya , Balaji Veeraraghavan , Biswas Indranil
Published: September 2015

Acinetobacter baumannii
is an emerging Gram-negative pathogen responsible for health care–associated infections. In this study, we determined the genome of a motility-positive clinical strain, B8342, isolated from a hospital in southern India. The B8342 genome, which is 3.94 Mbp, was generated by
de novo
assembly of PacBio long-read sequencing data.
Genome Sequences of Klebsiella variicola Isolates from Dairy Animals with Bovine Mastitis from Newfoundland, Canada
Authors: Davidson Fraser W. , Whitney Hugh G. , Tahlan Kapil
Published: September 2015

Klebsiella variicola
was recently reported as an emerging and/or previously misidentified species associated with opportunistic infections in humans. Here, we report the draft genome sequences of
K. variicola
isolates from two animals with clinical mastitis from a dairy farm in Newfoundland, Canada.
Complete Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype A Isolated from Vietnam in 2013
Authors: Hwang Ji-Hyeon , Nguyen Tho Dang , Mai Duoung Thuy , Kim Su-Mi , Park Jong-Hyeon , Kim Byounghan , To Thanh Long , Lee Kwang-Nyeong
Published: September 2015

The complete genome sequence of a foot-and-mouth disease virus (FMDV) found in an isolate collected in northern Vietnam in 2013 appears to be closely related to a genetic cluster formed with isolates from China, Mongolia, and Russia in 2013. All of these are classified to fall within the Sea-97 lineage, for which little complete genome data are available.
Complete Genome Sequence of the Type Strain Corynebacterium epidermidicanis DSM 45586, Isolated from the Skin of a Dog Suffering from Pruritus
Authors: Rückert Christian , Eimer Janine , Winkler Anika , Tauch Andreas
Published: September 2015

The complete genome sequence of
Corynebacterium epidermidicanis
DSM 45586 comprises 2,692,072 bp with 58.06% G+C content. The annotation revealed 2,466 protein-coding regions, including genes for surface-anchored proteins with Cna B-type or bacterial Ig-like domains and for an adhesive SpaABC-type pilus with similarity to fimbrial subunits of
Corynebacterium resistens
DSM 45100.
Genome Sequences of Two Multidrug-Resistant Acinetobacter baumannii Clinical Strains Isolated from Southern India
Authors: Balaji Veeraraghavan , Rajenderan Sangeetha , Anandan Shalini , Biswas Indranil
Published: September 2015

Acinetobacter baumannii
is an emerging nosocomial pathogen causing infections worldwide. In this study, we determined the genome sequences of two multidrug-resistant
A. baumannii
clinical strains isolated from a hospital in southern India. Genome analyses indicate that both the strains harbor numerous horizontally transferred genetic elements and antibiotic resistance cassettes.
Complete Genome Sequence and Methylome of Staphylococcus schleiferi, an Important Cause of Skin and Ear Infections in Veterinary Medicine
Authors: Misic Ana M. , Cain Christine L. , Morris Daniel O. , Rankin Shelley C. , Beiting Daniel P.
Published: September 2015

Staphylococcus schleiferi
, a Gram-positive and coagulase-variable organism, is an opportunistic human pathogen and a major cause of skin and soft tissue infections in dogs. Here, we report the first
S. schleiferi
genome sequence and methylome from four canine clinical isolates.
Complete Genome Sequence of Papaya Ringspot Virus Isolated from Genetically Modified Papaya in Hainan Island, China
Authors: Zhao Guangyuan , Yan Pu , Shen Wentao , Tuo Decai , Li Xiaoying , Zhou Peng
Published: September 2015

The complete genome sequence (10,326 nucleotides) of a papaya ringspot virus isolate infecting genetically modified papaya in Hainan Island of China was determined through reverse transcription (RT)-PCR. The virus shares 92% nucleotide sequence identity with the isolate that is unable to infect PRSV-resistant transgenic papaya.
Comment on “The velocity field due to an oscillating plate in an Oldroyd-B fluid” by C.C. Hopkins and J.R. de Bruyn [Can. J. Phys. 92, 533 (2014)]
Authors: Christov Ivan C.
Published: September 2015

We correct certain errors and ambiguities in the recent pedagogical article by Hopkins and de Bruyn (Can. J. Phys. 92, 533 (2014). doi:10.1139/cjp-2013-0334 ). The early-time asymptotics of the solution to the transient version of Stokes’ second problem for an Oldroyd-B fluid in a half-space is presented, as Appendix A , to complement the late-time asymptotics given by Hopkins and de Bruyn.
Lung Endoderm Morphogenesis: Gasping for Form and Function
Authors: Swarr Daniel T. , Morrisey Edward E.
Published: September 2015

The respiratory endoderm develops from a small cluster of cells located on the ventral anterior foregut. This population of progenitors generates the myriad epithelial lineages required for proper lung function in adults through a complex and delicately balanced series of developmental events controlled by many critical signaling and transcription factor pathways. In the past decade, understanding of this process has grown enormously, helped in part by cell lineage fate analysis and deep sequencing of the transcriptomes of various progenitors and differentiated cell types. This review explores how these new techniques, coupled with more traditional approaches, have provided a detailed picture of development of the epithelial lineages in the lung and insight into how aberrant development can lead to lung disease.
Horizontal Gene Flow in Managed Ecosystems
Authors: Andam Cheryl P. , Carver Sarah M. , Berthrong Sean T.
Published: September 2015

Mobilization of DNA by horizontal gene transfer (HGT) is an important process in the evolution of many organisms because it allows the recipient lineage to rapidly acquire metabolic innovations and adapt to new ecological niches. However, the significance of HGT in specific ecosystems remains poorly understood. In this review, we present major findings that illustrate how HGT affects managed ecosystems, such as farmlands, orchards, pastures, and managed grasslands. First, acquisition of functions via HGT can lead to the emergence of novel or more virulent pathogens and parasites of crops by allowing them to circumvent host defenses and currently used pest management approaches. Second, HGT of antibiotic resistance genes from the application of wastewater effluent for irrigation or manure as fertilizer can facilitate the emergence of highly resistant microbial lineages. Lastly, HGT can enhance the functional diversity of microbial communities and potentially influence biogeochemical processes. Characterization of lineages possessing horizontally acquired genetic material and their ecology will aid in enhancing the productivity and sustainability of managed ecosystems. We conclude with recommendations for key research directions that will advance our understanding of the causes and consequences of HGT in managed ecosystems.
Direct Mortality of Birds from Anthropogenic Causes
Authors: Loss Scott R. , Will Tom , Marra Peter P.
Published: September 2015

Understanding and reversing the widespread population declines of birds require estimating the magnitude of all mortality sources. Numerous anthropogenic mortality sources directly kill birds. Cause-specific annual mortality in the United States varies from billions (cat predation) to hundreds of millions (building and automobile collisions), tens of millions (power line collisions), millions (power line electrocutions, communication tower collisions), and hundreds of thousands (wind turbine collisions). However, great uncertainty exists about the independent and cumulative impacts of this mortality on avian populations. To facilitate this understanding, additional research is needed to estimate mortality for individual bird species and affected populations, to sample mortality throughout the annual cycle to inform full life-cycle population models, and to develop models that clarify the degree to which multiple mortality sources are additive or compensatory. We review sources of direct anthropogenic mortality in relation to the fundamental ecological objective of disentangling how mortality sources affect animal populations.
Stereotype Threat
Authors: Spencer Steven J. , Logel Christine , Davies Paul G.
Published: September 2015

When members of a stigmatized group find themselves in a situation where negative stereotypes provide a possible framework for interpreting their behavior, the risk of being judged in light of those stereotypes can elicit a disruptive state that undermines performance and aspirations in that domain. This situational predicament, termed stereotype threat, continues to be an intensely debated and researched topic in educational, social, and organizational psychology. In this review, we explore the various sources of stereotype threat, the mechanisms underlying stereotype-threat effects (both mediators and moderators), and the consequences of this situational predicament, as well as the means through which society and stigmatized individuals can overcome the insidious effects of stereotype threat. Ultimately, we hope this review alleviates some of the confusion surrounding stereotype threat while also sparking further research and debate.
In Pursuit of Three Theories: Authoritarianism, Relative Deprivation, and Intergroup Contact
Authors: Pettigrew Thomas F.
Published: September 2015

Throughout my career, I have pursued three theories related to intergroup prejudice—each with a different mentor. Each theory and its supporting research help us to understand prejudice and ways to ameliorate the problem. This autobiographical review article summarizes some of the advances in these three areas during the past six decades. For authoritarianism, the article advocates removing political content from its measurement, linking it with threat and dismissive-avoidant attachment, and studying how authoritarians avoid intergroup contact. Increased work on relative deprivation made possible an extensive meta-analysis that shows the theory, when appropriately measured, has far broader effects than previously thought. Increased research attention to intergroup contact similarly made possible a meta-analysis that established the pervasive effectiveness of intergroup contact to reduce prejudice under a wide range of conditions. The article closes by demonstrating how the three theories relate to each other and contribute to our understanding of prejudice and its reduction.
A Systematic Hardware Sharing Method for Unified Architecture Design of H.264 Transforms
Authors: Chen Po-Hung , Chen Hung-Ming , Lin Ing-Chao
Published: September 2015

Multitransform techniques have been widely used in modern video coding and have better compression efficiency than the single transform technique that is used conventionally. However, every transform needs a corresponding hardware implementation, which results in a high hardware cost for multiple transforms. A novel method that includes a five-step operation sharing synthesis and architecture-unification techniques is proposed to systematically share the hardware and reduce the cost of multitransform coding. In order to demonstrate the effectiveness of the method, a unified architecture is designed using the method for all of the six transforms involved in the H.264 video codec: 2D 4 × 4 forward and inverse integer transforms, 2D 4 × 4 and 2 × 2 Hadamard transforms, and 1D 8 × 8 forward and inverse integer transforms. Firstly, the six H.264 transform architectures are designed at a low cost using the proposed five-step operation sharing synthesis technique. Secondly, the proposed architecture-unification technique further unifies these six transform architectures into a low cost hardware-unified architecture. The unified architecture requires only 28 adders, 16 subtractors, 40 shifters, and a proposed mux-based routing network, and the gate count is only 16308. The unified architecture processes 8 pixels/clock-cycle, up to 275 MHz, which is equal to 707 Full-HD 1080 p frames/second.
Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson’s Disease
Authors: Tuon Talita , Souza Priscila S. , Santos Marcela F. , Pereira Fernanda T. , Pedroso Giulia S. , Luciano Thais F. , De Souza Claudio T. , Dutra Rafael C. , Silveira Paulo C. L. , Pinho Ricardo A.
Published: September 2015

This study aimed to evaluate the effects of two different protocols for physical exercise (strength and aerobic training) on mitochondrial and inflammatory parameters in the 6-OHDA experimental model of Parkinson’s disease. Six experimental groups were used (n=12per group): untrained + vehicle (Sham), strength training + vehicle (STR), treadmill training + vehicle (TTR), untrained + 6-OHDA (U + 6-OHDA), strength training + 6-OHDA (STR + 6-OHDA), and treadmill training + 6-OHDA (TTR + 6-OHDA). The mice were subjected to strength or treadmill training for 8 weeks. PD was inducedviastriatal injection of 6-OHDA 24 h after the last exercise session. Mice were euthanized by cervical dislocation and the striatum and hippocampus were homogenized to determine levels of tyrosine hydroxylase (TH), nuclear factor kappa B (NF-κB) p65, and sirtuin 1 (Sirt1) by western blot; tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-17, interferon-γ(IFN-γ), and transforming growth factorβ1 (TGF-β1) levels by ELISA; NO content; and complex I (CI) activity. STR + 6-OHDA mice had higher TH levels and CI activity and lower NF-κB p65 and IFN-γlevels in the striatum compared to U + 6-OHDA mice, while TTR + 6-OHDA mice had higher Sirt1 levels and CI activity in both the striatum and the hippocampus, compared to U + 6-OHDA mice. Strength training increased CI activity and TH and Sirt1 levels and reduced NO, NF-κB p65, TNF-α, IFN-γ, IL-1β, and TGF-β1 levels in 6-OHDA mice, while treadmill exercise increased CI activity and NO, TH, and Sirt1 levels and reduced NF-κB p65, TNF-α, IFN-γ, and IL-1βlevels. Our results demonstrated that both treadmill training and strength training promote neuroprotection, possibly by stimulating Sirt1 activity, which may in turn regulate both mitochondrial function and neuroinflammationviadeacetylation of NF-κB p65. Changes in nitric oxide levels may also be a mechanism by which 6-OHDA-induced inflammation is controlled.
Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases
Authors: Sherman Larry S. , Matsumoto Steven , Su Weiping , Srivastava Taasin , Back Stephen A.
Published: September 2015

The glycosaminoglycan hyaluronan (HA), a component of the extracellular matrix, has been implicated in regulating neural differentiation, survival, proliferation, migration, and cell signaling in the mammalian central nervous system (CNS). HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity. HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes. Insults to the CNS lead to long-term elevation of HA within damaged tissues, which is linked at least in part to increased transcription of HA synthases. HA accumulation is often accompanied by elevated expression of at least some transmembrane HA receptors including CD44. Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities. A number of studies, for example, suggest that both the removal of high molecular weight HA and the accumulation of hyaluronidase-generated HA digestion products can impact CNS injuries through mechanisms that include the regulation of progenitor cell differentiation and proliferation. These studies, reviewed here, suggest that targeting HA synthesis, catabolism, and signaling are all potential strategies to promote CNS repair.
Quality of the Governing Temperature Variables in WRF in relation to Simulation of Primary Biological Aerosols
Authors: Skjøth C. A. , Werner M. , Kryza M. , Adams-Groom B. , Wakeham A. , Lewis M. , Kennedy R.
Published: September 2015

We have evaluated three prognostic variables in Weather Research and Forecasting (WRF) model, mean daily temperature, daily maximum temperature, and daily minimum temperature using 9 months of model simulations at 36 and 12 km resolution, and compared the results with 1182 observational sites in north and central Europe. The quality of the results is then determined in the context of the governing variables used in crop science, forestry, and aerobiological models. We use the results to simulate the peak of the birch pollen season (aerobiology), growth of barley (crop science), and development of the invasive plant pathogenHymenoscyphus pseudoalbidus(the cause of ash-dieback). The results show that the crop and aerobiological models are particularly sensitive to grid resolution and much higher quality is obtained from the 12 km simulations compared to 36 km. The results also show that the summer months have a bias, in particular for maximum and minimum temperatures, and that the low/high bias is clustered in two areas: continental and coastal influenced areas. It is suggested that the use of results from meteorological models as an input into biological models needs particular attention in the quality of the modelled surface data as well as the applied land surface modules.
Radiation and MHD Boundary Layer Stagnation-Point of Nanofluid Flow towards a Stretching Sheet Embedded in a Porous Medium: Analysis of Suction/Injection and Heat Generation/Absorption with Effect of the Slip Model
Authors: Aly Emad H.
Published: September 2015

In existence of the velocity slip model, suction/injection, and heat source/sink, the boundary layer flow near a stagnation-point over a heated stretching sheet in a porous medium saturated by a nanofluid, with effect of the thermal radiation and magnetic field, has been studied. The governing system of partial differential equations was transformed into a system of nonlinear ordinary equations using the appropriate similarity transforms. Then, the obtained system has been numerically solved by the Chebyshev pseudospectral differentiation matrix (ChPDM) approach. It was found that, at some special cases, the current results are in a very good agreement with those presented in the literature. In addition, the flow velocity, surface shear stress, temperature, and concentration are strongly influenced on applying the slip model, which is, therefore, extremely important to predict the flow characteristics accurately in the nanofluid mechanics. It was proved that this velocity slip condition is mandatory and should be taken into account in nanoscale research; otherwise, false results and a spurious physical sight are to be gained. Further, it was deduced that the influence of the stream velocity and shear stress reaches very rapidly the stable manner for both cases of the velocity ratio. However, when this ratio is equal to one, the skin friction coefficient, reduced Nusselt number, and reduced Sherwood number are constant and equal to zero, 0.721082, and 3.06155, respectively. Furthermore, it was proved that the reduced Nusselt number decreases with increase of Brownian motion and thermophoresis; has a very weak effect on increasing Lewis number; increases with increase of Prandtl number; and is higher in the cases of suction, velocity ratio > 1 and heat source in comparison with injection, velocity ratio < 1, and heat sink, respectively. Moreover, the reduced Sherwood number increases with increase of Brownian motion, thermophoresis, and Lewis number; decreases with increase of Prandtl number; is higher in the cases of suction and velocity ratio > 1 in comparison with injection and velocity ratio < 1, respectively; and is approximately the same in the heat source and heat sink cases. Finally, it was shown that the most effective region for radiation effect is[0,1].
Analysis on Strong Tracking Filtering for Linear Dynamic Systems
Authors: Ge Quanbo , Shao Teng , Wen Chenglin , Sun Ruoyu
Published: September 2015

Strong tracking filtering (STF) is a popular adaptive estimation method to effectively deal with state estimation for linear and nonlinear dynamic systems with inaccurate models or sudden change of state. The key of the STF is to use a time-variant fading factor, which can be evaluated based on the current measurement innovation in real time, to forcefully correct one step state prediction error covariance. The strong tracking filtering technology has been extensively applied in many practical systems, but the theoretical analysis is highly lacking. In an effort to better understand STF, a novel analysis framework is developed for the strong tracking filtering and some new problems are discussed for the first time. For this, we propose a new perspective that correcting the state prediction error covariance by using the fading factor can be thought of directly modifying the state model by correcting the covariance of the process noise. Based on this proposed point of view, the conditions for the STF function to be effective are deeply analyzed in a certain linear dynamic system. Meanwhile, issues of false alarm and alarm failure are also briefly discussed for the strong tracking filtering function. Some numerical simulation examples are demonstrated to validate the results.
Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis
Authors: Ghatak Shibnath , Maytin Edward V. , Mack Judith A. , Hascall Vincent C. , Atanelishvili Ilia , Moreno Rodriguez Ricardo , Markwald Roger R. , Misra Suniti
Published: September 2015

A wound is a type of injury that damages living tissues. In this review, we will be referring mainly to healing responses in the organs including skin and the lungs.Fibrosisis a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis). In tissues such as the skin, the repair of the dermis after wounding requires not only thefibroblaststhat produce the ECM molecules, but also the overlying epithelial layer (keratinocytes), theendothelial cells, andsmooth muscle cellsof the blood vessel and white blood cells such asneutrophilsandmacrophages, which together orchestrate the cytokine-mediated signaling and paracrine interactions that are required to regulate the proper extent and timing of the repair process. This review will focus on the importance of extracellular molecules in the microenvironment, primarily the proteoglycans and glycosaminoglycan hyaluronan, and their roles in wound healing. First, we will briefly summarize the physiological, cellular, and biochemical elements of wound healing, including the importance of cytokine cross-talk between cell types. Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes. Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.
Short-Course Induction Treatment with Intrathecal Amphotericin B Lipid Emulsion for HIV Infected Patients with Cryptococcal Meningitis
Authors: Alvarez-Uria Gerardo , Midde Manoranjan , Pakam Raghavakalyan , Yalla Pradeep Sukumar , Naik Praveen Kumar , Reddy Raghuprakash
Published: September 2015

Cryptococcal meningitis (CM) is a common cause of death among HIV infected patients in developing countries, especially in sub-Saharan Africa. In this observational HIV cohort study in a resource-limited setting in India, we compared the standard two-week intravenous amphotericin B deoxycholate (AmBd) (Regimen I) with one week of intravenous AmBd along with daily therapeutic lumbar punctures and intrathecal AmB lipid emulsion (Regimen II) during the intensive phase of CM treatment. 78 patients received Regimen I and 45 patients received Regimen II. After adjustment for baseline characteristics (gender, age, altered mental status or seizures at presentation, CD4 cell count, white blood cells, cerebrospinal fluid white cells, and haemoglobin), the use of Regimen II was associated with a significant relative risk reduction in mortality (adjusted hazard ratio 0.4, 95% confidence interval, 0.22–0.76) and 26.7% absolute risk reduction (95% confidence interval, 9.9–43.5) at 12 weeks. The use of Regimen II resulted in lower costs of drugs and hospital admission days. Since the study is observational in nature, we should be cautious about our results. However, the good tolerability of intrathecal administration of AmB lipid emulsion and the clinically important mortality reduction observed with the short-course induction treatment warrant further research, ideally through a randomized clinical trial.
Cancer Stem Cell Marker Phenotypes Are Reversible and Functionally Homogeneous in a Preclinical Model of Pancreatic Cancer
Authors: Dosch Joseph S. , Ziemke Elizabeth K. , Shettigar Amrith , Rehemtulla Alnawaz , Sebolt-Leopold Judith S.
Published: September 2015

Survival rates associated with pancreatic cancer remain dismal despite advancements in detection and experimental treatment strategies. Genetically engineered mouse models of pancreatic tumorigenesis have gained considerable attention based on their ability to recapitulate key clinical features of human disease including chemotherapeutic resistance and fibrosis. However, it is unclear if transgenic systems exemplified by the KrasG12D/Trp53R172H/Pdx-1-Cre (KPC) mouse model recapitulate the functional heterogeneity of human pancreatic tumors harboring distinct cells with tumorigenic properties. To facilitate tracking of heterogeneous tumor cell populations, we incorporated a luciferase-based tag into the genetic background of the KPC mouse model. We isolated pancreatic cancer cells from multiple independent tumor lines and found that roughly 1 out of 87 cells exhibited tumorigenic capability. Notably, this frequency is significantly higher than reported for human pancreatic adenocarcinomas. Cancer stem cell (CSC) markers, including CD133, CD24, Sca-1, and functional Aldefluor activity, were unable to discriminate tumorigenic from nontumorigenic cells in syngeneic transplants. Furthermore, three-dimensional spheroid cultures originating from KPC tumors did not enrich for cells with stem-like characteristics and were not significantly more tumorigenic than cells cultured as monolayers. Additionally, we did not observe significant differences in response to gemcitabine or salinomycin in several isolated subpopulations. Taken together, these studies show that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. Cancer Res; 75(21); 4582–92. ©2015 AACR.
Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma
Authors: Hemachandra L.P. Madhubhani P. , Shin Dong-Hui , Dier Usawadee , Iuliano James N. , Engelberth Sarah A. , Uusitalo Larissa M. , Murphy Susan K. , Hempel Nadine
Published: September 2015

Epithelial ovarian cancer (EOC) is the fourth leading cause of death due to cancer in women and comprises distinct histologic subtypes, which vary widely in their genetic profiles and tissues of origin. It is therefore imperative to understand the etiology of these distinct diseases. Ovarian clear cell carcinoma (OCCC), a very aggressive subtype, comprises >10% of EOCs. In the present study, we show that mitochondrial superoxide dismutase (Sod2) is highly expressed in OCCC compared with other EOC subtypes. Sod2 is an antioxidant enzyme that converts highly reactive superoxide (O2•−) to hydrogen peroxide (H2O2) and oxygen (O2), and our data demonstrate that Sod2 is protumorigenic and prometastatic in OCCC. Inhibiting Sod2 expression reduces OCCC ES-2 cell tumor growth and metastasis in a chorioallantoic membrane (CAM) model. Similarly, cell proliferation, migration, spheroid attachment and outgrowth on collagen, and Akt phosphorylation are significantly decreased with reduced expression of Sod2. Mechanistically, we show that Sod2 has a dual function in supporting OCCC tumorigenicity and metastatic spread. First, Sod2 maintains highly functional mitochondria, by scavenging O2•−, to support the high metabolic activity of OCCC. Second, Sod2 alters the steady-state ROS balance to drive H2O2-mediated migration. While this higher steady-state H2O2 drives prometastatic behavior, it also presents a doubled-edged sword for OCCC, as it pushed the intracellular H2O2 threshold to enable more rapid killing by exogenous sources of H2O2. Understanding the complex interaction of antioxidants and ROS may provide novel therapeutic strategies to pursue for the treatment of this histologic EOC subtype. Cancer Res; 75(22); 4973–84. ©2015 AACR.
Combining miR-10b–Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer
Authors: Yoo Byunghee , Kavishwar Amol , Ross Alana , Wang Ping , Tabassum Doris P. , Polyak Kornelia , Barteneva Natalia , Petkova Victoria , Pantazopoulos Pamela , Tena Aseda , Moore Anna , Medarova Zdravka
Published: September 2015

The therapeutic promise of microRNA (miRNA) in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b–inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent antiproliferative, proapoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration. Cancer Res; 75(20); 4407–15. ©2015 AACR.
Feed-Forward Reciprocal Activation of PAFR and STAT3 Regulates Epithelial–Mesenchymal Transition in Non–Small Cell Lung Cancer
Authors: Chen Jie , Lan Tian , Zhang Weimin , Dong Lijia , Kang Nan , Zhang Shumin , Fu Ming , Liu Bing , Liu Kangtai , Zhan Qimin
Published: September 2015

Platelet-activating factor receptor (PAFR), a G-protein–coupled receptor, has been implicated in tumorigenesis, but its contributions to metastatic progression have not been investigated. Here, we show that PAFR is overexpressed in non–small cell lung cancer (NSCLC) as well as in breast, colorectal, and gastric carcinomas. Expression of PAFR correlates closely with clinical stages, survival time, and distant metastasis. In human NSCLC cells, activation of the PAF/PAFR signaling axis accentuated malignant character, including by stimulating epithelial–mesenchymal transition (EMT). In contrast, silencing PAFR in aggressive NSCLC cells inhibited these effects. Mechanistic investigations showed that PAFR stimulated EMT by activating STAT3 via upregulation of G-protein–dependent SRC or JAK2 kinase activity. Notably, STAT3 transcriptionally elevated PAFR expression. Thus, activation of PAFR in NSCLC cells initiated a forward feedback loop responsible for mediating the aggressive malignant character of NSCLC cells in vitro and in vivo. Reinforcing this reciprocal activation loop, PAF/PAFR signaling also upregulated IL6 expression and thereby STAT3 activation. Overall, our results elucidated an important role for PAFR dysregulation in the pathogenicity of NSCLC and unraveled a forward feedback loop between PAFR and STAT3 that acts to drive the malignant progression of NSCLC. Cancer Res; 75(19); 4198–210. ©2015 AACR.
Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5
Authors: Le Gall Marianne , Crépin Ronan , Neiveyans Madeline , Auclair Christian , Fan Yongfeng , Zhou Yu , Marks James D. , Pèlegrin André , Poul Marie-Alix
Published: September 2015

KIT is a cell surface tyrosine kinase receptor whose ligand stem cell factor (SCF) triggers homodimerization and activation of downstream effector pathways involved in cell survival, proliferation, homing, or differentiation. KIT-activating mutations are major oncogenic drivers in subsets of acute myeloid leukemia (AML), in mast cell leukemia, and in gastrointestinal stromal tumors (GIST). The overexpression of SCF and/or wild-type (WT) KIT is also observed in a number of cancers, including 50% of AML and small cell lung cancer. The use of tyrosine kinase inhibitors (TKI) in these pathologies is, however, hampered by initial or acquired resistance following treatment. Using antibody phage display, we obtained two antibodies (2D1 and 3G1) specific for the most membrane proximal extracellular immunoglobulin domain (D5) of KIT, which is implicated in KIT homodimerization. Produced as single chain variable antibody fragments fused to the Fc fragment of a human IgG1, bivalent 2D1-Fc and 3G1-Fc inhibited KIT-dependent growth of leukemic cell lines expressing WT KIT (UT7/Epo) or constitutively active KIT mutants, including the TKI imatinib-resistant KIT D816V mutant (HMC1.2 cell line). In all models, either expressing WT KIT or mutated KIT, 2D1 and 3G1-Fc induced KIT internalization and sustained surface downregulation. However, interestingly, KIT degradation was only observed in leukemic cell lines with oncogenic KIT, a property likely to limit the toxicity of these antibodies in patients. These fully human antibody formats may represent therapeutic tools to target KIT signaling in leukemia or GIST, and to bypass TKI resistance of certain KIT mutants. Mol Cancer Ther; 14(11); 2595–605. ©2015 AACR.